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Sample records for adult-onset stills disease

  1. Adult Onset Still's Disease and Rocky Mountain Spotted Fever.

    PubMed

    Persad, Paul; Patel, Rajendrakumar; Patel, Niki

    2010-01-01

    Adult Still's Disease was first described in 1971 by Bywaters in fourteen adult female patients who presented with symptoms indistinguishable from that of classic childhood Still's Disease (Bywaters, 1971). George Still in 1896 first recognized this triad of quotidian (daily) fevers, evanescent rash, and arthritis in children with what later became known as juvenile inflammatory arthritis (Still, 1990). Adult Onset Still's Disease (AOSD) is an inflammatory condition of unknown etiology characterized by an evanescent rash, quotidian fevers, and arthralgias. Numerous infectious agents have been associated with its presentation. This case is to our knowledge the first presentation of AOSD in the setting of Rocky Mountain Spotted Fever. Although numerous infectious agents have been suggested, the etiology of this disorder remains elusive. Nevertheless, infection may in fact play a role in triggering the onset of symptoms in those with this disorder. Our case presentation is, to our knowledge, the first case of Adult Onset Still's Disease associated with Rocky Mountain spotted fever (RMSF).

  2. Hepatitis A infection mimicking adult onset Still's disease.

    PubMed

    Sridharan, S; Mossad, S; Hoffman, G

    2000-07-01

    Fever, rash, and arthritis may be components of the prodrome of viral hepatitis. In the absence of jaundice and abnormal liver function tests, this form of polyarthritis is easily confused with primary autoimmune diseases. Whereas the association of systemic illness with musculoskeletal symptoms and numerous viral infections is well known, such an association with hepatitis A has only been rarely reported. We describe a case of hepatitis A infection mimicking adult onset Still's disease, and review the pathogenesis and differential diagnosis of Still's disease and the extraarticular manifestations of hepatitis.

  3. Refractory Genital HPV Infection and Adult-Onset Still Disease

    PubMed Central

    Yu, Xin; Zheng, Heyi

    2016-01-01

    Abstract Adult-onset Still disease (AOSD) is a systemic autoimmune disease (AIID) that can develop after exposure to infectious agents. Genital human papillomavirus (HPV) infection has been reported to induce or exacerbate AIIDs, such as systemic lupus erythematosus (SLE). No guidelines are available for the management of genital warts in AOSD. Case report and literature review. We report a patient who was diagnosed AOSD in the setting of refractory and recurrent genital HPV infection, demonstrating a possible link between HPV infection and AOSD. In addition, we also discuss the management of genital warts in patients with AOSD. To the best of our knowledge, no previous cases of AOSD with genital HPV infection have been reported in literature. We then conclude that the patient AOSD may be triggered by primary HPV infection. Larger number of patient samples is needed to confirm whether HPV could trigger AOSD. PMID:27082556

  4. Parenchymal lung involvement in adult-onset Still disease

    PubMed Central

    Gerfaud-Valentin, Mathieu; Cottin, Vincent; Jamilloux, Yvan; Hot, Arnaud; Gaillard-Coadon, Agathe; Durieu, Isabelle; Broussolle, Christiane; Iwaz, Jean; Sève, Pascal

    2016-01-01

    Abstract Parenchymal lung involvement (PLI) in adult-onset Still's disease (AOSD) has seldom, if ever, been studied. We examine here retrospective cohort AOSD cases and present a review of the literature (1971–2014) on AOSD-related PLI cases. Patients with PLI were identified in 57 AOSD cases. For inclusion, the patients had to fulfill Yamaguchi or Fautrel classification criteria, show respiratory symptoms, and have imaging evidence of pulmonary involvement, and data allowing exclusion of infectious, cardiogenic, toxic, or iatrogenic cause of PLI should be available. This AOSD + PLI group was compared with a control group (non–PLI-complicated AOSD cases from the same cohort). AOSD + PLI was found in 3 out of the 57 patients with AOSD (5.3%) and the literature mentioned 27 patients. Among these 30 AOSD + PLI cases, 12 presented an acute respiratory distress syndrome (ARDS) and the remaining 18 another PLI. In the latter, a nonspecific interstitial pneumonia computed tomography pattern prevailed in the lower lobes, pulmonary function tests showed a restrictive lung function, the alveolar differential cell count was neutrophilic in half of the cases, and the histological findings were consistent with bronchiolitis and nonspecific interstitial pneumonia. Corticosteroids were fully efficient in all but 3 patients. Ten out of 12 ARDS cases occurred during the first year of the disease course. All ARDS-complicated AOSD cases received corticosteroids with favorable outcomes in 10 (2 deceased). Most PLIs occurred during the systemic onset of AOSD. PLI may occur in 5% of AOSDs, of which ARDS is the most severe. Very often, corticosteroids are efficient in controlling this complication. PMID:27472698

