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  1. Skin Manifestations of Endocrine Diseases.

    Science.gov (United States)

    Demirkesen, Cuyan

    2015-01-01

    Endocrine diseases may result in changes in cutaneous function and morphology, which cause various skin manifestations, including nonspecific or pathognomonic signs. Some of these manifestations are already known dermatologic diseases with only increased frequency in this patient group. As a result the skin may the play role of a screen displaying endocrine disorders, either due to hormone excess or deficiency. Awareness of the skin manifestations may permit prompt and adequate approach to the patients, and therefore facilitate the early diagnosis of the endocrine disease and even be life saving. Some of these manifestations may be recognized clinically, but sometimes they need to be confirmed histopathologically. In this article, many endocrine diseases and their associated skin lesions will be reviewed briefly.

  2. Otolaryngic manifestations of Cushing disease.

    Science.gov (United States)

    Kuan, Edward C; Peng, Kevin A; Suh, Jeffrey D; Bergsneider, Marvin; Wang, Marilene B

    2017-08-01

    Cushing disease is a relatively rare cause of Cushing syndrome secondary to a hyperfunctioning pituitary adenoma. In addition to signs and symptoms of hypercortisolism, Cushing disease may present with diverse otolaryngic manifestations, which may guide diagnosis and management. We performed a retrospective chart review of patients who were found to have Cushing disease and who underwent transnasal transsphenoidal surgery for pituitary adenomas between January 1, 2007, and July 1, 2014, at a tertiary academic medical center. There were 37 consecutive patients in this series with Cushing disease caused by a pituitary adenoma. Fifteen (41%) patients complained of visual changes. Five (14%) patients suffered from obstructive sleep apnea. Four (11%) patients had thyroid disease. Other symptoms included hearing loss, vertigo, tinnitus, epistaxis, dysphagia, and salivary gland swelling. Although Cushing disease traditionally presents with classic "Cushingoid" systemic features, it also may present with various otolaryngic manifestations. A thorough workup by otolaryngologists is critical in the comprehensive management of these patients.

  3. [Corneal manifestations in systemic diseases].

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    Zarranz Ventura, J; De Nova, E; Moreno-Montañés, J

    2008-01-01

    Systemic diseases affecting the cornea have a wide range of manifestations. The detailed study of all pathologies that cause corneal alteration is unapproachable, so we have centered our interest in the most prevalent or characteristic of them. In this paper we have divided these pathologies in sections to facilitate their study. Pulmonar and conective tissue (like colagen, rheumatologic and idiopathic inflamatory diseases), dermatologic, cardiovascular, hematologic, digestive and hepatopancreatic diseases with corneal alteration are described. Endocrine and metabolic diseases, malnutrition and carential states are also studied, as well as some otorhinolaryngologic and genetic diseases that affect the cornea. Finally, a brief report of ocular toxicity induced by drugs is referred.

  4. Breast manifestations of systemic diseases

    Directory of Open Access Journals (Sweden)

    Dilaveri CA

    2012-02-01

    Full Text Available Christina A Dilaveri, Maire Brid Mac Bride, Nicole P Sandhu, Lonzetta Neal, Karthik Ghosh, Dietlind L Wahner-RoedlerDivision of General Internal Medicine, Mayo Clinic, Rochester, MN, USAAbstract: Although much emphasis has been placed on the primary presentations of breast cancer, little focus has been placed on how systemic illnesses may affect the breast. In this article, we discuss systemic illnesses that can manifest in the breast. We summarize the clinical features, imaging, histopathology, and treatment recommendations for endocrine, vascular, systemic inflammatory, infectious, and hematologic diseases, as well as for the extramammary malignancies that can present in the breast. Despite the rarity of these manifestations of systemic disease, knowledge of these conditions is critical to the appropriate evaluation and treatment of patients presenting with breast symptoms.Keywords: breast, endocrine, hematologic, infectious, vascular

  5. Respiratory manifestations in endocrine diseases

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    LENCU, CODRU?A; ALEXESCU, TEODORA; PETRULEA, MIRELA; LENCU, MONICA

    2016-01-01

    The control mechanisms of respiration as a vital function are complex: voluntary ? cortical, and involuntary ? metabolic, neural, emotional and endocrine. Hormones and hypothalamic neuropeptides (that act as neurotrasmitters and neuromodulators in the central nervous system) play a role in the regulation of respiration and in bronchopulmonary morphology. This article presents respiratory manifestations in adult endocrine diseases that evolve with hormone deficit or hypersecretion. In hyperthy...

  6. Endocrine manifestations of celiac disease

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    R Philip

    2012-01-01

    Full Text Available Background: Celiac disease can have extra gastrointestinal tract (GIT presentations, most of which are endocrine. The aim of this study was to present patients diagnosed to have celiac disease from an endocrine department and to study the prevalence of endocrinopathies in celiac disease. Materials and Methods: A total of 36 patients from the endocrinology department (LLRM Medical College, Meerut between January 2011 and July 2012 and who were diagnosed to have celiac disease were included in the study. Results: Short stature was the commonest presentation (25%, other presentations included short stature and delayed puberty (20%, delayed puberty (11%, screening for celiac disease in type-1 DM patients (17%, rickets (6%, anemia not responding to oral therapy (6%, type-1 DM with recurrent hypoglycaemia (6%, and osteomalacia (3%. The endocrine manifestations include (after complete evaluation short stature (58%, delayed puberty (31%, elevated alkaline phospahatase (67%, low calcium (22%, X-rays suggestive of osteomalacia or rickets (8%, capopedal spasm (6%, and night blindness (6%. Anti-TPO antibody positivity was found in 53%, hypothyroidism in 28%, subclinical hypothyroidism in 17%, and type-1 DM in 25% of the patients. A total of 14% patients had no GI symptoms. Conclusion: Celiac disease is an endocrine disrupter as well as the great masquerader having varied presentations including short stature, delayed puberty, and rickets. Some patients who have celiac disease may not have any GI symptoms, making the diagnosis all the more difficult. Also, there is significant incidence of celiac disease with hypothyroidism and type-1 DM, making screening for it important in these diseases.

  7. Migraine- and dystonia-related disease-mutations of Na+/K+-ATPases: Relevance of behavioral studies in mice to disease symptoms and neurological manifestations in humans

    DEFF Research Database (Denmark)

    Bøttger, Pernille; Doganli, Canan; Lykke-Hartmann, Karin

    2012-01-01

    The two autosomal dominantly inherited neurological diseases: familial hemiplegic migraine type 2 (FHM2) and familial rapid-onset of dystonia-parkinsonism (Familial RDP) are caused by in vivo mutations of specific alpha subunits of the sodium–potassium pump (Na+/K+-ATPase). Intriguingly, patients...... with classical FHM2 and RDP symptoms additionally suffer from other manifestations, such as epilepsy/seizures and developmental disabilities. Recent studies of FHM2 and RDP mouse models provide valuable tools for dissecting the vital roles of the Na+/K+-ATPases, and we discuss their relevance to the complex...

  8. Cystic thymic diseases: CT manifestations

    International Nuclear Information System (INIS)

    Song, Soon Young; Choi, Yo Won; Jeon, Eui Yong; Jeon, Seok Chol; Seo, Heung Suk; Hahm, Chang Kok

    1995-01-01

    To describe CT findings and differential points of cystic thymic lesions. We evaluated retrospectively total 19 masses with well marginated cystic lesions at thymic area on CT scans. They were 10 teratomas, 3 congenital thymic cysts, 2 multilocular thymic cysts(associated with thymoma and myasthenia gravis in each), 2 cysts Assciated with thymic Hodgkin's lymphomas an ectopic parathyroid cyst, and an infected thymic cyst. The radiological abnormalities evaluated were thickness of the wall, presence or abscene of septa, mural nodule, solid component, calcification and fat component. All three cases of congenital thymic cysts and an ectopic parathyroid cyst appeared as thin-walled unilocular cyst with homogeneous internal density and without identifiable solid component. In multilocular thymic cyst, there were thick wall and solid components(n =2), thick internal septa and calcifications(n = 1). The cysts of teratomas manifested thick walls(n = 9), internal septa(n = 4), calcifications(n = 6), fat components(n = 4), and solid components(n = 4). Cysts in Hodgkin's diseases appeared as multilocular or unilocular and had thick wall and septa without calcification. Infected thymic cyst presented with multilocular cystic mass with identifiable wall and septa, calcification, and solid components. The thymic diseases with cystic lesion include teratomas, congenital thymic cysts, multilocular thymic cysts, parathyroid cyst, and Hodgkin's disease. Congenital thymic cyst and ectopic parathyroid cyst are thin-walled unilocular cystic lesions. Cystic lesions associated with teratoma, Hodgkin's disease, and multilocular thymic cyst are thick-walled cystic lesions with or without solid component

  9. Esophageal manifestations of celiac disease.

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    Lucendo, A J

    2011-09-01

    Celiac disease (CD) may often be associated with various motor disorders affecting the different segments of the digestive tract, including the esophagus. Although it has not been universally reported, some available evidences indicate that pediatric and adult celiac patients could manifest a higher frequency of esophagitis and gastroesophageal reflux disease-related symptoms compared to nonceliac patients. In addition, several published studies have consistently shown the efficacy of a gluten-free diet in rapidly controlling esophageal symptoms and in preventing their recurrence. Since the participation of gluten in the esophageal symptoms of CD seems clear, its intimate mechanisms have yet to be elucidated, and several hypothesis have been proposed, including the specific immune alterations characterizing CD, the reduction in nutrient absorption determining the arrival of intact gluten to distal gastrointestinal segments, and various dysregulations in the function of gastrointestinal hormones and peptides. Recent studies have suggested the existence of a possible relationship between CD and eosinophilic esophagitis, which should be more deeply investigated. © 2011 Copyright the Author. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

  10. Cystic thymic diseases: CT manifestations

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    Song, Soon Young; Choi, Yo Won; Jeon, Eui Yong; Jeon, Seok Chol; Seo, Heung Suk; Hahm, Chang Kok [School of Medicine, Hanyang University, Seoul (Korea, Republic of)

    1995-09-15

    To describe CT findings and differential points of cystic thymic lesions. We evaluated retrospectively total 19 masses with well marginated cystic lesions at thymic area on CT scans. They were 10 teratomas, 3 congenital thymic cysts, 2 multilocular thymic cysts(associated with thymoma and myasthenia gravis in each), 2 cysts Assciated with thymic Hodgkin's lymphomas an ectopic parathyroid cyst, and an infected thymic cyst. The radiological abnormalities evaluated were thickness of the wall, presence or abscene of septa, mural nodule, solid component, calcification and fat component. All three cases of congenital thymic cysts and an ectopic parathyroid cyst appeared as thin-walled unilocular cyst with homogeneous internal density and without identifiable solid component. In multilocular thymic cyst, there were thick wall and solid components(n =2), thick internal septa and calcifications(n = 1). The cysts of teratomas manifested thick walls(n = 9), internal septa(n = 4), calcifications(n = 6), fat components(n = 4), and solid components(n = 4). Cysts in Hodgkin's diseases appeared as multilocular or unilocular and had thick wall and septa without calcification. Infected thymic cyst presented with multilocular cystic mass with identifiable wall and septa, calcification, and solid components. The thymic diseases with cystic lesion include teratomas, congenital thymic cysts, multilocular thymic cysts, parathyroid cyst, and Hodgkin's disease. Congenital thymic cyst and ectopic parathyroid cyst are thin-walled unilocular cystic lesions. Cystic lesions associated with teratoma, Hodgkin's disease, and multilocular thymic cyst are thick-walled cystic lesions with or without solid component.

  11. [Lyme disease--clinical manifestations and treatment].

    Science.gov (United States)

    Stock, Ingo

    2016-05-01

    Lyme disease (Lyme borreliosis) is a systemic infectious disease that can present in a variety of clinical manifestations. The disease is caused by a group of spirochaetes--Borrelia burgdorferi sensu lato or Lyme borrelia--that are transmitted to humans by the bite of Ixodes ticks. Lyme disease is the most common arthropode-borne infectious disease in many European countries including Germany. Early localized infection is typically manifested by an erythema migrans skin lesion, in rarer cases as a borrelial lymphocytoma. The most common early disseminated manifestation is (early) neuroborreliosis. In adults, neuroborreliosis appears typically as meningoradiculoneuritis. Neuroborreliosis in children, however, is typically manifested by meningitis. In addition, multiple erythema migrans lesions and Lyme carditis occur relatively frequently. The most common manifestation oflate Lyme disease is Lyme arthritis. Early manifestations (and usually also late manifestations) of Lyme disease can be treated successfully by application of suitable antibacterial agents. For the treatment of Lyme disease, doxycycline, certain penicillins such as amoxicillin and some cephalosporins (ceftriaxone, cefotaxime, cefuroxime axetil) are recommended in current guidelines. A major challenge is the treatment of chronic, non-specific disorders, i. e., posttreatment Lyme disease syndrome and "chronic Lyme disease". Prevention of Lyme disease is mainly accomplished by protecting against tick bites. Prophylactic administration of doxycycline after tick bites is generally not recommended in Germany. There is no vaccine available for human beings.

  12. Neuropsychiatric Manifestations of Parkinson`s Disease

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    Ana Peixinho

    2014-10-01

    Full Text Available Parkinson’s disease affects about 1% of the world population older than 65 years. It’s most frequently considered a movement disorder, but the neuropsychiatric manifestations associated with the disease and/or its treatment may be of equal or greater significance in some patients. We will discuss briefly the epidemiology, physiopathology and diagnosis of Parkinson’s disease, highlighting the neuropsychiatric manifestations: depression, anxiety, psychosis, dementia, sleep disorders, dopamine dysregulation syndrome.

  13. Intrathoracic manifestations of Rosai-Dorfman disease.

    Science.gov (United States)

    Cartin-Ceba, Rodrigo; Golbin, Jason M; Yi, Eunhee S; Prakash, Udaya B S; Vassallo, Robert

    2010-09-01

    Rosai-Dorfman Disease (RDD), also known as Sinus Histiocytosis with Massive Lymphadenopathy (SHML), is a rare monocyte/macrophage proliferative disorder of varied biological behavior. Although cutaneous and lymph node involvement are relatively well-described, intrathoracic manifestations of RDD have only occasionally been reported. We conducted a retrospective computer-assisted search of the Mayo Clinic record from 1976 to 2005 for patients with histopathologic evidence of RDD on organ biopsy. Clinical characteristics were abstracted from charts and thoracic manifestations recorded. Survival was estimated using the national social security database. A total of 21 patients were diagnosed with RDD over a period of 30 years; 9 had intrathoracic manifestations (43%). Main pulmonary symptoms included dyspnea and cough. Age at the time of diagnosis, gender, race, smoking history, mortality and time of survival after diagnosis were no different between RDD patients with and without intrathoracic manifestations. The most common radiographic thoracic manifestation was mediastinal lymphadenopathy (6 patients). Cystic change, interstitial lung disease, and airway disease were radiographically evident in 4 patients. Seven patients were treated at some point in the course of their disease, most commonly with oral corticosteroids. At the time of last follow-up 87% were alive, with a median (IQR) time interval since diagnosis of 8 years (4-9.7). Intrathoracic manifestations of RDD are relatively common and include mediastinal lymphadenopathy, airway disease, pleural effusion, cystic and interstitial lung disease. Although limited in size, this series suggests the prognosis of patients with RDD and intrathoracic manifestations is relatively good.

  14. Hepatic manifestations of celiac disease

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    Hugh James Freeman

    2010-05-01

    Full Text Available Hugh James FreemanDepartment of Medicine (Gastroenterology, University of British Columbia, Vancouver, British Columbia, CanadaAbstract: Different hepatic and biliary tract disorders may occur with celiac disease. Some have been hypothesized to share genetic or immunopathogenetic factors, such as primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis. Other hepatic changes in celiac disease may occur with malnutrition resulting from impaired nutrient absorption, including hepatic steatosis. In addition, celiac disease may be associated with rare hepatic complications, such as hepatic T-cell lymphoma.Keywords: celiac disease, autoimmune liver disease, primary biliary cirrhosis, fatty liver, gluten-free diet

  15. Pulmonary manifestations of tsutsugamushi disease

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    Im, Jung Gi; Lee, Kyung Soo; Kim, Jae Hyoung; Lee, Won Jae [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1988-10-15

    Tsutsugamushi disease is an acute febrile systemic disease caused by Rickettsia tsutsugamushi. Attention to Tsutsugamushi disease is increasing as it has recently been known that Tsutsugamushi disease is one of the epidemic febrile disease that occur in late fall in Korea. We analysed chest radiographic findings of 60 serologically confirmed Tsutsugamushi disease patients. 47 infiltration, mostly reticulonodular interstitial pattern. High resolution CT in a patient strongly supported that the lesions are interstitial location. 29 patients (62%) showed findings of hilar lymphadenopathy and septal lines were seen in 22 patients (47%). Other findings were cardiomegaly (10 patients), pleural effusion (6 patients), mediastinal lymphadenopathy (3 patients). Diffuse bilateral interstitial lung infiltration, hilar lymphadenopathy and septal lines are typical chest ratio graphic findings of Tsutsugamushi disease.

  16. Pulmonary manifestations of tsutsugamushi disease

    International Nuclear Information System (INIS)

    Im, Jung Gi; Lee, Kyung Soo; Kim, Jae Hyoung; Lee, Won Jae

    1988-01-01

    Tsutsugamushi disease is an acute febrile systemic disease caused by Rickettsia tsutsugamushi. Attention to Tsutsugamushi disease is increasing as it has recently been known that Tsutsugamushi disease is one of the epidemic febrile disease that occur in late fall in Korea. We analysed chest radiographic findings of 60 serologically confirmed Tsutsugamushi disease patients. 47 infiltration, mostly reticulonodular interstitial pattern. High resolution CT in a patient strongly supported that the lesions are interstitial location. 29 patients (62%) showed findings of hilar lymphadenopathy and septal lines were seen in 22 patients (47%). Other findings were cardiomegaly (10 patients), pleural effusion (6 patients), mediastinal lymphadenopathy (3 patients). Diffuse bilateral interstitial lung infiltration, hilar lymphadenopathy and septal lines are typical chest ratio graphic findings of Tsutsugamushi disease.

  17. Extraintestinal manifestations of inflammatory bowel disease: epidemiology, diagnosis, and management

    DEFF Research Database (Denmark)

    Larsen, Signe; Bendtzen, Klaus; Nielsen, Ole Haagen

    2010-01-01

    ', 'bronchiectasis', 'bronchitis', 'cutaneous manifestations', 'erythema nodosum', 'extraintestinal manifestations', 'hyperhomocysteinemia', 'infliximab', 'iridocyclitis', 'lung disease', 'ocular manifestations', 'osteomalacia', 'pancreatitis', 'primary sclerosing cholangitis', 'renal stones', 'sulfasalazine...

  18. Neurological Manifestations In Inflammatory Bowel Disease

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    youssef HNACH

    2015-06-01

    Full Text Available IntroductionThe purpose of this retrospective study was to report neurological manifestations noted in patients who were monitored for inflammatory bowel disease, in order to document the pathophysiological, clinical, progressive, and therapeutic characteristics of this entity.Material and methodsWe conducted a retrospective study on patients monitored -in the gastroenterology service in Ibn Sina Hospital in Rabat, Morocco- for inflammatory bowel disease from 1992 till 2013 and who developed neurological manifestations during its course. Patients with iatrogenic complications were excluded, as well as patients with cerebrovascular risk factors.ResultsThere were 6 patients, 4 of whom have developed peripheral manifestations. Electromyography enabled the diagnosis to be made and the outcome was favorable with disappearance of clinical manifestations and normalization of the electromyography.The other 2 patients, monitored for Crohn’s disease, developed ischemic stroke. Cerebral computed tomography angiography provided positive and topographic diagnosis. Two patients were admitted to specialized facilities.ConclusionNeurological manifestations in inflammatory bowel disease are rarely reported.  Peripheral neuropathies and stroke remain the most common manifestations. The mechanisms of these manifestations are not clearly defined yet. Currently, we hypothesize the interaction of immune mediators.

  19. Endocrine manifestations in celiac disease.

    Science.gov (United States)

    Freeman, Hugh James

    2016-10-14

    Celiac disease (CD) is an autoimmune small intestinal mucosal disorder that often presents with diarrhea, malabsorption and weight loss. Often, one or more associated endocrine disorders may be associated with CD. For this review, methods involved an extensive review of published English-language materials. In children and adolescents, prospective studies have demonstrated a significant relationship to insulin-dependent or type 1 diabetes, whereas in adults, autoimmune forms of thyroid disease, particularly hypothyroidism, may commonly co-exist. In some with CD, multiple glandular endocrinopathies may also occur and complicate the initial presentation of the intestinal disease. In others presenting with an apparent isolated endocrine disorder, serological screening for underlying subclinical CD may prove to be positive, particularly if type 1 diabetes, autoimmune thyroid or other autoimmune endocrine diseases, such as Addison's disease are first detected. A number of reports have also recorded hypoparathyroidism or hypopituitarism or ovarian failure in CD and these may be improved with a strict gluten-free diet.

  20. Neurological manifestations in Fabry's disease

    DEFF Research Database (Denmark)

    Møller, Anette Torvin; Jensen, Troels Staehelin

    2007-01-01

    . Neurological symptoms, such as burning sensations (occasionally accompanied by acroparesthesia) and stroke, are among the first to appear, and occur in both male and female patients. A delay in establishing the diagnosis of Fabry's disease can cause unnecessary problems, especially now that enzyme replacement...... treatment is available to prevent irreversible organ damage. Females with Fabry's disease who present with pain have often been ignored and misdiagnosed because of the disorder's X-linked inheritance. This Review will stress the importance of recognizing neurological symptoms for the diagnosis of Fabry...

  1. Unusual manifestations of hydatid disease

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    Meyer, E.; Adam, T.

    1989-05-01

    Hydatid disease is mostly located in the liver. It then has a characteristic appearance allowing a definite diagnosis by means of ultrasound and/or CT examination. Isolated extrahepatic infestation is much less common. We report a number of cases of hydatid cysts in the tail of the pancreas, the adrenal, the spleen, and in bones and muscles. With reference to these examples we discuss the potential usefulness of radiological examination for the diagnosis and also its limitations and the pitfalls that may be encountered.

  2. Bilingualism delays clinical manifestation of Alzheimer's disease

    OpenAIRE

    Woumans, Evy; Santens, Patrick; Sieben, Anne; Versijpt, Jan; Stevens, Michaël; Duyck, Wouter

    2015-01-01

    The current study investigated the effects of bilingualism on the clinical manifestation of Alzheimer's disease (AD) in a European sample of patients. We assessed all incoming AD patients in two university hospitals within a specified timeframe. Sixty-nine monolinguals and 65 bilinguals diagnosed with probable AD were compared for time of clinical AD manifestation and diagnosis. The influence of other potentially interacting variables was also examined. Results indicated a significant delay f...

  3. Cochleovestibular Manifestations in Fabry Disease

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    Alberto Ciceran MD

    2016-09-01

    Full Text Available Fabry disease is a rare, X-linked lysosomal storage disorder resulting from deficient α-galactosidase A activity and globotriaosylceramide accumulation throughout the body. This accumulation leads to various clinical disorders, including inner ear lesions, with sensorineural hearing loss and dizziness. Although hearing loss is recognized in these patients, its incidence and natural history have not been characterized. Hearing disorders develop mainly in adulthood, and tinnitus may be an earlier symptom in Fabry disease. A significant incidence of mid- and high-frequency sensorineural hearing loss in affected males is commonly reported, whereas in female carriers, it is much less frequent. In addition, a high incidence of vestibular disorders with dizziness and chronic instability is also observed in these patients. The few studies about the effects of enzyme replacement therapy (ERT on cochleovestibular symptoms show controversial results. Based on the model of densely stained material accumulation in the inner ear, stria vascularis cell, and organ damage, an early indication of ERT may prevent hearing loss due to the reduction in substrate accumulation.

  4. The chronic gastrointestinal manifestations of Chagas disease

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    Nilce Mitiko Matsuda

    2009-01-01

    Full Text Available Chagas disease is an infectious disease caused by the protozoan Trypanosoma cruzi. The disease mainly affects the nervous system, digestive system and heart. The objective of this review is to revise the literature and summarize the main chronic gastrointestinal manifestations of Chagas disease. The chronic gastrointestinal manifestations of Chagas disease are mainly a result of enteric nervous system impairment caused by T. cruzi infection. The anatomical locations most commonly described to be affected by Chagas disease are salivary glands, esophagus, lower esophageal sphincter, stomach, small intestine, colon, gallbladder and biliary tree. Chagas disease has also been studied in association with Helicobacter pylori infection, interstitial cells of Cajal and the incidence of gastrointestinal cancer.

  5. Articular manifestations in patients with Lyme disease.

    Science.gov (United States)

    Vázquez-López, María Esther; Díez-Morrondo, Carolina; Sánchez-Andrade, Amalia; Pego-Reigosa, Robustiano; Díaz, Pablo; Castro-Gago, Manuel

    To determine the percentage of Lyme patients with articular manifestations in NW Spain and to know their evolution and response to treatment. A retrospective study (2006-2013) was performed using medical histories of confirmed cases of Lyme disease showing articular manifestations. Clinical and laboratory characteristics, together with the treatment and evolution of the patients, were analysed. Seventeen out of 108 LD confirmed patients (15.7%) showed articular manifestations. Regarding those 17 patients, 64.7%, 29.4% and 5.9% presented arthritis, arthralgia and bursitis, respectively. The knee was the most affected joint. Articular manifestations were often associated to neurological, dermatological and cardiac pathologies. Otherwise, most patients were in Stage III. The 11.8% of the cases progressed to a recurrent chronic arthritis despite the administration of an appropriate treatment. Lyme disease patients showing articular manifestations should be included in the diagnosis of articular affections in areas of high risk of hard tick bite, in order to establish a suitable and early treatment and to avoid sequels. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  6. Mandibular and Dental Manifestations of Gaucher Disease

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    Saranjam, Hamid R.; Sidransky, Ellen; Levine, William Z.; Zimran, Ari; Elstein, Deborah

    2012-01-01

    Gaucher disease is a systemic lysosomal storage disorder with a high prevalence among Ashkenazi Jews. It is caused by an inherited deficiency of the lysosomal enzyme glucocerebrosidase. Common signs and symptoms include hepatosplenomegaly, anemia, thrombocytopenia, and skeletal involvement. Oral and dental manifestations are less commonly seen. These manifestations are often asymptomatic, although they may be detected by routine dental x-rays. There are several case reports and a few larger series published describing patients with Gaucher disease who have mandibulo-maxillofacial involvement. This review aims to examine the oral manifestations observed in Gaucher disease and to suggest practical guidelines for dealing with these often worrisome signs. Among the critical issues are the benign nature of Gaucher cell infiltration of the mandible and the critical importance of being prepared for post-procedure bleeding and/or infections. Therefore, it is essential that dental practitioners be aware of the possible oral and dental complications of Gaucher disease, as well as the available treatment modalities. PMID:22251146

  7. The radiological manifestations of sickle cell disease

    International Nuclear Information System (INIS)

    Madani, G.; Papadopoulou, A.M.; Holloway, B.; Robins, A.; Davis, J.; Murray, D.

    2007-01-01

    Sickle cell disease (SCD) is an inherited abnormality of the ss-globin chain, which causes a spectrum of haemolytic anaemias. Clinical manifestations in SCD include anaemia, jaundice, recurrent vaso-occlusive crises, and infections (particularly by encapsulated bacteria) due to functional asplenia and cerebrovascular accidents. Radiological investigations play a critical role both in the diagnosis and in the primary prevention of the complications of SCD

  8. The radiological manifestations of sickle cell disease

    Energy Technology Data Exchange (ETDEWEB)

    Madani, G. [Department of Radiology, Royal Free Hospital NHS Trust, London (United Kingdom)]. E-mail: gittamadani@yahoo.com; Papadopoulou, A.M. [Department of Radiology, Royal Free Hospital NHS Trust, London (United Kingdom); Holloway, B. [Department of Radiology, Royal Free Hospital NHS Trust, London (United Kingdom); Robins, A. [Department of Paediatrics, Whittington Hospital NHS Trust, London (United Kingdom); Davis, J. [Department of Radiology, Whittington Hospital NHS Trust, London (United Kingdom); Murray, D. [Department of Radiology, Whittington Hospital NHS Trust, London (United Kingdom)

    2007-06-15

    Sickle cell disease (SCD) is an inherited abnormality of the ss-globin chain, which causes a spectrum of haemolytic anaemias. Clinical manifestations in SCD include anaemia, jaundice, recurrent vaso-occlusive crises, and infections (particularly by encapsulated bacteria) due to functional asplenia and cerebrovascular accidents. Radiological investigations play a critical role both in the diagnosis and in the primary prevention of the complications of SCD.

  9. Ocular Manifestations of Mosquito-Transmitted Diseases.

    Science.gov (United States)

    Karesh, James W; Mazzoli, Robert A; Heintz, Shannon K

    2018-03-01

    Of the 3,548 known mosquito species, about 100 transmit human diseases. Mosquitoes are distributed globally throughout tropical and temperate regions where standing water sources are available for egg laying and the maturation of larva. Female mosquitoes require blood meals for egg production. This is the main pathway for disease transmission. Mosquitoes carry several pathogenic organisms responsible for significant ocular pathology and vision loss including West Nile, Rift Valley, chikungunya, dengue viruses, various encephalitis viruses, malarial parasites, Francisella tularensis, microfilarial parasites, including Dirofilaria, Wuchereria, and Brugia spp., and human botfly larvae. Health care providers may not be familiar with many of these mosquito-transmitted diseases or their associated ocular findings delaying diagnosis, treatment, and recovery of visual function. This article aims to provide an overview of the ocular manifestations associated with mosquito-transmitted diseases.

  10. Neurological manifestations of Batch s disease

    International Nuclear Information System (INIS)

    Borhani-Haghighi, Afshin; Ashjazadeh, Nahid; Nikseresht, Alireza; Shariat, Abdolhamid; Yousefipour, Gholamali; Samangooie, Shahdokht; Safari, Anahid

    2006-01-01

    To determine the prevalence, clinical manifestations, and laboratory features of Neuro-Behcets disease. This prospective study was carried out in the Behcets Research Clinic in Shiraz (south-west Iran) and included the patients referred from 1990-1999. The patients' clinical records, images, CSF analyses, and electrodiagnostic studies were reviewed. Eighteen (15 males and 3 females) out of 690 Behcet s patients (2.6%, 95% CI = 1.4-3.8%) were found to have neurological involvement. The mean +/- standard deviation age of these patients was 34.7 +/- 8.6 years. All fulfilled the criteria of the International Study Group of Behcet s Disease. Central nervous system involvement was more common than peripheral nervous system manifestations. Headache, weakness, tingling, and numbness were the most common symptoms. Hyperreflexia, upward plantar reflex, and somatosensory findings were the most frequent signs. Hemispheral and brainstem stroke-like syndromes and cerebral venous thrombosis were the major neurologic presentations. There were also cases of myelitic, pure meningoencephalitic, amyotrophic lateral sclerosis-like, multiple sclerosis-like, and Guillain Barre syndromes. Neuro-Behcets disease must be considered in the differential diagnosis of stroke in young adults, chronic meningitis, intracranial hypertension, multiple sclerosis, myelopathies, and peripheral neuropathies. (author)

  11. Crohn’s Disease Ocular Manifestations

    Directory of Open Access Journals (Sweden)

    Koev Kr.

    2014-12-01

    Full Text Available Crohn’s disease is an inflammatory bowel disease which causes inflammation of the digestive tract. Crohn’s disease most frequently affects the ileum and the colon. In the active stage of the disease signs and symptoms may include diarrhea, abdominal pain and cramping, blood in the stools, reduced appetite and weight loss. In patients with severe Crohn’s disease the following signs and symptoms may be observed: fever, fatigue, arthritis, eye inflammation, oral ulcers, skin disorders, inflammation of the liver or bile ducts or delayed growth. Heredity and dysfunctions of the immune system are considered to cause the development of Crohn’s disease. About 10% of people with inflammatory bowel disease have also ocular problems. The most common ocular manifestations of Crohn’s disease are uveitis, iritis, episcleritis, keratopathy, keratoconjunctivitis and retinal vasculitis. Untreated uveitis may cause glaucoma and vision loss. Uveitis and iritis are four times more common in women than in men. In patients in the active stage of the disease, episcleritis also flares. Symptoms of episcleritis include inflammation, bright red spots on the sclera and localized pain. Keratoconjunctivitis in Crohn’s disease is caused by decreased tear production or increased tear film evaporation. Dry eyes can cause itching, burning or infection. Keratopathy usually causes no pain or vision loss, therefore in most cases no treatment is needed. In retinal vasculitis tortuosity of retinal veins, retinal edema at the posterior pole and intraretinal blood near blood vessels are observed. Intravenous fluorescein angiography shows intraretinal neovascularisation and haemorrhage in the posterior pole.

  12. Skin manifestations of chronic kidney disease.

    Science.gov (United States)

    Robles-Mendez, J C; Vazquez-Martinez, O; Ocampo-Candiani, J

    2015-10-01

    Skin manifestations associated with chronic kidney disease are very common. Most of these conditions present in the end stages and may affect the patient's quality of life. Knowledge of these entities can contribute to establishing an accurate diagnosis and prognosis. Severe renal pruritus is associated with increased mortality and a poor prognosis. Nail exploration can provide clues about albumin and urea levels. Nephrogenic systemic fibrosis is a preventable disease associated with gadolinium contrast. Comorbidities, such as diabetes mellitus and secondary hyperparathyroidism, can lead to acquired perforating dermatosis and calciphylaxis, respectively. Effective and innovative treatments are available for all of these conditions. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

  13. Clinical manifestations and management of Gaucher disease.

    Science.gov (United States)

    Linari, Silvia; Castaman, Giancarlo

    2015-01-01

    Gaucher disease is a rare multi-systemic metabolic disorder caused by the inherited deficiency of the lysosomal enzyme β-glucocerebrosidase, which leads to the accumulation of its normal substrate, glucocerebroside, in tissue macrophages with damage to haematological, visceral and bone systems. Anaemia, thrombocytopenia, enlargement of liver and/or spleen, skeletal abnormalities (osteopenia, lytic lesions, pathological fractures, chronic bone pain, bone crisis, bone infarcts, osteonecrosis and skeletal deformities) are typical manifestations of the most prevalent form of the disease, the so-called non-neuronopathic type 1. However, severity and coexistence of different symptoms are highly variable. The determination of deficient β-glucocerebrosidase activity in leukocytes or fibroblasts by enzymatic assay is the gold standard for the diagnosis of Gaucher disease. Comprehensive and reproducible evaluation and monitoring of all clinically relevant aspects are fundamental for the effective management of Gaucher disease patients. Enzyme replacement therapy has been shown to be effective in reducing glucocerebroside storage burden and diminishing the deleterious effects caused by its accumulation. Tailored treatment plan for each patient should be directed to symptom relief, general improvement of quality of life, and prevention of irreversible damage.

  14. Corneal manifestations of selected systemic diseases: A review

    Directory of Open Access Journals (Sweden)

    Wayne D.H. Gillan

    2015-08-01

    Full Text Available The corneal manifestations of several selected systemic diseases are reviewed. Metabolic, immunologic and inflammatory and infectious diseases are included. A brief overview of each disease and how it manifests in the cornea is discussed. The importance of conducting a slit-lamp examination on every patient is emphasised.

  15. Metabolic and hormonal signatures in pre-manifest and manifest Huntington’s disease patients

    Directory of Open Access Journals (Sweden)

    Rui eWang

    2014-06-01

    Full Text Available Huntington's disease (HD is an inherited neurodegenerative disorder typified by involuntary body movements, and psychiatric and cognitive abnormalities. Many HD patients also exhibit metabolic changes including progressive weight loss and appetite dysfunction. Here we have investigated metabolic function in pre-manifest and manifest HD subjects to establish an HD subject metabolic hormonal plasma signature. Individuals at risk for HD who have had predictive genetic testing showing the cytosine-adenine-guanine (CAG expansion causative of HD, but who do not yet present signs and symptoms sufficient for the diagnosis of manifest HD are said to be pre-manifest. Pre-manifest and manifest HD patients, as well as both familial and non-familial controls, were evaluated for multiple peripheral metabolism signals including circulating levels of hormones, growth factors, lipids and cytokines. Both pre-manifest and manifest HD subjects exhibited significantly reduced levels of circulating growth factors, including growth hormone and prolactin. HD-related changes in the levels of metabolic hormones such as ghrelin, glucagon and amylin were also observed. Total cholesterol, HDL-C and LDL-C were significantly decreased in HD subjects. C-reactive protein was significantly elevated in pre-manifest HD subjects. The observation of metabolic alterations, even in subjects considered to be in the pre-manifest stage of HD, suggests that in addition, and prior, to overt neuronal damage, HD affects metabolic hormone secretion and energy regulation, which may shed light on pathogenesis, and provide opportunities for biomarker development.

  16. Dermatitis Herpetiformis: Skin Manifestation of Celiac Disease

    Science.gov (United States)

    ... Petronic-Rosic V. Dermatitis herpetiformis: part II. Diagnosis, management, and prognosis. Journal of the American Academy of Dermatology. 2011;64( ... 30 a.m. to 5 p.m. eastern time, M-F Follow Us NIH… Turning Discovery Into ... Disease Urologic Diseases Endocrine Diseases Diet & Nutrition ...

  17. Clinical manifestations of small vessel disease

    NARCIS (Netherlands)

    Kooistra, M.

    2014-01-01

    Cardiovascular disease is a major health problem worldwide. However, the mortality risk in patients with cardiovascular disease has decreased due to early detection of the disease and improved treatment possibilities. The downside of increased survival rates are higher rates of long-term functional

  18. Lung Manifestations in the Rheumatic Diseases.

    Science.gov (United States)

    Doyle, Tracy J; Dellaripa, Paul F

    2017-12-01

    Lung ailments in rheumatic diseases present unique challenges for diagnosis and management and are a source of significant morbidity and mortality for patients. Unlike the idiopathic interstitial pneumonias, patients with rheumatic diseases experience lung disease in the context of a systemic disease that may make it more difficult to recognize and that may present greater risks with treatment. Despite recent advances in our awareness of these diseases, there is still a significant lack of understanding of natural history to elucidate which patients will have disease that is progressive and thus warrants treatment. What we do know is that a subset of patients with rheumatic disease experience parenchymal lung disease that can prognostically resemble idiopathic pulmonary fibrosis, such as in rheumatoid arthritis, and that others can have aggressive inflammatory lung disease in the context of autoimmune myositis, systemic sclerosis, or an undifferentiated autoimmune process. As we enter into a paradigm shift where we view lung health as a cornerstone of our care of patients with rheumatic diseases, we hopefully will improve our ability to identify those patients at highest risk for pulmonary disease and progression, and offer emerging treatments which will result in better outcomes and a better quality of life. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  19. Clinical Manifestations and Treatment of Lyme Disease.

    Science.gov (United States)

    Sanchez, Joyce L

    2015-12-01

    Lyme disease is the most common tick-borne illness in the United States and is also seen in areas of Europe and Asia. The growing deer and Ixodes species tick populations in many areas underscore the importance of clinicians to properly recognize and treat the different stages of Lyme disease. Controversy regarding the cause and management of persistent symptoms following treatment of Lyme disease persists and is highlighted in this review. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Imaging findings in systemic childhood diseases presenting with dermatologic manifestations.

    Science.gov (United States)

    Fink, Adam Z; Gittler, Julia K; Nakrani, Radhika N; Alis, Jonathan; Blumfield, Einat; Levin, Terry L

    Many childhood diseases often present with skin abnormalities with which radiologists are largely unfamiliar. Knowledge of associated dermatologic manifestations may aid the radiologist in confirming the diagnosis and recommending targeted imaging of affected organs. We review the imaging findings in childhood diseases associated with dermatologic manifestations. Diseases include dermatologic findings which herald underlying malignancy (Neuroblastoma, leukemia/lymphoma, Langerhans cell histiocytosis),are associated with risk of malignancy (Epidermolysis Bullosa, basal cell nevus syndrome, Cowden's syndrome, Tuberous Sclerosis),or indicate a systemic inflammatory/immune disorder (Kawasaki's disease, Henoch Schonlein Purpura, systemic lupus erythematosus, scleroderma, sarcoidosis, dermatomyositis and immune thrombocytopenic purpura). Familiarity with pertinent findings in childhood diseases presenting with dermatologic manifestations in childhood diseases aids the radiologist in confirming the diagnosis and guiding imaging workup. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Computed tomography manifestations of peritoneal diseases

    International Nuclear Information System (INIS)

    Gordon, K.; Lee, W.K.; Hennessy, O.

    2005-01-01

    The peritoneal cavity is a potential space that is divided by the peritoneal reflections into various complex subspaces. It can be involved in many disease processes including developmental, inflammatory, neoplastic and traumatic conditions. Computed tomography is highly sensitive and consistent in detecting peritoneal pathology. This pictorial essay aims to emphasize and illustrate the CT features of the spectrum of peritoneal diseases. Copyright (2005) Blackwell Science Pty Ltd

  2. Visual system manifestations of Alzheimer's disease.

    Science.gov (United States)

    Kusne, Yael; Wolf, Andrew B; Townley, Kate; Conway, Mandi; Peyman, Gholam A

    2017-12-01

    Alzheimer's disease (AD) is an increasingly common disease with massive personal and economic costs. While it has long been known that AD impacts the visual system, there has recently been an increased focus on understanding both pathophysiological mechanisms that may be shared between the eye and brain and how related biomarkers could be useful for AD diagnosis. Here, were review pertinent cellular and molecular mechanisms of AD pathophysiology, the presence of AD pathology in the visual system, associated functional changes, and potential development of diagnostic tools based on the visual system. Additionally, we discuss links between AD and visual disorders, including possible pathophysiological mechanisms and their relevance for improving our understanding of AD. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  3. Type gaucher disease: radiographic and MRI manifestations

    International Nuclear Information System (INIS)

    Dong Yanqing; Li Kuncheng; Wang Yunzhao; Tian Ding

    1999-01-01

    Objective: To enhance the understanding of Gaucher disease (GD) type I bone involvement on imaging findings. Methods: The X-ray plain film and MRI findings of GD type I were reported, and literature reviewed. Results: The X-ray plain film of GD had characteristic change. The extent of bone involvement demonstrated could be depicted in longitudinal direction and the changes of marrow involvement on MRI. Conclusions: MRI is the best way to diagnose the bone involvement of GD

  4. Graves' disease. Manifestations and therapeutic options

    International Nuclear Information System (INIS)

    McFarland, K.F.; Saleeby, G.

    1988-01-01

    Graves' disease is the most common cause of hyperthyroidism. Clinical features include thyroid enlargement, eye signs, tachycardia, heat intolerance, emotional lability, weight loss, and hyperkinesis. Three modes of therapy are available. The preferences of the patient and physician are usually prime considerations in devising the therapeutic plan. Radioactive iodine is the most frequently used and safest method of treatment for adults. Antithyroid drugs are preferred for children and pregnant women. Surgery is usually reserved for patients in whom the other forms of treatment are not acceptable. Considerable patient education during the decision-making process enhances the success of the therapeutic plan

  5. The Spectrum of Neurological Manifestations Associated with Gaucher Disease

    Directory of Open Access Journals (Sweden)

    Tamanna Roshan Lal

    2017-03-01

    Full Text Available Gaucher disease, the most common lysosomal storage disorder, is due to a deficiency in the enzyme glucocerebrosidase. This leads to the accumulation of its normal substrate, glucocerebroside, in tissue macrophages, affecting the hematological, visceral, bone and neurologic systems. Gaucher disease is classified into three broad phenotypes based upon the presence or absence of neurological involvement: type 1 (non-neuronopathic, type 2 (acute neuronopathic, and type 3 (subacute neuronopathic. Phenotypically, there is a wide spectrum of visceral and neurological manifestations. Enzyme replacement is effective in managing the visceral disease; however, treating the neurological manifestations has proved to be more challenging. This review discusses the various neurological manifestations encountered in Gaucher disease, and provides a brief overview regarding the treatment and ongoing research challenges.

  6. Case report of Graves’ disease manifesting with odynophagia and heartburn

    Science.gov (United States)

    Evsyutina, Yulia; Trukhmanov, Alexander; Ivashkin, Vladimir; Storonova, Olga; Godjello, Elina

    2015-01-01

    Graves’ disease is an autoimmune disease, which can manifest with a variety of extrathyroidal clinical syndromes like ophthalmopathy, pretibial myxedema (dermopathy), acropathy, cardiomyopathy, and encephalopathy. Though quite rare, this disease can also manifest with gastrointestinal symptoms such as dysphagia, heartburn, nausea, vomiting and diarrhea. We report a clinical case of Graves’ disease manifesting with dysfunction of the esophagus and heartburn in a 61-year-old man. In the muscular layer of the esophagus we found dystrophic changes led to its atony, which was documented by endoscopy and high-resolution manometry. The pathology features of esophageal symptoms were: focal proliferation of the basal cells, vascular distension, and dystrophy of the epithelial cells. Antithyroid treatment led to decrease of all clinical symptoms after 5 d of Thiamazole administration. Complete restoration of peristalsis in the esophagus, according to manometry, was observed in 1 mo after initiation of treatment. PMID:26730171

  7. Case report of Graves' disease manifesting with odynophagia and heartburn.

    Science.gov (United States)

    Evsyutina, Yulia; Trukhmanov, Alexander; Ivashkin, Vladimir; Storonova, Olga; Godjello, Elina

    2015-12-28

    Graves' disease is an autoimmune disease, which can manifest with a variety of extrathyroidal clinical syndromes like ophthalmopathy, pretibial myxedema (dermopathy), acropathy, cardiomyopathy, and encephalopathy. Though quite rare, this disease can also manifest with gastrointestinal symptoms such as dysphagia, heartburn, nausea, vomiting and diarrhea. We report a clinical case of Graves' disease manifesting with dysfunction of the esophagus and heartburn in a 61-year-old man. In the muscular layer of the esophagus we found dystrophic changes led to its atony, which was documented by endoscopy and high-resolution manometry. The pathology features of esophageal symptoms were: focal proliferation of the basal cells, vascular distension, and dystrophy of the epithelial cells. Antithyroid treatment led to decrease of all clinical symptoms after 5 d of Thiamazole administration. Complete restoration of peristalsis in the esophagus, according to manometry, was observed in 1 mo after initiation of treatment.

  8. [Otorhinolaryngological manifestations in patients with Behçet disease].

    Science.gov (United States)

    Morales-Angulo, Carmelo; Vergara Pastrana, Sandra; Obeso-Agüera, Sergio; Acle, Leticia; González-Gay, Miguel Ángel

    2014-01-01

    Behçet disease (BD) is a systemic immune-mediated vasculitis of unknown origin characterised by recurrent orogenital ulceration, ocular inflammation and skin lesions. The aim of our study was to identify ear, nose and throat (ENT) manifestations associated with BD. Retrospective review of the medical records of all patients diagnosed with BD who attended a tertiary public hospital in Cantabria (Spain) over a period of 22 years. Clinical manifestations, in particular those concerning ENT, were retrieved from medical records. A medical literature review of ENT manifestations was conducted. Thirty-three patients (age range: 17-64 years) were included in the study. Most of them presented oral ulcers (97%). Eight patients (24%) presented oropharyngeal ulcers and 5 patients (15%) experienced audiovestibular symptoms (high frequency sensorineural hearing loss, vertigo and bilateral vestibular hypofunction). One patient had symptoms compatible with vestibular neuronitis as the presentation manifestation of Neuro-Behçet. In 4 patients (12%) the presence of odynophagia secondary to the presence of oropharyngeal lesions, initially interpreted as acute or recurrent tonsillitis, was the first manifestation of the disease, alone or associated with cutaneous or ocular lesions. In addition to the characteristic oral ulcers present in most patients with BD, ulcers in the oropharynx, occasionally interpreted as acute pharyngitis, are also common in these patients. Audiovestibular manifestations frequently appear during the course of the disease and may be the first symptom of central nervous system involvement. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  9. Radiologic manifestations of Hippel-Lindau disease

    International Nuclear Information System (INIS)

    Ziemianski, A.; Pecold, K.; Sosnowski, P.; Paprzycki, W.; Juszkat, R.

    1994-01-01

    Examinations have been performed in 15 patients from 5 families. CT of abdomen as well as MR of eyeballs and of the subtentorial part of the central nervous system were performed. Three patients who exhibited changes in MR and 2 patients who showed changes in CT underwent additional examinations with contrast media. In MR the most frequently observed changes have been found in eyeballs, in cerebellum and spinal cord. In CT kidney changes and pancreas changes were most frequently observed. In 2 patients neither CT nor MR changes have been found. It is believed that appropriate diagnostic procedure in Hippel-Lindau disease should include MR examination of the central nervous system, and CT examination of abdomen. Both examinations should be performed with contrast enhancement. (author)

  10. Extrahepatic manifestations of cholestatic liver diseases: pathogenesis and therapy

    NARCIS (Netherlands)

    Pusl, Thomas; Beuers, Ulrich

    2005-01-01

    Pruritus, fatigue, and metabolic bone disease are frequent complications of cholestatic liver diseases, which can be quite distressing for the patient and can considerably reduce the quality of life. The molecular pathogenesis of these extrahepatic manifestations of cholestasis is poorly understood,

  11. Calcium pyrophosphate deposition disease: clinical manifestations

    Directory of Open Access Journals (Sweden)

    M.A. Cimmino

    2012-01-01

    Full Text Available Calcium pyrophosphate deposition (CPPD disease is an arthropathy caused by calcium pyrophosphate dihydrate (CPP crystal deposits in articular tissues, most commonly fibrocartilage and hyaline cartilage. According to EULAR, four different clinical presentations can be observed: 1 asymptomatic CPPD; 2 osteoarthritis (OA with CPPD; 3 acute CPP crystal arthritis; 4 chronic CPP inflammatory crystal arthritis. Acute CPP crystal arthritis is characterized by sudden onset of pain, swelling and tenderness with overlying erythema, usually in a large joint, most often the knee, wrist, shoulder, and hip. Occasionally, ligaments, tendons, bursae, bone and the spine can be involved. CPPD of the atlanto-occipital joint (crowned dens syndrome can cause periodic acute cervico-occipital pain with fever, neck stiffness and laboratory inflammatory syndrome. Chronic inflammatory arthritis is characterized by joint swelling, morning stiffness, pain, and high ESR and CRP. The relationship between OA and CPPD is still unclear. The main problem is whether such crystals are directly involved in the pathogenesis of OA or if they are the result of joint degeneration. Diagnosis is based on evaluation of history and clinical features, conventional radiology, and synovial fluid examination. Non-polarized light microscopy should be used initially to screen for CPPD crystals based upon their characteristic morphology, and compensated polarized light microscopy, showing the crystals to be weakly positive birefringent, is recommended for definitive identification, although this last pattern only occurs in about 20% of samples. The main goals of CPPD therapy are control of the acute or chronic inflammatory reaction and prevention of further episodes.

  12. Emerging infectious diseases with cutaneous manifestations: Viral and bacterial infections.

    Science.gov (United States)

    Nawas, Zeena Y; Tong, Yun; Kollipara, Ramya; Peranteau, Andrew J; Woc-Colburn, Laila; Yan, Albert C; Lupi, Omar; Tyring, Stephen K

    2016-07-01

    Given increased international travel, immigration, and climate change, bacterial and viral infections that were once unrecognized or uncommon are being seen more frequently in the Western Hemisphere. A delay in diagnosis and treatment of these diseases can lead to significant patient morbidity and mortality. However, the diagnosis and management of these infections is fraught with a lack of consistency because there is a dearth of dermatology literature on the cutaneous manifestations of these infections. We review the epidemiology, cutaneous manifestations, diagnosis, and management of these emerging bacterial and viral diseases. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  13. Extra-cardiac manifestations of adult congenital heart disease.

    Science.gov (United States)

    Gaeta, Stephen A; Ward, Cary; Krasuski, Richard A

    2016-10-01

    Advancement in correction or palliation of congenital cardiac lesions has greatly improved the lifespan of congenital heart disease patients, resulting in a rapidly growing adult congenital heart disease (ACHD) population. As this group has increased in number and age, emerging science has highlighted the systemic nature of ACHD. Providers caring for these patients are tasked with long-term management of multiple neurologic, pulmonary, hepatic, renal, and endocrine manifestations that arise as syndromic associations with congenital heart defects or as sequelae of primary structural or hemodynamic abnormalities. In this review, we outline the current understanding and recent research into these extra-cardiac manifestations. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. [Anorectal manifestations of sexually transmissible diseases. Kaposi's sarcoma].

    Science.gov (United States)

    Libeskind, M; Malbran, J; Agard, D; Pannetier, C; Lecouillard, C; Ivanovic, A

    1984-01-01

    The proctologist is above all concerned with the known recrudescence of venereal diseases. Examples reviewed are diseases of bacterial origin (syphilis, gonorrhea, soft chancre, donovanosis and chlamydiosis), appropriate antibiotic therapy and diseases of viral origin (herpes, condyloma acuminatum). Also noted are other bacterial, viral and parasitic diseases and, indeed, cancers of which Kaposi's sarcoma is the example, even though these are not manifested anorectally. New data on Kaposi's sarcoma, its' relationships with venereal disease and AIDS are presented. With these complex problems, the central role of male homosexuality and lowered cellular immunity widens considerably the professional scope of the proctologist.

  15. COPD is a systemic disease – the ex trapulmonary manifestations ...

    African Journals Online (AJOL)

    COPD is a systemic disease – the ex trapulmonary manifestations. C Smith. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's ...

  16. Very early disease manifestations of macular telangiectasia type 2

    NARCIS (Netherlands)

    Issa, P.C.; Heeren, T.F.C.; Kupitz, E.H.; Holz, F.G.; Berendschot, T.T.J.M.

    Background: To report very early morphologic and functional alterations in patients with macular telangiectasia type 2. Methods: Patients with asymmetric disease manifestations, in whom retinal alterations characteristic for macular telangiectasia type 2 were present in one but not in the apparently

  17. Hematologic manifestations of Crohn's disease: two clinical cases

    Directory of Open Access Journals (Sweden)

    O. V. Taratina

    2017-01-01

    Full Text Available Inflammatory bowel diseases (IBD are commonly associated with extraintestinal manifestations, hematological disorders being the most special among them. In some cases, they dominate the clinical picture masking the intestinal manifestations of the underlying disease. Aplastic anemia is an extremely rare extraintestinal IBD manifestation. There are only two clinical cases of aplastic anemia associated with ulcerative colitis and non with Crohn's disease reported in the literature. Combination of Crohn's disease and В₁₂-deficient anemia is more prevalent, but is seen usually only after more than 20 cm of the ileus has been resected. The first clinical case presented in this paper is a  combination of severe fistula-forming Crohn's disease with a constriction in the terminal part of the ileus and profound pancytopenia as an outcome of aplastic anemia. This profound pancytopenia is associated with an extremely high risk of life-threatening complications both of surgical treatment, as well as of several chemotherapeutic agents, which made the management of this patient difficult. The second clinical case demonstrates the manifestation of Crohn's disease as ileocolitis starting from the symptoms of cobalamin deficiency: severe В₁₂-deficient anemia, funicular myelosis and sensory ataxia, with blunted intestinal symptoms. This made the initial diagnosis and timely treatment difficult. Replacement therapy with cobalamin injections and treatment with glucocorticoids and antibacterials led to endoscopically confirmed remission of Crohn's disease and normalization of hematological parameters, with persistent polyneuropathy. Thus, management of patients with Crohn's disease should be multidisciplinary. In the case of anemia, leucopenia and/or thrombocytopenia in IBD patients it is necessary to exclude potential myelodysplasia and bone marrow aplasia. In the event of megaloblastic anemia and/or progressive polyneuropathy one should bear in mind

  18. Ocular manifestations of Gaucher disease: case report and literature review

    Directory of Open Access Journals (Sweden)

    Mejía-Turizo, Juan Carlos

    2017-07-01

    Full Text Available We report the case of a patient with Gaucher disease (GD type 3b, with a homozygous GBA gene mutation (c.1448T > C p.L483P (L444P. Ocular findings characteristic of this mutation are described, including vitreous condensation and macular edema. To our knowledge this is the first case reported in Colombia with these characteristics. A review of the ocular manifestations of this disease is also presented.

  19. Extraintestinal manifestations in Crohn's disease and ulcerative colitis

    DEFF Research Database (Denmark)

    Isene, Rune; Bernklev, Tomm; Høie, Ole

    2015-01-01

    BACKGROUND: In chronic inflammatory bowel disease (IBD) (Crohn's disease [CD] and ulcerative colitis [UC]), symptoms from outside the gastrointestinal tract are frequently seen, and the joints, skin, eyes, and hepatobiliary area are the most usually affected sites (called extraintestinal......, skin, and liver) manifestations: 20.1% versus 10.4% (p colitis compared to proctitis in UC increased the risk of EIM. CONCLUSION: In a European inception cohort, EIMs in IBD...

  20. Imaging Manifestations in Systemic Cat Scratch Disease: Case report

    International Nuclear Information System (INIS)

    Forero M, Julian F; Perez A, Maria C; Cerquera C, Fredy M

    2011-01-01

    Cat scratch disease is a zoonosis caused by Bartonella henselae, which is transmitted by scratches, bites or exposition to cats saliva (1). The disease typically manifests with local lymphadenitis after bacterial inoculation in the skin, however, there is an atypical systemic presentation in 5 to 10% of patients, which causes unspecific symptoms. There are several imaging findings that lead the radiologist to consider this diagnosis, in order to prevent an invasive procedure, especially if we consider that the majority of cases occur in the pediatric population (2,3). Although in the majority of cases the symptoms and imaging findings resolve spontaneously, there are specific indications like the systemic form of the disease,which requires antibiotic treatment. In the present article we are exposing a case report from Fundacion Cardioinfantil; we will review some epidemiologic aspects, clinical manifestations, diagnostic methods as well as imaging findings in Ultrasonography, Computed Tomography, Magnetic Resonance and Nuclear Medicine.

  1. Imaging Manifestations in Systemic Cat Scratch Disease: Case report

    International Nuclear Information System (INIS)

    Forero Melo, Julian Francisco; Perez Alvarado, Maria Carolina; Cerquera Cabrera, Fredy Martin

    2011-01-01

    Cat scratch disease is a zoonosis caused by Bartonella henselae, which is transmitted by scratches, bites or exposition to cats saliva (1). The disease typically manifests with local lymphadenitis after bacterial inoculation in the skin, however, there is an atypical systemic presentation in 5 to 10% of patients, which causes unspecific symptoms. There are several imaging findings that lead the radiologist to consider this diagnosis, in order to prevent an invasive procedure, especially if we consider that the majority of cases occur in the pediatric population (2,3). Although in the majority of cases the symptoms and imaging findings resolve spontaneously, there are specific indications like the systemic form of the disease, which requires antibiotic treatment. In the present article we are exposing a case report from Fundacion Cardio infantil; we will review some epidemiologic aspects, clinical manifestations, diagnostic methods as well as imaging findings in Ultrasonography, Computed Tomography, Magnetic Resonance and Nuclear Medicine.

  2. Extraintestinal manifestations of inflammatory bowel disease: epidemiology, diagnosis, and management

    DEFF Research Database (Denmark)

    Larsen, Signe; Bendtzen, Klaus; Nielsen, Ole Haagen

    2010-01-01

    Abstract Extraintestinal manifestations occur rather frequently in inflammatory bowel disease (IBD), e.g. ulcerative colitis (UC) and Crohn's disease (CD). The present paper provides an overview of the epidemiology, clinical characteristics, diagnostic process, and management of rheumatic......, metabolic, dermatologic (mucocutaneous), ophthalmologic, hepatobiliary, hematologic, thromboembolic, urinary tract, pulmonary, and pancreatic extraintestinal manifestations related to IBD. Articles were identified through search of the PubMed and Embase databases, the Cochrane Library, and the web sites......', 'thromboembolism', and 'treatment'. The search was performed on English-language reviews, practical guidelines, letters, and editorials. Articles were selected based on their relevance, and additional papers were retrieved from their reference lists. Since some of the diseases discussed are uncommon, valid...

  3. Systemic disease manifestations associated with epilepsy in tuberous sclerosis complex.

    Science.gov (United States)

    Jeong, Anna; Wong, Michael

    2016-09-01

    Epilepsy is one of the most disabling symptoms of tuberous sclerosis complex (TSC) and is a leading cause of morbidity and mortality in affected individuals. The relationship between systemic disease manifestations and the presence of epilepsy has not been thoroughly investigated. This study utilizes a multicenter TSC Natural History Database including 1,816 individuals to test the hypothesis that systemic disease manifestations of TSC are associated with epilepsy. Univariate analysis was used to identify patient characteristics (e.g., age, gender, race, and TSC mutation status) associated with the presence of epilepsy. Individual logistic regression models were built to examine the association between epilepsy and each candidate systemic or neurologic disease variable, controlling for the patient characteristics found to be significant on univariate analysis. Finally, a multivariable logistic regression model was constructed, using the variables found to be significant on the individual analyses as well as the patient characteristics that were significant on univariate analysis. Nearly 88% of our cohort had a history of epilepsy. After adjusting for age, gender, and TSC mutation status, multiple systemic disease manifestations including cardiac rhabdomyomas (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.3-3.9, p = 0.002), retinal hamartomas (OR 2.1, CI 1.0-4.3, p = 0.04), renal cysts (OR 2.1, CI 1.3-3.4, p = 0.002), renal angiomyolipomas (OR 3.0, CI 1.8-5.1, p epilepsy. In the multivariable logistic regression model, cardiac rhabdomyomas (OR 1.9, CI 1.0-3.5, p = 0.04) remained significantly associated with the presence of epilepsy. The identification of systemic disease manifestations such as cardiac rhabdomyomas that confer a higher risk of epilepsy development in TSC could contribute to disease prognostication and assist in the identification of individuals who may receive maximal benefit from potentially novel, targeted, preventative therapies. Wiley

  4. Atypical Clinical Manifestations of Graves' Disease: An Analysis in Depth

    Science.gov (United States)

    Hegazi, Mohamed Osama; Ahmed, Sherif

    2012-01-01

    Over the past few decades, there has been an increase in the number of reports about newly recognized (atypical or unusual) manifestations of Graves' disease (GD), that are related to various body systems. One of these manifestations is sometimes the main presenting feature of GD. Some of the atypical manifestations are specifically related to GD, while others are also similarly seen in patients with other forms of hyperthyroidism. Lack of knowledge of the association between these findings and GD may lead to delay in diagnosis, misdiagnosis, or unnecessary investigations. The atypical clinical presentations of GD include anemia, vomiting, jaundice, and right heart failure. There is one type of anemia that is not explained by any of the known etiological factors and responds well to hyperthyroidism treatment. This type of anemia resembles anemia of chronic disease and may be termed GD anemia. Other forms of anemia that are associated with GD include pernicious anemia, iron deficiency anemia of celiac disease, and autoimmune hemolytic anemia. Vomiting has been reported as a presenting feature of Graves' disease. Some cases had the typical findings of hyperthyroidism initially masked, and the vomiting did not improve until hyperthyroidism has been detected and treated. Hyperthyroidism may present with jaundice, and on the other hand, deep jaundice may develop with the onset of overt hyperthyroidism in previously compensated chronic liver disease patients. Pulmonary hypertension is reported to be associated with GD and to respond to its treatment. GD-related pulmonary hypertension may be so severe to produce isolated right-sided heart failure that is occasionally found as the presenting manifestation of GD. PMID:22132347

  5. Oral manifestations of connective tissue disease and novel therapeutic approaches.

    Science.gov (United States)

    Heath, Kenisha R; Rogers, Roy S; Fazel, Nasim

    2015-10-16

    Connective tissue diseases such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and Sjögren syndrome (SS) have presented many difficulties both in their diagnosis and treatment. Known causes for this difficulty include uncertainty of disease etiology, the multitude of clinical presentations, the unpredictable disease course, and the variable cell types, soluble mediators, and tissue factors that are believed to play a role in the pathogenesis of connective tissue diseases. The characteristic oral findings seen with these specific connective tissue diseases may assist with more swift diagnostic capability. Additionally, the recent use of biologics may redefine the success rate in the treatment and management of the disease. In this review we describe the oral manifestations associated with SLE, SSc, and SS and review the novel biologic drugs used to treat these conditions.

  6. Peripheral Nervous System Manifestations in Systemic Autoimmune Diseases

    OpenAIRE

    COJOCARU, Inimioara Mihaela; COJOCARU, Manole; SILOSI, Isabela; VRABIE, Camelia Doina

    2014-01-01

    The peripheral nervous system refers to parts of the nervous system outside the brain and spinal cord. Systemic autoimmune diseases can affect both the central and peripheral nervous systems in a myriad of ways and through a heterogeneous number of mechanisms leading to many different clinical manifestations. As a result, neurological complications of these disorders can result in significant morbidity and mortality. The most common complication of peripheral nervous system (PNS) involvement ...

  7. Syphilitic hepatitis: An uncommon manifestation of a common disease

    Directory of Open Access Journals (Sweden)

    Sukriti Baveja

    2014-01-01

    Full Text Available Hepatitis being first manifestation of secondary syphilis is rare. Here in we report a case of 39 years old male who was being treated for hepatitis and presented to us subsequently with itchy maculopapular rash. Venereal disease research laboratory (VDRL titre was 1:16. Treponema pallidum hemagglutination assay (TPHA was positive. He was treated with intramuscular Benzathine Penicillin. His hepatitis improved rapidly.

  8. Norrie disease: extraocular clinical manifestations in 56 patients.

    Science.gov (United States)

    Smith, Sharon E; Mullen, Thomas E; Graham, Dionne; Sims, Katherine B; Rehm, Heidi L

    2012-08-01

    Norrie disease (ND) is an X-linked recessive disorder characterized by congenital blindness, progressive sensorineural hearing loss and cognitive impairment. The ocular phenotype has been well described, while the extraocular manifestations of the disorder are not well understood. We present the data from the Norrie Disease Registry, which consists of 56 patients with detailed clinical histories and genotype data. This study represents the largest, detailed investigation into the phenotypic spectrum of ND to date and more importantly expands knowledge of the extraocular clinical manifestations. We identify several novel aspects of the syndrome that will improve the management of these patients. In particular, we expand our understanding of the neurologic manifestations in ND and identify a chronic seizure disorder in approximately 10% of all patients. In addition, details of the hearing phenotype are described including the median age of onset (12 years of age) and how genotype affects onset. Moreover, we find vascular disease to be a significant component of ND; and vascular health should be, in the future, a component of patient clinical care. In summary, the results expand our understanding of the phenotypic variability and genotypic heterogeneity in ND patients. Copyright © 2012 Wiley Periodicals, Inc.

  9. Oral Crohn′s disease without intestinal manifestations

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    Gingisetty Harikishan

    2012-01-01

    Full Text Available Crohn′s disease is a granulomatous inflammatory bowel disease and was described in 1932 as a chronic granulomatous disorder of the terminal ileum and is now considered a distinct member of the inflammatory bowel disease family. It may affect any part of the gastrointestinal tract. Oral Crohn′s disease has been reported frequently in the last three decades with or without intestinal manifestations. In the latter case, it is considered as one of the orofacial granulomatosis. There has been much doubt whether intestinal manifestations of Crohn′s disease will eventually develop in the orofacial granulomatosis. We present a female patient aged 22 years with prominent clinical findings such as persistent swelling of lower and upper lip with fissuring and angular cheilitis, granulomatous gingival enlargement, and cobblestone or corrugated appearance of labial mucosa, which are suggestive of Crohn′s disease, but with no evidence of other gastrointestinal involvement. The patient underwent surgical treatment with external gingivectomy procedure. A 6-month follow-up showed minimal recurrence.

  10. Skeletal Manifestations in Gaucher Disease: A Case Report

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    Altınay Göksel Karatepe

    2005-09-01

    Full Text Available Gauchers disease is the most frequent hereditary lysosomal deposit storage disorder. It is characterized by a deficiency of the enzyme glucocerebrosidase that leads to an accumulation of glucocerebroside in the macrophage lysosomes. It is classified in three types, according to the presence of central nervous system involvement (type 2 and 3 or not (type 1. In the majority of patients there are hepatosplenomegaly, anemia and thrombocytopenia. Skeletal involvement is also important and it is the most disabling manifestation. In this case report, there is presented a case of Gauchers disease with multiple skeletal involvement and the literature is reviewed.

  11. Texas Occurrence of Lyme Disease and Its Neurological Manifestations.

    Science.gov (United States)

    Dandashi, Jad A; Nizamutdinov, Damir; Dayawansa, Samantha; Fonkem, Ekokobe; Huang, Jason H

    2016-06-01

    Today, Lyme disease is the most commonly reported tick-borne disease in the United States and Europe. The culprits behind Lyme disease are the Borrelia species of bacteria. In the USA, Borrelia burgdorferi causes the majority of cases, while in Europe and Asia Borrelia afzelii and Borrelia garinii carry the greatest burden of disease. The clinical manifestations of Lyme disease have been identified as early localized, early disseminated, and late chronic. The neurological effects of Lyme disease include both peripheral and central nervous systems involvement, including focal nerve abnormalities, cranial neuropathies, painful radiculoneuritis, meningitis, and/or toxic metabolic encephalopathy, known as Lyme encephalopathy. Given the geographic predominance of Lyme disease in the Northeast and Midwest of the USA, no major studies have been conducted regarding Southern states. Between 2005 and 2014, the Center for Disease Control has reported 582 confirmed cases of Lyme disease in Texas. Because of the potential for increased incidence and prevalence in Texas, it has become essential for research and clinical efforts to be diverted to the region. The Texas A&M College of Veterinary Medicine and Biomedical Sciences Lyme Lab has been investigating the ecology of Lyme disease in Texas and developing a pan-specific serological test for Lyme diagnosis. This report aimed to exposure materials and raise awareness of Lyme disease to healthcare providers.

  12. MRI manifestation of Wilson's disease accompanied with central pontine myelinolysis

    International Nuclear Information System (INIS)

    Zhang Jingsong; Huan Yi; Chang Yingjuan; Chang Yingjuan; Ge Yali; Zhang Guangyun; Han Yuedong; Zhao Haitao; Yang Chunmin; Yang Yan

    2004-01-01

    Objective: To discuss MRI manifestation of Wilson's disease accompanied with central pontine myelinolysis (CPM), and to especially detect the value of diffusion-weighted MRI (DWI) in this disease. Methods: Two cases of Wilson's disease accompanied with CPM were performed with sequent MR examination including T 1 WI, T 2 WI, FLAIR, DWI, and contrast-enhanced MRI (CE MRI) by a 1.5 T magnetic resonance system (Philips gyroscan master). Results: Symmetric long T 1 and T 2 signals were found in central pontine region, lenticular nucleus, caudate nucleus, and thalamus. CEMRI showed no apparent enhanced lesions. DWI showed obviously high signal intensities in central pontine region with apparent diffusion coefficient values fluctuated between (100-300) x 10 -6 mm 2 /s while FLAIR images just showed slightly high signal in the same area, which suggested that cytotoxic edema did in fact exist in CPM. Meanwhile, DWI also showed high signals in bilateral lenticular nucleus with apparent diffusion coefficient values fluctuated between (300-600) x 10 -6 mm 2 /s, however, FLAIR images showed heterogeneous high signals and one case presented low DWI signals in bilateral head of caudate nucleus, all these signs might be explained by mixed-changes of cytotoxic edema and vasogenic edema in long period of Wilson's disease. Conclusion: Wilson's disease and CPM have characteristic MRI manifestation and DWI may be a very useful way to confirm a correct diagnosis. (authors)

  13. Structural imaging in premanifest and manifest Huntington disease.

    Science.gov (United States)

    Scahill, Rachael I; Andre, Ralph; Tabrizi, Sarah J; Aylward, Elizabeth H

    2017-01-01

    Huntington disease (HD) neuropathology has a devastating effect on brain structure and consequently brain function; neuroimaging provides a means to assess these effects in gene carriers. In this chapter we first outline the unique utility of structural imaging in understanding HD and discuss some of the acquisition and analysis techniques currently available. We review the existing literature to summarize what we know so far about structural brain changes across the spectrum of disease from premanifest through to manifest disease. We then consider how these neuroimaging findings relate to patient function and nonimaging biomarkers, and can be used to predict disease onset. Finally we review the utility of imaging measures for assessment of treatment efficacy in clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Medical management of motor manifestations of Huntington disease.

    Science.gov (United States)

    McCusker, Elizabeth A; Loy, Clement T

    2017-01-01

    The motor and movement disorders of Huntington disease (HD) are managed in the context of the other disease features. Chorea and dystonia are the most common HD-associated movement disorders, and they can be assessed on research rating scales. However other motor manifestations have a significant impact. In particular, dysphagia influences choice and tolerance of treatment for the movement disorder, as will comorbidities, patient awareness, and distress related to the motor feature or movement. Treatment for other disease features may aggravate the motor disorder, e.g., increased swallowing difficulty associated with antipsychotic agents. Basic principles in deciding to institute a treatment are outlined as well as treatment of specific motor manifestations and movements. There is a paucity of evidence to support the treatments available for the motor disorder, with only one agent with class 1 evidence, tetrabenazine, for chorea. There are, however, treatments informed by expert opinion which reflect the management of a wider HD phenotype than that represented in clinical trials. Some treatments are based on evidence from use in other conditions. Medical management is usually undertaken later in the disease with concurrent nonmedical interventions after multidisciplinary assessments. Medication review with HD progression is essential. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Dermatitis herpetiformis: a cutaneous manifestation of coeliac disease.

    Science.gov (United States)

    Collin, Pekka; Salmi, Teea T; Hervonen, Kaisa; Kaukinen, Katri; Reunala, Timo

    2017-02-01

    Dermatitis herpetiformis (DH) is an itchy blistering skin disease with predilection sites on elbows, knees, and buttocks. Diagnosis is confirmed by showing granular immunoglobulin A deposits in perilesional skin. DH is one manifestation of coeliac disease; the skin symptoms heal with gluten free diet (GFD) and relapse on gluten challenge. Of the first-degree relatives, 5% may be affected by either condition. Tissue transglutaminase (TG2) is the autoantigen in coeliac disease and epidermal transglutaminase (TG3) in DH. Both diseases conditions exhibit TG2-specific autoantibodies in serum and small bowel mucosa; patients with DH have IgA-TG3 in the skin. There are some divergencies between these two phenotypes. One-fourth of DH patients do not have small bowel mucosal villous atrophy, but virtually all have coeliac-type inflammatory changes. The skin symptoms respond slowly to GFD. The incidence of coeliac disease is increasing, whereas the opposite is true for DH. A female predominance is evident in coeliac disease, while DH may be more common in males. Coeliac disease carries the risk of small intestinal T-cell lymphoma; in DH B-cell lymphomas at any site may prevail. Adult coeliac disease carries a slightly increased elevated mortality risk, whereas in DH, the relative mortality rate is significantly decreased. Key messages Dermatitis herpetiformis is a cutaneous manifestation of coeliac disease; both conditions are genetically determined and gluten-dependent. Gastrointestinal symptoms and the degree of villous atrophy are less obvious in dermatitis herpetiformis than in coeliac disease. Both show tissue transglutaminase (TG2) specific autoantibodies in serum and small bowel mucosa. In addition, TG3-targeted IgA antibodies are found in the skin of DH patients Both conditions carry an increased elevated risk of lymphoma, in coeliac disease small intestinal T-cell lymphoma, in dermatitis herpetiformis mainly B-cell lymphoma at various sites. Coeliac disease is

  16. Deep Vein Thrombosis as Initial Manifestation of Whipple Disease

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    Mônica Souza de Miranda Henriques

    2016-11-01

    Full Text Available Introduction: Wipple disease (WD is a rare chronic disease caused by the bacillus Tropheryma whipplei. Constitutive, rheumatologic, gastrointestinal, cardiac, cerebral, lymphatic, cutaneous, and ophthalmological signs are possible systemic symptoms. However, thrombotic manifestations are rarely described as “stroke-like syndrome” or arterial thrombosis. Diagnosis is based on clinical manifestations and pathological examination. Laboratory findings may include anemia, leukocytosis, and thrombocytosis. Objective: We report a case of venous thrombosis as initial manifestation of WD. Case Report: We describe the case of a 53-year-old male with iliofemoral vein thrombosis followed by intermittent diarrhea, loss of appetite, abdominal distension, and bloating. A mild malnutrition state with a weight loss of 13 kg, pallor (+/4 +, presence of lower-limb edema (+/4 +, and hypertympanic distended abdomen occurred. Laboratory tests on admission revealed anemia, positive inflammatory activity tests, and normal coagulation. Endoscopic examination showed villous edema with white dotted infiltrates in the second duodenal portion and intestinal lymphangiectasia in the terminal ileum. Pathological examination revealed numerous macrophages with positive periodic acid-Schiff inclusions. Venous Doppler ultrasound showed extensive deep thrombosis on the left lower limb and recanalization of the femoral vein in the right lower limb. The patient was treated with ceftriaxone and enoxaparin sodium, which led to an improvement of gastrointestinal and thrombosis symptoms. Comments: Hypercoagulability, endothelial damage, vasculitis, and blood stasis are present in T. whipplei infection, which are associated with the activation of inflammatory mechanisms as well as procoagulant and thromboembolic events. WD should be part of the differential diagnosis of diseases that cause venous thrombosis of unknown origin.

  17. The most common otorhinolaryngologic manifestations of granulomatous diseases

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    Heshiki, Rosana Emiko

    2008-09-01

    Full Text Available Introduction: Granulomatous diseases result from immunopathologic processes in which there is a failure in the fagocitosis of intracellular organisms. They can cause oral, nasal and pharyngeal mucosa ulcers, vocal cords lesions, otorrhoea and oropharyngeal vegetant lesions. Objective: Describing the most frequent otorhinolaryngologic manifestations in common granulomatous diseases: hanseniasis, paracoccidioidomycosis, leishmaniasis. Method: A retrospective study has been carried out from records of patients diagnosed with the abovementioned diseases between January 1, 2005 and October 31, 2007 in an infectology ambulatory of a tertiary hospital. Results: 142 patients were evaluated; 93 with leishmaniasis, 39 with paracoccidioidomycosis and 10 with hanseniasis. In 93 cases of leishmaniasis, 16 (17.2% had mucosal affection, and the most common signs were septum perforation and nasal mucosal ulcers, both with 8 cases. In paracoccidioidomycosis, oropharyngeal ulcer was the most frequent, with 15 cases (38,4%. Conclusion: Head and neck signs and symptoms are common in patients with leishmaniasis and paracoccidioidomycosis. Nasal manifestations prevail in leishmaniasis and oropharyngeal ones in paracoccidioidomycosis.

  18. Pulmonary manifestations in collagen vascular diseases; Pulmonale Manifestationen bei Kollagenosen

    Energy Technology Data Exchange (ETDEWEB)

    Vogel, M.N.A. [Thoraxklinik, Universitaetsklinikum Heidelberg, Abteilung fuer Diagnostische und Interventionelle Radiologie mit Nuklearmedizin, Heidelberg (Germany); Universitaetsklinikum Heidelberg, Translational Lung Research Center (TLRC), Heidelberg (Germany); Kreuter, M. [Thoraxklinik, Universitaetsklinikum Heidelberg, Zentrum fuer interstitielle und seltene Lungenerkrankungen, Pneumologie und Beatmungsmedizin, Heidelberg (Germany); Universitaetsklinikum Heidelberg, Translational Lung Research Center (TLRC), Heidelberg (Germany); Kauczor, H.U. [Radiologische Klinik, Universitaetsklinikum Heidelberg, Abteilung fuer Diagnostische und Interventionelle Radiologie, Heidelberg (Germany); Universitaetsklinikum Heidelberg, Translational Lung Research Center (TLRC), Heidelberg (Germany); Heussel, C.P. [Thoraxklinik, Universitaetsklinikum Heidelberg, Abteilung fuer Diagnostische und Interventionelle Radiologie mit Nuklearmedizin, Heidelberg (Germany); Radiologische Klinik, Universitaetsklinikum Heidelberg, Abteilung fuer Diagnostische und Interventionelle Radiologie, Heidelberg (Germany); Universitaetsklinikum Heidelberg, Translational Lung Research Center (TLRC), Heidelberg (Germany)

    2016-10-15

    Pulmonary complications are frequent in patients with collagen vascular diseases (CVD). Frequent causes are a direct manifestation of the underlying disease, side effects of specific medications and lung infections. The standard radiological procedure for the work-up of pulmonary pathologies in patients with CVD is multidetector computed tomography (MDCT) with thin-slice high-resolution reconstruction. The accuracy of thin-slice CT for the identification of particular disease patterns is very high. The pattern of usual interstitial pneumonia (UIP) representing the direct pulmonary manifestation of rheumatoid arthritis (RA) can be identified with a sensitivity of 45 % and a specificity of 96 %. Both direct pulmonary manifestations, drug-induced toxicity and certain infections can have a similar appearance in thin-slice MDCT in various forms of CVD. Knowledge of the patterns and causes contributes to the diagnostic certainty. At first diagnosis of a CVD and associated pulmonary symptoms thin-slice MDCT is recommended. Clinical, lung function and imaging follow-up examinations should be performed every 6-12 months depending on the results of the MDCT. In every case the individual CT morphological patterns of pulmonary involvement must be identified. The combination of information on the anamnesis, clinical and imaging results is a prerequisite for an appropriate disease management. (orig.) [German] Pulmonale Komplikationen sind bei Patienten mit Kollagenosen keine Seltenheit. Haeufig sind eine direkte Manifestation der Grunderkrankung, eine Nebenwirkung der medikamentoesen Therapie oder eine Lungeninfektion die Ursachen. Das radiologische Standardverfahren zur Klaerung pulmonaler Pathologien bei Patienten mit Kollagenosen ist die Multidetektorcomputertomographie mit duennschichtigen Rekonstruktionen (Duennschicht-MDCT). Die Treffsicherheit der Duennschicht-MDCT ist fuer die Identifikation eines Erkrankungsmusters sehr hoch. So kann beispielsweise das Muster einer

  19. Spontaneous autoimmune gastritis and hypochlorhydria are manifest in the ileitis-prone SAMP1/YitFcs mice

    Science.gov (United States)

    Erickson, L. D.; Loo, W. M.; Scott, K. G.; Wiznerowicz, E. B.; Brown, C. C.; Torres-Velez, F. J.; Alam, M. S.; Black, S. G.; McDuffie, M.; Feldman, S. H.; Wallace, J. L.; McKnight, G. W.; Padol, I. T.; Hunt, R. H.; Tung, K. S.

    2012-01-01

    SAMP1/YitFcs mice serve as a model of Crohn's disease, and we have used them to assess gastritis. Gastritis was compared in SAMP1/YitFcs, AKR, and C57BL/6 mice by histology, immunohistochemistry, and flow cytometry. Gastric acid secretion was measured in ligated stomachs, while anti-parietal cell antibodies were assayed by immunofluorescence and enzyme-linked immunosorbent spot assay. SAMP1/YitFcs mice display a corpus-dominant, chronic gastritis with multifocal aggregates of mononuclear cells consisting of T and B lymphocytes. Relatively few aggregates were observed elsewhere in the stomach. The infiltrates in the oxyntic mucosa were associated with the loss of parietal cell mass. AKR mice, the founder strain of the SAMP1/YitFcs, also have gastritis, although they do not develop ileitis. Genetic studies using SAMP1/YitFcs-C57BL/6 congenic mice showed that the genetic regions regulating ileitis had comparable effects on gastritis. The majority of the cells in the aggregates expressed the T cell marker CD3 or the B cell marker B220. Adoptive transfer of SAMP1/YitFcs CD4+ T helper cells, with or without B cells, into immunodeficient recipients induced a pangastritis and duodenitis. SAMP1/YitFcs and AKR mice manifest hypochlorhydria and anti-parietal cell antibodies. These data suggest that common genetic factors controlling gastroenteric disease in SAMP1/YitFcs mice regulate distinct pathogenic mechanisms causing inflammation in separate sites within the digestive tract. PMID:21921286

  20. Spontaneous autoimmune gastritis and hypochlorhydria are manifest in the ileitis-prone SAMP1/YitFcs mice.

    Science.gov (United States)

    Ernst, P B; Erickson, L D; Loo, W M; Scott, K G; Wiznerowicz, E B; Brown, C C; Torres-Velez, F J; Alam, M S; Black, S G; McDuffie, M; Feldman, S H; Wallace, J L; McKnight, G W; Padol, I T; Hunt, R H; Tung, K S

    2012-01-01

    SAMP1/YitFcs mice serve as a model of Crohn's disease, and we have used them to assess gastritis. Gastritis was compared in SAMP1/YitFcs, AKR, and C57BL/6 mice by histology, immunohistochemistry, and flow cytometry. Gastric acid secretion was measured in ligated stomachs, while anti-parietal cell antibodies were assayed by immunofluorescence and enzyme-linked immunosorbent spot assay. SAMP1/YitFcs mice display a corpus-dominant, chronic gastritis with multifocal aggregates of mononuclear cells consisting of T and B lymphocytes. Relatively few aggregates were observed elsewhere in the stomach. The infiltrates in the oxyntic mucosa were associated with the loss of parietal cell mass. AKR mice, the founder strain of the SAMP1/YitFcs, also have gastritis, although they do not develop ileitis. Genetic studies using SAMP1/YitFcs-C57BL/6 congenic mice showed that the genetic regions regulating ileitis had comparable effects on gastritis. The majority of the cells in the aggregates expressed the T cell marker CD3 or the B cell marker B220. Adoptive transfer of SAMP1/YitFcs CD4(+) T helper cells, with or without B cells, into immunodeficient recipients induced a pangastritis and duodenitis. SAMP1/YitFcs and AKR mice manifest hypochlorhydria and anti-parietal cell antibodies. These data suggest that common genetic factors controlling gastroenteric disease in SAMP1/YitFcs mice regulate distinct pathogenic mechanisms causing inflammation in separate sites within the digestive tract.

  1. Multisystem Radiologic Manifestations of Erdheim-Chester Disease

    Directory of Open Access Journals (Sweden)

    Umairullah Lodhi

    2016-01-01

    Full Text Available Erdheim-Chester Disease is a rare form of multiorgan non-Langerhans’ cell histiocytosis that affects individuals between the ages of 50 and 70 with an equal distribution among males and females. It is associated with significant morbidity and mortality that is mostly due to infiltration of critical organs. Some of the sites that Erdheim-Chester Disease affects include the skeletal system, central nervous system, cardiovascular system, lungs, kidneys (retroperitoneum, and skin. The most common presenting symptom of Erdheim-Chester Disease is bone pain although a large majority of patients are diagnosed incidentally during a workup for a different disease process. Diagnosing Erdheim-Chester Disease is challenging due its rarity and mimicry to other infiltrative processes. Therefore, a multimodality diagnostic approach is employed with imaging being at the forefront. As of date, a comprehensive radiologic review of the manifestations of Erdheim-Chester Disease has rarely been reported. Here we present radiologic findings of an individual suffering from Erdheim-Chester Disease.

  2. Soft tissue manifestations of early rheumatic disease. Imaging with MRI

    International Nuclear Information System (INIS)

    Treitl, M.; Panteleon, A.; Koerner, M.; Becker-Gaab, C.; Reiser, M.; Wirth, S.

    2006-01-01

    The aim of this study was to evaluate typical magnetic resonance imaging (MRI) findings in early rheumatic diseases manifesting at the soft tissues of the hand using a retrospective analysis. A total of 186 MRI examinations of patients with clinical suspicion of a rheumatic disease were evaluated in a consensus reading by two experienced radiologists. All imaging patterns were assessed with respect to their type and localization. Under blinded and non-blinded conditions diagnoses were correlated with final clinical diagnosis. The most frequent diagnoses were rheumatoid arthritis (RA, 45.7%) and psoriatic arthritis (PsA, 15.6%). The mean correlation between clinical and MRI diagnosis (r) was 0.75 in blinded and 0.853 in non-blinded reading (p [de

  3. Endocrine-Manifestations of Cirrhosis and Liver Disease

    Directory of Open Access Journals (Sweden)

    M Khalili

    2014-04-01

    cirrhosis. Here it reviews some endocrine-manifestations related to cirrhosis and the liver disease.        

  4. Intrathoracic Manifestations of IgG4-Related Disease

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    Sian Yik Lim

    2016-10-01

    Full Text Available Intrathoracic involvement with IgG4-related disease (IgG4-RD is frequently overlooked in IgG4-related disease patients. In this article we review the intrathoracic findings of IgG4-RD which are variable and protean. IgG4-related disease has been reported to affect the lung parenchyma, pleura, mediastinal/hilar lymph nodes, vasculature, and pericardium within the thorax. Mediastinal and hilar lymphadenopathy is the most common intrathoracic manifestation of IgG4-RD. Four main patterns of pulmonary disease have been described, including the solid nodular type, the bronchovascular type, the alveolar interstitial type, and the round shaped ground glass type. When feasible, a biopsy should be obtained to confirm the diagnosis. Most lesions show characteristic pathologic findings of IgG4-RD: dense lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis. While this helps establish the diagnosis, the interpretation of pathology findings in the clinical context is key in making an accurate diagnosis. Mimickers of IgG4-RD should be ruled out, before making a diagnosis. The intrathoracic findings of IgG4-RD can be treated effectively with prednisone, but may require additional immunosuppressive therapies, including rituximab.

  5. Alcohol consumption and risk of recurrent cardiovascular events and mortality in patients with clinically manifest vascular disease and diabetes mellitus: The Second Manifestations of ARTerial (SMART) disease study

    NARCIS (Netherlands)

    Beulens, J.W.J.; Algra, A.; Soedamah-Muthu, S.S.; Visseren, F.L.J.; Grobbee, D.E.; Graaf, van der Y.

    2010-01-01

    OBJECTIVE: This study investigated the relation between alcohol consumption and specific vascular events and mortality in a high risk population of patients with clinical manifestations of vascular disease and diabetes. METHODS: Patients with clinically manifest vascular disease or diabetes (n=5447)

  6. Pulmonary cystic disease associated with integumentary and renal manifestations

    Science.gov (United States)

    Cayetano, Katherine S.; Albertson, Timothy E.; Chan, Andrew L.

    2013-01-01

    A 69-year-old man with multiple skin lesions on his face, neck and upper torso, which first appeared in the 3rd decade of his life, was admitted to our hospital. He had cystic changes in his lungs noted on chest computed tomography (CT) scanning, as well as a left kidney mass. This patient exhibited a rare complex of renal, cutaneous and pulmonary manifestations, eponymously named Birt-Hogg-Dube syndrome, with characteristic skin features (fibrofolliculomas, trichodiscomas and acrochordons). This syndrome is due to an autosomal dominant germ-line mutation of the folliculin (FLCN) gene located at chromosome 17p11.2. Diagnosis and differentiation from other disease complexes including the skin, kidneys and lungs are important in prognostication and management of potentially life-threatening complications such as renal cell carcinoma and pneumothoraces. PMID:24285950

  7. Risk prediction and risk reduction in patients with manifest arterial disease

    NARCIS (Netherlands)

    Goessens, B.M.B.; Goessens, B.M.B.

    2006-01-01

    Risicovoorspelling en risicoverlaging bij patienten met manifest vaatlijden Engelstalig abstract The number of patients with clinical manifest arterial disease is increasing because of the aging of the population. Patients with manifest arterial disease have an increased risk of a new vascular event

  8. Endocrine manifestations related to inherited metabolic diseases in adults

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    Vantyghem Marie-Christine

    2012-01-01

    Full Text Available Abstract Most inborn errors of metabolism (IEM are recessive, genetically transmitted diseases and are classified into 3 main groups according to their mechanisms: cellular intoxication, energy deficiency, and defects of complex molecules. They can be associated with endocrine manifestations, which may be complications from a previously diagnosed IEM of childhood onset. More rarely, endocrinopathies can signal an IEM in adulthood, which should be suspected when an endocrine disorder is associated with multisystemic involvement (neurological, muscular, hepatic features, etc.. IEM can affect all glands, but diabetes mellitus, thyroid dysfunction and hypogonadism are the most frequent disorders. A single IEM can present with multiple endocrine dysfunctions, especially those involving energy deficiency (respiratory chain defects, and metal (hemochromatosis and storage disorders (cystinosis. Non-autoimmune diabetes mellitus, thyroid dysfunction and/or goiter and sometimes hypoparathyroidism should steer the diagnosis towards a respiratory chain defect. Hypogonadotropic hypogonadism is frequent in haemochromatosis (often associated with diabetes, whereas primary hypogonadism is reported in Alström disease and cystinosis (both associated with diabetes, the latter also with thyroid dysfunction and galactosemia. Hypogonadism is also frequent in X-linked adrenoleukodystrophy (with adrenal failure, congenital disorders of glycosylation, and Fabry and glycogen storage diseases (along with thyroid dysfunction in the first 3 and diabetes in the last. This is a new and growing field and is not yet very well recognized in adulthood despite its consequences on growth, bone metabolism and fertility. For this reason, physicians managing adult patients should be aware of these diagnoses.

  9. Subjective cognitive decline: The first clinical manifestation of Alzheimer's disease?

    Directory of Open Access Journals (Sweden)

    Adalberto Studart Neto

    Full Text Available ABSTRACT Background: Mild cognitive impairment is considered as the first clinical manifestation of Alzheimer's disease (AD, when the individual exhibits below performance on standardized neuropsychological tests. However, some subjects before having a lower performance on cognitive assessments already have a subjective memory complaint. Objective: A review about subjective cognitive decline, the association with AD biomarkers and risk of conversion to dementia. Methods: We performed a comprehensive non-systematic review on PubMed. The keywords used in the search were terms related to subjective cognitive decline. Results: Subjective cognitive decline is characterized by self-experience of deterioration in cognitive performance not detected objectively through formal neuropsychological testing. However, various terms and definitions have been used in the literature and the lack of a widely accepted concept hampers comparison of studies. Epidemiological data have shown that individuals with subjective cognitive decline are at increased risk of progression to AD dementia. In addition, there is evidence that this group has a higher prevalence of positive biomarkers for amyloidosis and neurodegeneration. However, Alzheimer's disease is not the only cause of subjective cognitive decline and various other conditions can be associated with subjective memory complaints, such as psychiatric disorders or normal aging. The features suggestive of a neurodegenerative disorder are: onset of decline within the last five years, age at onset above 60 years, associated concerns about decline and confirmation by an informant. Conclusion: These findings support the idea that subjective cognitive complaints may be an early clinical marker that precedes mild cognitive impairment due to Alzheimer's disease.

  10. Ocular manifestations of graft-versus-host disease

    Science.gov (United States)

    Nassar, Amr; Tabbara, Khalid F.; Aljurf, Mahmoud

    2013-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) has evolved over the past two decades to become the standard of care for hematologic and lymphoid malignancies. Major ocular complications after allogeneic HSCT have been increasing in number and severity. Graft-versus-host disease (GVHD) remains a major cause of ocular morbidity after allogeneic HSCT. The main objective of this review is to elucidate the ocular complications in patients developing GVHD following HSCT. Ocular complications secondary to GVHD are common and include dry eye syndrome, acquisition of ocular allergy from donors with allergic disorders. Eyelid changes may occur in GVHD leading to scleroderma-like changes. Patients may develop poliosis, madarosis, vitiligo, lagophthalmos, and entropion. The cornea may show filamentary keratitis, superficial punctate keratitis, corneal ulcers, and peripheral corneal melting which may lead to perforation in severe cases. Scleritis may also occur which can be anterior or posterior. Keratoconjunctivis sicca appears to be the most common presentation of GVHD. The lacrimal glands may be involved with mononuclear cell infiltration of both the major and accessory lacrimal glands and decrease in tear production. Severe dry eye syndrome in patients with GVHD may develop conjunctival scarring, keratinization, and cicatrization of the conjunctiva. Therapy of GVHD includes systemic immunosuppression and local therapy. Surgical treatment in refractory cases includes surgical intervention to improve the manifestation of GVHD of the eye. This may include tarsorrhapy, prose lenses, punctal occlusions and corneal transplantation. PMID:24227989

  11. Mice lacking cyclin-dependent kinase-like 5 manifest autistic and ADHD-like behaviors.

    Science.gov (United States)

    Jhang, Cian-Ling; Huang, Tzyy-Nan; Hsueh, Yi-Ping; Liao, Wenlin

    2017-10-15

    Neurodevelopmental disorders frequently share common clinical features and appear high rate of comorbidity, such as those present in patients with attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). While characterizing behavioral phenotypes in the mouse model of cyclin-dependent kinase-like 5 (CDKL5) disorder, a neurodevelopmental disorder caused by mutations in the X-linked gene encoding CDKL5, we found that these mice manifested behavioral phenotypes mimicking multiple key features of ASD, such as impaired social interaction and communication, as well as increased stereotypic digging behaviors. These mice also displayed hyper-locomotion, increased aggressiveness and impulsivity, plus deficits in motor and associative learning, resembling primary symptoms of ADHD. Through brain region-specific biochemical analysis, we uncovered that loss of CDKL5 disrupts dopamine synthesis and the expression of social communication-related key genes, such as forkhead-box P2 and mu-opioid receptor, in the corticostriatal circuit. Together, our findings support that CDKL5 plays a role in the comorbid features of autism and ADHD, and mice lacking CDKL5 may serve as an animal model to study the molecular and circuit mechanisms underlying autism-ADHD comorbidity. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Early Lung Adenocarcinoma in Mice: Micro-Computed Tomography Manifestations and Correlation with Pathology

    Directory of Open Access Journals (Sweden)

    Lin Deng

    2017-06-01

    Full Text Available Lung cancer is the most common fatal malignancy for both men and women and adenocarcinoma is the most common histologic type. Early diagnosis of lung cancer can significantly improve the survival rate of patients. This study aimed to investigate the micro-computed tomography (micro-CT manifestations of early lung adenocarcinoma (LAC in mice and to provide a new perspective for early clinical diagnosis. Early LAC models in 10 mice were established by subcutaneously injecting 1-methyl-3-nitro-1-nitrosoguanidine (MNNG solution. Micro-CT scan and multiple planar reconstruction (MPR were used for mouse lungs. Micro-CT features of early LAC, especially the relationships between tumor and bronchus, were analyzed and correlated with pathology. Micro-CT findings of early LAC were divided into three types: non-solid (n = 8, 6%, partly solid (n = 85, 64% and totally solid (n = 39, 30%. Tumor-bronchus relationships, which could be observed in 110 of 132(83% LAC, were classified into four patterns: type I (n = 16, 15%, bronchus was truncated at the margin of the tumor; type II (n = 33, 30%, bronchus penetrated into the tumor with tapered narrowing and interruption; type III (n = 38, 35%, bronchus penetrated into the tumor with a patent and intact lumen; type IV (n = 99, 90%, bronchus ran at the border of the tumor with an intact or compressed lumen. Micro-CT manifestations of early LAC correlated well with pathological findings. Micro-CT can clearly demonstrate the features of mouse early LAC and bronchus-tumor relationships, and can also provide a new tool and perspective for the study of early LAC.

  13. Cryptogenic Organizing Pneumonia With Lung Nodules Secondary to Pulmonary Manifestation of Crohn Disease

    Directory of Open Access Journals (Sweden)

    Taufiq Zaman

    2017-05-01

    Full Text Available Crohn disease is an immune-mediated inflammatory condition with gastrointestinal and extraintestinal manifestations in patients. Pulmonary involvement of Crohn disease is one manifestation. There have been case reports which have shown Crohn disease and lung nodules which were noted to be histopathological as cryptogenic organizing pneumonia (COP. In our case, a 22-year-old woman with Crohn disease was seen with complaints of chest pain and cough. Computed tomographic scan of chest showed multiple bilateral lung nodules, for which biopsy was done, which showed COP. The case study is followed by a deeper discussion of COP and the extraintestinal manifestation seen in inflammatory bowel disease.

  14. The aging brain in patients with manifest arterial disease

    NARCIS (Netherlands)

    Veen, P.H. van der

    2014-01-01

    Cardiovascular disease is a major health problem worldwide. Accumulating evidence suggests that cardiovascular disease and a high cardiovascular risk play an important role in the etiology of cognitive decline and dementia. As intermediates in this relation between cardiovascular disease and

  15. Spectacular manifestations of systemic diseases of the snake

    DEFF Research Database (Denmark)

    Da Silva, Mari-Ann Otkjær; Bertelsen, Mads Frost; Heegaard, Steffen

    2015-01-01

    This paper reports histopathological findings in the spectacles of four snakes diagnosed with systemic gout, inclusion body disease, disseminated lymphoma and myeloproliferative disease, respectively. Gout was characterised by urate ghost tophi in the stroma and outer epithelium of the spectacle...... to four different systemic diseases with world-wide distribution........ Inclusion body disease affected all layers of the spectacle with intracytoplasmic eosinophilic inclusions. Two cases of neoplasia, lymphoma and myeloproliferative disease, affected the ocular adnexa and the spectacular transition zone. These cases provide novel insight into how the spectacle may respond...

  16. Intrathoracic manifestations of collagen vascular diseases on high-resolution chest computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Silva, C. Isabela S. [University of British Columbia, Vancouver (Canada). Vancouver General Hospital]. E-mail: isabela.silva@vch.ca; Mueller, Nestor L. [University of British Columbia, Vancouver (Canada). Vancouver General Hospital. Dept. of Radiology

    2008-05-15

    Intrathoracic manifestations of collagen vascular diseases are very common. The frequency of intrathoracic manifestations and the patterns of abnormality are variable depending on the type of collagen vascular disease and may simultaneously involve one or more of the following: lung parenchyma, airways, pulmonary vessels, pericardium, and pleura. The most common pulmonary manifestations are diffuse interstitial pneumonia and pulmonary hypertension which together represent the main causes of morbidity and mortality of these patients. Pulmonary, airway and pleural involvement may also be secondary to the disease therapy, or result from bacterial pneumonia or opportunistic infection. In the present review, the authors summarize the main intrathoracic manifestations of collagen vascular diseases and the differential diagnosis on high-resolution chest computed tomography. (author)

  17. Immunoglobulin G4-related disease: autoimmune pancreatitis and extrapancreatic manifestations

    Directory of Open Access Journals (Sweden)

    Daniel Alvarenga Fernandes

    2016-04-01

    Full Text Available Abstract We present a case of immunoglobulin G4 (IgG4-related disease with pancreatic and extrapancreatic involvement, including the biliary and renal systems. Given the importance of imaging methods for the diagnosis of IgG4-related disease and its differentiation from pancreatic adenocarcinoma, we emphasize important abdominal computed tomography and magnetic resonance imaging findings related to this recently recognized systemic autoimmune disease.

  18. What rheumatologists should know about orofacial manifestations of autoimmune rheumatic diseases.

    Science.gov (United States)

    Abrão, Aline Lauria Pires; Santana, Caroline Menezes; Bezerra, Ana Cristina Barreto; Amorim, Rivadávio Fernandes Batista de; Silva, Mariana Branco da; Mota, Licia Maria Henrique da; Falcão, Denise Pinheiro

    2016-02-11

    Orofacial manifestations occur frequently in rheumatic diseases and usually represent early signs of disease or of its activity that are still neglected in clinical practice. Among the autoimmune rheumatic diseases with potential for oral manifestations, rheumatoid arthritis (RA), inflammatory myopathies (IM), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), relapsing polychondritis (RP) and Sjögren's syndrome (SS) can be cited. Signs and symptoms such as oral hyposalivation, xerostomia, temporomandibular joint disorders, lesions of the oral mucosa, periodontal disease, dysphagia, and dysphonia may be the first expression of these rheumatic diseases. This article reviews the main orofacial manifestations of rheumatic diseases that may be of interest to the rheumatologist for diagnosis and monitoring of autoimmune rheumatic diseases. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

  19. Multiple sclerosis or neurological manifestations of Celiac disease

    Directory of Open Access Journals (Sweden)

    Vahid Shaygannejad

    2013-01-01

    Full Text Available Multiple sclerosis (MS and celiac disease (CD are considered to be T-cell-mediated autoimmune disease. We discuss about a known case of CD-showed relapsing - remitting neurological symptoms compatible with MS. In this rare co-occurrence subject, MS-CD patient, the interaction between MS - and CD-related inflammatory processes is open to discussion.

  20. Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus

    Science.gov (United States)

    Barnett, Timothy C.; McArthur, Jason D.; Cole, Jason N.; Gillen, Christine M.; Henningham, Anna; Sriprakash, K. S.; Sanderson-Smith, Martina L.; Nizet, Victor

    2014-01-01

    SUMMARY Streptococcus pyogenes, also known as group A Streptococcus (GAS), causes mild human infections such as pharyngitis and impetigo and serious infections such as necrotizing fasciitis and streptococcal toxic shock syndrome. Furthermore, repeated GAS infections may trigger autoimmune diseases, including acute poststreptococcal glomerulonephritis, acute rheumatic fever, and rheumatic heart disease. Combined, these diseases account for over half a million deaths per year globally. Genomic and molecular analyses have now characterized a large number of GAS virulence determinants, many of which exhibit overlap and redundancy in the processes of adhesion and colonization, innate immune resistance, and the capacity to facilitate tissue barrier degradation and spread within the human host. This improved understanding of the contribution of individual virulence determinants to the disease process has led to the formulation of models of GAS disease progression, which may lead to better treatment and intervention strategies. While GAS remains sensitive to all penicillins and cephalosporins, rising resistance to other antibiotics used in disease treatment is an increasing worldwide concern. Several GAS vaccine formulations that elicit protective immunity in animal models have shown promise in nonhuman primate and early-stage human trials. The development of a safe and efficacious commercial human vaccine for the prophylaxis of GAS disease remains a high priority. PMID:24696436

  1. Smoking is associated with extra-intestinal manifestations in inflammatory bowel disease

    NARCIS (Netherlands)

    M. Severs; S.J.H. van Erp; M.E. van der Valk (Mirthe); M.J.J. Mangen; M. Fidder (Melissa); M. van der Have (Mike); A.A. van Bodegraven (Ad); D.J. de Jong; C.J. van der Woude (Janneke); M. Romberg-Camps (Mariëlle); P.R. Clemens (Paula ); J.M. Jansen (Jeroen); P.C. van de Meeberg (Paul); N. Mahmmod (Nofel); C.Y. Ponsioen (Cyril); C. Bolwerkm; J.R. Vermeijden (J. Reinoud); M. Pierik (Marieke); P.D. Siersema (Peter); M. Leenders (Max); A.E. van der Meulen-de Jong (Andrea); G. Dijkstra (Gerard); B. Oldenburg (Bas)

    2016-01-01

    textabstractBackground and aims: Smoking affects the course of disease in patients with ulcerative colitis (UC) and Crohn's disease (CD). We aimed to study the association between smoking and extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD). Methods: We cross-sectionally

  2. Smoking is Associated With Extra-intestinal Manifestations in Inflammatory Bowel Disease

    NARCIS (Netherlands)

    Severs, M.; Erp, S.J. van; Valk, M.E. van der; Mangen, M.J.; Fidder, H.H.; Have, M. van der; Bodegraven, A.A. van; Jong, D.J. de; Woude, C.J. van der; Romberg-Camps, M.J.; Clemens, C.H.; Jansen, J.M.; Meeberg, P.C. van de; Mahmmod, N.; Ponsioen, C.Y.; Bolwerk, C.; Vermeijden, J.R.; Pierik, M.J.; Siersema, P.D.; Leenders, M.; Meulen-Jong, A.E. van der; Dijkstra, G.; Oldenburg, B.

    2016-01-01

    BACKGROUND AND AIMS: Smoking affects the course of disease in patients with ulcerative colitis (UC) and Crohn's disease (CD). We aimed to study the association between smoking and extra-intestinal manifestations (EIMs) in inflammatory bowel disease (IBD). METHODS: We cross-sectionally explored the

  3. Smoking is Associated With Extra-intestinal Manifestations in Inflammatory Bowel Disease

    NARCIS (Netherlands)

    Severs, M.; van Erp, S. J. H.; van der Valk, M. E.; Mangen, M. J. J.; Fidder, H. H.; van der Have, M.; van Bodegraven, A. A.; de Jong, D. J.; van der Woude, C. J.; Romberg-Camps, M. J. L.; Clemens, C. H. M.; Jansen, J. M.; van de Meeberg, P. C.; Mahmmod, N.; Ponsioen, C. Y.; Bolwerk, C.; Vermeijden, J. R.; Pierik, M. J.; Siersema, P. D.; Leenders, M.; van der Meulen-de Jong, A. E.; Dijkstra, G.; Oldenburg, B.

    2016-01-01

    Smoking affects the course of disease in patients with ulcerative colitis (UC) and Crohn's disease (CD). We aimed to study the association between smoking and extra-intestinal manifestations (EIMs) in inflammatory bowel disease (IBD). We cross-sectionally explored the association between smoking and

  4. Skin manifestations of growth hormone-induced diseases.

    Science.gov (United States)

    Kanaka-Gantenbein, Christina; Kogia, Christina; Abdel-Naser, Mohamed Badawy; Chrousos, George P

    2016-09-01

    The human skin is a well-organized organ bearing different types of cells in a well-structured interference to each other including epidermal and follicular keratinocytes, sebocytes, melanocytes, dermal papilla cells and fibroblasts, endothelial cells, sweat gland cells as well as nerves. Several hormones act on different cell types of the skin, while it is also considered an endocrine organ secreting hormones that act at several sites of the organism. GH receptors are found in almost all cell types forming the skin, while IGF-1 receptors' expression is restricted to the epidermal keratinocytes. Both Growth Hormone (GH) excess, as in the case of Acromegaly in adults, or Gigantism in growing children, and GH deficiency states lead to skin manifestations. In case of GH excess the main dermatological findings are skin thickening, coarsening of facial features, acrochordons, puffy hands and feet, oily skin and hyperhidrosis, while GH deficiency, on the contrary, is characterized by thin, dry skin and disorder of normal sweating. Moreover, special disorders associated with GH excess may have specific characteristics, as is the case of café-au-lait spots in Neurofibromatosis, or big café-au-lait skin hyperpigmented regions with irregular margins, as is the case in McCune-Albright syndrome. Meticulous examination of the skin may therefore contribute to the final diagnosis in cases of GH-induced disorders.

  5. Chikungunya fever. Rheumatic manifestations of an emerging disease in Europe.

    Science.gov (United States)

    Horcada, M Loreto; Díaz-Calderón, Carlos; Garrido, Laura

    2015-01-01

    Chikungunya fever is a viral disease caused by an alphavirus belonging to the Togaviridae family, transmitted by several species of Aedes mosquitoes: Aedes aegypti and Aedes albopictus (A. albopictus). It is endemic in Africa and Asia with recurrent outbreaks. It is an emerging disease and cases in Europe transmitted by A. albopictus have been established in Mediterranean areas. The first autochthonous cases detected on the Caribbean islands suppose a serious threat of spreading disease to America, which so far has been disease free. Clinical symptoms begin abruptly with fever, skin rash and polyarthritis. Although mortality is low, a high percentage of patients develop a chronic phase defined by persistent arthritis for months or even years. A severe immune response is responsible for joint inflammation. The absence of specific treatment and lack of vaccine requires detailed studies about its immunopathogenesis in order to determine the most appropriate target. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  6. COPD is a systemic disease – the ex trapulmonary manifestations

    African Journals Online (AJOL)

    Peripheral skeletal muscle dysfunction is an established systemic feature of COPD.12 .... vitamin A status in chronic obstructive pulmonary disease patients and ... Kempainen RR, Savik K, Whelan TP, Dunitz JM, Herrington CS, Billings. JL.

  7. Altered brain mechanisms of emotion processing in pre-manifest Huntington's disease.

    Science.gov (United States)

    Novak, Marianne J U; Warren, Jason D; Henley, Susie M D; Draganski, Bogdan; Frackowiak, Richard S; Tabrizi, Sarah J

    2012-04-01

    Huntington's disease is an inherited neurodegenerative disease that causes motor, cognitive and psychiatric impairment, including an early decline in ability to recognize emotional states in others. The pathophysiology underlying the earliest manifestations of the disease is not fully understood; the objective of our study was to clarify this. We used functional magnetic resonance imaging to investigate changes in brain mechanisms of emotion recognition in pre-manifest carriers of the abnormal Huntington's disease gene (subjects with pre-manifest Huntington's disease): 16 subjects with pre-manifest Huntington's disease and 14 control subjects underwent 1.5 tesla magnetic resonance scanning while viewing pictures of facial expressions from the Ekman and Friesen series. Disgust, anger and happiness were chosen as emotions of interest. Disgust is the emotion in which recognition deficits have most commonly been detected in Huntington's disease; anger is the emotion in which impaired recognition was detected in the largest behavioural study of emotion recognition in pre-manifest Huntington's disease to date; and happiness is a positive emotion to contrast with disgust and anger. Ekman facial expressions were also used to quantify emotion recognition accuracy outside the scanner and structural magnetic resonance imaging with voxel-based morphometry was used to assess the relationship between emotion recognition accuracy and regional grey matter volume. Emotion processing in pre-manifest Huntington's disease was associated with reduced neural activity for all three emotions in partially separable functional networks. Furthermore, the Huntington's disease-associated modulation of disgust and happiness processing was negatively correlated with genetic markers of pre-manifest disease progression in distributed, largely extrastriatal networks. The modulated disgust network included insulae, cingulate cortices, pre- and postcentral gyri, precunei, cunei, bilateral putamena

  8. Norrie disease in a family with a manifesting female carrier.

    Science.gov (United States)

    Sims, K B; Irvine, A R; Good, W V

    1997-04-01

    To show that Norrie disease can occur in a girl and to describe her ophthalmologic and genetic features. Amplification of DNA polymerase chain reaction and sequencing of asymmetric polymerase chain reaction for exon 3 were performed on the blood specimen obtained from a girl born with bilateral retinal detachments. A female child with bilateral retinal detachment who had 2 uncles in whom Norrie disease had already been diagnosed. The child had a mutation in the third exon (T776-->A; Ile 123-->Asn) identical to the mutation found in her uncles. Norrie disease can occur in girls. The most likely explanation is nonrandom or unfavorable X inactivation, although timing of development of the peripheral retina and its blood supply could render it vulnerable to effects of the mutant allele at a critical developmental phase.

  9. ORAL MANIFESTATIONS OF CROHN'S DISEASE: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Muhvić-Urek Miranda

    2015-12-01

    Full Text Available Crohn´s disease is a chronic inflammatory bowel disease still with unknown etiology. In 0.5-20 % of patients, extraintestinal lesions in the oral cavity can be presented in forms of orofacial granulomatosis, cobblestone and corrugated oral mucosa, mucosal tags, deep linear ulcerations with hyperplastic folds, pyostomatits vegetans, aphthous ulcers, angular cheilitis, labial/facial edema and gingival erythema/edema. We describe a case of a 28-year-old male who was presented with oral lesions of Crohn´s disease and treatment procedure. The patient was candidate for biologic treatment so dental procedures and preparation of the patient for treatment are described. Good communication and cooperation between the patient's doctor and dentist are important for successful treatment.

  10. Cancer: a single disease with a multitude of manifestions?

    Directory of Open Access Journals (Sweden)

    Grandics Peter

    2003-01-01

    Full Text Available Abstract The relationships of critical nutrients such as plant phenolics, vitamins, minerals and lipids are considered with respect to the incidence of a variety of cancers, and analyzed in terms of how these nutrient deficiencies alter immune function, DNA integrity and cell proliferation. With a significant correlation found between cancer and these nutrient deficiencies, the hypothesis is presented here that nutrition could provide a unifying perception of cancer and recast it as a single disease. This further suggests that a coordinated administration of specific, critical nutrients to cancer patients could lead to the reversal of the disease. It is also proposed that the concurrent presence of a variety of nutritional deficiencies in cancer patients requires a multilevel, systemic approach to this disease as opposed to the single active therapeutic agent approach that is the cornerstone of contemporary research and pharmacology.

  11. Neurological Manifestation of Behcet's Disease: A Case Report ...

    African Journals Online (AJOL)

    Behcet's disease causes inflammation of blood vessels but it is of unknown aetiology. When it involves the nervous system, it may present with benign headaches, aseptic meningitis, meningoencephalitis, cranial nerve palsies, seizures, personality changes, and cerebral venous thrombosis. We present the case of A.G is a ...

  12. Race and Association With Disease Manifestations and Mortality in Scleroderma

    Science.gov (United States)

    Manno, Rebecca L.; Shah, Ami A.; Woods, Adrianne; Le, Elizabeth N.; Boin, Francesco; Hummers, Laura K.; Wigley, Fredrick M.

    2013-01-01

    Abstract Experience suggests that African Americans may express autoimmune disease differently than other racial groups. In the context of systemic sclerosis (scleroderma), we sought to determine whether race was related to a more adverse expression of disease. Between January 1, 1990, and December 31, 2009, a total of 409 African American and 1808 white patients with scleroderma were evaluated at a single university medical center. While the distribution by sex was virtually identical in both groups, at 82% female, African American patients presented to the center at a younger mean age than white patients (47 vs. 53 yr; p scleroderma-specific autoantibody status, and for the socioeconomic measures of educational attainment and health insurance status, diminished these risk estimates (RR, 1.3; 95% CI, 1.0–1.6). The heightened risk of mortality persisted in strata defined by age at disease onset, diffuse cutaneous disease, anticentromere seropositivity, decade of care at the center, and among women. These findings support the notion that race is related to a distinct phenotypic profile in scleroderma, and a more unfavorable prognosis among African Americans, warranting heightened diagnostic evaluation and vigilant care of these patients. Further, we provide a chronologic review of the literature regarding race, organ system involvement, and mortality in scleroderma; we furnish synopses of relevant reports, and summarize findings. PMID:23793108

  13. Graves' disease. Manifestations and therapeutic options

    Energy Technology Data Exchange (ETDEWEB)

    McFarland, K.F.; Saleeby, G.

    1988-03-01

    Graves' disease is the most common cause of hyperthyroidism. Clinical features include thyroid enlargement, eye signs, tachycardia, heat intolerance, emotional lability, weight loss, and hyperkinesis. Three modes of therapy are available. The preferences of the patient and physician are usually prime considerations in devising the therapeutic plan. Radioactive iodine is the most frequently used and safest method of treatment for adults. Antithyroid drugs are preferred for children and pregnant women. Surgery is usually reserved for patients in whom the other forms of treatment are not acceptable. Considerable patient education during the decision-making process enhances the success of the therapeutic plan.

  14. Altered Markers of Brain Development in Crohn's Disease with Extraintestinal Manifestations - A Pilot Study.

    Directory of Open Access Journals (Sweden)

    Anne K Thomann

    Full Text Available Alterations of brain morphology in Crohn's disease have been reported, but data is scarce and heterogenous and the possible impact of disease predisposition on brain development is unknown. Assuming a systemic course of the disease, brain involvement seems more probable in presence of extraintestinal manifestations, but this question has not yet been addressed. The present study examined the relationship between Crohn's disease and brain structure and focused on the connection with extraintestinal manifestations and markers of brain development.In a pilot study, brains of 15 patients with Crohn's disease (of which 9 had a history of extraintestinal manifestations, i.e. arthritis, erythema nodosum and primary sclerosing cholangitis were compared to matched healthy controls using high resolution magnetic resonance imaging. Patients and controls were tested for depression, fatigue and global cognitive function. Cortical thickness, surface area and folding were determined via cortical surface modeling.The overall group comparison (i.e. all patients vs. controls yielded no significant results. In the patient subgroup with extraintestinal manifestations, changes in cortical area and folding, but not thickness, were identified: Patients showed elevated cortical surface area in the left middle frontal lobe (p<0.05 and hypergyrification in the left lingual gyrus (p<0.001 compared to healthy controls. Hypogyrification of the right insular cortex (p<0.05 and hypergyrification of the right anterior cingulate cortex (p<0.001 were detected in the subgroup comparison of patients with against without extraintestinal manifestations. P-values are corrected for multiple comparisons.Our findings lend further support to the hypothesis that Crohn's disease is associated with aberrant brain structure and preliminary support for the hypothesis that these changes are associated with a systemic course of the disease as indicated by extraintestinal manifestations. Changes

  15. Parkinson disease: systemic and orofacial manifestations, medical and dental management.

    Science.gov (United States)

    Friedlander, Arthur H; Mahler, Michael; Norman, Keith M; Ettinger, Ronald L

    2009-06-01

    More than 1.5 million Americans have Parkinson disease (PD), and this figure is expected to rise as the population ages. However, the dental literature offers little information about the illness. The authors conducted a MEDLINE search using the key terms "Parkinson's disease," "medical management" and "dentistry." They selected contemporaneous articles published in peer-reviewed journals and gave preference to articles reporting randomized controlled trials. PD is a progressive neurodegenerative disorder caused by loss of dopaminergic and nondopaminergic neurons in the brain. These deficits result in tremor, slowness of movement, rigidity, postural instability and autonomic and behavioral dysfunction. Treatment consists of administering medications that replace dopamine, stimulate dopamine receptors and modulate other neurotransmitter systems. Oral health may decline because of tremors, muscle rigidity and cognitive deficits. The dentist should consult with the patient's physician to establish the patient's competence to provide informed consent and to determine the presence of comorbid illnesses. Scheduling short morning appointments that begin 90 minutes after administration of PD medication enhances the patient's ability to cooperate with care. Inclination of the dental chair at 45 degrees, placement of a bite prop, use of a rubber dam and high-volume oral evacuation enhance airway protection. To avoid adverse drug interactions with levodopa and entacapone, the dentist should limit administration of local anesthetic agents to three cartridges of 2 percent lidocaine with 1:100,000 epinephrine per half hour, and patients receiving selegiline should not be given agents containing epinephrine or levonordefrin. The dentist should instruct the patient and the caregiver in good oral hygiene techniques.

  16. Oral Manifestations in Pediatric Patients with Coeliac Disease – A Review Article

    Science.gov (United States)

    Macho, Viviana Marisa Pereira; Coelho, Ana Sofia; Veloso e Silva, Diana Maria; de Andrade, David José Casimiro

    2017-01-01

    Background: Coeliac disease is a chronic enteropathy that remains a challenge for the clinician, due to its atypical manifestations and etiopathogenic complexity. Objective: This article intends to describe the oral characteristics of Coeliac Disease in children in order to facilitate their management in the dental office. Methods: A review of the literature was performed electronically in PubMed (PubMed Central, and MEDLINE) for articles published in English from 2000 to April of 2017. The article is also based on the authors' clinical experience with children with coeliac disease. The searched keywords were “coeliac disease “,”oral manifestations “, “dental enamel defects”, “recurrent aphthous stomatitis” and “oral aphthous ulcers”. Results: There are some oral manifestations which are strictly related to coeliac disease: dental enamel defects, recurrent aphthous stomatitis, delayed tooth eruption, multiple caries, angular cheilitis, atrophic glossitis, dry mouth and burning tongue. Conclusion: The complete knowledge of the oral manifestations of coeliac disease can trigger an effective change in the quality of life of the patients with this disease. PMID:29238414

  17. Oral Manifestations in Pediatric Patients with Coeliac Disease - A Review Article.

    Science.gov (United States)

    Macho, Viviana Marisa Pereira; Coelho, Ana Sofia; Veloso E Silva, Diana Maria; de Andrade, David José Casimiro

    2017-01-01

    Coeliac disease is a chronic enteropathy that remains a challenge for the clinician, due to its atypical manifestations and etiopathogenic complexity. This article intends to describe the oral characteristics of Coeliac Disease in children in order to facilitate their management in the dental office. A review of the literature was performed electronically in PubMed (PubMed Central, and MEDLINE) for articles published in English from 2000 to April of 2017. The article is also based on the authors' clinical experience with children with coeliac disease. The searched keywords were "coeliac disease ","oral manifestations ", "dental enamel defects", "recurrent aphthous stomatitis" and "oral aphthous ulcers". There are some oral manifestations which are strictly related to coeliac disease: dental enamel defects, recurrent aphthous stomatitis, delayed tooth eruption, multiple caries, angular cheilitis, atrophic glossitis, dry mouth and burning tongue. The complete knowledge of the oral manifestations of coeliac disease can trigger an effective change in the quality of life of the patients with this disease.

  18. Magnetic biomineralisation in Huntington's disease transgenic mice

    International Nuclear Information System (INIS)

    Beyhum, W; Hautot, D; Dobson, J; Pankhurst, Q A

    2005-01-01

    The concentration levels of biogenic magnetite nanoparticles in transgenic R6/2 Huntington's disease (HD) mice have been investigated, using seven control and seven HD mice each from an 8 week-old litter and from a 12 week-old litter. Hysteresis and isothermal remnant magnetisation data were collected on a SQUID magnetometer, and analysed using a model comprising dia/paramagnetic, ferrimagnetic and superparamagnetic contributions, to extract the magnetite and ferritin concentrations present. It was found that magnetite was present in both superparamagnetic and blocked states. A larger spread and higher concentration of magnetite levels was found in the diseased mice for both the 8 week-old and 12 week-old batches, compared to the controls

  19. Extraosseous manifestation of Gaucher's disease type I: MR and histological appearance

    International Nuclear Information System (INIS)

    Poll, L.W.; Koch, J.A.; Moedder, U.

    2000-01-01

    Gaucher's disease type I is the most prevalent lysosomal storage disorder caused by an autosomal-recessive inherited deficiency of glucocerebrosidase activity with secondary accumulation of glucocerebrosides within the lysosomes of macrophages. The storage disorder produces a multisystem disease characterized by progressive visceral enlargement and gradual replacement of bone marrow with lipid-laden macrophages. Skeletal disease is a major source of disability in Gaucher's disease. Extraosseous extension of Gaucher cells is an extremely rare manifestation of skeletal Gaucher's disease. This is a report on the MRI and histopathological findings of an extraosseous Gaucher-cell extension into the midface in a patient with Gaucher's disease. (orig.)

  20. Association of extraintestinal manifestations and anaemia with disease outcomes in patients with inflammatory bowel disease.

    Science.gov (United States)

    Vegh, Zsuzsanna; Kurti, Zsuzsanna; Gonczi, Lorant; Golovics, Petra Anna; Lovasz, Barbara Dorottya; Szita, Istvan; Balogh, Mihaly; Pandur, Tunde; Vavricka, Stephan R; Rogler, Gerhard; Lakatos, Laszlo; Lakatos, Peter Laszlo

    2016-07-01

    The association between extraintestinal manifestations (EIMs) and disease activity suggest a common pathogenetic link with inflammatory bowel disease (IBD). We report on the association of EIMs and anaemia with long-term disease outcomes, including treatment steps, hospitalization, and surgery in the prospective population-based IBD inception cohort from Veszprem province. Data of 678 incident IBD patients (Crohn's disease/ulcerative colitis(CD/UC): 331/347) diagnosed from 1st January 2000 to 31st December 2012 were analyzed (CD: m/f: 176/155, median age at diagnosis: 28, IQR: 21-40 years, disease duration: 6, IQR: 2-9 years; UC: m/f: 200/147, median age at diagnosis: 36, IQR: 26-50 years, duration: 7, IQR: 4-10 years). EIMs were present in 30% of the CD and 17.3% of the UC patients. In CD, female gender (p = 0.02) need for steroid (p  < 0.001) and azathioprine (AZA) (p = 0.02), while in UC, young age at onset (p = 0.03), extensive disease (p = 0.003), female gender (p = 0.07), need for steroids (p < 0.001) and AZA (p = 0.004) and need for IBD-related hospitalization (p = 0.01) were associated with the presence of EIMs. Anaemia was present in 56.7% of the CD and 30.2% of the UC patients. In both CD and UC anaemia was associated with age at onset (pCD = 0.001, pUC = 0.04), disease location/extent (pCD = 0.02, pUC < 0.001), steroid and AZA use (for both pCD,UC < 0.001), need for surgery/colectomy (pCD < 0.001, pUC = 0.002) and hospitalization (pCD = 0.004, pUC < 0.001) and in CD, it was associated with anti TNF therapy(p = 0.002). The presence of EIMs was associated with disease phenotype in UC and with treatment strategy in both CD and UC. Additionally, anaemia was associated with hospitalization and surgery in both CD and UC, suggesting that EIMs and anaemia may be helpful in stratifying disease severity in IBD.

  1. Lyme Disease Manifestations in the Foot and Ankle: A Retrospective Case Series.

    Science.gov (United States)

    Miller, Jason R; Dunn, Karl W; Braccia, Domenick; Ciliberti, Louis J; Becker, Dina K; Hollinger, Joshua K; Brand, Shelley M

    Lyme disease is the result of Borrelia burgdorferi bacterial infection after exposure from a tick bite. A pathognomonic finding in early-stage Lyme disease is an expanding, red macular ring known as erythema migrans. Lyme arthritis is a late-stage manifestation of this disease, affecting the large, weightbearing joints with intermittent pain and swelling. The existing data on Lyme disease and subsequent arthritis have reported manifestations in the lower extremity, primarily in the knee and ankle and less commonly the small joints of the foot. We present a retrospective case series of 11 cases of painful arthritis in the foot and ankle with confirmatory Lyme disease testing. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  2. Metabolic syndrome and incidence of type 2 diabetes in patients with manifest vascular disease

    NARCIS (Netherlands)

    Wassink, A.M.J.; Graaf, van der Y.; Soedamah-Muthu, S.S.; Spiering, W.; Visseren, F.L.J.

    2008-01-01

    Risk reduction in patients with clinically manifest vascular disease focuses on preventing new vascular events and not on prevention of type 2 diabetes. However, given the common pathophysiological pathways involved in the development of atherosclerosis and type 2 diabetes, it is probable that

  3. Zika and Spondweni Viruses: Historic Evidence of Misidentification, Misdiagnosis and Serious Clinical Disease Manifestations

    Science.gov (United States)

    2016-10-01

    isolations of 153 Zika virus from Aedes (Stegomyia) africanus (Theobald) taken in and above a Uganda Forest. 154 Bulletin of the World Health...1 Zika and Spondweni viruses : Historic evidence of misidentification, misdiagnosis, and serious clinical disease manifestations Andrew D...serogroup (family Flaviviridae, genus Flavivirus) consists of two members: Zika 3 and Spondweni viruses . Both viruses have been historically misidentified

  4. Erythema multiforme and persistent erythema as early cutaneous manifestations of Lyme disease

    NARCIS (Netherlands)

    Schuttelaar, M L; Laeijendecker, R; Heinhuis, R J; Van Joost, T

    1997-01-01

    We report two cases of borreliosis (Lyme disease) with unusual cutaneous manifestations, erythema multiforme, and persistent erythema. The lesions in both of our patients had distinctive histopathologic features. To our knowledge, this is the first report of erythema multiforme and persistent

  5. Clinical manifestations in uveitis patients with and without rheumatic disease in a Chinese population in Taiwan.

    Science.gov (United States)

    Tseng, Shi-Ting; Yao, Tsung-Chieh; Huang, Jing-Long; Yeh, Kuo-Wei; Hwang, Yih-Shiou

    2017-12-01

    Uveitis can be a local eye disease or a manifestation of systemic rheumatologic disorders. However, the differences of clinical manifestations between uveitis patients with or without systemic rheumatologic disease have been seldom described in literature. We investigated the clinical features and complications of rheumatic disease-related uveitis, and compared the characteristics in patients with and without rheumatic disease in a Chinese population in Taiwan. A retrospective review was performed for all patients who had been diagnosed with uveitis between January 2009 and June 2014 at the Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan. A total of 823 uveitis patients were enrolled in the study, including 123 patients with rheumatic diseases. The most frequent rheumatic diseases included ankylosing spondylitis (5.8%), followed by Behçet's disease (2.8%), sarcoidosis (1.4%), psoriasis (1.1%), and juvenile idiopathic arthritis (1.1%). Compared with patients without rheumatic disease, those with rheumatic disease-related uveitis had a lower mean age at onset (35.1 ± 15.8 years vs. 44.0 ± 17.5 years), a longer follow-up period (27.1 ± 25.3 months vs. 22.2 ± 23.0 months), a higher incidence of anterior uveitis (69.0% vs. 46.3%), less frequent posterior uveitis (4.9% vs. 21.4%), a higher incidence of recurrence (26.8% vs. 14.1%), more frequent bilateral involvement (53.7% vs. 38.8%), and more frequent posterior synechiae (17.2% vs. 9.4%). The disease course and clinical manifestations of rheumatic disease-related uveitis were different from those unrelated. Patients with rheumatic disease-related uveitis had a higher recurrent rate and more frequent posterior synechiae than patients without rheumatic diseases. Copyright © 2015. Published by Elsevier B.V.

  6. Mice lacking prostaglandin E receptor subtype 4 manifest disrupted lipid metabolism attributable to impaired triglyceride clearance.

    Science.gov (United States)

    Cai, Yin; Ying, Fan; Song, Erfei; Wang, Yu; Xu, Aimin; Vanhoutte, Paul M; Tang, Eva Hoi-Ching

    2015-12-01

    Upon high-fat feeding, prostaglandin E receptor subtype 4 (EP4)-knockout mice gain less body weight than their EP4(+/+) littermates. We investigated the cause of the lean phenotype. The mice showed a 68.8% reduction in weight gain with diminished fat mass that was not attributable to reduced food intake, fat malabsorption, or increased energy expenditure. Plasma triglycerides in the mice were elevated by 244.9%. The increase in plasma triglycerides was independent of changes in hepatic very low density lipoprotein (VLDL)-triglyceride production or intestinal chylomicron-triglyceride synthesis. However, VLDL-triglyceride clearance was drastically impaired in the EP4-knockout mice. The absence of EP4 in mice compromised the activation of lipoprotein lipase (LPL), the key enzyme responsible for trafficking of plasma triglycerides into peripheral tissues. Deficiency in EP4 reduced hepatic mRNA expression of the transcriptional factor cAMP response element binding protein H (by 36.8%) and LPL activators, including apolipoprotein (Apo)a5 (by 40.2%) and Apoc2 (by 61.3%). In summary, the lean phenotype of EP4-deficient mice resulted from reduction in adipose tissue and accretion of other peripheral organs caused by impaired triglyceride clearance. The findings identify a new metabolic dimension in the physiologic role played by endogenous EP4. © FASEB.

  7. Lactococcus lactis NCC 2287 Alleviates Food Allergic Manifestations in Sensitized Mice by Reducing IL-13 Expression Specifically in the Ileum

    Directory of Open Access Journals (Sweden)

    Adrian W. Zuercher

    2012-01-01

    Full Text Available Objective. Utilizing a food allergy murine model, we have investigated the intrinsic antiallergic potential of the Lactococcus lactis NCC 2287 strain. Methods. BALB/c mice were sensitized at weekly intervals with ovalbumin (OVA plus cholera toxin (CT by the oral route for 7 weeks. In this model, an oral challenge with a high dose of OVA at the end of the sensitization period leads to clinical symptoms. Lactococcus lactis NCC 2287 was given to mice via the drinking water during sensitization (prevention phase or after sensitization (management phase. Results. Lactococcus lactis NCC 2287 administration to sensitized mice strikingly reduced allergic manifestations in the management phase upon challenge, when compared to control mice. No preventive effect was observed with the strain. Lactococcus lactis NCC 2287 significantly decreased relative expression levels of the Th-2 cytokine, IL-13, and associated chemokines CCL11 (eotaxin-1 and CCL17 (TARC in the ileum. No effect was observed in the jejunum. Conclusion/Significance. These results taken together designate Lactococcus lactis NCC 2287 as a candidate probiotic strain appropriate in the management of allergic symptoms.

  8. Neuroligin 2 R215H Mutant Mice Manifest Anxiety, Increased Prepulse Inhibition, and Impaired Spatial Learning and Memory

    Directory of Open Access Journals (Sweden)

    Chia-Hsiang Chen

    2017-11-01

    Full Text Available Neuroligin 2 (NLGN2 is a postsynaptic adhesion protein that plays an essential role in synaptogenesis and function of inhibitory neuron. We previously identified a missense mutation R215H of the NLGN2 in a patient with schizophrenia. This missense mutation was shown to be pathogenic in several cell-based assays. The objective of this study was to better understand the behavioral consequences of this mutation in vivo. We generated a line of transgenic mice carrying this mutation using a recombinant-based method. The mice were subjected to a battery of behavioral tests including open field locomotor activity assay, prepulse inhibition (PPI assay, accelerated rotarod test, novel location and novel recognition tests, elevated plus-maze (EPM test, and Morris water maze test. The transgenic animals were viable and fertile, but the Nlgn2 R215H knock-in (KI homozygous mice showed growth retardation, anxiety-like behavior, increased PPI, and impaired spatial learning and memory. There was no significant interaction between sex and genotype in most behavioral tests; however, we observed a significant interaction between sex and genotype in EPM test in this study. Also, we found that the Nlgn2 R215H homozygous KI mice did not express the NLGN2 protein, resembling Nlgn2 knockout mice. Our results demonstrate that Nlgn2 R215H KI homozygous mice manifest several behavioral abnormalities similar to those found in psychiatric patients carrying NLGN2 mutations, indicating that dysfunction of NLGN2 contributes to the pathogenesis of certain psychiatric symptoms commonly present in various mental disorders, not limited to schizophrenia.

  9. Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride metabolism without impaired glucose homeostasis.

    Science.gov (United States)

    Wang, Yan; Quagliarini, Fabiana; Gusarova, Viktoria; Gromada, Jesper; Valenzuela, David M; Cohen, Jonathan C; Hobbs, Helen H

    2013-10-01

    Angiopoietin-like protein (ANGPTL)8 (alternatively called TD26, RIFL, Lipasin, and Betatrophin) is a newly recognized ANGPTL family member that has been implicated in both triglyceride (TG) and glucose metabolism. Hepatic overexpression of ANGPTL8 causes hypertriglyceridemia and increased insulin secretion. Here we examined the effects of inactivating Angptl8 on TG and glucose metabolism in mice. Angptl8 knockout (Angptl8(-/-)) mice gained weight more slowly than wild-type littermates due to a selective reduction in adipose tissue accretion. Plasma levels of TGs of the Angptl8(-/-) mice were similar to wild-type animals in the fasted state but paradoxically decreased after refeeding. The lower TG levels were associated with both a reduction in very low density lipoprotein secretion and an increase in lipoprotein lipase (LPL) activity. Despite the increase in LPL activity, the uptake of very low density lipoprotein-TG is markedly reduced in adipose tissue but preserved in hearts of fed Angptl8(-/-) mice. Taken together, these data indicate that ANGPTL8 plays a key role in the metabolic transition between fasting and refeeding; it is required to direct fatty acids to adipose tissue for storage in the fed state. Finally, glucose and insulin tolerance testing revealed no alterations in glucose homeostasis in mice fed either a chow or high fat diet. Thus, although absence of ANGPTL8 profoundly disrupts TG metabolism, we found no evidence that it is required for maintenance of glucose homeostasis.

  10. Zoopharmacognosy in diseased laboratory mice: conflicting evidence.

    Directory of Open Access Journals (Sweden)

    Minesh Kapadia

    Full Text Available Zoopharmacognosy denotes a constellation of learned ingestive responses that promote healing and survival of infected or poisoned animals. A similar self-medication phenomenon was reported in diseased laboratory rodents. In particular, a series of studies revealed that autoimmune MRL/lpr mice readily consume solutions paired or laced with cyclophosphamide (CY, an immunosuppressive drug that prevents inflammatory damage to internal organs. However, due to design limitations, it could not be elucidated whether such a response reflects the learned therapeutic effect of CY, or a deficit in sensory input. We presently assess the behavioural effects of prolonged consumption of CY-laced, 16% sucrose solution in a continuous choice paradigm, with tap water available ad lib. Contrary to overall expectation, MRL/lpr mice did not increase their intake of CY with disease progression. Moreover, they ingested lower doses of CY and preferred less CY-laced sucrose solution than age-matched controls. The results obtained could not confirm zoopharmacognosy in diseased MRL/lpr mice, likely due to impaired responsiveness to palatable stimulation, or attenuated survival mechanisms after prolonged inbreeding in captivity. However, by revealing the effectiveness of unrestricted drinking of drug-laced sucrose solution on behavior and immunity, the current study supports broader use of such an administration route in behavioural studies sensitive to external stressors.

  11. Acute Myocardial Infarction: The First Manifestation of Ischemic Heart Disease and Relation to Risk Factors

    Directory of Open Access Journals (Sweden)

    Manfroi Waldomiro Carlos

    2002-01-01

    Full Text Available OBJECTIVE: To assess the association between cardiovascular risk factors and acute myocardial infarction as the first manifestation of ischemic heart disease, correlating them with coronary angiographic findings. METHODS: We carried out a cross-sectional study of 104 patients with previous acute myocardial infarction, who were divided into 2 groups according to the presence or absence of angina prior to acute myocardial infarction. We assessed the presence of angina preceding acute myocardial infarction and risk factors, such as age >55 years, male sex, smoking, systemic arterial hypertension, lipid profile, diabetes mellitus, obesity, sedentary lifestyle, and familial history of ischemic heart disease. On coronary angiography, the severity of coronary heart disease and presence of left ventricular hypertrophy were assessed. RESULTS: Of the 104 patients studied, 72.1% were males, 90.4% were white, 73.1% were older than 55 years, and 53.8% were hypertensive. Acute myocardial infarction was the first manifestation of ischemic heart disease in 49% of the patients. The associated risk factors were systemic arterial hypertension (RR=0.19; 95% CI=0.06-0.59; P=0.04 and left ventricular hypertrophy (RR=0.27; 95% CI=0,.8-0.88; P=0.03. The remaining risk factors were not statistically significant. CONCLUSION: Prevalence of acute myocardial infarction as the first manifestation of ischemic heart disease is high, approximately 50%. Hypertensive individuals more frequently have symptoms preceding acute myocardial infarction, probably due to ventricular hypertrophy associated with high blood pressure levels.

  12. Case Reports of Cat Scratch Disease with Typical and Atypical Clinical Manifestations: A Literature Review

    Directory of Open Access Journals (Sweden)

    Gulshan Umbreen

    2017-04-01

    Full Text Available Cat scratch disease (CSD is the most well-known zoonotic disease spread by domestic animals like cats. Cats are the source of Bartonella henselae. Most patients more than ninety percent 3-12 days after a scratch from a cat, undoubtedly a little cat with insects present with one or more erythematous injuries at the site of inoculation, the sore is typically a crusted papule or, once in a while, a pustule. More than half of cases in one study show that the systemic indications went with the lymphadenopathy. These may incorporate fever, discomfort, migraine and anorexia and frequently happen in immunocompromised patients. Atypically clinical manifestations happen are altered mental status, perplexity, prolonged fever, respiratory protestations (atypical pneumonitis, Joint pain, synovitis, Back agony is uncommon. The hypothesis of the study to find out that cat scratch disease cause typical and atypical clinical manifestation. Study was conducted July 2015 to September 2015. The methodology sections of a review article are listed all of the databases and citation indexes that were searched such as Web of Science and PubMed and any individual journals that were searched. Various case reports were mentioned in the study. Case reports of cat scratch diseases with typical and atypical clinical manifestation included in the study. The objective of review of these reporting cases is to make physicians aware about cat scratch diseases and also need to create awareness about cat scratch disease in pet owner. Although it is self-limiting needs to report to health authorities. There are few cases reported in which mostly cases reported in twain, japan, Brazil, Texas, United States, Dhaka, Spain with typical and atypical clinical manifestation

  13. Clinical and Laboratory Features and Extraintestinal Manifestations of Celiac Disease in Adults

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    Mete Akın

    2012-04-01

    Full Text Available Aim: Celiac disease an autoimmune disorder resulting from an immune response to the gluten in genetically predisposed patients. Although, diarrhea is the most common finding at presentation in adults, disease may present with extraintestinal manifestations such as anemia, osteoporosis, elevated transaminase levels and growth retardation. In this article, symptoms, extraintestinal manifestations and coexistence with other autoimmune disorders of adult patients with celiac disease were evaluated. Material and Method: 22 patients whose followed with the diagnosis of celiac disease in Suleyman Demirel University Department of Gastroenterology, between January 2007 and Semptember 2010, were evaluated retrospectively. Symptoms, extraintestinal manifestations and coexistence with other autoimmune disorders of patients at presentation were investigated. Results: 13 (59% of all cases were female and 9 (41% were male. Mean age at presentation was 38,5 years. Most common complaints were diarrhea and weakness . Tissue transglutaminase and/or antiendomysium antibody were positive, and diagnosis was confirmed by histopathologic examination in all patients. Iron deficiency, vitamine B12 deficiency and folic acid deficiency were detected in 17 (77%, 8 (36% and 6 (27% patients, respectively. There were elevated transaminase levels in 8 (36% patients. Osteoporosis was detected in 4 female and 1 male patients. Sensorimotor polineuropathy was detected in 2 patients. There was growth retardation in 2 patients. Autoimmune hypothyroidism and Type 1 diabetes mellitus were detected in 2 and 1 patients, respectively. Coexistence with Crohn%u2019s disease was detected in a patient. Discussion: Celiac disease may present with extraintestinal manifestations in adults. It should be remembered, especially in patients with iron deficiency and mild to moderate transaminase elevations with unexplained etiology. It should be considered in patients with chronic diarrhea and

  14. Neuropsychiatric manifestation of celiac disease: A case-control study in North India

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    Mahendra Nimel

    2016-01-01

    Full Text Available Background: Celiac disease (CD is an immune-mediated disease dependent on gluten. Prevalence of CD is about 1% and beside gastrointestinal complaints, neuropsychiatric symptoms may represent an atypical feature of CD. Some studies suggest that a gluten-free diet is effective in treating them. Settings and Design: This case-control study of 49 cases was done during the period of January to March 2013. Aim: To know the spectrum of psychiatric manifestations and cognitive functions in children with CD. Materials and Methods: We took 49 diagnosed cases of CD (based on the demonstration of IgA tissue transglutaminase antibodies and duodenal biopsy and compared with demographically matched control group (n = 50 on Seguin Form Board Test for cognitive functions and Behavioral Summarized Evaluation-Revised scale for assessment of psychiatric and behavior disturbances. All possible psychiatric diagnosis was made on the basis of International Statistical Classification of Disease and Related Health Problems-Tenth Revision criteria. Statistical Analysis: Statistical analyses were done by using Chi-square test and two-tailed P-values. Results: Neuropsychiatric manifestations were seen in 29% of cases as against 4% of controls which was statistically significant (P=0.001. Only four cases and 1 control fount to be mild mental retardation (P = 0.16. Autism, dyslexia, developmental delay, disruptive behavior disorder, and tic disorder present in cases were not found. Conclusion: Clinical manifestations of CD vary from typical malabsorption syndrome to neuropsychiatric manifestations. Those psychiatric patients who are not responding to standard pharmacological modalities, a diagnosis of CD should be taken into consideration. Only behavioral problem can be the sole clinical manifestation of CD.

  15. Extraneural manifestations of prion infection in GPI-anchorless transgenic mice

    International Nuclear Information System (INIS)

    Lee, Andrew M.; Paulsson, Johan F.; Cruite, Justin; Andaya, Abegail A.; Trifilo, Matthew J.; Oldstone, Michael B.A.

    2011-01-01

    Earlier studies indicated that transgenic (tg) mice engineered to express prion protein (PrP) lacking the glycophosphatidylinositol (GPI -/- ) membrane anchor formed abnormal proteinase-resistant prion (PrPsc) amyloid deposits in their brains and hearts when infected with the RML strain of murine scrapie. In contrast, RML scrapie infection of normal mice with a GPI-anchored PrP did not deposit amyloid with PrPsc in the brain or the heart. Here we report that scrapie-infected GPI -/- PrP tg mice also deposit PrP and transmissible infectious material in the gut, kidneys, and islets of Langerhans. Similar to previously reported amyloid deposits in the brain and heart, amyloid deposits were found in the gut; however, no amyloid deposited in the islets. By high-resolution electron microscopy, we show PrP is located primarily in α cells and also β cells. Islets contain abundant insulin and there is no abnormality in glucose metabolism in infected GPI -/- PrP tg mice.

  16. Developmental Stage-Specific Manifestations of Absent TPO/c-MPL Signalling in Newborn Mice.

    Science.gov (United States)

    Lorenz, Viola; Ramsey, Haley; Liu, Zhi-Jian; Italiano, Joseph; Hoffmeister, Karin; Bihorel, Sihem; Mager, Donald; Hu, Zhongbo; Slayton, William B; Kile, Benjamin T; Sola-Visner, Martha; Ferrer-Marin, Francisca

    2017-12-01

    Congenital amegakaryocytic thrombocytopaenia (CAMT) is a disorder caused by c-MPL mutations that impair thrombopoietin (TPO) signalling, resulting in a near absence of megakaryocytes (MKs). While this phenotype is consistent in adults, neonates with CAMT can present with severe thrombocytopaenia despite normal MK numbers. To investigate this, we characterized MKs and platelets in newborn c-MPL –/– mice. Liver MKs in c-MPL –/– neonates were reduced in number and size compared with wild-type (WT) age-matched MKs, and exhibited ultrastructural abnormalities not found in adult c-MPL –/– MKs. Platelet counts were lower in c-MPL –/– compared with WT mice at birth and did not increase over the first 2 weeks of life. In vivo biotinylation revealed a significant reduction in the platelet half-life of c-MPL –/– newborn mice (P2) compared with age-matched WT pups, which was not associated with ultrastructural abnormalities. Genetic deletion of the pro-apoptotic Bak did not rescue the severely reduced platelet half-life of c-MPL –/– newborn mice, suggesting that it was due to factors other than platelets entering apoptosis early. Indeed, adult GFP+ (green fluorescent protein transgenic) platelets transfused into thrombocytopenic c-MPL –/– P2 pups also had a shortened lifespan, indicating the importance of cell-extrinsic factors. In addition, neonatal platelets from WT and c-MPL –/– mice exhibited reduced P-selectin surface expression following stimulation compared with adult platelets of either genotype, and platelets from c-MPL –/– neonates exhibited reduced glycoprotein IIb/IIIa (GPIIb/IIIa) activation in response to thrombin compared with age-matched WT platelets. Taken together, our findings indicate that c-MPL deficiency is associated with abnormal maturation of neonatal MKs and developmental stage-specific defects in platelet function.

  17. CLINICAL MANIFESTATION, DIAGNOSTICS AND TREATMENT OF KAWASAKI DISEASE: KNOWN DATA AND UNSOLVED QUESTIONS

    Directory of Open Access Journals (Sweden)

    G. А. Lyskina

    2013-01-01

    Full Text Available The lecture deals with the most common systemic vasculitis in pediatric practice — Kawasaki disease. This disorder is associated with risk of myocardial infarction and sudden cardiac death in children and young adults and at present is considered to be the main cause of the acquired heard diseases in children. The authors give historical aspects and modern opinions on etiology, pathogenesis, clinical manifestation, diagnostics and treatment of Kawasaki disease. The data were summarized from Russian and foreign literature as well as from the own authors’ experience.

  18. Subglotic Stenosis as manifestation in Wegener’s Disease. A case report

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    Sofía VALLE-OLSEN

    2017-03-01

    Full Text Available Introduction and objective: Subglottic stenosis in Wegener’s disease (WD represents a diagnostic challenge because it’s ability to be the unique manifestation. Description: A case of subglottic GW described in a woman 14 years. Discussion: Subglottic stenosis secondary to Wegener’s disease use to be associated with ENT symptoms, so these can give us the etiological suspicion. In the absence of these, we should include it in the differential diagnosis and try a histopathologic confirmation. Conclusions: In an isolated subglottic stenosis, rule Wegener's disease performing a biopsy of nasal mucosa and two serology tests.

  19. Oromandibular Dyskinesia as the Initial Manifestation of Late-Onset Huntington Disease

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    Dong-Seok Oh

    2011-10-01

    Full Text Available Huntington’s disease (HD is a neurodegenerative disorder characterized by a triad of choreoathetosis, dementia and dominant inheritance. The cause of HD is an expansion of CAG trinucleotide repeats in the HD gene. Typical age at onset of symptoms is in the 40s, but the disorder can manifest at any time. Late-onset (≥ 60 years HD is clinically different from other adult or juvenile onset HD and characterized by mild motor problem as the initial symptoms, shorter disease duration, frequent lack of family history, and relatively low CAG repeats expansion. We report a case of an 80-year-old female with oromandibular dyskinesia as an initial manifestation of HD and 40 CAG repeats.

  20. Oral Manifestations of Crohn’s Disease: A Case Report and Review of the Literature

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    Victoria L. Woo

    2015-01-01

    Full Text Available Crohn’s disease (CD is an inflammatory disorder of the gastrointestinal tract that is likely caused by an inappropriate mucosal inflammatory response to intestinal bacteria in a genetically predisposed host. The lesions of CD can involve any region of the GI tract as well as extraintestinal sites such as the skin, joints, and eyes. The most common presenting symptoms are abdominal pain and prolonged diarrhea associated with fevers, fatigue, and malaise. Delayed growth and failure to thrive may also be observed in pediatric patients. Oral manifestations of CD are known as oral CD and may precede GI involvement, thus serving as early markers of this condition. We describe a 6-year-old male who presented with oral lesions as his initial manifestation of disease and review the current literature pertaining to oral CD.

  1. The role of the amygdala during emotional processing in Huntington's disease: from pre-manifest to late stage disease.