  5. Efficacy of Anakinra in Refractory Adult-Onset Still's Disease

    PubMed Central

    Ortiz-Sanjuán, Francisco; Blanco, Ricardo; Riancho-Zarrabeitia, Leyre; Castañeda, Santos; Olivé, Alejandro; Riveros, Anne; Velloso-Feijoo, María.L.; Narváez, Javier; Jiménez-Moleón, Inmaculada; Maiz-Alonso, Olga; Ordóñez, Carmen; Bernal, José A.; Hernández, María V.; Sifuentes-Giraldo, Walter A.; Gómez-Arango, Catalina; Galíndez-Agirregoikoa, Eva; Blanco-Madrigal, Juan; Ortiz-Santamaria, Vera; del Blanco-Barnusell, Jordi; De Dios, Juan R.; Moreno, Mireia; Fiter, Jordi; Riscos, Marina de los; Carreira, Patricia; Rodriguez-Valls, María J.; González-Vela, M. Carmen; Calvo-Río, Vanesa; Loricera, Javier; Palmou-Fontana, Natalia; Pina, Trinitario; Llorca, Javier; González-Gay, Miguel A.

    2015-01-01

    Abstract Adult-onset Still's disease (AOSD) is often refractory to standard therapy. Anakinra (ANK), an interleukin-1 receptor antagonist, has demonstrated efficacy in single cases and small series of AOSD. We assessed the efficacy of ANK in a series of AOSD patients. Multicenter retrospective open-label study. ANK was used due to lack of efficacy to standard synthetic immunosuppressive drugs and in some cases also to at least 1 biologic agent. Forty-one patients (26 women/15 men) were recruited. They had a mean age of 34.4 ± 14 years and a median [interquartile range (IQR)] AOSD duration of 3.5 [2–6] years before ANK onset. At that time the most common clinical features were joint manifestations 87.8%, fever 78%, and cutaneous rash 58.5%. ANK yielded rapid and maintained clinical and laboratory improvement. After 1 year of therapy, the frequency of joint and cutaneous manifestations had decreased to 41.5% and to 7.3% respectively, fever from 78% to 14.6%, anemia from 56.1% to 9.8%, and lymphadenopathy from 26.8% to 4.9%. A dramatic improvement of laboratory parameters was also achieved. The median [IQR] prednisone dose was also reduced from 20 [11.3–47.5] mg/day at ANK onset to 5 [0–10] at 12 months. After a median [IQR] follow-up of 16 [5–50] months, the most important side effects were cutaneous manifestations (n = 8), mild leukopenia (n = 3), myopathy (n = 1), and infections (n = 5). ANK is associated with rapid and maintained clinical and laboratory improvement, even in nonresponders to other biologic agents. However, joint manifestations are more refractory than the systemic manifestations. PMID:26426623

  6. Adult-onset Still's disease with atypical cutaneous manifestations

    PubMed Central

    Narváez Garcia, Francisco Javier; Pascual, María; López de Recalde, Mercè; Juarez, Pablo; Morales-Ivorra, Isabel; Notario, Jaime; Jucglà, Anna; Nolla, Joan M.