    Science.gov (United States)

    Mason, Sarah L; Zhang, Jiaxiang; Begeti, Faye; Guzman, Natalie Valle; Lazar, Alpar S; Rowe, James B; Barker, Roger A; Hampshire, Adam

    2015-04-01

    Deficits in emotional processing can be detected in the pre-manifest stage of Huntington's disease and negative emotion recognition has been identified as a predictor of clinical diagnosis. The underlying neuropathological correlates of such deficits are typically established using correlative structural MRI studies. This approach does not take into consideration the impact of disruption to the complex interactions between multiple brain circuits on emotional processing. Therefore, exploration of the neural substrates of emotional processing in pre-manifest HD using fMRI connectivity analysis may be a useful way of evaluating the way brain regions interrelate in the period prior to diagnosis. We investigated the impact of predicted time to disease onset on brain activation when participants were exposed to pictures of faces with angry and neutral expressions, in 20 pre-manifest HD gene carriers and 23 healthy controls. On the basis of the results of this initial study went on to look at amygdala dependent cognitive performance in 79 Huntington's disease patients from a cross-section of disease stages (pre-manifest to late disease) and 26 healthy controls, using a validated theory of mind task: "the Reading the Mind in the Eyes Test" which has been previously been shown to be amygdala dependent. Psychophysiological interaction analysis identified reduced connectivity between the left amygdala and right fusiform facial area in pre-manifest HD gene carriers compared to controls when viewing angry compared to neutral faces. Change in PPI connectivity scores correlated with predicted time to disease onset (r=0.45, pneural networks underlying social cognition and emotional processing can be detected prior to clinical diagnosis in Huntington's disease. Connectivity between the amygdala and other brain regions is impacted by the disease process in pre-manifest HD and may therefore be a useful way of identifying participants who are approaching a clinical diagnosis

  2. OCULAR MANIFESTATIONS IN PATIENTS WITH CHRONIC KIDNEY DISEASE- A HOSPITALBASED STUDY

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    Shobha Ponmudy

    2017-08-01

    Full Text Available BACKGROUND Chronic kidney disease affects every organ system including the eye. The aim of the study is to conduct a thorough ocular examination and to study the occurrence of various ocular manifestations exhibited by patients with chronic kidney disease and to analyse the findings. MATERIALS AND METHODS 100 patients from Department of Nephrology, Stanley Medical College diagnosed with chronic kidney disease were examined for ocular manifestations at the Department of Ophthalmology, Stanley Medical College. This is a cross-sectional, descriptive, non-interventional, hospital-based study. The period of study was from August 2010 to October 2011. RESULTS The commonest cause of CKD was hypertension in 47 pts. (52.2% followed by both diabetes and hypertension in 30 patients. Patients with only diabetes were 6 patients (6.7% and with other causes were 7 patients (7.8%.10% of patients were legally blind with visual acuity <6/60. In this study, 65 patients belonged to less than 50 years. 49.3% of the presenile patients had cataract. A reduced Schirmer’s value was noted in 54 eyes of the 200 eyes. The incidence of ocular surface disease in the study was 27%. 92 eyes out of 200 eyes studied showed hypertensive retinopathy. Higher grades of hypertensive retinopathy was more in advanced stages of CKD, i.e. 24 eyes in stage IV and 23 eyes in stage V. 51 eyes out of 40 diabetics showed diabetic retinopathy changes of which a majority of 25 eyes belonged to stage V disease. Prevalence of diabetic retinopathy in CKD patients is significantly more when compared to diabetic patients without CKD. CONCLUSION Study demonstrates that routine ocular evaluation is necessary in all patients with chronic kidney disease irrespective of the presence of ocular symptoms. It also highlights the occurrence of a variety of treatable ocular manifestations, which can become vision threatening if not taken care of at the earliest.

  3. Critical Role of Airway Macrophages in Modulating Disease Severity during Influenza Virus Infection of Mice

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    Tate, Michelle D.; Pickett, Danielle L.; van Rooijen, Nico; Brooks, Andrew G.; Reading, Patrick C.

    2010-01-01

    Airway macrophages provide a first line of host defense against a range of airborne pathogens, including influenza virus. In this study, we show that influenza viruses differ markedly in their abilities to infect murine macrophages in vitro and that infection of macrophages is nonproductive and no infectious virus is released. Virus strain BJx109 (H3N2) infected macrophages with high efficiency and was associated with mild disease following intranasal infection of mice. In contrast, virus strain PR8 (H1N1) was poor in its ability to infect macrophages and highly virulent for mice. Depletion of airway macrophages by clodronate-loaded liposomes led to the development of severe viral pneumonia in BJx109-infected mice but did not modulate disease severity in PR8-infected mice. The severe disease observed in macrophage-depleted mice infected with BJx109 was associated with exacerbated virus replication in the airways, leading to severe airway inflammation, pulmonary edema, and vascular leakage, indicative of lung injury. Thymic atrophy, lymphopenia, and dysregulated cytokine and chemokine production were additional systemic manifestations associated with severe disease. Thus, airway macrophages play a critical role in limiting lung injury and associated disease caused by BJx109. Furthermore, the inability of PR8 to infect airway macrophages may be a critical factor contributing to its virulence for mice. PMID:20504924

  4. EXTRAOESOPHAGEAL MANIFESTATIONS OF GASTROESOPHAGEAL REFLUX DISEASE IN THE PRACTICE OF PEDIATRIC OTORHINOLARYNGOLOGIST

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    A. I. Asmanov

    2017-01-01

    Full Text Available Gastroesophageal reflux disease (GERD is a chronic recurrent disorder with esophageal and extraesophageal symptoms and a variety of morphological changes of the mucous membrane of the esophagus caused by retrograde reflux of the gastric or gastro-intestinal contents. Extraesophageal (atypical symptoms are mainly complaints which indicate involvement in the process of bronchopulmonary, cardiovascular diseases and ENT-organs. This article discusses the pathogenesis of extraesophageal manifestations of GERD, and recommendations on diagnosis and treatment based on the author’s own experience and data of international publications.

  5. Primary coenzyme Q deficiency in Pdss2 mutant mice causes isolated renal disease.

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    Min Peng

    2008-04-01

    Full Text Available Coenzyme Q (CoQ is an essential electron carrier in the respiratory chain whose deficiency has been implicated in a wide variety of human mitochondrial disease manifestations. Its multi-step biosynthesis involves production of polyisoprenoid diphosphate in a reaction that requires the enzymes be encoded by PDSS1 and PDSS2. Homozygous mutations in either of these genes, in humans, lead to severe neuromuscular disease, with nephrotic syndrome seen in PDSS2 deficiency. We now show that a presumed autoimmune kidney disease in mice with the missense Pdss2(kd/kd genotype can be attributed to a mitochondrial CoQ biosynthetic defect. Levels of CoQ9 and CoQ10 in kidney homogenates from B6.Pdss2(kd/kd mutants were significantly lower than those in B6 control mice. Disease manifestations originate specifically in glomerular podocytes, as renal disease is seen in Podocin/cre,Pdss2(loxP/loxP knockout mice but not in conditional knockouts targeted to renal tubular epithelium, monocytes, or hepatocytes. Liver-conditional B6.Alb/cre,Pdss2(loxP/loxP knockout mice have no overt disease despite demonstration that their livers have undetectable CoQ9 levels, impaired respiratory capacity, and significantly altered intermediary metabolism as evidenced by transcriptional profiling and amino acid quantitation. These data suggest that disease manifestations of CoQ deficiency relate to tissue-specific respiratory capacity thresholds, with glomerular podocytes displaying the greatest sensitivity to Pdss2 impairment.

  6. Clinical and immunological relevance of anti-neuronal antibodies in celiac disease with neurological manifestations

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    Caio, Giacomo; Giorgio, Roberto De; Venturi, Alessandro; Giancola, Fiorella; Latorre, Rocco; Boschetti, Elisa; Serra, Mauro; Ruggeri, Eugenio; Volta, Umberto

    2015-01-01

    Aim: To assess anti-neuronal antibodies (NA) prevalence and their correlation with neurological disorders and bowel habits in celiac disease (CD) patients. Background: Neurological manifestations are estimated to occur in about 10% of celiac disease patients and NA to central nervous system (CNS) and enteric nervous system (ENS) are found in a significant proportion of them. Little is known about the clinical and immunological features in CD patients with neurological manifestations. Patients and methods: NA to CNS and ENS were investigated in 106 CD patients and in 60 controls with autoimmune disorders by indirect immunofluorescence on rat / primate cerebellar cortex and intestinal (small and large bowel) sections. Results: IgG NA to CNS (titer 1:50 - 1:400) were positive in 23 celiacs (21%), being more frequently detected in those with neurological disorders that in those without neurological dysfunction (49% vs. 8%, P 1:200 had severe constipation. Only one patient with cerebellar ataxia and intestinal sub-occlusion was positive for NA to CNS and ENS. NA to CNS and ENS were found in 7% and 5% of controls, respectively. Conclusion: In CD the positivity of NA to CNS can be regarded as a marker of neurological manifestations. High titer NA to ENS are associated with severe constipation. The demonstration of NA to CNS and ENS suggests an immune-mediated pathogenesis leading to central neural impairment as well as gut dysfunction (hence constipation), respectively. PMID:25926940

  7. Association between oral manifestations and inhaler use in asthmatic and chronic obstructive pulmonary disease patients

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    Bhargavi Krishna Ayinampudi

    2016-01-01

    Full Text Available Objectives: To examine the association between oral manifestations and type, frequency and duration of inhaler usage, also type and dosage of medication used in asthmatic and chronic obstructive pulmonary disease (COPD patients. Materials and Methods: A cross-sectional study was conducted on 250 patients of both sexes suffering from asthma and COPD who were using inhalers. Frequency of oral manifestation seen on the tongue, buccal mucosa, teeth, periodontium, palate, floor of the mouth, lips, and xerostomia in inhaler users depending on the type of inhaler, type and dosage of medication, frequency and duration of use of inhaler were examined. Chi-square test was used for statistical analysis and P 0.05. Gingivitis/gingival enlargement (53.6% and 51.5% was almost similar but periodontitis was higher in those using >500 μg. Significant association (P < 0.05 was observed with duration <1 year; oral manifestations seen were taste alterations (53.2% in tongue, ulcerations (63.6% in the buccal mucosa, teeth affected (87%, gingivitis/gingival enlargement (66.2%, and xerostomia (89.6%. Conclusions: As asthmatics and COPD patients are at a higher risk of developing oral diseases during inhalation therapy, it is necessary to educate patients on proper oral health care and maintenance.

  8. Manifestaciones reumatológicas de la enfermedad inflamatoria intestinal Rheumatologic manifestations of inflammatory bowel disease

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    Octavio Germán Muñoz Maya

    2006-01-01

    Full Text Available La enfermedad inflamatoria intestinal (EII se caracteriza por la activación inapropiada del sistema inmune de la mucosa intestinal y sus dos formas de presentación son: la colitis ulcerativa y la enfermedad de Crohn. Las manifestaciones extraintestinales se presentan hasta en el 36% de los pacientes y pueden comprometer cualquier órgano o sistema. La disfunción inmune se caracteriza por el desequilibrio entre los mediadores proinflamatorios y los antinflamatorios y se expresa como una enfermedad sistémica. Las manifestaciones reumatológicas asociadas a la EII son de tres tipos: la artritis periférica, la espondiloartropatía y una tercera categoría que incluye lesiones dérmicas, oftálmicas y del metabolismo óseo, entre otras. El manejo de estas manifestaciones se basa en la terapia sistémica para el control de la actividad inflamatoria local utilizando esteroides, derivados de la 5-ASA, inmunomoduladores y, en los últimos años, terapia anti-TNF. The main feature of inflammatory bowel disease (IBD is the continuous activation of the mucosa-associated immune system; the disease has two major forms of presentation: ulcerative colitis and Crohn´s disease. The extraintestinal manifestations are present in 36% of patients, and any organ can be affected. There is an imbalance between proinflammatory and antinflammatory cytokines leading to a systemic disease. The rheumatologic manifestations of the IBD are: Peripheral arthritis, spondyloarthropathy and a third category that includes dermic and ocular lesions as well as metabolic bone disease. Control of the extraintestinal manifestations is based on systemic therapy with steroids, 5-ASA derivatives and biological anti-TNF therapy.

  9. Osteoarticular manifestations of celiac disease and non-celiac gluten hypersensitivity.

    Science.gov (United States)

    Dos Santos, Stéphanie; Lioté, Frédéric

    2017-05-01

    Celiac disease is a chronic inflammatory autoimmune enteropathy based disorder that is triggered by the ingestion of gluten in genetically susceptible individuals. The global prevalence of 1% to 2% represents only the tip of the iceberg. The diagnosis is confirmed by positive specific antibody, anti-transglutaminase or anti-endomysium, specific lesions of the small intestine and a response to strict gluten-free diet. The diagnosis is difficult and often delayed because the clinical variability is very large, ranging from digestive clinical presentation "classic" to "atypical" symptoms, often extra-intestinal, that are sometimes attributed to a concomitant disease or a complication. Among them, there are frequent musculoskeletal manifestations such as osteoporosis and osteomalacia. In the absence of risk factor, osteoporosis, in a premenopausal women or in a man less than 55 years, more is if it is severe and refractory to medications, need to rheumatologists on the track of celiac disease in the absence of digestive symptoms. Osteomalacia is related to secondary hypovitaminosis D malabsorption. Supplementation by calcifediol, water-soluble vitamin D, may be indicated. Celiac disease is associated with an autoimmune disease in almost 1/3 of the cases. Knowing these potential associations allows earlier diagnosis in patients whose only manifestation, a concomitant disease. Anemia, chronic fatigue or unexplained polyarthralgia are symptoms associated with celiac disease to look for specific antibodies. The aim of early diagnosis is to prevent the emergence of other systemic disorders and avoid complications such as bone fractures and cancer, especially intestinal lymphoma. Non-celiac gluten intolerance is a new entity defined by symptomatology similar to that of celiac disease induced by the ingestion of gluten and disappearing after crowding-out, among patients without specific antibodies and without intestinal lesion of celiac disease. This entity is a cause, at

  10. A case of membranous nephropathy as a manifestation of graft-versus-host disease

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    Jae Hyun Han

    2013-03-01

    Full Text Available Nephrotic syndrome (NS rarely occurs after hematopoietic stem cell transplantation (HSCT as a late manifestation of graft-versus-host disease (GVHD. Herein, we report a case of HSCT-associated membranous nephropathy in a female patient with aplastic anemia. The patient received an allogeneic HSCT from her human leukocyte antigen-identical brother following myeloablative conditioning chemotherapy. NS occurred 21 months after HSCT without any concurrent features of chronic GVHD. The patient was treated with prednisolone and cyclosporine after renal biopsy confirmed membranous nephropathy, and achieved complete remission. Our report contradicts previous assumptions that concomitant chronic GVHD is responsible for the development of NS, suggesting that NS can develop as a new, independent manifestation of GVHD.

  11. Tics as an initial manifestation of juvenile Huntington's disease: case report and literature review.

    Science.gov (United States)

    Cui, Shi-Shuang; Ren, Ru-Jing; Wang, Ying; Wang, Gang; Chen, Sheng-Di

    2017-08-08

    Huntington's disease (HD) is an autosomal dominant disorder, typically characterized by chorea due to a trinucleotide repeat expansion in the HTT gene, although the clinical manifestations of patients with juvenile HD (JHD) are atypical. A 17-year-old boy with initial presentation of tics attended our clinic and his DNA analysis demonstrated mutation in the HTT gene (49 CAG repeats). After treatment, his symptoms improved. Furthermore, we performed literature review through searching the databases and summarized clinical features in 33 JHD patients. The most prevalent symptoms are ataxia, and two cases reported that tics as initial and prominent manifestation in JHD. Among them, 88% patients carried CAG repeats beyond 60 and most of them have family history. This case here illustrates the variable range of clinical symptoms of JHD and the necessity of testing for the HD mutation in young patients with tics with symptoms unable to be explained by Tourette's syndrome (TS).

  12. Gaucher disease in children: radiology of non-central nervous system manifestations

    International Nuclear Information System (INIS)

    McHugh, K.; Olsen, Oe.E.; Vellodi, A.

    2004-01-01

    The radiological findings in paediatric Gaucher disease (GD) are reviewed and future challenges for radiology are discussed. This overview is based on a literature review and our experience of children with GD in one of two national institutions for paediatric GD in the UK. GD is known to progress more rapidly in childhood. Current imaging is mainly suitable for ascertaining the complications of GD. The UK recommendations for routine radiological surveillance are discussed. With enzyme replacement therapy (ERT), which dramatically modifies the course of the disorder, the challenge for radiology in the future is likely to be assessing treatment efficacy rather than the detection of disease complications. Disease manifestations are likely to change in those on ERT and the most notable recent alteration in the disease profile in childhood is the virtual disappearance of the acute bone crisis in this population

  13. Gaucher disease in children: radiology of non-central nervous system manifestations

    Energy Technology Data Exchange (ETDEWEB)

    McHugh, K. E-mail: kmchugh@gosh.nhs.uk; Olsen, Oe.E.; Vellodi, A

    2004-02-01

    The radiological findings in paediatric Gaucher disease (GD) are reviewed and future challenges for radiology are discussed. This overview is based on a literature review and our experience of children with GD in one of two national institutions for paediatric GD in the UK. GD is known to progress more rapidly in childhood. Current imaging is mainly suitable for ascertaining the complications of GD. The UK recommendations for routine radiological surveillance are discussed. With enzyme replacement therapy (ERT), which dramatically modifies the course of the disorder, the challenge for radiology in the future is likely to be assessing treatment efficacy rather than the detection of disease complications. Disease manifestations are likely to change in those on ERT and the most notable recent alteration in the disease profile in childhood is the virtual disappearance of the acute bone crisis in this population.

  14. The Forgotten Plague: Psychiatric Manifestations of Ebola, Zika, and Emerging Infectious Diseases.

    Science.gov (United States)

    Tucci, Veronica; Moukaddam, Nidal; Meadows, Jonathan; Shah, Suhal; Galwankar, Sagar C; Kapur, G Bobby

    2017-01-01

    The media and public health generally focus on the biological and physical ramifications of epidemics. Mental health issues that coincide with emerging diseases and epidemics are rarely examined and sometimes, even eschewed due to cultural considerations. Psychiatric manifestations of various infectious diseases, especially with a focus on Ebola Virus disease (EVD) and Zika Virus, are discussed in this commentary to illustrate the continued need of care after the resolution of the actual illness. Various infectious diseases have associations with mental illness, such as an increased risk of obsessive-compulsive disorders and Tourette syndrome in children with Group B streptococcal infection. Current EVD literature does not demonstrate a strong association of mental illness symptoms or diseases but there is a necessity of care that extends beyond the illness. Patients and their families experience depression, anxiety, trauma, suicidal ideation, panic and other manifestations. Zika virus has been associated neuronal injury, genetic alteration that affects fetal development and detrimental maternal mental health symptoms are being documented. While funding calls from the international community are present, there are no specific epidemiological data or fiscal estimates solely for mental health during or after infectious diseases epidemics or disasters that support health care providers and strengthen policies and procedures for responding to such situations. Therefore, those on the frontlines of epidemics including emergency physicians, primary care providers and infectious disease specialists should serve communicate this need and advocate for sustained and increased funding for mental health programs to heighten public awareness regarding acute psychiatric events during infectious diseases outbreaks and offer treatment and support when necessary.

  15. Oral manifestations of sexually transmitted diseases identified in three stomatology services in South America

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    Martha Carmona-Lorduy

    2018-01-01

    Full Text Available Introduction: Sexually transmitted diseases are defined as a group of infections caused by various agents which are acquired during sexual intercourse. They also tend to generate manifestations in the mouth. Objective: To determine the typical lesions in oral cavity of sexually transmitted diseases. Materials and methods: A descriptive transversal study was conducted with 37 patients who attended the stomatology services of the University of Buenos Aires, University of Cartagena and the Aleman Hospital in Buenos Aires during 2015 and 2016. A complete clinical history was carried out with Venereal Disease Research Laboratory (VDRL and Fluorescent Treponemal Antibody Absortion (FTA-ABS tests in patients with presumption of syphilis. In addition, histopathological analysis and Polymerase Chain Reaction (PCR was made in patients with presumption of Human papillomavirus (HPV. Results: The average age of the patients was 38, where male sex predominated. 54.1% were diagnosed with syphilis and the most found lesion in them was the papule. The remaining 45.9% were diagnosed with HPV, the predominant lesion in them was a wart. Conclusions: The dentist should contribute to the early detection of sexually transmitted diseases by identifying manifestations of these in the mouth in order to prevent their evolution and prevent their transmission.

  16. Probable late lyme disease: a variant manifestation of untreated Borrelia burgdorferi infection

    Science.gov (United States)

    2012-01-01

    Background Lyme disease, a bacterial infection with the tick-borne spirochete Borrelia burgdorferi, can cause early and late manifestations. The category of probable Lyme disease was recently added to the CDC surveillance case definition to describe patients with serologic evidence of exposure and physician-diagnosed disease in the absence of objective signs. We present a retrospective case series of 13 untreated patients with persistent symptoms of greater than 12 weeks duration who meet these criteria and suggest a label of ‘probable late Lyme disease’ for this presentation. Methods The sample for this analysis draws from a retrospective chart review of consecutive, adult patients presenting between August 2002 and August 2007 to the author (JA), an infectious disease specialist. Patients were included in the analysis if their current illness had lasted greater than or equal to 12 weeks duration at the time of evaluation. Results Probable late Lyme patients with positive IgG serology but no history of previous physician-documented Lyme disease or appropriate Lyme treatment were found to represent 6% of our heterogeneous sample presenting with ≥ 12 weeks of symptom duration. Patients experienced a range of symptoms including fatigue, widespread pain, and cognitive complaints. Approximately one-third of this subset reported a patient-observed rash at illness onset, with a similar proportion having been exposed to non-recommended antibiotics or glucocorticosteroid treatment for their initial disease. A clinically significant response to antibiotics treatment was noted in the majority of patients with probable late Lyme disease, although post-treatment symptom recurrence was common. Conclusions We suggest that patients with probable late Lyme disease share features with both confirmed late Lyme disease and post-treatment Lyme disease syndrome. Physicians should consider the recent inclusion of probable Lyme disease in the CDC Lyme disease surveillance

  17. Pulmonary toxicity of trichloroethylene in mice. Covalent binding and morphological manifestations

    International Nuclear Information System (INIS)

    Forkert, P.G.; Birch, D.W.

    1989-01-01

    We examined the time course of trichloroethylene (TCE)-induced pulmonary injury and focused on morphological changes and covalent binding of [ 14 C]TCE soon after administration of a single dose of TCE (2000 mg/kg) to CD-1 male mice. At 1 hr after chemical treatment, Clara cells of the bronchiolar epithelium exhibited necrotic changes involving the mitochondria and endoplasmic reticulum. Dilatation of the endoplasmic reticulum became more severe at 2 hr after TCE administration and, by 4 hr, distended cisternae coalesced to form small vacuoles within the cytoplasmic matrix of the Clara cell. The severity of cellular damage increased progressively between 8 and 12 hr and, by 24 hr, the majority of Clara cells within an airway were severely vacuolated. Covalent binding of [ 14 C]TCE to lung macromolecules was evident at 1 hr, peaked at 4 hr, declined thereafter, and reached a plateau between 12 and 24 hr. Peak binding (142.6 +/- 31.8 nmol/g of wet weight) represented approximately 20% of [ 14 C]TCE distributed to the lung. Although the levels of binding in the liver were at all times greater than those in the lung, liver injury was relatively insignificant. The results demonstrate a positive correlation between the onset of Clara cell injury and the formation of reactive metabolites, as assessed by covalent binding of [ 14 C]TCE

  18. Cross sectional PET study of cerebral adenosine A1 receptors in premanifest and manifest Huntington's disease

    International Nuclear Information System (INIS)

    Matusch, Andreas; Elmenhorst, David; Saft, Carsten; Kraus, Peter H.; Gold, Ralf; Hartung, Hans-Peter; Bauer, Andreas

    2014-01-01

    To study cerebral adenosine receptors (AR) in premanifest and manifest stages of Huntington's disease (HD). We quantified the cerebral binding potential (BP ND ) of the A 1 AR in carriers of the HD CAG trinucleotide repeat expansion using the radioligand [ 18 F]CPFPX and PET. Four groups were investigated: (i) premanifest individuals far (preHD-A; n = 7) or (ii) near (preHD-B; n = 6) to the predicted symptom onset, (iii) manifest HD patients (n = 8), and (iv) controls (n = 36). Cerebral A 1 AR values of preHD-A subjects were generally higher than those of controls (by up to 31 %, p 1 AR BP ND was observed to the levels of controls in preHD-B and undercutting controls in manifest HD by down to 25 %, p 1 AR BP ND and years to onset. Before onset of HD, the assumed annual rates of change of A 1 AR density were -1.2 % in the caudatus, -1.7 % in the thalamus and -3.4 % in the amygdala, while the corresponding volume losses amounted to 0.6 %, 0.1 % and 0.2 %, respectively. Adenosine receptors switch from supra to subnormal levels during phenoconversion of HD. This differential regulation may play a role in the pathophysiology of altered energy metabolism. (orig.)

  19. Natural variation in sensory-motor white matter organization influences manifestations of Huntington's disease.

    Science.gov (United States)

    Orth, Michael; Gregory, Sarah; Scahill, Rachael I; Mayer, Isabella Sm; Minkova, Lora; Klöppel, Stefan; Seunarine, Kiran K; Boyd, Lara; Borowsky, Beth; Reilmann, Ralf; Bernhard Landwehrmeyer, G; Leavitt, Blair R; Roos, Raymund Ac; Durr, Alexandra; Rees, Geraint; Rothwell, John C; Langbehn, Douglas; Tabrizi, Sarah J

    2016-12-01

    While the HTT CAG-repeat expansion mutation causing Huntington's disease (HD) is highly correlated with the rate of pathogenesis leading to disease onset, considerable variance in age-at-onset remains unexplained. Therefore, other factors must influence the pathogenic process. We asked whether these factors were related to natural biological variation in the sensory-motor system. In 243 participants (96 premanifest and 35 manifest HD; 112 controls), sensory-motor structural MRI, tractography, resting-state fMRI, electrophysiology (including SEP amplitudes), motor score ratings, and grip force as sensory-motor performance were measured. Following individual modality analyses, we used principal component analysis (PCA) to identify patterns associated with sensory-motor performance, and manifest versus premanifest HD discrimination. We did not detect longitudinal differences over 12 months. PCA showed a pattern of loss of caudate, grey and white matter volume, cortical thickness in premotor and sensory cortex, and disturbed diffusivity in sensory-motor white matter tracts that was connected to CAG repeat length. Two further major principal components appeared in controls and HD individuals indicating that they represent natural biological variation unconnected to the HD mutation. One of these components did not influence HD while the other non-CAG-driven component of axial versus radial diffusivity contrast in white matter tracts were associated with sensory-motor performance and manifest HD. The first component reflects the expected CAG expansion effects on HD pathogenesis. One non-CAG-driven component reveals an independent influence on pathogenesis of biological variation in white matter tracts and merits further investigation to delineate the underlying mechanism and the potential it offers for disease modification. Hum Brain Mapp 37:4615-4628, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. A rare cardiac manifestation in autosomal-dominant polycystic kidney disease

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    Meriam Hajji

    2017-01-01

    Full Text Available Autosomal-dominant polycystic kidney disease (ADPKD is a systemic disorder associated with various extrarenal complications. There is little information regarding the occurrence and distribution of cardiovascular abnormalities during the course of ADPKD. The major cardiovascular complications of ADPKD include valvulopathies and vascular ectasia. Aneurysm of the atrial septum (ASA is a very rare manifestation in ADPKD. A 37-year-old woman who was diagnosed with ADPKD was admitted to our hospital for advanced renal failure. Pelvic computed tomography revealed multiple variable-sized cysts in both kidneys. Trans-thoracic echocardiography showed ASA while the patient was completely asymptomatic.

  1. Is there a role for scintigraphic imaging of bone manifestations in Gaucher disease? A review of the literature

    International Nuclear Information System (INIS)

    Mikosch, P.; State Hospital Klagenfurt; Kohlfuerst, S.; Gallowitsch, H.J.; Kresnik, E.; Lind, P.; Mehta, A.B.; Hughes, D.A.

    2008-01-01

    Gaucher disease is the most prevalent inherited, lysosomal storage disease and is caused by deficient activity of the enzyme β-glucocerebrosidase. Bone and bone marrow alterations are frequent in the most prevalent non-neuronopathic form of Gaucher disease. Imaging of bone manifestations in Gaucher disease is performed by a variety of imaging methods, conventional X-ray and MRI as the most frequently and most important ones. However, different modalities of scintigraphic imaging have also been used. This article gives an overview on scintigraphic imaging with respect to bone manifestations in Gaucher disease discussing the advantages and limitations of scintigraphic imaging in comparison to other imaging methods. (orig.)

  2. A case of celiac disease with neurologic manifestations misdiagnosed as amyotrophic lateral sclerosis

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    Hyoju Ham

    2017-10-01

    Full Text Available Celiac disease (CD is an immune-mediated enteropathy and is a rare disease in Asia, including in Korea. However, the ingestion of wheat products, which can act as a precipitating factor of CD, has increased rapidly. CD is a common cause of malabsorption, but many patients can present with various atypical manifestations as first presented symptoms, including anemia, osteopenia, infertility, and neurological symptoms. Thus, making a diagnosis is challenging. We report a case of CD that mimicked amyotrophic lateral sclerosis (ALS. The patient was a sexagenary man with a history of progressive motor weakness for 2 years. He was highly suspected as having ALS. During evaluation of his neurological symptoms, esophagogastroduodenoscopy (EGD was performed because he had experienced loose stools and weight loss for the previous 7 months. On EGD, the duodenal mucosa appeared smooth. A biopsy revealed severe lymphoplasma cell infiltration with flattened villi. His serum endomysial antibody (immunoglobulin A titer was 1:160 (reference, <1:40. Finally, he was diagnosed as having CD, and a gluten-free diet was immediately begun. At a 4-month follow-up, his weight and the quality of his stool had improved gradually, and the neurological manifestations had not progressed.

  3. Clinical manifestations of combined methamphetamine with morphine and their effects on brain dopamine and 5-hydroxytryptamine release in mice

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    Shing-Hwa Liu

    2015-01-01

    Full Text Available Background: Methamphetamine (MA is often mixed with morphine by polydrug addicts, and polydrug abuse has become a serious health problem worldwide. The purpose of this study was to investigate the major signs and symptoms of combined MA and morphine abuse in the Emergency Department (ED. In addition, we used a mouse model to study their effects on the release of dopamine (DA and 5-hydroxytryptamine (5-HT in the central nervous system. Materials and Methods: Seventy-two patients with combined MA and morphine abuse were collected during a 3-year period, and their medical records were reviewed. Mice were intraperitoneally administered MA (0.75 and 2.5 mg/kg/day and morphine (5 mg/kg/day either alone or in combination for 5 consecutive days. The mechanisms underlying the interaction between MA and morphine were explored by measuring the extracellular levels of DA and 5-HT in the shell of the nucleus accumbens using an in vivo microdialysis technique. Results: The most common manifestations of combined MA and morphine abuse included tachypnea, tachycardia, confusion, anxiety, delirium, insomnia, and diaphoresis in the ED. Of those, 25% of acute intoxication required hospitalization for intensive care. The group of mice treated with a combination of MA and morphine had higher concentrations of DA and 5-HT in the accumbens than with either drug alone. Conclusion: These findings suggest that MA pharmacologically interacts with morphine to induce characteristic signs and symptoms. Our preclinical results also implicate the involvement of increased DAergic and 5-HTergic neurotransmission among polydrug abusers with a combination of MA and morphine.

  4. [Limb lymphedema as a first manifestation of primary intestinal lymphangiectasia (Waldmann's disease)].

    Science.gov (United States)

    Boursier, V; Vignes, S

    2004-05-01

    Primary intestinal lymphangiectasia (Waldmann's disease) is characterized by protein-losing enteropathy occurring more frequently in childhood. Chronic diarrhea and diffuse edema are the main clinical manifestations. Peripheral lymphedema may also be associated. Lymphedema is usually present at the time of diagnosis or appears later in the course of the disease. We report the observation of a 31-year-old man suffering from an upper, lower limb and genital lymphedema many years before diagnosis of primary intestinal lymphangiectasia was established. Lower limb lymphoscintigraphy confirmed lymphedema and duodenal biopsies lymphangiectasia. Hypoproteinemia, lymphopenia and hypogammaglobulinemia were also noted. Treatment of lymphedema included low stretch bandaging and elastic stocking. No dietary management with a low-fat diet was added. Search for primary intestinal lymphangiectasia with biological parameters would be useful when primary lymphedema is present. Especially since primary intestinal lymphangiectasia may be complicated by occurrence of B cell lymphoma.

  5. Langerhans Cells Histiocytosis: Features of Clinical and Laboratory Manifestations and Course of the Disease

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    O.I. Dorosh

    2014-08-01

    Results of the Study. An analysis of 25 cases of LCH in children was presented. Monosystem LCH most often affects the skeletal system. Multisystem LCH is characterized by diversity of clinical manifestations, more severe course and high risk of death. One third of patients with multisystem LCH are infants. In children with monosystem LCH we observed complete clinical response to first-line therapy. At the same time, complete response to polychemotherapy is observed only in 30 % of children with multisystem LCH. Prognosis of the disease depends on the initial affection of risk organs (bone marrow, liver, lungs, spleen, their dysfunction and the child’s age at the time of diagnosis. Process reactivation in children with multisystem LCH occurs in the first 12 months from the onset of the disease.

  6. MRI manifestation for the diagnosis of sporadic Creutzfeldt-Jakob disease

    International Nuclear Information System (INIS)

    Xue Yonggang; Qi Ji; Xia Shuang

    2007-01-01

    Objective: To study the MRI features of sporadic Creutzfeldt-Jakob disease (sCJD). Methods: Three patients with clinically diagnosed sCJD underwent MR study, including SE T 1 WI, FSE T 2 WI, and DWI sequences. The MR imaging features were analyzed. Results: The lesions were not definite either in SE T 1 WI or in FSE T 2 WI, but were prominent in DWI. Abnormal hyperintensive signal appeared in the cerebral cortex, with the frontal, parietal, and occipital lobes being the mostly involved region. The subcortical white matter was normal. The bilateral caudate nuclei and thalami could also be involved. The abnormal signal could be either symmetrical or asymmetrical. There was diffuse atrophy of the brain parenchyma in the late phase of disease, especially in the cortex. Conclusion: With the application of MR study, especially the DWI, combined with its characteristic clinical manifestation, the diagnosis of sCJD can be made definitely. (authors)

  7. Differential Diagnoses of Overgrowth Syndromes: The Most Important Clinical and Radiological Disease Manifestations

    International Nuclear Information System (INIS)

    Lacerda, L.S.; Alves, U.D.; Zanier, J.F.C.; Machado, D.C.; Camilo, G.B.; Machado, D.C.; Camilo, G.B.; Lopes, A.J.

    2014-01-01

    Overgrowth syndromes comprise a heterogeneous group of diseases that are characterized by excessive tissue development. Some of these syndromes may be associated with dysfunction in the receptor tyrosine kinase (RTK)/PI3K/AKT pathway, which results in an increased expression of the insulin receptor. In the current review, four overgrowth syndromes were characterized (Proteus syndrome, Klippel-Trenaunay-Weber syndrome, Made lung’s disease, and neurofibromatosis type I) and illustrated using cases from our institution. Because these syndromes have overlapping clinical manifestations and have no established genetic tests for their diagnosis, radiological methods are important contributors to the diagnosis of many of these syndromes. The correlation of genetic discoveries and molecular pathways that may contribute to the phenotypic expression is also of interest, as this may lead to potential therapeutic interventions

  8. Bilateral pleural effusion and interstitial lung disease as unusual manifestations of kikuchi-fujimoto disease: case report and literature review

    Directory of Open Access Journals (Sweden)

    Magdalena Fernandez-Martinez

    2010-11-01

    Full Text Available Abstract Background Kikuchi-Fujimoto's disease (KFD, also called histiocytic necrotizing lymphadenitis, is a rare, idiopathic and self-limited condition usually characterized by cervical lymphadenopathy and fever, most often affecting young patients. Aetiology is unknown. Differential diagnosis includes mainly malignant lymphoma, tuberculous lymphadenitis and systemic lupus erythematosus (SLE, so early diagnosis is crucial. Pleuropulmonary involvement due to isolated KFD has been seldom reported. Case Presentation a 32-year-old man, on treatment for iatrogenic hypothyroidism, was admitted due to high grade fever and painful cervical lymphadenopathies. KFD was diagnosed by lymph node biopsy. Some days after admission the patient got worse, he developed generalized lymphadenopathy, bilateral pleural effusion and interstitial lung disease. All of them resolved with prednisone and after two years of following up he remains asymptomatic and without evidence of any other associated disease. Conclusion Pleural effusion and interstitial lung disease are very uncommon manifestations of KFD. In our experience, treatment with oral prednisone was effective.

  9. 20 CFR 702.603 - Determining the payrate for compensating occupational disease claims which become manifest after...

    Science.gov (United States)

    2010-04-01

    ... occupational disease claims which become manifest after retirement. 702.603 Section 702.603 Employees' Benefits... AND RELATED STATUTES ADMINISTRATION AND PROCEDURE Occupational Disease Which Does Not Immediately Result in Death or Disability § 702.603 Determining the payrate for compensating occupational disease...

  10. 20 CFR 702.604 - Determining the amount of compensation for occupational disease claims which become manifest...

    Science.gov (United States)

    2010-04-01

    ... occupational disease claims which become manifest after retirement. 702.604 Section 702.604 Employees' Benefits... AND RELATED STATUTES ADMINISTRATION AND PROCEDURE Occupational Disease Which Does Not Immediately Result in Death or Disability § 702.604 Determining the amount of compensation for occupational disease...

  11. Brain development in mice after prenatal irradiation: Modes of effect manifestation; dose-response-relationships and the RBE of neutrons

    International Nuclear Information System (INIS)

    Konermann, G.

    1986-01-01

    Postnatal effect manifestation in the CNS after exposures during advanced prenatal stages of development is due to both the prolonged period of neurogenesis and its complexity. Apart from acute proliferative effects, examples of two types of long-term effects in the brains of prenatally exposed mice are represented. Namely, persistent structural damage, and, fluctuating responses during the histochemical and biochemical brain maturation. Structural effects following X-ray exposure are quantified on the basis of data for diameter diminution of the cortical plate, corpus callosum and fimbria hippocampi. The studies include computerized micro-videoanalysis of neuronal branching defects. Continuous extension of exposure levels to doses as low as 0.05 Gy give evidence for the existence of thresholds for these types of structural damage in the vicinity of exposures to 0.1 Gy. The effects following X-ray exposures are partly compared with corresponding effects after neutron exposures. Our studies on postnatal maturation disturbances include proliferative responses, myelin formation, as well as the determination of different biochemical parameters (ATP, myelin-proteins, Na + /K + -balance). From our experimental findings we are able to stress the special significance of neurogenetical long-term effects for risk estimates in man. (orig.)

  12. Frosted branch angiitis, neuroretinitis as initial ocular manifestation in Behçet disease

    Directory of Open Access Journals (Sweden)

    Abdullah Al-Mujaini

    2011-01-01

    Full Text Available Behçet disease is an idiopathic, multisystem disorder characterized by recurrent episodes of orogenital ulceration and vasculitis of the veins and arteries of all calibers. Ocular involvement may affect the conjunctiva, sclera, uveal tract, vitreous, blood vessels, and retina. Many theories have pointed toward an autoimmune response behind its pathogenesis, which may be triggered by exposure to an infectious agent. Frosted branch angiitis is characterized by vascular inflammation, sheathing, retinal edema, and retinal hemorrhages. The disease may be idiopathic in a majority of the cases or may be associated with ocular and systemic pathology. Association between Behηet disease, Frosted branch angiitis, and neuroretinitis is not reported in literature. This uncommon combination reflects the varied systemic and ocular manifestations in Behηet disease, especially in patients who are not diagnosed and treated in time. We hereby report a case of bilateral frosted branch angiitis and neuroretinitis in a young male from Middle-east, suffering from Behçet disease.

  13. Disease outcome for children who present with oral manifestations of Crohn's disease.

    LENUS (Irish Health Repository)

    Hussey, S

    2011-06-01

    To describe the outcome for children with oral Crohn\\'s disease (OCD) at diagnosis, and to determine if there was a difference in the Paediatric Crohn\\'s Disease Activity Index (PCDAI) scores between those with and those without oral lesions at follow-up.

  14. Striatal hypometabolism in premanifest and manifest Huntington's disease patients

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Mora, Diego Alfonso; Camacho, Valle; Fernandez, Alejandro; Montes, Alberto; Carrio, Ignasi [Autonomous University of Barcelona, Nuclear Medicine Department, Hospital Sant Pau, Barcelona (Spain); Perez-Perez, Jesus; Martinez-Horta, Sauel; Kulisevsky, Jaime [Autonomous University of Barcelona, Movement Disorders Unit, Neurology Department, Hospital Sant Pau, Barcelona (Spain); Sampedro, Frederic [University of Barcelona, Barcelona (Spain); Lozano-Martinez, Gloria Andrea; Gomez-Anson, Beatriz [Autonomous University of Barcelona, Neuroradiology, Radiology Department, Hospital Sant Pau, Barcelona (Spain)

    2016-11-15

    To assess metabolic changes in cerebral {sup 18}F-FDG PET/CT in premanifest and manifest Huntington's disease (HD) subjects compared to a control group and to correlate {sup 18}F-FDG uptake patterns with different disease stages. Thirty-three gene-expanded carriers (Eight males; mean age: 43 y/o; CAG > 39) were prospectively included. Based on the Unified Huntington's Disease Rating Scale Total Motor Score and the Total Functional Capacity, subjects were classified as premanifest (preHD = 15) and manifest (mHD = 18). Estimated time disease-onset was calculated using the Langbehn formula, which allowed classifying preHD as far-to (preHD-A) and close-to (PreHD-B) disease-onset. Eighteen properly matched participants were included as a control group (CG). All subjects underwent brain {sup 18}F-FDG PET/CT and MRI. {sup 18}F-FDG PET/CT were initially assessed by two nuclear medicine physicians identifying qualitative metabolic changes in the striatum. Quantitative analysis was performed using SPM8 with gray matter atrophy correction using the BPM toolbox. Visual analysis showed a marked striatal hypometabolism in mHD. A normal striatal distribution of {sup 18}F-FDG uptake was observed for most of the preHD subjects. Quantitative analysis showed a significant striatal hypometabolism in mHD subjects compared to CG (p < 0.001 uncorrected, k = 50 voxels). In both preHD groups we observed a significant striatal hypometabolism with respect to CG (p < 0.001 uncorrected, k = 50 voxels). In mHD subjects we observed a significant striatal hypometabolism with respect to both preHD groups (p < 0.001 uncorrected, k = 50 voxels). {sup 18}F-FDG PET/CT might be a helpful tool to identify patterns of glucose metabolism in the striatum across the stages of HD and might be relevant in assessing the clinical status of gene-expanded HD carriers due to the fact that dysfunctional glucose metabolism begins at early preHD stages of the disease. {sup 18}F-FDG PET/CT appears as a

  15. Specificity of the STAT4 Genetic Association for Severe Disease Manifestations of Systemic Lupus Erythematosus

    Science.gov (United States)

    Taylor, Kimberly E.; Remmers, Elaine F.; Lee, Annette T.; Ortmann, Ward A.; Plenge, Robert M.; Tian, Chao; Chung, Sharon A.; Nititham, Joanne; Hom, Geoffrey; Kao, Amy H.; Demirci, F. Yesim; Kamboh, M. Ilyas; Petri, Michelle; Manzi, Susan; Kastner, Daniel L.; Seldin, Michael F.; Gregersen, Peter K.; Behrens, Timothy W.; Criswell, Lindsey A.

    2008-01-01

    Systemic lupus erythematosus (SLE) is a genetically complex disease with heterogeneous clinical manifestations. A polymorphism in the STAT4 gene has recently been established as a risk factor for SLE, but the relationship with specific SLE subphenotypes has not been studied. We studied 137 SNPs in the STAT4 region genotyped in 4 independent SLE case series (total n = 1398) and 2560 healthy controls, along with clinical data for the cases. Using conditional testing, we confirmed the most significant STAT4 haplotype for SLE risk. We then studied a SNP marking this haplotype for association with specific SLE subphenotypes, including autoantibody production, nephritis, arthritis, mucocutaneous manifestations, and age at diagnosis. To prevent possible type-I errors from population stratification, we reanalyzed the data using a subset of subjects determined to be most homogeneous based on principal components analysis of genome-wide data. We confirmed that four SNPs in very high LD (r2 = 0.94 to 0.99) were most strongly associated with SLE, and there was no compelling evidence for additional SLE risk loci in the STAT4 region. SNP rs7574865 marking this haplotype had a minor allele frequency (MAF) = 31.1% in SLE cases compared with 22.5% in controls (OR = 1.56, p = 10−16). This SNP was more strongly associated with SLE characterized by double-stranded DNA autoantibodies (MAF = 35.1%, OR = 1.86, p<10−19), nephritis (MAF = 34.3%, OR = 1.80, p<10−11), and age at diagnosis<30 years (MAF = 33.8%, OR = 1.77, p<10−13). An association with severe nephritis was even more striking (MAF = 39.2%, OR = 2.35, p<10−4 in the homogeneous subset of subjects). In contrast, STAT4 was less strongly associated with oral ulcers, a manifestation associated with milder disease. We conclude that this common polymorphism of STAT4 contributes to the phenotypic heterogeneity of SLE, predisposing specifically to more severe disease. PMID

  16. Specificity of the STAT4 genetic association for severe disease manifestations of systemic lupus erythematosus.

    Directory of Open Access Journals (Sweden)

    Kimberly E Taylor

    2008-05-01

    Full Text Available Systemic lupus erythematosus (SLE is a genetically complex disease with heterogeneous clinical manifestations. A polymorphism in the STAT4 gene has recently been established as a risk factor for SLE, but the relationship with specific SLE subphenotypes has not been studied. We studied 137 SNPs in the STAT4 region genotyped in 4 independent SLE case series (total n = 1398 and 2560 healthy controls, along with clinical data for the cases. Using conditional testing, we confirmed the most significant STAT4 haplotype for SLE risk. We then studied a SNP marking this haplotype for association with specific SLE subphenotypes, including autoantibody production, nephritis, arthritis, mucocutaneous manifestations, and age at diagnosis. To prevent possible type-I errors from population stratification, we reanalyzed the data using a subset of subjects determined to be most homogeneous based on principal components analysis of genome-wide data. We confirmed that four SNPs in very high LD (r(2 = 0.94 to 0.99 were most strongly associated with SLE, and there was no compelling evidence for additional SLE risk loci in the STAT4 region. SNP rs7574865 marking this haplotype had a minor allele frequency (MAF = 31.1% in SLE cases compared with 22.5% in controls (OR = 1.56, p = 10(-16. This SNP was more strongly associated with SLE characterized by double-stranded DNA autoantibodies (MAF = 35.1%, OR = 1.86, p<10(-19, nephritis (MAF = 34.3%, OR = 1.80, p<10(-11, and age at diagnosis<30 years (MAF = 33.8%, OR = 1.77, p<10(-13. An association with severe nephritis was even more striking (MAF = 39.2%, OR = 2.35, p<10(-4 in the homogeneous subset of subjects. In contrast, STAT4 was less strongly associated with oral ulcers, a manifestation associated with milder disease. We conclude that this common polymorphism of STAT4 contributes to the phenotypic heterogeneity of SLE, predisposing specifically to more severe disease.

  17. Abnormal resting-state connectivity of motor and cognitive networks in early manifest Huntington's disease.

    Science.gov (United States)

    Wolf, R C; Sambataro, F; Vasic, N; Depping, M S; Thomann, P A; Landwehrmeyer, G B; Süssmuth, S D; Orth, M

    2014-11-01

    Functional magnetic resonance imaging (fMRI) of multiple neural networks during the brain's 'resting state' could facilitate biomarker development in patients with Huntington's disease (HD) and may provide new insights into the relationship between neural dysfunction and clinical symptoms. To date, however, very few studies have examined the functional integrity of multiple resting state networks (RSNs) in manifest HD, and even less is known about whether concomitant brain atrophy affects neural activity in patients. Using MRI, we investigated brain structure and RSN function in patients with early HD (n = 20) and healthy controls (n = 20). For resting-state fMRI data a group-independent component analysis identified spatiotemporally distinct patterns of motor and prefrontal RSNs of interest. We used voxel-based morphometry to assess regional brain atrophy, and 'biological parametric mapping' analyses to investigate the impact of atrophy on neural activity. Compared with controls, patients showed connectivity changes within distinct neural systems including lateral prefrontal, supplementary motor, thalamic, cingulate, temporal and parietal regions. In patients, supplementary motor area and cingulate cortex connectivity indices were associated with measures of motor function, whereas lateral prefrontal connectivity was associated with cognition. This study provides evidence for aberrant connectivity of RSNs associated with motor function and cognition in early manifest HD when controlling for brain atrophy. This suggests clinically relevant changes of RSN activity in the presence of HD-associated cortical and subcortical structural abnormalities.

  18. Emerging infectious diseases with cutaneous manifestations: Fungal, helminthic, protozoan and ectoparasitic infections.

    Science.gov (United States)

    Kollipara, Ramya; Peranteau, Andrew J; Nawas, Zeena Y; Tong, Yun; Woc-Colburn, Laila; Yan, Albert C; Lupi, Omar; Tyring, Stephen K

    2016-07-01

    Given increased international travel, immigration, changing climate conditions, and the increased incidence of iatrogenic immunosuppression, fungal, protozoan, helminthic, and ectoparasitic infections that were once uncommon are being seeing more frequently in the Western hemisphere. However, the diagnosis and management of these infections is fraught with a lack of consistency because there is a dearth of dermatology literature on the cutaneous manifestations of these infections. In addition, delays in the diagnosis and treatment of these diseases can lead to significant patient morbidity and mortality. We review the epidemiology, cutaneous manifestations, diagnostic modalities, and treatment options for emerging fungal, protozoan, helminthic, and ectoparasitic infections. It should be noted, however, that throughout this review we cite statistics documenting their increased incidence to back-up these infections as emerging, and although some of the diagnoses are clinical, others rely on newer laboratory tests, and the possibility exists that the increased incidence could be caused by better detection methods. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  19. Mucocutaneous manifestations in patients with chronic kidney disease: A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Rattan S Rashpa

    2018-01-01

    Full Text Available Background: Chronic kidney disease (CKD-associated mucocutaneous manifestations significantly impair the quality of life but often remain understudied. They may also vary across regions, socioeconomic and nutritional status, and racial differences. Objectives: To study the patterns of mucocutaneous disorders and their prevalence in CKD patients irrespective of clinical stage or dialysis status. Materials and Methods: 122 (M:F = 77:45 patients aged 21‒85 (Mean ± SD = 57.5 ± 14.0 years having CKD for 3 month to 5 years were studied for mucocutaneous manifestations. Fifty (41% patients were on hemodialysis for 1‒42 months. Detailed medical history, clinical and mucocutaneous examination, and lab investigations were performed. KOH mounts, skin biopsy, Gram's and Giemsa staining, bacterial or fungal cultures were performed as required. Results: Xerosis in 93 (76.2%, skin pallor in 61 (50%, pruritus in 57 (46.7%, pigmentation in 47 (38.5%, and purpura in 18 (14.8% patients were the major dermatoses. Bullous lesions and perforating folliculitis occurred in 3 (2.5% patients each. Major nail abnormalities were pallor (in 35.2%, absent lunula (in 23.8%, nail discoloration (in 18%, and “half-and-half nails” in 16.4% patients, respectively. Hair abnormalities included sparse scalp and body hairs (in 35.2% and 13.1%, respectively and lusterless hair in 12.3% patients. Coated tongue (in 14.8%, xerostomia (in 12.3%, and macroglossia with teeth indention (in 7.4% patients were the mucosal manifestations. Conclusions: Xerosis, pruritus, skin pallor/pigmentary changes, nail pallor, absent lunula, nail discoloration, sparse hairs, coated tongue, xerostomia, macroglossia, and infections were the most common mucocutaneous manifestations in the studied patients irrespective of hemodialysis status. Cold and dry climates might be additional aggravators for xerosis/pruritus. Lifelong follow-up may be needed to reduce the morbidity associated with CKD

  20. [Subclinical and manifested hypothyroidism as a consequence of thyroid autoimmune disease].

    Science.gov (United States)

    Milosević, Dragoslav P; Djurica, Snezana; Davidović, Mladen; Stević, Radmila; Rajić, Miodrag; Marković, Natasa

    2005-10-01

    Chronic thyroiditis (Hashimoto's disease) is a slowly developing persistent inflamation of the thyroid gland, which frequently leads to hypothyroidism. Some of the up-to-date knowledge about hypothyroidism, both subclinical and manifested, caused by autoimmune disease, was presented. Autoimmune thyroid gland disease can occur at any age, but predominantly affects women after periods of high emotional and physical stress or accidents, as well as during periods of hormonal changes. It can also develop in families, and having an autoimmune disease slightly increases the risk of developing another. This paper showed an increasing incidence of subclinical hypothyroidism (4.17%) in elderly, and, at the same time, the incidence of primary hypothyroidism accounting for 1%. It is very usefull to estimate the stimulated thyrotropin (TSH) response, as well as the value of fast, short time thyroid gland reserves, analyzed by T3 and T4 serum level at 60th minute after TRH stimulation. Treatment of choice for HT (hypothyroidism of any cause) is thyroid hormone replacement. Drug of choice is orally administered levothyroxine sodium, usually for life-time. The standard dose is 1.6-1.8 mcg/kg body weight per day, but is in most cases patient dependent. Elderly patients usually require smaller replacement dose of levothyroxine, sometimes less than 1 mcg/kg body weight per day with coronary dilatator at the same time.

  1. Celiac disease manifesting as isolated cobalamin deficiency megaloblastic anemia: Case series and review

    Directory of Open Access Journals (Sweden)

    Vikram Sakaleshpur Kumar

    2014-01-01

    Full Text Available Celiac disease (CD is an immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. It has been identified as one of the most common lifelong disorders on a worldwide basis. Enteropathy in CD is thought to be the final consequence of an abnormal immune reaction, showing features of both an innate and adaptive response to gluten prolamins. The clinical spectrum is wide, including cases with either typical intestinal or atypical extra intestinal features, or silent forms. Anemia has frequently been reported as the only manifestation or the most frequent extra-intestinal symptom of CD. The only available treatment consists in dietary exclusion of grains containing gluten.

  2. Disease-toxicant interactions in manganese exposed Huntington disease mice: early changes in striatal neuron morphology and dopamine metabolism.

    Directory of Open Access Journals (Sweden)

    Jennifer L Madison

    Full Text Available YAC128 Huntington's disease (HD transgenic mice accumulate less manganese (Mn in the striatum relative to wild-type (WT littermates. We hypothesized that Mn and mutant Huntingtin (HTT would exhibit gene-environment interactions at the level of neurochemistry and neuronal morphology. Twelve-week-old WT and YAC128 mice were exposed to MnCl(2-4H(2O (50 mg/kg on days 0, 3 and 6. Striatal medium spiny neuron (MSN morphology, as well as levels of dopamine (DA and its metabolites (which are known to be sensitive to Mn-exposure, were analyzed at 13 weeks (7 days from initial exposure and 16 weeks (28 days from initial exposure. No genotype-dependent differences in MSN morphology were apparent at 13 weeks. But at 16 weeks, a genotype effect was observed in YAC128 mice, manifested by an absence of the wild-type age-dependent increase in dendritic length and branching complexity. In addition, genotype-exposure interaction effects were observed for dendritic complexity measures as a function of distance from the soma, where only YAC128 mice were sensitive to Mn exposure. Furthermore, striatal DA levels were unaltered at 13 weeks by genotype or Mn exposure, but at 16 weeks, both Mn exposure and the HD genotype were associated with quantitatively similar reductions in DA and its metabolites. Interestingly, Mn exposure of YAC128 mice did not further decrease DA or its metabolites versus YAC128 vehicle exposed or Mn exposed WT mice. Taken together, these results demonstrate Mn-HD disease-toxicant interactions at the onset of striatal dendritic neuropathology in YAC128 mice. Our results identify the earliest pathological change in striatum of YAC128 mice as being between 13 to 16 weeks. Finally, we show that mutant HTT suppresses some Mn-dependent changes, such as decreased DA levels, while it exacerbates others, such as dendritic pathology.

  3. Transgenic mice expressing human glucocerebrosidase variants: utility for the study of Gaucher disease.

    Science.gov (United States)

    Sanders, Angela; Hemmelgarn, Harmony; Melrose, Heather L; Hein, Leanne; Fuller, Maria; Clarke, Lorne A

    2013-08-01

    Gaucher disease is an autosomal recessively inherited storage disorder caused by deficiency of the lysosomal hydrolase, acid β-glucosidase. The disease manifestations seen in Gaucher patients are highly heterogeneous as is the responsiveness to therapy. The elucidation of the precise factors responsible for this heterogeneity has been challenging as the development of clinically relevant animal models of Gaucher disease has been problematic. Although numerous murine models for Gaucher disease have been described each has limitations in their specific utility. We describe here, transgenic murine models of Gaucher disease that will be particularly useful for the study of pharmacological chaperones. We have produced stable transgenic mouse strains that individually express wild type, N370S and L444P containing human acid β-glucosidase and show that each of these transgenic lines rescues the lethal phenotype characteristic of acid β-glucosidase null mice. Both the N370S and L444P transgenic models show early and progressive elevations of tissue sphingolipids with L444P mice developing progressive splenic Gaucher cell infiltration. We demonstrate the potential utility of these new transgenic models for the study of Gaucher disease pathogenesis. In addition, since these mice produce only human enzyme, they are particularly relevant for the study of pharmacological chaperones that are specifically targeted to human acid β-glucosidase and the common mutations underlying Gaucher disease. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Zr-89-Bevacizumab PET Visualizes Disease Manifestations in Patients with von Hippel-Lindau Disease

    NARCIS (Netherlands)

    Oosting, Sjoukje F.; van Asselt, Sophie J.; Brouwers, Adrienne H.; Bongaerts, Alfons H. H.; Steinberg, Julia D. J.; de Jong, Johan; Lub-de Hooge, Marjolijn N.; Horst-Schrivers, van der Anouk N. A.; Walenkamp, Annemiek M. E.; Hoving, Eelco W.; Sluiter, Wim J.; Zonnenberg, Bernard A.; de Vries, Elisabeth G. E.; Links, Thera P.

    2016-01-01

    Patients with von Hippel-Lindau disease (VHL) are at risk to develop multiple tumors. The growth of lesions is unpredictable, and regular surveillance is critical for early treatment to control local damage. Vascular endothelial growth factor A (VEGF-A) produced locally is supposed to play an

  5. Mantle Cell Hyperplasia of Peripheral Lymph Nodes as Initial Manifestation of Sickle Cell Disease.

    Science.gov (United States)

    Monabbati, Ahmad; Noori, Sadat; Safaei, Akbar; Ramzi, Mani; Eghbali, Seyedsajjad; Adib, Ali

    2016-01-01

    Sickle cell disease (SCD) is a well known hemoglobinopathy with usual manifestations including anemia, hyperbilirubinemia, and vasoocclusive complications. Despite presence of mild splenomegaly in early phase of the disease, lymphadenopathy is not an often finding of SCD. We introduce an undiagnosed case of SCD who presented in third decade of his life with multiple cervical lymphadenopathies and mild splenomegaly persistent for about five years. Histopathologic examination of the resected lymph nodes showed expansion of the mantle cell layers of secondary follicles as well as several monomorphic mantle cell nodules. To rule out possibility of a malignant process involving lymph nodes, an immunohistochemical panel was ordered which was in favor of benign mantle cell hyperplasia. Immunoglobulin gene rearrangement study showed no clonal bands and confirmed benign nature of the process. Respecting mild abnormalities on Complete Blood Count, peripheral blood smear was reviewed revealing some typical sickle red blood cells as well as rare nucleated red blood cells. Solubility test for hemoglobin (HB) S was positive. Hemoglobin electrophoresis confirmed diagnosis of homozygous HbS disease.

  6. Two cases of possible neuro-Sweet disease with meningoencephalitis as the initial manifestation

    Directory of Open Access Journals (Sweden)

    Go Makimoto

    2012-02-01

    Full Text Available We report 2 cases that were considered to be neuro-Sweet disease. They initially manifested with meningoencephalitis and no skin lesions, and rapidly improved with corticosteroid therapy. In both cases, patients complained of meningitic symptoms such as fever and headache, and HLA-B54 and -Cw1 turned out to be positive over the clinical course. Cerebrospinal fluid analysis showed increased levels of lymphocytes and protein. In case #1, fluid-attenuated inversion recovery (FLAIR, magnetic resonance imaging (MRI and diffusion-weighted images (DWI showed high-intensity signals in the right dorsal medulla oblongata, bilateral dorsal midbrain, and left thalamus. In case #2, FLAIR and DWI showed high-intensity signals in the bilateral cerebellar cortex and left caudate nucleus. Symptoms and MRI images were markedly improved in both cases after corticosteroid pulse therapy. According to published diagnostic criteria, these 2 cases were considered possible neuro-Sweet disease. These cases suggest that the combination of meningoencephalitis and HLA specificity is important to consider the possibility of neuro-Sweet disease, even without skin lesions.

  7. Rosai-Dorfman disease manifesting as a solitary lesion of the radius in a 41-year-old woman

    International Nuclear Information System (INIS)

    George, J.; Stacy, G.; Peabody, T.; Montag, A.

    2003-01-01

    Rosai-Dorfman disease is a rare entity predominantly affecting children and young adults, characterized in 83-95% of cases by painless bilateral cervical lymphadenopathy. We report the unusual case of a 41-year-old woman with Rosai-Dorfman disease that presented as a solitary lesion of the radius without other clinical manifestations. (orig.)

  8. Early manifestations of type 1 Gaucher disease in presymptomatic children diagnosed after parental carrier screening.

    Science.gov (United States)

    Yang, Amy C; Bier, Louise; Overbey, Jessica R; Cohen-Pfeffer, Jessica; Desai, Khyati; Desnick, Robert J; Balwani, Manisha

    2017-06-01

    The overall published experience with pediatric type 1 Gaucher disease (GD1) has been based on ascertainment through clinical presentation of the disease. We describe the longitudinal follow-up in a presymptomatic pediatric cohort. The cohort includes children diagnosed with GD1, either prenatally or postnatally by molecular genetic testing, and followed for clinical care at our center from 1998 to 2016. All patients' parents were GBA mutation carriers identified through carrier screening programs. Longitudinal clinical, laboratory, and imaging data were obtained through chart review. Thirty-eight patients aged 1-18 years (mean at last visit 6.9 ± 4.1 years) were followed, including 32 p.N409S homozygotes and 6 p.N409S/p.R535H compound heterozygotes. At the last evaluation, a minority had hematological (5%), bone (15%), or linear growth (19%) issues. Only 12% had splenomegaly and 74% had moderate hepatomegaly. Chitotriosidase activity varied widely (6-5,640 nmol/hour/ml) and generally increased with age. Pediatric Gaucher severity scores (GSS) remained stable and within the mild-disease range for most (95%). Treatment for progressive disease during this period was recommended for four children. Most children with the p.N409S/p.N409S and p.N409S/p.R535H GD1 genotypes have minimal disease manifestations and progression during childhood and can be monitored using limited assessments. Those with other mutations may require additional monitoring. These data are valuable for newborn screening and counseling.Genet Med advance online publication 13 October 2016.

  9. Neurological manifestations of Behçet's disease: Case report and literature review.

    Science.gov (United States)

    López Bravo, Alba; Parra Soto, Carlos; Bellosta Diago, Elena; Cecilio Irazola, Álvaro; Santos-Lasaosa, Sonia

    2017-05-22

    Neurological involvement in Behçet's disease is rare, especially at the onset. It can present in the form of parenchymal changes or as damage to the vascular structures in its nonparenchymal form. The coexistence of both kinds of manifestations in the same patient is exceptional. We report the case of a 32-year-old patient with a history of deep venous thrombosis, who was being treated for holocranial headache, apathy, and oral and genital ulcers. Brain magnetic resonance imaging showed hyperintense lesions in the basal ganglia and white matter, and the vascular study evidenced venous thrombosis of the left transverse sinus. After confirming the diagnosis of Behçet's disease with parenchymal and nonparenchymal cerebral involvement, immunosuppressive and corticosteroid therapy was started, resulting in the remission of the symptoms. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  10. Study on Analysis and Pattern Recognition of the Manifestation of the Pulse Detection of Cerebrovascular Disease

    Energy Technology Data Exchange (ETDEWEB)

    Jing, J; Wang, Y C; Hong, W X; Zhang, W P [Department of Biomedical Engineering, University of Yanshan, Qinhuangdao, Hebei Province, 066004 (China)

    2006-10-15

    Cerebrovascular Disease (CVD) is also called stroke in Traditional Chinese Medicine (TCM). CVD is a kind of frequent diseases with high incidence, high death rate, high deformity rate and high relapse rate. The pathogenesis of CVD has relation to many factors. In modern medicine, we can make use of various instruments to check many biochemical parameters. However, at present, the early detection of CVD can mostly be done artificially by specialists. In TCM the salted expert can detect the state of a CVD patient by felling his (or her) pulse. It is significant to apply the modern information and engineering techniques to the early discovery of CVD. It is also a challenge to do this in fact. In this paper, the authors presented a detection method of CVD basing on analysis and pattern recognition of Manifestation of the Pulse of TCM using wavelet technology and Neural Networks. Pulse signals from normal health persons and CVD patients were studied comparatively. This research method is flexible to deal with other physiological signals.

  11. Motor impulsivity in APP-SWE mice: a model of Alzheimer's disease.

    Science.gov (United States)

    Adriani, Walter; Ognibene, Elisa; Heuland, Emilie; Ghirardi, Orlando; Caprioli, Antonio; Laviola, Giovanni

    2006-09-01

    Among transgenic mouse models of Alzheimer's disease, APP-SWE mice have been shown to develop beta-amyloid plaques and to exhibit progressive impairment of cognitive function. Human Alzheimer's disease, however, also includes secondary clinical manifestations, spanning from hyperactivity to agitation. The aim of this study was a better characterization of motor impulsivity in APP-SWE mice, observed at 12 months of age, when levels of soluble beta-amyloid are elevated and beta-amyloid neuritic plaques start to appear. Mice were tested for spatial learning abilities in the Morris water maze (seven daily sessions, four trials per day). The distance traveled to reach the hidden platform showed a learning curve in both groups. This profile, however, was somewhat delayed in APP-SWE mice, thus confirming slightly impaired spatial capacities. To evaluate motor impulsivity, animals were trained to nose-poke for a food reward, which was delivered after a waiting interval that increased over days (15-60 s). Further nose-poking during this signaled waiting interval resulted in food-reward loss and electric-shock punishment. APP-SWE mice received an increased quantity of punishment and were able to earn fewer food rewards, suggesting inability to wait already at the lowest delay. After the animals were killed, prefrontal cortex samples were assessed for neurochemical parameters. Serotonin turnover was elevated in the prefrontal cortex of APP-SWE mice compared with controls. The results clearly confirm cognitive deficits, and are consistent with the hypothesis of reduced behavioral-inhibition abilities. Together with recent findings, APP-SWE mice emerge as a suitable animal model, characterized by a number of specific behavioral alterations, resembling primary and secondary symptoms of human Alzheimer's disease.

  12. Serum Homocysteine Level in Parkinson's Disease and Its Association with Duration, Cardinal Manifestation, and Severity of Disease.

    Science.gov (United States)

    Saadat, Payam; Ahmadi Ahangar, Alijan; Samaei, Seyed Ehsan; Firozjaie, Alireza; Abbaspour, Fatemeh; Khafri, Sorrayya; Khoddami, Azam

    2018-01-01

    Due to the high prevalence of Parkinson's disease (PD) in the elderly, a large financial burden is imposed on the families and health systems of countries in addition to the problems related to the mobility impairment caused by the disease for the patients. Studies on controversial issues in this disease are taken into consideration, and one of these cases is the role of serum homocysteine level in Parkinson's patients. In this study, the serum level of homocysteine and its association with various variables in relation to this disease was compared with healthy individuals. In this study, 100 patients with PD and 100 healthy individuals as control group were investigated. Serum homocysteine level and demographic and clinical data were included in the checklist. Data were analyzed by SPSS version 23. In all tests, the significance level was below 0.05. The mean level of serum homocysteine in case and control groups was 14.93 ± 8.30 and 11.52 ± 2.86  µ mol/L, respectively (95% CI: 1.68; 5.14, P level, while 15 had high serum homocysteine level. In controls, the homocysteine level was 98 and 2, respectively ( P =0.002). In multivariate logistic regression analysis, serum homocysteine level higher than 20  µ mol/L was accompanied by 8.64-fold in Parkinson's disease involvement (95% CI: 1.92; 38.90, P =0.005). Increasing serum homocysteine level elevates the rate to having PD. Serum homocysteine levels did not have any relationship with the duration of the disease, type of cardinal manifestation, and the severity of Parkinson's disease.

  13. Serum Homocysteine Level in Parkinson’s Disease and Its Association with Duration, Cardinal Manifestation, and Severity of Disease

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    Payam Saadat

    2018-01-01

    Full Text Available Background and Purpose. Due to the high prevalence of Parkinson’s disease (PD in the elderly, a large financial burden is imposed on the families and health systems of countries in addition to the problems related to the mobility impairment caused by the disease for the patients. Studies on controversial issues in this disease are taken into consideration, and one of these cases is the role of serum homocysteine level in Parkinson’s patients. In this study, the serum level of homocysteine and its association with various variables in relation to this disease was compared with healthy individuals. Materials and Methods. In this study, 100 patients with PD and 100 healthy individuals as control group were investigated. Serum homocysteine level and demographic and clinical data were included in the checklist. Data were analyzed by SPSS version 23. In all tests, the significance level was below 0.05. Results. The mean level of serum homocysteine in case and control groups was 14.93 ± 8.30 and 11.52 ± 2.86 µmol/L, respectively (95% CI: 1.68; 5.14, P<0.001. In total patients, 85 had normal serum homocysteine level, while 15 had high serum homocysteine level. In controls, the homocysteine level was 98 and 2, respectively (P=0.002. In multivariate logistic regression analysis, serum homocysteine level higher than 20 µmol/L was accompanied by 8.64-fold in Parkinson’s disease involvement (95% CI: 1.92; 38.90, P=0.005. Conclusion. Increasing serum homocysteine level elevates the rate to having PD. Serum homocysteine levels did not have any relationship with the duration of the disease, type of cardinal manifestation, and the severity of Parkinson’s disease.

  14. Factors affecting dermatological manifestations in patients with end stage renal disease

    International Nuclear Information System (INIS)

    Anees, M.; Gull, S.; Nazeer, A.

    2018-01-01

    To determine skin changes in patients of End Stage Renal Disease (ESRD) on maintenance hemodialysis (MHD) and factors affecting these changes. Study Design:Cross-sectional observational study. Place and Duration of Study:Nephrology Department, Mayo Hospital, Lahore in collaboration with Dermatology Department, King Edward Medical University, Lahore, from October 2015 to January 2016. Methodology:Two hundred patients who were undergoing MHD for more than three months were included in the study. Patients' demographic data, laboratory reports and dialysis records were noted in a predesigned questionnaire. Skin examination was carried out by consultant dermatologist after patient's permission. Results:Among 200 patients included in study, 105 were males and rest of them were females. Major causes of ESRD were Diabetes Mellitus (n=83, 41.5%, followed by Hypertension (n=80, 40%), Nephrolithiasis (n=15, 7.5%) and Chronic glomerulonephritis (n=5, 2.5%). At least one cutaneous finding was present in every patient. Common skin findings observed were pigmentation (86%), xerosis (83%), pallor (79%), pruritus (69%), acquired ichthyosis (50.5%), and bacterial skin infections (18.5%). Among them, nail manifestations were half-and-half nails (52%), nychomycosis (30.5%), onycholysis (20.5%), subungual hyperkeratosis (23.5%), and Mee's lines (7.5). Among hair changes were sparse scalp hair (38.5%), brittle and lustreless hair (28%). The factors contributing to skin changes were patient's age, cause of ESRD, anti HCV positivity, high urea and creatinine levels, duration and frequency of hemodialysis, hemoglobin levels, calcium phosphate product and socioeconomic status. Some skin manifestations were interrelated with each other like xerosis with pruritus (p<0.001), pruritus with bacterial infection (p<0.022), acquired Ichthyosis (p=0.008) and hair changes (p=0.035). Conclusion:ESRD patients on hemodialysis develop various skin changes during the course of disease

  15. Methotrexate in ocular manifestations of Behcet's disease: a longitudinal study up to 15 years.

    Science.gov (United States)

    Davatchi, Fereydoun; Shams, Hormoz; Shahram, Farhad; Nadji, Abdolhadi; Chams-Davatchi, Cheyda; Sadeghi Abdollahi, Bahar; Faezi, Tahereh; Akhlaghi, Massoomeh; Ashofteh, Farimah

    2013-10-01

    Ocular manifestations of Behcet's disease (BD) need aggressive treatment to prevent severe loss of vision or blindness. Cytotoxic drugs are the main therapeutic agents and the first line treatment. Methotrexate is the least toxic, used mainly for posterior uveitis. We present here the outcome of eye lesions with methotrexate and prednisolone, in a longitudinal study of up to 15 years, on 682 patients (5447 eye-years of follow-up). Methotrexate was started at 7.5-15 mg/week. Prednisolone was added at 0.5 mg/kg/daily, then adjusted as needed. (i) fulfilling the International Criteria for Behcet's Disease; and (ii) having active posterior uveitis (PU). Visual acuity (VA) was calculated on a scale of 10. Activity indexes were calculated for PU and retinal vasculitis (RV) for each eye. Total Inflammatory Activity Index (TIAI) demonstrating the inflammatory index of both eyes of the patient, and Total Adjusted Disease Activity Index (TADAI) showing both TIAI + VA were also calculated. Overall results: the mean VA improvement was 0.4 (P < 001), PU 1.2 (P < 0.001) and RV 0.6 (P < 0.001). VA improved in 46.5%, PU in 75.4%, and RV in 53.7% of eyes. TIAI improved in 74% of patients and TADAI in 69.4%. VA was aggravated in 37.2%, PU in 11.1%, and RV in 30.3% of eyes. TIAI was aggravated in 17.4% and TADAI in 21.6% of the patients. The remaining kept their baseline values. All parameters improved, PU better than RV. Improvement of VA was the least, mainly due to secondary cataracts. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  16. 'Non-neuronopathic' Gaucher disease reconsidered. Prevalence of neurological manifestations in a Dutch cohort of type I Gaucher disease patients and a systematic review of the literature

    NARCIS (Netherlands)

    Biegstraaten, M.; van Schaik, I. N.; Aerts, J. M. F. G.; Hollak, C. E. M.

    2008-01-01

    Gaucher disease is a lysosomal storage disorder, which is classically divided into three types. Type I Gaucher disease is differentiated from types II and III disease by the absence of nervous system involvement. However, an increasing number of reports has emerged on neurological manifestations in

  17. Ethnicity and association with disease manifestations and mortality in Behçet's disease.

    Science.gov (United States)

    Savey, Lea; Resche-Rigon, Mathieu; Wechsler, Bertrand; Comarmond, Cloé; Piette, Jean Charles; Cacoub, Patrice; Saadoun, David

    2014-03-27

    Behçet's disease (BD) significantly increases morbidity and mortality. BD mainly affects young adults with a peculiar geographical distribution. It has been suggested that BD varies in its phenotypic expression in different ethnic groups. We investigated potential ethnicity-related differences relative to phenotype and prognosis of BD patients in a French multiethnic country. We included 769 consecutive patients fulfilling the international criteria of classification for BD, in the 3 largest ethnic groups of our cohort [European (n = 369), North African (n = 350) and sub Saharan African (n = 50)]. Factors that affect prognosis were assessed by multivariate analysis. 535 (69.6%) patients were male and the median (IQR) age at diagnosis was of 30.9 (24.9-37.2) years. Sub Saharan African BD patients had a higher frequency of CNS involvement (48% vs 32.3% vs 29.5%, p = 0 .035), a higher rate of death (12% vs 6% vs 3.5%, p = 0.029) and a lower frequency of HLA B51 allele (29.4% vs 49.2% vs 55.8%, p = 0.009) compared to those from North Africa and Europe, respectively. Multivariate analysis showed that male gender (HR: 5.01, CI: 1.51-16.65), cardiovascular involvement (HR: 2.24, CI: 1.15-4.36), and sub Saharan African origin (HR 2.62 (0.98-6.97) were independently associated with mortality. The 15-year mortality rate was of 19%, 9% and 6% in sub Saharan African, North African and European BD patients, respectively (p = 0.015). We reported ethnicity-related differences with respect to phenotype of BD. Sub Saharan Africans patients exhibited a worse prognosis.

  18. Enterocolic lymphocytic phlebitis as a newly recognized manifestation of IgG4-related disease.

    Science.gov (United States)

    Laco, Jan; Örhalmi, Július; Bártová, Jolana; Zimandlová, Dana

    2015-04-01

    Herein we present a case of a 65-year-old woman with enterocolic lymphocytic phlebitis (ELP) who presented with anemic syndrome and in whom severe stenosis of the right flexure of large bowel was detected. The microscopic examination revealed fibrosis of the submucosa and lymphoplasmacytic phlebitis of small veins and venules, whereas arteries were spared. There were 110 IgG4-positive and 160 IgG-positive plasma cells in 1 high-power field, respectively, with corresponding IgG4/IgG ratio of 0.69. The IgG4 serum level was 2.42 g/L. According to the currently proposed criteria, this ELP case is the first that may be diagnosed as definite IgG4-related disease (IgG4-RD). Although based on the sole case description, taken together with a recent review and a case report, we presume that a subset of ELPs is a manifestation of IgG4-RD. © The Author(s) 2014.

  19. Peripheral neuropathy is a common manifestation of mitochondrial diseases: a single-centre experience.

    Science.gov (United States)

    Luigetti, M; Sauchelli, D; Primiano, G; Cuccagna, C; Bernardo, D; Lo Monaco, M; Servidei, S

    2016-06-01

    Peripheral neuropathy in mitochondrial diseases (MDs) may vary from a subclinical finding in a multisystem syndrome to a severe, even isolated, manifestation in some patients. To investigate the involvement of the peripheral nervous system in MDs extensive electrophysiological studies were performed in 109 patients with morphological, biochemical and genetic diagnosis of MD [12 A3243G progressive external ophthalmoplegia (PEO)/mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), 16 myoclonic epilepsy with ragged-red fibres (MERRF), four mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), 67 PEO with single or multiple deletions of mitochondrial DNA, 10 others]. A neuropathy was found in 49 patients (45%). The incidence was very high in MNGIE (100%), MELAS (92%) and MERRF (69%), whilst 28% of PEO patients had evidence of peripheral involvement. The most frequent abnormality was a sensory axonal neuropathy found in 32/49 patients (65%). A sensory-motor axonal neuropathy was instead detected in 16% of the patients and sensory-motor axonal demyelinating neuropathy in 16%. Finally one Leigh patient had a motor axonal neuropathy. It is interesting to note that the great majority had preserved tendon reflexes and no sensory disturbances. In conclusion, peripheral involvement in MD is frequent even if often mild or asymptomatic. The correct identification and characterization of peripheral neuropathy through electrophysiological studies represents another tile in the challenge of MD diagnosis. © 2016 EAN.

  20. A Case of Early Disseminated Neurological Lyme Disease Followed by Atypical Cutaneous Manifestations

    Directory of Open Access Journals (Sweden)

    Vamsi Kantamaneni

    2017-01-01

    Full Text Available Lyme disease (LD is a tick-borne illness caused by Borrelia burgdorferi sensu stricto. An 80-year-old female from Pennsylvania, USA, presented to an outside hospital with fever, confusion, lower extremity weakness, and stool incontinence. CT head and MRI spine were unremarkable. An infectious work-up including lumbar puncture was negative. She was transferred to our tertiary care hospital. Patient was noted to have mild unilateral right-sided facial droop and a diffuse macular rash throughout the body. She denied any outdoor activities, tick bites, or previous rash. Intravenous ceftriaxone was started for suspected LD. The patient’s symptoms including facial droop resolved within 24 hours of antibiotic therapy. Polymerase chain reaction of the blood, IgM ELISA, and IgM Western blot testing for LD came back positive a few days after initiation of therapy. She was treated for a total of 21 days for neurological LD with complete symptom resolution. Not all patients have the classic “targetoid” EM rash on initial presentation, rash could develop after neurological manifestations, and prompt initiation of antibiotics without awaiting serology is paramount to making a quick and a full recovery. There should be a high index of suspicion for early disseminated LD, as presentations can be atypical.

  1. Ocular manifestations of graft-versus-host disease: 10 years’ experience

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    Lin X

    2015-07-01

    Full Text Available Xihui Lin, Harrison Dwight Cavanagh Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, USA Purpose: To evaluate the ocular presentation, treatment, and clinical course of graft-versus-host disease (GVHD. Design: Retrospective case series. Participants: Two hundred and forty-nine patients with systemic GVHD were included in the study. Methods: Ocular and systemic data were collected from 2003 to 2013. Main outcome measures: Mortality, visual acuity, and response of ocular symptoms. Results: Sixty-four patients had ocular manifestations (25.7%. At presentation, the mean age was 44.5 years and mean latency was 16.4 months. The most common presentations were keratoconjunctivitis sicca, cataract, blepharitis, ocular hypertension, and filamentary keratitis. Visual acuity at presentation was 20/49; at the worst point in the disease was 20/115; and at most recent visit was 20/63. When topical anti-inflammatory drops were used in addition to tears, 54.3% of patients’ ocular symptoms stabilized. When autologous serum was used in addition, 80% stabilized. The overall 10-year mortality of GVHD was 29.7%. For those with ocular involvement, it was 21.9%. Conclusion: Systemic GVHD has a high mortality rate, but ocular involvement does not suggest a worse prognosis. The main ocular presentations were keratoconjunctivitis sicca, cataracts, and ocular hypertension. Dry eyes in this population were very severe with overall worsening in visual acuity. However, with a step-wise approach involving topical anti-inflammatory medications and autologous serum tears, ocular symptoms do improve. It is important to monitor these patients closely, as they are prone to serious ocular complications such as corneal perforation and endophthalmitis. Keywords: dry eye, keratitis, corneal ulceration

  2. Extraintestinal Manifestations of Celiac Disease: Effectiveness of the Gluten-Free Diet.

    Science.gov (United States)

    Jericho, Hilary; Sansotta, Naire; Guandalini, Stefano

    2017-07-01

    The aim of the study was to evaluate the effectiveness of the gluten-free diet (GFD) on extraintestinal symptoms in pediatric and adult celiac populations at the University of Chicago. We conducted a retrospective chart review of the University of Chicago Celiac Center clinic charts from January 2002 to October 2014. Demographics, serologic testing, intestinal biopsies, and extraintestinal symptoms at presentation, 12, 24, and >24 months were recorded. Extraintestinal symptoms included abnormal liver enzymes, arthralgia/arthritis, dermatitis herpetiformis, alopecia, fatigue, headache, anemia, stomatitis, myalgias, psychiatric disorders, rashes, seizures, neuropathy, short stature, delayed puberty, osteoporosis, and infertility. A total of 737 patients with biopsy-confirmed celiac disease or skin biopsy-confirmed dermatitis herpetiformis were included. Patients lost to follow-up, or with insufficient data were excluded leaving 328 patients (157 pediatrics younger than 18 years). For pediatrics, the female to male ratio was 2:1 and the mean age at diagnosis was 8.9 years. For adults, 4:1 and 40.6 years old. Extraintestinal symptom rates were similar in children (60%) and adults (62%). Short stature (33%), fatigue (28%), and headache (20%) were most common in children. Iron deficiency anemia (48%), fatigue (37%), and headache/psychiatric disorders (24%) were common in adults. Children had faster/higher rates of symptom resolution compared with adults. Twenty-eight percent of children with unresolved short stature on a GFD were found to have other comorbidities. Children and adults with celiac disease have similar rates of extraintestinal manifestations. In children short stature, fatigue, and headache were most common, whereas anemia, fatigue, and headache/psychiatric disorders were most common in adults. Children on a strict GFD showed faster and higher rates of symptom resolution as compared to adults. Unresponsive children with short stature must be assessed for

  3. Man made disease: clinical manifestations of low phenylalanine levels in an inadequately treated phenylketonuria patient and mouse study.

    Science.gov (United States)

    Pode-Shakked, Ben; Shemer-Meiri, Lilach; Harmelin, Alon; Stettner, Noa; Brenner, Ori; Abraham, Smadar; Schwartz, Gerard; Anikster, Yair

    2013-01-01

    Phenylalanine (Phe) deficiency and its clinical manifestations have been previously described mostly as sporadic case reports dating back to the 1960's and 1970's. In these reports, low plasma Phe levels were associated with listlessness, eczematous eruptions and failure to gain weight, most often in infants in their first year of life. Herein we describe a 9 month old female patient with known phenylketonuria, who presented with an unusual constellation of symptoms, including severe erythema and desquamation, alopecia, keratomalacia, corneal perforation, failure to thrive and prolonged diarrhea. The diagnostic possibilities of acrodermatitis enteropathica and vitamin deficiencies were ruled out, and further investigation into her medical history led to the conclusion that during the weeks preceding the hospitalization, the patient's diet consisted of the phenylalanine-free medical formula alone, without the addition of a standard infant formula or food as recommended. Subsequently, dietary control of the blood phenylalanine levels brought swift and marked resolution of the dermatological lesions, with renewal of hair growth. Following this experience, and due to the relative paucity of data regarding the clinical manifestations of low serum phenylalanine levels in humans and their putative pathogenetic mechanisms, we sought to further investigate the effects of a phenylalanine-free diet in a mouse study. For this purpose, twenty mice were randomly allocated to receive either a phenylalanine-deficient diet (n=10) or a normal diet (n=10). Weight was measured weekly, and laboratory tests were obtained including complete blood count, electrolyte studies, and phenylalanine and tyrosine levels. Finally, necropsies and histopathological examinations of different tissues were performed in selected mice, either early after diet initiation, late after diet initiation or following re-introduction of normal diets. The study was then repeated in additional two groups of mice

  4. Imaging manifestations of acquired elastopathy resembling pseudoxanthoma elasticum in patients with beta thalassaemia major and sickle cell disease

    International Nuclear Information System (INIS)

    Narayana, Harish; Cheng, Ken; Lau, Ken; Harish, Radhika; Bowden, Donald K.

    2016-01-01

    Development of an acquired systemic elastopathy resembling pseudoxanthoma elasticum in patients with chronic haemoglobinopathies such as beta thalassaemia major and sickle cell disease is well documented. There is paucity of any comprehensive literature on the radiological manifestations of this entity. This pictorial review aims to describe and illustrate the multi system and multi modality imaging findings of this condition.

  5. Hemoglobin, hematocrit, and changes in cerebral blood flow : The Second Manifestations of ARTerial disease-Magnetic Resonance study

    NARCIS (Netherlands)

    van der Veen, Pieternella H.; Muller, Majon; Vincken, Koen L.; Westerink, Jan; Mali, Willem P. T. M.; van der Graaf, Yolanda; Geerlings, Mirjam I.; Doevendans, PAFM

    Hemoglobin and hematocrit are important determinants of blood viscosity and arterial oxygen content and may therefore influence cerebral blood flow (CBF). We examined cross-sectional and prospective associations of hemoglobin and hematocrit with CBF in 569 patients with manifest arterial disease

  6. Clinical and microbiological characteristics of unusual manifestations of invasive pneumococcal disease.

    Science.gov (United States)

    Sousa, Adrian; Pérez-Rodríguez, Maria Teresa; Nodar, Andrés; Martínez-Lamas, Lucía; Vasallo, Francisco Jose; Álvarez-Fernández, Maximiliano; Crespo, Manuel

    2017-06-22

    Invasive pneumococcal disease (IPD) typically presents as bacterial pneumonia, meningitis or primary bacteraemia. However, Streptococcus pneumoniae can produce infection at any level of the body (endocarditis, arthritis, spontaneous bacterial peritonitis, etc.), which is also known as unusual IPD (uIPD). There are very limited data available about the clinical and microbiological profile of these uncommon manifestations of pneumococcal disease. Our aim was to analyse clinical forms, microbiological profile, epidemiology and prognosis of a cohort of patients with unusual invasive pneumococcal disease (uIPD). We present a retrospective study of 389 patients (all adult and paediatric patients diagnosed during the period) diagnosed with IPD at our hospital (Complejo Hospitalario Universitario de Vigo) between 1992 and 2014. We performed an analysis of clinical, microbiological and demographical characteristics of patients comparing the pre-pneumococcal conjugate vaccine (PCV) period with the post-vaccination phase. IPD and uIPD were defined as follows; IPD: infection confirmed by the isolation of S. pneumoniae from a normally sterile site, which classically presented as bacterial pneumonia, meningitis or primary bacteraemia; uIPD: any case of IPD excluding pneumonia, meningitis, otitis media, rhinosinusitis or primary bacteraemia. A total of 22 patients (6%) met the criteria of uIPD. A Charlson index >2 was more prevalent in uIPD patients than IPD patients (45% vs 24%; p=0.08). The most common clinical presentation of uIPD was osteoarticular infection (8 patients, 36%), followed by gastrointestinal disease (4 patients, 18%). Infection with serotypes included in PCV-13 was significantly higher in IPD patients (65%) than in patients with uIPD, 35% (p=0.018). Conversely, infection with multidrug-resistant strains was higher among patient with uIPD (27% vs 9%; p=0.014). The all-cause mortality rate was 15%, 13% in the IPD group and 32% among patients with uIPD (p=0

  7. High-resolution respirometry of fine-needle muscle biopsies in pre-manifest Huntington's disease expansion mutation carriers shows normal mitochondrial respiratory function.

    Directory of Open Access Journals (Sweden)

    Eva Buck

    Full Text Available Alterations in mitochondrial respiration are an important hallmark of Huntington's disease (HD, one of the most common monogenetic causes of neurodegeneration. The ubiquitous expression of the disease causing mutant huntingtin gene raises the prospect that mitochondrial respiratory deficits can be detected in skeletal muscle. While this tissue is readily accessible in humans, transgenic animal models offer the opportunity to cross-validate findings and allow for comparisons across organs, including the brain. The integrated respiratory chain function of the human vastus lateralis muscle was measured by high-resolution respirometry (HRR in freshly taken fine-needle biopsies from seven pre-manifest HD expansion mutation carriers and nine controls. The respiratory parameters were unaffected. For comparison skeletal muscle isolated from HD knock-in mice (HdhQ111 as well as a broader spectrum of tissues including cortex, liver and heart muscle were examined by HRR. Significant changes of mitochondrial respiration in the HdhQ knock-in mouse model were restricted to the liver and the cortex. Mitochondrial mass as quantified by mitochondrial DNA copy number and citrate synthase activity was stable in murine HD-model tissue compared to control. mRNA levels of key enzymes were determined to characterize mitochondrial metabolic pathways in HdhQ mice. We demonstrated the feasibility to perform high-resolution respirometry measurements from small human HD muscle biopsies. Furthermore, we conclude that alterations in respiratory parameters of pre-manifest human muscle biopsies are rather limited and mirrored by a similar absence of marked alterations in HdhQ skeletal muscle. In contrast, the HdhQ111 murine cortex and liver did show respiratory alterations highlighting the tissue specific nature of mutant huntingtin effects on respiration.

  8. Mice lacking collapsin response mediator protein 1 manifest hyperactivity, impaired learning and memory, and impaired prepulse inhibition

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    Naoya eYamashita

    2013-12-01

    Full Text Available Collapsin response mediator protein 1 (CRMP1 is one of the CRMP family members that are involved in various aspects of neuronal development such as axonal guidance and neuronal migration. Here we provide evidence that crmp1-/- mice exhibited behavioral abnormalities related to schizophrenia. The crmp1-/- mice exhibited hyperactivity and/or impaired emotional behavioral phenotype. These mice also exhibited impaired context-dependent memory and long-term memory retention. Furthermore, crmp1-/- mice exhibited decreased prepulse inhibition, and this phenotype was rescued by administration of chlorpromazine, a typical antipsychotic drug. In addition, in vivo microdialysis revealed that the methamphetamine-induced release of dopamine in prefrontal cortex was exaggerated in crmp1-/- mice, suggesting that enhanced mesocortical dopaminergic transmission contributes to their hyperactivity phenotype. These observations suggest that impairment of CRMP1 function may be involved in the pathogenesis of schizophrenia. We propose that crmp1-/- mouse may model endophenotypes present in this neuropsychiatric disorder.

  9. Nephrolithiasis as a common urinary system manifestation of inflammatory bowel diseases; a clinical review and meta-analysis.

    Science.gov (United States)

    Ganji-Arjenaki, Mahboube; Nasri, Hamid; Rafieian-Kopaei, Mahmoud

    2017-07-01

    The extra-intestinal manifestations of inflammatory bowel disease (IBD) are common and involve other organs or systems for example; urinary system. For this review, we used a variety of sources by searching through Web of Science, PubMed, EMBASE, Scopus and directory of open access journals (DOAJ). Urinary complications may occur in up to 22% of patients and nephrolithiasis or renal/kidney stones have been suggested to be a common manifestation of disease in forms of uric acid, calcium phosphate or calcium oxalate. We performed a meta-analysis on five clinical trials and reported that correlation between IBD and formation of stone in renal system is positive and significant (Fix-effect model; CI: 95%, P <0.001, and randomeffect model; CI: 95%, P = 0.03). Based on the reports of the clinical trials, calcium oxalate is more prevalent in Crohn's disease (CD) than in ulcerative colitis (UC).

  10. [Effects of chronic fluoxetine treatment on manifestation of sexual motivation and social behavior in mice of ASC line].

    Science.gov (United States)

    Tikhonova, M A; Otroshchenko, E A; Kulikov, A V

    2010-02-01

    Sexual dysfunctions are the typical symptoms accompanying depressive disorders. However antidepressants which improve general state of the patients have no effect on sexual disorders. Mice of ASC (Antidepressant Sensitive Catalepsy) line with high hereditary predisposition to catalepsy were proposed as a model of genetically associated depressive-like condition. The work was aimed at comparison of behavioral indices of sexual motivation and social interest of ASC mice with those of mice of parental inbred AKR and CBA strains, and at the study of the effects of chronic fluoxetine treatment in doses of 10 and 20 mg/kg on these parameters in ASC mice. ASC males demonstrated reduced sexual motivation which was not corrected by fluoxetine. ASC mice did not differ in the expression of social interest and aggression towards juvenile intruder from mice of parental strains. Fluoxetine failed to alter social behavior of ASC mice in social interaction test but its higher dose decreased percentage of aggressors. ASC mouse line seems to be a perspective model to study genetic mechanisms of sexual dysfunctions associated with depressive conditions.

  11. Latent Lymphocytic Enterocolitis Associated with Celiac Disease Manifesting after Resection for Colon Cancer: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Vikram Tangri

    2008-01-01

    Full Text Available Lymphocytic colitis, a cause of chronic watery diarrhea, is histologically characterized by increased intraepithelial lymphocytosis. Studies have associated this disorder with celiac disease, although there are no reports of patients with both lymphocytic colitis and colon cancer. The present case report describes a patient with lymphocytic colitis, which manifested five years after he presented with a cecal adenocarcinoma, and three years following a diagnosis of celiac disease. Pathological review of his initial resection specimen demonstrated lymphocytic enterocolitis, indicating a five-year latency in the presentation of this disease.

  12. Menkes' disease in Mottled mice and man

    International Nuclear Information System (INIS)

    Hamer, C.J.A. van den; Prins, H.W.; Nooijen, J.L.

    1979-01-01

    Biochemically the defect of the Brindled allelic mutant of the Mottled mouse and of Menkes' disease in man are very similar if not identical. A modification of a normal Cu-binding protein or an unrestrained synthesis of a Cu-binding protein that normally is present only in small amounts is proposed as the basis of this disease

  13. Association of immune response to endothelial cell growth factor with early disseminated and late manifestations of Lyme disease but not posttreatment Lyme disease syndrome.

    Science.gov (United States)

    Tang, Kevin S; Klempner, Mark S; Wormser, Gary P; Marques, Adriana R; Alaedini, Armin

    2015-12-01

    Endothelial cell growth factor has been recently proposed as a potential autoantigen in manifestations of Lyme disease that are thought to involve immune-mediated mechanisms. Our findings indicate that a humoral immune response to this protein is not associated with posttreatment Lyme disease syndrome. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Pulmonary lymphangioleiomyomatosis: Analysis of disease manifestation by region-based quantification of lung parenchyma

    Energy Technology Data Exchange (ETDEWEB)

    Theilig, D., E-mail: dorothea.theilig@charite.de [Charité, Universitätsmedizin Berlin, Department of Radiology, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin (Germany); Doellinger, F. [Charité, Universitätsmedizin Berlin, Department of Radiology, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin (Germany); Kuhnigk, J.M. [Fraunhofer MEVIS, Universitaetsallee 29, 28359 Bremen (Germany); Temmesfeld-Wollbrueck, B.; Huebner, R.H. [Charité, Department of Pneumology, Augustenburger Platz 1, 13353 Berlin (Germany); Schreiter, N.; Poellinger, A. [Charité, Universitätsmedizin Berlin, Department of Radiology, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin (Germany)

    2015-04-15

    Highlights: •The distribution of cystic lesions in LAM was evaluated with quantitative CT. •There were more cystic lesions in the central lung compared to peripheral areas. •Cystic changes were more frequent in apical two thirds compared to lower third. •Results might help to obviate the need for biopsy in more cases. -- Abstract: Purpose: Lymphangioleiomyomatosis (LAM) is characterized by proliferation of smooth muscle tissue that causes bronchial obstruction and secondary cystic destruction of lung parenchyma. The aim of this study was to evaluate the typical distribution of cystic defects in LAM with quantitative volumetric chest computed tomography (CT). Materials and methods: CT examinations of 20 patients with confirmed LAM were evaluated with region-based quantification of lung parenchyma. Additionally, 10 consecutive patients were identified who had recently undergone CT imaging of the lung at our institution, in which no pathologies of the lung were found, to serve as a control group. Each lung was divided into three regions (upper, middle and lower thirds) with identical number of slices. In addition, we defined a “peel” and “core” of the lung comprising the 2 cm subpleural space and the remaining inner lung area. Computerized detection of lung volume and relative emphysema was performed with the PULMO 3D software (v3.42, Fraunhofer MEVIS, Bremen, Germany). This software package enables the quantification of emphysematous lung parenchyma by calculating the pixel index, which is defined as the ratio of lung voxels with a density <−950 HU to the total number of voxels in the lung. Results: Cystic changes accounted for 0.1–39.1% of the total lung volume in patients with LAM. Disease manifestation in the central lung was significantly higher than in peripheral areas (peel median: 15.1%, core median: 20.5%; p = 0.001). Lower thirds of lung parenchyma showed significantly less cystic changes than upper and middle lung areas combined (lower

  15. [The relationship between extraesophageal manifestations of gastroesophageal reflux disease, the frequency of heartburn and severity of oesophagitis].

    Science.gov (United States)

    2011-01-01

    We performed clinico-epidemiologic screening for the heartburn in a representative sample from a total of 1138 subjects and for oesophagitis from 371 ones. In a separate study 120 patients were divided into groups differing in the severity of oesophagitis based on the Savary-Miller classification. The extraesophageal manifestations were diagnosed by clinical and instrumental methods. The close relationship of these manifestations with heartburn and oesophagitis was more pronounced in men than in women. Enhanced severity of the lesions in eosophageal mucosa in patients with oesophagitis was related to increased frequency of ENT diseases and cardialgia but not respiratory disorders. The data obtained give evidence of direct association of heartburn and eosophagitis with coughing, ENT diseases and cardialgia.

  16. Quality of life, fatigue and mental health in patients with the m.3243A > G mutation and its correlates with genetic characteristics and disease manifestation

    NARCIS (Netherlands)

    Verhaak, Christianne; de Laat, Paul; Koene, Saskia; Tibosch, Marijke; Rodenburg, Richard; de Groot, Imelda; Knoop, Hans; Janssen, Mirian; Smeitink, Jan

    2016-01-01

    Background: Mitochondrial disorders belong to the most prevalent inherited metabolic diseases with the m.3243A > G mutation reflecting being one of the most common mutations in mitochondrial DNA. Previous studies showed little relationship between mitochondrial genetics and disease manifestation.

  17. Glutamate-system defects behind psychiatric manifestations in a familial hemiplegic migraine type 2 disease-mutation mouse model

    DEFF Research Database (Denmark)

    Bøttger, Pernille; Pedersen, Simon Glerup; Gesslein, Bodil

    2016-01-01

    Migraine is a complex brain disorder, and understanding the complexity of this prevalent disease could improve quality of life for millions of people. Familial Hemiplegic Migraine type 2 (FHM2) is a subtype of migraine with aura and co-morbidities like epilepsy/seizures, cognitive impairments...... sex hormone cycle and the glutamate system and a link to co-morbid psychiatric manifestations of FHM2....

  18. Characterisation of an atypical manifestation of black band disease on Porites lutea in the Western Indian Ocean

    Directory of Open Access Journals (Sweden)

    Mathieu Séré

    2016-07-01

    Full Text Available Recent surveys conducted on Reunion Island coral reefs revealed an atypical manifestation of black band disease on the main framework building coral, Porites lutea. This BBD manifestation (PorBBD presented a thick lighter-colored band, which preceded the typical BBD lesion. Whilst BBD aetiology has been intensively described worldwide, it remains unclear if corals with apparently similar lesions across coral reefs are affected by the same pathogens. Therefore, a multidisciplinary approach involving field surveys, gross lesion monitoring, histopathology and 454-pyrosequencing was employed to provide the first comprehensive characterization of this particular manifestation. Surveys conducted within two geomorphological zones over two consecutive summers and winters showed spatial and seasonal patterns consistent with those found for typical BBD. Genetic analyses suggested an uncharacteristically high level of Vibrio spp. bacterial infection within PorBBD. However, microscopic analysis revealed high densities of cyanobacteria, penetrating the compromised tissue as well as the presence of basophilic bodies resembling bacterial aggregates in the living tissue, adjacent to the bacterial mat. Additionally, classical BBD-associated cyanobacterial strains, genetically related to Pseudoscillatoria coralii and Roseofilum reptotaenium were identified and isolated and the presence of sulfate-reducers or sulfide-oxidizers such as Desulfovibrio and Arcobacter, previously shown to be associated with anoxic microenvironment within typical BBD was also observed, confirming that PorBBD is a manifestation of classical BBD.

  19. Febrile urticaria in a family: uncommon manifestation of a common disease.

    Science.gov (United States)

    Sharma, Vishal; Singhal, Mayank; Sharma, Alka; Kumar, Vivek

    2012-12-15

    Cutaneous manifestations are uncommon with malaria. These include urticaria, purpura fulminans, and petechial rash. We report on a series of three patients from a single family who had an urticarial rash with fever that was subsequently diagnosed to be caused by malaria. Urticarial rash has been previously reported with both falciparum and vivax malaria infections. Although the exact pathogenesis is not clear urticarial rash might be related with IgE mediated mast cell degranulation.

  20. Multiple factors interact to produce responses resembling spectrum of human disease in Campylobacter jejuni infected C57BL/6 IL-10-/- mice

    Directory of Open Access Journals (Sweden)

    Wolf John E

    2009-03-01

    Full Text Available Abstract Background Campylobacter jejuni infection produces a spectrum of clinical presentations in humans – including asymptomatic carriage, watery diarrhea, and bloody diarrhea – and has been epidemiologically associated with subsequent autoimmune neuropathies. This microorganism is genetically variable and possesses genetic mechanisms that may contribute to variability in nature. However, relationships between genetic variation in the pathogen and variation in disease manifestation in the host are not understood. We took a comparative experimental approach to explore differences among different C. jejuni strains and studied the effect of diet on disease manifestation in an interleukin-10 deficient mouse model. Results In the comparative study, C57BL/6 interleukin-10-/- mice were infected with seven genetically distinct C. jejuni strains. Four strains colonized the mice and caused disease; one colonized with no disease; two did not colonize. A DNA:DNA microarray comparison of the strain that colonized mice without disease to C. jejuni 11168 that caused disease revealed that putative virulence determinants, including loci encoding surface structures known to be involved in C. jejuni pathogenesis, differed from or were absent in the strain that did not cause disease. In the experimental study, the five colonizing strains were passaged four times in mice. For three strains, serial passage produced increased incidence and degree of pathology and decreased time to develop pathology; disease shifted from watery to bloody diarrhea. Mice kept on an ~6% fat diet or switched from an ~12% fat diet to an ~6% fat diet just before infection with a non-adapted strain also exhibited increased incidence and severity of disease and decreased time to develop disease, although the effects of diet were only statistically significant in one experiment. Conclusion C. jejuni strain genetic background and adaptation of the strain to the host by serial passage

  1. Expression of C-Reactive Protein and Serum Amyloid A in Early to Late Manifestations of Lyme Disease.

    Science.gov (United States)

    Uhde, Melanie; Ajamian, Mary; Li, Xueting; Wormser, Gary P; Marques, Adriana; Alaedini, Armin

    2016-12-01

     Infection with Borrelia burgdorferi, the causative agent of Lyme disease, triggers host immune responses that affect the clinical outcome and are a source of biomarkers with diagnostic utility. Although adaptive immunity to B. burgdorferi has been extensively characterized, considerably less information is available about the development of innate acute-phase responses in Lyme disease. Our aim in this study was to evaluate the expression of C-reactive protein (CRP) and serum amyloid A (SAA), the prototype acute-phase response proteins, in the context of the varying manifestations associated with Lyme borreliosis.  Circulating concentrations of CRP and SAA in patients with a range of early to late objective manifestations of Lyme disease and in individuals with post-treatment Lyme disease syndrome were compared with those in healthy control groups.  CRP and SAA levels were significantly elevated in early localized and early disseminated Lyme disease but not in the later stages of active infection. Levels of CRP, but not SAA, were also found to be significantly increased in patients with antibiotic-refractory Lyme arthritis and in those with post-treatment Lyme disease syndrome.  These findings indicate that circulating CRP and SAA levels are highest when the concentration of spirochetes is greatest in skin and/or blood and that levels decline after the dissemination of the organism to extracutaneous sites in subsequent stages of infection. The data also suggest that antibiotic-refractory Lyme arthritis and post-treatment Lyme disease syndrome are associated with elevated CRP responses that are driven by inflammatory mechanisms distinct from those in active infection. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  2. Extrahepatic manifestations of cholestasis

    NARCIS (Netherlands)

    Glasova, Helena; Beuers, Ulrich

    2002-01-01

    Pruritus, fatigue and metabolic bone disease represent three major extrahepatic manifestations of chronic cholestatic liver disease that considerably affect the patient's quality of life. The present article reviews pathogenetic aspects of and current therapeutic approaches to extrahepatic

  3. Behavioral phenotyping of Parkin-deficient mice: looking for early preclinical features of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Daniel Rial

    Full Text Available There is considerable evidence showing that the neurodegenerative processes that lead to sporadic Parkinson's disease (PD begin many years before the appearance of the characteristic motor symptoms. Neuropsychiatric, sensorial and cognitive deficits are recognized as early non-motor manifestations of PD, and are not attenuated by the current anti-parkinsonian therapy. Although loss-of-function mutations in the parkin gene cause early-onset familial PD, Parkin-deficient mice do not display spontaneous degeneration of the nigrostriatal pathway or enhanced vulnerability to dopaminergic neurotoxins such as 6-OHDA and MPTP. Here, we employed adult homozygous C57BL/6 mice with parkin gene deletion on exon 3 (parkin-/- to further investigate the relevance of Parkin in the regulation of non-motor features, namely olfactory, emotional, cognitive and hippocampal synaptic plasticity. Parkin-/- mice displayed normal performance on behavioral tests evaluating olfaction (olfactory discrimination, anxiety (elevated plus-maze, depressive-like behavior (forced swimming and tail suspension and motor function (rotarod, grasping strength and pole. However, parkin-/- mice displayed a poor performance in the open field habituation, object location and modified Y-maze tasks suggestive of procedural and short-term spatial memory deficits. These behavioral impairments were accompanied by impaired hippocampal long-term potentiation (LTP. These findings indicate that the genetic deletion of parkin causes deficiencies in hippocampal synaptic plasticity, resulting in memory deficits with no major olfactory, emotional or motor impairments. Therefore, parkin-/- mice may represent a promising animal model to study the early stages of PD and for testing new therapeutic strategies to restore learning and memory and synaptic plasticity impairments in PD.

  4. Aging-associated renal disease in mice is fructokinase dependent.

    Science.gov (United States)

    Roncal-Jimenez, Carlos A; Ishimoto, Takuji; Lanaspa, Miguel A; Milagres, Tamara; Hernando, Ana Andres; Jensen, Thomas; Miyazaki, Makoto; Doke, Tomohito; Hayasaki, Takahiro; Nakagawa, Takahiko; Marumaya, Shoichi; Long, David A; Garcia, Gabriela E; Kuwabara, Masanari; Sánchez-Lozada, Laura G; Kang, Duk-Hee; Johnson, Richard J

    2016-10-01

    Aging-associated kidney disease is usually considered a degenerative process associated with aging. Recently, it has been shown that animals can produce fructose endogenously, and that this can be a mechanism for causing kidney damage in diabetic nephropathy and in association with recurrent dehydration. We therefore hypothesized that low-level metabolism of endogenous fructose might play a role in aging-associated kidney disease. Wild-type and fructokinase knockout mice were fed a normal diet for 2 yr that had minimal (renal injury was amplified by provision of high-salt diet for 3 wk, as noted by the presence of glomerular hypertrophy, mesangial matrix expansion, and alpha smooth muscle actin expression, and with segmental thrombi. Fructokinase knockout mice were protected from renal injury both at baseline and after high salt intake (3 wk) compared with wild-type mice. This was associated with higher levels of active (phosphorylated serine 1177) endothelial nitric oxide synthase in their kidneys. These studies suggest that aging-associated renal disease might be due to activation of specific metabolic pathways that could theoretically be targeted therapeutically, and raise the hypothesis that aging-associated renal injury may represent a disease process as opposed to normal age-related degeneration.

  5. Virus Infections on Prion Diseased Mice Exacerbate Inflammatory Microglial Response

    Science.gov (United States)

    Lins, Nara; Mourão, Luiz; Trévia, Nonata; Passos, Aline; Farias, José Augusto; Assunção, Jarila; Bento-Torres, João; Consentino Kronka Sosthenes, Marcia; Diniz, José Antonio Picanço; Vasconcelos, Pedro Fernando da Costa

    2016-01-01

    We investigated possible interaction between an arbovirus infection and the ME7 induced mice prion disease. C57BL/6, females, 6-week-old, were submitted to a bilateral intrahippocampal injection of ME7 prion strain (ME7) or normal brain homogenate (NBH). After injections, animals were organized into two groups: NBH (n = 26) and ME7 (n = 29). At 15th week after injections (wpi), animals were challenged intranasally with a suspension of Piry arbovirus 0.001% or with NBH. Behavioral changes in ME7 animals appeared in burrowing activity at 14 wpi. Hyperactivity on open field test, errors on rod bridge, and time reduction in inverted screen were detected at 15th, 19th, and 20th wpi respectively. Burrowing was more sensitive to earlier hippocampus dysfunction. However, Piry-infection did not significantly affect the already ongoing burrowing decline in the ME7-treated mice. After behavioral tests, brains were processed for IBA1, protease-resistant form of PrP, and Piry virus antigens. Although virus infection in isolation did not change the number of microglia in CA1, virus infection in prion diseased mice (at 17th wpi) induced changes in number and morphology of microglia in a laminar-dependent way. We suggest that virus infection exacerbates microglial inflammatory response to a greater degree in prion-infected mice, and this is not necessarily correlated with hippocampal-dependent behavioral deficits. PMID:28003864

  6. Clinical and pathological manifestations of cardiovascular disease in rat models: the influence of acute ozone exposure

    Science.gov (United States)

    This paper shows that rat models of cardiovascular diseases have differential degrees of underlying pathologies at a young age. Rodent models of cardiovascular diseases (CVD) and metabolic disorders are used for examining susceptibility variations to environmental exposures. How...

  7. Inhibition of UDP-glucosylceramide synthase in mice prevents Gaucher disease-associated B-cell malignancy.

    Science.gov (United States)

    Pavlova, Elena V; Archer, Joy; Wang, Susan; Dekker, Nick; Aerts, Johannes Mfg; Karlsson, Stefan; Cox, Timothy M

    2015-01-01

    Clonal B-cell proliferation is a frequent manifestation of Gaucher disease - a sphingolipidosis associated with a high risk of multiple myeloma and non-Hodgkin lymphoma. Gaucher disease is caused by genetic deficiency of acid β-glucosidase, the natural substrates of which (β-d-glucosylceramide and β-d-glucosylsphingosine) accumulate, principally in macrophages. Mice with inducible deficiency of β-glucosidase [Gba(tm1Karl/tm1Karl)Tg(MX1-cre)1Cgn/0] serve as an authentic model of human Gaucher disease; we have recently reported clonal B-cell proliferation accompanied by monoclonal serum paraproteins and cognate tumours in these animals. To explore the relationship between B-cell malignancy and the biochemical defect, we treated Gaucher mice with eliglustat tartrate (GENZ 112638), a potent and selective inhibitor of the first committed step in glycosphingolipid biosynthesis. Twenty-two Gaucher mice received 300 mg/kg of GENZ 112638 daily for 3-10 months from 6 weeks of age. Plasma concentrations of β-d-glucosylceramide and the unacylated glycosphingolipid, β-d-glucosylsphingosine, declined. After administration of GENZ 112638 to Gaucher mice for 3-10 months, serum paraproteins were not detected and there was a striking reduction in the malignant lymphoproliferation: neither lymphomas nor plasmacytomas were found in animals that had received the investigational agent. In contrast, 14 out of 60 Gaucher mice without GENZ 112638 treatment developed these tumours; monoclonal paraproteins were detected in plasma from 18 of the 44 age-matched mice with Gaucher disease that had not received GENZ 112638. Long-term inhibition of glycosphingolipid biosynthesis suppresses the development of spontaneous B-cell lymphoma and myeloma in Gaucher mice. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  8. Fabry Disease in Families With Hypertrophic Cardiomyopathy: Clinical Manifestations in the Classic and Later-Onset Phenotypes.

    Science.gov (United States)

    Adalsteinsdottir, Berglind; Palsson, Runolfur; Desnick, Robert J; Gardarsdottir, Marianna; Teekakirikul, Polakit; Maron, Martin; Appelbaum, Evan; Neisius, Ulf; Maron, Barry J; Burke, Michael A; Chen, Brenden; Pagant, Silvere; Madsen, Christoffer V; Danielsen, Ragnar; Arngrimsson, Reynir; Feldt-Rasmussen, Ulla; Seidman, Jonathan G; Seidman, Christine E; Gunnarsson, Gunnar Th

    2017-08-01

    The screening of Icelandic patients clinically diagnosed with hypertrophic cardiomyopathy resulted in identification of 8 individuals from 2 families with X-linked Fabry disease (FD) caused by GLA (α-galactosidase A gene) mutations encoding p.D322E (family A) or p.I232T (family B). Familial screening of at-risk relatives identified mutations in 16 family A members (8 men and 8 heterozygotes) and 25 family B members (10 men and 15 heterozygotes). Clinical assessments, α-galactosidase A (α-GalA) activities, glycosphingolipid substrate levels, and in vitro mutation expression were used to categorize p.D322E as a classic FD mutation and p.I232T as a later-onset FD mutation. In vitro expression revealed that p.D322E and p.I232T had α-GalA activities of 1.4% and 14.9% of the mean wild-type activity, respectively. Family A men had markedly decreased α-GalA activity and childhood-onset classic manifestations, except for angiokeratoma and cornea verticillata. Family B men had residual α-GalA activity and developed FD manifestations in adulthood. Despite these differences, all family A and family B men >30 years of age had left ventricular hypertrophy, which was mainly asymmetrical, and had similar late gadolinium enhancement patterns. Ischemic stroke and severe white matter lesions were more frequent among family A men, but neither family A nor family B men had overt renal disease. Family A and family B heterozygotes had less severe or no clinical manifestations. Men with classic or later-onset FD caused by GLA missense mutations developed prominent and similar cardiovascular disease at similar ages, despite markedly different α-GalA activities. © 2017 American Heart Association, Inc.

  9. Long-term pruritus as the initial and sole clinical manifestation of occult Hodgkin's disease.

    Science.gov (United States)

    Omidvari, Shapour H; Khojasteh, Habib Noorani; Mohammadianpanah, Mohammad; Monabati, Ahmad; Mosalaei, Ahmad; Ahmadloo, Niloofar

    2004-06-01

    Pruritus or itch is a frequent symptom of patients with Hodgkin's disease. It often occurs during the clinical course of the disease and rarely may precede the diagnosis of underlying disease. In this report, we present a 16-year-old patient who had history of generalized pruritus without any skin rash for 4 years before the diagnosis of Hodgkin's disease. Within that period, she had received symptom-oriented medications, with no significant effect. After the first cycle of chemotherapy, her pruritus resolved completely. This case suggests that long-term generalized pruritus may be indicative of a significant underlying problem like Hodgkin's disease.

  10. Bitot’s Spots following Bariatric Surgery: An Ocular Manifestation of a Systemic Disease

    Directory of Open Access Journals (Sweden)

    Amanda R. Crum

    2017-12-01

    Full Text Available Background: To present a case of ocular complications from vitamin A deficiency following bariatric surgery. Case Report: A 41-year-old woman presented with symptoms of dryness and diminished night vision. Examination revealed corneal punctate staining, keratinization of the conjunctiva, and multiple mid-peripheral white lesions at the level of the retinal pigment epithelium. Given the patient’s history of bariatric surgery, anemia, and vitamin D deficiency, further investigation into micronutrient levels was performed and indicated a severe vitamin A deficiency. Oral vitamin A supplementation resulted in the complete resolution of her symptoms within two months. Conclusions: Nutritional deficiencies following bariatric surgery are common and can be disruptive to normal systemic health and visual function. Given that the number of patients pursuing bariatric surgery for weight loss management has increased over the past 50 years, eye care professionals should be aware of the ophthalmic manifestations associated with micronutrient deficiency.

  11. Unilateral pitting edema of the leg as a manifestation of Graves’ disease: a case report

    Directory of Open Access Journals (Sweden)

    Volke Vallo

    2012-08-01

    Full Text Available Abstract Introduction Graves’ hyperthyroidism has a number of well-recognized but relatively rare extrathyroid manifestations such as thyroid acropachy, pretibial myxedema, and congestive heart failure. Case presentation A 38-year-old Caucasian woman presented to the out-patient clinic with symptoms of hyperthyroidism lasting for approximately five months. Remarkably, she had developed pitting edema of her left leg four months before. She had gone through a conventional assessment, but the reason for the edema was not revealed. At presentation to the endocrinology clinic, the skin of both legs was of normal color and pitting edema on her left leg was of a diffuse nature and spread from her toes to two thirds of her leg. The skin surface of her left leg was smooth and had no elevations or discoloration, whereas her right leg appeared normal. Based on signs and symptoms of thyrotoxicosis and suppressed thyroid-stimulating hormone level (less than 0.001mIU/L, local reference of 0.4 to 4, treatment of 10mg of thiamazole three times a day was started. Additional blood tests revealed marked Graves’ hyperthyroidism with elevated free T4 and anti-thyroid receptor antibodies. Within a month, the free T4 level was normalized and the edema was completely cleared and never reappeared during the treatment course of 12 months. Conclusions To the best of our knowledge, this is the first description of unilateral treatment-responsive leg edema as a manifestation of Graves’ hyperthyroidism. However, the pathophysiological mechanism underlying this case of edema remains unclear.

  12. Spectrum of lymphoid hyperplasia: colonic manifestations of sarcoidosis, infectious mononucleosis, and Crohn's disease

    Energy Technology Data Exchange (ETDEWEB)

    Ell, S.R.; Frank, P.H.

    1981-10-15

    The radiographic pattern of nodular lymphoid hyperplasia, perhaps better called the lymphoid follicular pattern, has variously been described as an indication of disease and as a normal variant in the adult, with current opinion favoring the latter. We report 3 cases wherein this pattern resulted from definite pathologic processes: sarcoidosis, infectious mononucleosis, and Crohn's disease. Although usually of no pathological significance, the benign follicular pattern may reflect a variety of diseases.

  13. Spectrum of lymphoid hyperplasia: Colonic manifestations of sarcoidosis, infectious mononucleosis, and Crohn's disease

    International Nuclear Information System (INIS)

    Ell, S.R.; Frank, P.H.

    1981-01-01

    The radiographic pattern of nodular lmyphoid hyperplasia, perhaps better called the lymphoid follicular pattern, has variously been described as an indication of disease and as a normal variant in the adult, with current opinion favoring the latter. We report 3 cases wherein this pattern resulted from definite pathologic processes: sarcoidosis, infectious mononucleosis, and Crohn's disease. Although usually of no pathological significance, the benign follicular pattern may reflect a variety of diseases. (orig.)

  14. Altered Liver Proteoglycan/Glycosaminoglycan Structure as a Manifestation of Extracellular Matrix Remodeling upon BCG-induced Granulomatosis in Mice.

    Science.gov (United States)

    Kim, L B; Shkurupy, V A; Putyatina, A N

    2017-01-01

    Experimental BCG-induced granulomatosis in mice was used to study changes in the dynamics of individual liver proteoglycan components reflecting phasic extracellular matrix remodeling, determined by the host-parasite interaction and associated with granuloma development. In the early BCG-granulomatosis period, the increase in individual proteoglycan components promotes granuloma formation, providing conditions for mycobacteria adhesion to host cells, migration of phagocytic cells from circulation, and cell-cell interaction leading to granuloma development and fibrosis. Later, reduced reserve capacity of the extracellular matrix, development of interstitial fibrosis and granuloma fibrosis can lead to trophic shortage for cells within the granulomas, migration of macrophages out of them, and development of spontaneous necrosis and apoptosis typical of tuberculosis.

  15. Type II autosomal dominant osteopetrosis (Albers-Schönberg disease): clinical and radiological manifestations in 42 patients.

    Science.gov (United States)

    Bénichou, O D; Laredo, J D; de Vernejoul, M C

    2000-01-01

    Type II autosomal dominant osteopetrosis (ADO II, Albers-Schonberg disease) is a genetic condition characterized by generalized osteosclerosis predominating in some skeletal sites such as the spine and pelvis. ADO II is rare, and most available clinical descriptions are based on small numbers of patients. We report the clinical and radiological manifestations in 42 ADO II patients. To our knowledge, this is the largest series reported so far. Our inclusion criterion was presence on radiographs of the spine of vertebral endplate thickening, producing the classic sandwich vertebra appearance. We found various patterns of sandwich vertebra, of which we provide a description to assist physicians in diagnosing ADO II. The classic bone-within-bone appearance was present in most but not all skeletal sites. The radiological penetrance of the disease was high (90%) and increased after 20 years of age. As many as 81% of our patients experienced clinical manifestations. Fractures were common (78% of patients) and healed slowly. Hip osteoarthritis developed in 27% of patients and required arthroplasty in 9 of the 16 affected hips. Nonmandibular osteomyelitis occurred in 4 cases (11%). Twenty-four percent of patients had thoracic or lumbar scoliosis. Orthopedic surgery was performed in 52.8% of patients, of whom half had at least three surgical procedures for internal fracture fixation, arthroplasty, limb deformity correction, or treatment of surgical complications. There was a high rate of surgical complications including nonunion, infection, prosthesis loosening, and intraoperative fractures. Nearly two-thirds of patients (64%) had stomatologic manifestations, including mandibular osteomyelitis in 4 patients (11%). Cranial nerve involvement responsible for hearing loss, bilateral optic atrophy, and/or facial palsy was present in 14 patients but was clearly attributable to ADO II in only 6 cases (16%). This large series sheds new light on several aspects of ADO II, most

  16. The association between uric acid levels and different clinical manifestations of coronary artery disease

    DEFF Research Database (Denmark)

    Larsen, Trine R; Gerke, Oke; Diederichsen, Axel C P

    2018-01-01

    AIMS: Uric acid (UA) has been associated with the presence and severity of coronary artery disease. To further assess the role of UA role in coronary artery disease, we investigated UA levels in both healthy asymptomatic middle-aged individuals and in different subgroups of hospitalized patients...

  17. Extraintestinal manifestations in Crohn's disease and ulcerative colitis: results from a prospective, population-based European inception cohort.

    Science.gov (United States)

    Isene, Rune; Bernklev, Tomm; Høie, Ole; Munkholm, Pia; Tsianos, Epameonondas; Stockbrügger, Reinhold; Odes, Selwyn; Palm, Øyvind; Småstuen, Milada; Moum, Bjørn

    2015-03-01

    In chronic inflammatory bowel disease (IBD) (Crohn's disease [CD] and ulcerative colitis [UC]), symptoms from outside the gastrointestinal tract are frequently seen, and the joints, skin, eyes, and hepatobiliary area are the most usually affected sites (called extraintestinal manifestations [EIM]). The reported prevalence varies, explained by difference in study design and populations under investigation. The aim of our study was to determine the prevalence of EIM in a population-based inception cohort in Europe and Israel. IBD patients were incepted into a cohort that was prospectively followed from 1991 to 2004. A total of 1145 patients were followed for 10 years. The cumulative prevalence of first EIM was 16.9% (193/1145 patients) over a median follow-up time of 10.1 years. Patients with CD were more likely than UC patients to have immune-mediated (arthritis, eye, skin, and liver) manifestations: 20.1% versus 10.4% (p colitis compared to proctitis in UC increased the risk of EIM. In a European inception cohort, EIMs in IBD were consistent with that seen in comparable studies. Patients with CD are twice as likely as UC patients to experience EIM, and more extensive distribution of inflammation in UC increases the risk of EIM.

  18. Relationship between disease characteristics and orofacial manifestations in systemic sclerosis: Canadian Systemic Sclerosis Oral Health Study III.

    Science.gov (United States)

    Baron, Murray; Hudson, Marie; Tatibouet, Solène; Steele, Russell; Lo, Ernest; Gravel, Sabrina; Gyger, Geneviève; El Sayegh, Tarek; Pope, Janet; Fontaine, Audrey; Masetto, Ariel; Matthews, Debora; Sutton, Evelyn; Thie, Norman; Jones, Niall; Copete, Maria; Kolbinson, Dean; Markland, Janet; Nogueira, Getulio; Robinson, David; Fritzler, Marvin; Gornitsky, Mervyn

    2015-05-01

    Systemic sclerosis (SSc; scleroderma) is associated with decreased saliva production and interincisal distance, more missing teeth, and periodontal disease. We undertook this study to determine the clinical correlates of SSc with these oral abnormalities. Subjects were recruited from the Canadian Scleroderma Research Group cohort. Detailed dental and clinical examinations were performed according to standardized protocols. Associations between dental abnormalities and selected clinical and serologic manifestations of SSc were examined. One hundred sixty-three SSc subjects were included: 90% women, mean ± SD age 56 ± 11 years, mean ± SD disease duration 14 ± 8 years, 72% with limited cutaneous disease, and 28% with diffuse cutaneous disease. Decreased saliva production was associated with Sjögren's syndrome-related autoantibodies (β = -43.32; 95% confidence interval [95% CI] -80.89, -5.75), but not with disease severity (β = -2.51; 95% CI -8.75, 3.73). Decreased interincisal distance was related to disease severity (β = -1.02; 95% CI -1.63, -0.42) and the modified Rodnan skin thickness score (β = -0.38; 95% CI -0.53, -0.23). The number of missing teeth was associated with decreased saliva production (relative risk [RR] 0.97; 95% CI 0.94, 0.99), worse hand function (RR 1.52; 95% CI 1.13, 2.02), and the presence of gastroesophageal reflux disease (GERD; RR 1.68 [95% CI 1.14, 2.46]). No clinical or serologic variables were correlated with periodontal disease. In SSc, diminished interincisal distance is related to overall disease severity. Decreased saliva production is related to concomitant Sjögren's syndrome antibodies. Tooth loss is associated with poor upper extremity function, GERD, and decreased saliva. The etiology of excess periodontal disease is likely multifactorial and remains unclear. © 2015, American College of Rheumatology.

  19. Normal villous architecture with increased intraepithelial lymphocytes: a duodenal manifestation of Crohn disease.

    Science.gov (United States)

    Patterson, Emily R; Shmidt, Eugenia; Oxentenko, Amy S; Enders, Felicity T; Smyrk, Thomas C

    2015-03-01

    To assess a possible association between inflammatory bowel disease (IBD) and the histologic finding in duodenal biopsy specimens of increased intraepithelial lymphocytes (IELs) with normal villous architecture. We identified all patients with duodenal biopsy specimens obtained between 2000 and 2010 showing increased IELs and normal architecture. Among the 74 such patients who also had IBD, we characterized the clinical features of IBD and reviewed all available upper gastrointestinal biopsy specimens. Fifty-eight patients had Crohn disease, 13 had ulcerative colitis, and three had IBD, type unclassified. No duodenal sample with increased IELs had other histologic features of IBD. Among gastric biopsy specimens from 34 patients with Crohn disease, nearly half (16) had focal gastritis. We propose that Crohn disease be included in the differential diagnosis for increased IELs with normal villous architecture in duodenal biopsy specimens, particularly when gastric biopsy specimens show focal gastritis. Copyright© by the American Society for Clinical Pathology.

  20. The case of Cushings disease imaging by SPECT examination without manifestation of adenoma in MRI examination

    International Nuclear Information System (INIS)

    Gierach, M.; Pufal, J.; Pilecki, S.; Junik, R.

    2005-01-01

    The aim of our study was to evaluate the possibility of imaging the pathological accumulation of 99mT c-MIBI in the pituitary gland in patients with Cushings disease when MRI examination does not show microadenomas. Cushings disease was diagnosed in a 27 year old male on the basis of clinical and biochemical findings. The blood cortisol level of the patient was elevated (the average level was 47 microgram/dl) and it showed no changeability of day and night rhythm. In the patient with Cushing's disease, during the SPECT examination, an increased accumulation of 99mT c-MIBI in the pituitary gland was noticed. MRI scanning was negative. Single photon emission computed tomography using 99mT c-MIBI is a useful and sensitive means of pituitary gland microadenoma detection in patients with Cushings disease when microadenoma is not detected during MRI scanning and when the results of dexamethasone suppression test is positive. (author)

  1. Pedicle marrow signal intensity changes in the lumbar spine: a manifestation of facet degenerative joint disease

    International Nuclear Information System (INIS)

    Morrison, J.L.; Kaplan, P.A.; Dussault, R.G.; Anderson, M.W.

    2000-01-01

    Objective. Signal intensity changes in lumbar pedicles, similar to those described in vertebral body endplates adjacent to degenerated discs, have been described as an ancillary sign of spondylolysis on MRI. The purpose of this study was to determine whether pedicle marrow signal intensity changes also occur in association with facet degenerative joint disease.Design. Eighty-nine lumbar spine MRI examinations without spondylolysis were reviewed for marrow signal intensity changes in pedicles and vertebral bodies as well as for facet degenerative joint disease.Results. Five percent (46/890) of lumbar pedicles in 23 patients had marrow signal intensity changes. Ninety-one percent (42/46) of the abnormal pedicles had adjacent degenerative joint disease of the facets, while only 21% (189/890) of normal pedicles had adjacent facet degenerative joint disease (p<0.001). Eighty-nine percent (41/46) of the pedicles with marrow signal intensity changes had adjacent degenerative disc disease.Conclusions. Pedicle marrow signal intensity changes are not a specific sign of spondylolysis; they are commonly seen with adjacent facet degenerative joint disease in the absence of spondylolysis. Pedicle marrow signal intensity changes are probably a response to abnormal stresses related to abnormal motion or loading caused by the degenerative changes in the spinal segment. (orig.)

  2. Pedicle marrow signal intensity changes in the lumbar spine: a manifestation of facet degenerative joint disease

    Energy Technology Data Exchange (ETDEWEB)

    Morrison, J.L.; Kaplan, P.A.; Dussault, R.G.; Anderson, M.W. [Dept. of Radiology, Univ. of Virginia Health System, Charlottesville, VA (United States)

    2000-12-01

    Objective. Signal intensity changes in lumbar pedicles, similar to those described in vertebral body endplates adjacent to degenerated discs, have been described as an ancillary sign of spondylolysis on MRI. The purpose of this study was to determine whether pedicle marrow signal intensity changes also occur in association with facet degenerative joint disease.Design. Eighty-nine lumbar spine MRI examinations without spondylolysis were reviewed for marrow signal intensity changes in pedicles and vertebral bodies as well as for facet degenerative joint disease.Results. Five percent (46/890) of lumbar pedicles in 23 patients had marrow signal intensity changes. Ninety-one percent (42/46) of the abnormal pedicles had adjacent degenerative joint disease of the facets, while only 21% (189/890) of normal pedicles had adjacent facet degenerative joint disease (p<0.001). Eighty-nine percent (41/46) of the pedicles with marrow signal intensity changes had adjacent degenerative disc disease.Conclusions. Pedicle marrow signal intensity changes are not a specific sign of spondylolysis; they are commonly seen with adjacent facet degenerative joint disease in the absence of spondylolysis. Pedicle marrow signal intensity changes are probably a response to abnormal stresses related to abnormal motion or loading caused by the degenerative changes in the spinal segment. (orig.)

  3. Intracerebroventricular Delivery in Mice for Motor Neuron Diseases.

    Science.gov (United States)

    Nizzardo, M; Rizzuti, M

    2017-01-01

    The use of antisense oligonucleotides to target specific mRNA sequences represents a promising therapeutic strategy for neurological disorders. Recent advances in antisense technology enclose the development of phosphorodiamidate morpholino oligomers (MO), which is one of the best candidates for molecular therapies due to MO's excellent pharmacological profile.Nevertheless, the route of administration of antisense compounds represents a critical issue in the neurological field. Particularly, as regards motor neuron diseases, intracerebroventricular (ICV) injection is undoubtedly the most efficient procedure to directly deliver therapeutic molecules in the central nervous system (CNS). Indeed, we recently demonstrated the outstanding efficacy of the MO antisense approach by its direct administration to CNS of the transgenic mouse models of Spinal Muscular Atrophy (SMA) and Amyotrophic Lateral Sclerosis (ALS).Here, we describe methods to perform the ICV delivery of MO in neonatal SMA mice and in adult ALS mice.

  4. Periodic Paralysis and Encephalopathy as Initial Manifestations of Graves' Disease: Case Report and Review of the Literature.

    Science.gov (United States)

    Tsironis, Theocharis; Tychalas, Athanasios; Kiourtidis, Dimitrios; Kountouras, Jannis; Xiromerisiou, Georgia; Rudolf, Jobst; Deretzi, Georgia

    2017-07-01

    Thyrotoxic periodic paralysis (TPP) is an uncommon complication of Graves' disease, characterized by the triad of acute hypokalemia without total body potassium deficit, episodic muscle paralysis, and thyrotoxicosis. Graves' encephalopathy is an extremely rare form of encephalopathy associated with autoimmune thyroid disease (EAATD), characterized by neuropsychiatric symptoms, increased antithyroid antibodies and cerebrospinal fluid protein concentration, nonspecific electroencephalogram abnormalities, and cortico-responsiveness. Coexistence of both these complications in the same patient has not been reported before. We herein present a 48-year-old white male patient with TPP and encephalopathy as initial presentations of Graves' disease. Flaccid tetraparesis was reversed a few hours after potassium level correction and the patient did not suffer any relapse with the successful pharmaceutical management of the thyroid function. One month later, the patient presented with dizziness and behavioral symptoms, such as inappropriate laughter and anger. Brain magnetic resonance imaging revealed meningeal enhancement and cerebrospinal fluid analysis showed a mild protein increase, with a blood-brain barrier disruption. With the suspicion of EAATD, the patient was treated with high doses of corticosteroids and improved dramatically. To our knowledge this is the first reported coexistence of potentially treatable TPP and EAATD as initial neurological manifestations of Graves' disease, thereby underscoring the necessity of suspicion of possible underlying Graves' disease in patients with acute paralysis and encephalopathy of unclear origin.

  5. Chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases.

    Science.gov (United States)

    Al-Bari, Md Abdul Alim

    2015-01-01

    Antimalarial drugs (e.g. chloroquine and its close structural analogues) were developed primarily to treat malaria; however, they are beneficial for many dermatological, immunological, rheumatological and severe infectious diseases, for which they are used mostly today. Chloroquine and hydroxychloroquine, two of the most fascinating drugs developed in the last 50 years, are increasingly recognized for their effectiveness in myriad non-malarial diseases. In advanced research, chloroquine and hydroxychloroquine have been shown to have various immunomodulatory and immunosuppressive effects, and currently have established roles in the management of rheumatic diseases, lupus erythematosus (different forms) and skin diseases, and in the treatment of different forms of cancer. Recently, chloroquine analogues have also been found to have metabolic, cardiovascular, antithrombotic and antineoplastic effects. This review is concerned with the lysosomotropic, anti-inflammatory and immunomodulatory mechanisms of chloroquine, hydroxychloroquine, quinacrine and related analogues, and the current evidence for both their beneficial effects and potential adverse manifestations in various diseases. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. THE РERSONALITY PROFILE OF PATIENTS WITH EARLY MANIFESTATIONS OF PARKINSON'S DISEASE

    Directory of Open Access Journals (Sweden)

    R. R. Bogdanov

    2016-01-01

    Full Text Available Background: Mental disorders that sometimes may precede motor dysfunction have an important value in Parkinson's disease, especially at its earlier stages. Personality characteristics of patients with Parkinson's disease have not been studied enough and require a  detailed assessment, because it is a  major factor contributing to treatment efficacy. Aim: To assess personality profiles of patients with early stages of Parkinson's disease and an impact of a dopamine receptor agonist on the personality profile. Materials and methods: We assessed 33 treatment-naïve patients with early symptoms of Parkinson's disease (Hoehn-Yahr stage I and II. The following scales were used before treatment and at 1, 3 and 6 months of treatment with pramipexol: for motor disorders (UPDRS, Unified Parkinson's Disease Rating Scale, depressive disorders (MADRS, Montgomery Asberg Depression Rating Scale and anxiety disorders (HARS, Hamilton Anxiety Rating Scale, as well as personality profile (MMPI, Minnesota Multiphasic Personality Inventory. Results: The personality profile assessed by MMPI in patients with early stage Parkinson's disease was characterized by highest T scores on scales 2 (pessimism (74 [64; 86], 1 (neurotic excess control (67 [63; 74], 3  (emotional instability (64 [56; 70], 7 (anxiousness (63 [52; 70], 8 (autism (64 [58; 74], 0  (introversion (63 [59; 66]. This indicates basic pathopsychological characteristics of patients with early stages of the disease. In particular, their emotional sphere demonstrated anxiety- and depression-related affective disorders. Their personality structure was characterized by dysthymic, anxious, rigid and explosive traits, and susceptibility to hypochondriasis. With a background of a dramatic motivational conflict, frustration of high-level need in self-actualization and recognition due to a chronic disease with motor dysfunction triggered a depressive response type. Pharmacological treatment with

  7. Carcinoid Syndrome and Carcinoid Heart Disease as Manifestations of Non-Metastatic Ovarian Neuroendocrine Tumour

    Directory of Open Access Journals (Sweden)

    Joana Simões-Pereira

    2017-05-01

    Full Text Available The carcinoid syndrome is rare but it is associated with carcinoid heart disease in more than a half of the cases. Carcinoid heart disease is typically characterised by morphological and functional modifications of right-sided valves. Its aetiology is probable multifactorial but serotonin appears to play a key role in the development of this valvular disease. Unlike gastrointestinal neuroendocrine tumours, ovarian neuroendocrine tumours can present with carcinoid syndrome and carcinoid heart disease in the absence of liver metastases; such ovarian neuroendocrine tumours are a unique clinical entity. The additional burden of cardiac impairment in these patients represents a significant reduction in survival. Early recognition and surgical valve replacement before advanced heart failure is established may improve the clinical outcome. We report the case of a woman with an ovarian neuroendocrine tumour and highly symptomatic carcinoid heart disease who was submitted to tumour resection followed by valvuloplasty. She demonstrated an outstanding clinical improvement and has remained free of tumour and symptomatology.

  8. Comparison between the radiological manifestations of thoracic involvement in collagen vascular diseases and idiopathic pulmonary fibrosis

    International Nuclear Information System (INIS)

    Kirova, G.; Rashkov, R.; Georgiev, O.

    2002-01-01

    The purpose of the study is to compare the presentation and distribution of lung abnormalities seen in Collagen Vascular Diseases (CVD) with those specifics for Idiopathic Pulmonary Fibrosis (IPF). The HRCT scans of 92 patients fulfilling the ARA criteria's for the diagnosis of four different CVD were reviewed and compared with those of 18 patients with IPF. The presentations of three main patterns of lung disease were assessed into the both groups. In order to find out the trend distribution in each disease, the grade and severity of presentation for the main abnormalities were assessed, using a scoring system.The incidence of reticular lung abnormalities for the group of IPF is 100 % versus 57.3 % for the CVD (p<0.0009). At the same time CVD, except for PSS, had a low incidence of reticular diseases (37 %). The incidence of alveolar abnormalities in CVD (57.3 %) were similar as these in IPF (66.6 %) (p=NS). The severity of the disease was greatest in IPF and PSS without significant difference between them. Nevertheless of uniform character of the abnormalities in the rest of CVD, they were presented with lesser degree and severity. The main abnormalities, seen in pulmonary parenchyma in patients with IPF and CVD were similar but with different grade, severity and distribution. (authors)

  9. The manifestation of 18F-FDG imaging of coincidence SPECT in benign pulmonary diseases

    International Nuclear Information System (INIS)

    Miao Jisheng; Liu Jinjun; Wu Jiyong; Pan Huizhong; Wang Huoqiang; Shen Yi; Shi Degang

    2001-01-01

    Objective: To study the uptake of the 18 F-FDG in the benign pulmonary diseases with dual head SPECT coincidence detection system. Methods: Scanning were performed with dual head SPECT coincidence detection system for patients with pulmonary diseases,the uptake and the imaging characteristic of the diseases were analysed. Results: 1) In 28 tuberculosis (TB) patients, 19 cases with a negative imaging (68%, 19/28), whereas 9 cases with a positive result (32%, 9/28). The T/N value of the TB is 1.7 +- 1.2, but the T/N of the lung cancer is 4.1 +- 2.4, significantly different from them. In the skin PPD test, 9 cases with positive scans showed a 16.2 (12 - 22) mm diameter red spot, but 7 cases of negative scans with a 8.6 (0 - 15) mm diameter, both also have a significant difference. 2) Out of the 8 patients suffered from sarcoidosis, among them 5 active stage with positive scans, whereas another 3 remission cases with negative results. 3) In 18 inflammation cases, positive imagings were showed in 6 patients with cryptococcosis, mycoplasma pneumonia, mycosis, organized pneumonia, lung abscess and bacteria pneumonia. Conclusions: In some benign pulmonary diseases, 18 F-FDG imaging can be positive also. Analysing the characteristic of the imaging could rise specificity in lung cancer and also give some new clues to treatment of these benign pulmonary diseases

  10. THE CLINICAL MANIFESTATIONS AND COURSE OF DUODENAL ULCER DISEASE AFTER PERFORATED ULCER

    Directory of Open Access Journals (Sweden)

    L. A. Lyubskaya

    2014-01-01

    Full Text Available Objective: to compare clinical manifestations, course, mental status in duodenal ulcer (DU patients with a history of perforated ulcer and its uncomplicated course.Subjects and methods. One hundred and thirteen patents with DU were examined. Group 1 included 61 patients with uncomplicated DUand Group 2 comprised 52 patients with a history of perforated ulcer. A comparison group consisted of 20 patients who had undergone laparotomy. Physical and mental status examinations, esophagogastroduodenoscopy (EGDS, and 24-hour pH-metry were performed.Results. Classical pain syndrome was observed in 75 % of the patients with uncomplicated DU. Prior to perforation, the pain and dyspeptic syndromes were distinguished only by a significantly lower degree in Group 2; following perforation, the pain syndrome was recorded more frequently, it was more extensive, meal-unrelated, and similar to that in the patients who had undergone laparotomy and had diminished appetite (36.5 %. EGDS showed that the complicated course was accompanied by the significantly higher incidence of erosive esophagitis (21.2 %, gastritis (51.9 %, duodenitis (25.0 %, multiple ulcers (28.8 %, and larger ulcers. 24-hour pH-metry indicated that the level of hyperacidity in Group 2 was higher and the circadian intragastric pH variations were less marked than those in uncomplicated DU. The patients with a history of perforated ulcer showed a high rate of anxiety and depressive changes. Conclusion. In complicated DU, marked monotonic hyperacidity causes common erosive-ulcerative lesions in the gastroduodenal area in relatively mild pain syndrome, late referrals, and long-term ulcer healing. After perforation followed by wound closure, the pain and dyspeptic syndromes become more pronounced, which is associated with anxiety and depressive changes in the mental status, as well as with early referrals and less healing time.

  11. [Premature immunosenescence in triple-transgenic mice for Alzheimer's disease].

    Science.gov (United States)

    Mate, Ianire; Cruces, Julia; Vida, Carmen; Sanfeliu, Coral; Manassra, Rashed; Giménez-Llort, Lydia; De la Fuente, Mónica

    2014-01-01

    A deterioration of the neuroimmunoendocrine network has been observed in Alzheimer's disease (AD). However, the peripheral immune response has hardly been investigated in this pathology. Since some immune function parameters have been established as good markers of the rate of ageing, and can predict longevity, the aim of the present work was to study some of these functions in splenic leucocytes in transgenic mice for AD of different ages. Young female (4 ± 1 months), adult (9 ± 1 months), and mature (12 ± 1 months) triple-transgenic mice for AD (3 xTgAD) and non-transgenic (NTg) control mice of the same ages were used. The chemotaxis, the anti-tumour activity of « natural killer » (NK) cells and the lymphoproliferative response in the presence of the mitogens concanavalin A and lipopolysaccharide, functions that decrease with age, were determined in splenic leucocytes. In addition, the differences in lifespan between 3 xTgAD and NTg were studied in parallel using other animals, until their death through natural causes. In 3 xTgAD, with respect to NTg, chemotaxis decreased at all ages studied, whereas in lymphoproliferative response this reduction was shown at 4 months and 9 months. NK activity was diminished only in young 3 xTgAD with respect to NTg. The 3 xTgAD showed a shorter lifespan than the NTg control group. The 3 xTgAD mice show a premature immunosenescence, which could explain their early mortality. The determination of these immune functions at peripheral level could serve as a marker of the progression of the Alzheimer's disease. Copyright © 2013 SEGG. Published by Elsevier Espana. All rights reserved.

  12. Somatostatin receptor 1 and 5 double knockout mice mimic neurochemical changes of Huntington's disease transgenic mice.

    Directory of Open Access Journals (Sweden)

    Padmesh S Rajput

    Full Text Available Selective degeneration of medium spiny neurons and preservation of medium sized aspiny interneurons in striatum has been implicated in excitotoxicity and pathophysiology of Huntington's disease (HD. However, the molecular mechanism for the selective sparing of medium sized aspiny neurons and vulnerability of projection neurons is still elusive. The pathological characteristic of HD is an extensive reduction of the striatal mass, affecting caudate putamen. Somatostatin (SST positive neurons are selectively spared in HD and Quinolinic acid/N-methyl-D-aspartic acid induced excitotoxicity, mimic the model of HD. SST plays neuroprotective role in excitotoxicity and the biological effects of SST are mediated by five somatostatin receptor subtypes (SSTR1-5.To delineate subtype selective biological responses we have here investigated changes in SSTR1 and 5 double knockout mice brain and compared with HD transgenic mouse model (R6/2. Our study revealed significant loss of dopamine and cAMP regulated phosphoprotein of 32 kDa (DARPP-32 and comparable changes in SST, N-methyl-D-aspartic acid receptors subtypes, calbindin and brain nitric oxide synthase expression as well as in key signaling proteins including calpain, phospho-extracellular-signal-regulated kinases1/2, synapsin-IIa, protein kinase C-α and calcineurin in SSTR1/5(-/- and R6/2 mice. Conversely, the expression of somatostatin receptor subtypes, enkephalin and phosphatidylinositol 3-kinases were strain specific. SSTR1/5 appears to be important in regulating NMDARs, DARPP-32 and signaling molecules in similar fashion as seen in HD transgenic mice.This is the first comprehensive description of disease related changes upon ablation of G- protein coupled receptor gene. Our results indicate that SST and SSTRs might play an important role in regulation of neurodegeneration and targeting this pathway can provide a novel insight in understanding the pathophysiology of Huntington's disease.

  13. Periodontal manifestations of inflammatory bowel disease: emerging epidemiologic and biologic evidence.

    Science.gov (United States)

    Agossa, K; Dendooven, A; Dubuquoy, L; Gower-Rousseau, C; Delcourt-Debruyne, E; Capron, M

    2017-06-01

    Inflammatory bowel disease and periodontitis are both described as a disproportionate mucosal inflammatory response to a microbial environment in susceptible patients. Moreover, these two conditions share major environmental and lifestyle-related risk factors. Despite this intriguing pathogenic parallel, large-scale studies and basic research have only recently considered periodontal outcomes as relevant data. There are mounting and consistent arguments, from recent epidemiologic studies and animal models, that these two conditions might be related. This article is a comprehensive and critical up-to-date review of the current evidence and future prospects in understanding the biologic and epidemiologic relationships between periodontal status and inflammatory bowel disease. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. An unusual case of Extranodal Rosai-Dorfman Disease manifesting as a bilateral Epibulbar mass.

    OpenAIRE

    Dr. Swati Ravani; Dr. Jaideep Sharma

    2017-01-01

    Purpose: To report an unusual presentation of a 24-year-old man with bilateral epibulbar mass, whose presentation was confirmed histopathologically as Rosai Dorfman disease. Method: We studied a retrospective and interventional case report. Results: A 24-year-old man presented with a mass over both eyes, gradually and, progressively increasing over one year. Visual acuity and intraocular pressures were normal in both eyes. Examination revealed bilateral non tender mobile soft in consistency ...

  15. The central nervous system manifestation and CT findings of Fabry's disease

    International Nuclear Information System (INIS)

    Toyonaga, Kazutaka; Nishihira, Takeo

    1983-01-01

    A case of Fabry's disease with central nervous system dysfunction is reported. This 27-year-old man had recurrent episodes of pains in the extremities when he was a child. Spontaneous clinical remission occured around puberty. He had been well until age 22 when he experienced transient weakness of the left arm. The following year he developed transient blindness of the right eye. Then, he developed weakness in the extremities, dysphagia, dysarthria, and was brought to the hospital in unconscious state. Several members of his family are affected with the same disease presenting leg pains, kidney disease and angiokeratoma. Physical examination disclosed an optic atrophy, pseudobulbar palsy with spastic weakness in the all extremities and multiple angiokeratoma in the flank, buttocks and thighs. Abnormal laboratory findings included leukocytosis, increased ESR and strongly positive CRP. Biopsy of the skin disclosed dilated capilaries with numerous vacuoles in the cytoplasm of the epithelial cells. Thin-layer chromatography of the urine sediment showed a marked increase in ceramide trihexoside. Leukocyte alphagalactosidase level was abnormally low. CT scan showed diffuse cerebral atrophy and multiple low density areas in the thalamus, ventral pons and centrum semiovale. The CT findings and possible mechanism of the response to predonisolone were also discussed. (author)

  16. Thoracic Paravertebral Mass as an Infrequent Manifestation of IgG4-Related Disease

    Directory of Open Access Journals (Sweden)

    Melissa Matzumura Kuan

    2017-01-01

    Full Text Available Case. A 50-year-old African American male presented with abdominal pain and significant weight loss. On physical examination, he had parotid and submandibular gland enlargement associated with right eye proptosis. Computed tomography showed a thoracic paravertebral soft tissue mass, enlarged lymph nodes, and ascending aortic aneurysm. Laboratory results were remarkable for elevated total IgG and IgG4 subclass. The submandibular gland pathology revealed chronic sclerosing sialadenitis, with a large subset of inflammatory cells positively staining for IgG4. The histology of the paravertebral mass demonstrated fibrosclerosis with increased lymphocytic infiltrate, associated with increased IgG4 plasma cells. He was diagnosed with immunoglobulin G4-related disease (IgG4-RD. Steroid therapy initially yielded improvement; however, after steroids were stopped, there was disease recurrence. Prednisone was restarted, and the plan was to start him on rituximab. Interestingly, the patient’s brother also had IgG4-RD. Conclusion. IgG4-RD can present as a paravertebral mass which is usually responsive to steroids; however, recurrent and resistant disease can be seen for which steroid-sparing agents such as rituximab should be considered. In addition, to the best of our knowledge, this is the first reported case of IgG4-RD in two family members presenting as a paravertebral mass, highlighting an exciting area for more research in the future.

  17. [Clinical and radiological features of pulmonary tuberculosis manifested as interstitial lung diseases.].

    Science.gov (United States)

    Shi, Ju-Hong; Feng, Rui-E; Tian, Xin-Lun; Xu, Wen-Bing; Xu, Zuo-Jun; Liu, Hong-Rui; Zhu, Yuan-Jue

    2009-12-01

    The purpose of this paper was to investigate the clinical and radiological features of pulmonary tuberculosis presenting as interstitial lung diseases (ILD). We analyzed the data of cases suspected of diffuse parenchyma lung diseases at this hospital between October 2003 and October 2007. The diagnosis of active pulmonary tuberculosis was based on epithelioid granuloma or positive acid-fast bacilli in lung biopsy and changes on serial radiographs obtained during treatment. The data of a series of 230 consecutive patients with suspected ILD were retrospectively analyzed. The diagnosis was confirmed by lung biopsy. Twelve patients were confirmed to have pulmonary tuberculosis. There were 5 males and 7 females with a mean age of 38 +/- 11 years (range, 17 - 68). The median course of disease in these patients was 3 months (range, 0.5 - 18 months). Patients with pulmonary tuberculosis presented with fever (11/12), cough (9/12), weight loss (7/12), dyspnea (7/12), lymphadenopathy (4/12), and splenohepatomegaly (2/12). On chest CT scan, ground-glass attenuation was identified in 4, bilateral patchy infiltration in 5, tree-in-bud appearance 1, and centrilobular lesions in 2 of the 12 patients. During the follow-up period (median, 9 month, range from 3 to 12 month), 11 patients improved, but 1 died of diabetic ketoacidosis. The diagnosis of pulmonary tuberculosis should be considered in suspected ILD patients presenting with fever, splenohepatomegaly and lymphadenopathy.