    2017-01-01

    Abstract The diagnosis of adult-onset Still's disease (AOSD) can be very difficult. There are no specific tests available, and diagnosis is usually based on a symptom complex and the well-described typical evanescent rash seen in the majority of patients. However, in recent years, other atypical cutaneous manifestations of AOSD have been reported. These atypical skin eruptions often present in addition to the typical evanescent rash but may also be the only skin manifestation, resulting in delayed diagnosis because of under-recognition. In this study, we present 3 new cases of AOSD with atypical cutaneous manifestations diagnosed during a 30-year period in our department and review 78 additional cases previously reported (PubMed 1990–2016). These 81 patients form the basis of the present analysis. The overall prevalence of atypical cutaneous manifestations in our AOSD population was 14%. These manifestations may appear at any time over the course of the disease, and usually occur in patients who have persistent and severe disease, with a considerable frequency of clinical complications (23%), including serositis, myopericarditis, lung involvement, abdominal pain, neurologic involvement, and reactive hemophagocytic syndrome. The most representative and frequent lesion among the nonclassical skin rashes is the development of persistent pruritic papules and/or plaques. Interestingly, these lesions show a distinctive histological pattern. Other, less frequently observed lesions include urticaria and urticaria-like eruptions, generalized or widespread non-pruritic persistent erythema, vesiculopustular eruptions, a widespread peau d’orange appearance of the skin, and edema of the eyelids mimicking dermatomyositis without any accompanying skin lesion. The great majority of these patients required medium or high doses of glucocorticoids (including intravenous methylprednisolone pulse therapy in some cases) and, in nearly 40%, a more potent or maintenance immunotherapy

  7. Adult-onset Still's disease and cardiac tamponade: a rare association.

    PubMed

    Carrilho-Ferreira, Pedro; Silva, Doroteia; de Jesus Silva, Maria; André, Rui; Varela, Manuel Gato; Diogo, António Nunes

    2015-06-01

    Adult-onset Still's disease is a rare disorder with potentially severe clinical features, including cardiac involvement. This systemic inflammatory disease of unknown origin should be considered in the differential diagnosis of pericarditis, with or without pericardial effusion. Cardiac tamponade is a very rare sequela that requires an invasive approach, such as percutaneous or surgical pericardial drainage, in addition to the usual conservative therapy. The authors describe a case of adult-onset Still's disease rendered more difficult by pericarditis and cardiac tamponade, and they briefly review the literature on this entity.

  8. Adult-Onset Still's Disease and Cardiac Tamponade: A Rare Association

    PubMed Central

    Silva, Doroteia; de Jesus Silva, Maria; André, Rui; Varela, Manuel Gato; Diogo, António Nunes

    2015-01-01

    Adult-onset Still's disease is a rare disorder with potentially severe clinical features, including cardiac involvement. This systemic inflammatory disease of unknown origin should be considered in the differential diagnosis of pericarditis, with or without pericardial effusion. Cardiac tamponade is a very rare sequela that requires an invasive approach, such as percutaneous or surgical pericardial drainage, in addition to the usual conservative therapy. The authors describe a case of adult-onset Still's disease rendered more difficult by pericarditis and cardiac tamponade, and they briefly review the literature on this entity. PMID:26175648

  9. [Adult onset Still's disease as a diagnostics challenge in case of fever of unknown origin].

    PubMed

    Debski, Marcin; Stepniewski, Piotr; Wróbel, Michał

    2013-01-01

    Fever of unknown origin is often a diagnostic challenge. Here we present a case of 55-year-old woman with a history of a few months fever, progressing weakness and salmon-coloured, macular skin rash. The differential diagnosis included neoplasmatic conditions, infections and connective tissue disorders. Finally adult onset Still's disease was suspected. Glucocorticosteroid treatment was induced. During the therapy a central nervous system infection occurred, which was fatal for the patient. The presented clinical case shows that among many causes of fever of unknown origin, adult onset Still's disease should be taken into account.