  18. Tetranectin Knockout Mice Develop Features of Parkinson Disease

    Directory of Open Access Journals (Sweden)

    Er-song Wang

    2014-07-01

    Full Text Available Background/Aims: Aggregation of insoluble α-synuclein to form Lewy bodies (LBs may contribute to the selective loss of midbrain dopaminergic neurons in Parkinson disease (PD. Lack of robust animal models has impeded elucidation of the molecular mechanisms of LB formation and other critical aspects of PD pathogenesis. Methods: We established a mouse model with targeted deletion of the plasminogen-binding protein tetranectin (TN gene (TN-/- and measured the behavioral and histopathological features of PD. Results: Aged (15-to 20-month-old TN-/- mice displayed motor deficits resembling PD symptoms, including limb rigidity and both slower ambulation (bradykinesia and reduced rearing activity in the open field. In addition, these mice exhibited more numerous α-synuclein-positive LB-like inclusions within the substantia nigra pars compacta (SNc and reduced numbers of SNc dopaminergic neurons than age-matched wild type (WT mice. These pathological changes were also accompanied by loss of dopamine terminals in the dorsal striatum. Conclusion: The TN-/- mouse exhibits several key features of PD and so may be a valuable model for studying LB formation and testing candidate neuroprotective therapies for PD and other synucleinopathies.

  19. Plasma calprotectin and its association with cardiovascular disease manifestations, obesity and the metabolic syndrome in type 2 diabetes mellitus patients

    DEFF Research Database (Denmark)

    Pedersen, Lise; Nybo, M.; Poulsen, M. K.

    2014-01-01

    Background: Plasma calprotectin is a potential biomarker of cardiovascular disease (CVD), insulin resistance (IR), and obesity. We examined the relationship between plasma calprotectin concentrations, CVD manifestations and the metabolic syndrome (MetS) in patients with type 2 diabetes mellitus (T2......DM) in order to evaluate plasma calprotectin as a risk assessor of CVD in diabetic patients without known CVD. Methods: An automated immunoassay for determination of plasma calprotectin was developed based on a fecal Calprotectin ELIA, and a reference range was established from 120 healthy adults...... associated with obesity, MetS status, autonomic neuropathy, PAD, and MI. However, plasma calprotectin was not an independent predictor of CVD, MI, autonomic neuropathy or PAD....

  20. Ocular Manifestations of Ebola Virus Disease: An Ophthalmologist's Guide to Prevent Infection and Panic

    Science.gov (United States)

    Vingolo, Enzo Maria; Messano, Giuseppe Alessio; Fragiotta, Serena; Petti, Stefano

    2015-01-01

    Ebola virus disease (EVD—formerly known as Ebola hemorrhagic fever) is a severe hemorrhagic fever caused by lipid-enveloped, nonsegmented, negative-stranded RNA viruses belonging to the genus Ebolavirus. Case fatality rates may reach up to 76% of infected individuals, making this infection a deadly health problem in the sub-Saharan population. At the moment, there are still no indications on ophthalmological clinical signs and security suggestions for healthcare professionals (doctors and nurses or cooperative persons). This paper provides a short but complete guide to reduce infection risks. PMID:26557674

  1. Changes in cognitive control in pre-manifest Huntington's disease examined using pre-saccadic EEG potentials - a longitudinal study.

    Science.gov (United States)

    Ness, Vanessa; Bestgen, Anne-Kathrin; Saft, Carsten; Beste, Christian

    2014-01-01

    It is well-known that Huntington's disease (HD) affects saccadic processing. However, saccadic dysfunctions in HD may be seen as a result of dysfunctional processes occurring at the oculomotor level prior to the execution of saccades, i.e., at a pre-saccadic level. Virtually nothing is known about possible changes in pre-saccadic processes in HD. This study examines pre-saccadic processing in pre-manifest HD gene mutation carriers (pre-HDs) by using clinically available EEG measures. Error rates, pre-saccadic EEG potentials and saccade onset EEG potentials were measured in 14 pre-HDs and case-matched controls performing prosaccades and antisaccades in a longitudinal study over a 15-month period. The results show that pre-saccadic potentials were changed in pre-HDs, relative to controls and also revealed changes across the 15-month longitudinal period. In particular, pre-saccadic ERP in pre-HDs were characterized by lower amplitudes and longer latencies, which revealed longitudinal changes. These changes were observed for anti-saccades, but not for pro-saccades. Overt saccadic trajectories (potentials) were not different to those in controls, showing that pre-saccadic processes are sensitive to subtle changes in fronto-striatal networks in pre-HDs. Deficits in pre-saccadic processes prior the execution of an erroneous anti-saccade can be seen as an effect of dysfunctional cognitive control in HD. This may underlie saccadic abnormalities and hence a major phenotype of HD. Pre-saccadic EEG potentials preceding erroneous anti-saccades are sensitive to pre-manifest disease progression in HD.

  2. Autopsy-confirmed hippocampal-sparing Alzheimer's disease with delusional jealousy as initial manifestation.

    Science.gov (United States)

    Fujishiro, Hiroshige; Iritani, Shuji; Hattori, Miho; Sekiguchi, Hirotaka; Matsunaga, Shinji; Habuchi, Chikako; Torii, Youta; Umeda, Kentaro; Ozaki, Norio; Yoshida, Mari; Fujita, Kiyoshi

    2015-09-01

    Alzheimer's disease (AD) is clinically characterized by gradual onset over years with worsening of cognition. The initial and most prominent cognitive deficit is commonly memory dysfunction. However, a subset of AD cases has less hippocampal atrophy than would be expected relative to the predominance of cortical atrophy. These hippocampal-sparing cases have distinctive clinical features, including the presence of focal cortical clinical syndromes. Given that previous studies have indicated that severe hippocampal atrophy corresponds to prominent loss of episodic memory, it is likely that memory impairment is initially absent in hippocampal-sparing AD cases. Here, we report on a patient with an 8-year history of delusional jealousy with insidious onset who was clinically diagnosed as possible AD and pathologically confirmed to have AD with relatively preserved neurons in the hippocampus. This patient had delusional jealousy with a long pre-dementia stage, which initially was characterized by lack of memory impairment. Head magnetic resonance imaging findings showed preserved hippocampal volume with bilateral enlarged ventricles and mild-to-moderate cortical atrophy. Head single-photon emission computed tomography revealed severely decreased regional cerebral blood flow in the right temporal lobe. The resolution of the delusion was attributed to pharmacotherapy by an acetylcholinesterase inhibitor, suggesting that the occurrence of delusional jealousy was due to the disease process of AD. Although the neural basis of delusional jealousy remains unclear, this hippocampal-sparing AD case may be classified as an atypical presentation of AD. © 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.

  3. Nailfold capillaroscopic changes in patients with systemic lupus erythematosus: correlations with disease activity, skin manifestation and nephritis.

    Science.gov (United States)

    Shenavandeh, S; Habibi, S

    2017-08-01

    Introduction The clinical expression of systemic lupus erythematosus (SLE) is the consequence of endothelial cell damage leading to serious multiple organ dysfunction. The aim of this study was to assess the association between nailfold capillaroscopic changes and disease activity, skin and renal involvement in patients with SLE. Methods Demographic variables, clinical manifestations and laboratory data of 108 patients with SLE were investigated. Nailfold capillaroscopy (NFC) was performed in all patients. Result Morphological changes in NFC were observed in 102 out of 108 (94.4%) SLE patients. Minor changes were found in 33 (30.6%) and major changes in 69 (63.9%) cases. The disease activity was significantly higher in the patients with major changes ( p  0.05), except for the elongated capillary loops, which were seen more often in patients with renal involvement than in patients without it ( p < 0.03). Conclusion The results of the study showed that capillary changes (abnormal capillaroscopy) were very common in patients with SLE, although there were no specific patterns like the ones in scleroderma patients, and some changes may be associated with disease activity, especially in patients with active skin involvement.

  4. Intracranial menigioma manifested after delivery in a patient with Hodgkin's disease

    Directory of Open Access Journals (Sweden)

    Nagulić Mirjana

    2006-01-01

    Full Text Available Background. Intracranial meningioma is rarely reported in the patients treated for Hodgkin’s disease (HD, known to mainly occur in the area of radiation therapy. Case report. A 26-year-old woman with HD, and intracranial meningioma following the delivery, was presented. As we knew, a similar case had not been reported in the literature before. Three years prior the surgery for intracranial tumor, the patient had been started to be treated for HD of neoplasm stage I (NS I type, by the use of the standard (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone BEA-COPP protocol. The remission of HD, achieved after 7 cycles, persisted over a 27-month-period up to the delivery. Within this period, the patient was without neurologic disorder, but with the obvious psychotic behavior, for which the patient was treated with haloperidol. Two days following the normal delivery, during the acute disorder of the consciousness, intracranial tumor was found. A complete bilateral meningioma (11.7 × 8.3 × 8.1 cm of the frontal parietal zone was removed. Conclusion. there were no reliable signs of the use of an intensive hemotherapy in the reported case (alkylating cytostatics and topoisomerases inhibitors which might have caused the proliferation of a benign solid tumor. The pregnancy was supposed to be the possible second risk factor for causing the growth of a meningioma. On the basis of the significant psychic disorders before the pregnancy, as well as upon the size of the operated on tumor, we concluded that the occurrence of intracranial meningioma could be regarded the parallel neoplastic disease or the second primary tumor.

  5. Maternal Antibody-Mediated Disease Enhancement in Type I Interferon-Deficient Mice Leads to Lethal Disease Associated with Liver Damage.

    Directory of Open Access Journals (Sweden)

    Julia María Martínez Gómez

    2016-03-01

    Full Text Available Epidemiological studies have reported that most of the severe dengue cases occur upon a secondary heterologous infection. Furthermore, babies born to dengue immune mothers are at greater risk of developing severe disease upon primary infection with a heterologous or homologous dengue virus (DENV serotype when maternal antibodies reach sub-neutralizing concentrations. These observations have been explained by the antibody mediated disease enhancement (ADE phenomenon whereby heterologous antibodies or sub-neutralizing homologous antibodies bind to but fail to neutralize DENV particles, allowing Fc-receptor mediated entry of the virus-antibody complexes into host cells. This eventually results in enhanced viral replication and heightened inflammatory responses. In an attempt to replicate this ADE phenomenon in a mouse model, we previously reported that upon DENV2 infection 5-week old type I and II interferon (IFN receptors-deficient mice (AG129 born to DENV1-immune mothers displayed enhancement of disease severity characterized by increased virus titers and extensive vascular leakage which eventually led to the animals' death. However, as dengue occurs in immune competent individuals, we sought to reproduce this mouse model in a less immunocompromised background. Here, we report an ADE model that is mediated by maternal antibodies in type I IFN receptor-deficient A129 mice. We show that 5-week old A129 mice born to DENV1-immune mothers succumbed to a DENV2 infection within 4 days that was sub-lethal in mice born to naïve mothers. Clinical manifestations included extensive hepatocyte vacuolation, moderate vascular leakage, lymphopenia, and thrombocytopenia. Anti-TNFα therapy totally protected the mice and correlated with healthy hepatocytes. In contrast, blocking IL-6 did not impact the virus titers or disease outcome. This A129 mouse model of ADE may help dissecting the mechanisms involved in dengue pathogenesis and evaluate the efficacy of

  6. Reduction of globotriaosylceramide in Fabry disease mice by substrate deprivation.

    Science.gov (United States)

    Abe, A; Gregory, S; Lee, L; Killen, P D; Brady, R O; Kulkarni, A; Shayman, J A

    2000-06-01

    We used a potent inhibitor of glucosylceramide synthase to test whether substrate deprivation could lower globotriaosylceramide levels in alpha-galactosidase A (alpha-gal A) knockout mice, a model of Fabry disease. C57BL/6 mice treated twice daily for 3 days with D-threo-1-ethylendioxyphenyl-2-palmitoylamino-3-pyrrolidi no-propanol (D-t-EtDO-P4) showed a concentration-dependent decrement in glucosylceramide levels in kidney, liver, and spleen. A single intraperitoneal injection of D-t-EtDO-P4 resulted in a 55% reduction in renal glucosylceramide, consistent with rapid renal glucosylceramide metabolism. A concentration-dependent decrement in renal and hepatic globotriaosylceramide levels was observed in alpha-Gal A(-) males treated for 4 weeks with D-t-EtDO-P4. When 8-week-old alpha-Gal A(-) males were treated for 8 weeks with 10 mg/kg twice daily, renal globotriaosylceramide fell to below starting levels, consistent with an alpha-galactosidase A-independent salvage pathway for globotriaosylceramide degradation. Complications observed with another glucosylceramide synthase inhibitor, N-butyldeoxynojirimycin, including weight loss and acellularity of lymphatic organs, were not observed with D-t-EtDO-P4. These data suggest that Fabry disease may be amenable to substrate deprivation therapy.

  7. Increased intracellular Th1 cytokines in scid mice with inflammatory bowel disease

    DEFF Research Database (Denmark)

    Bregenholt, S; Claesson, Mogens Helweg

    1998-01-01

    Severe combined immunodeficient (scid) mice engrafted with small pieces of full thickness gut wall from immunocompetent syngenic donors develop a chronic and lethal colitis. Lymphocytes from the lamina propria of engrafted mice were analyzed for phorbol ester/ionomycin-induced cytokine production...... by intracellular staining. A 4-5-fold increase in the fraction of IFN-gamma-producing CD4+ lamina propria T cells was found in moderately and severely diseased mice when compared to healthy congenic C.B-17 control mice. The number of IL-2-producing T cells was increased by approximately 2-fold when comparing mice...... suffering from severe disease to healthy control mice. The fraction of TNF-alpha positive CD4+ T cells was increased by a factor of two in both moderately and severely diseased mice. When analyzing Th2 cytokines, it was found that the levels of IL-4-producing CD4+ T cells was not altered in diseased animals...

  8. [Diastolic dysfunction in the elderly subjects. Disease or a physiological manifestation of ageing?].

    Science.gov (United States)

    Meluzín, J; Podroužková, H; Gregorová, Z; Panovský, R

    2013-05-01

    The purpose of this summary paper is to discuss the current knowledge of the impact of age on diastolic function of the left ventricle. Data from the literature: Reports published till this time have convincingly demonstrated a significant relationship of age to diastolic function of the left ventricle. Ageing is a physiological process accompanied by structural changes in both myocardium and arterial bed resulting in worsening of parameters characterizing the left ventricular diastolic function. This "physiological" diastolic dysfunction in the elderly subjects can be explained by the deterioration of passive left ventricular filling properties and by worsening of left ventricular relaxation. The detailed analysis of published reports shows problems in distiguishing this "physiological" diastolic dysfunction resulting from physiological tissue ageing from "pathological" diastolic dysfunction reflecting a disease of cardiovascular system. To interprete correctly values of parameters quantifying diastolic function of the left ventricle, one should take into account the age of subjects under the examination. Further studies are necessary to distinguish exactly "physiological" deterioration of diastolic function associated with ageing from really "pathological" diastolic dysfunction in the elderly subjects.

  9. Hypofibrinolytic State in Subjects with Type 2 Diabetes Mellitus Aggravated by the Metabolic Syndrome before Clinical Manifestations of Atherothrombotic Disease

    Directory of Open Access Journals (Sweden)

    Elsa Aburto-Mejía

    2017-01-01

    Full Text Available Background. Metabolic and genetic factors induce plasminogen activator inhibitor type-1 (PAI-1 overexpression; higher PAI-1 levels decrease fibrinolysis and promote atherothrombosis. Aim. To assess PAI-1 antigen levels among subjects with type 2 diabetes mellitus (T2DM plus Metabolic Syndrome (MetS before clinical manifestations of atherothrombosis and the contribution of metabolic factors and 4G/5G polymorphism of PAI-1 gene on the variability of PAI-1. Methods. We conducted an observational, cross-sectional assay in a hospital in Mexico City from May 2010 to September 2011. MetS was defined by the International Diabetes Federation criteria. PAI-1 levels and 4G/5G polymorphism were determined by ELISA and PCR-RFLP analysis. Results. We enrolled 215 subjects with T2DM plus MetS and 307 controls. Subjects with T2DM plus MetS had higher PAI-1 levels than the reference group (58.4 ± 21 versus 49.9 ± 16 ng/mL, p=0.026. A model with components of MetS explained only 12% of variability on PAI-1 levels (R2 = 0.12; p=0.001, with β=0.18 (p=0.03 for hypertension, β=-0.16 (p=0.05 for NL HDL-c, and β=0.15 (p=0.05 for NL triglycerides. Conclusion. Subjects with T2DM plus MetS have elevated PAI-1 levels before clinical manifestations of atherothrombotic disease. Metabolic factors have a more important contribution than 4G/5G polymorphism on PAI-1 plasma variability.

  10. Hypofibrinolytic State in Subjects with Type 2 Diabetes Mellitus Aggravated by the Metabolic Syndrome before Clinical Manifestations of Atherothrombotic Disease.

    Science.gov (United States)

    Aburto-Mejía, Elsa; Santiago-Germán, David; Martínez-Marino, Manuel; María Eugenia Galván-Plata; Almeida-Gutiérrez, Eduardo; López-Alarcón, Mardia; Hernández-Juárez, Jesús; Alvarado-Moreno, Antonio; Leaños-Miranda, Alfredo; Majluf-Cruz, Abraham; Isordia-Salas, Irma

    2017-01-01

    Background . Metabolic and genetic factors induce plasminogen activator inhibitor type-1 (PAI-1) overexpression; higher PAI-1 levels decrease fibrinolysis and promote atherothrombosis. Aim . To assess PAI-1 antigen levels among subjects with type 2 diabetes mellitus (T2DM) plus Metabolic Syndrome (MetS) before clinical manifestations of atherothrombosis and the contribution of metabolic factors and 4G/5G polymorphism of PAI-1 gene on the variability of PAI-1. Methods . We conducted an observational, cross-sectional assay in a hospital in Mexico City from May 2010 to September 2011. MetS was defined by the International Diabetes Federation criteria. PAI-1 levels and 4G/5G polymorphism were determined by ELISA and PCR-RFLP analysis. Results . We enrolled 215 subjects with T2DM plus MetS and 307 controls. Subjects with T2DM plus MetS had higher PAI-1 levels than the reference group (58.4 ± 21 versus 49.9 ± 16 ng/mL, p = 0.026). A model with components of MetS explained only 12% of variability on PAI-1 levels ( R 2 = 0.12; p = 0.001), with β = 0.18 ( p = 0.03) for hypertension, β = -0.16 ( p = 0.05) for NL HDL-c, and β = 0.15 ( p = 0.05) for NL triglycerides. Conclusion . Subjects with T2DM plus MetS have elevated PAI-1 levels before clinical manifestations of atherothrombotic disease. Metabolic factors have a more important contribution than 4G/5G polymorphism on PAI-1 plasma variability.

  11. Hypofibrinolytic State in Subjects with Type 2 Diabetes Mellitus Aggravated by the Metabolic Syndrome before Clinical Manifestations of Atherothrombotic Disease

    Science.gov (United States)

    Aburto-Mejía, Elsa; Santiago-Germán, David; Martínez-Marino, Manuel; María Eugenia Galván-Plata; Almeida-Gutiérrez, Eduardo; Hernández-Juárez, Jesús; Alvarado-Moreno, Antonio; Leaños-Miranda, Alfredo

    2017-01-01

    Background. Metabolic and genetic factors induce plasminogen activator inhibitor type-1 (PAI-1) overexpression; higher PAI-1 levels decrease fibrinolysis and promote atherothrombosis. Aim. To assess PAI-1 antigen levels among subjects with type 2 diabetes mellitus (T2DM) plus Metabolic Syndrome (MetS) before clinical manifestations of atherothrombosis and the contribution of metabolic factors and 4G/5G polymorphism of PAI-1 gene on the variability of PAI-1. Methods. We conducted an observational, cross-sectional assay in a hospital in Mexico City from May 2010 to September 2011. MetS was defined by the International Diabetes Federation criteria. PAI-1 levels and 4G/5G polymorphism were determined by ELISA and PCR-RFLP analysis. Results. We enrolled 215 subjects with T2DM plus MetS and 307 controls. Subjects with T2DM plus MetS had higher PAI-1 levels than the reference group (58.4 ± 21 versus 49.9 ± 16 ng/mL, p = 0.026). A model with components of MetS explained only 12% of variability on PAI-1 levels (R2 = 0.12; p = 0.001), with β = 0.18 (p = 0.03) for hypertension, β = −0.16 (p = 0.05) for NL HDL-c, and β = 0.15 (p = 0.05) for NL triglycerides. Conclusion. Subjects with T2DM plus MetS have elevated PAI-1 levels before clinical manifestations of atherothrombotic disease. Metabolic factors have a more important contribution than 4G/5G polymorphism on PAI-1 plasma variability. PMID:28271069

  12. Encephalopathy associated with autoimmune thyroid disease in patients with Graves' disease: clinical manifestations, follow-up, and outcomes

    LENUS (Irish Health Repository)

    Tamagno, Gianluca

    2010-04-28

    Abstract Background The encephalopathy associated with autoimmune thyroid disease (EAATD) is characterized by neurological\\/psychiatric symptoms, high levels of anti-thyroid antibodies, increased cerebrospinal fluid protein concentration, non-specific electroencephalogram abnormalities, and responsiveness to the corticosteroid treatment in patients with an autoimmune thyroid disease. Almost all EAATD patients are affected by Hashimoto\\'s thyroiditis (HT), although fourteen EAATD patients with Graves\\' disease (GD) have been also reported. Methods We have recorded and analyzed the clinical, biological, radiological, and electrophysiological findings and the data on the therapeutic management of all GD patients with EAATD reported so far as well as the clinical outcomes in those followed-up in the long term. Results Twelve of the fourteen patients with EAATD and GD were women. The majority of GD patients with EAATD presented with mild hyperthyroidism at EAATD onset or shortly before it. Active anti-thyroid autoimmunity was detected in all cases. Most of the patients dramatically responded to corticosteroids. The long term clinical outcome was benign but EAATD can relapse, especially at the time of corticosteroid dose tapering or withdrawal. GD and HT patients with EAATD present with a similar clinical, biological, radiological, and electrophysiological picture and require an unaffected EAATD management. Conclusions GD and HT equally represent the possible background condition for the development of EAATD, which should be considered in the differential diagnosis of all patients with encephalopathy of unknown origin and an autoimmune thyroid disease, regardless of the nature of the underlying autoimmune thyroid disease.

  13. Encephalopathy associated with autoimmune thyroid disease in patients with Graves' disease: clinical manifestations, follow-up, and outcomes.

    LENUS (Irish Health Repository)

    Tamagno, Gianluca

    2012-02-01

    BACKGROUND: The encephalopathy associated with autoimmune thyroid disease (EAATD) is characterized by neurological\\/psychiatric symptoms, high levels of anti-thyroid antibodies, increased cerebrospinal fluid protein concentration, non-specific electroencephalogram abnormalities, and responsiveness to the corticosteroid treatment in patients with an autoimmune thyroid disease. Almost all EAATD patients are affected by Hashimoto\\'s thyroiditis (HT), although fourteen EAATD patients with Graves\\' disease (GD) have been also reported. METHODS: We have recorded and analyzed the clinical, biological, radiological, and electrophysiological findings and the data on the therapeutic management of all GD patients with EAATD reported so far as well as the clinical outcomes in those followed-up in the long term. RESULTS: Twelve of the fourteen patients with EAATD and GD were women. The majority of GD patients with EAATD presented with mild hyperthyroidism at EAATD onset or shortly before it. Active anti-thyroid autoimmunity was detected in all cases. Most of the patients dramatically responded to corticosteroids. The long term clinical outcome was benign but EAATD can relapse, especially at the time of corticosteroid dose tapering or withdrawal. GD and HT patients with EAATD present with a similar clinical, biological, radiological, and electrophysiological picture and require an unaffected EAATD management. CONCLUSIONS: GD and HT equally represent the possible background condition for the development of EAATD, which should be considered in the differential diagnosis of all patients with encephalopathy of unknown origin and an autoimmune thyroid disease, regardless of the nature of the underlying autoimmune thyroid disease.

  14. Encephalopathy associated with autoimmune thyroid disease in patients with Graves' disease: clinical manifestations, follow-up, and outcomes

    Directory of Open Access Journals (Sweden)

    Lee Byung I

    2010-04-01

    Full Text Available Abstract Background The encephalopathy associated with autoimmune thyroid disease (EAATD is characterized by neurological/psychiatric symptoms, high levels of anti-thyroid antibodies, increased cerebrospinal fluid protein concentration, non-specific electroencephalogram abnormalities, and responsiveness to the corticosteroid treatment in patients with an autoimmune thyroid disease. Almost all EAATD patients are affected by Hashimoto's thyroiditis (HT, although fourteen EAATD patients with Graves' disease (GD have been also reported. Methods We have recorded and analyzed the clinical, biological, radiological, and electrophysiological findings and the data on the therapeutic management of all GD patients with EAATD reported so far as well as the clinical outcomes in those followed-up in the long term. Results Twelve of the fourteen patients with EAATD and GD were women. The majority of GD patients with EAATD presented with mild hyperthyroidism at EAATD onset or shortly before it. Active anti-thyroid autoimmunity was detected in all cases. Most of the patients dramatically responded to corticosteroids. The long term clinical outcome was benign but EAATD can relapse, especially at the time of corticosteroid dose tapering or withdrawal. GD and HT patients with EAATD present with a similar clinical, biological, radiological, and electrophysiological picture and require an unaffected EAATD management. Conclusions GD and HT equally represent the possible background condition for the development of EAATD, which should be considered in the differential diagnosis of all patients with encephalopathy of unknown origin and an autoimmune thyroid disease, regardless of the nature of the underlying autoimmune thyroid disease.

  15. Encephalopathy associated with autoimmune thyroid disease in patients with Graves' disease: clinical manifestations, follow-up, and outcomes.

    LENUS (Irish Health Repository)

    Tamagno, Gianluca

    2010-01-01

    BACKGROUND: The encephalopathy associated with autoimmune thyroid disease (EAATD) is characterized by neurological\\/psychiatric symptoms, high levels of anti-thyroid antibodies, increased cerebrospinal fluid protein concentration, non-specific electroencephalogram abnormalities, and responsiveness to the corticosteroid treatment in patients with an autoimmune thyroid disease. Almost all EAATD patients are affected by Hashimoto\\'s thyroiditis (HT), although fourteen EAATD patients with Graves\\' disease (GD) have been also reported. METHODS: We have recorded and analyzed the clinical, biological, radiological, and electrophysiological findings and the data on the therapeutic management of all GD patients with EAATD reported so far as well as the clinical outcomes in those followed-up in the long term. RESULTS: Twelve of the fourteen patients with EAATD and GD were women. The majority of GD patients with EAATD presented with mild hyperthyroidism at EAATD onset or shortly before it. Active anti-thyroid autoimmunity was detected in all cases. Most of the patients dramatically responded to corticosteroids. The long term clinical outcome was benign but EAATD can relapse, especially at the time of corticosteroid dose tapering or withdrawal. GD and HT patients with EAATD present with a similar clinical, biological, radiological, and electrophysiological picture and require an unaffected EAATD management. CONCLUSIONS: GD and HT equally represent the possible background condition for the development of EAATD, which should be considered in the differential diagnosis of all patients with encephalopathy of unknown origin and an autoimmune thyroid disease, regardless of the nature of the underlying autoimmune thyroid disease.

  16. Significant CD4, CD8, and CD19 lymphopenia in peripheral blood of sarcoidosis patients correlates with severe disease manifestations.

    Science.gov (United States)

    Sweiss, Nadera J; Salloum, Rafah; Gandhi, Seema; Ghandi, Seema; Alegre, Maria-Luisa; Sawaqed, Ray; Badaracco, Maria; Pursell, Kenneth; Pitrak, David; Baughman, Robert P; Moller, David R; Garcia, Joe G N; Niewold, Timothy B

    2010-02-05

    Sarcoidosis is a poorly understood chronic inflammatory condition. Infiltration of affected organs by lymphocytes is characteristic of sarcoidosis, however previous reports suggest that circulating lymphocyte counts are low in some patients with the disease. The goal of this study was to evaluate lymphocyte subsets in peripheral blood in a cohort of sarcoidosis patients to determine the prevalence, severity, and clinical features associated with lymphopenia in major lymphocyte subsets. Lymphocyte subsets in 28 sarcoid patients were analyzed using flow cytometry to determine the percentage of CD4, CD8, and CD19 positive cells. Greater than 50% of patients had abnormally low CD4, CD8, or CD19 counts (p<4x10(-10)). Lymphopenia was profound in some cases, and five of the patients had absolute CD4 counts below 200. CD4, CD8, and CD19 lymphocyte subset counts were significantly correlated (Spearman's rho 0.57, p = 0.0017), and 10 patients had low counts in all three subsets. Patients with severe organ system involvement including neurologic, cardiac, ocular, and advanced pulmonary disease had lower lymphocyte subset counts as a group than those patients with less severe manifestations (CD4 p = 0.0043, CD8 p = 0.026, CD19 p = 0.033). No significant relationships were observed between various medical therapies and lymphocyte counts, and lymphopenia was present in patients who were not receiving any medical therapy. Significant lymphopenia involving CD4, CD8, and CD19 positive cells was common in sarcoidosis patients and correlated with disease severity. Our findings suggest that lymphopenia relates more to disease pathology than medical treatment.

  17. Blood to skin recirculation of CD4+ memory T cells associates with cutaneous and systemic manifestations of psoriatic disease.

    Science.gov (United States)

    Diani, Marco; Galasso, Marco; Cozzi, Chiara; Sgambelluri, Francesco; Altomare, Andrea; Cigni, Clara; Frigerio, Elena; Drago, Lorenzo; Volinia, Stefano; Granucci, Francesca; Altomare, Gianfranco; Reali, Eva

    2017-07-01

    Blood to skin recirculation could play a role in the pathogenesis of psoriasis. To investigate this possibility we dissected the phenotype of circulating T cells in psoriasis patients, calculated the correlation the clinical parameters of the disease and performed a parallel bioinformatics analysis of gene expression data in psoriatic skin. We found that circulating CCR6 + CD4 + T EM and T EFF cells significantly correlated with systemic inflammation. Conversely, the percentage of CXCR3 + CD4 + T EM cells negatively correlated with the severity of the cutaneous disease. Importantly CLA + CD4 + T CM cells expressing CCR6 + or CCR4 + CXCR3 + negatively correlated with psoriasis severity suggesting recruitment to the skin compartment. This assumption was reinforced by gene expression data showing marked increase of CCR7 and CLA-encoding gene SELPLG expression in psoriatic skin and strong association of their expression. The data enlightens a role for CD4 + T cells trafficking between blood and skin in cutaneous and systemic manifestations of psoriasis. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Associations of cardiovascular risk factors, carotid intima-media thickness and manifest atherosclerotic vascular disease with carpal tunnel syndrome

    Directory of Open Access Journals (Sweden)

    Liira Helena

    2011-04-01

    Full Text Available Abstract Background The role of atherosclerosis in carpal tunnel syndrome (CTS has not previously been addressed in population studies. The aim of this study was to investigate the associations of cardiovascular risk factors, carotid artery intima-media thickness (IMT, and clinical atherosclerotic diseases with CTS. Methods In this cross sectional study, the target population consisted of subjects aged 30 or over who had participated in the national Finnish Health Survey in 2000-2001. Of the 7977 eligible subjects, 6254 (78.4% were included in our study. Carotid IMT was measured in a sub-sample of subjects aged 45 to 74 (N = 1353. Results Obesity (adjusted odds ratio (OR 2.4, 95% confidence interval (CI 1.1-5.4, high LDL cholesterol (OR 3.8, 95% CI 1.6-9.1 for >190 vs. 200 vs. Conclusions Our findings suggest an association between CTS and cardiovascular risk factors in young people, and carotid IMT and clinical atherosclerotic vascular disease in older people. CTS may either be a manifestation of atherosclerosis, or both conditions may share similar risk factors.

  19. Partial Body Weight-Supported Treadmill Training in Patients With Parkinson Disease: Impact on Gait and Clinical Manifestation.

    Science.gov (United States)

    Ganesan, Mohan; Sathyaprabha, Talakad N; Pal, Pramod Kumar; Gupta, Anupam

    2015-09-01

    To evaluate the effect of conventional gait training (CGT) and partial weight-supported treadmill training (PWSTT) on gait and clinical manifestation. Prospective experimental research design. Hospital. Patients with idiopathic Parkinson disease (PD) (N=60; mean age, 58.15±8.7y) on stable dosage of dopaminomimetic drugs were randomly assigned into the 3 following groups (20 patients in each group): (1) nonexercising PD group, (2) CGT group, and (3) PWSTT group. The interventions included in the study were CGT and PWSTT. The sessions of the CGT and PWSTT groups were given in patient's self-reported best on status after regular medications. The interventions were given for 30min/d, 4d/wk, for 4 weeks (16 sessions). Clinical severity was measured by the Unified Parkinson Disease Rating Scale (UPDRS) and its subscores. Gait was measured by 2 minutes of treadmill walking and the 10-m walk test. Outcome measures were evaluated in their best on status at baseline and after the second and fourth weeks. Four weeks of CGT and PWSTT gait training showed significant improvements of UPDRS scores, its subscores, and gait performance measures. Moreover, the effects of PWSTT were significantly better than CGT on most measures. PWSTT is a promising intervention tool to improve the clinical and gait outcome measures in patients with PD. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  20. Electrocardiographic manifestations of inherited heart diseases – a sports cardiologist’s point ofview. Part 2. Ion channel diseases

    Directory of Open Access Journals (Sweden)

    Zbigniew Krenc

    2015-09-01

    Full Text Available Physical activity is associated with an increased risk of sudden death for individuals with an undiagnosed cardiovascular disease. Medical evaluations, including a resting electrocardiogram, conducted before and during physical training, enable the identification of still asymptomatic athletes with life-threatening heart diseases and help to protect them from sudden cardiac death. The incidence of sudden cardiac death is estimated at two cases for each 100,000 young athletes per year and it is 2–4 times higher when compared with non-athletes. The most common causes of sudden cardiac death in athletes younger than 35 are cardiomyopathies: hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy. Three to four per cent of young athletes who die suddenly have no evidence of a structural heart disease, and the cause of their cardiac arrest is primarily electrical heart diseases, such as inherited cardiac ion channel defects (channelopathies, including long and short QT syndromes, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia The clinical courses of all these channelopathies are highly varied. They can be asymptomatic. In certain cases, episodic syncope or aborted cardiac arrest can occur. Sudden cardiac death, especially during physical exercise, can be the first sign. The aim of this article was to provide some information helpful in the recognition of electrocardiographic changes in genetic ion channel diseases, especially in the context of the prevention of sudden cardiac events in young athletes.

  1. Multiple pathogenic proteins implicated in neuronopathic Gaucher disease mice.

    Science.gov (United States)

    Xu, You-hai; Xu, Kui; Sun, Ying; Liou, Benjamin; Quinn, Brian; Li, Rong-hua; Xue, Ling; Zhang, Wujuan; Setchell, Kenneth D R; Witte, David; Grabowski, Gregory A

    2014-08-01

    Gaucher disease, a prevalent lysosomal storage disease (LSD), is caused by insufficient activity of acid β-glucosidase (GCase) and the resultant glucosylceramide (GC)/glucosylsphingosine (GS) accumulation in visceral organs (Type 1) and the central nervous system (Types 2 and 3). Recent clinical and genetic studies implicate a pathogenic link between Gaucher and neurodegenerative diseases. The aggregation and inclusion bodies of α-synuclein with ubiquitin are present in the brains of Gaucher disease patients and mouse models. Indirect evidence of β-amyloid pathology promoting α-synuclein fibrillation supports these pathogenic proteins as a common feature in neurodegenerative diseases. Here, multiple proteins are implicated in the pathogenesis of chronic neuronopathic Gaucher disease (nGD). Immunohistochemical and biochemical analyses showed significant amounts of β-amyloid and amyloid precursor protein (APP) aggregates in the cortex, hippocampus, stratum and substantia nigra of the nGD mice. APP aggregates were in neuronal cells and colocalized with α-synuclein signals. A majority of APP co-localized with the mitochondrial markers TOM40 and Cox IV; a small portion co-localized with the autophagy proteins, P62/LC3, and the lysosomal marker, LAMP1. In cultured wild-type brain cortical neural cells, the GCase-irreversible inhibitor, conduritol B epoxide (CBE), reproduced the APP/α-synuclein aggregation and the accumulation of GC/GS. Ultrastructural studies showed numerous larger-sized and electron-dense mitochondria in nGD cerebral cortical neural cells. Significant reductions of mitochondrial adenosine triphosphate production and oxygen consumption (28-40%) were detected in nGD brains and in CBE-treated neural cells. These studies implicate defective GCase function and GC/GS accumulation as risk factors for mitochondrial dysfunction and the multi-proteinopathies (α-synuclein-, APP- and Aβ-aggregates) in nGD. © The Author 2014. Published by Oxford University

  2. Pulmonary granulomatous diseases and pulmonary manifestations of systemic granulomatous disease. Including tuberculosis and nontuberculous mycobacteriosis; Pulmonale granulomatoese Erkrankungen und pulmonale Manifestationen systemischer Granulomatosen. Inklusive Tuberkulose und nichttuberkuloese Mykobakteriosen

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    Piel, S. [Universitaet Heidelberg, Zentrum fuer interstitielle und seltene Lungenerkrankungen, Pneumologie und Beatmungsmedizin, Thoraxklinik, Heidelberg (Germany); Kreuter, M.; Herth, F. [Universitaet Heidelberg, Zentrum fuer interstitielle und seltene Lungenerkrankungen, Pneumologie und Beatmungsmedizin, Thoraxklinik, Heidelberg (Germany); Universitaetsklinikum Heidelberg, Translational Lung Research Center (TLRC), Heidelberg (Germany); Kauczor, H.U. [Universitaetsklinikum Heidelberg, Abteilung fuer Diagnostische und Interventionelle Radiologie, Heidelberg (Germany); Universitaetsklinikum Heidelberg, Translational Lung Research Center (TLRC), Heidelberg (Germany); Heussel, C.P. [Universitaet Heidelberg, Abteilung fuer Diagnostische und Interventionelle Radiologie mit Nuklearmedizin, Thoraxklinik, Heidelberg (Germany); Universitaetsklinikum Heidelberg, Translational Lung Research Center (TLRC), Heidelberg (Germany)

    2016-10-15

    Granulomas as signs of specific inflammation of the lungs are found in various diseases with pulmonary manifestations and represent an important imaging finding. The standard imaging modality for the work-up of granulomatous diseases of the lungs is most often thin-slice computed tomography (CT). There are a few instances, e. g. tuberculosis, sarcoidosis and silicosis, where a chest radiograph still plays an important role. Further radiological modalities are usually not needed in the routine work-up of granulomatous diseases of the chest. In special cases magnetic resonance imaging (MRI) and positron emission tomography (PET)-CT scans play an important role, e. g. detecting cardiac sarcoidosis by cardiac MRI or choline C-11 PET-CT in diagnosing lung carcinoma in scar tissue after tuberculosis. The accuracy of thin-slice CT is very high for granulomatous diseases. In cases of chronic disease and fibrotic interstitial lung disease it is important to perform thin-slice CT in order to diagnose a specific disease pattern. Thin-slice CT is also highly sensitive in detecting disease complications and comorbidities, such as malignancies. Given these indications thin-slice CT is generally accepted in the routine daily practice. A thin-slice CT and an interdisciplinary discussion are recommended in many cases with a suspected diagnosis of pulmonary granulomatous disease due to clinical or radiographic findings. (orig.) [German] Granulome als Zeichen der spezifischen Entzuendung im Lungengewebe treten bei zahlreichen Erkrankungen mit pulmonaler Manifestation auf und stellen einen wichtigen Befund in der Bildgebung dar. Das radiologische Standardverfahren bei pulmonalen Granulomatosen ist meistens die Duennschichtcomputertomographie, in wenigen Faellen, wie z. B. bei Tuberkulose, Sarkoidose und Silikose, spielt die Roentgenthoraxuebersicht immer noch eine wichtige Rolle. Bei der Standardabklaerung der meisten Granulomatosen ist die Hinzunahme weiterer Verfahren nicht

  3. Desmin common mutation is associated with multi-systemic disease manifestations and depletion of mitochondria and mitochondrial DNA

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    Elizabeth eMcCormick

    2015-06-01

    Full Text Available Desmin (DES is a major muscle scaffolding protein that also functions to anchor mitochondria. Pathogenic DES mutations, however, have not previously been recognized as a cause of multi-systemic mitochondrial disease. Here, we describe a 45-year-old man who presented to The Children’s Hospital of Philadelphia Mitochondrial-Genetics Diagnostic Clinic for evaluation of progressive cardiac, neuromuscular, gastrointestinal, and mood disorders. Muscle biopsy at age 45 was remarkable for cytoplasmic bodies, as well as ragged red fibers and SDH positive/COX negative fibers that were suggestive of a mitochondrial myopathy. Muscle also showed significant reductions in mitochondrial content (16% of control mean for citrate synthase activity and mitochondrial DNA (35% of control mean. His family history was significant for cardiac conduction defects and myopathy in multiple maternal relatives. Multiple single gene and panel-based sequencing studies were unrevealing. Whole exome sequencing identified a known pathogenic p.S13F mutation in DES that had previously been associated with desmin-related myopathy. Desmin-related myopathy is an autosomal dominant disorder characterized by right ventricular hypertrophic cardiomyopathy, myopathy, and arrhythmias. However, neuropathy, gastrointestinal dysfunction, and depletion of both mitochondria and mitochondrial DNA have not previously been widely recognized in this disorder. Recognition that mitochondrial dysfunction occurs in desmin-related myopathy clarifies the basis for the multi-systemic manifestations, as are typical of primary mitochondrial disorders. Understanding the mitochondrial pathophysiology of desmin-related myopathy highlights the possibility of new therapies for the otherwise untreatable and often fatal class of disease. We postulate that drug treatments aimed at improving mitochondrial biogenesis or reducing oxidative stress may be effective therapies to ameliorate the effects of desmin

  4. Hypercholesterolemia causes psychomotor abnormalities in mice and alterations in cortico-striatal biogenic amine neurotransmitters: Relevance to Parkinson's disease.

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    Paul, Rajib; Choudhury, Amarendranath; Chandra Boruah, Dulal; Devi, Rajlakshmi; Bhattacharya, Pallab; Choudhury, Manabendra Dutta; Borah, Anupom

    2017-09-01

    The symptoms of Parkinson's disease (PD) include motor behavioral abnormalities, which appear as a result of the extensive loss of the striatal biogenic amine, dopamine. Various endogenous molecules, including cholesterol, have been put forward as putative contributors in the pathogenesis of PD. Earlier reports have provided a strong link between the elevated level of plasma cholesterol (hypercholesterolemia) and onset of PD. However, the role of hypercholesterolemia on brain functions in terms of neurotransmitter metabolism and associated behavioral manifestations remain elusive. We tested in Swiss albino mice whether hypercholesterolemia induced by high-cholesterol diet would affect dopamine and serotonin metabolism in discrete brain regions that would precipitate in psychomotor behavioral manifestations. High-cholesterol diet for 12 weeks caused a significant increase in blood total cholesterol level, which validated the model as hypercholesterolemic. Tests for akinesia, catalepsy, swimming ability and gait pattern (increased stride length) have revealed that hypercholesterolemic mice develop motor behavioral abnormalities, which are similar to the behavioral phenotypes of PD. Moreover, hypercholesterolemia caused depressive-like behavior in mice, as indicated by the increased immobility time in the forced swim test. We found a significant depletion of dopamine in striatum and serotonin in cortex of hypercholesterolemic mice. The significant decrease in tyrosine hydroxylase immunoreactivity in striatum supports the observed depleted level dopamine in striatum, which is relevant to the pathophysiology of PD. In conclusion, hypercholesterolemia-induced depleted levels of cortical and striatal biogenic amines reported hereby are similar to the PD pathology, which might be associated with the observed psychomotor behavioral abnormalities. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Coronary heart disease clinical manifestation and risk factors in Japanese immigrants and their descendents in the city of São Paulo

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    Amato Reynaldo Vicente

    2003-01-01

    Full Text Available OBJECTIVE: To assess whether a difference exists in coronary heart disease clinical manifestations and the prevalence of risk factors between Japanese immigrants and their descendents in the city of São Paulo. METHODS: Retrospective analysis of coronary artery disease clinical manifestations and the prevalence of risk factors, comparing 128 Japanese immigrants (Japanese group with 304 Japanese descendents (Nisei group. RESULTS: The initial manifestation of the disease was earlier in the Nisei group (mean = 53 years, a difference of 12 years when compared with that in the Japanese group (mean = 65 years (P<0.001. Myocardial infarction was the first manifestation in both groups (P = 0.83. The following parameters were independently associated with early coronary events: smoking (OR = 2.25; 95% CI = 1.35-3.77; P<0.002; Nisei group (OR = 10.22; 95% CI = 5.64-18.5; P<0.001; and female sex (OR = 5.04; 95% CI = 2.66-9.52; P<0.001. CONCLUSION: The clinical presentation of coronary heart disease in the Japanese and their descendents in the city of São Paulo was similar, but coronary heart disease onset occurred approximately 12 years earlier in the Nisei group than in the Japanese group.

  6. Inter-arm systolic blood pressure differences, relations with future vascular events and mortality in patients with and without manifest vascular disease.

    Science.gov (United States)

    Kranenburg, Guido; Spiering, Wilko; de Jong, Pim A; Kappelle, L Jaap; de Borst, Gert Jan; Cramer, Maarten J; Visseren, Frank L J; Aboyans, Victor; Westerink, Jan

    2017-10-01

    Inter-arm systolic blood pressure difference (SBPD) is an easily obtained patient characteristic which relates to vascular disease. We aimed to identify determinants of large inter-arm SBPD and to investigate the relation between inter-arm SBPD and vascular events in patients with and without manifest vascular disease. In a cohort of 7344 patients with manifest vascular disease or vascular risk factors alone enrolled in the Second Manifestations of ARTerial disease (SMART) study, single bilateral non-simultaneous blood pressure measurements were performed. Logistic and Cox regression was used to identify determinants of large inter-arm SBPD (≥15mmHg) and to investigate the relation between inter-arm SBPD and vascular events (composite of non-fatal myocardial infarction, stroke, and vascular mortality) and all-cause mortality. In all patients the median inter-arm SBPD was 7mmHg (IQR 3-11) and 1182 (16%) patients had inter-arm SBPD ≥15mmHg. Higher age, higher systolic blood pressure, diabetes mellitus, peripheral artery disease, carotid artery stenosis, higher carotid intima-media thickness, and lower ankle-brachial indices were related to large inter-arm SBPD (≥15mmHg). Each 5mmHg increase in inter-arm SBPD was related to a 12% higher risk of vascular events in patients without manifest vascular disease (HR 1.12; 95% CI 1.00-1.27), whereas no relation was apparent in patients with manifest vascular disease (HR 0.98; 95% CI 0.93-1.04, interaction p-value 0.036). Inter-arm SBPD was not related to all-cause mortality (HR 1.05; 95% CI 0.93-1.19). Inter-arm SBPD relates to a higher risk of vascular events in patients without manifest vascular disease, whereas this relation is not apparent in patients with manifest vascular disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. MITRAL ANNULAR CALCIFICATION IN ELDERLY PATIENTS: RELATIONSHIP WITH CLINICAL MANIFESTATIONS AND RISK FACTORS OF CARDIOVASCULAR DISEASES CAUSED BY ATHEROSCLEROSIS

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    G. M. Urvacheva

    2011-01-01

    Full Text Available The aim – to study the association of the mitral annular calcification (MAC with traditional risk factors and clinical manifestations of atherosclerosisin patients aged over 65 years without diabetes.Materials and methods. The prospective study included 100 patients over 65 years with MAC consistently identified among 910 ambulatory patients after transthoracic Doppler echocardiography in relation to the symptoms of cardiovascular disease. The comparison group consisted of 65 consecutively examined patients aged over 65 with no MAC.Results. When comparing risk factors in patients with and without MAC, MAC statistically significant differences was found with age (72,4 ± 5,4 and 70,2 ± 4,3 years, respectively; p = 0,006, the incidence of hypertension of moderate and severe degree (99 % and 90.8 % of patients, p = 0.012, levels of total cholesterol – TC (6,91 ± 0,92 and 6,2 ± 0,90 mmol / l, p = 0.0008 and lipoproteinlow density (3,57 ± 0,95 and 2,96 ± 0,96 mmol / l, p = 0.004 in subgroups of patients aged 65 to 70 years. In multivariate analysis remained statistically significant association of MAC only with age (p = 0,025, β = 0,173 and total cholesterol levels (p = 0,040; β = 0,160. Averages of the coefficient of atherogenicity of blood lipids, systolic and diastolic blood pressure, C-reactive protein, body mass index, waist circumference, the frequency of smoking, and risk assessment on a scale of SCORE in groups of patients with and without MAC did not differ significantly. In patients with MAC was higher incidence of myocardial infarction (p = 0.024 and more often than in patients without MAC, diagnosed coronary heart disease (p = 0.029. In the multivariate analysis adjusted for age and total cholesterol level is set significantly associated with the presence and extent of MAC with symptomatic atherosclerotic peripheral arterial disease (p < 0,00001; β = 0,410.Conclusion. In patients with MAC older than 65 years without diabetes

  8. Emotional face recognition deficits and medication effects in pre-manifest through stage-II Huntington's disease.

    Science.gov (United States)

    Labuschagne, Izelle; Jones, Rebecca; Callaghan, Jenny; Whitehead, Daisy; Dumas, Eve M; Say, Miranda J; Hart, Ellen P; Justo, Damian; Coleman, Allison; Dar Santos, Rachelle C; Frost, Chris; Craufurd, David; Tabrizi, Sarah J; Stout, Julie C

    2013-05-15

    Facial emotion recognition impairments have been reported in Huntington's disease (HD). However, the nature of the impairments across the spectrum of HD remains unclear. We report on emotion recognition data from 344 participants comprising premanifest HD (PreHD) and early HD patients, and controls. In a test of recognition of facial emotions, we examined responses to six basic emotional expressions and neutral expressions. In addition, and within the early HD sample, we tested for differences on emotion recognition performance between those 'on' vs. 'off' neuroleptic or selective serotonin reuptake inhibitor (SSRI) medications. The PreHD groups showed significant (precognition, compared to controls, on fearful, angry and surprised faces; whereas the early HD groups were significantly impaired across all emotions including neutral expressions. In early HD, neuroleptic use was associated with worse facial emotion recognition, whereas SSRI use was associated with better facial emotion recognition. The findings suggest that emotion recognition impairments exist across the HD spectrum, but are relatively more widespread in manifest HD than in the premanifest period. Commonly prescribed medications to treat HD-related symptoms also appear to affect emotion recognition. These findings have important implications for interpersonal communication and medication usage in HD. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  9. Hemoglobin, hematocrit, and changes in cerebral blood flow: the Second Manifestations of ARTerial disease-Magnetic Resonance study.

    Science.gov (United States)

    van der Veen, Pieternella H; Muller, Majon; Vincken, Koen L; Westerink, Jan; Mali, Willem P T M; van der Graaf, Yolanda; Geerlings, Mirjam I

    2015-03-01

    Hemoglobin and hematocrit are important determinants of blood viscosity and arterial oxygen content and may therefore influence cerebral blood flow (CBF). We examined cross-sectional and prospective associations of hemoglobin and hematocrit with CBF in 569 patients with manifest arterial disease (mean age 57 ± 10 years) with available data on magnetic resonance angiography to measure parenchymal CBF. Mean (SD) parenchymal CBF at baseline was 52.3 (9.8) mL/min/100 mL and decreased with 1.5 (11.0) mL/min/100 mL after on average 3.9 years of follow-up. Linear regression analyses showed that greater hemoglobin and hematocrit values were associated with lower baseline parenchymal CBF and more decline in parenchymal CBF over time, independent of cardiovascular risk factors, use of antiplatelet drugs, anticoagulants, or diuretics, and brain measures: adjusted mean differences (95% confidence interval [CI]) in decline in parenchymal CBF between patients in the lower and upper quartiles of hemoglobin and hematocrit were -2.48 (95% CI -3.70 to -1.25) and -3.69 (95% CI -5.45 to -1.94) mL/min/100 mL. Higher hemoglobin and hematocrit were associated with lower baseline parenchymal CBF and a greater decline in parenchymal CBF over time, possibly as a result of physiological compensating mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Differential replication of foot-and-mouth disease viruses in mice determine lethality

    Science.gov (United States)

    Adult C57BL/6J mice have been used to study foot-and-mouth disease virus (FMDV) biology. In this work, two variants of an FMDV A/Arg/01 strain exhibiting differential pathogenicity in adult mice were identified and characterized: a non-lethal virus (A01NL) caused mild signs of disease, whereas a let...

  11. Immunomorphologic Manifestations in Mice Liver Infected with Influenza A/H5N1, A/Goose/Krasnoozerskoye/627/05 Strain

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    Oxana V. Potapova

    2013-01-01

    Full Text Available Highly pathogenic avian influenza H5N1 (HPAI H5N1 viruses can infect mammals, including humans, causing severe systemic disease with the inhibition of the immune system and a high mortality rate. In conditions of lymphoid tissue depletion, the liver plays an important role in host defence against viruses. The changes in mice liver infected with HPAI H5N1 virus A/goose/Krasnoozerskoye/627/05 have been studied. It has been shown that the virus persistence in the liver leads to the expression of proinflammatory cytokines (TNF-α, IL-6 and intracellular proteases (lysozyme, cathepsin D, and myeloperoxidase by Kupffer cells. Defective antiviral response exacerbates destructive processes in the liver accelerating the development of liver failure.

  12. MR Microimaging of amyloid plaques in Alzheimer's disease transgenic mice

    International Nuclear Information System (INIS)

    Wengenack, Thomas M.; Poduslo, Joseph F.; Jack, Clifford R.; Garwood, Michael

    2008-01-01

    Alzheimer's disease (AD) is the most prevalent neurological condition affecting industrialized nations and will rapidly become a healthcare crisis as the population ages. Currently, the post-mortem histological observation of amyloid plaques and neurofibrillary tangles is the only definitive diagnosis available for AD. A pre-mortem biological or physiological marker specific for AD used in conjunction with current neurological and memory testing could add a great deal of confidence to the diagnosis of AD and potentially allow therapeutic intervention much earlier in the disease process. Our group has developed MRI techniques to detect individual amyloid plaques in AD transgenic mouse brain in vivo. We are also developing contrast-enhancing agents to increase the specificity of detection of amyloid plaques. Such in vivo imaging of amyloid plaques will also allow the evaluation of anti-amyloid therapies being developed by the pharmaceutical industry in pre-clinical trials of AD transgenic mice. This short review briefly discusses our progress in these areas. (orig.)

  13. Dynamics of Cellular Proliferation during 'Acute Homologous Disease' in Mice

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    Vitale, B.; Silobrcic, V.; Jurin, M.; Matosic, M.; Tomazic, Vesna [Laboratory for Transplantation and Tumour Immunology, Department of Biology, Institute Ruder Boskovic, Zagreb, Yugoslavia (Croatia)

    1968-08-15

    CBA mice, lethally irradiated and injected with 20 x 10{sup 6} bone-marrow cells derived from C57BL donors, develop a chronic form of 'homologous disease' and die between 20 and 40 days after treatment. If 10 x 10{sup 6} lymph node cells are added to the bone-marrow suspension, all recipients develop 'acute' homologous disease and die 6 to 10 days after irradiation. Different parameters of the disease were systematically observed. Among them, changes in spleen weight indicated early cell proliferation, which reached its maximum on day 4 and progressively decreased later on. Chromosomal analysis showed that all dividing cells in the spleen were of donor origin. Their number decreased concomitantly with the shrinkage and devastation of the organ, which started on day 6. The period of devastation of the spleen fully corresponds to the time in which all animals die. The use of cyclophosphamide in the treatment of 'acute' homologous disease transformed the disease into a chronic form with a mortality very similar to that obtained when only bone-marrow cells were injected. Among other effects, treatment with cyclophosphamide prevented early proliferation of donor cells in the spleen, and delayed spleen weight increase for about 10 days. After that period spleen weight increased, reaching its maximum on day 12. At first only donor type cells could be detected, but towards the end of the period in which spleen weight increase was registered host type cells appeared among the cells in mitosis. Their number gradually increased, and in some cases the majority or all of the dividing cells were of the host type. After a transitional decrease in spleen weight, another peak in cellular proliferation consisting of either host or donor or both types of cells was observed about day 30. In spite of the observed irregularities in the origin of dividing cells, all animals died by day 40 after application of cyclophosphamide. The relationship between proliferation of injected lymph node

  14. Microbiological, immunological and genetic factors in family members with periodontitis as a manifestation of systemic disease, associated with hematological disorders.

    Science.gov (United States)

    Okada, Mitsugi; Awane, Saori; Suzuki, Junji; Hino, Takamune; Takemoto, Toshinobu; Kurihara, Hidemi; Miura, Kazuo

    2002-08-01

    The microflora, immunological profiles of host defence functions, and human leukocyte antigen (HLA) findings are reported for a mother, son and daughter who were diagnosed as having 'periodontitis as a manifestation of systemic diseases, associated with hematological disorders'. Examinations were made of the bacterial flora from the periodontal pocket, neutrophil chemotaxis, neutrophil phagocytosis, and the genotypes (DQB1) and serotypes (DR locus) of HLA class II antigens. Phenotypic analyses of the peripheral lymphocytes were also conducted. The subgingival microflora from the mother was dominated by Gram-negative rods, especially Porphyromonas endodontalis, Prevotella intermedia/Prevotella nigrescens and Fusobacterium nucleatum. Subgingival microflora samples from the son and daughter were dominated by Gram-positive cocci and Gram-positive rods. Through the use of polymerase chain reaction, Campylobacter rectus and Capnocytophaga gingivalis were detected in all subjects, whereas Porphyromonas gingivalis, P. intermedia, and Treponema denticola were not detected in any subjects. All three subjects showed a remarkable level of depressed neutrophil chemotaxis to N-formyl-methionyl-leucyl-phenylalanine, although their phagocyte function levels were normal, in comparison to healthy control subjects. Each subject had the same genotype, HLA-DQB1*0601, while the mother had HLA-DR2 and HLA-DR8, and the son and daughter had HLA-DR2 only. In summary, the members of this family showed a similar predisposition to periodontitis with regard to certain host defence functions. It is suggested that the depressed neutrophil chemotaxis that was identified here could be a significant risk factor for periodontitis in this family.

  15. Faster and stronger manifestation of mitochondrial diseases in skeletal muscle than in heart related to cytosolic inorganic phosphate (Pi) accumulation.

    Science.gov (United States)

    Korzeniewski, Bernard

    2016-08-01

    A model of the cell bioenergetic system was used to compare the effect of oxidative phosphorylation (OXPHOS) deficiencies in a broad range of moderate ATP demand in skeletal muscle and heart. Computer simulations revealed that kinetic properties of the system are similar in both cases despite the much higher mitochondria content and "basic" OXPHOS activity in heart than in skeletal muscle, because of a much higher each-step activation (ESA) of OXPHOS in skeletal muscle than in heart. Large OXPHOS deficiencies lead in both tissues to a significant decrease in oxygen consumption (V̇o2) and phosphocreatine (PCr) and increase in cytosolic ADP, Pi, and H(+) The main difference between skeletal muscle and heart is a much higher cytosolic Pi concentration in healthy tissue and much higher cytosolic Pi accumulation (level) at low OXPHOS activities in the former, caused by a higher PCr level in healthy tissue (and higher total phosphate pool) and smaller Pi redistribution between cytosol and mitochondria at OXPHOS deficiency. This difference does not depend on ATP demand in a broad range. A much greater Pi increase and PCr decrease during rest-to-moderate work transition in skeletal muscle at OXPHOS deficiencies than at normal OXPHOS activity significantly slows down the V̇o2 on-kinetics. Because high cytosolic Pi concentrations cause fatigue in skeletal muscle and can compromise force generation in skeletal muscle and heart, this system property can contribute to the faster and stronger manifestation of mitochondrial diseases in skeletal muscle than in heart. Shortly, skeletal muscle with large OXPHOS deficiencies becomes fatigued already during low/moderate exercise. Copyright © 2016 the American Physiological Society.

  16. Is type 2 diabetes mellitus a vascular disease (atheroscleropathy with hyperglycemia a late manifestation? The role of NOS, NO, and redox stress.

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    Tyagi Suresh C

    2003-02-01

    Full Text Available Abstract Background Cardiovascular disease accounts for at least 85 percent of deaths for those patients with type 2 diabetes mellitus (T2DM. Additionally, 75 percent of these deaths are due to ischemic heart disease. Hypothesis Is type 2 diabetes mellitus a vascular disease (atheroscleropathy with hyperglycemia a late manifestation? The role of NOS, NO, and redox stress. Testing of the hypothesis The vulnerable three arms of the eNOS reaction responsible for the generation of eNO is discussed in relation to the hypothesis: (1. The L-arginine substrate. (2. The eNOS enzyme. (3. The BH4 cofactor. Implications of the hypothesis If we view T2DM as a vascular disease initially with a later manifestation of hyperglycemia, we may be able to better understand and modify the multiple toxicities associated with insulin resistance, metabolic syndrome, prediabetes, overt T2DM, and accelerated atherosclerosis (atheroscleropathy. The importance of endothelial nitric oxide synthase, endothelial nitric oxide, tetrahydrobiopterin (BH4, L-arginine, and redox stress are discussed in relation to endothelial cell dysfunction and the development and progression of atheroscleropathy and T2DM. In addition to the standard therapies to restore endothelial cell dysfunction and stabilization of vulnerable atherosclerotic plaques, this article will discuss the importance of folic acid (5MTHF supplementation in this complex devastating disease process. Atheroscleropathy and hyperglycemia could be early and late manifestations, respectively, in the natural progressive history of T2DM.

  17. Quality of life, fatigue and mental health in patients with the m.3243A > G mutation and its correlates with genetic characteristics and disease manifestation.

    Science.gov (United States)

    Verhaak, Christianne; de Laat, Paul; Koene, Saskia; Tibosch, Marijke; Rodenburg, Richard; de Groot, Imelda; Knoop, Hans; Janssen, Mirian; Smeitink, Jan

    2016-03-18

    Mitochondrial disorders belong to the most prevalent inherited metabolic diseases with the m.3243A > G mutation reflecting being one of the most common mutations in mitochondrial DNA. Previous studies showed little relationship between mitochondrial genetics and disease manifestation. Relationship between genotype and disease manifestation with patient reported quality of life and other patient reported outcomes is still unexplored. Seventy-two out of the 122 invited adult patients with m.3243A > G mutation completed online standardized questionnaires on quality of life, functional impairment, fatigue and mental health as assessed by the RAND-SF36, the Sickness Impact Profile (SIP), the Checklist Individual Strength (CIS) and the Hospital Anxiety and Depression scale (HADS). Data were related to clinical manifestation reflected by the Newcastle Mitochondrial Disease Adult Scale (NMDAS) score and heteroplasmy levels of the mutation in urine epithelial cells. Patients reported impaired quality of life. Sixty percent showed severe levels of fatigue, and 37% showed clinical relevant mental health problems, which was significantly more than healthy norms. These patient reported health outcomes showed negligible relationship with levels of heteroplasmy (r = mental health problems, are only partly reflected by clinical assessments. In order to support patients more effectively, integration of patient reported outcomes, alongside symptoms of their disease, in clinical practice is warranted.

  18. Spectrum of ocular manifestations in CLN2-associated batten (Jansky-Bielschowsky disease correlate with advancing age and deteriorating neurological function.

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    Anton Orlin

    Full Text Available BACKGROUND: Late infantile neuronal ceroid lipofuscinosis (LINCL, one form of Batten's disease is a progressive neurodegenerative disorder resulting from a CLN2 gene mutation. The spectrum of ophthalmic manifestations of LINCL and the relationship with neurological function has not been previously described. METHODS: Patients underwent ophthalmic evaluations, including anterior segment and dilated exams, optical coherence tomography, fluorescein and indocyanine green angiography. Patients were also assessed with the LINCL Neurological Severity Scale. Ophthalmic findings were categorized into one of five severity scores, and the association of the extent of ocular disease with neurological function was assessed. RESULTS: Fifty eyes of 25 patients were included. The mean age at the time of exam was 4.9 years (range 2.5 to 8.1. The mean ophthalmic severity score was 2.6 (range 1 to 5. The mean neurological severity score was 6.1 (range 2 to 11. Significantly more severe ophthalmic manifestations were observed among older patients (p<0.005 and patients with more severe neurological findings (p<0.03. A direct correlation was found between the Ophthalmic Severity Scale and the Weill Cornell Neurological Scale (p<0.002. A direct association was also found between age and the ophthalmic manifestations (p<0.0002, with older children having more severe ophthalmic manifestations. CONCLUSIONS: Ophthalmic manifestations of LINCL correlate closely with the degree of neurological function and the age of the patient. The newly established LINCL Ophthalmic Scale may serve as an objective marker of LINCL severity and disease progression, and may be valuable in the evaluation of novel therapeutic strategies for LINCL, including gene therapy.

  19. Haematological manifestations of lupus

    Science.gov (United States)

    Fayyaz, Anum; Igoe, Ann; Kurien, Biji T; Danda, Debashish; James, Judith A; Stafford, Haraldine A; Scofield, R Hal

    2015-01-01

    Our purpose was to compile information on the haematological manifestations of systemic lupus erythematosus (SLE), namely leucopenia, lymphopenia, thrombocytopenia, autoimmune haemolytic anaemia (AIHA), thrombotic thrombocytopenic purpura (TTP) and myelofibrosis. During our search of the English-language MEDLINE sources, we did not place a date-of-publication constraint. Hence, we have reviewed previous as well as most recent studies with the subject heading SLE in combination with each manifestation. Neutropenia can lead to morbidity and mortality from increased susceptibility to infection. Severe neutropenia can be successfully treated with granulocyte colony-stimulating factor. While related to disease activity, there is no specific therapy for lymphopenia. Severe lymphopenia may require the use of prophylactic therapy to prevent select opportunistic infections. Isolated idiopathic thrombocytopenic purpura maybe the first manifestation of SLE by months or even years. Some manifestations of lupus occur more frequently in association with low platelet count in these patients, for example, neuropsychiatric manifestation, haemolytic anaemia, the antiphospholipid syndrome and renal disease. Thrombocytopenia can be regarded as an important prognostic indicator of survival in patients with SLE. Medical, surgical and biological treatment modalities are reviewed for this manifestation. First-line therapy remains glucocorticoids. Through our review, we conclude glucocorticoids do produce a response in majority of patients initially, but sustained response to therapy is unlikely. Glucocorticoids are used as first-line therapy in patients with SLE with AIHA, but there is no conclusive evidence to guide second-line therapy. Rituximab is promising in refractory and non-responding AIHA. TTP is not recognised as a criteria for classification of SLE, but there is a considerable overlap between the presenting features of TTP and SLE, and a few patients with SLE have concurrent

  20. Differential Muscle Involvement in Mice and Humans Affected by McArdle Disease

    DEFF Research Database (Denmark)

    Krag, Thomas O; Pinós, Tomàs; Nielsen, Tue L

    2016-01-01

    McArdle disease (muscle glycogenosis type V) is caused by myophosphorylase deficiency, which leads to impaired glycogen breakdown. We investigated how myophosphorylase deficiency affects muscle physiology, morphology, and glucose metabolism in 20-week-old McArdle mice and compared the findings...... to those in McArdle disease patients. Muscle contractions in the McArdle mice were affected by structural degeneration due to glycogen accumulation, and glycolytic muscles fatigued prematurely, as occurs in the muscles of McArdle disease patients. Homozygous McArdle mice showed muscle fiber disarray...... no substitution for the missing muscle isoform. In the mice, the tibialis anterior (TA) muscles were invariably more damaged than the quadriceps muscles. This may relate to a 7-fold higher level of myophosphorylase in TA compared to quadriceps in wild-type mice and suggests higher glucose turnover in the TA. Thus...

  1. Clinical Manifestations of Kaposi Sarcoma Herpesvirus Lytic Activation: Multicentric Castleman Disease (KSHV-MCD) and the KSHV Inflammatory Cytokine Syndrome.

    Science.gov (United States)

    Polizzotto, Mark N; Uldrick, Thomas S; Hu, Duosha; Yarchoan, Robert

    2012-01-01

    Soon after the discovery of Kaposi sarcoma (KS)-associated herpesvirus (KSHV), it was appreciated that this virus was associated with most cases of multicentric Castleman disease (MCD) arising in patients infected with human immunodeficiency virus. It has subsequently been recognized that KSHV-MCD is a distinct entity from other forms of MCD. Like MCD that is unrelated to KSHV, the clinical presentation of KSHV-MCD is dominated by systemic inflammatory symptoms including fevers, cachexia, and laboratory abnormalities including cytopenias, hypoalbuminemia, hyponatremia, and elevated C-reactive protein. Pathologically KSHV-MCD is characterized by polyclonal, IgM-lambda restricted plasmacytoid cells in the intrafollicular areas of affected lymph nodes. A portion of these cells are infected with KSHV and a sizable subset of these cells express KSHV lytic genes including a viral homolog of interleukin-6 (vIL-6). Patients with KSHV-MCD generally have elevated KSHV viral loads in their peripheral blood. Production of vIL-6 and induction of human (h) IL-6 both contribute to symptoms, perhaps in combination with overproduction of IL-10 and other cytokines. Until recently, the prognosis of patients with KSHV-MCD was poor. Recent therapeutic advances targeting KSHV-infected B cells with the anti-CD20 monoclonal antibody rituximab and utilizing KSHV enzymes to target KSHV-infected cells have substantially improved patient outcomes. Recently another KSHV-associated condition, the KSHV inflammatory cytokine syndrome (KICS) has been described. Its clinical manifestations resemble those of KSHV-MCD but lymphadenopathy is not prominent and the pathologic nodal changes of KSHV-MCD are absent. Patients with KICS exhibit elevated KSHV viral loads and elevation of vIL-6, homolog of human interleukin-6 and IL-10 comparable to those seen in KSHV-MCD; the cellular origin of these is a matter of investigation. KICS may contribute to the inflammatory symptoms seen in some patients with

  2. Clinical Manifestations of Kaposi Sarcoma Herpesvirus Lytic Activation: Multicentric Castleman Disease (KSHV–MCD) and the KSHV Inflammatory Cytokine Syndrome

    Science.gov (United States)

    Polizzotto, Mark N.; Uldrick, Thomas S.; Hu, Duosha; Yarchoan, Robert

    2012-01-01

    Soon after the discovery of Kaposi sarcoma (KS)-associated herpesvirus (KSHV), it was appreciated that this virus was associated with most cases of multicentric Castleman disease (MCD) arising in patients infected with human immunodeficiency virus. It has subsequently been recognized that KSHV–MCD is a distinct entity from other forms of MCD. Like MCD that is unrelated to KSHV, the clinical presentation of KSHV–MCD is dominated by systemic inflammatory symptoms including fevers, cachexia, and laboratory abnormalities including cytopenias, hypoalbuminemia, hyponatremia, and elevated C-reactive protein. Pathologically KSHV–MCD is characterized by polyclonal, IgM-lambda restricted plasmacytoid cells in the intrafollicular areas of affected lymph nodes. A portion of these cells are infected with KSHV and a sizable subset of these cells express KSHV lytic genes including a viral homolog of interleukin-6 (vIL-6). Patients with KSHV–MCD generally have elevated KSHV viral loads in their peripheral blood. Production of vIL-6 and induction of human (h) IL-6 both contribute to symptoms, perhaps in combination with overproduction of IL-10 and other cytokines. Until recently, the prognosis of patients with KSHV–MCD was poor. Recent therapeutic advances targeting KSHV-infected B cells with the anti-CD20 monoclonal antibody rituximab and utilizing KSHV enzymes to target KSHV-infected cells have substantially improved patient outcomes. Recently another KSHV-associated condition, the KSHV inflammatory cytokine syndrome (KICS) has been described. Its clinical manifestations resemble those of KSHV–MCD but lymphadenopathy is not prominent and the pathologic nodal changes of KSHV–MCD are absent. Patients with KICS exhibit elevated KSHV viral loads and elevation of vIL-6, homolog of human interleukin-6 and IL-10 comparable to those seen in KSHV–MCD; the cellular origin of these is a matter of investigation. KICS may contribute to the inflammatory symptoms seen in some

  3. Primary biochemical defect in copper metabolism in mice with a recessive X-linked mutation analogous to Menkes' disease in man

    International Nuclear Information System (INIS)

    Prins, H.W.; Hamer, C.J.A. van den.

    1979-01-01

    The defect in Menkes' disease in man is identical to that in Brindled mice. The defect manifests itself in a accumulation of copper in some tissues, such as renal, intestinal (mucosa and muscle), pancreatic, osseous, muscular, and dermal. Hence a fatal copper deficiency results in other tissues (e.g., hepatic). The copper transport through the intestine is impaired and copper, which circumvents the block in the copper resorption, is irreversibly trapped in the above-mentioned, copper accumulating tissues where it is bound to a cytoplasmatic protein with molecular weight 10,000 daltons, probably the primary cytoplasmatic copper transporting protein. This protein shows a Cu-S absorption band at 250 nm, and the copper:protein ratio is increased. Such copper rich protein was found neither in the kidneys of the unaffected mica nor in the liver of the mice that do have the defect. Three models of the primary defect in Menkes' disease are proposed

  4. Pulmonary manifestations of leptospirosis

    Directory of Open Access Journals (Sweden)

    Sameer Gulati

    2012-01-01

    Full Text Available Leptospirosis has a spectrum of presentation which ranges from mild disease to a severe form comprising of jaundice and renal failure. Involvement of the lung can vary from subtle clinical features to deadly pulmonary hemorrhage and acute respiratory distress syndrome. Of late, it has been identified that leptospirosis can present atypically with predominant pulmonary manifestations. This can delay diagnosis making and hence optimum treatment. The purpose of this review is to bring together all the reported pulmonary manifestations of leptospirosis and the recent trends in the management.

  5. Clinical manifestation and aetiology of a genital associated disease in Olive baboons (Papio hamadryas anubis) at Lake Manyara National Park, Tanzania

    OpenAIRE

    Knauf, Sascha

    2011-01-01

    The aim of the study was to investigate a genitally associated disease and to describe its clinical manifestation and aetiology in baboons at Lake Manyara National Park in the United Republic of Tanzania. Lake Manyara National Park is located in the northern part of the country, 160 km northwest of the Mt. Kilimanjaro. It is among the smallest protected areas, but belongs to the extended ecosystem of the Serengeti, Ngorongoro Conservation Area, Lake Manyara and Tarangire National Park. The...

  6. A multicentre study of 513 Danish patients with systemic lupus erythematosus. I. Disease manifestations and analyses of clinical subsets

    DEFF Research Database (Denmark)

    Jacobsen, S; Petersen, J; Ullman, S

    1998-01-01

    duration of follow-up was 8.2 years from diagnosis and 12.8 years from first symptom. This paper describes the most common clinical and laboratory manifestations and their relationship to sex and age at the time of onset and diagnosis. Cluster analysis revealed three clinically defined clusters at the time...

  7. Homocysteine, progression of ventricular enlargement, and cognitive decline: the Second Manifestations of ARTerial disease-Magnetic Resonance study

    NARCIS (Netherlands)

    Jochemsen, Hadassa M.; Kloppenborg, Raoul P.; de Groot, Lisette C. P. G. M.; Kampman, Ellen; Mali, Willem P. T. M.; van der Graaf, Yolanda; Geerlings, Mirjam I.; Doevendans, P. A.; van der Graaf, Y.; Grobbee, D. E.; Rutten, G. E. H. M.; Kappelle, L. J.; Mali, W. P. Th M.; Moll, F. L.; Visseren, F. L. J.

    2013-01-01

    Homocysteine may be a modifiable risk factor for cognitive decline and brain atrophy, particularly in older persons. We examined whether homocysteine increased the risk for cognitive decline and brain atrophy, and evaluated the modifying effect of age. Within the Second Manifestations of ARTerial

  8. Metabolic bone disease as a presenting manifestation of primary Sjögren′s syndrome: Three cases and review of literature

    Directory of Open Access Journals (Sweden)

    Deepak Khandelwal

    2011-01-01

    Full Text Available Primary Sjögren′s syndrome (pSS is a chronic autoimmune disease characterized by a progressive lymphocytic infiltration of the exocrine glands with varying degrees of systemic involvement. Chronic inflammation compromises the glands′ function that leads to dry symptoms in the mouth/eyes. Renal involvement is a well recognized extraglandular manifestation of pSS. Metabolic bone disease (MBD, however, rarely occurs as the primary manifestation of a renal tubule disorder due to pSS. To the best of our knowledge there are only 6 reported cases of metabolic bone disease as the primary manifestation of pSS to date. Four of these had distal renal tubular acidosis (RTA, and 2 had a combined picture of distal and proximal tubular dysfunction. We herein present our experience of 3 cases who presented to us with a clinical picture suggestive of MBD. While investigating these patients, we found evidence of RTA, which was found to be secondary to pSS.

  9. Traumatic brain injury precipitates cognitive impairment and extracellular Aβ aggregation in Alzheimer's disease transgenic mice.