  10. Epidemiology and outcome of articular complications in adult onset Still's disease.

    PubMed

    Mahfoudhi, Madiha; Shimi, Rafik; Turki, Sami; Kheder, Adel

    2015-01-01

    The adult onset Still's disease is a rare inflammatory pathology of unknown pathogeny. The clinical features are variable. The diagnosis is difficult since exclusion of infectious, systemic and tumoral pathologies should be done. The articular complications are frequent and can be revelatory of this pathology. The articular prognosis depends on the diagnosis delay and the treatment efficiency. Our study aims to analyze different aspects of articular manifestations complicating adult onset Still disease to define epidemiological, clinical and evolving characteristics of these complications. It was a cross-sectional study concerning 18 cases of adult onset Still disease diagnosed from 1990 to 2014 in the internal medicine A department of Charles Nicolle Hospital in Tunis, meeting Yamaguchi criteria. We identified clinical, radiological, evolving and therapeutic profile of the articular manifestations occurred in these patients. There were 11 women and 7 men. The average age was 27 years. The arthralgias were reported in all cases; while, the arthritis interested thirteen patients. A hand deformation was found in four patients. A wrist ankylosis was noted in one case and a flexion elbow in one patient. The Standard articular radiographs were normal in ten cases. The treatment associated essentially non-steroidal anti-inflammatory and/or corticosteroids and/or methotrexate. Concerning the evolving profile, the monocyclic form was present in 25% of the cases, the intermittent form in 40% and the chronic articular form in 35% of our patients. The adult onset Still's disease is rare and heterogeneous. The articular disturbances are frequent and have various outcomes.

  11. Adult-onset Still's disease as a mask of Hodgkin lymphoma

    PubMed Central

    Pawlak-Buś, Katarzyna; Leszczyński, Piotr

    2015-01-01

    Adult-onset Still's disease is a rare disorder, which creates difficulties in making a proper diagnosis. Ambiguous symptoms and results of auxiliary tests, lack of unequivocal diagnostic tests and the need to exclude other causes of the disease are major problems in clinical practice. A case of a 22-year-old woman with dominated recurrent fever, significantly elevated inflammation markers and arthritis is presented. Based on clinical signs after exclusion of infection, hematological and other reasons, the patient was diagnosed with adult-onset Still's disease. Standard treatment, with high doses of glucocorticoids and a disease-modifying drug, was applied, without the anticipated effects. The diagnostic tests were conducted again due to the lack of clinical improvement, increase of inflammatory markers and unusual response to treatment. A new symptom of significance, i.e. mediastinal lymphadenopathy, was found. After the histopathological examination of lymph nodes, Hodgkin's disease was diagnosed and targeted therapy for hematological malignancy was applied. PMID:27407236

  12. Adult-onset Still's disease as a mask of Hodgkin lymphoma.

    PubMed

    Dudziec, Ewa; Pawlak-Buś, Katarzyna; Leszczyński, Piotr

    2015-01-01

    Adult-onset Still's disease is a rare disorder, which creates difficulties in making a proper diagnosis. Ambiguous symptoms and results of auxiliary tests, lack of unequivocal diagnostic tests and the need to exclude other causes of the disease are major problems in clinical practice. A case of a 22-year-old woman with dominated recurrent fever, significantly elevated inflammation markers and arthritis is presented. Based on clinical signs after exclusion of infection, hematological and other reasons, the patient was diagnosed with adult-onset Still's disease. Standard treatment, with high doses of glucocorticoids and a disease-modifying drug, was applied, without the anticipated effects. The diagnostic tests were conducted again due to the lack of clinical improvement, increase of inflammatory markers and unusual response to treatment. A new symptom of significance, i.e. mediastinal lymphadenopathy, was found. After the histopathological examination of lymph nodes, Hodgkin's disease was diagnosed and targeted therapy for hematological malignancy was applied.

  13. Adult-onset Still's disease revealed by perimyocarditis and a concomitant reactivation of an EBV infection

    PubMed Central

    Meckenstock, Roderich; Therby, Audrey; Gibault-Genty, Geraldine; Khau, David; Monnier, Sebastien; Greder-Belan, Alix

    2012-01-01

    We describe a 17-year-old patient presenting perimyocarditis as the initial manifestation of the adult-onset Still's disease. Corticotherapy was rapidly successful but induced major acute hepatitis in relation with Epstein-Barr virus reactivation. After 1 year, even if the global outcome is favourable, a slightly lowered ejection fraction still persists. Former case reports and differential diagnosis with reactive haemophagocytic syndrome would be discussed. PMID:23166163

  14. [Pathophysiology, subtypes, and treatments of adult-onset Still's disease: An update].

    PubMed

    Gerfaud-Valentin, M; Sève, P; Hot, A; Broussolle, C; Jamilloux, Y

    2015-05-01

    Adult-onset Still's disease is a rare and difficult to diagnose multisystemic disorder considered as a multigenic autoinflammatory syndrome. Its immunopathogenesis seems to be at the crossroads between inflammasomopathies and hemophagocytic lymphohistiocytosis, the most severe manifestation of the disease. According to recent insights in the pathophysiology and thanks to cohort studies and therapeutic trials, two phenotypes of adult-onset Still's disease may be distinguished: a systemic pattern, initially highly symptomatic and with a higher risk to exhibit life-threatening complications such as reactive hemophagocytic lymphohistiocytosis, where interleukin-1 blockade seems to be very effective, a chronic articular pattern, more indolent with arthritis in the foreground and less severe systemic manifestations, which would threat functional outcome and where interleukin-6 blockade seems to be more effective. This review focuses on these data.

  15. Adult Onset Still's Disease: A Review on Diagnostic Workup and Treatment Options

    PubMed Central

    Gopalarathinam, Rajesh; Orlowsky, Eric; Kesavalu, Ramesh; Yelaminchili, Sreeteja

    2016-01-01

    Adult onset Still's disease (AOSD) is a rare systemic inflammatory disease of unknown etiology and pathogenesis that presents in 5 to 10% of patients as fever of unknown origin (FUO) accompanied by systemic manifestations. We report an interesting case of a 33-year-old African-American male who presented with one-month duration of FUO along with skin rash, sore throat, and arthralgia. After extensive workup, potential differential diagnoses were ruled out and the patient was diagnosed with AOSD based on the Yamaguchi criteria. The case history, incidence, pathogenesis, clinical manifestations, differential diagnoses, diagnostic workup, treatment modalities, and prognosis of AOSD are discussed in this case report. PMID:27042373

  16. [Adult-onset Still's disease with liver failure requiring liver transplantation].

    PubMed

    Terán, Alvaro; Casafont, Fernando; Fábrega, Emilio; Martínez-Taboada, Víctor Manuel; Rodríguez-Valverde, Vicente; Pons-Romero, Fernando

    2009-12-01

    We present the case of a 23-year-old man with fever of unknown origin, who developed acute liver failure 2 months after symptom onset, requiring an urgent liver transplantation. The diagnosis of adult-onset Still's disease was established after the reappearance of symptoms after transplantation, and high doses of corticosteroids were used to control disease activity. Subsequently, given the impossibility of tapering the steroid dose, interleukin-1 receptor blocking treatment was started with satisfactory outcome. We also review the published literature.

  17. Herpes Zoster Meningitis Complicating Combined Tocilizumab and Cyclosporine Therapy for Adult-Onset Still's Disease

    PubMed Central

    Tsurukawa, Shinichiro; Iwanaga, Nozomi; Izumi, Yasumori; Shirakawa, Atsunori; Kawahara, Chieko; Shukuwa, Tetsuo; Inamoto, Miwako; Kawakami, Atsushi; Migita, Kiyoshi

    2016-01-01

    A 56-year-old female with refractory adult-onset Still's disease presented with ocular herpes zoster infection during TCZ treatment. After three days of acyclovir treatment (5 mg/kg), she developed a severe headache and high fever. Viral DNA isolation and cerebral spinal fluid abnormalities led to a herpes zoster meningitis diagnosis. Her meningitis was cured by high doses of intravenous acyclovir (10 mg/kg for 14 days). To our knowledge, this is the first report of meningeal herpes zoster infection in rheumatic diseases under TCZ treatment. PMID:27092286

  18. Piriform sinus carcinoma with a paraneoplastic syndrome misdiagnosed as adult onset Still's disease: a case report.

    PubMed

    Yang, Liu; Li, Wen; Du, Jintao

    2015-01-01

    Paraneoplastic syndromes (PS) occur less commonly in association with otolaryngologic neoplasms than other carcinomas such as those of lung or breast. Piriform sinus carcinoma with PS is extremely rare. We here report a case of piriform sinus carcinoma accompanied by PS that was initially misdiagnosed as adult onset Still's disease and describe our diagnosis and treatment. One lesson we have drawn from the experience of this misdiagnosis is that PS symptoms may manifest before the primary tumor is evident and complicate the diagnostic process.