    Directory of Open Access Journals (Sweden)

    Naoki Tajiri

    Full Text Available Traumatic brain injury (TBI has become a signature wound of the wars in Iraq and Afghanistan. Many American soldiers, even those undiagnosed but likely suffering from mild TBI, display Alzheimer's disease (AD-like cognitive impairments, suggesting a pathological overlap between TBI and AD. This study examined the cognitive and neurohistological effects of TBI in presymptomatic APP/PS1 AD-transgenic mice. AD mice and non-transgenic (NT mice received an experimental TBI on the right parietal cortex using the controlled cortical impact model. Animals were trained in a water maze task for spatial memory before TBI, and then reevaluated in the same task at two and six weeks post-TBI. The results showed that AD mice with TBI made significantly more errors in the task than AD mice without TBI and NT mice regardless of TBI. A separate group of AD mice and NT mice were evaluated neurohistologically at six weeks after TBI. The number of extracellular beta-amyloid (Aβ-deposits significantly increased by at least one fold in the cortex of AD mice that received TBI compared to the NT mice that received TBI or the AD and NT mice that underwent sham surgery. A significant decrease in MAP2 positive cells, indicating neuronal loss, was observed in the cortex of both the AD and NT mice that received TBI compared to the AD and NT mice subjected to sham surgery. Similar changes in extracellular Aβ deposits and MAP2 positive cells were also seen in the hippocampus. These results demonstrate for the first time that TBI precipitates cognitive impairment in presymptomatic AD mice, while also confirming extracellular Aβ deposits following TBI. The recognition of this pathological link between TBI and AD should aid in developing novel treatments directed at abrogating cellular injury and extracellular Aβ deposition in the brain.

  10. Sclerodermatomyositis, ocular manifestations.

    Science.gov (United States)

    Pedroza-Seres, M; Serna-Ojeda, J C; Flores-Suárez, L F

    2017-07-01

    Sclerodermatomyositis is an overlap syndrome of myositis and scleroderma, with dermatological, muscular and joint involvement, but may also present with ocular manifestations. A 57 year-old woman presented with ophthalmological manifestations, including scleral thinning 360°, and the presence of cells in the anterior and posterior chamber. Oriented physical examination and laboratory studies led to the diagnosis, with the need for systemic treatment. Sclerodermatomyositis is a rare disease. Its diagnosis needs thorough clinical and laboratory studies, and its management should be multidisciplinary when inflammatory ocular manifestations may be present. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Efficacy of TNF-α antagonist and other immunomodulators in the treatment of patients with ophthalmologic manifestations of Behcet's disease and HLA B51 positive vasculitis

    Directory of Open Access Journals (Sweden)

    Zlatanović Gordana

    2012-01-01

    Full Text Available Bacground/Aim. Behcet's disease is genetically conditioned, immune-mediated multisystem occlusive vasculitis of small blood vessels, espesially venules, of unknown etiology. The aim of this study was to analyze the clinical features, disease activity and therapy of the patients with ophthalmologic manifestation of Behcet's disease. Methods. In this study symptoms and signs of the disease were analyzed both prospectively and retrospectively during the active manifestation of the disease. The diagnosis was reached according to the International Criteria for Behcet's Disease (2006. The treatment effects were evaluated based on the presence of the best corrected visual acuity and the inflammation of the vitreous humour before and after the application of our therapeutic method. The applied therapeutic modality consisted of the primary application of corticosteroid therapy in the active stage of the disease complemented with the choice of drugs from the immunosuppressive group. In this study there drugs were cyclosporine or methotrexate. A treatment refractory patients with poor vision prognosis were treated with a third drug, the biological preparation infliximab, a tumor necrosis factor-alpha (TNF-α antagonist. Results. The mean age of 11 patients with ophthalmologic manifestation of Behcet's disease was 50.6 years. HLA B-5(51 was positive in 81% of the patients while 36% of the patients had positive pathergy test. Changes in affected eyes included vitritis (100%, posterior uveitis (45%, panuveitis (54%, retinal vasculitis (54%, cystoid macular edema (54%, and cystoid degeneration (18%. Increased intraocular pressure was observed in 27% of the patients. There was no statistically significant variation in disease activity parameters in any of the patients (p > 0.05. A statistically significant improvement in visual acuity (p < 0.05 and a high statistically significant decrease of inflammation of the worst affected eyes (p = 0.001 were detected

  12. Report of two patients with Paget′s disease - one with typical clinical and radiological manifestations including cardiac involvement and the other subclinical but with radiological changes

    Directory of Open Access Journals (Sweden)

    B Sivapatha Sundharam

    2006-01-01

    Full Text Available Osteitis deformans or Paget′s disease of bone, fondly referred to as the ′collage of matrix madness′, is a unique skeletal disease characterized by furious osteoclastic bone resorption followed by a period of hectic bone formation, resulting in again in the bone mass wherein the newly formed bone is disordered and architecturally unsound. A disease of obscure etiology, it usually manifests as progressive enlargement of one or multiple bones of the skeleton. Herewith we present a typical example of a polyostotic form of Paget′s disease with classical clinical features and radiologic changes in one patient and a subclinical form of Paget′s disease with marked radiological changes in the other patient.

  13. Neuroprotective properties of cannabigerol in Huntington's disease: studies in R6/2 mice and 3-nitropropionate-lesioned mice.

    Science.gov (United States)

    Valdeolivas, Sara; Navarrete, Carmen; Cantarero, Irene; Bellido, María L; Muñoz, Eduardo; Sagredo, Onintza

    2015-01-01

    Different plant-derived and synthetic cannabinoids have shown to be neuroprotective in experimental models of Huntington's disease (HD) through cannabinoid receptor-dependent and/or independent mechanisms. Herein, we studied the effects of cannabigerol (CBG), a nonpsychotropic phytocannabinoid, in 2 different in vivo models of HD. CBG was extremely active as neuroprotectant in mice intoxicated with 3-nitropropionate (3NP), improving motor deficits and preserving striatal neurons against 3NP toxicity. In addition, CBG attenuated the reactive microgliosis and the upregulation of proinflammatory markers induced by 3NP, and improved the levels of antioxidant defenses that were also significantly reduced by 3NP. We also investigated the neuroprotective properties of CBG in R6/2 mice. Treatment with this phytocannabinoid produced a much lower, but significant, recovery in the deteriorated rotarod performance typical of R6/2 mice. Using HD array analysis, we were able to identify a series of genes linked to this disease (e.g., symplekin, Sin3a, Rcor1, histone deacetylase 2, huntingtin-associated protein 1, δ subunit of the gamma-aminobutyric acid-A receptor (GABA-A), and hippocalcin), whose expression was altered in R6/2 mice but partially normalized by CBG treatment. We also observed a modest improvement in the gene expression for brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and peroxisome proliferator-activated receptor-γ (PPARγ), which is altered in these mice, as well as a small, but significant, reduction in the aggregation of mutant huntingtin in the striatal parenchyma in CBG-treated animals. In conclusion, our results open new research avenues for the use of CBG, alone or in combination with other phytocannabinoids or therapies, for the treatment of neurodegenerative diseases such as HD.

  14. Rheumatic manifestations at presentation of Hodgkin's disease and non-Hodgkin's malignant lymphoma. A national survey of one hundred forty-six patients

    International Nuclear Information System (INIS)

    Gaudin, P.; Rozand, Y.; Fauconnier, J.; Phelip, X.

    1995-01-01

    The authors report the findings of a national survey conducted at the request for the French Society for Rheumatology to list the rheumatic manifestations that can be inaugural in Hodgkin's disease on non-Hodgkin's malignant lymphoma. This was an exploratory, retrospective, descriptive study of 146 patients from 22 rheumatology departments. A number of clinical features (young male, nocturnal sweats, generalized pruritus, protracted fever, central or peripheral lymphadenopathy) and laboratory test abnormalities (evidence of severe inflammation) considerably increased the likelihood of Hodgkin's disease rather than malignant lymphoma. The diagnosis of bony involvement requires multidisciplinary studies of tumor specimens. (authors). 4 figs., 7 tabs., 71 refs

  15. Protean manifestations of vitamin D deficiency, part 3: association with cardiovascular disease and disorders of the central and peripheral nervous systems.

    Science.gov (United States)

    Bell, David S H

    2011-05-01

    Vitamin D deficiency is associated with the risk factors of inflammation, insulin resistance and endothelial dysfunction, and left ventricular hypertrophy. As a result there is an increase in cardiovascular events (CVEs) associated with vitamin D deficiency. Vitamin D deficiency itself or secondary hyperparathyroidism or both may be responsible for the increase in CVEs. Correction of vitamin D deficiency may decrease the incidence of CVEs. Vitamin D deficiency is also associated with Alzheimer disease, schizophrenia, depression, and chronic pain and muscle weakness. Vitamin D deficiency is early treated with oral vitamin D supplements which may improve the manifestations of the diseases associated with vitamin D deficiency.

  16. Cardiovascular manifestations of Alkaptonuria.

    Science.gov (United States)

    Pettit, Stephen J; Fisher, Michael; Gallagher, James A; Ranganath, Lakshminarayan R

    2011-12-01

    The cardiovascular manifestations of alkaptonuria relate to deposition of ochronotic pigment within heart valves, endocardium, aortic intima and coronary arteries. We assessed 16 individuals with alkaptonuria for cardiovascular disease, including full electrocardiographic and echocardiographic assessment. The self reported prevalence of valvular heart disease and coronary artery disease was low. There was a significant burden of previously undiagnosed aortic valve disease, reaching a prevalence of over 40% by the fifth decade of life. The aortic valve disease was found to increase in both prevalence and severity with advancing age. In contrast to previous reports, we did not find a significant burden of mitral valve disease or coronary artery disease. These findings are important for the clinical follow-up of patients with alkaptonuria and suggest a role for echocardiographic surveillance of patients above 40 years old.

  17. Hepatoprotective Effect and Synergism of Bisdemethoycurcumin against MCD Diet-Induced Nonalcoholic Fatty Liver Disease in Mice.

    Science.gov (United States)

    Kim, Sung-Bae; Kang, Ok-Hwa; Lee, Young-Seob; Han, Sin-Hee; Ahn, Young-Sup; Cha, Seon-Woo; Seo, Yun-Soo; Kong, Ryong; Kwon, Dong-Yeul

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, has become one of the most common causes of chronic liver disease over the last decade in developed countries. NAFLD includes a spectrum of pathological hepatic changes, such as steatosis, steatohepatitis, advanced fibrosis, and cirrhosis. Bisdemethoxycurcumin (BDMC) is polyphenolic compounds with a diarylheptanoid skeleton, curcumin close analogues, which is derived from the Curcumae Longae Rhizoma. While the rich bioavailability research of curcumin, BDMC is the poor studies. We investigated whether BDMC has the hepatoprotective effect and combinatory preventive effect with silymarin on methionine choline deficient (MCD)-diet-induced NAFLD in C57BL/6J mice. C57BL/6J mice were divided into five groups of normal (normal diet without any treatment), MCD diet (MCD diet only), MCD + silymarin (SIL) 100 mg/kg group, MCD + BDMC 100 mg/kg group, MCD + SIL 50 mg/kg + BDMC 50 mg/kg group. Body weight, liver weight, liver function tests, histological changes were assessed and quantitative real-time polymerase chain reaction and Western blot analyses were conducted after 4 weeks. Mice lost body weight on the MCD-diet, but BDMC did not lose less than the MCD-diet group. Liver weights decreased from BDMC, but they increased significantly in the MCD-diet groups. All liver function test values decreased from the MCD-diet, whereas those from the BDMC increased significantly. The MCD- diet induced severe hepatic fatty accumulation, but the fatty change was reduced in the BDMC. The BDMC showed an inhibitory effect on liver lipogenesis by reducing associated gene expression caused by the MCD-diet. In all experiments, the combinations of BDMC with SIL had a synergistic effect against MCD-diet models. In conclusion, our findings indicate that BDMC has a potential suppressive effect on NAFLD. Therefore, our data suggest that BDMC may act as a novel and potent therapeutic agent against NAFLD.

  18. Hepatoprotective Effect and Synergism of Bisdemethoycurcumin against MCD Diet-Induced Nonalcoholic Fatty Liver Disease in Mice.

    Directory of Open Access Journals (Sweden)

    Sung-Bae Kim

    Full Text Available Nonalcoholic fatty liver disease (NAFLD, the hepatic manifestation of the metabolic syndrome, has become one of the most common causes of chronic liver disease over the last decade in developed countries. NAFLD includes a spectrum of pathological hepatic changes, such as steatosis, steatohepatitis, advanced fibrosis, and cirrhosis. Bisdemethoxycurcumin (BDMC is polyphenolic compounds with a diarylheptanoid skeleton, curcumin close analogues, which is derived from the Curcumae Longae Rhizoma. While the rich bioavailability research of curcumin, BDMC is the poor studies. We investigated whether BDMC has the hepatoprotective effect and combinatory preventive effect with silymarin on methionine choline deficient (MCD-diet-induced NAFLD in C57BL/6J mice. C57BL/6J mice were divided into five groups of normal (normal diet without any treatment, MCD diet (MCD diet only, MCD + silymarin (SIL 100 mg/kg group, MCD + BDMC 100 mg/kg group, MCD + SIL 50 mg/kg + BDMC 50 mg/kg group. Body weight, liver weight, liver function tests, histological changes were assessed and quantitative real-time polymerase chain reaction and Western blot analyses were conducted after 4 weeks. Mice lost body weight on the MCD-diet, but BDMC did not lose less than the MCD-diet group. Liver weights decreased from BDMC, but they increased significantly in the MCD-diet groups. All liver function test values decreased from the MCD-diet, whereas those from the BDMC increased significantly. The MCD- diet induced severe hepatic fatty accumulation, but the fatty change was reduced in the BDMC. The BDMC showed an inhibitory effect on liver lipogenesis by reducing associated gene expression caused by the MCD-diet. In all experiments, the combinations of BDMC with SIL had a synergistic effect against MCD-diet models. In conclusion, our findings indicate that BDMC has a potential suppressive effect on NAFLD. Therefore, our data suggest that BDMC may act as a novel and potent therapeutic agent

  19. Death Receptor 3 Signaling Controls the Balance between Regulatory and Effector Lymphocytes in SAMP1/YitFc Mice with Crohn’s Disease-Like Ileitis

    Directory of Open Access Journals (Sweden)

    Zhaodong Li

    2018-03-01

    Full Text Available Death receptor 3 (DR3, a member of the tumor necrosis factor receptor (TNFR superfamily, has been implicated in regulating T-helper type-1 (TH1, type-2 (TH2, and type-17 (TH17 responses as well as regulatory T cell (Treg and innate lymphoid cell (ILC functions during immune-mediated diseases. However, the role of DR3 in controlling lymphocyte functions in inflammatory bowel disease (IBD is not fully understood. Recent studies have shown that activation of DR3 signaling modulates Treg expansion suggesting that stimulation of DR3 represents a potential therapeutic target in human inflammatory diseases, including Crohn’s disease (CD. In this study, we tested a specific DR3 agonistic antibody (4C12 in SAMP1/YitFc (SAMP mice with CD-like ileitis. Interestingly, treatment with 4C12 prior to disease manifestation markedly worsened the severity of ileitis in SAMP mice despite an increase in FoxP3+ lymphocytes in mesenteric lymph node (MLN and small-intestinal lamina propria (LP cells. Disease exacerbation was dominated by overproduction of both TH1 and TH2 cytokines and associated with expansion of dysfunctional CD25−FoxP3+ and ILC group 1 (ILC1 cells. These effects were accompanied by a reduction in CD25+FoxP3+ and ILC group 3 (ILC3 cells. By comparison, genetic deletion of DR3 effectively reversed the inflammatory phenotype in SAMP mice by promoting the expansion of CD25+FoxP3+ over CD25−FoxP3+ cells and the production of IL-10 protein. Collectively, our data demonstrate that DR3 signaling modulates a multicellular network, encompassing Tregs, T effectors, and ILCs, governing disease development and progression in SAMP mice with CD-like ileitis. Manipulating DR3 signaling toward the restoration of the balance between protective and inflammatory lymphocytes may represent a novel and targeted therapeutic modality for patients with CD.

  20. Mitochondrial-nuclear genome interactions in non-alcoholic fatty liver disease in mice.

    Science.gov (United States)

    Betancourt, Angela M; King, Adrienne L; Fetterman, Jessica L; Millender-Swain, Telisha; Finley, Rachel D; Oliva, Claudia R; Crowe, David R; Ballinger, Scott W; Bailey, Shannon M

    2014-07-15

    NAFLD (non-alcoholic fatty liver disease) involves significant changes in liver metabolism characterized by oxidative stress, lipid accumulation and fibrogenesis. Mitochondrial dysfunction and bioenergetic defects also contribute to NAFLD. In the present study, we examined whether differences in mtDNA influence NAFLD. To determine the role of mitochondrial and nuclear genomes in NAFLD, MNX (mitochondrial-nuclear exchange) mice were fed an atherogenic diet. MNX mice have mtDNA from C57BL/6J mice on a C3H/HeN nuclear background and vice versa. Results from MNX mice were compared with wild-type C57BL/6J and C3H/HeN mice fed a control or atherogenic diet. Mice with the C57BL/6J nuclear genome developed more macrosteatosis, inflammation and fibrosis compared with mice containing the C3H/HeN nuclear genome when fed the atherogenic diet. These changes were associated with parallel alterations in inflammation and fibrosis gene expression in wild-type mice, with intermediate responses in MNX mice. Mice with the C57BL/6J nuclear genome had increased State 4 respiration, whereas MNX mice had decreased State 3 respiration and RCR (respiratory control ratio) when fed the atherogenic diet. Complex IV activity and most mitochondrial biogenesis genes were increased in mice with the C57BL/6J nuclear or mitochondrial genome, or both fed the atherogenic diet. These results reveal new interactions between mitochondrial and nuclear genomes and support the concept that mtDNA influences mitochondrial function and metabolic pathways implicated in NAFLD.

  1. Mitochondrial-nuclear genome interactions in nonalcoholic fatty liver disease in mice

    Science.gov (United States)

    Betancourt, Angela M.; King, Adrienne L.; Fetterman, Jessica L.; Millender-Swain, Telisha; Finley, Rachel D.; Oliva, Claudia R.; Crowe, David Ralph; Ballinger, Scott W.; Bailey, Shannon M.

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) involves significant changes in liver metabolism characterized by oxidative stress, lipid accumulation, and fibrogenesis. Mitochondrial dysfunction and bioenergetic defects also contribute to NAFLD. Herein, we examined whether differences in mtDNA influence NAFLD. To determine the role of mitochondrial and nuclear genomes in NAFLD, Mitochondrial-Nuclear eXchange (MNX) mice were fed an atherogenic diet. MNX mice have mtDNA from C57BL/6J mice on a C3H/HeN nuclear background and vice versa. Results from MNX mice were compared to wild-type C57BL/6J and C3H/HeN mice fed a control or atherogenic diet. Mice with the C57BL/6J nuclear genome developed more macrosteatosis, inflammation, and fibrosis compared with mice containing the C3H/HeN nuclear genome when fed the atherogenic diet. These changes were associated with parallel alterations in inflammation and fibrosis gene expression in wild-type mice, with intermediate responses in MNX mice. Mice with the C57BL/6J nuclear genome had increased State 4 respiration, whereas MNX mice had decreased State 3 respiration and RCR when fed the atherogenic diet. Complex IV activity and most mitochondrial biogenesis genes were increased in mice with the C57BL/6J nuclear or mitochondrial genome, or both fed the atherogenic diet. These results reveal new interactions between mitochondrial and nuclear genomes and support the concept that mtDNA influences mitochondrial function and metabolic pathways implicated in NAFLD. PMID:24758559

  2. Autologous neural progenitor cell transplantation into newborn mice modeling for E200K genetic prion disease delays disease progression.

    Science.gov (United States)

    Frid, Kati; Binyamin, Orli; Fainstein, Nina; Keller, Guy; Ben-Hur, Tamir; Gabizon, Ruth

    2018-05-01

    TgMHu2ME199K mice, a transgenic line mimicking genetic prion disease, are born healthy and gradually deteriorate to a terminal neurological condition concomitant with the accumulation of disease-related PrP. To investigate whether transplantation of neural progenitor cells (NPCs) to these mice can delay disease aggravation, we first tested the properties of mutant PrP in homogenates and enriched NPCs from TgMHu2ME199K embryos, as compared to PrP in sick TgMHu2ME199K brains. Next, we tested the clinical effect of NPCs transplantation into newborn TgMHu2ME199K mice. We show that mutant PrP does not convert into a disease-related isoform while in progenitor cells. Most important, transplantation of both wild type and transgenic NPCs significantly delayed the progression of spontaneous prion disease in TgMHu2ME199K mice. While the strong clinical effect was not accompanied by a reduced accumulation of disease-related PrP, treated mouse brains presented a significant reduction in amyloid glycosaminoglycans and preservation of neurogenesis levels, indicating a strong neuroprotective effect. These results may encourage the investigation of new pathways for treatment in these terrible diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Pulmonary manifestation of immunoglobulin G4-related disease in a 7-year-old immunodeficient boy with Epstein-Barr virus infection: a case report.

    Science.gov (United States)

    Szczawinska-Poplonyk, Aleksandra; Wojsyk-Banaszak, Irena; Jonczyk-Potoczna, Katarzyna; Breborowicz, Anna

    2016-06-08

    Immunoglobulin G4-related disease (IgG4-RD) is a multiorgan fibroinflammatory condition with lymphoplasmacytic infiltrates containing abundant IgG4-positive plasma cells. The immunopathogenesis of the disease and the potential role of triggering autoantigens or infectious factors have not been clearly defined. Immunoglobulin G4-related lung disease is a new and emerging condition in pediatric patients and to date, there have been only two reports regarding pulmonary manifestation of IgG4-RD in children recently published. This is the first report of IgG4-related lung disease in an immunodeficient child with Epstein-Barr virus infection. We report on the case of a 7-year old atopic boy who was hospitalized with an initial clinical and radiological diagnosis of pneumonia, positive Epstein-Barr virus (EBV)-DNA in the blood and defective adaptive immunity. The lung CT showed a consolidated mass lesion adjacent to the posterior wall of the chest and the diaphragm. The child underwent surgical resection of the tumor, and the histologic examination of the lung specimens revealed lymphoplasmacytic infiltrates with fibrosis and vasculitis correlating with IgG4-related lung disease. Subsequent monitoring of the patient with lung CT, pulmonary function tests and IgG4 levels did not show signs of active disease. The diagnosis of IgG4-related lung disease in children is challenging because of its rarity, nonspecific symptomatology and heterogeneous morphological manifestations. Further studies are required in children with pulmonary presentation of IgG4-RD to better understand pathogenesis of this condition, possible immunological or infectious triggering factors, and finally, to determine pediatric patient-targeted therapeutic interventions.

  4. Differential glucose metabolism in mice and humans affected by McArdle disease

    DEFF Research Database (Denmark)

    Krag, Thomas O; Pinós, Tomàs; Nielsen, Tue L

    2016-01-01

    McArdle disease (muscle glycogenosis type V) is a disease caused by myophosphorylase deficiency leading to "blocked" glycogen breakdown. A significant but varying glycogen accumulation in especially distal hind limb muscles of mice affected by McArdle disease has recently been demonstrated......, which could lead to lower glycogen accumulation. In comparison, tibialis anterior, extensor digitorum longus, and soleus had massive glycogen accumulation, but few, if any, changes or adaptations in glucose metabolism compared with wild-type mice. The findings suggest plasticity in glycogen metabolism....... In this study, we investigated how myophosphorylase deficiency affects glucose metabolism in hind limb muscle of 20-wk-old McArdle mice and vastus lateralis muscles from patients with McArdle disease. Western blot analysis and activity assay demonstrated that glycogen synthase was inhibited in glycolytic muscle...

  5. C1q nephropathy and isolated CD59 deficiency manifesting as necrotizing crescentic glomerulonephritis: A rare association of two diseases

    Directory of Open Access Journals (Sweden)

    Ruchika Gupta

    2015-01-01

    Full Text Available C1q nephropathy is a recently described clinico-pathologic entity with a variable clinical presentation and pathology. Crescentic glomerulonephritis (GN has been reported in only two patients in the available literature. CD59 deficiency, along with lack of CD55, is responsible for paroxysmal nocturnal hemoglobinuria (PNH. Few cases of isolated CD59 deficiency have been described with PNH-like features. A middle-aged adult male presented with rapidly progressive renal failure. Serological investigations were negative. A renal biopsy revealed necrotizing crescentic GN with rupture of Bowman′s capsule. Immunofluorescence on the frozen sections showed dominant mesangial deposits of C1q along with IgM. Hematological work-up of the patient revealed isolated CD59 deficiency. Hence, a final diagnosis of C1q nephropathy and CD59 deficiency manifesting as crescentic GN and hemolytic anemia was made. The co-existence of two rare disorders, C1q nephropathy and CD59 deficiency, in a patient with necrotizing crescentic GN is described for the first time to the best of our knowledge. The pathogenetic link of these two entities with the clinical manifestation requires further study.

  6. Motor, emotional and cognitive deficits in adult BACHD mice : A model for Huntington's disease

    NARCIS (Netherlands)

    Abada, Yah-se K.; Schreiber, Rudy; Ellenbroek, Bart

    2013-01-01

    Rationale: Huntington's disease (HD) is characterized by progressive motor dysfunction, emotional disturbances and cognitive deficits. It is a genetic disease caused by an elongation of the polyglutamine repeats in the huntingtin gene. Whereas HD is a complex disorder, previous studies in mice

  7. Gastrointestinal Manifestations of Cystic Fibrosis

    Science.gov (United States)

    2016-01-01

    Cystic fibrosis has historically been considered a pulmonary disease, but with the increasing life expectancy of these patients, gastrointestinal manifestations are becoming more important. Furthermore, nutritional status is closely linked to pulmonary function and, thus, overall mortality. This article discusses gastrointestinal manifestations (which involve nutritional, pancreatic, hepatobiliary, and, in particular, gastrointestinal tract issues) of cystic fibrosis as well as management of the disease. In addition, the article discusses studies that have been critical to our understanding of gastrointestinal manifestations of cystic fibrosis. PMID:27330503

  8. Two Thai families with Norrie disease (ND): association of two novel missense mutations with severe ND phenotype, seizures, and a manifesting carrier.

    Science.gov (United States)

    Yamada, K; Limprasert, P; Ratanasukon, M; Tengtrisorn, S; Yingchareonpukdee, J; Vasiknanonte, P; Kitaoka, T; Ghadami, M; Niikawa, N; Kishino, T

    2001-04-15

    We describe two Thai families with Norrie disease (ND) in three generations, including 10 affected males and one manifesting female. All affected males in each family had severely defective eye development with complete loss of vision. In addition, three male patients (one from family 1 and two from family 2) suffered from epilepsy, and one female carrier from one family manifested blindness with phthisis bulbi in her right eye. Mutation analysis of the ND gene (NDP) revealed two different novel missense mutations (L16P and S75P) that co-segregated with ND in each family, suggesting that the newly appearing proline at codon 16 or codon 75 alters the conformation of the ND protein and contributes to the severe phenotype of ND in each family. Other studies suggest that epileptic seizures or growth retardation that is associated with ND is the consequence of loss of contiguous genes, because most such patients had deletions extending beyond the Norrie locus. Our finding that the three affected males in the two families with the missense mutations had epilepsy does not support a contiguous gene effect, but favors the pleiotropism of NDP, at least as far as the epileptic manifestation is concerned. The unilateral blindness in the female carrier may have been due to non-random X-inactivation. Copyright 2001 Wiley-Liss, Inc.

  9. Assessing Impairment of Executive Function and Psychomotor Speed in Premanifest and Manifest Huntington's Disease Gene-expansion Carriers

    DEFF Research Database (Denmark)

    Unmack Larsen, Ida; Vinther-Jensen, Tua; Gade, Anders

    2015-01-01

    Executive functions (EF) and psychomotor speed (PMS) has been widely studied in Huntington's disease (HD). Most studies have focused on finding markers of disease progression by comparing group means at different disease stages. Our aim was to investigate performances on nine measures of EF and PMS...

  10. CD30-Positive T-Cell Lymphoproliferative Disease of the Oral Mucosa in Children: A Manifestation of Epstein-Barr Virus-Associated T-Lymphoproliferative Disorder.

    Science.gov (United States)

    Hong, Mineui; Ko, Young Hyeh

    2015-11-01

    Eosinophilic ulcer of the oral mucosa (EUOM) is a very rare, benign, self-limiting ulcerative lesion of the oral cavity of unknown pathogenesis, and belongs to the same spectrum of CD30(+) T-cell lymphoproliferative disease (LPD) of the oral mucosa. The etiology and pathogenesis of the disease are unknown. We report two cases in children who were initially diagnosed with EUOM and CD30(+) T-cell LPD, respectively. However, retrospective analysis revealed that a majority of infiltrated atypical T cells were positive for Epstein-Barr virus (EBV). The present cases suggest that the pathogenesis and etiology of EUOM or CD30(+) T-cell LPD occurring in children are different from those in adults. EUOM or CD30(+) T-cell LPD in children is a manifestation of EBV-positive T-cell LPD, and should therefore be distinguished from the disease in adults.

  11. Effect of aging and Alzheimer's disease-like pathology on brain monoamines in mice

    DEFF Research Database (Denmark)

    Von Linstow, C. U.; Severino, Maurizio; Metaxas, Athanasios

    2017-01-01

    , but these can both be age- and/or disease-related. We examined whether brain monoamine levels change as part of physiological aging and/or AD-like disease in APPSWE/PS1δE9 (APP/PS1) transgenic mice. The neocortex, hippocampus, striatum, brainstem and cerebellum of 6-, 12-, 18- and 24-month-old B6C3 wild......-type (WT) mice and of 18-month old APP/PS1 and WT mice were analysed for 5-HT, DA and NA contents by high pressure liquid chromatography (HPLC), along with neocortex from 14-month-old APP/PS1 and WT mice. While, we observed no aging effect in WT mice, we detected region-specific changes in the levels...... of all monoamines in 18-month-old transgenic compared with WT mice. This included reductions in 5-HT (-30%), DA (-47%) and NA (-32%) levels in the neocortex and increases of 5-HT in the brainstem (+18%). No changes were observed in any of the monoamines in the neocortex from 14-month-old APP/PS1 mice...

  12. Orofacial granulomatosis in children can be the initial manifestation of systemic disease: a presentation of two cases

    DEFF Research Database (Denmark)

    Simonsen, Anne Birgitte; Deleuran, Mette

    2014-01-01

    Orofacial granulomatosis is a chronic granulomatous condition characterized by relapsing and remitting lip swelling and oral involvement that may include deep ulcers, tags and cobblestone formation. It occurs as an independent entity but also in conjunction with systemic diseases...... such as tuberculosis, sarcoidosis and Crohn's disease. The clinical presentation is not indicative of concomitant systemic disease. To highlight the importance of thorough examination to rule out systemic disease, we present two childhood cases of orofacial granulomatosis, one of which was associated to Crohn......'s disease....

  13. Antibodies against a tick protein, Salp15, protect mice from the Lyme disease agent

    OpenAIRE

    Dai, Jianfeng; Wang, Penghua; Adusumilli, Sarojini; Booth, Carmen J.; Narasimhan, Sukanya; Anguita, Juan; Fikrig, Erol

    2009-01-01

    Traditionally, vaccines directly target a pathogen or microbial toxin. Lyme disease, caused by Borrelia burgdorferi, is a tick-borne illness for which a human vaccine is not currently available. B. burgdorferi binds a tick salivary protein, Salp15, during transmission from the vector, and this interaction facilitates infection of mice. We now show that Salp15-antiserum significantly protected mice from B. burgdorferi infection. Salp15-antiserum also markedly enhanced the protective capacity o...

  14. Mitochondrial-nuclear genome interactions in nonalcoholic fatty liver disease in mice

    OpenAIRE

    Betancourt, Angela M.; King, Adrienne L.; Fetterman, Jessica L.; Millender-Swain, Telisha; Finley, Rachel D.; Oliva, Claudia R.; Crowe, David Ralph; Ballinger, Scott W.; Bailey, Shannon M.

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) involves significant changes in liver metabolism characterized by oxidative stress, lipid accumulation, and fibrogenesis. Mitochondrial dysfunction and bioenergetic defects also contribute to NAFLD. Herein, we examined whether differences in mtDNA influence NAFLD. To determine the role of mitochondrial and nuclear genomes in NAFLD, Mitochondrial-Nuclear eXchange (MNX) mice were fed an atherogenic diet. MNX mice have mtDNA from C57BL/6...

  15. Microglial TNF and IL-1 as early disease-modifiers in Alzheimer's-like disease in mice

    DEFF Research Database (Denmark)

    Ilkjær, Laura; Babcock, Alicia; Finsen, Bente

    2015-01-01

    In Alzheimer's disease (AD) signs of microglial activation is evident already in prodromal and early AD. This and other evidence suggest that neuroinflammation contributes to the progression of the early disease development in AD. Microglial cells have the capacity to produce cytokines such as TNF...... in the APPswe/PS1DE9 mouse model of AD. In these mice, cortical As plaque load shows a sigmoidal trajectory with age, as it does in AD. At 12 months of age, when As pathology is welldeveloped, TNF and IL-1s are produced in significantly higher proportions of microglia in the APPswe/PS1DE9 mice, than in wildtype...

  16. Inhibition of myeloperoxidase decreases vascular oxidative stress and increases vasodilatation in sickle cell disease mice.

    Science.gov (United States)

    Zhang, Hao; Xu, Hao; Weihrauch, Dorothee; Jones, Deron W; Jing, Xigang; Shi, Yang; Gourlay, David; Oldham, Keith T; Hillery, Cheryl A; Pritchard, Kirkwood A

    2013-11-01

    Activated leukocytes and polymorphonuclear neutrophils (PMN) release myeloperoxidase (MPO), which binds to endothelial cells (EC), is translocated, and generates oxidants that scavenge nitric oxide (NO) and impair EC function. To determine whether MPO impairs EC function in sickle cell disease (SCD), control (AA) and SCD mice were treated with N-acetyl-lysyltyrosylcysteine-amide (KYC). SCD humans and mice have high plasma MPO and soluble L-selectin (sL-selectin). KYC had no effect on MPO but decreased plasma sL-selectin and malondialdehyde in SCD mice. MPO and 3-chlorotyrosine (3-ClTyr) were increased in SCD aortas. KYC decreased MPO and 3-ClTyr in SCD aortas to the levels in AA aortas. Vasodilatation in SCD mice was impaired. KYC increased vasodilatation in SCD mice more than 2-fold, to ∼60% of levels in AA mice. KYC inhibited MPO-dependent 3-ClTyr formation in EC proteins. SCD mice had high plasma alanine transaminase (ALT), which tended to decrease in KYC-treated SCD mice (P = 0.07). KYC increased MPO and XO/XDH and decreased 3-ClTyr and 3-nitrotyrosine (3-NO₂Tyr) in SCD livers. These data support the hypothesis that SCD increases release of MPO, which generates oxidants that impair EC function and injure livers. Inhibiting MPO is an effective strategy for decreasing oxidative stress and liver injury and restoring EC function in SCD.

  17. The absence of later wave components in auditory brainstem responses as an initial manifestation of type 2 Gaucher disease.

    Science.gov (United States)

    Okubo, Yusuke; Goto, Masahiro; Sakakibara, Hiroshi; Terakawa, Toshiro; Kaneko, Takashi; Miyama, Sahoko

    2014-12-01

    Type 2 Gaucher disease is the most severe neuronopathic form of Gaucher disease and is characterized by severe neurodegeneration with brainstem involvement and organ failure. Prediction or diagnosis of type 2 Gaucher disease before the development of neurological complications is difficult. A 5-month-old female infant presented with deafness without other neurological abnormalities. Auditory brainstem response analysis revealed the absence of later wave components. Two months later, muscular rigidity became evident, followed by the development of opisthotonus and strabismus. Rapid progression of splenomegaly led to the diagnosis of type 2 Gaucher disease. Abnormal auditory brainstem response findings may already exist before the development of severe brainstem abnormalities such as muscular rigidity and opisthotonus in type 2 Gaucher disease. When patients present with deafness and absent later wave components on auditory brainstem response, type 2 Gaucher disease should be included in the differential diagnosis even in the absence of other neurological abnormalities. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. R wave amplitude: a new determinant of failure of patients with coronary heart disease to manifest ST segment depression during exercise

    International Nuclear Information System (INIS)

    Hakki, A.H.; Iskandrian, A.S.; Kutalek, S.; Hare, T.W.; Sokoloff, N.M.

    1984-01-01

    Patients with coronary artery disease may not manifest ST segment depression during exercise. Inadequate stress, mild coronary artery disease and severe left ventricular dysfunction have been postulated as mechanisms. The purpose of this study was to determine the influence of exercise R wave amplitude on ST segment depression in 81 patients with coronary artery disease (50% or greater diameter narrowing of one or more vessels). All patients underwent symptom-limited treadmill exercise testing and 71 patients (88%) had concomitant thallium-201 imaging. In 26 patients, the exercise R wave amplitude in electrocardiographic lead V5 was less than 11 mm (Group I), and in 55 patients it was 11 mm or greater (Group II). The two groups were similar with regard to age, sex, propranolol administration and left ventricular function. There was a significant difference in the incidence of positive exercise electrocardiograms in the two groups (2 patients [8%] in Group I and 27 patients [49%] in Group II; p . 0.002), despite similar exercise heart rate and extent of coronary artery disease. Myocardial ischemia, manifested by exercise-induced angina or exercise-induced thallium-201 perfusion defects, was similar in both groups. Thallium-201 imaging showed perfusion defects in 73% of patients in Group I and in 76% of patients in Group II (p . not significant). Thus, R wave amplitude is a new determinant of failure to develop ST depression during exercise. A low R wave amplitude (less than 11 mm) is rarely associated with ST depression, even in patients with multivessel coronary artery disease. Exercise thallium-201 imaging is a valuable diagnostic tool in patients with low R wave amplitude

  19. Transformation in pretreatment manifestations of Gaucher disease type 1 during two decades of alglucerase/imiglucerase enzyme replacement therapy in the International Collaborative Gaucher Group (ICGG) Gaucher Registry.

    Science.gov (United States)

    Mistry, Pramod K; Batista, Julie L; Andersson, Hans C; Balwani, Manisha; Burrow, Thomas Andrew; Charrow, Joel; Kaplan, Paige; Khan, Aneal; Kishnani, Priya S; Kolodny, Edwin H; Rosenbloom, Barry; Scott, C Ronald; Weinreb, Neal

    2017-09-01

    This study tests the hypothesis that the prevalence of severe clinical manifestations in Gaucher disease type 1 (GD1) patients at the time of treatment initiation has changed since alglucerase/imiglucerase enzyme replacement therapy (ERT) was approved in the United States (US) in 1991. US alglucerase/imiglucerase-treated GD1 patients from the International Collaborative Gaucher Group Gaucher Registry clinicaltrials.gov NCT00358943 were stratified by age at ERT initiation (<18, 18 to <50, ≥50 years), era of ERT initiation (1991-1995, 1996-2000, 2001-2005, 2006-2009), and splenectomy status pre-ERT. Prevalence of splenectomy decreased dramatically across the eras among all age groups. Bone manifestations were more prevalent in splenectomized patients than non-splenectomized patients in all age groups. Prevalence of bone manifestations differed across eras in certain age groups: non-splenectomized patients had a lower prevalence of ischemic bone events (pediatric patients) and bone crisis (pediatric patients and adults 18 to <50 years) in later eras; splenectomized adult (18 to <50 years) patients had a lower prevalence of ischemic bone events and bone crisis in later eras. Over two decades after the introduction of ERT, the prevalence of splenectomy and associated skeletal complications has declined dramatically. Concomitantly, the interval between diagnosis and initiation of ERT has decreased, most strikingly in pediatric patients who have the most severe disease. Together, these findings suggest that since the introduction of alglucerase/imiglucerase ERT, optimal standard of care has become established in the US to prevent destructive complications of GD1. © 2017 The Authors American Journal of Hematology Published by Wiley Periodicals, Inc.

  20. p.H1069Q mutation in ATP7B and biochemical parameters of copper metabolism and clinical manifestation of Wilson's disease.

    Science.gov (United States)

    Gromadzka, Graznya; Schmidt, Harmut H J; Genschel, Janine; Bochow, Bettina; Rodo, M; Tarnacka, Beatek; Litwin, Thomas; Chabik, Grzegorz; Członkowska, Anna

    2006-02-01

    We compared the effect of the p.H1069Q mutation and other non-p.H1069Q mutations in ATP7B on the phenotypic expression of Wilson's disease (WD), and assessed whether the clinical phenotype of WD in compound heterozygotes depends on the type of mutation coexisting with the p.H1069Q. One hundred forty-two patients with clinically, biochemically, and genetically diagnosed WD were studied. The mutational analysis of ATP7B was performed by direct sequencing. A total number of 26 mutations in ATP7B were identified. The p.His1069Gln was the most common mutation (allelic frequency: 72%). Seventy-three patients were homozygous for this mutation. Of compound heterozygotes, 37 had frameshift/nonsense mutation, and 20 had other missense mutation on one of their ATP7B alleles. Twelve patients had two non-p.H1069Q mutations. Patients homozygous for the p.H1069Q mutation had the less severe disturbances of copper metabolism and the latest presentation of first WD symptoms. The most severely disturbed copper metabolism and the earliest age at initial disease manifestation was noticed in non-p.H1069Q patients. In compound heterozygotes, the type of mutation coexisting with the p.H1069Q to a small extent influenced WD phenotype. The phenotype of WD varied considerably among patients with the same genotype. The p.H1069Q mutation is associated with late WD manifestation and with a mild disruption of copper metabolism. In compound heterozygotes, the phenotype of WD to a small extent depends on the type of mutation coexisting with the p.H1069Q. Besides genotype, additional modifying factors seem to determine WD manifestations. Copyright (c) 2005 Movement Disorder Society.

  1. Modeling cognition and disease using human glial chimeric mice

    DEFF Research Database (Denmark)

    Goldman, Steven A.; Nedergaard, Maiken; Windrem, Martha S.

    2015-01-01

    , oligodendrocytes as well. As a result, the recipient brains may become inexorably humanized with regards to their resident glial populations, yielding human glial chimeric mouse brains. These brains provide us a fundamentally new tool by which to assess the species-specific attributes of glia in modulating human...... for studying the human-specific contributions of glia to psychopathology, as well as to higher cognition. As such, the assessment of human glial chimeric mice may provide us new insight into the species-specific contributions of glia to human cognitive evolution, as well as to the pathogenesis of human...

  2. Immunologic manifestations of autophagy

    DEFF Research Database (Denmark)

    Deretic, Vojo; Kimura, Tomonori; Timmins, Graham

    2015-01-01

    The broad immunologic roles of autophagy span innate and adaptive immunity and are often manifested in inflammatory diseases. The immune effects of autophagy partially overlap with its roles in metabolism and cytoplasmic quality control but typically expand further afield to encompass unique...... immunologic adaptations. One of the best-appreciated manifestations of autophagy is protection against microbial invasion, but this is by no means limited to direct elimination of intracellular pathogens and includes a stratified array of nearly all principal immunologic processes. This Review summarizes...... the broad immunologic roles of autophagy. Furthermore, it uses the autophagic control of Mycobacterium tuberculosis as a paradigm to illustrate the breadth and complexity of the immune effects of autophagy....

  3. Significance of Haemodynamic and Haemostatic Factors in the Course of Different Manifestations of Cerebral Small Vessel Disease: The SHEF-CSVD Study—Study Rationale and Protocol

    Directory of Open Access Journals (Sweden)

    Jacek Staszewski

    2013-01-01

    Full Text Available Rationale. This paper describes the rationale and design of the SHEF-CSVD Study, which aims to determine the long-term clinical and radiological course of cerebral small vessel disease (CSVD and to evaluate haemostatic and haemodynamic prognostic factors of the condition. Design. This single-centre, prospective, non-interventional cohort study will follow 150 consecutive patients with different clinical manifestations of CSVD (lacunar ischaemic stroke, vascular dementia, vascular parkinsonism or spontaneous deep, intracerebral haemorrhage and 50 age- and sex-matched controls over a period of 24 months. The clinical and radiological course will be evaluated basing on a detailed neurological, neuropsychological and MRI examinations. Haemodynamic (cerebral vasoreactivity, 24 h blood pressure control and haemostatic factors (markers of endothelial and platelet dysfunction, brachial artery flow-mediated dilatation test will be determined. Discussion. The scheduled study will specifically address the issue of haemodynamic and haemostatic prognostic factors and their course over time in various clinical manifestations of CSVD. The findings may aid the development of prophylactic strategies and individualised treatment plans, which are critical during the early stages of the disease.

  4. Extraintestinal manifestations were common in children with coeliac disease and were more prevalent in patients with more severe clinical and histological presentation.

    Science.gov (United States)

    Nurminen, Samuli; Kivelä, Laura; Huhtala, Heini; Kaukinen, Katri; Kurppa, Kalle

    2018-03-22

    This study investigated the prevalence of extraintestinal manifestations (EIM) in paediatric coeliac disease and their associations with other disease features. Researchers at the University of Tampere, Finland, compared EIM in 511 children diagnosed with coeliac disease from 2003 to 2014 and 180 diagnosed with functional gastrointestinal disorders from 2007 to 2013. Disease severity and dietary responses were also compared between coeliac children diagnosed by screening (n = 146) or because of EIM (n = 116) or gastrointestinal symptoms (n = 249). Coeliac patients had more EIM (62%) than those with functional disorders (33%). The most common EIM in coeliac children were poor growth (27%) and anaemia (18%). Children with coeliac disease often showed fatigue (8%) and symptoms affecting the skin (15%), nervous system (9%) and joints (6%). Coeliac patients with EIM as their main clinical presentation had more severe symptoms and histological damage at diagnosis than those with gastrointestinal presentation and screen-detected cases. The subgroups did not differ with regard to other clinical and laboratory parameters and dietary adherence. Concomitant EIM were also common in children diagnosed because of gastrointestinal presentation (60%) and by screening (37%). EIM were common in coeliac disease and associated with more severe clinical and histological presentation. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  5. Manifestações extra-esofágicas da doença do refluxo gastroesofágico Extraesophageal manifestations of gastroesophageal reflux disease

    Directory of Open Access Journals (Sweden)

    Richard Ricachenevski Gurski

    2006-04-01

    Full Text Available A doença do refluxo gastroesofágico freqüentemente se apresenta com pirose e regurgitação, os chamados sintomas típicos. Porém, um subgrupo de pacientes apresenta um conjunto de sinais e sintomas que não estão relacionados diretamente ao dano esofágico. A esse conjunto dá-se o nome de manifestações extra-esofágicas da doença do refluxo gastroesofágico. Compreendem, principalmente, broncoespasmo, tosse crônica e alterações inflamatórias na laringe (chamados manifestações atípicas. Apesar de essas manifestações formarem um grupo heterogêneo, algumas considerações gerais englobam todos os subgrupos: embora a associação entre a doença do refluxo gastroesofágico e as manifestações extra-esofágicas esteja bem estabelecida, uma relação entre causa e efeito definitiva ainda não está elucidada; em relação à patogênese das manifestações extra-esofágicas, os principais mecanismos propostos são a injúria direta do tecido extra-esofágico pelo conteúdo ácido gástrico refluído e o reflexo esôfago-brônquico mediado pelo nervo vago; a doença do refluxo gastroesofágico pode não ser incluída no diagnóstico diferencial do grupo de pacientes que apresenta somente os sintomas atípicos. Este artigo revisa as manifestações extra-esofágicas da doença do refluxo gastroesofágico encontradas na literatura, discutindo a epidemiologia, patogênese, diagnóstico e tratamento, com foco nas apresentações mais estudadas e estabelecidas.Gastroesophageal reflux disease often presents as heartburn and acid reflux, the so-called "typical" symptoms. However, a subgroup of patients presents a collection of signs and symptoms that are not directly related to esophageal damage. These are known collectively as the extraesophageal manifestations of gastroesophageal reflux disease. Principal among such manifestations are bronchospasm, chronic cough and laryngitis, which are classified as atypical symptoms. These

  6. Telomere shortening reduces Alzheimer's disease amyloid pathology in mice

    NARCIS (Netherlands)

    Rolyan, Harshvardhan; Scheffold, Annika; Heinrich, Annette; Begus-Nahrmann, Yvonne; Langkopf, Britta Heike; Hoelter, Sabine M.; Vogt-Weisenhorn, Daniela M.; Liss, Birgit; Wurst, Wolfgang; Lie, Dieter Chichung; Thal, Dietmar Rudolf; Biber, Knut; Rudolph, Karl Lenhard

    Alzheimer's disease is a neurodegenerative disorder of the elderly and advancing age is the major risk factor for Alzheimer's disease development. Telomere shortening represents one of the molecular causes of ageing that limits the proliferative capacity of cells, including neural stem cells.

  7. Dental erosion, an extraesophageal manifestation of gastroesophageal reflux disease: the experience of a center for digestive physiology in Southeastern Mexico

    Directory of Open Access Journals (Sweden)

    Laura Roesch-Ramos

    2014-02-01

    Full Text Available Background: Dental erosion (DE is the loss of the hard tissues of the tooth produced by the action of gastric juice, pepsin and acid on the dental enamel, its frequency ranges from 5to 53.41%. In Mexico there are no reports on the frequency and possible association. Objective: To establish the prevalence of dental erosion and its relationship to GERD. Patients and methods: Prospective, observational, descriptive and comparative study was conducted in 60patients diagnosed with GERD and 60healthy patients at the Institute of Medical and Biological Research of the Universidad Veracruzana in Veracruz city. Anthropometric characteristics, dietary habits, oral hygiene, alcohol consumption, smoking, ED index and Index of decayed/missing dental pieces/sealed and correlation between severity of ED and GERD were analyzed. Results: 78.67% of patients with GERD had ED, 23.33% corresponded to grade 0, 41.67% to N1, N2and 23.33% to 11.67% to N3. Predominance of females (2.3:1. The mean age was 50.92± 13.52years. The severity of dental erosion was significantly related to the severity of reflux, halitosis, CPO index and poor eating habits. There was no statistically significant difference in the other variables analyzed. Conclusions: Dental erosion has a high frequency in patients with GERD and reflux characteristics are directly related to their severity and therefore should be considered as a manifestation of GERD extraesophageal.

  8. Dental erosion, an extraesophageal manifestation of gastroesophageal reflux disease. The experience of a center for digestive physiology in Southeastern Mexico.

    Science.gov (United States)

    Roesch-Ramos, Laura; Roesch-Dietlen, Federico; Remes-Troche, José María; Romero-Sierra, Graciela; Mata-Tovar, Carlos de Jesús; Azamar-Jácome, Amyra Ali; Barranca-Enríquez, Antonia

    2014-02-01

    Dental erosion (DE) is the loss of the hard tissues of the tooth produced by the action of gastric juice, pepsin and acid on the dental enamel, its frequency ranges from 5 to 53.41 %. In Mexico there are no reports on the frequency and possible association. To establish the prevalence of dental erosion and its relationship to GERD. Prospective, observational, descriptive and comparative study was conducted in 60 patients diagnosed with GERD and 60 healthy patients at the Institute of Medical and Biological Research of the Universidad Veracruzana in Veracruz city. Anthropometric characteristics, dietary habits, oral hygiene, alcohol consumption, smoking, ED index and Index of decayed/missing dental pieces/sealed and correlation between severity of ED and GERD were analyzed. 78.67 % of patients with GERD had ED, 23.33 % corresponded to grade 0, 41.67 % to N1, N2 and 23.33 % to 11.67 % to N3. Predominance of females (2,3:1). The mean age was 50.92 +/- 13.52 years. The severity of dental erosion was significantly related to the severity of reflux, halitosis, CPO index and poor eating habits. There was no statistically significant difference in the other variables analyzed. Dental erosion has a high frequency in patients with GERD and reflux characteristics are directly related to their severity and therefore should be considered as a manifestation of GERD extraesophageal.

  9. Sequential colonization of periodontal pathogens in induction of periodontal disease and atherosclerosis in LDLRnull mice.

    Science.gov (United States)

    Chukkapalli, Sasanka S; Easwaran, Meena; Rivera-Kweh, Mercedes F; Velsko, Irina M; Ambadapadi, Sriram; Dai, Jiayin; Larjava, Hannu; Lucas, Alexandra R; Kesavalu, Lakshmyya

    2017-01-01

    Periodontal disease (PD) and atherosclerotic vascular disease (ASVD) are both chronic inflammatory diseases with a polymicrobial etiology and have been epidemiologically associated. The purpose is to examine whether periodontal bacteria that infect the periodontium can also infect vascular tissues and enhance pre-existing early aortic atherosclerotic lesions in LDLRnull mice. Mice were orally infected with intermediate bacterial colonizer Fusobacterium nucleatum for the first 12 weeks followed by late bacterial colonizers (Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia) for the remaining 12 weeks mimicking the human oral microbiota ecological colonization. Genomic DNA from all four bacterial was detected in gingival plaque by PCR, consistently demonstrating infection of mouse gingival surfaces. Infected mice had significant levels of IgG and IgM antibodies, alveolar bone resorption, and showed apical migration of junctional epithelium revealing the induction of PD. These results support the ability of oral bacteria to cause PD in mice. Detection of bacterial genomic DNA in systemic organs indicates hematogenous dissemination from the gingival pockets. Bacterial infection did not alter serum lipid fractions or serum amyloid A levels and did not induce aortic atherosclerotic plaque. This is the first study examining the causal role of periodontal bacteria in induction of ASVD in LDLRnull mice. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Effect of Goiter Dispersion Formula on Serum Cytokines in Hyperthyroidism Patients with Neurologic Manifestations of Graves' Disease: A Randomized Trial on 80 Cases.

    Science.gov (United States)

    Tian, Wen-Hong; Wang, Ying; Yang, Rui; Hu, Hai-Bing

    2018-05-01

    This study is aimed to explore the combined use of goiter dispersion formula and antithyroid drugs in the treatment of patients with neurologic manifestations of Graves' disease by examining its modulating effects on patients' cytokines. A total of 80 patients with Graves' disease were randomly divided into treatment and control groups. Patients of the treatment group received goiter dispersion formula and antithyroid drugs (methimazole or propylthiouracil), whereas those of the control group received antithyroid drug alone. FT3, FT4, and TSH contents were detected by chemiluminescence immunoassay at pre- and post-treatment; interleukin (IL)-2, IL-8, and IL-17 serum levels before and after the treatment were detected by radioimmunoassay; thyroid B-mode ultrasound and liver and renal function tests were performed in all patients of both groups. An additional cohort of 40 healthy subjects was recruited for baseline measurement. All the enrolled patients completed the trial. The effective treatment rate was higher in the treatment group than in the control group, of which the difference was statistically significant (treatment group, 95%; control group, 75%, p Graves' disease comparing with those in healthy subjects (p Graves' disease by modulating IL-2, IL-8, and IL-17. The data supported the rationale for the use of goiter dispersion formula in Graves' disease treatment.

  11. Recent advances in knowledge regarding the head and neck manifestations of IgG4-related disease.

    Science.gov (United States)

    Takano, Kenichi; Yamamoto, Motohisa; Takahashi, Hiroki; Himi, Tetsuo

    2017-02-01

    IgG4-related disease (IgG4-RD) is a chronic inflammatory disorder, characterized by elevated serum IgG4 levels as well as abundant infiltration of IgG4-positive plasmacytes and fibrosis in various organs, including the head and neck region. In particular, the salivary glands, orbit, and thyroid are common sites of disease involvement. IgG4-RD is diagnosed based on various clinical, serological, and histopathological findings, none of which are pathognomonic. Hence, various differential diagnoses, which exhibit elevated serum IgG4 levels and infiltration of IgG4-postive cells into tissues, need to be excluded, especially malignant diseases and mimicking disorders. Systemic corticosteroids are generally effective in inducing IgG4-RD remission; however, recurrent or refractory cases are common. In addition, although the pathogenic mechanisms of IgG4-RD remain unclear, an antigen-driven inflammatory condition is believed to be involved. Recent studies have indicated the important pathogenic role of B cell/T cell collaboration and innate immunity in this disease. Nevertheless, additional research and discussions are needed to resolve many remaining questions. In this review, we provide an overview of the recent insights on the history, clinical features, diagnosis, and treatment of IgG4-RD in the head and neck region. Furthermore, we have also addressed the pathogenesis of this disease. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Mottled Mice and Non-Mammalian Models of Menkes Disease

    DEFF Research Database (Denmark)

    Lenartowicz, Małgorzata; Krzeptowski, Wojciech; Lipiński, Paweł

    2015-01-01

    Menkes disease is a multi-systemic copper metabolism disorder caused by mutations in the X-linked ATP7A gene and characterized by progressive neurodegeneration and severe connective tissue defects. The ATP7A protein is a copper (Cu)-transporting ATPase expressed in all tissues and plays a critica......-mammalian models of Menkes disease, Drosophila melanogaster and Danio rerio mutants were used in experiments which would be technically difficult to carry out in mammals....

  13. The role of T cell PPAR gamma in mice with experimental inflammatory bowel disease.

    Science.gov (United States)

    Guri, Amir J; Mohapatra, Saroj K; Horne, William T; Hontecillas, Raquel; Bassaganya-Riera, Josep

    2010-06-10

    Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor whose activation has been shown to modulate macrophage and T cell-mediated inflammation. The objective of this study was to investigate the mechanisms by which the deletion of PPAR gamma in T cells modulates immune cell distribution and colonic gene expression and the severity of experimental IBD. PPAR gamma flfl; CD4 Cre+ (CD4cre) or Cre- (WT) mice were challenged with 2.5% dextran sodium sulfate in their drinking water for 0, 2, or 7 days. Mice were scored on disease severity both clinically and histopathologically. Flow cytometry was used to assess lymphocyte and macrophage populations in the blood, spleen, and mesenteric lymph nodes (MLN). Global gene expression in colonic mucosa was profiled using Affymetrix microarrays. The deficiency of PPAR gamma in T cells accelerated the onset of disease and body weight loss. Examination of colon histopathology revealed significantly greater epithelial erosion, leukocyte infiltration, and mucosal thickening in the CD4cre mice on day 7. CD4cre mice had more CD8+ T cells than WT mice and fewer CD4+ FoxP3+ regulatory T cells (Treg) and IL10+ CD4+ T cells in blood and MLN, respectively. Transcriptomic profiling revealed around 3000 genes being transcriptionally altered as a result of DSS challenge in CD4cre mice. These included up-regulated mRNA expression of adhesion molecules, proinflammatory cytokines interleukin-6 (IL-6) and IL-1beta, and suppressor of cytokine signaling 3 (SOCS-3) on day 7. Gene set enrichment analysis (GSEA) showed that the ribosome and Krebs cycle pathways were downregulated while the apoptosis pathway was upregulated in colons of mice lacking PPAR gamma in T cells. The expression of PPAR gamma in T cells is involved in preventing gut inflammation by regulating colonic expression of adhesion molecules and inflammatory mediators at later stages of disease while favoring the recruitment of Treg to the mucosal inductive

  14. Effect of aging and Alzheimer's disease-like pathology on brain monoamines in mice.

    Science.gov (United States)

    Von Linstow, C U; Severino, M; Metaxas, A; Waider, J; Babcock, A A; Lesch, K P; Gramsbergen, J B; Finsen, B

    2017-09-01

    Aging is the greatest single risk factor of the neurodegenerative disorder Alzheimer's disease (AD). The monoaminergic system, including serotonin (5-HT), dopamine (DA) and noradrenaline (NA) modulates cognition, which is affected in AD. Changes in monoamine levels have been observed in AD, but these can both be age- and/or disease-related. We examined whether brain monoamine levels change as part of physiological aging and/or AD-like disease in APP SWE /PS1 ΔE9 (APP/PS1) transgenic mice. The neocortex, hippocampus, striatum, brainstem and cerebellum of 6-, 12-, 18- and 24-month-old B6C3 wild-type (WT) mice and of 18-month old APP/PS1 and WT mice were analysed for 5-HT, DA and NA contents by high pressure liquid chromatography (HPLC), along with neocortex from 14-month-old APP/PS1 and WT mice. While, we observed no aging effect in WT mice, we detected region-specific changes in the levels of all monoamines in 18-month-old transgenic compared with WT mice. This included reductions in 5-HT (-30%), DA (-47%) and NA (-32%) levels in the neocortex and increases of 5-HT in the brainstem (+18%). No changes were observed in any of the monoamines in the neocortex from 14-month-old APP/PS1 mice. In combination, these findings indicate that aging alone is not sufficient to affect brain monoamine levels, unlike the APP SWE /PS1 ΔE9 genotype. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. The effect of vitamin D on clinical manifestations and activity of Behçet’s disease

    Directory of Open Access Journals (Sweden)

    Nurşad Aslan

    2017-02-01

    Full Text Available Introduction: Immune mechanisms have been implemented to have a role in the pathogenesis of Behçet’s disease (BD and vitamin D has been shown to have a regulatory role in the immune system function. Aim: To evaluate the vitamin D levels of BD patients and its relationship between clinical findings and disease activity of BD. Material and methods: Sixty-eight patients with BD and 70 age- and sex-matched controls were examined retrospectively. Demographic features, vitamin D levels for both groups and clinical findings, disease activity, drug usage for BD patients were examined from their medical reports. Disease activity was calculated for each patient according to Krause’s BD activity assessment. Results: Mean vitamin D levels of patients and controls were 15.35 ±7.18 ng/ml and 18.44 ±5.79 ng/ml, respectively. Vitamin D levels were significantly lower in BD patients than in controls (p = 0.006. Mean vitamin D levels of active and inactive BD cases were 15.68 ±7.31 ng/ml and 15.08 ±7.17 ng/ml, respectively (p = 0.73. Disease activity of patients using and not using vitamin D was similar (p = 0.51. Conclusions : Significantly lower levels of vitamin D were observed in BD patients. Our results indicate that there is no correlation between BD activity and a vitamin D level. Together with these, vitamin D replacement treatment was found to have no effect on disease activity.

  16. Cross sectional PET study of cerebral adenosine A{sub 1} receptors in premanifest and manifest Huntington's disease

    Energy Technology Data Exchange (ETDEWEB)

    Matusch, Andreas; Elmenhorst, David [Institute of Neuroscience and Medicine (INM-2), Juelich (Germany); Saft, Carsten; Kraus, Peter H.; Gold, Ralf [St. Josef Hospital, Ruhr University Bochum, Department of Neurology, Huntington Centre NRW, Bochum (Germany); Hartung, Hans-Peter [Heinrich Heine University Duesseldorf, Department of Neurology, Medical Faculty, Duesseldorf (Germany); Bauer, Andreas [Institute of Neuroscience and Medicine (INM-2), Juelich (Germany); Heinrich Heine University Duesseldorf, Department of Neurology, Medical Faculty, Duesseldorf (Germany)

    2014-06-15

    To study cerebral adenosine receptors (AR) in premanifest and manifest stages of Huntington's disease (HD). We quantified the cerebral binding potential (BP{sub ND}) of the A{sub 1}AR in carriers of the HD CAG trinucleotide repeat expansion using the radioligand [{sup 18} F]CPFPX and PET. Four groups were investigated: (i) premanifest individuals far (preHD-A; n = 7) or (ii) near (preHD-B; n = 6) to the predicted symptom onset, (iii) manifest HD patients (n = 8), and (iv) controls (n = 36). Cerebral A{sub 1}AR values of preHD-A subjects were generally higher than those of controls (by up to 31 %, p <.01, in the thalamus on average). Across stages a successive reduction of A{sub 1}AR BP{sub ND} was observed to the levels of controls in preHD-B and undercutting controls in manifest HD by down to 25 %, p <.01, in the caudatus and amygdala. There was a strong correlation between A{sub 1}AR BP{sub ND} and years to onset. Before onset of HD, the assumed annual rates of change of A{sub 1}AR density were -1.2 % in the caudatus, -1.7 % in the thalamus and -3.4 % in the amygdala, while the corresponding volume losses amounted to 0.6 %, 0.1 % and 0.2 %, respectively. Adenosine receptors switch from supra to subnormal levels during phenoconversion of HD. This differential regulation may play a role in the pathophysiology of altered energy metabolism. (orig.)

  17. Atypical scrapie prions from sheep and lack of disease in transgenic mice overexpressing human prion protein.

    Science.gov (United States)

    Wadsworth, Jonathan D F; Joiner, Susan; Linehan, Jacqueline M; Balkema-Buschmann, Anne; Spiropoulos, John; Simmons, Marion M; Griffiths, Peter C; Groschup, Martin H; Hope, James; Brandner, Sebastian; Asante, Emmanuel A; Collinge, John

    2013-11-01

    Public and animal health controls to limit human exposure to animal prions are focused on bovine spongiform encephalopathy (BSE), but other prion strains in ruminants may also have zoonotic potential. One example is atypical/Nor98 scrapie, which evaded statutory diagnostic methods worldwide until the early 2000s. To investigate whether sheep infected with scrapie prions could be another source of infection, we inoculated transgenic mice that overexpressed human prion protein with brain tissue from sheep with natural field cases of classical and atypical scrapie, sheep with experimental BSE, and cattle with BSE. We found that these mice were susceptible to BSE prions, but disease did not develop after prolonged postinoculation periods when mice were inoculated with classical or atypical scrapie prions. These data are consistent with the conclusion that prion disease is less likely to develop in humans after exposure to naturally occurring prions of sheep than after exposure to epizootic BSE prions of ruminants.

  18. [Pulmonary Manifestations of Vasculitis].

    Science.gov (United States)

    von Vietinghoff, S

    2016-11-01

    The variable symptoms and signs of pulmonary vasculitis are a diagnostic and therapeutic challenge. Vasculitis should be considered in rapidly progressing, severe and unusual manifestations of pulmonary disease. Clinical examination of other organ systems typically affected by vasculitis such as skin and kidney and autoantibody measurements are complementary approaches to manage this situation. Pulmonary involvement is common in small vessel vasculitis including anti-GBM disease (Goodpasture syndrome) and the ANCA-associated vasculitides. Life threatening pulmonary hemorrhage and irreversible damage of other organs, frequently the kidney, are important complications necessitating rapid diagnosis of these conditions.Vasculitides are rare diseases of multiple organs and therapies including biologics are evolving rapidly, requiring cooperation of specialities and with specialized centres to achieve best patient care. All involved physicians should be aware of typical complications of immunosuppressive therapy. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Mastoiditis and facial paralysis as initial manifestations of temporal bone systemic diseases - the significance of the histopathological examination.

    Science.gov (United States)

    Maniu, Alma Aurelia; Harabagiu, Oana; Damian, Laura Otilia; Ştefănescu, Eugen HoraŢiu; FănuŢă, Bogdan Marius; Cătană, Andreea; Mogoantă, Carmen Aurelia

    2016-01-01

    Several systemic diseases, including granulomatous and infectious processes, tumors, bone disorders, collagen-vascular and other autoimmune diseases may involve the middle ear and temporal bone. These diseases are difficult to diagnose when symptoms mimic acute otomastoiditis. The present report describes our experience with three such cases initially misdiagnosed. Their predominating symptoms were otological with mastoiditis, hearing loss, and subsequently facial nerve palsy. The cases were considered an emergency and the patients underwent tympanomastoidectomy, under the suspicion of otitis media with cholesteatoma, in order to remove a possible abscess and to decompress the facial nerve. The common features were the presence of severe granulation tissue filling the mastoid cavity and middle ear during surgery, without cholesteatoma. The definitive diagnoses was made by means of biopsy of the granulation tissue from the middle ear, revealing granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) in one case, middle ear tuberculosis and diffuse large B-cell lymphoma respectively. After specific associated therapy facial nerve functions improved, and atypical inflammatory states of the ear resolved. As a group, systemic diseases of the middle ear and temporal bone are uncommon, but aggressive lesions. After analyzing these cases and reviewing the literature, we would like to stress upon the importance of microscopic examination of the affected tissue, required for an accurate diagnosis and effective treatment.

  20. Glutamate-system defects behind psychiatric manifestations in a familial hemiplegic migraine type 2 disease-mutation mouse model

    DEFF Research Database (Denmark)

    Bøttger, Pernille; Pedersen, Simon Glerup; Gesslein, Bodil

    2016-01-01

    Migraine is a complex brain disorder, and understanding the complexity of this prevalent disease could improve quality of life for millions of people. Familial Hemiplegic Migraine type 2 (FHM2) is a subtype of migraine with aura and co-morbidities like epilepsy/seizures, cognitive impairments...

  1. Manifestation of Non-Alcoholic Fatty Liver Disease/Non-Alcoholic Steatohepatitis in Different Dietary Mouse Models

    Directory of Open Access Journals (Sweden)

    Vera HI Fengler

    2016-05-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD and non-alcoholic steatohepatitis (NASH, which are usually associated with obesity and metabolic syndrome, are considerable health and economic issues due to the rapid increase of their prevalence in Western society. Histologically, the diseases are characterised by steatosis, hepatic inflammation, and if further progressed, fibrosis. Dietary-induced mouse models are widely used in investigations of the development and progression of NAFLD and NASH; these models attempt to mimic the histological and metabolic features of the human diseases. However, the majority of dietary mouse models fail to reflect the whole pathophysiological spectrum of NAFLD and NASH. Some models exhibit histological features similar to those seen in humans while lacking the metabolic context, while others resemble the metabolic conditions leading to NAFLD in humans but fail to mimic the whole histological spectrum, including progression from steatosis to liver fibrosis, and thus fail to mimic NASH. This review summarises the advantages and disadvantages of the different dietary-induced mouse models of NAFLD and NASH, with a focus on the genetic background of several commonly used wild-type mouse strains as well as gender and age, which influence the development and progression of these liver diseases.

  2. Atypical Manifestations of Hyperthyroidism

    Science.gov (United States)

    Boxall, E. A.; Lauener, R. W.; McIntosh, H. W.

    1964-01-01

    Patients with hyperthyroidism usually present with symptoms of hypermetabolism with or without goitre and/or eye signs. Occasionally, however, the chief complaints are not immediately suggestive of hyperthyroidism. Patients with hyperthyroidism are described who presented with such atypical manifestations as periodic muscular paralysis, myasthenia, myopathy, encephalopathy, psychosis, angina pectoris, atrial fibrillation, heart failure without underlying heart disease, skeletal demineralization, pretibial myxedema, unilateral eye signs, and pitting edema of the ankles. ImagesFig. 2Fig. 3Fig. 5Fig. 7Fig. 8Fig. 9Fig. 10 PMID:14178405

  3. Effect of early-life gut mucosal compromise on disease progression in NOD mice

    DEFF Research Database (Denmark)

    Bendtsen, Katja M.; Hansen, Camilla HF; Krych, Lukasz

    2017-01-01

    Disease expression in spontaneous nonobese diabetic (NOD) mice depends on environmental stimuli such as stress, diet, and gut microbiota composition. We evaluated a brief, early-life gut intervention in which pups were weaned to low-dose dextran sulfate sodium (DSS). We hypothesized that the mucus...

  4. Reduction of Dacarbazine cytogenetic effects on somatic cells in male mice using bee glue (Propolis) to manifest the scientific miracles in the Quran.

    Science.gov (United States)

    Kurdi, Lina Abdul-Fattah; Aljeddani, Fatimah Aliyan

    2016-09-01

    This study was carried out to investigate the ability of Propolis to ameliorate the adverse cytogenetic effects of Dacarbazine on bone marrow cells. In this experimental in vivo study, 18 mice were used, divided into four groups: control group; Propolis-treated group (treated with 50mg/kg Propolis); and Dacarbazine-treated group (treated with 3.5mg/kg Dacarbazine). The fourth, fifth, and sixth were treated with Dacarbazine and Propolis as pre 2h, post 2h, and concomitant treatment. After five days, the Bone Marrow (BM) samples were obtained for cytogenetic investigation. The in vivo studies revealed that Dacarbazine induced an abnormalities in polychromatic erythrocytes cells (PECs) as increase of cell with micronuclei, while the dual treatment accompanied with improvement of this abnormalities. It could be concluded that there are protective effects of Propolis against the adverse effects of Dacarbazine. It could be recommended to use Propolis as an adjuvant with chemotherapeutic agents.

  5. Physical Activity and Characteristics of the Carotid Artery Wall in High-Risk Patients-The SMART (Second Manifestations of Arterial Disease) Study.

    Science.gov (United States)

    Boss, H Myrthe; van der Graaf, Yolanda; Visseren, Frank L J; Van den Berg-Vos, Renske M; Bots, Michiel L; de Borst, Gert Jan; Cramer, Maarten J; Kappelle, L Jaap; Geerlings, Mirjam I

    2017-07-23

    Physical activity reduces the risk of vascular disease. This benefit is not entirely explained through an effect on vascular risk factors. We examined the relationship of physical activity and characteristics of the carotid artery wall in patients with vascular disease or risk factors. Cross-sectional analyses were performed in 9578 patients from the SMART (Second Manifestations of Arterial Disease) study, a prospective cohort study among patients with vascular disease or risk factors. Physical activity was assessed using questionnaires. Carotid intima-media thickness and carotid artery stenosis of both common carotid arteries was measured. In a subset of 3165 participants carotid diastolic diameter and distension were assessed. Carotid stiffness was expressed as the distensibility coefficient and Young's elastic modulus. Regression analyses adjusted for vascular risk factors showed that physical activity was inversely associated with diastolic diameter (fifth versus first quintile B=-0.13 mm; 95% CI, -0.21 to -0.05) and decreased risk of carotid artery stenosis (relative risk, 0.58; 95% CI, 0.48-0.69). A light level of physical activity was associated with less carotid stiffness (second versus first quintile; Young's elastic modulus B=-0.11 kPa -1 ×10 -3 ; 95% CI, -0.16 to -0.06; distensibility coefficient B=0.93 kPa×10 3 ; 95% CI, 0.34-1.51), but there was no additional benefit with increasing levels of physical activity. In patients with vascular disease, physical activity was inversely associated with common carotid intima-media thickness, but not in patients with vascular risk factors. In patients with vascular disease or risk factors, increased physical activity was associated with smaller carotid diastolic diameter, decreased risk of carotid artery stenosis, and less carotid stiffness, but it only showed benefits on carotid intima-media thickness in patients with vascular disease. © 2017 The Authors. Published on behalf of the American Heart

  6. Both anti-TNF and CTLA4 Ig treatments attenuate the disease severity of staphylococcal dermatitis in mice.

    Directory of Open Access Journals (Sweden)

    Manli Na

    Full Text Available RA patients being treated with biologics are known to have an increased risk of infections. We recently demonstrated that both CTLA4 Ig and anti-TNF treatment aggravate systemic Staphylococcus aureus (S. aureus infection in mice, but with distinct clinical manifestations. However, the effects of CTLA4 Ig and anti-TNF treatments on a local S. aureus infection (e.g., skin infection might differ from their effects on a systemic infection.The aim of this study was to examine the differential effects of anti-TNF versus CTLA4 Ig treatment on S. aureus skin infections in mice.Abatacept (CTLA4 Ig, etanercept (anti-TNF treatment or PBS was given to NMRI mice subcutaneously inoculated with S. aureus strain SH1000. The clinical signs of dermatitis, along with histopathological changes due to skin infection, were compared between the groups.Both CTLA4 Ig and anti-TNF treatment resulted in less severe skin infections and smaller post-infectious hyperpigmentation compared with controls. Consistent with the clinical signs of dermatitis, smaller lesion size, more epithelial hyperplasia and more granulation were found in skin biopsies from mice receiving anti-TNF compared with PBS controls. However, both CTLA4 Ig and anti-TNF therapy tended to prolong the healing time, although this finding was not statistically significant. Serum MCP-1 levels were elevated in the anti-TNF group relative to the CTLA4 Ig and PBS groups, whereas IL-6 levels were higher in PBS controls than in the other two groups. Both anti-TNF and CTLA4 Ig treatments tended to down-regulate the necrosis/apoptosis ratio in the locally infected skin tissue. Importantly, no tangible difference was found in the bacterial burden among groups.Both CTLA4 Ig and anti-TNF therapies attenuate disease severity but may prolong the healing time required for S. aureus skin infections. Neither treatment has an impact on bacterial clearance in skin tissues.

  7. Immunoglobulin G4-related sclerosing disease manifesting as bilateral tonsillar hypertrophy on MRI images: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Mee Hyun; Woo, Ji Young; Lee, Yul; Yoon, Dae Young; Hong, Hye Sook; Hong, Min Eui [Hallym University College of Medicine, Kangnam Sacred Heart Hospital, Seoul (Korea, Republic of)

    2016-02-15

    Immunoglobulin G4-related sclerosing disease (IgG4-SD) is currently recognized as a distinct systemic disease involving various organs. We reported the imaging findings of a case of pathologically confirmed IgG4-SD involving bilateral palatine tonsils. CT and MRI showed diffuse enlargement of both palatine tonsils with homogeneous contrast enhancement. Focal contour bulging was noted in the right palatine tonsil. Lesions appeared as isointense on T1-weighted and slightly hyperintense on T2-weighted MRI images, as compared with muscle. The T2-weighted MRI image showed a striated pattern in both tonsils. Despite its rare occurrence, IgG4-SD should be included in the differential diagnoses of patients with symptomatic bilateral tonsillar hypertrophy that is non-responsive to medication.