  19. Adult-onset Still disease with peculiar persistent plaques and papules.

    PubMed

    Yoshifuku, A; Kawai, K; Kanekura, T

    2014-06-01

    Adult-onset Still disease (AOSD) is a systemic inflammatory disorder characterized clinically by high spiking fever, polyarthralgia/arthritis, a salmon-pink evanescent rash, predominantly neutrophilic leucocytosis, lymphadenopathy, liver dysfunction, and splenomegaly. Recently, a nonclassic, nonevanescent skin rash has been reported. We report a 27-year-old woman with AOSD showing persistent pruritic papular lesions. Histologically, dyskeratotic keratinocytes were seen in the upper epidermis. We describe this case in detail and review the previous literature. Nonclassic pruritic eruptions with characteristic dyskeratotic keratinocytes might provide an important clue for the diagnosis of AOSD.

  20. Adult-onset Still's disease and chronic recurrent multifocal osteomyelitis: a hitherto undescribed manifestation of autoinflammation.

    PubMed

    Rech, J; Manger, B; Lang, B; Schett, G; Wilhelm, M; Birkmann, J

    2012-06-01

    Still's disease and chronic recurrent multifocal osteomyelitis (CRMO) are febrile rheumatic diseases of unknown etiology, which predominantly affect children but can also have their initial manifestation in adults. Both can present as intermittent, relapsing episodes and are considered potential candidates within the expanding spectrum of autoinflammatory disorders, although no genetic abnormalities have been described for either of them. Here, we describe a man with an initial manifestation of abacterial multifocal osteitis at the age of 41. During a relapsing-remitting course of his illness, he increasingly developed symptoms of adult-onset Still's disease (AOSD), and the diagnosis was established according to the Yamaguchi criteria. When treated with anakinra, not only the acute symptoms disappeared promptly, but also the osteitis went into complete remission. This is to our knowledge the first description of a simultaneous occurrence of these two manifestations of autoinflammation in adulthood.

  1. Macrophage Activation Syndrome Associated with Adult-Onset Still's Disease Successfully Treated with Anakinra

    PubMed Central

    Kato, Hiroshi

    2016-01-01

    Macrophage activation syndrome (MAS) is a potentially fatal complication of Adult-Onset Still's disease (Still's disease). Whereas an increasing body of evidence supports interleukin-1 (IL-1) blockade as a promising treatment for Still's disease, whether it is therapeutic for MAS associated with Still's disease remains unclear. We report a 34-year-old Caucasian man with one-decade history of TNF-blockade-responsive seronegative arthritis who presented with abrupt onset of fever, serositis, bicytopenia, splenomegaly, hepatitis, and disseminated intravascular coagulation. Striking hyperferritinemia was noted without evidence of infection, malignancy, or hemophagocytosis on bone marrow biopsy. NK cells were undetectable in the peripheral blood, whereas soluble IL-2 receptor was elevated. His multiorgan disease resolved in association with methylprednisolone pulse therapy, Anakinra, and a tapering course of prednisone. This case reinforces the notion that Still's disease is inherently poised to manifest MAS as one of the clinical phenotypes by shedding light on the role of IL-1 underlying both Still's disease and related MAS. PMID:27818826

  2. Limited diagnostic value of procalcitonin in early diagnosis of adult onset Still's disease.

    PubMed

    Gowin, Ewelina; Wysocki, Jacek

    2016-01-01

    A 17-year-old female patient was referred to the Infectious Diseases Ward because of fever lasting for 14 days. On admission to the hospital the patient was in a generally good state, without any abnormalities on physical examination. Laboratory investigation revealed elevated inflammatory markers. Diagnostic imaging comprising chest X-ray, abdominal ultrasonography, and echocardiography showed no abnormalities. During the hospitalization, there occurred episodes of fever with skin rash and musculoskeletal pain of the lower limbs. Procalcitonin concentrations continued to increase. C-reactive protein concentrations decreased during therapy, starting from 191 mg/l. On the 23(rd) day of the disease, edema of the feet, ankles, and knees appeared. On the basis of the clinical picture and after excluding other possible causes of fever, the patient was diagnosed with adult onset Still's disease. The procalcitonin concentration was normalized after 5 days of steroid therapy. The patient was discharged under ambulatory rheumatologic supervision.

  3. Hidden in plain sight: macrophage activation syndrome complicating Adult Onset Still's Disease.

    PubMed

    Benitez, Lourdes; Vila, Salvador; Mellado, Robert Hunter

    2010-01-01

    Hemophagocytic Lymphystiocytosis is a rare and fatal complication of rheumatic diseases, particularly Adult Onset Still's Disease (AOSD). It may be precipitated with immunosuppressive drugs and with viral and bacterial infections. A diagnosis depends on a high index of suspicion associated to certain clinical manifestations (fever, rash, Splemomegaly, any cytology blood dyscrasia, hipertrigliceridemia, hiperfibrinogenemia, and others), as well as pathologic evidence of hemophagocitosis from bone marrow biopsy or tissue samples of affected organs. Therapy consists of high dose corticosteroids and immunosuppressive drugs. We present a 42 year old woman with AOSD in remission who developed HLH in spite of receiving therapy with high dose steroids and immunosuppressive drugs. She had 2 negative bone marrow aspirates. Evidence of Hemophagocytosis was detected in both bone marrow biopsies. Timely evaluation and recognition of the signs and symptoms of HLH is crucial for the prompt management and a decrease in the mortality associated with this disease.

  4. Updates in adult-onset Still disease: Atypical cutaneous manifestations and associations with delayed malignancy.

    PubMed

    Sun, Natalie Z; Brezinski, Elizabeth A; Berliner, Jacqueline; Haemel, Anna; Connolly, M Kari; Gensler, Lianne; McCalmont, Timothy H; Shinkai, Kanade

    2015-08-01

    Adult-onset Still disease (AOSD) is a systemic inflammatory disorder that is clinically characterized by a heterogeneous constellation of symptoms and signs. Though an evanescent eruption is the classic cutaneous finding, recent literature has highlighted atypical rashes associated with Still disease. A second emerging concept in presentations of AOSD is its association with malignancy. This review focuses on these concepts: the clinical spectrum of atypical skin manifestations and AOSD as a paraneoplastic phenomenon. PubMed-MEDLINE was screened for peer-reviewed articles describing atypical presentations of AOSD and cases associated with malignancy. Erythematous, brown or violaceous, persistent papules and plaques were the most common cutaneous finding (28/30 [93%]). Linear configurations were also rarely described. Of these patients, 81% concurrently had the typical evanescent skin eruption. There were 31 patients with associated malignancies, most commonly breast cancer and lymphoma. The diagnosis of malignancy did not precede or immediately follow a clinical presentation otherwise consistent with AOSD in a considerable subset of patients (42%). Understanding the cutaneous spectrum of AOSD and heightened awareness for its delayed association with malignancy may lead to improved recognition of cutaneous variants and reinforce the need for diagnostic evaluation and long-term follow-up for malignancy in patients with this clinical presentation.

  5. Clinical and histopathological features of cutaneous manifestations of adult-onset Still disease.

    PubMed

    Santa, Erin; McFalls, Jeanne M; Sahu, Joya; Lee, Jason B

    2017-03-25

    Adult-onset Still disease (AOSD) is a rare autoinflammatory syndrome characterized by recurring fevers, arthralgia, and consistent laboratory abnormalities that include leukocytosis and hyperferritinemia. Skin findings accompany the disease in nearly 90% of the cases. Early reports described evanescent, pruritic, salmon-pink or urticarial lesions, referred to as the typical eruption of AOSD. Histopathologic findings consist of superficial perivascular dermatitis with varying number of interstitial neutrophils. Later reports described a more persistent rash that tended to be photodistributed, hyperpigmented, often in a linear configuration, sometimes in a rippled pattern, referred to as the atypical eruption of AOSD. The presence of individual necrotic keratinocytes in the upper spinous layer has been the consistent histopathologic finding. The persistent rash may not represent an atypical presentation of AOSD as recent reports indicate a high prevalence of the rash. Emerging data also suggest that patients with persistent eruption have a worse prognosis. The recognition of the clinical and histopathological findings of skin eruptions of AOSD may facilitate an earlier diagnosis, potentially improving disease outcome. Herein, clinical and histopathological features of cutaneous manifestation of AOSD in two Asian women are highlighted accompanied by relevant review of the disease.