  8. Immunoglobulin G4-related sclerosing disease manifesting as bilateral tonsillar hypertrophy on MRI images: A case report

    International Nuclear Information System (INIS)

    Park, Mee Hyun; Woo, Ji Young; Lee, Yul; Yoon, Dae Young; Hong, Hye Sook; Hong, Min Eui

    2016-01-01

    Immunoglobulin G4-related sclerosing disease (IgG4-SD) is currently recognized as a distinct systemic disease involving various organs. We reported the imaging findings of a case of pathologically confirmed IgG4-SD involving bilateral palatine tonsils. CT and MRI showed diffuse enlargement of both palatine tonsils with homogeneous contrast enhancement. Focal contour bulging was noted in the right palatine tonsil. Lesions appeared as isointense on T1-weighted and slightly hyperintense on T2-weighted MRI images, as compared with muscle. The T2-weighted MRI image showed a striated pattern in both tonsils. Despite its rare occurrence, IgG4-SD should be included in the differential diagnoses of patients with symptomatic bilateral tonsillar hypertrophy that is non-responsive to medication

  9. Graves' Disease as a Manifestation of Immune Reconstitution in HIV-Infected Individuals after Initiation of Highly Active Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Samad Rasul

    2011-01-01

    Full Text Available Graves' disease after the initiation of highly active antiretroviral therapy (HAART in certain HIV-1-infected individuals has been described as an immune reconstitution inflammatory syndrome (IRIS. This phenomenon should be suspected in individuals who present with clinical deterioration and a presentation suggestive of hyperthyroidism despite good virological and immunological response to HAART. Signs and symptoms of hyperthyroidism may be discrete or overt and typically develop 8–33 months after initiating therapy. One to two percent of HIV-infected patients can present with overt thyroid disease. Relatively few cases of Graves' IRIS have been reported in the literature to date. We describe four cases of Graves' IRIS in HIV-infected patients who were started on HAART therapy.

  10. Paget's disease of jaw bones as primary manifestation: A case report of a proper diagnosis made by general dentist.

    Science.gov (United States)

    Campolongo, Martin G; Cabras, Marco; Bava, Luca; Arduino, Paolo G; Carbone, Mario

    2018-06-01

    To present a case of early diagnosis mandibular Paget's disease of bone (PDB), recognised by a general dentist. PDB is responsible of rapid bone resorption and disorganised bone formation. The patient was a 72-year-old female patient complaining of dental malposition and blatant prognathism. Clinicians should consider PDB in differential diagnosis for an elderly patient undergoing unexplained alteration in face profile and occlusion. © 2018 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

  11. Cognitive abilities of Alzheimer's disease transgenic mice are modulated by social context and circadian rhythm.

    Science.gov (United States)

    Kiryk, Anna; Mochol, Gabriela; Filipkowski, Robert K; Wawrzyniak, Marcin; Lioudyno, Victoria; Knapska, Ewelina; Gorkiewicz, Tomasz; Balcerzyk, Marcin; Leski, Szymon; Leuven, Fred Van; Lipp, Hans-Peter; Wojcik, Daniel K; Kaczmarek, Leszek

    2011-12-01

    In the present study, we used a new training paradigm in the intelliCage automatic behavioral assessment system to investigate cognitive functions of the transgenic mice harboring London mutation of the human amyloid precursor protein (APP.V717I). Three groups of animals: 5-, 12- and 18-24-month old were subjected to both Water Maze training and the IntelliCage-based appetitive conditioning. The spatial memory deficit was observed in all three groups of transgenic mice in both behavioral paradigms. However, the APP mice were capable to learn normally when co-housed with the wild-type (WT) littermates, in contrast to clearly impaired learning observed when the transgenic mice were housed alone. Furthermore, in the transgenic mice kept in the Intellicage alone, the cognitive deficit of the young animals was modulated by the circadian rhythm, namely was prominent only during the active phase of the day. The novel approach to study the transgenic mice cognitive abilities presented in this paper offers new insight into cognitive dysfunctions of the Alzheimer's disease mouse model.

  12. Cold hypersensitivity increases with age in mice with sickle cell disease

    Science.gov (United States)

    Zappia, Katherine J.; Garrison, Sheldon R.; Hillery, Cheryl A.; Stucky, Cheryl L.

    2014-01-01

    Sickle cell disease (SCD) is associated with acute vaso-occlusive crises that trigger painful episodes and frequently involves ongoing, chronic pain. Additionally, both humans and mice with SCD experience heighted cold sensitivity. However, studies have not addressed the mechanism(s) underlying the cold sensitization, nor its progression with age. Here we measured thermotaxis behavior in young and aged mice with severe SCD. Sickle mice had a marked increase in cold sensitivity measured by a cold preference test. Further, cold hypersensitivity worsened with advanced age. We assessed whether enhanced peripheral input contributes to the chronic cold pain behavior by recording from C fibers, many of which are cold-sensitive, in skin-nerve preparations. We observed that C fibers from sickle mice displayed a shift to warmer (more sensitive) cold-detection thresholds. To address mechanisms underlying the cold sensitization in primary afferent neurons, we quantified mRNA expression levels for ion channels thought to be involved in cold detection. These included the Transient Receptor Potential Melastatin 8 (Trpm8) and TRP Ankyrin 1 (Trpa1) channels, as well as the two-pore domain potassium channels, TREK-1 (Kcnk2), TREK-2 (Kcnk4), and TRAAK (Kcnk10). Surprisingly, transcript expression levels of all of these channels were comparable between sickle and control mice. We further examined transcript expression of 83 additional pain-related genes and found increased mRNA levels for endothelin 1 and tachykinin receptor 1. These factors may contribute to hypersensitivity in sickle mice at both the afferent and behavioral levels. Sensory neurons from sickle cell disease mice are sensitized to cold, mirroring behavioral observations, and have increased expression of endothelin 1 and tachykinin receptor 1. PMID:24953902

  13. Optogenetic stimulation of dentate gyrus engrams restores memory in Alzheimer's disease mice.

    Science.gov (United States)

    Perusini, Jennifer N; Cajigas, Stephanie A; Cohensedgh, Omid; Lim, Sean C; Pavlova, Ina P; Donaldson, Zoe R; Denny, Christine A

    2017-10-01

    Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques and tau neurofibrillary tangles. APPswe/PS1dE9 (APP/PS1) mice have been developed as an AD model and are characterized by plaque formation at 4-6 months of age. Here, we sought to better understand AD-related cognitive decline by characterizing various types of memory. In order to better understand how memory declines with AD, APP/PS1 mice were bred with ArcCreER T2 mice. In this line, neural ensembles activated during memory encoding can be indelibly tagged and directly compared with neural ensembles activated during memory retrieval (i.e., memory traces/engrams). We first administered a battery of tests examining depressive- and anxiety-like behaviors, as well as spatial, social, and cognitive memory to APP/PS1 × ArcCreER T2 × channelrhodopsin (ChR2)-enhanced yellow fluorescent protein (EYFP) mice. Dentate gyrus (DG) neural ensembles were then optogenetically stimulated in these mice to improve memory impairment. AD mice had the most extensive differences in fear memory, as assessed by contextual fear conditioning (CFC), which was accompanied by impaired DG memory traces. Optogenetic stimulation of DG neural ensembles representing a CFC memory increased memory retrieval in the appropriate context in AD mice when compared with control (Ctrl) mice. Moreover, optogenetic stimulation facilitated reactivation of the neural ensembles that were previously activated during memory encoding. These data suggest that activating previously learned DG memory traces can rescue cognitive impairments and point to DG manipulation as a potential target to treat memory loss commonly seen in AD. © 2017 Wiley Periodicals, Inc.

  14. Facial manifestations of Epstein-Barr virus-related lymphoproliferative disease in childhood acute lymphoblastic leukemia in remission: Two atypical presentations.

    Science.gov (United States)

    Lu, Benjamin Y; Kojima, Lisa; Huang, Mary S; Friedmann, Alison M; Ferry, Judith A; Weinstein, Howard J

    2016-11-01

    Epstein-Barr virus-related lymphoproliferative disease (EBV-LPD) rarely occurs in patients with acute lymphoblastic leukemia (ALL), who have not received hematopoietic transplantation. We describe EBV-LPD manifesting as facial lesions in two children with ALL in remission. One patient was a 16-year-old male with T-cell ALL with an EBV-positive angiocentric polymorphous lip lesion presenting as right-sided facial swelling. The other patient was a 12-year-old male with B-cell ALL with an EBV-positive polymorphous lymphoplasmacytic infiltrate presenting as bilateral dacryoadenitis. Neither patient had known primary immunodeficiencies. Both cases improved with immunosuppressant de-escalation. These cases suggest that immunosuppression induced by maintenance chemotherapy is sufficient to promote EBV-LPD. © 2016 Wiley Periodicals, Inc.

  15. Oral Manifestations of Tropical Infectious Diseases of Central and South America. Part II. Bacterial and Mycotic Infections.

    Science.gov (United States)

    1979-05-24

    resemble pulmonary tuberculosis , in which 8% of the patients develop ora l or pha ryngea l lesions. In patients with disseminated paracocc idioido...ions , par t icularl y Mexico , Panama , and northern South America .1 The disease occurs most fre- quentl y before the age of ten years and is rare...30-50 years of age.7’’8 Infect i on most comon l y occurs through inhalation of spores resulting in a pulmonary infection which may or may not become

  16. Interdependence of physical inactivity, loss of muscle mass and low dietary intake: Extrapulmonary manifestations in older chronic obstructive pulmonary disease patients.

    Science.gov (United States)

    Yoshimura, Kazuya; Sato, Susumu; Muro, Shigeo; Yamada, Minoru; Hasegawa, Koichi; Kiyokawa, Hirofumi; Mishima, Michiaki; Aoyama, Tomoki

    2018-01-01

    Extrapulmonary manifestations, such as reductions in skeletal muscle and physical inactivity, are important clinical features of patients with chronic obstructive pulmonary disease (COPD), and might depend on the severity of COPD. As it is still unclear whether the relationship between muscle loss and physical inactivity is dominated by a disease-specific relationship or caused by patient factors, including physiological aging, we aimed to investigate the pulmonary or extrapulmonary factors associated with physical inactivity among older COPD patients. A total of 38 older male COPD patients (aged ≥65 years) were enrolled, and were evaluated cross-sectionally. Skeletal muscle mass was measured using bioelectrical impedance, and physical activity and energy intake were recorded for 2 weeks using a pedometer and diary. Daily step counts were successfully evaluated in 28 participants (mean forced expiratory volume in 1 s [%predicted; %FEV 1 ]; 49.5%), and ranged widely. The mean step counts was 5166 steps/day, and found to have a significant relationship with dyspnea (r = -0.46), diffusing capacity (r = 0.47), %FEV1 (r = 0.44), skeletal muscle index (r = 0.59) and total dietary intake (r = 0.47), but not with age (P = 0.14). A stepwise multivariate analysis showed that the skeletal muscle index (β = 0.50) and total dietary intake (β = 0.35) were significant determinants of the daily step count (R 2 = 0.46, p physical activity, skeletal muscle mass and dietary intake are more closely correlated with physical activity in COPD patients. Because physical inactivity might be the strongest predictor of prognosis, the present results suggest that a comprehensive treatment strategy must be considered for older COPD patients to improve their extrapulmonary manifestations and pulmonary dysfunction. Geriatr Gerontol Int 2018; 18: 88-94. © 2017 Japan Geriatrics Society.

  17. The lemon balm extract ALS-L1023 inhibits obesity and nonalcoholic fatty liver disease in female ovariectomized mice.

    Science.gov (United States)

    Kim, Jeongjun; Lee, Hyunghee; Lim, Jonghoon; Lee, Haerim; Yoon, Seolah; Shin, Soon Shik; Yoon, Michung

    2017-08-01

    Increasing evidence indicates that angiogenesis inhibitors regulate obesity. This study aimed to determine whether the lemon balm extract ALS-L1023 inhibits diet-induced obesity and nonalcoholic fatty liver disease (NAFLD) in female ovariectomized (OVX) mice. OVX mice received a low fat diet (LFD), a high fat diet (HFD) or HFD supplemented with ALS-L1023 (ALS-L1023) for 15 weeks. HFD mice exhibited increases in visceral adipose tissue (VAT) angiogenesis, body weight, VAT mass and VAT inflammation compared with LFD mice. In contrast, all of these effects were reduced in ALS-L1023 mice compared with HFD mice. Serum lipids and liver injury markers were improved in ALS-L1023 mice. Hepatic lipid accumulation, inflammatory cells and collagen levels were lower in ALS-L1023 mice than in HFD mice. ALS-L1023 mice exhibited a tendency to normalize hepatic expression of genes involved in lipid metabolism, inflammation and fibrosis to levels in LFD mice. ALS-L1023 also induced Akt phosphorylation and increased Nrf2 mRNA expression in livers of obese mice. Our results indicate that the angiogenesis inhibitor ALS-L1023 can regulate obesity, hepatic steatosis and fibro-inflammation, in part through improvement of VAT function, in obese OVX mice. These findings suggest that angiogenesis inhibitors may contribute to alleviation of NAFLD in post-menopausal women with obesity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Disruption of bbe02 by Insertion of a Luciferase Gene Increases Transformation Efficiency of Borrelia burgdorferi and Allows Live Imaging in Lyme Disease Susceptible C3H Mice.

    Directory of Open Access Journals (Sweden)

    Kamfai Chan

    Full Text Available Lyme disease is the most prevalent tick-borne disease in North America and Europe. The causative agent, Borrelia burgdorferi persists in the white-footed mouse. Infection with B. burgdorferi can cause acute to persistent multisystemic Lyme disease in humans. Some disease manifestations are also exhibited in the mouse model of Lyme disease. Genetic manipulation of B. burgdorferi remains difficult. First, B. burgdorferi contains a large number of endogenous plasmids with unique sequences encoding unknown functions. The presence of these plasmids needs to be confirmed after each genetic manipulation. Second, the restriction modification defense systems, including that encoded by bbe02 gene lead to low transformation efficiency in B. burgdorferi. Therefore, studying the molecular basis of Lyme pathogenesis is a challenge. Furthermore, investigation of the role of a specific B. burgdorferi protein throughout infection requires a large number of mice, making it labor intensive and expensive. To overcome the problems associated with low transformation efficiency and to reduce the number of mice needed for experiments, we disrupted the bbe02 gene of a highly infectious and pathogenic B. burgdorferi strain, N40 D10/E9 through insertion of a firefly luciferase gene. The bbe02 mutant shows higher transformation efficiency and maintains luciferase activity throughout infection as detected by live imaging of mice. Infectivity and pathogenesis of this mutant were comparable to the wild-type N40 strain. This mutant will serve as an ideal parental strain to examine the roles of various B. burgdorferi proteins in Lyme pathogenesis in the mouse model in the future.

  19. Immune dysregulation may contribute to disease pathogenesis in spinal muscular atrophy mice.

    Science.gov (United States)

    Deguise, Marc-Olivier; De Repentigny, Yves; McFall, Emily; Auclair, Nicole; Sad, Subash; Kothary, Rashmi

    2017-02-15

    Spinal muscular atrophy (SMA) has long been solely considered a neurodegenerative disorder. However, recent work has highlighted defects in many other cell types that could contribute to disease aetiology. Interestingly, the immune system has never been extensively studied in SMA. Defects in lymphoid organs could exacerbate disease progression by neuroinflammation or immunodeficiency. Smn depletion led to severe alterations in the thymus and spleen of two different mouse models of SMA. The spleen from Smn depleted mice was dramatically smaller at a very young age and its histological architecture was marked by mislocalization of immune cells in the Smn2B/- model mice. In comparison, the thymus was relatively spared in gross morphology but showed many histological alterations including cortex thinning in both mouse models at symptomatic ages. Thymocyte development was also impaired as evidenced by abnormal population frequencies in the Smn2B/- thymus. Cytokine profiling revealed major changes in different tissues of both mouse models. Consistent with our observations, we found that survival motor neuron (Smn) protein levels were relatively high in lymphoid organs compared to skeletal muscle and spinal cord during postnatal development in wild type mice. Genetic introduction of one copy of the human SMN2 transgene was enough to rescue splenic and thymic defects in Smn2B/- mice. Thus, Smn is required for the normal development of lymphoid organs, and altered immune function may contribute to SMA disease pathogenesis. © The Author 2017. Published by Oxford University Press.

  20. Manifestações esqueléticas da doença de gaucher Skeletal manifestations in Gaucher's disease

    Directory of Open Access Journals (Sweden)

    Vinicius França de Mendonça

    2001-06-01

    Full Text Available A doença de Gaucher é manifestação genética causada pela deficiência da enzima glicocerebrosidase, resultando no acúmulo secundário de glicocerebrosídeos nos órgãos do sistema reticuloendotelial. Apresenta-se sob três formas clínicas distintas, podendo ser rapidamente fatal ou crônica com poucos sintomas. O presente trabalho tem o objetivo de analisar os achados da radiografia simples do esqueleto em 32 pacientes comprovadamente portadores da doença, de ambos os sexos e em diferentes faixas etárias. Foram observadas as seguintes alterações: osteopenia difusa em todos os casos, deformidade em "frasco de Erlenmeyer" em 93,7%, alterações articulares em 40,6%, necrose da cabeça do fêmur e lesões líticas em 28,1%, respectivamente, fratura patológica em 9,3% e necrose da cabeça do úmero em 6,2% dos casos. Estes resultados encontram-se de acordo com as descrições da literatura, demonstrando a importância da radiologia convencional como método complementar no diagnóstico desta enfermidade.Gaucher's disease has a genetic background and is characterized by the deficiency of enzyme glucocerebrosidase, resulting in secondary accumulation of glucocerebrosides in the reticuloendothelial organs. The objective of the present study is to evaluate the x-ray findings in the skeleton of a group of 32 male and female patients of different ages, with biochemical diagnosis of Gaucher's disease. The following bone lesions were observed: diffuse osteopenia (100% of the patients, "Erlenmeyer flask" deformities (93.7% of the patients, abnormalities of the joints (40.6% of the patients, necrosis of the femoral head (28.1% of the patients, lytic lesions (28.1% of the patients, pathological fractures (9.3% of the patients and necrosis of the humeral head (6.2% of the patients. These results are concordant with the literature, and demonstrate the importance of conventional x-ray as a complementary method in the diagnosis of Gaucher's disease.

  1. Vitamin D status in rheumatoid arthritis patients: relation to clinical manifestations, disease activity, quality of life and fibromyalgia syndrome.

    Science.gov (United States)

    Gheita, Tamer A; Sayed, Safaa; Gheita, Heba A; Kenawy, Sanaa A

    2016-03-01

    To assess vitamin D levels in rheumatoid arthritis (RA) patients and to find their relation to clinical parameters, fibromyalgia syndrome (FMS), quality of life (QoL) and disease activity. The study included 63 RA patients and 62 controls. Clinical examination and laboratory investigations were performed. For patients, the Disease Activity Score (DAS-28), QoL index, Health Assessment Questionnaire II (HAQ II) and Modified Larsen score were calculated. 25-OH-vitamin D was measured in patients and controls. The patients' mean age was 41.59 ± 9.69 years and disease duration 5.89 ± 3.67 years. The level of vitamin D in RA patients was significantly lower (23.11 ± 12.71 ng/mL) than that in the controls (32.59 ± 13.06 ng/mL) (P = 0.005) being deficient in 50.8%, insufficient in 23.8% and normal in 25.4%. The RA patients with FMS (n = 33) had significantly lower levels of vitamin D (19.08 ± 10.59 ng/mL) than those without (27.55 ± 13.51 ng/mL) (P = 0.008). The difference was significant on comparing those receiving hydroxychloroquine (17.39 ± 7.84 ng/mL) to those not (31.85 ± 13.85 ng/mL) (P < 0.001). Vitamin D significantly correlated with QoL index (r = 0.58, P < 0.001) and negatively with HAQ II (r = -0.36, P = 0.004) and BMI (r = -0.39, P = 0.001). Special attention is required regarding vitamin D levels in RA patients with FMS and decreased QoL. Vitamin D should be corrected and supplementation considered among the RA management armamentarium. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  2. Transient ischemic attack and minor stroke are the most common manifestations of acute cerebrovascular disease: a prospective, population-based study--the Aarhus TIA study.

    Science.gov (United States)

    von Weitzel-Mudersbach, Paul; Andersen, Grethe; Hundborg, Heidi H; Johnsen, Søren P

    2013-01-01

    Severity of acute vascular illness may have changed in the last decades due to improvements in primary and secondary prevention. Population-based data on the severity of acute ischemic cerebrovascular disease are sparse. We aimed to examine incidence, characteristics and severity of acute ischemic cerebrovascular disease in a well-defined population. All patients admitted with transient ischemic attack (TIA) or acute ischemic stroke from March 1, 2007, to February 29, 2008, with residence in the Aarhus area, were included. Incidence rates and characteristics of TIA and ischemic stroke were compared. TIA accounted for 30%, TIA and minor stroke combined for 65% of all acute ischemic cerebrovascular events. Age-adjusted incidence rates of TIA and ischemic stroke were 72.2/100,000 and 129.5/100,000 person-years, respectively. TIA patients were younger than stroke patients (66.3 vs. 72.7 years; p TIA and stroke patients share many characteristics; however, TIA patients are younger and have fewer manifestations of atherosclerotic diseases, indicating a high potential for secondary prevention. Copyright © 2012 S. Karger AG, Basel.

  3. Early treatment with infliximab in bilateral occlusive vasculitis as a presenting manifestation of Behçet' disease.

    Science.gov (United States)

    Bañeros-Rojas, P; Berrozpe-Villabona, C; Peraza-Nieves, J E; Díaz-Valle, D

    2015-06-01

    A 24 year old woman who complained of maculo-papulo rash, genital and bucal aphthous ulcers, abdominal pain, minor dyspnea and visual loss in both eyes. Funduscopy revealed a bilateral occlusive vasculitis including central vessels. Treatment was initiated with a methylprednisolone bolus (1 g/24h) and infliximab 5mg/kg/day (0-2-6 weeks and every 8 weeks). The treatment prescribed induced a fast remission. Visual acuity improved. The patient did not suffer any other relapse after one year of follow-up. An initial treatment with Infliximab should be considered in Behçet disease for serious outbreaks, such as macular occlusive vasculitis with ischemia. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  4. A case of thyrotoxic periodic paralysis as initial manifestation of Graves' disease in a 16-year-old Korean adolescent

    Directory of Open Access Journals (Sweden)

    Se Yong Jung

    2014-09-01

    Full Text Available Thyrotoxic periodic paralysis (TPP is a rare complication of hyperthyroidism, with recurrent muscle paralysis and hypokalemia that are caused by an intracellular shift of potassium. TPP is relatively common in Asian males, but is extremely rare in children and adolescents, even for those of Asian descent. We describe a 16-year-old Korean adolescent presenting with a two-week history of episodic leg weakness in the morning. He showed sinus tachycardia, lower leg weakness, and hypokalemia. Thyroid function test showed hyperthyroidism, and thyroid ultrasonography revealed a diffuse enlarged thyroid with increased vascularity, consistent with Graves' disease. He was treated with β-adrenergic blocker and antithyroid drugs. He has been symptom free for one year, as his hyperthyroidism has been controlled well with antithyroid drugs. TPP should be considered in children and adolescents with acute paralysis of the lower extremities and hypokalemia.

  5. Manifestations and management of veno-occlusive disease/sinusoidal obstruction syndrome in the era of contemporary therapies.

    Science.gov (United States)

    Tewari, Priti; Wallis, Whitney; Kebriaei, Partow

    2017-02-01

    The concept of veno-occlusive disease (VOD), along with our understanding of it, has historically been and remains an evolving phenomenon. This review presents a broad view of VOD, also known as sinusoidal obstruction syndrome (SOS), including (1) traditional hematopoietic stem cell transplant-associated VOD/SOS, (2) late-onset VOD/SOS, (3) pulmonary VOD, and (4) VOD/SOS associated with chemotherapy only. Several VOD/SOS management modalities exist that include modes for both prophylaxis and treatment. An extensive review of the literature on monoclonal antibodies, both approved and pending approval by the US Food and Drug Administration, reveals that only a few have been associated with an increased risk for VOD/SOS. In fact, bevacizumab appears to have a protective effect against the development of VOD/SOS. As the landscape of cancer treatment changes, careful attention needs to be focused on how new therapies affect the incidence of VOD/SOS.

  6. Genetic biomarkers for ALS disease in transgenic SOD1(G93A mice.

    Directory of Open Access Journals (Sweden)

    Ana C Calvo

    Full Text Available The pathophysiological mechanisms of both familial and sporadic Amyotrophic Lateral Sclerosis (ALS are unknown, although growing evidence suggests that skeletal muscle tissue is a primary target of ALS toxicity. Skeletal muscle biopsies were performed on transgenic SOD1(G93A mice, a mouse model of ALS, to determine genetic biomarkers of disease longevity. Mice were anesthetized with isoflurane, and three biopsy samples were obtained per animal at the three main stages of the disease. Transcriptional expression levels of seventeen genes, Ankrd1, Calm1, Col19a1, Fbxo32, Gsr, Impa1, Mef2c, Mt2, Myf5, Myod1, Myog, Nnt, Nogo A, Pax7, Rrad, Sln and Snx10, were tested in each muscle biopsy sample. Total RNA was extracted using TRIzol Reagent according to the manufacturer's protocol, and variations in gene expression were assayed by real-time PCR for all of the samples. The Pearson correlation coefficient was used to determine the linear correlation between transcriptional expression levels throughout disease progression and longevity. Consistent with the results obtained from total skeletal muscle of transgenic SOD1(G93A mice and 74-day-old denervated mice, five genes (Mef2c, Gsr, Col19a1, Calm1 and Snx10 could be considered potential genetic biomarkers of longevity in transgenic SOD1(G93A mice. These results are important because they may lead to the exploration of previously unexamined tissues in the search for new disease biomarkers and even to the application of these findings in human studies.

  7. Cerebral blood flow reduction in Alzheimer's disease: impact of capillary occlusions on mice and humans

    Science.gov (United States)

    Berg, Maxime; Merlo, Adlan; Peyrounette, Myriam; Doyeux, Vincent; Smith, Amy; Cruz-Hernandez, Jean; Bracko, Oliver; Haft-Javaherian, Mohammad; Nishimura, Nozomi; Schaffer, Chris B.; Davit, Yohan; Quintard, Michel; Lorthois, Sylvie

    2017-11-01

    Alzheimer's disease may be the most common form of dementia, yet a satisfactory diagnosis procedure has still to be found. Recent studies suggest that a significant decrease of cerebral blood flow, probably caused by white blood cells stalling small vessels, may be among the earliest biological markers. To assess this hypothesis we derive a blood flow model, validate it against in vitro controlled experiments and in vivo measurements made on mice. We then investigate the influence of capillary occlusions on regional perfusion (sum of all arteriole flowrates feeding the network) of large mice and humans anatomical networks. Consistent with experiments, we observe no threshold effect, so that even a small percentage of occlusions (2-4%) leads to significant blood flow decrease (5-12%). We show that both species share the same linear dependance, suggesting possible translation from mice to human. ERC BrainMicroFlow GA61510, CALMIP HPC (Grant 2017-1541).

  8. Diseases of aging untreated virgin female RFM and BALB/c mice

    International Nuclear Information System (INIS)

    Cosgrove, G.E.; Satterfield, L.C.; Bowles, N.D.; Klima, W.C.

    1978-01-01

    Diseases of untreated, virgin female barrier-maintained RFM and BALB/c mice used as controls in a large radiation aging experiment were necropsied after natural death. The spectrum and incidence of neoplastic and nonneoplastic diseases were somewhat different in the two strains. Both strains show a high incidence of neoplasma (largely reticulum cell sarcomas and lung tumors) and of glomerulosclerosis. A wide variety of other diseases was noted in much lower incidence. The findings in the RF were briefly compared with those in earlier experiments with that strain in this laboratory

  9. Manifestações sistêmicas na doença pulmonar obstrutiva crônica Systemic manifestations in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Victor Zuniga Dourado

    2006-04-01

    Full Text Available A doença pulmonar obstrutiva crônica é progressiva e está relacionada a uma resposta inflamatória anormal dos pulmões à inalação de partículas e/ou gases tóxicos, sobretudo a fumaça de cigarro. Embora acometa primariamente os pulmões, diversas manifestações extrapulmonares relacionadas a esta enfermidade têm sido descritas. O aumento do número de células inflamatórias, que resulta em produção anormal de citocinas pró-inflamatórias, e o desequilíbrio entre a formação de radicais livres e a capacidade antioxidante, resultando em sobrecarga oxidativa, provavelmente são mecanismos envolvidos na inflamação local e sistêmica. Além disso, a diminuição do condicionamento físico secundária às limitações ventilatórias pode estar envolvida no desenvolvimento de alterações musculares. A doença pulmonar obstrutiva crônica apresenta diversas manifestações sistêmicas que incluem a depleção nutricional, a disfunção dos músculos esqueléticos, que contribui para a intolerância ao exercício, e as manifestações relacionadas a co-morbidades comumente observadas nestes pacientes. Essas manifestações têm sido relacionadas à sobrevida e ao estado geral de saúde dos pacientes. Nesse sentido, esta revisão tem como objetivo discutir os achados da literatura relacionados às manifestações sistêmicas da doença pulmonar obstrutiva crônica, ressaltando o papel da inflação sistêmica, e algumas perspectivas de tratamento.Chronic obstructive pulmonary disease is progressive and is characterized by abnormal inflammation of the lungs in response to inhalation of noxious particles or toxic gases, especially cigarette smoke. Although this infirmity primarily affects the lungs, diverse extrapulmonary manifestations have been described. The likely mechanisms involved in the local and systemic inflammation seen in this disease include an increase in the number of inflammatory cells (resulting in abnormal production

  10. The impact of non-motor manifestations of Parkinson's disease on partners: understanding and application of chronic sorrow theory.

    Science.gov (United States)

    Mercer, Christine J

    2015-09-01

    Parkinson's disease (PD) can cause many emotions, including grief and a sense of isolation for both the person with PD (referred to as Parkinsonian) and their partner. Such ongoing grief and emotional turmoil can be termed chronic sorrow. The aim of this research is to present accounts of partners' perspectives, analysed in the context of chronic sorrow theory, to offer health professionals an insight into the impact of non-motor PD symptoms on partners. A group of partners of Parkinsonians provided the data through individual stories. These stories were subjected to thematic analysis, using a seven-step process leading to the establishment of themes. Caregiver burden and chronic sorrow is not related to providing physical care, but the emotional care of attempting to minimise the effect of PD, coping with disturbance to sleep, and helping the Parkinsonian to maintain as much independence as possible. Contributors to this article found chronic sorrow theory provided a framework for understanding their emotions. Sharing their experiences with others provided an opportunity to be heard, and enabled them to make sense of individual situations. Chronic sorrow theory provides a useful framework for both partners of Parkinsonians in understanding their emotional responses, and for health professionals in considering the challenges partners face in coping with living with a person with PD.

  11. Molecular crosstalk between a chemical and a biological stressor and consequences on disease manifestation in rainbow trout

    International Nuclear Information System (INIS)

    Burki, Richard; Krasnov, Aleksei; Bettge, Kathrin; Rexroad, Caird E.; Afanasyev, Sergey; Antikainen, Miia; Burkhardt-Holm, Patricia; Wahli, Thomas; Segner, Helmut

    2013-01-01

    The aim of the present study was to examine the molecular and organism reaction of rainbow trout, Oncorhynchus mykiss, to the combined impact of two environmental stressors. The two stressors were the myxozoan parasite, Tetracapsuloides bryosalmonae, which is the etiological agent of proliferative kidney disease (PKD) and a natural stressor to salmonid populations, and 17β-estradiol (E2) as prototype of estrogen-active chemical stressors in the aquatic environment. Both stressors, the parasite and estrogenic contaminants, co-exist in Swiss rivers and are discussed as factors contributing to the decline of Swiss brown trout populations over the last decades. Using a microarray approach contrasting parasite-infected and non-infected rainbow trout at low or high estrogen levels, it was observed that molecular response patterns under joint exposure differed from those to the single stressors. More specifically, three major response patterns were present: (i) expression responses of gene transcripts to one stressor are weakened by the presence of the second stressor; (ii) expression responses of gene transcripts to one stressor are enhanced by the presence of the second stressor; (iii) expression responses of gene transcripts at joint treatment are dominated by one of the two stressors. Organism-level responses to concurrent E2 and parasite treatment – assessed through measuring parasite loads in the fish host and cumulative mortalities of trout – were dominated by the pathogen, with no modulating influence of E2. The findings reveal function- and level-specific responses of rainbow trout to stressor combinations, which are only partly predictable from the response to the single stressors.

  12. Molecular crosstalk between a chemical and a biological stressor and consequences on disease manifestation in rainbow trout

    Energy Technology Data Exchange (ETDEWEB)

    Burki, Richard [Centre for Fish and Wildlife Health, University of Bern, Laenggassstrasse 122, CH-3001 Bern (Switzerland); Krasnov, Aleksei [NOFIMA Marin, Postboks. 5010, 1432As (Norway); Bettge, Kathrin [Centre for Fish and Wildlife Health, University of Bern, Laenggassstrasse 122, CH-3001 Bern (Switzerland); Rexroad, Caird E. [National Center for Cool and Cold Water Aquaculture, USDA-ARS, 11876 Leetown Road, Kearneysville, WV 25430 (United States); Afanasyev, Sergey [Sechenov Institute of Evolutionary Physiology and Biochemistry, M. Toreza av. 44, Peterburg 194223 (Russian Federation); Antikainen, Miia [Institute of Applied Biotechnology, University of Kuopio (Finland); Burkhardt-Holm, Patricia [Man-Society-Environment, University of Basel, Vesalgasse 1, CH-4051 Basel (Switzerland); Wahli, Thomas [Centre for Fish and Wildlife Health, University of Bern, Laenggassstrasse 122, CH-3001 Bern (Switzerland); Segner, Helmut, E-mail: helmut.segner@vetsuisse.unibe.ch [Centre for Fish and Wildlife Health, University of Bern, Laenggassstrasse 122, CH-3001 Bern (Switzerland)

    2013-02-15

    The aim of the present study was to examine the molecular and organism reaction of rainbow trout, Oncorhynchus mykiss, to the combined impact of two environmental stressors. The two stressors were the myxozoan parasite, Tetracapsuloides bryosalmonae, which is the etiological agent of proliferative kidney disease (PKD) and a natural stressor to salmonid populations, and 17{beta}-estradiol (E2) as prototype of estrogen-active chemical stressors in the aquatic environment. Both stressors, the parasite and estrogenic contaminants, co-exist in Swiss rivers and are discussed as factors contributing to the decline of Swiss brown trout populations over the last decades. Using a microarray approach contrasting parasite-infected and non-infected rainbow trout at low or high estrogen levels, it was observed that molecular response patterns under joint exposure differed from those to the single stressors. More specifically, three major response patterns were present: (i) expression responses of gene transcripts to one stressor are weakened by the presence of the second stressor; (ii) expression responses of gene transcripts to one stressor are enhanced by the presence of the second stressor; (iii) expression responses of gene transcripts at joint treatment are dominated by one of the two stressors. Organism-level responses to concurrent E2 and parasite treatment - assessed through measuring parasite loads in the fish host and cumulative mortalities of trout - were dominated by the pathogen, with no modulating influence of E2. The findings reveal function- and level-specific responses of rainbow trout to stressor combinations, which are only partly predictable from the response to the single stressors.

  13. Chronic exposure to trichloroethene causes early onset of SLE-like disease in female MRL +/+ mice

    International Nuclear Information System (INIS)

    Cai Ping; Koenig, Rolf; Boor, Paul J.; Kondraganti, Shakuntala; Kaphalia, Bhupendra S.; Khan, M. Firoze; Ansari, G.A.S.

    2008-01-01

    Trichloroethene (TCE) exacerbates the development of autoimmune responses in autoimmune-prone MRL +/+ mice. Although TCE-mediated autoimmune responses are associated with an increase in serum immunoglobulins and autoantibodies, the underlying mechanism of autoimmunity is not known. To determine the progression of TCE-mediated immunotoxicity, female MRL +/+ mice were chronically exposed to TCE through the drinking water (0.5 mg/ml of TCE) for various periods of time. Serum concentrations of antinuclear antibodies increased after 36 and 48 weeks of TCE exposure. Histopathological analyses showed lymphocyte infiltration in the livers of MRL +/+ mice exposed to TCE for 36 or 48 weeks. Lymphocyte infiltration was also apparent in the pancreas, lungs, and kidneys of mice exposed to TCE for 48 weeks. Immunoglobulin deposits in kidney glomeruli were found after 48 weeks of exposure to TCE. Our results suggest that chronic exposure to TCE promotes inflammation in the liver, pancreas, lungs, and kidneys, which may lead to SLE-like disease in MRL +/+ mice

  14. Uric acid demonstrates neuroprotective effect on Parkinson's disease mice through Nrf2-ARE signaling pathway.

    Science.gov (United States)

    Huang, Ting-Ting; Hao, Dong-Lin; Wu, Bo-Na; Mao, Lun-Lin; Zhang, Jin

    2017-12-02

    Uric acid has neuroprotective effect on Parkinson's disease (PD) by inhibiting oxidative damage and neuronal cell death. Our previous study has shown that uric acid protected dopaminergic cell line damage through inhibiting accumulation of NF-E2-related factor 2 (Nrf2). This study aimed to investigate its in vivo neuroprotective effect. PD was induced by MPTP intraperitoneally injection for 7 d in male C57BL/6 mice. Mice were treated with either uric acid (intraperitoneally injection 250 mg/kg) or saline for a total of 13 d. We showed that uric acid improved behavioral performances and cognition of PD mice, increased TH-positive dopaminergic neurons and decreased GFAP-positive astrocytes in substantia nigra (SN). Uric acid increased mRNA and protein expressions of Nrf2 and three Nrf2-responsive genes, including γ-glutamate-cysteine ligase catalytic subunit (γ-GCLC), heme oxygenase-1 (HO-1) and NQO1. Uric acid significantly increased superoxide dismutase (SOD), CAT, glutathione (GSH) levels and decreased malondialdehyde (MDA) level in SN regions of MPTP-treated mice. Uric acid inhibited the hippocampal expression of IL-1β and decreased serum and hippocampus levels of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α). In conclusion, uric acid demonstrates neuroprotective properties for dopaminergic neurons in PD mice through modulation of neuroinflammation and oxidative stress. Copyright © 2017. Published by Elsevier Inc.

  15. Complement component 5 contributes to poor disease outcome in humans and mice with pneumococcal meningitis

    Science.gov (United States)

    Woehrl, Bianca; Brouwer, Matthijs C.; Murr, Carmen; Heckenberg, Sebastiaan G.B.; Baas, Frank; Pfister, Hans W.; Zwinderman, Aeilko H.; Morgan, B. Paul; Barnum, Scott R.; van der Ende, Arie; Koedel, Uwe; van de Beek, Diederik

    2011-01-01

    Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the proinflammatory response in the subarachnoid space. The complement system, which mediates key inflammatory processes, has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. Additionally, SNPs in genes encoding complement pathway proteins have been linked to susceptibility to pneumococcal infection, although no associations with disease severity or outcome have been established. Here, we have performed a robust prospective nationwide genetic association study in patients with bacterial meningitis and found that a common nonsynonymous complement component 5 (C5) SNP (rs17611) is associated with unfavorable disease outcome. C5 fragment levels in cerebrospinal fluid (CSF) of patients with bacterial meningitis correlated with several clinical indicators of poor prognosis. Consistent with these human data, C5a receptor–deficient mice with pneumococcal meningitis had lower CSF wbc counts and decreased brain damage compared with WT mice. Adjuvant treatment with C5-specific monoclonal antibodies prevented death in all mice with pneumococcal meningitis. Thus, our results suggest C5-specific monoclonal antibodies could be a promising new antiinflammatory adjuvant therapy for pneumococcal meningitis. PMID:21926466

  16. Toll-like receptor 9 suppresses lupus disease in Fas-sufficient MRL Mice.

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    Kevin M Nickerson

    Full Text Available Genetic deficiency in TLR9 accelerates pathogenesis in the spontaneous polygenic MRL.Faslpr murine model of systemic lupus erythematosus, despite the absence of anti-nucleosome autoantibodies. However, it could be argued that this result was dependent on Fas-deficiency rather than lupus-promoting genes in the MRL genetic background. Here we report the effects of TLR9 deficiency on autoimmune disease independent of the lpr mutation in Fas by characterizing Tlr9-/- and Tlr9+/+ mice on the Fas-intact MRL/+ genetic background. By 30 weeks of age, Tlr9-deficient MRL/+ had more severe renal disease, increased T cell activation, and higher titers of anti-Sm and anti-RNA autoantibodies than Tlr9-intact animals, as had been the case in the MRL.Faslpr model. In addition, Tlr9-deficient MRL/+ mice had increased numbers of germinal center phenotype B cells and an increase in splenic neutrophils and conventional dendritic cell populations. Thus, the disease accelerating effects of Tlr9 deficiency are separable from those mediated by the Fas mutation in the lupus-prone MRL genetic background. Nonetheless, disease acceleration in Tlr9-deficient MRL/+ mice was phenotypically distinct from that in Fas-deficient counterparts, which has important implications.

  17. Chronic Proliferative Dermatitis in Mice: NFκB Activation Autoinflammatory Disease

    Directory of Open Access Journals (Sweden)

    Yanhua Liang

    2011-01-01

    Full Text Available Autoinflammatory diseases are a heterogeneous group of congenital diseases characterized by the presence of recurrent inflammation, in the absence of infectious agents, detectable autoantibodies or antigen-specific autoreactive T-cells. SHARPIN deficient mice presents multiorgan chronic inflammation without known autoantibodies or autoreactive T-cells, designated Sharpincpdm. Histological studies demonstrated epidermal hyperproliferation, Th-2 inflammation, and keratinocyte apoptosis in this mutant. The mutant mice have decreased behavioral mobility, slower growth, and loss of body weight. Epidermal thickness and mitotic epidermal cells increase along with disease development. K5/K14 expression is distributed through all layers of epidermis, along with K6 expression in interfollicular epidermis, suggesting epidermal hyperproliferation. K1/K10 is only detectable in outer layers of spinosum epidermis, reflecting accelerated keratinocyte migration. Alpha smooth muscle actin is overexpressed in skin blood vessels, which may release the elevated white blood cells to dermis. CD3+CD45+ cells and granulocytes, especially eosinophils and mast cells, aggregate in the mutant skin. TUNEL assay, together with Annexin-V/propidium iodide FACS analysis, confirmed the increase of apoptotic keratinocytes in skin. These data validate and provide new lines of evidence of the proliferation-inflammation-apoptosis triad in Sharpincpdm mice, an NFκB activation autoinflammatory disease.

  18. Features associated with the development of non-motor manifestations in Parkinson's disease Factores asociados con el desarrollo de complicaciones no motoras en la enfermedad de Parkinson

    Directory of Open Access Journals (Sweden)

    Carlos Juri

    2008-03-01

    Full Text Available Parkinson's disease (PD is a neurodegenerative disorder, predominantly characterized by the presence of motor symptoms. However, the non motor manifestations (NMM are a frequent complaint in the PD patients. There is a lack of information about the risk factors associated with the NMM in these patients. The aim of this study is to evaluate the prevalence of the more common NMM in a population of PD patients and to determine the features associated with its development. We studied 124 ambulatory PD patients. NMM were defined by the presence of neuropsychiatric manifestations, cognitive disorder, autonomic dysfunction or sleep related problems. In a multivariate analysis we found that the years of evolution of the PD and the presence of cognitive dysfunction are the risk factors for the neuropsychiatric and autonomic manifestations, whereas axial impairment is a risk factor for cognitive disorders and dyskinesias is for sleep related problems. In conclusion, this study shows that the features related to the PD progression appear as the main risk factors associated with NMM.La enfermedad de Parkinson (EP es un trastorno neurodegenerativo, caracterizado predominan-temente por la presencia de síntomas motores. No obstante, la presencia de manifestaciones no motoras (MNN son frecuentes en los pacientes con EP. Existe escasa información sobre los factores de riesgo asociados con la aparición de MNN en dichos pacientes. El objetivo de este estudio fue evaluar la prevalencia de las MNN más comunes en una población de pacientes portadores de EP y determinar los factores de riesgo asociados con su aparición. Estudiamos 124 pacientes portadores de EP atendidos en forma ambulatoria. La presencia de MNN fue definida por la aparición de manifestaciones neuropsiquiátricas, trastorno cognitivo, disfunción autonómica o alteraciones del sueño. En el análisis multivariado encontramos que los años de evolución de la EP y la presencia de disfunci

  19. Loss of hepatocyte-nuclear-factor-4alpha affects colonic ion transport and causes chronic inflammation resembling inflammatory bowel disease in mice.

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    Mathieu Darsigny

    Full Text Available BACKGROUND: Hnf4alpha, an epithelial specific transcriptional regulator, is decreased in inflammatory bowel disease and protects against chemically-induced colitis in mice. However, the precise role of this factor in maintaining normal inflammatory homeostasis of the intestine remains unclear. The aim of this study was to evaluate the sole role of epithelial Hnf4alpha in the maintenance of gut inflammatory homeostasis in mice. METHODOLOGY/PRINCIPAL FINDINGS: We show here that specific epithelial deletion of Hnf4alpha in mice causes spontaneous chronic intestinal inflammation leading to focal areas of crypt dropout, increased cytokines and chemokines secretion, immune cell infiltrates and crypt hyperplasia. A gene profiling analysis in diseased Hnf4alpha null colon confirms profound genetic changes in cell death and proliferative behaviour related to cancer. Among the genes involved in the immune protection through epithelial barrier function, we identify the ion transporter claudin-15 to be down-modulated early in the colon of Hnf4alpha mutants. This coincides with a significant decrease of mucosal ion transport but not of barrier permeability in young animals prior to the manifestation of the disease. We confirm that claudin-15 is a direct Hnf4alpha gene target in the intestinal epithelial context and is down-modulated in mouse experimental colitis and inflammatory bowel disease. CONCLUSION: Our results highlight the critical role of Hnf4alpha to maintain intestinal inflammatory homeostasis during mouse adult life and uncover a novel function for Hnf4alpha in the regulation of claudin-15 expression. This establishes Hnf4alpha as a mediator of ion epithelial transport, an important process for the maintenance of gut inflammatory homeostasis.

  20. Mice, humans and haplotypes--the hunt for disease genes in SLE.

    Science.gov (United States)

    Rigby, R J; Fernando, M M A; Vyse, T J

    2006-09-01

    Defining the polymorphisms that contribute to the development of complex genetic disease traits is a challenging, although increasingly tractable problem. Historically, the technical difficulties in conducting association studies across the entire human genome are such that murine models have been used to generate candidate genes for analysis in human complex diseases, such as SLE. In this article we discuss the advantages and disadvantages of this approach and specifically address some assumptions made in the transition from studying one species to another, using lupus as an example. These issues include differences in genetic structure and genetic organisation which are a reflection on the population history. Clearly there are major differences in the histories of the human population and inbred laboratory strains of mice. Both human and murine genomes do exhibit structure at the genetic level. That is to say, they comprise haplotypes which are genomic regions that carry runs of polymorphisms that are not independently inherited. Haplotypes therefore reduce the number of combinations of the polymorphisms in the DNA in that region and facilitate the identification of disease susceptibility genes in both mice and humans. There are now novel means of generating candidate genes in SLE using mutagenesis (with ENU) in mice and identifying mice that generate antinuclear autoimmunity. In addition, murine models still provide a valuable means of exploring the functional consequences of genetic variation. However, advances in technology are such that human geneticists can now screen large fractions of the human genome for disease associations using microchip technologies that provide information on upwards of 100,000 different polymorphisms. These approaches are aimed at identifying haplotypes that carry disease susceptibility mutations and rely less on the generation of candidate genes.

  1. Neglected Tropical Diseases: Treatment of Dermatological Manifestation of Filariasis with Combination Regimen of Albendazole, Ivermectin, and Loratadine: A Case Report from a Suburban Community in Nigeria

    Directory of Open Access Journals (Sweden)

    Osede Ignis Iribhogbe

    2017-06-01

    Full Text Available Threadlike filarial nematodes have been identified as the causative agent of filariasis. Cutaneous filariasis is caused primarily by Loa loa, Onchocerca volvulus, and Mansonella streptocerca. These parasites occupy the subcutaneous layer of the skin. However, other filarial parasites are usually associated with varying degrees of dermatological manifestations. In the present discourse, two cases of cutaneous filariasis were diagnosed in two female patients (21 and 40 years old, respectively in Remitch Clinic and Maternity located in a nonriverine community in Ekpoma, Edo State, Nigeria. In this report, patients with body mass index (BMI of 18.97 and 23.45 kg/m2, respectively, presented on two different occasions at least 6 months apart with hyperpigmented skin lesions in the upper and lower limbs, respectively. There was associated intense pruritus with no evidence of lymphadenopathy and lymphoedema. Following laboratory confirmation of filariasis, the patients were placed on a single oral dose combination of albendazole (400 mg + ivermectin (200 mcg/kg, while oral doses of loratadine 10 mg were administered daily for 5 days. Patients were carefully followed up for 6 weeks during which recession of the lesion and untoward reactions were monitored. It was observed that within 6 weeks of treatment, there was a dramatic recession of skin lesion. Adverse effect reported from use of the combination was mild. This case report revealed that cutaneous filariasis is not an uncommon presentation of filariasis infestation in Nigeria. The report also validates the safety and efficacy of the combination in the management of cutaneous manifestation of the disease.

  2. Pharmacological inhibition of myostatin suppresses systemic inflammation and muscle atrophy in mice with chronic kidney disease

    Science.gov (United States)

    Zhang, Liping; Rajan, Vik; Lin, Eugene; Hu, Zhaoyong; Han, H. Q.; Zhou, Xiaolan; Song, Yanping; Min, Hosung; Wang, Xiaonan; Du, Jie; Mitch, William E.

    2011-01-01

    Chronic kidney disease (CKD) and several other catabolic conditions are characterized by increased circulating inflammatory cytokines, defects in IGF-1 signaling, abnormal muscle protein metabolism, and progressive muscle atrophy. In these conditions, no reliable treatments successfully block the development of muscle atrophy. In mice with CKD, we found a 2- to 3-fold increase in myostatin expression in muscle. Its pharmacological inhibition by subcutaneous injections of an anti-myostatin peptibody into CKD mice (IC50 ∼1.2 nM) reversed the loss of body weight (≈5–7% increase in body mass) and muscle mass (∼10% increase in muscle mass) and suppressed circulating inflammatory cytokines vs. results from CKD mice injected with PBS. Pharmacological myostatin inhibition also decreased the rate of protein degradation (16.38±1.29%; Pmyostatin expression via a NF-κB-dependent pathway, whereas muscle cells exposed to myostatin stimulated IL-6 production via p38 MAPK and MEK1 pathways. Because IL-6 stimulates muscle protein breakdown, we conclude that CKD increases myostatin through cytokine-activated pathways, leading to muscle atrophy. Myostatin antagonism might become a therapeutic strategy for improving muscle growth in CKD and other conditions with similar characteristics.—Zhang, L., Rajan, V., Lin, E., Hu, Z., Han, H.Q., Zhou, X., Song, Y., Min, H., Wang, X., Du, J., Mitch, W. E. Pharmacological inhibition of myostatin suppresses systemic inflammation and muscle atrophy in mice with chronic kidney disease. PMID:21282204

  3. Cell therapy of congenital corneal diseases with umbilical mesenchymal stem cells: lumican null mice.

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    Hongshan Liu

    Full Text Available BACKGROUND: Keratoplasty is the most effective treatment for corneal blindness, but suboptimal medical conditions and lack of qualified medical personnel and donated cornea often prevent the performance of corneal transplantation in developing countries. Our study aims to develop alternative treatment regimens for congenital corneal diseases of genetic mutation. METHODOLOGY/PRINCIPAL FINDINGS: Human mesenchymal stem cells isolated from neonatal umbilical cords were transplanted to treat thin and cloudy corneas of lumican null mice. Transplantation of umbilical mesenchymal stem cells significantly improved corneal transparency and increased stromal thickness of lumican null mice, but human umbilical hematopoietic stem cells failed to do the same. Further studies revealed that collagen lamellae were re-organized in corneal stroma of lumican null mice after mesenchymal stem cell transplantation. Transplanted umbilical mesenchymal stem cells survived in the mouse corneal stroma for more than 3 months with little or no graft rejection. In addition, these cells assumed a keratocyte phenotype, e.g., dendritic morphology, quiescence, expression of keratocyte unique keratan sulfated keratocan and lumican, and CD34. Moreover, umbilical mesenchymal stem cell transplantation improved host keratocyte functions, which was verified by enhanced expression of keratocan and aldehyde dehydrogenase class 3A1 in lumican null mice. CONCLUSIONS/SIGNIFICANCE: Umbilical mesenchymal stem cell transplantation is a promising treatment for congenital corneal diseases involving keratocyte dysfunction. Unlike donated corneas, umbilical mesenchymal stem cells are easily isolated, expanded, stored, and can be quickly recovered from liquid nitrogen when a patient is in urgent need.

  4. Manifestações da apraxia de fala na doença de Alzheimer Manifestations of apraxia of speech in Alzheimer's disease

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    Maysa Luchesi Cera

    2011-09-01

    Full Text Available OBJETIVO: Identificar as manifestações práxicas de pacientes com doença de Alzheimer em diferentes estágios da doença e verificar as similaridades entre as suas ocorrências. MÉTODOS: Foram avaliados noventa pacientes com doença de Alzheimer, 30 em cada fase da doença (leve, moderada e grave, por meio dos instrumentos: Escala de Avaliação Clínica da Demência (CDR, Mini-Exame do Estado Mental (MEEM, Avaliação das Atividades Instrumentais de Vida Diária (Índice Lawton e Protocolo de Avaliação da Apraxia Verbal e Não-verbal. Foram avaliados 66 pacientes do gênero feminino e 24 do masculino, a média da idade foi 80,2±7,2 e da escolaridade foi 4,2±3,5 anos. RESULTADOS: Na fase leve, as proporções de ensaio, repetição e adição foram semelhantes, assim como omissão, substituição e autocorreção. Na fase moderada foram semelhantes: ensaio e repetição, substituição, omissão e adição, e autocorreção. Na fase grave, todas as manifestações se assemelharam, exceto a adição. O erro do tipo adição diferenciou os pacientes em relação às fases da doença. CONCLUSÃO: Os pacientes dos três estágios da doença apresentam diferentes padrões de manifestações práxicas verbais.PURPOSE: To identify praxic speech manifestations in patients diagnosed with different stages of Alzheimer's disease, and to verify similarities among their occurrences. METHODS: Participants were 90 patients with Alzheimer's, 30 in each stage of the disease (mild, moderate and severe, who were assessed using the following instruments: Clinical Dementia Rating (CDR, Mini-Mental State Examination (MMSE, Lawton Instrumental Activities of Daily Living, and the Assessment Protocol of Verbal and Orofacial Apraxia. Sixty six female subjects and 24 male subjects were assessed; mean age was 80.2±7.2 years, and mean level of education was 4.2±3.5 years. RESULTS: In the mild stage, the proportions of trial-and-error, repetition and addition were

  5. Manifestações cutâneas na doença renal terminal Cutaneous manifestations in end-stage renal disease

    Directory of Open Access Journals (Sweden)

    Omar Lupi

    2011-04-01

    Full Text Available A prevalência da doença renal crônica aumentou nos últimos anos. Os efeitos dessa doença são complexos e podem levar à disfunção de múltiplos órgãos, entre eles, a pele. A maioria dos pacientes apresenta pelo menos uma alteração dermatológica. Algumas vezes, esses sintomas podem ser o primeiro sinal evidente de doença renal. Este artigo aborda as manifestações cutâneas relacionadas a disfunção renal grave ou doença renal terminal, divididas em não específicas e específicas, revisando quadro clínico, etiopatogenia e opções terapêuticas dessas dermatoses. Seu reconhecimento e trata mento precoces diminuem a morbidade, melhorando a qualidade de vida desses doentes.The prevalence of chronic kidney disease has increased over the last years. The effects of this disease are complex and may lead to dysfunction of multiple organs, including the skin, with most patients presenting with at least one dermatologic alteration. Sometimes these symptoms can be the first clear sign of kidney disease. This article discusses the skin manifestations related to severe renal impairment or end-stage renal disease (ESRD, which are divided into nonspecific and specific, and reviews the clinical features, etiopathogenesis and therapeutic options for these dermatoses. Early recognition and treatment reduce morbidity and improve these patients' quality of life.

  6. Spontaneous nonalcoholic fatty liver disease and ER stress in Sidt2 deficiency mice

    International Nuclear Information System (INIS)

    Gao, Jialin; Zhang, Yao; Yu, Cui; Tan, Fengbiao; Wang, Lizhuo

    2016-01-01

    disease (NAFLD) accompanied by ERS. In summary, as a lysosomal membrane protein, Sidt2 plays an important role in the pathogenesis of NAFLD, and ERS may mediate the occurrence and development of this disease in Sdit2 deficiency mice.

  7. Spontaneous nonalcoholic fatty liver disease and ER stress in Sidt2 deficiency mice

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Jialin [Department of Endocrinology and Genetic Metabolism, Yijishan Hospital of Wannan Medical College, Wuhu, 241002 (China); Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, 241001 (China); Zhang, Yao [Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, 241001 (China); Department of Biochemistry and Molecular Biology, Wannan Medical Collage, Wuhu, 241002 (China); Yu, Cui [Department of Endocrinology and Genetic Metabolism, Yijishan Hospital of Wannan Medical College, Wuhu, 241002 (China); Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, 241001 (China); Tan, Fengbiao [Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, 241001 (China); Department of Biochemistry and Molecular Biology, Wannan Medical Collage, Wuhu, 241002 (China); Wang, Lizhuo, E-mail: 19277924@qq.com [Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, 241001 (China); Department of Biochemistry and Molecular Biology, Wannan Medical Collage, Wuhu, 241002 (China)

    2016-08-05

    nonalcoholic fatty liver disease (NAFLD) accompanied by ERS. In summary, as a lysosomal membrane protein, Sidt2 plays an important role in the pathogenesis of NAFLD, and ERS may mediate the occurrence and development of this disease in Sdit2 deficiency mice.

  8. Treatment of lysosomal storage disease in MPS VII mice using a recombinant adeno-associated virus.

    Science.gov (United States)

    Watson, G L; Sayles, J N; Chen, C; Elliger, S S; Elliger, C A; Raju, N R; Kurtzman, G J; Podsakoff, G M

    1998-12-01

    Mucopolysaccharidosis type VII (MPS VII) is a lysosomal storage disease caused by a genetic deficiency of beta-glucuronidase (GUS). We used a recombinant adeno-associated virus vector (AAV-GUS) to deliver GUS cDNA to MPS VII mice. The route of vector administration had a dramatic effect on the extent and distribution of GUS activity. Intramuscular injection of AAV-GUS resulted in high, localized production of GUS, while intravenous administration produced low GUS activity in several tissues. This latter treatment of MPS VII mice reduced glycosaminoglycan levels in the liver to normal and reduced storage granules dramatically. We show that a single administration of AAV-GUS can provide sustained expression of GUS in a variety of cell types and is sufficient to reverse the disease phenotype at least in the liver.

  9. Candidate chromosome 1 disease susceptibility genes for Sjogren’s syndrome xerostomia are narrowed by novel NOD.B10 congenic mice

    Science.gov (United States)

    Mongini, Patricia K. A.; Kramer, Jill M.; Ishikawa, Tomo-o; Herschman, Harvey; Esposito, Donna

    2014-01-01

    Sjogren’s syndrome (SS) is characterized by salivary gland leukocytic infiltrates and impaired salivation (xerostomia). Cox-2 (Ptgs2) is located on chromosome 1 within the span of the Aec2 region. In an attempt to demonstrate that COX-2 drives antibody-dependent hyposalivation, NOD.B10 congenic mice bearing a Cox-2flox gene were generated. A congenic line with non-NOD alleles in Cox-2-flanking genes failed manifest xerostomia. Further backcrossing yielded disease-susceptible NOD.B10 Cox-2flox lines; fine genetic mapping determined that critical Aec2 genes lie within a 1.56 to 2.17 Mb span of DNA downstream of Cox-2. Bioinformatics analysis revealed that susceptible and non-susceptible lines exhibit non-synonymous coding SNPs in 8 protein-encoding genes of this region, thereby better delineating candidate Aec2 alleles needed for SS xerostomia. PMID:24685748

  10. The Role of T cell PPAR γ in mice with experimental inflammatory bowel disease

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    Hontecillas Raquel

    2010-06-01

    Full Text Available Abstract Background Peroxisome proliferator-activated receptor γ (PPAR γ is a nuclear receptor whose activation has been shown to modulate macrophage and T cell-mediated inflammation. The objective of this study was to investigate the mechanisms by which the deletion of PPAR γ in T cells modulates immune cell distribution and colonic gene expression and the severity of experimental IBD. Methods PPAR γ flfl; CD4 Cre+ (CD4cre or Cre- (WT mice were challenged with 2.5% dextran sodium sulfate in their drinking water for 0, 2, or 7 days. Mice were scored on disease severity both clinically and histopathologically. Flow cytometry was used to assess lymphocyte and macrophage populations in the blood, spleen, and mesenteric lymph nodes (MLN. Global gene expression in colonic mucosa was profiled using Affymetrix microarrays. Results The deficiency of PPAR γ in T cells accelerated the onset of disease and body weight loss. Examination of colon histopathology revealed significantly greater epithelial erosion, leukocyte infiltration, and mucosal thickening in the CD4cre mice on day 7. CD4cre mice had more CD8+ T cells than WT mice and fewer CD4+FoxP3+ regulatory T cells (Treg and IL10+CD4+ T cells in blood and MLN, respectively. Transcriptomic profiling revealed around 3000 genes being transcriptionally altered as a result of DSS challenge in CD4cre mice. These included up-regulated mRNA expression of adhesion molecules, proinflammatory cytokines interleukin-6 (IL-6 and IL-1β, and suppressor of cytokine signaling 3 (SOCS-3 on day 7. Gene set enrichment analysis (GSEA showed that the ribosome and Krebs cycle pathways were downregulated while the apoptosis pathway was upregulated in colons of mice lacking PPAR γ in T cells. Conclusions The expression of PPAR γ in T cells is involved in preventing gut inflammation by regulating colonic expression of adhesion molecules and inflammatory mediators at later stages of disease while favoring the recruitment

  11. Proliferation and apoptosis of lamina propria CD4+ T cells from scid mice with inflammatory bowel disease

    DEFF Research Database (Denmark)

    Bregenholt, S; Reimann, J; Claesson, Mogens Helweg

    1998-01-01

    Scid mice transplanted with low numbers of syngeneic CD4+ T cells, develop a chronic and lethal inflammatory bowel disease (IBD) within 4-6 months. We have used in vivo 5-bromo2-deoxy-uridine (BrdU) labeling to assess the proliferation of lamina propria-derived CD4+ T cells in diseased scid mice....... The hourly rate of renewal of colonic lamina propria CD4+ T cells in diseased mice was 7% compared with 1.5% in normal BALB/c control mice. Transplantation of scid mice with in vitro activated CD4+ T cells accelerated the disease onset and development in a cell dose-dependent fashion when compared with non......-activated CD4+ T cells. In pulse-chase experiments it was shown that BrdU-labeled cells disappeared rapidly from the lamina propria of diseased mice. DNA analysis revealed that this was due to the presence of nearly four times as many apoptotic CD4+ T cells in diseased than in control mice. Further analyses...

  12. Transmission and Adaptation of Chronic Wasting Disease to Hamsters and Transgenic Mice: Evidence for Strains▿

    OpenAIRE

    Raymond, Gregory J.; Raymond, Lynne D.; Meade-White, Kimberly D.; Hughson, Andrew G.; Favara, Cynthia; Gardner, Donald; Williams, Elizabeth S.; Miller, Michael W.; Race, Richard E.; Caughey, Byron

    2007-01-01

    In vitro screening using the cell-free prion protein conversion system indicated that certain rodents may be susceptible to chronic wasting disease (CWD). Therefore, CWD isolates from mule deer, white-tailed deer, and elk were inoculated intracerebrally into various rodent species to assess the rodents' susceptibility and to develop new rodent models of CWD. The species inoculated were Syrian golden, Djungarian, Chinese, Siberian, and Armenian hamsters, transgenic mice expressing the Syrian g...

  13. Inhibition of UDP-glucosylceramide synthase in mice prevents Gaucher disease-associated B-cell malignancy

    NARCIS (Netherlands)

    Pavlova, Elena V.; Archer, Joy; Wang, Susan; Dekker, Nick; Aerts, Johannes Mfg; Karlsson, Stefan; Cox, Timothy M.

    2015-01-01

    Clonal B-cell proliferation is a frequent manifestation of Gaucher disease - a sphingolipidosis associated with a high risk of multiple myeloma and non-Hodgkin lymphoma. Gaucher disease is caused by genetic deficiency of acid β-glucosidase, the natural substrates of which (β-d-glucosylceramide and

  14. Chronic wasting disease prions are not transmissible to transgenic mice overexpressing human prion protein.

    Science.gov (United States)

    Sandberg, Malin K; Al-Doujaily, Huda; Sigurdson, Christina J; Glatzel, Markus; O'Malley, Catherine; Powell, Caroline; Asante, Emmanuel A; Linehan, Jacqueline M; Brandner, Sebastian; Wadsworth, Jonathan D F; Collinge, John

    2010-10-01

    Chronic wasting disease (CWD) is a prion disease that affects free-ranging and captive cervids, including mule deer, white-tailed deer, Rocky Mountain elk and moose. CWD-infected cervids have been reported in 14 USA states, two Canadian provinces and in South Korea. The possibility of a zoonotic transmission of CWD prions via diet is of particular concern in North America where hunting of cervids is a popular sport. To investigate the potential public health risks posed by CWD prions, we have investigated whether intracerebral inoculation of brain and spinal cord from CWD-infected mule deer transmits prion infection to transgenic mice overexpressing human prion protein with methionine or valine at polymorphic residue 129. These transgenic mice have been utilized in extensive transmission studies of human and animal prion disease and are susceptible to BSE and vCJD prions, allowing comparison with CWD. Here, we show that these mice proved entirely resistant to infection with mule deer CWD prions arguing that the transmission barrier associated with this prion strain/host combination is greater than that observed with classical BSE prions. However, it is possible that CWD may be caused by multiple prion strains. Further studies will be required to evaluate the transmission properties of distinct cervid prion strains as they are characterized.

  15. Clinical manifestations of scrub typhus.

    Science.gov (United States)

    Rajapakse, Senaka; Weeratunga, Praveen; Sivayoganathan, Sriharan; Fernando, Sumadhya Deepika

    2017-02-01

    The mite-borne rickettsial zoonosis scrub typhus is widely prevalent in parts of Southeast and Far East Asia, and northern Australia. The disease is an acute febrile illness, associated with rash and often an eschar, which responds dramatically to treatment with antibiotics. In some cases it results in a serious illness leading to multiple organ involvement and death. The disease manifestations are thought to result from a systemic vasculitis, caused by both direct effects of the organisms as well as an exaggerated immune response, although little is understood about its pathogenesis. A wide spectrum of clinical manifestations, affecting nearly every organ system, have been described with scrub typhus. Some of these manifestations are serious and life threatening. In this systematic review, we summarise the typical and atypical manifestations of scrub typhus reported in the literature. Awareness of these unusual manifestations will hopefully guide clinicians towards diagnosing the condition early, and initiating early appropriate antibiotics and other supportive measures. © The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. The antimicrobial peptide cathelicidin protects mice from Escherichia coli O157:H7-mediated disease.

    Directory of Open Access Journals (Sweden)

    Milan Chromek

    Full Text Available This study investigated the role of the antimicrobial peptide cathelicidin in Escherichia coli O157:H7 infection and subsequent renal damage. Mouse and human cathelicidin, CRAMP and LL-37, respectively, killed E. coli O157:H7 in vitro. Intestines from healthy wild-type (129/SvJ and cathelicidin-knock-out (Camp(-/- mice were investigated, showing that cathelicidin-deficient mice had a thinner colonic mucus layer compared with wild-type mice. Wild-type (n = 11 and cathelicidin-knock-out (n = 11 mice were inoculated with E. coli O157:H7. Cathelicidin-deficient animals exhibited higher fecal counts of E. coli O157:H7 and bacteria penetrated the mucus forming attaching-and-effacing lesions to a much higher extent than in wild-type animals. Cathelicidin knock-out mice developed symptoms (9/11 as well as anemia, thrombocytopenia and extensive renal tubular damage while all cathelicidin-producing mice remained asymptomatic with normal laboratory findings. When injected with Shiga toxin intraperitoneally, both murine strains developed the same degree of renal tubular damage and clinical disease indicating that differences in sensitivity to infection between the murine strains were related to the initial intestinal response. In conclusion, cathelicidin substantially influenced the antimicrobial barrier in the mouse colon mucosa. Cathelicidin deficiency lead to increased susceptibility to E. coli O157:H7 infection and subsequent renal damage. Administration of cathelicidin or stimulation of endogenous production may prove to be novel treatments for E. coli O157:H7-induced hemolytic uremic syndrome.

  17. Association of the interferon signature metric with serological disease manifestations but not global activity scores in multiple cohorts of patients with SLE

    Science.gov (United States)

    Kennedy, William P; Maciuca, Romeo; Wolslegel, Kristen; Tew, Wei; Abbas, Alexander R; Chaivorapol, Christina; Morimoto, Alyssa; McBride, Jacqueline M; Brunetta, Paul; Richardson, Bruce C; Davis, John C; Behrens, Timothy W; Townsend, Michael J

    2015-01-01

    Objectives The interferon (IFN) signature (IS) in patients with systemic lupus erythematosus (SLE) includes over 100 genes induced by type I IFN pathway activation. We developed a method to quantify the IS using three genes—the IS metric (ISM)—and characterised the clinical characteristics of patients with SLE with different ISM status from multiple clinical trials. Methods Blood microarray expression data from a training cohort of patients with SLE confirmed the presence of the IS and identified surrogate genes. We assayed these genes in a quantitative PCR (qPCR) assay, yielding an ISM from the IS. The association of ISM status with clinical disease characteristics was assessed in patients with extrarenal lupus and lupus nephritis from four clinical trials. Results Three genes, HERC5, EPSTI and CMPK2, correlated well with the IS (p>0.96), and composed the ISM qPCR assay. Using the 95th centile for healthy control data, patients with SLE from different studies were classified into two ISM subsets—ISM-Low and ISM-High—that are longitudinally stable over 36 weeks. Significant associations were identified between ISM-High status and higher titres of anti-dsDNA antibodies, presence of anti extractable nuclear antigen autoantibodies, elevated serum B cell activating factor of the tumour necrosis factor family (BAFF) levels, and hypocomplementaemia. However, measures of overall clinical disease activity were similar for ISM-High and ISM-Low groups. Conclusions The ISM is an IS biomarker that divides patients with SLE into two subpopulations—ISM-High and ISM-Low—with differing serological manifestations. The ISM does not distinguish between high and low disease activity, but may have utility in identifying patients more likely to respond to treatment(s) targeting IFN-α. Clinicaltrials.gov registration number NCT00962832. PMID:25861459

  18. A mouse-adapted SARS-coronavirus causes disease and mortality in BALB/c mice.

    Directory of Open Access Journals (Sweden)

    Anjeanette Roberts

    2007-01-01

    Full Text Available No single animal model for severe acute respiratory syndrome (SARS reproduces all aspects of the human disease. Young inbred mice support SARS-coronavirus (SARS-CoV replication in the respiratory tract and are available in sufficient numbers for statistical evaluation. They are relatively inexpensive and easily accessible, but their use in SARS research is limited because they do not develop illness following infection. Older (12- to 14-mo-old BALB/c mice develop clinical illness and pneumonitis, but they can be hard to procure, and immune senescence complicates pathogenesis studies. We adapted the SARS-CoV (Urbani strain by serial passage in the respiratory tract of young BALB/c mice. Fifteen passages resulted in a virus (MA15 that is lethal for mice following intranasal inoculation. Lethality is preceded by rapid and high titer viral replication in lungs, viremia, and dissemination of virus to extrapulmonary sites accompanied by lymphopenia, neutrophilia, and pathological changes in the lungs. Abundant viral antigen is extensively distributed in bronchial epithelial cells and alveolar pneumocytes, and necrotic cellular debris is present in airways and alveoli, with only mild and focal pneumonitis. These observations suggest that mice infected with MA15 die from an overwhelming viral infection with extensive, virally mediated destruction of pneumocytes and ciliated epithelial cells. The MA15 virus has six coding mutations associated with adaptation and increased virulence; when introduced into a recombinant SARS-CoV, these mutations result in a highly virulent and lethal virus (rMA15, duplicating the phenotype of the biologically derived MA15 virus. Intranasal inoculation with MA15 reproduces many aspects of disease seen in severe human cases of SARS. The availability of the MA15 virus will enhance the use of the mouse model for SARS because infection with MA15 causes morbidity, mortality, and pulmonary pathology. This virus will be of value as

  19. Essential veterinary education in emerging infections, modes of introduction of exotic animals, zoonotic diseases, bioterrorism, implications for human and animal health and disease manifestation.

    Science.gov (United States)

    Chomel, B B; Marano, N

    2009-08-01

    A fundamental role of the veterinary profession is the protection of human health through wholesome food and control of diseases of animal origin, especially zoonoses. Therefore, training of veterinary students worldwide needs to face the new challenges posed by emerging infections, both from wildlife and domestic animals, as well as risks from bio/agroterrorism. New courses emphasising recognition, response, recovery and prevention must be developed to respond to natural or intentionally induced emerging diseases and zoonoses. Training programmes in applied epidemiology, zoonoses and foreign animal diseases are crucial for the development of a strong workforce to deal with microbial threats. Students should learn the reporting pathways for reportable diseases in their countries or states. Knowledge of the principles of ecology and ecosystems should be acquired during pre-veterinary studies. Elective classes on wildlife diseases, emphasising wildlife zoonotic diseases, should be offered during the veterinary curriculum, as well as a course on risk communication, since veterinarians are frequently in the position of having to convey complex information under adverse circumstances.

  20. Interventions Targeting Glucocorticoid-Krüppel-like Factor 15-Branched-Chain Amino Acid Signaling Improve Disease Phenotypes in Spinal Muscular Atrophy Mice

    Directory of Open Access Journals (Sweden)

    Lisa M. Walter

    2018-05-01

    Full Text Available The circadian glucocorticoid-Krüppel-like factor 15-branched-chain amino acid (GC-KLF15-BCAA signaling pathway is a key regulatory axis in muscle, whose imbalance has wide-reaching effects on metabolic homeostasis. Spinal muscular atrophy (SMA is a neuromuscular disorder also characterized by intrinsic muscle pathologies, metabolic abnormalities and disrupted sleep patterns, which can influence or be influenced by circadian regulatory networks that control behavioral and metabolic rhythms. We therefore set out to investigate the contribution of the GC-KLF15-BCAA pathway in SMA pathophysiology of Taiwanese Smn−/−;SMN2 and Smn2B/− mouse models. We thus uncover substantial dysregulation of GC-KLF15-BCAA diurnal rhythmicity in serum, skeletal muscle and metabolic tissues of SMA mice. Importantly, modulating the components of the GC-KLF15-BCAA pathway via pharmacological (prednisolone, genetic (muscle-specific Klf15 overexpression and dietary (BCAA supplementation interventions significantly improves disease phenotypes in SMA mice. Our study highlights the GC-KLF15-BCAA pathway as a contributor to SMA pathogenesis and provides several treatment avenues to alleviate peripheral manifestations of the disease. The therapeutic potential of targeting metabolic perturbations by diet and commercially available drugs could have a broader implementation across other neuromuscular and metabolic disorders characterized by altered GC-KLF15-BCAA signaling. Keywords: Spinal muscular atrophy, KLF15, Glucocorticoids, Branched-chain amino acids, Metabolism, Therapy

  1. Corneal manifestations in systemic diseases

    OpenAIRE

    Zarranz-Ventura, J.; Nova, E. De; Moreno-Montañés, J.

    2008-01-01

    Un gran número de enfermedades sistémicas presentan manifestaciones corneales dentro de su espectro de enfermedad. El estudio detallado de todos los cuadros que asocian patología corneal resulta inabarcable, por ello se presentan las enfermedades más prevalentes o características. Este estudio contempla las enfermedades pulmonares y conectivopatías (colagenosis, enfermedades reumatológicas y enfermedades inflamatorias idiopáticas), las enfermedades dermatológicas, cardiovasculares, hematológi...

  2. Ocular manifestations of systemic diseases

    OpenAIRE

    Andonegui, J.

    2008-01-01

    Existe un gran número de enfermedades sistémicas que pueden presentar en algún momento de su evolución manifestaciones oculares. Estas alteraciones pueden provocar sintomatología por sí mismas, pueden ayudar a diagnosticar la enfermedad sistémica que las originó o pueden servir para monitorizar el curso evolutivo de la misma. Se destacan las principales características de una serie de enfermedades sistémicas asociadas a patología ocular que serán estudiadas en detalle a lo largo de esta monog...

  3. IFN-{gamma} enhances neurogenesis in wild-type mice and in a mouse model of Alzheimer's disease

    DEFF Research Database (Denmark)

    Baron, Rona; Nemirovsky, Anna; Harpaz, Idan

    2008-01-01

    the spatial learning and memory performance of the animals. In older mice, the effect of IFN-gamma is more pronounced in both wild-type mice and mice with Alzheimer's-like disease and is associated with neuroprotection. In addition, IFN-gamma reverses the increase in oligodendrogenesis observed in a mouse...... mechanisms can generate immunity to such deficits in neuronal repair. We demonstrate that in contrast to primarily innate immunity cytokines, such as interleukin-6 and tumor necrosis factor-alpha, the adaptive immunity cytokine IFN-gamma enhances neurogenesis in the dentate gyrus of adult mice and improves...

  4. Anti-Inflammatory Effects of Fargesin on Chemically Induced Inflammatory Bowel Disease in Mice

    Directory of Open Access Journals (Sweden)

    Bei Yue

    2018-06-01

    Full Text Available Fargesin is a bioactive lignan from Flos Magnoliae, an herb widely used in the treatment of allergic rhinitis, sinusitis, and headache in Asia. We sought to investigate whether fargesin ameliorates experimental inflammatory bowel disease (IBD in mice. Oral administration of fargesin significantly attenuated the symptoms of dextran sulfate sodium (DSS-induced colitis in mice by decreasing the inflammatory infiltration and myeloperoxidase (MPO activity, reducing tumor necrosis factor (TNF-α secretion, and inhibiting nitric oxide (NO production in colitis mice. The degradation of inhibitory κBα (IκBα, phosphorylation of p65, and mRNA expression of nuclear factor κB (NF-κB target genes were inhibited by fargesin treatment in the colon of the colitis mice. In vitro, fargesin blocked the nuclear translocation of p-p65, downregulated the protein levels of inducible NO synthase (iNOS and cyclooxygenase-2 (COX-2, and dose-dependently inhibited the activity of NF-κB-luciferase in lipopolysaccharide (LPS-stimulated RAW264.7 macrophages. Taken together, for the first time, the current study demonstrated the anti-inflammatory effects of fargesin on chemically induced IBD might be associated with NF-κB signaling suppression. The findings may contribute to the development of therapies for human IBD by using fargesin or its derivatives.

  5. Fetal loss in homozygous mutant Norrie disease mice: a new role of Norrin in reproduction.

    Science.gov (United States)

    Luhmann, Ulrich F O; Meunier, Dominique; Shi, Wei; Lüttges, Angela; Pfarrer, Christiane; Fundele, Reinald; Berger, Wolfgang

    2005-08-01

    Mutations in the Norrie disease pseudoglioma gene (NDP) are known to cause X-linked recessive Norrie disease. In addition, NDP mutations have been found in other vasoproliferative retinopathies such as familial exudative vitreoretinopathy, retinopathy of prematurity, and Coats disease, suggesting a role for Norrin in vascular development. Here we report that female mice homozygous for the Norrie disease pseudoglioma homolog (Ndph) knockout allele exhibit almost complete infertility, while heterozygous females and hemizygous males are fertile. Histological examinations and RNA in situ hybridization analyses revealed defects in vascular development and decidualization in pregnant Ndph-/- females from embryonic day 7 (E7) onwards, resulting in embryonic loss. Using RT-PCR analyses we also demonstrate, for the first time, the expression of Ndph in mouse uteri and deciduae as well as the expression of NDP in human placenta. Taken together, these data provide strong evidence for Norrin playing an important role in female reproductive tissues. Copyright 2005 Wiley-Liss, Inc

  6. Cosegregation and functional analysis of mutant ABCR (ABCA4) alleles in families that manifest both Stargardt disease and age-related macular degeneration.

    Science.gov (United States)

    Shroyer, N F; Lewis, R A; Yatsenko, A N; Wensel, T G; Lupski, J R

    2001-11-01

    Mutations in ABCR (ABCA4) have been reported to cause a spectrum of autosomal recessively inherited retinopathies, including Stargardt disease (STGD), cone-rod dystrophy and retinitis pigmentosa. Individuals heterozygous for ABCR mutations may be predisposed to develop the multifactorial disorder age-related macular degeneration (AMD). We hypothesized that some carriers of STGD alleles have an increased risk to develop AMD. We tested this hypothesis in a cohort of families that manifest both STGD and AMD. With a direct-sequencing mutation detection strategy, we found that AMD-affected relatives of STGD patients are more likely to be carriers of pathogenic STGD alleles than predicted based on chance alone. We further investigated the role of AMD-associated ABCR mutations by testing for expression and ATP-binding defects in an in vitro biochemical assay. We found that mutations associated with AMD have a range of assayable defects ranging from no detectable defect to apparent null alleles. Of the 21 missense ABCR mutations reported in patients with AMD, 16 (76%) show abnormalities in protein expression, ATP-binding or ATPase activity. We infer that carrier relatives of STGD patients are predisposed to develop AMD.

  7. Familial tumoral calcinosis and hyperostosis-hyperphosphataemia syndrome are different manifestations of the same disease: novel missense mutations in GALNT3

    International Nuclear Information System (INIS)

    Joseph, Leo; Joseph, Selvanayagam; Hing, Sandra N.; Idowu, Bernadine D.; Delaney, David; Presneau, Nadege; O'Donnell, Paul; Diss, Tim; Flanagan, Adrienne Margaret

    2010-01-01

    To report on the biochemistry and clinical and genetic findings of two siblings, the younger sister presenting with recurrent bone pain of the radius and ulna, and medullary sclerosis, and the older brother with soft tissue calcific deposits (tumoral calcinosis) but who later developed bone pain. Both were found to be hyperphosphaturic. The index family comprised four individuals (father, mother, brother, sister). The affected siblings were the offspring of a non-consanguineous Indian family of Tamil origin. Bidirectional sequencing was performed on the DNA from the index family and on 160 alleles from a population of 80 unrelated unaffected control individuals of Tamil extraction and 72 alleles from individuals of non-Tamil origin. Two symptomatic siblings were found to harbour previously unreported compound heterozygous missense UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase 3 (GalNAc-transferase; GALNT3) mutations in exon 4 c.842A>G and exon 5 c.1097T>G. This sequence variation was not detected in the control DNA. This is the first report of siblings exhibiting stigmata of familial tumoral calcinosis and hyperostosis-hyperphosphataemia syndrome with documented evidence of autosomal recessive missense GALNT3 mutations. The findings from this family add further evidence to the literature that familial tumoral calcinosis and hyperostosis-hyperphosphataemia syndrome are manifestations of the same disease and highlight the importance of appropriate metabolic and genetic investigations. (orig.)

  8. IgG4-Related Autoimmune Prostatitis: Is It an Unusual or Underdiagnosed Manifestation of IgG4-Related Disease?

    Directory of Open Access Journals (Sweden)

    María T. Bourlon

    2013-01-01

    Full Text Available IgG4-related disease (IgG4-RD encompasses a wide range of extrapancreatic manifestations. Albeit some are relatively well known, others such as autoimmune prostatitis remain poorly described. We present a 61-year-old Latin-American male with autoimmune pancreatitis (AIP who presented with lower urinary tract symptoms (LUTS, normal prostate specific antigen (PSA test, and prostate enlargement attributed to benign prostatic hyperplasia (BPH. He underwent a transurethral resection of the prostate (TURP after which symptoms were resolved. On histopathology, prostatic stroma had a dense inflammatory infiltrate rich in plasma cells and lymphocytes; immunohistochemical morphometric assessment showed >10 IgG4-positive plasma cells/high power field (HPF. The diagnosis of IgG4-related prostatitis was postoperatively. We compared the patient characteristics with those of previous reports on Asian patients. Shared findings included prostate enlargement, LUTS (symptoms that can be confused with BPH, and PSA within normal limits or mild elevations. IgG4-related prostatitis is rarely considered as a preprocedural diagnosis, even in patients with evidence of IgG4-RD. Involved prostate zones include mainly central and transitional zones and less frequently the peripheral. Currently, there is insufficient data about the natural history and outcome. Whether steroids, transurethral resection, or both are the treatment of choice needs to be elucidated.

  9. Familial tumoral calcinosis and hyperostosis-hyperphosphataemia syndrome are different manifestations of the same disease: novel missense mutations in GALNT3

    Energy Technology Data Exchange (ETDEWEB)

    Joseph, Leo; Joseph, Selvanayagam [Vinodhagan Memorial Hospital and Dr. Joseph' s Ortho Clinic, Department of Orthopaedic Surgery, Thanjavur (India); Hing, Sandra N.; Idowu, Bernadine D.; Delaney, David [Royal National Orthopaedic Hospital NHS Trust, Department of Histopathology, Stanmore, Middlesex (United Kingdom); Presneau, Nadege [University College London (UCL), Cancer Institute, London (United Kingdom); O' Donnell, Paul [Royal National Orthopaedic Hospital NHS Trust, Department of Radiology, Stanmore, Middlesex (United Kingdom); University College London (UCL), Institute of Orthopaedics and Musculoskeletal Science, Stanmore (United Kingdom); University College London (UCL), The Institute of Orthopaedics and Musculoskeletal Science, London (United Kingdom); Diss, Tim [University College London Hospital (UCLH) NHS Trust, Rockefeller Building, Department of Histopathology, London (United Kingdom); Flanagan, Adrienne Margaret [Royal National Orthopaedic Hospital NHS Trust, Department of Histopathology, Stanmore, Middlesex (United Kingdom); University College London (UCL), Cancer Institute, London (United Kingdom); University College London Hospital (UCLH) NHS Trust, Rockefeller Building, Department of Histopathology, London (United Kingdom); University College London (UCL), Institute of Orthopaedics and Musculoskeletal Science, Stanmore (United Kingdom); Institute of Orthopaedics and Musculoskeletal Science, Stanmore, Middlesex (United Kingdom)

    2010-01-15

    To report on the biochemistry and clinical and genetic findings of two siblings, the younger sister presenting with recurrent bone pain of the radius and ulna, and medullary sclerosis, and the older brother with soft tissue calcific deposits (tumoral calcinosis) but who later developed bone pain. Both were found to be hyperphosphaturic. The index family comprised four individuals (father, mother, brother, sister). The affected siblings were the offspring of a non-consanguineous Indian family of Tamil origin. Bidirectional sequencing was performed on the DNA from the index family and on 160 alleles from a population of 80 unrelated unaffected control individuals of Tamil extraction and 72 alleles from individuals of non-Tamil origin. Two symptomatic siblings were found to harbour previously unreported compound heterozygous missense UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase 3 (GalNAc-transferase; GALNT3) mutations in exon 4 c.842A>G and exon 5 c.1097T>G. This sequence variation was not detected in the control DNA. This is the first report of siblings exhibiting stigmata of familial tumoral calcinosis and hyperostosis-hyperphosphataemia syndrome with documented evidence of autosomal recessive missense GALNT3 mutations. The findings from this family add further evidence to the literature that familial tumoral calcinosis and hyperostosis-hyperphosphataemia syndrome are manifestations of the same disease and highlight the importance of appropriate metabolic and genetic investigations. (orig.)

  10. Liver manifestations of cystic fibrosis

    International Nuclear Information System (INIS)

    Akata, Deniz; Akhan, Okan

    2007-01-01

    Chronic liver disease is one of the major complications of cystic fibrosis (CF). Significant liver disease is seen in 13-25% of children with CF. Improved life expectancy and prolonged follow-up have favored better characterization of the hepatic manifestations of CF and allowed direct observation of an increasing number of liver-related events. Liver disease typically develops in the first decade of life, with the incidence dropping rapidly after the age of 10 years. The wide spectrum of liver disease ranging from asymptomatic gallbladder abnormalities to biliary cirrhosis will be reviewed in this article

  11. Differential replication of Foot-and-mouth disease viruses in mice determine lethality.

    Science.gov (United States)

    Cacciabue, Marco; García-Núñez, María Soledad; Delgado, Fernando; Currá, Anabella; Marrero, Rubén; Molinari, Paula; Rieder, Elizabeth; Carrillo, Elisa; Gismondi, María Inés

    2017-09-01

    Adult C57BL/6J mice have been used to study Foot-and-mouth disease virus (FMDV) biology. In this work, two variants of an FMDV A/Arg/01 strain exhibiting differential pathogenicity in adult mice were identified and characterized: a non-lethal virus (A01NL) caused mild signs of disease, whereas a lethal virus (A01L) caused death within 24-48h independently of the dose used. Both viruses caused a systemic infection with pathological changes in the exocrine pancreas. Virus A01L reached higher viral loads in plasma and organs of inoculated mice as well as increased replication in an ovine kidney cell line. Complete consensus sequences revealed 6 non-synonymous changes between A01L and A10NL genomes that might be linked to replication differences, as suggested by in silico prediction studies. Our results highlight the biological significance of discrete genomic variations and reinforce the usefulness of this animal model to study viral determinants of lethality. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Therapy of Pelizaeus-Merzbacher disease in mice by feeding a cholesterol-enriched diet.

    Science.gov (United States)

    Saher, Gesine; Rudolphi, Fabian; Corthals, Kristina; Ruhwedel, Torben; Schmidt, Karl-Friedrich; Löwel, Siegrid; Dibaj, Payam; Barrette, Benoit; Möbius, Wiebke; Nave, Klaus-Armin

    2012-07-01

    Duplication of PLP1 (proteolipid protein gene 1) and the subsequent overexpression of the myelin protein PLP (also known as DM20) in oligodendrocytes is the most frequent cause of Pelizaeus-Merzbacher disease (PMD), a fatal leukodystrophy without therapeutic options. PLP binds cholesterol and is contained within membrane lipid raft microdomains. Cholesterol availability is the rate-limiting factor of central nervous system myelin synthesis. Transgenic mice with extra copies of the Plp1 gene are accurate models of PMD. Dysmyelination followed by demyelination, secondary inflammation and axon damage contribute to the severe motor impairment in these mice. The finding that in Plp1-transgenic oligodendrocytes, PLP and cholesterol accumulate in late endosomes and lysosomes (endo/lysosomes), prompted us to further investigate the role of cholesterol in PMD. Here we show that cholesterol itself promotes normal PLP trafficking and that dietary cholesterol influences PMD pathology. In a preclinical trial, PMD mice were fed a cholesterol-enriched diet. This restored oligodendrocyte numbers and ameliorated intracellular PLP accumulation. Moreover, myelin content increased, inflammation and gliosis were reduced and motor defects improved. Even after onset of clinical symptoms, cholesterol treatment prevented disease progression. Dietary cholesterol did not reduce Plp1 overexpression but facilitated incorporation of PLP into myelin membranes. These findings may have implications for therapeutic interventions in patients with PMD.

  13. Ebola Virus Replication and Disease Without Immunopathology in Mice Expressing Transgenes to Support Human Myeloid and Lymphoid Cell Engraftment.

    Science.gov (United States)

    Spengler, Jessica R; Lavender, Kerry J; Martellaro, Cynthia; Carmody, Aaron; Kurth, Andreas; Keck, James G; Saturday, Greg; Scott, Dana P; Nichol, Stuart T; Hasenkrug, Kim J; Spiropoulou, Christina F; Feldmann, Heinz; Prescott, Joseph

    2016-10-15

    The study of Ebola virus (EBOV) pathogenesis in vivo has been limited to nonhuman primate models or use of an adapted virus to cause disease in rodent models. Herein we describe wild-type EBOV (Makona variant) infection of mice engrafted with human hematopoietic CD34 + stem cells (Hu-NSG™-SGM3 mice; hereafter referred to as SGM3 HuMice). SGM3 HuMice support increased development of myeloid immune cells, which are primary EBOV targets. In SGM3 HuMice, EBOV replicated to high levels, and disease was observed following either intraperitoneal or intramuscular inoculation. Despite the high levels of viral antigen and inflammatory cell infiltration in the liver, the characteristic histopathology of Ebola virus disease was not observed, and this absence of severe immunopathology may have contributed to the recovery and survival of some of the animals. Future investigations into the underlying mechanisms of the atypical disease presentation in SGM3 HuMice will provide additional insights into the immunopathogenesis of severe EBOV disease. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  14. Cutaneous manifestations of primary immunodeficiency

    Directory of Open Access Journals (Sweden)

    Safa Abdelhakim

    2017-01-01

    Full Text Available Primary immunodeficiency diseases (PIDs are a group of rare, chronic disorders with deficient or malfunctioning immune system. It commonly affects the hematopoietic system, with skin the second most affected organ. Skin involvement is observed in half of pediatric PID cases and often precedes the final diagnosis. Skin infections and eczemas are the two most common manifestations in PID.[1] Skin manifestations associated with PIDs can be of infectious and noninfectious causes. Common noninfectious causes are eczema, erythroderma, cutaneous granulomas, dysplasia, vasculitis, and telangiectasia. It is important to be aware of skin manifestations in pediatric patients as early detection of PID may aid in the management of serious immunologic conditions and prevent associated morbidity and mortality.

  15. Incremental value of a genetic risk score for the prediction of new vascular events in patients with clinically manifest vascular disease.

    Science.gov (United States)

    Weijmans, Maaike; de Bakker, Paul I W; van der Graaf, Yolanda; Asselbergs, Folkert W; Algra, Ale; Jan de Borst, Gert; Spiering, Wilko; Visseren, Frank L J

    2015-04-01

    Several genetic markers are related to incidence of cardiovascular events. We evaluated whether a genetic risk score (GRS) based on 30 single-nucleotide-polymorphisms associated with coronary artery disease (CAD) can improve prediction of 10-year risk of new cardiovascular events in patients with clinical manifest vascular disease. In 5742 patients with symptomatic vascular disease enrolled in the SMART study, we developed Cox regression models based on the SMART Risk Score (SRS) and based on the SRS plus the GRS in all patients, in patients with a history of acute arterial thrombotic events and in patients with a history of more stable atherosclerosis and without CAD. The discriminatory ability was expressed by the c-statistic. Model calibration was evaluated by calibration plots. The incremental value of adding the GRS was assessed by net reclassification index (NRI) and decision curve analysis. During a median follow-up of 6.5 years (IQR4.0-9.5), the composite outcome of myocardial infarction, stroke, or vascular death occurred in 933 patients. Hazard ratios of GRS ranging from 0.86 to 1.35 were observed. The discriminatory capacity of the SRS for prediction of 10-year risk of cardiovascular events was fairly good (c-statistic 0.70, 95%CI 0.68-0.72), similar to the model based on the SRS plus the GRS. Calibration of the models based on SRS and SRS plus GRS was adequate. No increase in c-statistics, categorical NRIs and decision curves was observed when adding the GRS. The continuous NRI improved only in patients with stable atherosclerosis (0.14, 95%CI 0.03-0.25), increasing further excluding patients with a history of CAD (0.21, 95%CI 0.06-0.36). In patients with symptomatic vascular disease, a GRS did not improve risk prediction of 10-year risk of cardiovascular events beyond clinical characteristics. The GRS might improve risk prediction of first vascular events in the subgroup of patients with a history of stable atherosclerosis. Copyright © 2015 Elsevier

  16. Of Mice and Men: Neurogenesis, Cognition and Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Orly eLazarov

    2013-08-01

    Full Text Available Neural stem cells are maintained in the subgranular layer of the dentate gyrus and in the subventricular zone in the adult mammalian brain throughout life. Neurogenesis is continuous, but its extent is tightly regulated by environmental factors, behavior, hormonal state, age and brain health. Increasing evidence supports a role for new neurons in cognitive function in rodents. Recent evidence delineates potential significant differences between adult neurogenesis in rodents and humans. Being context-dependent, neurogenesis in the human brain might be manifested differently than in the rodent brain. Decline in neurogenesis may play a role in cognitive deterioration, leading to the development of progressive learning and memory disorders, such as Alzheimer’s disease. This review discusses the different observations concerning neurogenesis in the rodent and human brain, and their functional implications for the healthy and diseased brain.

  17. The Effects of Pharmacological Inhibition of Histone Deacetylase 3 (HDAC3 in Huntington's Disease Mice.

    Directory of Open Access Journals (Sweden)

    Haiqun Jia

    Full Text Available An important epigenetic modification in Huntington's disease (HD research is histone acetylation, which is regulated by histone acetyltransferase and histone deacetylase (HDAC enzymes. HDAC inhibitors have proven effective in HD model systems, and recent work is now focused on functional dissection of the individual HDAC enzymes in these effects. Histone deacetylase 3 (HDAC3, a member of the class I subfamily of HDACs, has previously been implicated in neuronal toxicity and huntingtin-induced cell death. Hence, we tested the effects of RGFP966 ((E-N-(2-amino-4-fluorophenyl-3-(1-cinnamyl-1H-pyrazol-4-ylacrylamide, a benzamide-type HDAC inhibitor that selectively targets HDAC3, in the N171-82Q transgenic mouse model of HD. We found that RGFP966 at doses of 10 and 25 mg/kg improves motor deficits on rotarod and in open field exploration, accompanied by neuroprotective effects on striatal volume. In light of previous studies implicating HDAC3 in immune function, we measured gene expression changes for 84 immune-related genes elicited by RGFP966 using quantitative PCR arrays. RGFP966 treatment did not cause widespread changes in cytokine/chemokine gene expression patterns, but did significantly alter the striatal expression of macrophage migration inhibitory factor (Mif, a hormone immune modulator associated with glial cell activation, in N171-82Q transgenic mice, but not WT mice. Accordingly, RGFP966-treated mice showed decreased glial fibrillary acidic protein (GFAP immunoreactivity, a marker of astrocyte activation, in the striatum of N171-82Q transgenic mice compared to vehicle-treated mice. These findings suggest that the beneficial actions of HDAC3 inhibition could be related, in part, with lowered Mif levels and its associated downstream effects.

  18. Inhibition of the soluble epoxide hydrolase promotes albuminuria in mice with progressive renal disease.

    Directory of Open Access Journals (Sweden)

    Oliver Jung

    2010-08-01

    Full Text Available Epoxyeicotrienoic acids (EETs are cytochrome P450-dependent anti-hypertensive and anti-inflammatory derivatives of arachidonic acid, which are highly abundant in the kidney and considered reno-protective. EETs are degraded by the enzyme soluble epoxide hydrolase (sEH and sEH inhibitors are considered treatment for chronic renal failure (CRF. We determined whether sEH inhibition attenuates the progression of CRF in the 5/6-nephrectomy model (5/6-Nx in mice. 5/6-Nx mice were treated with a placebo, an ACE-inhibitor (Ramipril, 40 mg/kg, the sEH-inhibitor cAUCB or the CYP-inhibitor fenbendazole for 8 weeks. 5/6-Nx induced hypertension, albuminuria, glomerulosclerosis and tubulo-interstitial damage and these effects were attenuated by Ramipril. In contrast, cAUCB failed to lower the blood pressure and albuminuria was more severe as compared to placebo. Plasma EET-levels were doubled in 5/6 Nx-mice as compared to sham mice receiving placebo. Renal sEH expression was attenuated in 5/6-Nx mice but cAUCB in these animals still further increased the EET-level. cAUCB also increased 5-HETE and 15-HETE, which derive from peroxidation or lipoxygenases. Similar to cAUCB, CYP450 inhibition increased HETEs and promoted albuminuria. Thus, sEH-inhibition failed to elicit protective effects in the 5/6-Nx model and showed a tendency to aggravate the disease. These effects might be consequence of a shift of arachidonic acid metabolism into the lipoxygenase pathway.

  19. Generation of healthy mice from gene-corrected disease-specific induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Guangming Wu

    2011-07-01

    Full Text Available Using the murine model of tyrosinemia type 1 (fumarylacetoacetate hydrolase [FAH] deficiency; FAH⁻/⁻ mice as a paradigm for orphan disorders, such as hereditary metabolic liver diseases, we evaluated fibroblast-derived FAH⁻/⁻-induced pluripotent stem cells (iPS cells as targets for gene correction in combination with the tetraploid embryo complementation method. First, after characterizing the FAH⁻/⁻ iPS cell lines, we aggregated FAH⁻/⁻-iPS cells with tetraploid embryos and obtained entirely FAH⁻/⁻-iPS cell-derived mice that were viable and exhibited the phenotype of the founding FAH⁻/⁻ mice. Then, we transduced FAH cDNA into the FAH⁻/⁻-iPS cells using a third-generation lentiviral vector to generate gene-corrected iPS cells. We could not detect any chromosomal alterations in these cells by high-resolution array CGH analysis, and after their aggregation with tetraploid embryos, we obtained fully iPS cell-derived healthy mice with an astonishing high efficiency for full-term development of up to 63.3%. The gene correction was validated functionally by the long-term survival and expansion of FAH-positive cells of these mice after withdrawal of the rescuing drug NTBC (2-(2-nitro-4-fluoromethylbenzoyl-1,3-cyclohexanedione. Furthermore, our results demonstrate that both a liver-specific promoter (transthyretin, TTR-driven FAH transgene and a strong viral promoter (from spleen focus-forming virus, SFFV-driven FAH transgene rescued the FAH-deficiency phenotypes in the mice derived from the respective gene-corrected iPS cells. In conclusion, our data demonstrate that a lentiviral gene repair strategy does not abrogate the full pluripotent potential of fibroblast-derived iPS cells, and genetic manipulation of iPS cells in combination with tetraploid embryo aggregation provides a practical and rapid approach to evaluate the efficacy of gene correction of human diseases in mouse models.

  20. Reversal of experimental colitis disease activity in mice following administration of an adenoviral IL-10 vector.

    Science.gov (United States)

    Sasaki, Makoto; Mathis, J Michael; Jennings, Merilyn H; Jordan, Paul; Wang, Yuping; Ando, Tomoaki; Joh, Takashi; Alexander, J Steven

    2005-10-31

    Genetic deficiency in the expression of interleukin-10 (IL-10) is associated with the onset and progression of experimental inflammatory bowel disease (IBD). The clinical significance of IL-10 expression is supported by studies showing that immune-augmentation of IL-10 prevents inflammation and mucosal damage in animal models of colitis and in human colitis. Interleukin-10 (IL-10), an endogenous anti-inflammatory and immunomodulating cytokine, has been shown to prevent some inflammation and injury in animal and clinical studies, but the efficacy of IL-10 treatment remains unsatisfactory. We found that intra-peritoneal administration of adenoviral IL-10 to mice significantly reversed colitis induced by administration of 3% DSS (dextran sulfate), a common model of colitis. Adenoviral IL-10 (Ad-IL10) transfected mice developed high levels of IL-10 (394 +/- 136 pg/ml) within the peritoneal cavity where the adenovirus was expressed. Importantly, when given on day 4 (after the induction of colitis w/DSS), Ad-IL10 significantly reduced disease activity and weight loss and completely prevented histopathologic injury to the colon at day 10. Mechanistically, compared to Ad-null and DSS treated mice, Ad-IL10 and DSS-treated mice were able to suppress the expression of MAdCAM-1, an endothelial adhesion molecule associated with IBD. Our results suggest that Ad-IL10 (adenoviral IL-10) gene therapy of the intestine or peritoneum may be useful in the clinical treatment of IBD, since we demonstrated that this vector can reverse the course of an existing gut inflammation and markers of inflammation.

  1. Reversal of experimental colitis disease activity in mice following administration of an adenoviral IL-10 vector

    Directory of Open Access Journals (Sweden)

    Ando Tomoaki

    2005-10-01

    Full Text Available Abstract Genetic deficiency in the expression of interleukin-10 (IL-10 is associated with the onset and progression of experimental inflammatory bowel disease (IBD. The clinical significance of IL-10 expression is supported by studies showing that immune-augmentation of IL-10 prevents inflammation and mucosal damage in animal models of colitis and in human colitis. Interleukin-10 (IL-10, an endogenous anti-inflammatory and immunomodulating cytokine, has been shown to prevent some inflammation and injury in animal and clinical studies, but the efficacy of IL-10 treatment remains unsatisfactory. We found that intra-peritoneal administration of adenoviral IL-10 to mice significantly reversed colitis induced by administration of 3% DSS (dextran sulfate, a common model of colitis. Adenoviral IL-10 (Ad-IL10 transfected mice developed high levels of IL-10 (394 +/- 136 pg/ml within the peritoneal cavity where the adenovirus was expressed. Importantly, when given on day 4 (after the induction of colitis w/DSS, Ad-IL10 significantly reduced disease activity and weight loss and completely prevented histopathologic injury to the colon at day 10. Mechanistically, compared to Ad-null and DSS treated mice, Ad-IL10 and DSS-treated mice were able to suppress the expression of MAdCAM-1, an endothelial adhesion molecule associated with IBD. Our results suggest that Ad-IL10 (adenoviral IL-10 gene therapy of the intestine or peritoneum may be useful in the clinical treatment of IBD, since we demonstrated that this vector can reverse the course of an existing gut inflammation and markers of inflammation.

  2. Radiological pulmonary manifestations of acquired immunodeficiency syndrome

    International Nuclear Information System (INIS)

    Marchiori, Edson; Melo, Alessandro Severo Alves de; Ossa, Alfonso Jaramillo

    1999-01-01

    In this article are reviewed the principal radiologic manifestations of inflammatory and tumoral diseases the compromise the lungs of patients with acquired immunodeficiency syndrome. In the group of inflammatory diseases the radiologic aspects of pneumocystosis, cytomegalovirus disease, cryptococcosis, tuberculosis and bacterial pneumonias are emphasized. In the neoplasic diseases' group the aspects of lymphoma and Kaposi's sarcoma are specially presented. (author)

  3. ASIC1a Deficient Mice Show Unaltered Neurodegeneration in the Subacute MPTP Model of Parkinson Disease.

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    Daniel Komnig

    Full Text Available Inflammation contributes to the death of dopaminergic neurons in Parkinson disease and can be accompanied by acidification of extracellular pH, which may activate acid-sensing ion channels (ASIC. Accordingly, amiloride, a non-selective inhibitor of ASIC, was protective in an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP mouse model of Parkinson disease. To complement these findings we determined MPTP toxicity in mice deficient for ASIC1a, the most common ASIC isoform in neurons. MPTP was applied i.p. in doses of 30 mg per kg on five consecutive days. We determined the number of dopaminergic neurons in the substantia nigra, assayed by stereological counting 14 days after the last MPTP injection, the number of Nissl positive neurons in the substantia nigra, and the concentration of catecholamines in the striatum. There was no difference between ASIC1a-deficient mice and wildtype controls. We are therefore not able to confirm that ASIC1a are involved in MPTP toxicity. The difference might relate to the subacute MPTP model we used, which more closely resembles the pathogenesis of Parkinson disease, or to further targets of amiloride.

  4. Serum HSV-1 and 2 IgM in sexually transmitted diseases - more for screening less for diagnosis: An evaluation of clinical manifestation

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    Dharmishtha G Tada

    2012-01-01

    Full Text Available Background: Herpes simplex virus type 2 (HSV-2 is the cause of most genital herpes. Now, HSV-1 has become an important cause and represents even about 30% of genital herpes in some countries. So, study related to genital herpes should consider both HSV-1 and HSV-2. Aim: To examine trends in HSV-1 and 2 seroprevalence by Serum HSV-1 and 2 IgM in all type of sexually transmitted disease (STD patients and also to evaluate correlation of serum HSV-1 and 2 IgM in STD. Materials and Methods: 150 patients attending the STD clinic attached to a tertiary care hospital of Ahmedabad were included in the study. Serum HSV-1 and 2 IgM correlations with clinical manifestations of recurrent and non-recurrent type of genital herpes patients and other non-herpetic STD patients were studied. Results: The overall serum HSV-1 and 2 IgM in STD seroprevalence were 15.66%. Female has significant higher prevalence (P < 0.05. STD cases and HSV seroprevalence were specially concentrated in persons aged 21 to 30 years. Among those positive with HSV, the distribution of STD are wide spread and found in non-herpetic group at high frequency. Out of total 23 serum HSV-1 and 2 IgM positive, 12 and 11 are distributed in herpetic and non-herpetic STDs, respectively. Discussion and Conclusion: Though serum HSV-1 and 2 IgM in STDs are less diagnostic, they help to see the iceberg part of the infection among the population concerned in recent scenario or in another words, it provides recent infective burden.

  5. A High-Fat, High-Fructose Diet Induces Antioxidant Imbalance and Increases the Risk and Progression of Nonalcoholic Fatty Liver Disease in Mice

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    Kanokwan Jarukamjorn

    2016-01-01

    Full Text Available Excessive fat liver is an important manifestation of nonalcoholic fatty liver disease (NAFLD, associated with obesity, insulin resistance, and oxidative stress. In the present study, the effects of a high-fat, high-fructose diet (HFFD on mRNA levels and activities of the antioxidant enzymes, including superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GPx, were determined in mouse livers and brains. The histomorphology of the livers was examined and the state of nonenzymatic reducing system was evaluated by measuring the glutathione system and the lipid peroxidation. Histopathology of the liver showed that fat accumulation and inflammation depended on the period of the HFFD-consumption. The levels of mRNA and enzymatic activities of SOD, CAT, and GPx were raised, followed by the increases in malondialdehyde levels in livers and brains of the HFFD mice. The oxidized GSSG content was increased while the total GSH and the reduced GSH were decreased, resulting in the increase in the GSH/GSSG ratio in both livers and brains of the HFFD mice. These observations suggested that liver damage and oxidative stress in the significant organs were generated by continuous HFFD-consumption. Imbalance of antioxidant condition induced by long-term HFFD-consumption might increase the risk and progression of NAFLD.

  6. Cordyceps militaris alleviates non-alcoholic fatty liver disease in ob/ob mice

    OpenAIRE

    Choi, Ha-Neul; Jang, Yang-Hee; Kim, Min-Joo; Seo, Min Jeong; Kang, Byoung Won; Jeong, Yong Kee; Kim, Jung-In

    2014-01-01

    BACKGROUND/OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) is becoming an important public health problem as metabolic syndrome and type 2 diabetes have become epidemic. In this study we investigated the protective effect of Cordyceps militaris (C. militaris) against NAFLD in an obese mouse model. MATERIALS/METHODS Four-week-old male ob/ob mice were fed an AIN-93G diet or a diet containing 1% C. militaris water extract for 10 weeks after 1 week of adaptation. Serum glucose, insulin, free...

  7. Cordyceps militaris alleviates non-alcoholic fatty liver disease in ob/ob mice.

    Science.gov (United States)

    Choi, Ha-Neul; Jang, Yang-Hee; Kim, Min-Joo; Seo, Min Jeong; Kang, Byoung Won; Jeong, Yong Kee; Kim, Jung-In

    2014-04-01

    Non-alcoholic fatty liver disease (NAFLD) is becoming an important public health problem as metabolic syndrome and type 2 diabetes have become epidemic. In this study we investigated the protective effect of Cordyceps militaris (C. militaris) against NAFLD in an obese mouse model. Four-week-old male ob/ob mice were fed an AIN-93G diet or a diet containing 1% C. militaris water extract for 10 weeks after 1 week of adaptation. Serum glucose, insulin, free fatty acid (FFA), alanine transaminase (ALT), and proinflammatory cytokines were measured. Hepatic levels of lipids, glutathione (GSH), and lipid peroxide were determined. Consumption of C. militaris significantly decreased serum glucose, as well as homeostasis model assessment for insulin resistance (HOMA-IR), in ob/ob mice. In addition to lowering serum FFA levels, C. militaris also significantly decreased hepatic total lipids and triglyceride contents. Serum ALT activities and tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were reduced by C. militaris. Consumption of C. militaris increased hepatic GSH and reduced lipid peroxide levels. These results indicate that C. militaris can exert protective effects against development of NAFLD, partly by reducing inflammatory cytokines and improving hepatic antioxidant status in ob/ob mice.

  8. Transmission and adaptation of chronic wasting disease to hamsters and transgenic mice: evidence for strains.

    Science.gov (United States)

    Raymond, Gregory J; Raymond, Lynne D; Meade-White, Kimberly D; Hughson, Andrew G; Favara, Cynthia; Gardner, Donald; Williams, Elizabeth S; Miller, Michael W; Race, Richard E; Caughey, Byron

    2007-04-01

    In vitro screening using the cell-free prion protein conversion system indicated that certain rodents may be susceptible to chronic wasting disease (CWD). Therefore, CWD isolates from mule deer, white-tailed deer, and elk were inoculated intracerebrally into various rodent species to assess the rodents' susceptibility and to develop new rodent models of CWD. The species inoculated were Syrian golden, Djungarian, Chinese, Siberian, and Armenian hamsters, transgenic mice expressing the Syrian golden hamster prion protein, and RML Swiss and C57BL10 wild-type mice. The transgenic mice and the Syrian golden, Chinese, Siberian, and Armenian hamsters had limited susceptibility to certain of the CWD inocula, as evidenced by incomplete attack rates and long incubation periods. For serial passages of CWD isolates in Syrian golden hamsters, incubation periods rapidly stabilized, with isolates having either short (85 to 89 days) or long (408 to 544 days) mean incubation periods and distinct neuropathological patterns. In contrast, wild-type mouse strains and Djungarian hamsters were not susceptible to CWD. These results show that CWD can be transmitted and adapted to some species of rodents and suggest that the cervid-derived CWD inocula may have contained or diverged into at least two distinct transmissible spongiform encephalopathy strains.

  9. Early Detection of Apathetic Phenotypes in Huntington's Disease Knock-in Mice Using Open Source Tools.

    Science.gov (United States)

    Minnig, Shawn; Bragg, Robert M; Tiwana, Hardeep S; Solem, Wes T; Hovander, William S; Vik, Eva-Mari S; Hamilton, Madeline; Legg, Samuel R W; Shuttleworth, Dominic D; Coffey, Sydney R; Cantle, Jeffrey P; Carroll, Jeffrey B

    2018-02-02

    Apathy is one of the most prevalent and progressive psychiatric symptoms in Huntington's disease (HD) patients. However, preclinical work in HD mouse models tends to focus on molecular and motor, rather than affective, phenotypes. Measuring behavior in mice often produces noisy data and requires large cohorts to detect phenotypic rescue with appropriate power. The operant equipment necessary for measuring affective phenotypes is typically expensive, proprietary to commercial entities, and bulky which can render adequately sized mouse cohorts as cost-prohibitive. Thus, we describe here a home-built, open-source alternative to commercial hardware that is reliable, scalable, and reproducible. Using off-the-shelf hardware, we adapted and built several of the rodent operant buckets (ROBucket) to test Htt Q111/+ mice for attention deficits in fixed ratio (FR) and progressive ratio (PR) tasks. We find that, despite normal performance in reward attainment in the FR task, Htt Q111/+ mice exhibit reduced PR performance at 9-11 months of age, suggesting motivational deficits. We replicated this in two independent cohorts, demonstrating the reliability and utility of both the apathetic phenotype, and these ROBuckets, for preclinical HD studies.

  10. Interleukin-10 Modulation of Virus Clearance and Disease in Mice with Alphaviral Encephalomyelitis.

    Science.gov (United States)

    Martin, Nina M; Griffin, Diane E

    2018-03-15

    Alphaviruses are an important cause of mosquito-borne outbreaks of arthritis, rash, and encephalomyelitis. Previous studies in mice with a virulent strain (neuroadapted SINV [NSV]) of the alphavirus Sindbis virus (SINV) identified a role for Th17 cells and regulation by interleukin-10 (IL-10) in the pathogenesis of fatal encephalomyelitis (K. A. Kulcsar, V. K. Baxter, I. P. Greene, and D. E. Griffin, Proc Natl Acad Sci U S A 111:16053-16058, 2014, https://doi.org/10.1073/pnas.1418966111). To determine the role of virus virulence in generation of immune responses, we analyzed the modulatory effects of IL-10 on disease severity, virus clearance, and the CD4 + T cell response to infection with a recombinant strain of SINV of intermediate virulence (TE12). The absence of IL-10 during TE12 infection led to longer morbidity, more weight loss, higher mortality, and slower viral clearance than in wild-type mice. More severe disease and impaired virus clearance in IL-10 -/- mice were associated with more Th1 cells, fewer Th2 cells, innate lymphoid type 2 cells, regulatory cells, and B cells, and delayed production of antiviral antibody in the central nervous system (CNS) without an effect on Th17 cells. Therefore, IL-10 deficiency led to more severe disease in TE12-infected mice by increasing Th1 cells and by hampering development of the local B cell responses necessary for rapid production of antiviral antibody and virus clearance from the CNS. In addition, the shift from Th17 to Th1 responses with decreased virus virulence indicates that the effects of IL-10 deficiency on immunopathologic responses in the CNS during alphavirus infection are influenced by virus strain. IMPORTANCE Alphaviruses cause mosquito-borne outbreaks of encephalomyelitis, but determinants of outcome are incompletely understood. We analyzed the effects of the anti-inflammatory cytokine IL-10 on disease severity and virus clearance after infection with an alphavirus strain of intermediate virulence

  11. Serum Levels of Interleukin 33 and Soluble ST2 Are Associated with the Extent of Disease Activity and Cutaneous Manifestations in Patients with Active Adult-onset Still's Disease.

    Science.gov (United States)

    Han, Jae Ho; Suh, Chang-Hee; Jung, Ju-Yang; Ahn, Mi-Hyun; Kwon, Ji Eun; Yim, Hyunee; Kim, Hyoun-Ah

    2017-06-01

    Interleukin 33 (IL-33), a member of the IL-1 family and a ligand of the orphan receptor ST2, plays key roles in innate and adaptive immunity. We examined the associations between IL-33/ST2 levels and clinical manifestations of patients with active adult-onset Still's disease (AOSD). Blood samples were collected from 40 patients with active AOSD, 28 patients with rheumatoid arthritis (RA), and 27 healthy controls (HC). The serum levels of IL-33 and soluble ST2 were determined using ELISA. Expression levels of IL-33 and ST2 in biopsy specimens obtained from 34 AOSD patients with rash were immunohistochemically investigated. IL-33 levels of patients with AOSD were higher than those of patients with RA and HC. Soluble ST2 levels of patients with AOSD were higher than those of HC, but not of patients with RA. Serum IL-33 levels correlated with systemic score, erythrocyte sedimentation rate, ferritin levels, and aspartate transaminase levels. However, serum soluble ST2 levels correlated only with ferritin levels. The numbers of inflammatory cells expressing IL-33 and ST2 were elevated in skin lesions of patients with AOSD compared to HC, but did not differ from those of the skin lesions of eczema or psoriasis. We found significantly higher serum IL-33 and soluble ST2 levels in patients with active AOSD. Results indicate that the IL-33/ST2 signaling pathway may play a role in the pathogenesis of the acute inflammation and skin manifestations associated with AOSD.

  12. Specificity of anti-tau antibodies when analyzing mice models of Alzheimer's disease: problems and solutions.

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    Franck R Petry

    Full Text Available Aggregates of hyperphosphorylated tau protein are found in a group of diseases called tauopathies, which includes Alzheimer's disease. The causes and consequences of tau hyperphosphorylation are routinely investigated in laboratory animals. Mice are the models of choice as they are easily amenable to transgenic technology; consequently, their tau phosphorylation levels are frequently monitored by Western blotting using a panel of monoclonal/polyclonal anti-tau antibodies. Given that mouse secondary antibodies can recognize endogenous mouse immunoglobulins (Igs and the possible lack of specificity with some polyclonal antibodies, non-specific signals are commonly observed. Here, we characterized the profiles of commonly used anti-tau antibodies in four different mouse models: non-transgenic mice, tau knock-out (TKO mice, 3xTg-AD mice, and hypothermic mice, the latter a positive control for tau hyperphosphorylation. We identified 3 tau monoclonal antibody categories: type 1, characterized by high non-specificity (AT8, AT180, MC1, MC6, TG-3, type 2, demonstrating low non-specificity (AT270, CP13, CP27, Tau12, TG5, and type 3, with no non-specific signal (DA9, PHF-1, Tau1, Tau46. For polyclonal anti-tau antibodies, some displayed non-specificity (pS262, pS409 while others did not (pS199, pT205, pS396, pS404, pS422, A0024. With monoclonal antibodies, most of the interfering signal was due to endogenous Igs and could be eliminated by different techniques: i using secondary antibodies designed to bind only non-denatured Igs, ii preparation of a heat-stable fraction, iii clearing Igs from the homogenates, and iv using secondary antibodies that only bind the light chain of Igs. All of these techniques removed the non-specific signal; however, the first and the last methods were easier and more reliable. Overall, our study demonstrates a high risk of artefactual signal when performing Western blotting with routinely used anti-tau antibodies, and proposes

  13. R6/2 Huntington's disease mice develop early and progressive abnormal brain metabolism and seizures.

    Science.gov (United States)

    Cepeda-Prado, Efrain; Popp, Susanna; Khan, Usman; Stefanov, Dimitre; Rodríguez, Jorge; Menalled, Liliana B; Dow-Edwards, Diana; Small, Scott A; Moreno, Herman

    2012-05-09

    A hallmark feature of Huntington's disease pathology is the atrophy of brain regions including, but not limited to, the striatum. Though MRI studies have identified structural CNS changes in several Huntington's disease (HD) mouse models, the functional consequences of HD pathology during the progression of the disease have yet to be investigated using in vivo functional MRI (fMRI). To address this issue, we first established the structural and functional MRI phenotype of juvenile HD mouse model R6/2 at early and advanced stages of disease. Significantly higher fMRI signals [relative cerebral blood volumes (rCBVs)] and atrophy were observed in both age groups in specific brain regions. Next, fMRI results were correlated with electrophysiological analysis, which showed abnormal increases in neuronal activity in affected brain regions, thus identifying a mechanism accounting for the abnormal fMRI findings. [(14)C] 2-deoxyglucose maps to investigate patterns of glucose utilization were also generated. An interesting mismatch between increases in rCBV and decreases in glucose uptake was observed. Finally, we evaluated the sensitivity of this mouse line to audiogenic seizures early in the disease course. We found that R6/2 mice had an increased susceptibility to develop seizures. Together, these findings identified seizure activity in R6/2 mice and show that neuroimaging measures sensitive to oxygen metabolism can be used as in vivo biomarkers, preceding the onset of an overt behavioral phenotype. Since fMRI-rCBV can also be obtained in patients, we propose that it may serve as a translational tool to evaluate therapeutic responses in humans and HD mouse models.

  14. Characterization of a sensitive mouse Aβ40 PD biomarker assay for Alzheimer's disease drug development in wild-type mice.

    Science.gov (United States)

    Lu, Yanmei; Hoyte, Kwame; Montgomery, William H; Luk, Wilman; He, Dongping; Meilandt, William J; Zuchero, Y Joy Yu; Atwal, Jasvinder K; Scearce-Levie, Kimberly; Watts, Ryan J; DeForge, Laura E

    2016-05-01

    Transgenic mice that overexpress human amyloid precursor protein with Swedish or London (APPswe or APPlon) mutations have been widely used for preclinical Alzheimer's disease (AD) drug development. AD patients, however, rarely possess these mutations or overexpress APP. We developed a sensitive ELISA that specifically and accurately measures low levels of endogenous Aβ40 in mouse plasma, brain and CSF. In wild-type mice treated with a bispecific anti-TfR/BACE1 antibody, significant Aβ reductions were observed in the periphery and the brain. APPlon transgenic mice showed a slightly less reduction, whereas APPswe mice did not have any decrease. This sensitive and well-characterized mouse Aβ40 assay enables the use of wild-type mice for preclinical PK/PD and efficacy studies of potential AD therapeutics.

  15. Non-alcoholic fatty liver disease in mice with heterozygous mutation in TMED2.

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    Wenyang Hou

    Full Text Available The transmembrane emp24 domain/p24 (TMED family are essential components of the vesicular transport machinery. Members of the TMED family serve as cargo receptors implicated in selection and packaging of endoplasmic reticulum (ER luminal proteins into coatomer (COP II coated vesicles for anterograde transport to the Golgi. Deletion or mutations of Tmed genes in yeast and Drosophila results in ER-stress and activation of the unfolded protein response (UPR. The UPR leads to expression of genes and proteins important for expanding the folding capacity of the ER, degrading misfolded proteins, and reducing the load of new proteins entering the ER. The UPR is activated in non-alcoholic fatty liver disease (NAFLD in human and mouse and may contribute to the development and the progression of NAFLD. Tmed2, the sole member of the vertebrate Tmed β subfamily, exhibits tissue and temporal specific patterns of expression in embryos and developing placenta but is ubiquitously expressed in all adult organs. We previously identified a single point mutation, the 99J mutation, in the signal sequence of Tmed2 in an N-ethyl-N-nitrosourea (ENU mutagenesis screen. Histological and molecular analysis of livers from heterozygous mice carrying the 99J mutation, Tmed299J/+, revealed a requirement for TMED2 in liver health. We show that Tmed299J/+ mice had decreased levels of TMED2 and TMED10, dilated endoplasmic reticulum membrane, and increased phosphorylation of eIF2α, indicating ER-stress and activation of the UPR. Increased expression of Srebp1a and 2 at the newborn stage and increased incidence of NAFLD were also found in Tmed299J/+ mice. Our data establishes Tmed299J/+ mice as a novel mouse model for NAFLD and supports a role for TMED2 in liver health.

  16. e-Manifest

    Science.gov (United States)

    This is the primary hub for those seeking information about the e-Manifest system, its advisory board, and its development. Once the system is complete this area will serve as the portal into the e-Manifest system from EPA webpages.

  17. Surgical manifestations of filariasis

    Directory of Open Access Journals (Sweden)

    Subrahmanyam M

    1978-01-01

    Full Text Available Surgical manifestations of filariasis as seen in 150 cases over a period of three years in the department of Surgery, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Wardha are reviewed. The genital manifestations are more common than the elephantiasis in this endemic zone.

  18. Resistance to chronic wasting disease in transgenic mice expressing a naturally occurring allelic variant of deer prion protein

    NARCIS (Netherlands)

    Meade-White, K.; Race, B.; Trifilo, M.; Bossers, A.; Favara, C.; Lacasse, R.; Miller, M.; Williams, E.; Oldstone, M.; Race, R.; Chesebro, B.

    2007-01-01

    Prion protein (PrP) is a required factor for susceptibility to transmissible spongiform encephalopathy or prion diseases. In transgenic mice, expression of prion protein (PrP) from another species often confers susceptibility to prion disease from that donor species. For example, expression of deer

  19. Mesenchymal Stromal Cells Improve Salivary Function and Reduce Lymphocytic Infiltrates in Mice with Sjogren's-Like Disease

    NARCIS (Netherlands)

    Khalili, Saeed; Liu, Younan; Kornete, Mara; Roescher, Nienke; Kodama, Shohta; Peterson, Alan; Piccirillo, Ciriaco A.; Tran, Simon D.

    2012-01-01

    Background: Non-obese diabetic (NOD) mice develop Sjogren's-like disease (SS-like) with loss of saliva flow and increased lymphocytic infiltrates in salivary glands (SGs). There are recent reports using multipotent mesenchymal stromal cells (MSCs) as a therapeutic strategy for autoimmune diseases

  20. Neurological manifestations of celiac disease Manifestações neurológicas da doença celíaca

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    José Ibiapina Siqueira Neto

    2004-12-01

    Full Text Available Celiac disease (CD/ Nontropicalsprue, gluten-sensitive enteropathy is a malabsortive condition in which an allergic reaction to the cereal grain-protein gluten (present in wheat, rye and barley causes small intestine mucosal injury. The onset is in the first four decades of life, with a female to male ratio of 2:1. It may be associated with a wide spectrum of neurological manifestations including cerebellar ataxia, epileptic seizures, dementia, neuropathy, myopathy and multifocal leucoencephalopathy. We report three patients with neurological manifestations related with CD: one with cerebellar ataxia, one with epilepsy and one with cognitive impairment. The diagnosis of CD was confirmed by serologic tests (antiendomysial and antigliadin antibodies and biopsy of the small intestine. In two patients the neurological symptoms preceded the gastrointestinal abnormalities and in all of them gluten restriction failed to improve the neurological disability. Conclusion: CD should be ruled out in the differential diagnosis of neurological dysfunction of unknown cause, including ataxia, epilepsy and dementia. A gluten free diet, the mainstay of treatment, failed to improve the neurological disability.A doença celíaca (DC, enteropatia sensível ao glúten é desordem caracterizada por mal absorção causada por reação alérgica ao glúten, proteína presente em diversos cereais. As manifestações iniciais ocorrem nas primeiras quatro décadas de vida, sendo cerca de duas vezes mais freqüente no sexo feminino. DC pode estar associada a largo espectro de manifestações neurológicas incluindo ataxia cerebelar, epilepsia, demência, neuropatia, miopatia e leucoencefalopatia multifocal. Relatamos três casos de pacientes com manifestações neurológicas da DC: um com ataxia cerebelar, outro com epilepsia e o último com déficit cognitivo. O diagnóstico de DC foi estabelecido com base em testes sorológicos (anticorpos antiendomísio e antigliadina e

  1. Alzheimer’s Disease Mutant Mice Exhibit Reduced Brain Tissue Stiffness Compared to Wild-type Mice in both Normoxia and following Intermittent Hypoxia Mimicking Sleep Apnea

    Directory of Open Access Journals (Sweden)

    Maria José Menal

    2018-01-01

    Full Text Available BackgroundEvidence from patients and animal models suggests that obstructive sleep apnea (OSA may increase the risk of Alzheimer’s disease (AD and that AD is associated with reduced brain tissue stiffness.AimTo investigate whether intermittent hypoxia (IH alters brain cortex tissue stiffness in AD mutant mice exposed to IH mimicking OSA.MethodsSix-eight month old (B6C3-Tg(APPswe,PSEN1dE985Dbo/J AD mutant mice and wild-type (WT littermates were subjected to IH (21% O2 40 s to 5% O2 20 s; 6 h/day or normoxia for 8 weeks. After euthanasia, the stiffness (E of 200-μm brain cortex slices was measured by atomic force microscopy.ResultsTwo-way ANOVA indicated significant cortical softening and weight increase in AD mice compared to WT littermates, but no significant effects of IH on cortical stiffness and weight were detected. In addition, reduced myelin was apparent in AD (vs. WT, but no significant differences emerged in the cortex extracellular matrix components laminin and glycosaminoglycans when comparing baseline AD and WT mice.ConclusionAD mutant mice exhibit reduced brain tissue stiffness following both normoxia and IH mimicking sleep apnea, and such differences are commensurate with increased edema and demyelination in AD.

  2. Microbiome and metabolome modifying effects of several cardiovascular disease interventions in apo-E-/- mice.

    Science.gov (United States)

    Ryan, Paul M; London, Lis E E; Bjorndahl, Trent C; Mandal, Rupasri; Murphy, Kiera; Fitzgerald, Gerald F; Shanahan, Fergus; Ross, R Paul; Wishart, David S; Caplice, Noel M; Stanton, Catherine

    2017-03-13

    There is strong evidence indicating that gut microbiota have the potential to modify, or be modified by the drugs and nutritional interventions that we rely upon. This study aims to characterize the compositional and functional effects of several nutritional, neutraceutical, and pharmaceutical cardiovascular disease interventions on the gut microbiome, through metagenomic and metabolomic approaches. Apolipoprotein-E-deficient mice were fed for 24 weeks either high-fat/cholesterol diet alone (control, HFC) or high-fat/cholesterol in conjunction with one of three dietary interventions, as follows: plant sterol ester (PSE), oat β-glucan (OBG) and bile salt hydrolase-active Lactobacillus reuteri APC 2587 (BSH), or the drug atorvastatin (STAT). The gut microbiome composition was then investigated, in addition to the host fecal and serum metabolome. We observed major shifts in the composition of the gut microbiome of PSE mice, while OBG and BSH mice displayed more modest fluctuations, and STAT showed relatively few alterations. Interestingly, these compositional effects imparted by PSE were coupled with an increase in acetate and reduction in isovalerate (p metabolome, including alterations in several acylcarnitines previously associated with a state of metabolic dysfunction (p < 0.05). We observed functional alterations in microbial and host-derived metabolites, which may have important implications for systemic metabolic health, suggesting that cardiovascular disease interventions may have a significant impact on the microbiome composition and functionality. This study indicates that the gut microbiome-modifying effects of novel therapeutics should be considered, in addition to the direct host effects.

  3. Th2 Regulation of Viral Myocarditis in Mice: Different Roles for TLR3 versus TRIF in Progression to Chronic Disease

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    Eric D. Abston

    2012-01-01

    Full Text Available Viral infections are able to induce autoimmune inflammation in the heart. Here, we investigated the role of virus-activated Toll-like receptor (TLR3 and its adaptor TRIF on the development of autoimmune coxsackievirus B3 (CVB3 myocarditis in mice. Although TLR3- or TRIF-deficient mice developed similarly worse acute CVB3 myocarditis and viral replication compared to control mice, disease was significantly worse in TRIF compared to TLR3-deficient mice. Interestingly, TLR3-deficient mice developed an interleukin (IL-4-dominant T helper (Th2 response during acute CVB3 myocarditis with elevated markers of alternative activation, while TRIF-deficient mice elevated the Th2-associated cytokine IL-33. Treatment of TLR3-deficient mice with recombinant IL-33 improved heart function indicating that elevated IL-33 in the context of a classic Th2-driven response protects against autoimmune heart disease. We show for the first time that TLR3 versus TRIF deficiency results in different Th2 responses that uniquely influence the progression to chronic myocarditis.

  4. Oral Antibiotic Treatment of Mice Exacerbates the Disease Severity of Multiple Flavivirus Infections

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    Larissa B. Thackray

    2018-03-01

    Full Text Available Summary: Although the outcome of flavivirus infection can vary from asymptomatic to lethal, environmental factors modulating disease severity are poorly defined. Here, we observed increased susceptibility of mice to severe West Nile (WNV, Dengue, and Zika virus infections after treatment with oral antibiotics (Abx that depleted the gut microbiota. Abx treatment impaired the development of optimal T cell responses, with decreased levels of WNV-specific CD8+ T cells associated with increased infection and immunopathology. Abx treatments that resulted in enhanced WNV susceptibility generated changes in the overall structure of the gut bacterial community and in the abundance of specific bacterial taxa. As little as 3 days of treatment with ampicillin was sufficient to alter host immunity and WNV outcome. Our results identify oral Abx therapy as a potential environmental determinant of systemic viral disease, and they raise the possibility that perturbation of the gut microbiota may have deleterious consequences for subsequent flavivirus infections. : Thackray et al. observed increased susceptibility to West Nile, Zika, and Dengue virus infections following oral antibiotic treatment in mice. Antibiotics altered the bacterial abundance and community structure and the development of optimal T cell immunity. These data suggest that antibiotics may have deleterious consequences for subsequent flavivirus infections. Keywords: West Nile virus, Dengue virus, Zika virus, flavivirus, oral antibiotics, gut microbiota, risk factors, pathogenesis determinants, immunity

  5. Respiratory Syncytial Virus (RSV RNA loads in peripheral blood correlates with disease severity in mice

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    Torres Juan

    2010-09-01

    Full Text Available Abstract Background Respiratory Syncytial Virus (RSV infection is usually restricted to the respiratory epithelium. Few studies have documented the presence of RSV in the systemic circulation, however there is no consistent information whether virus detection in the blood correlates with disease severity. Methods Balb/c mice were inoculated with live RSV, heat-inactivated RSV or medium. A subset of RSV-infected mice was treated with anti-RSV antibody 72 h post-inoculation. RSV RNA loads were measured by PCR in peripheral blood from day 1-21 post-inoculation and were correlated with upper and lower respiratory tract viral loads, the systemic cytokine response, lung inflammation and pulmonary function. Immunohistochemical staining was used to define the localization of RSV antigens in the respiratory tract and peripheral blood. Results RSV RNA loads were detected in peripheral blood from day 1 to 14 post-inoculation, peaked on day 5 and significantly correlated with nasal and lung RSV loads, airway obstruction, and blood CCL2 and CXCL1 expression. Treatment with anti-RSV antibody reduced blood RSV RNA loads and improved airway obstruction. Immunostaining identified RSV antigens in alveolar macrophages and peripheral blood monocytes. Conclusions RSV RNA was detected in peripheral blood upon infection with live RSV, followed a time-course parallel to viral loads assessed in the respiratory tract and was significantly correlated with RSV-induced airway disease.

  6. Inhibition of myeloperoxidase decreases vascular oxidative stress and increases vasodilatation in sickle cell disease mice1[S

    Science.gov (United States)

    Zhang, Hao; Xu, Hao; Weihrauch, Dorothee; Jones, Deron W.; Jing, Xigang; Shi, Yang; Gourlay, David; Oldham, Keith T.; Hillery, Cheryl A.; Pritchard, Kirkwood A.

    2013-01-01

    Activated leukocytes and polymorphonuclear neutrophils (PMN) release myeloperoxidase (MPO), which binds to endothelial cells (EC), is translocated, and generates oxidants that scavenge nitric oxide (NO) and impair EC function. To determine whether MPO impairs EC function in sickle cell disease (SCD), control (AA) and SCD mice were treated with N-acetyl-lysyltyrosylcysteine-amide (KYC). SCD humans and mice have high plasma MPO and soluble L-selectin (sL-selectin). KYC had no effect on MPO but decreased plasma sL-selectin and malondialdehyde in SCD mice. MPO and 3-chlorotyrosine (3-ClTyr) were increased in SCD aortas. KYC decreased MPO and 3-ClTyr in SCD aortas to the levels in AA aortas. Vasodilatation in SCD mice was impaired. KYC increased vasodilatation in SCD mice more than 2-fold, to ∼60% of levels in AA mice. KYC inhibited MPO-dependent 3-ClTyr formation in EC proteins. SCD mice had high plasma alanine transaminase (ALT), which tended to decrease in KYC-treated SCD mice (P = 0.07). KYC increased MPO and XO/XDH and decreased 3-ClTyr and 3-nitrotyrosine (3-NO2Tyr) in SCD livers. These data support the hypothesis that SCD increases release of MPO, which generates oxidants that impair EC function and injure livers. Inhibiting MPO is an effective strategy for decreasing oxidative stress and liver injury and restoring EC function in SCD. PMID:23956444

  7. The Neuroprotective Mechanism of Low-Frequency rTMS on Nigral Dopaminergic Neurons of Parkinson's Disease Model Mice.

    Science.gov (United States)

    Dong, Qiaoyun; Wang, Yanyong; Gu, Ping; Shao, Rusheng; Zhao, Li; Liu, Xiqi; Wang, Zhanqiang; Wang, Mingwei

    2015-01-01

    Background. Parkinson's disease is a neurodegenerative disease in elder people, pathophysiologic basis of which is the severe deficiency of dopamine in the striatum. The purpose of the present study was to evaluate the neuroprotective effect of low-frequency rTMS on Parkinson's disease in model mice. Methods. The effects of low-frequency rTMS on the motor function, cortex excitability, neurochemistry, and neurohistopathology of MPTP-induced Parkinson's disease mice were investigated through behavioral detection, electrophysiologic technique, high performance liquid chromatography-electrochemical detection, immunohistochemical staining, and western blot. Results. Low-frequency rTMS could improve the motor coordination impairment of Parkinson's disease mice: the resting motor threshold significantly decreased in the Parkinson's disease mice; the degeneration of nigral dopaminergic neuron and the expression of tyrosine hydroxylase were significantly improved by low-frequency rTMS; moreover, the expressions of brain derived neurotrophic factor and glial cell line derived neurotrophic factor were also improved by low-frequency rTMS. Conclusions. Low-frequency rTMS had a neuroprotective effect on the nigral dopaminergic neuron which might be due to the improved expressions of brain derived neurotrophic factor and glial cell line-derived neurotrophic factor. The present study provided a theoretical basis for the application of low-frequency rTMS in the clinical treatment and recovery of Parkinson's disease.

  8. Manifestações otorrinolaringológicas nas doenças reumáticas auto-imunes Otorhinolaryngologic manifestations of autoimmune rheumatic diseases

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    Daniela Bergamim Pereira

    2006-04-01

    Full Text Available As manifestações otorrinolaringológicas nas doenças reumáticas representam um desafio diagnóstico para o reumatologista, o otorrinolaringologista e o médico generalista. Comumente, sintomas otorrinolaringológicos representam um sinal inicial de uma doença assintomática ou uma desordem auto-imune não diagnosticada, que freqüentemente exige um imediato e agressivo tratamento imunossupressor. Distúrbios auditivos podem ser vistos em pacientes com lúpus eritematoso sistêmico (LES, granulomatose de Wegener (GW, policondrite recidivante (PR, poliarterite nodosa, síndrome de Cogan, síndrome de Sjögren e menos freqüentemente na síndrome de Churg-Strauss e doença de Behçet. O nariz e seios paranasais são variavelmente afetados durante o curso da GW, síndrome de Churg-Strauss, PR e sarcoidose. Ulcerações mucosas recorrentes são comuns no LES e doença de Behçet. Xerostomia é uma manifestação comum da síndrome de Sjögren primária e secundária; aumento da glândula salivar pode ser visto nesses pacientes, assim como nos pacientes com sarcoidose. A articulação cricoaritenóide pode ser envolvida durante o curso da artrite reumatóide, espondilite anquilosante e gota; alterações osteoartríticas também têm sido descritas. Disfunção do nervo trigeminal pode ocorrer em pacientes com síndrome de Sjögren, esclerose sistêmica, LES e doença mista do tecido conjuntivo. Paralisia facial periférica tem sido descrita como complicação do curso da síndrome de Sjögren e sarcoidose.Otorhinolaryngologics manifestations of rheumatologic disorders represent a diagnostic challenge for the rheumatologist, the otorhinolaryngologist, and the general practicioner. Not uncommonly otorhinolaryngologics symptoms represent the initial sign of an otherwise asymptomatic or even undiagnosed autoimmune disorder which often calls for prompt and aggressive immunosuppressive treatment. Hearing disturbances may be seen in patients with

  9. Pulmonary manifestations from systemic vasculitides

    International Nuclear Information System (INIS)

    Reuter, M.; Both, M.; Schnabel, A.

    2007-01-01

    Pulmonary vasculitides predominantly involve the small arterioles, capillaries and venules and include Wegener's granulomatosis, microscopic polyangiitis and the Churg-Strauss syndrome. Takayasu's arteriitis is a large vessel disease and may affect the main pulmonary arteries causing stenoses and occlusions. Knowledge of the natural course of disease and of clinical manifestations of pulmonary disease is helpful for an understanding of imaging findings. For this reason this article gives an overview not only of radiologic findings in chest X-ray and high resolution CT of the lungs but as well of clinical aspects of pulmonary vasculitides. Next to determination of disease extension the determination of disease activity is in the foreground of diagnostic imaging in vasculitides. Within this context principals of immunosuppressive therapy will be recognized. (orig.)

  10. Ectopic norrin induces growth of ocular capillaries and restores normal retinal angiogenesis in Norrie disease mutant mice.

    Science.gov (United States)

    Ohlmann, Andreas; Scholz, Michael; Goldwich, Andreas; Chauhan, Bharesh K; Hudl, Kristiane; Ohlmann, Anne V; Zrenner, Eberhart; Berger, Wolfgang; Cvekl, Ales; Seeliger, Mathias W; Tamm, Ernst R

    2005-02-16

    Norrie disease is an X-linked retinal dysplasia that presents with congenital blindness, sensorineural deafness, and mental retardation. Norrin, the protein product of the Norrie disease gene (NDP), is a secreted protein of unknown biochemical function. Norrie disease (Ndp(y/-)) mutant mice that are deficient in norrin develop blindness, show a distinct failure in retinal angiogenesis, and completely lack the deep capillary layers of the retina. We show here that the transgenic expression of ectopic norrin under control of a lens-specific promoter restores the formation of a normal retinal vascular network in Ndp(y/-) mutant mice. The improvement in structure correlates with restoration of neuronal function in the retina. In addition, lenses of transgenic mice with ectopic expression of norrin show significantly more capillaries in the hyaloid vasculature that surrounds the lens during development. In vitro, lenses of transgenic mice in coculture with microvascular endothelial cells induce proliferation of the cells. Transgenic mice with ectopic expression of norrin show more bromodeoxyuridine-labeled retinal progenitor cells at embryonic day 14.5 and thicker retinas at postnatal life than wild-type littermates, indicating a putative direct neurotrophic effect of norrin. These data provide direct evidence that norrin induces growth of ocular capillaries and that pharmacologic modulation of norrin might be used for treatment of the vascular abnormalities associated with Norrie disease or other vascular disorders of the retina.

  11. Neutrophil depletion improves diet-induced non-alcoholic fatty liver disease in mice.

    Science.gov (United States)

    Ou, Rongying; Liu, Jia; Lv, Mingfen; Wang, Jingying; Wang, Jinmeng; Zhu, Li; Zhao, Liang; Xu, Yunsheng

    2017-07-01

    Non-alcoholic fatty liver disease is highly associated with morbidity and mortality in population. Although studies have already demonstrated that the immune response plays a pivotal role in the development of non-alcoholic fatty liver disease, the comprehensive regulation is unclear. Therefore, present study was carried out to investigate the non-alcoholic fatty liver disease development under neutrophil depletion. To achieve the aim of the study, C57BL/6 J mice were fed with high fat diet for 6 weeks before treated with neutrophil deplete antibody 1A8 or isotype control (200 μg/ mouse every week) for another 4 weeks. Treated with 1A8 antibody, obese mice exhibited better whole body metabolic parameters, including reduction of body weight gain and fasting blood glucose levels. Neutrophil depletion also effectively reduced hepatic structural disorders, dysfunction and lipid accumulation. Lipid β-oxidative markers, phosphorylated-AMP-activated protein kinase α and phosphorylated-acetyl-CoA carboxylase levels were increased in 1A8 antibody-treated obese mouse group. The mitochondrial number and function were also reversed after 1A8 antibody treatment, including increased mitochondrial number, reduced lipid oxidative damage and enhanced mitochondrial activity. Furthermore, the expression of inflammatory cytokines, tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1 were obviously reduced after neutrophil depletion, accompanied with decreased F4/80 mRNA level and macrophage percentage in liver. The decreased NF-κB signaling activity was also involved in the beneficial effect of neutrophil depletion. Taken together, neutrophil depletion could attenuate metabolic syndromes and hepatic dysfunction.

  12. Deficient Rab11 activity underlies glucose hypometabolism in primary neurons of Huntington’s disease mice

    International Nuclear Information System (INIS)

    Li, Xueyi; Valencia, Antonio; McClory, Hollis; Sapp, Ellen; Kegel, Kimberly B.; DiFiglia, Marian

    2012-01-01

    Highlights: ► Primary Huntington’s disease neurons are impaired in taking up glucose. ► Rab11 modulates glucose uptake in neurons. ► Increasing Rab11 activity attenuates the glucose uptake defect in disease neurons. ► We provide a novel mechanism for glucose hypometabolism in Huntington’s disease. -- Abstract: Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Positron emission tomography studies have revealed a decline in glucose metabolism in the brain of patients with HD by a mechanism that has not been established. We examined glucose utilization in embryonic primary cortical neurons of wild-type (WT) and HD knock-in mice, which have 140 CAG repeats inserted in the endogenous mouse huntingtin gene (HD 140Q/140Q ). Primary HD 140Q/140Q cortical neurons took up significantly less glucose than did WT neurons. Expression of permanently inactive and permanently active forms of Rab11 correspondingly altered glucose uptake in WT neurons, suggesting that normal activity of Rab11 is needed for neuronal uptake of glucose. It is known that Rab11 activity is diminished in HD 140Q/140Q neurons. Expression of dominant active Rab11 to enhance the activity of Rab11 normalized glucose uptake in HD 140Q/140Q neurons. These results suggest that deficient activity of Rab11 is a novel mechanism for glucose hypometabolism in HD.

  13. Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice.

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    Trevor D Lawley

    Full Text Available Relapsing C. difficile disease in humans is linked to a pathological imbalance within the intestinal microbiota, termed dysbiosis, which remains poorly understood. We show that mice infected with epidemic C. difficile (genotype 027/BI develop highly contagious, chronic intestinal disease and persistent dysbiosis characterized by a distinct, simplified microbiota containing opportunistic pathogens and altered metabolite production. Chronic C. difficile 027/BI infection was refractory to vancomycin treatment leading to relapsing disease. In contrast, treatment of C. difficile 027/BI infected mice with feces from healthy mice rapidly restored a diverse, healthy microbiota and resolved C. difficile disease and contagiousness. We used this model to identify a simple mixture of six phylogenetically diverse intestinal bacteria, including novel species, which can re-establish a health-associated microbiota and clear C. difficile 027/BI infection from mice. Thus, targeting a dysbiotic microbiota with a defined mixture of phylogenetically diverse bacteria can trigger major shifts in the microbial community structure that displaces C. difficile and, as a result, resolves disease and contagiousness. Further, we demonstrate a rational approach to harness the therapeutic potential of health-associated microbial communities to treat C. difficile disease and potentially other forms of intestinal dysbiosis.

  14. Quantum manifestations of chaos

    International Nuclear Information System (INIS)

    Borondo, F.; Benito, R.M.

    1998-01-01

    The correspondence between classical and quantum mechanics is considered both in the regular and chaotic regimes, and the main results regarding the quantum manifestations of chaos are reviewed. (Author) 16 refs

  15. Radiographic manifestations of hypochondroplasia

    Energy Technology Data Exchange (ETDEWEB)

    Heselson, N G; Cremin, B J [Groote Schuur Hospital, Cape Town (South Africa); Beighton, P

    1979-01-01

    Hypochrondroplasia is an inherited skeletal dysplasia that resembles achondroplasia in mild degree. Radiographic manifestations encountered in 12 affected individuals in South Africa include slight shortening of all segments of the tubular bones, moderate caudal diminution of the lumbar interpedicular distances, increased lumbar lordosis with cacral tilt and distal prolongation of the fibular. Hypochondroplasia can be distinguished from other osteochondrodystrophies such as achondroplasia, pseudo-achondroplasia and metaphyseal chondroplasia by the recognition of it clinical and radiographic manifestations.

  16. Targeted deletion of the 9p21 noncoding coronary artery disease risk interval in mice

    Energy Technology Data Exchange (ETDEWEB)

    Visel, Axel; Zhu, Yiwen; May, Dalit; Afzal, Veena; Gong, Elaine; Attanasio, Catia; Blow, Matthew J.; Cohen, Jonathan C.; Rubin, Edward M.; Pennacchio, Len A.

    2010-01-01

    Sequence polymorphisms in a 58kb interval on chromosome 9p21 confer a markedly increased risk for coronary artery disease (CAD), the leading cause of death worldwide 1,2. The variants have a substantial impact on the epidemiology of CAD and other life?threatening vascular conditions since nearly a quarter of Caucasians are homozygous for risk alleles. However, the risk interval is devoid of protein?coding genes and the mechanism linking the region to CAD risk has remained enigmatic. Here we show that deletion of the orthologous 70kb noncoding interval on mouse chromosome 4 affects cardiac expression of neighboring genes, as well as proliferation properties of vascular cells. Chr4delta70kb/delta70kb mice are viable, but show increased mortality both during development and as adults. Cardiac expression of two genes near the noncoding interval, Cdkn2a and Cdkn2b, is severely reduced in chr4delta70kb/delta70kb mice, indicating that distant-acting gene regulatory functions are located in the noncoding CAD risk interval. Allelespecific expression of Cdkn2b transcripts in heterozygous mice revealed that the deletion affects expression through a cis-acting mechanism. Primary cultures of chr4delta70kb/delta70kb aortic smooth muscle cells exhibited excessive proliferation and diminished senescence, a cellular phenotype consistent with accelerated CAD pathogenesis. Taken together, our results provide direct evidence that the CAD risk interval plays a pivotal role in regulation of cardiac Cdkn2a/b expression and suggest that this region affects CAD progression by altering the dynamics of vascular cell proliferation.

  17. Urine RAS components in mice and people with type 1 diabetes and chronic kidney disease.

    Science.gov (United States)

    Wysocki, Jan; Goodling, Anne; Burgaya, Mar; Whitlock, Kathryn; Ruzinski, John; Batlle, Daniel; Afkarian, Maryam

    2017-08-01

    The pathways implicated in diabetic kidney disease (DKD) are largely derived from animal models. To examine if alterations in renin-angiotensin system (RAS) in humans are concordant with those in rodent models, we measured concentration of angiotensinogen (AOG), cathepsin D (CTSD), angiotensin-converting enzyme (ACE), and ACE2 and enzymatic activities of ACE, ACE2, and aminopeptidase-A in FVB mice 13-20 wk after treatment with streptozotocin ( n = 9) or vehicle ( n = 15) and people with long-standing type 1 diabetes, with ( n = 37) or without ( n = 81) DKD. In streptozotocin-treated mice, urine AOG and CTSD were 10.4- and 3.0-fold higher than in controls, respectively ( P animals ( P animals ( P = 0.017). Compared with people without DKD, those with DKD had higher urine AOG (170 vs. 15 μg/g) and CTSD (147 vs. 31 μg/g). In people with DKD, urine ACE concentration was 1.8-fold higher (1.4 vs. 0.8 μg/g in those without DKD), while its enzymatic activity was 0.6-fold lower (1.0 vs. 1.6 × 10 9 RFU/g in those without DKD). Lower ACE activity, but not ACE protein concentration, was associated with ACE inhibitor (ACEI) treatment. After adjustment for clinical covariates, AOG, CTSD, ACE concentration, and ACE activity remained associated with DKD. In conclusion, in mice with streptozotocin-induced diabetes and in humans with DKD, urine concentrations and enzymatic activities of several RAS components are concordantly increased, consistent with enhanced RAS activity and greater angiotensin II formation. ACEI use was associated with a specific reduction in urine ACE activity, not ACE protein concentration, suggesting that it may be a marker of exposure to this widely-used therapy. Copyright © 2017 the American Physiological Society.

  18. Cerebral metabonomics study on Parkinson's disease mice treated with extract of Acanthopanax senticosus harms.

    Science.gov (United States)

    Li, Xu-zhao; Zhang, Shuai-nan; Lu, Fang; Liu,