  6. Occasional detection of thymic epithelial tumor 4 years after diagnosis of adult onset Still disease

    PubMed Central

    Lococo, Filippo; Bajocchi, Gianluigi; Caruso, Andrea; Valli, Riccardo; Ricchetti, Tommaso; Sgarbi, Giorgio; Salvarani, Carlo

    2016-01-01

    Abstract Background: Thymoma is a T cell neoplasm arising from the thymic epithelium that due to its immunological role, frequently undercover derangements of immunity such a tumors and autoimmune diseases. Methods: Herein, we report, to the best of our knowledge, the first description of an association between thymoma and adult onset Still disease (AOSD) in a 47-year-old man. The first one was occasionally detected 4 years later the diagnosis of AOSD, and surgically removed via right lateral thoracotomy. Histology confirmed an encapsulated thymic tumor (type AB sec. WHO-classification). Results: The AOSD was particularly resistant to the therapy, requiring a combination of immunosuppressant followed by anti-IL1R, that was the only steroids-sparing treatment capable to induce and maintain the remission. The differential diagnosis was particularly challenging because of the severe myasthenic-like symptoms that, with normal laboratory tests, were initially misinterpreted as fibromyalgia. The pathogenic link of this association could be a thymus escape of autoreactive T lymphocytes causing autoimmunity. Conclusion: Clinicians should be always include the possibility of a thymoma in the differential diagnosis of an unusual new onset of weakness and normal laboratories data, in particular once autoimmune disease is present in the medical history. PMID:27603335

  7. Unique histopathologic findings in a patient with adult-onset Still disease.

    PubMed

    Wolgamot, Greg; Yoo, Jane; Hurst, Stan; Gardner, Greg; Olerud, John; Argenyi, Zsolt

    2007-04-01

    Adult-onset Still disease (AOSD) is an uncommon disorder characterized by fever, polyarthralgia, elevated white blood cell count, and a maculopapular rash, the histologic features of which have not been well-known. A 55-year-old Asian woman presented initially with a "burning" and severely pruritic eruption on her face, hands, and arms, thought clinically to be urticaria. Within 1 month, she began spiking high fevers, developed diffuse joint pain, and had marked elevations of ferritin, C-reactive protein, and erythrocyte sedimentation rate, characteristic of AOSD. The cutaneous eruption became more widespread, involving the trunk, scalp, and remainder of the extremities, with diffuse thickening of the skin with papular and linear hyperpigmentation and accentuation. Biopsies from several locations showed focal hyperkeratosis associated with dyskeratotic keratinocytes with a peculiar, distinctive distribution in the upper epidermis and cornified layers. In addition, increased dermal mucin was present, with minimal fibroblast proliferation and inflammation. This unusual combination of diffuse dermal mucinosis and a unique pattern of dyskeratosis can present a challenge in generating an accurate differential diagnosis, and may represent an unusual response to chronic scratching or be a distinctive histologic manifestation of AOSD.

  8. Adult-onset Still's disease presenting as fever of unknown origin in a patient with HIV infection.

    PubMed

    DelVecchio, Sally; Skidmore, Peter

    2008-02-15

    A 43-year-old African American man with known human immunodeficiency virus (HIV) infection was found to have adult-onset Still's disease manifesting as fever of unknown origin. In the era of highly active antiretroviral therapy, HIV-infected patients are preserving their immune status and, thus, must be evaluated in a manner similar to that for the general population.

  9. Serum calprotectin--a promising diagnostic marker for adult-onset Still's disease.

    PubMed

    Guo, Qian; Zha, Xicao; Li, Chun; Jia, Yuan; Zhu, Lei; Guo, Jianping; Su, Yin

    2016-01-01

    Calprotectin is a calcium-binding cytosolic protein, mainly expressed in immune cells, such as neutrophils, monocytes, and macrophages. Our study aimed to evaluate the diagnostic value of calprotectin for adult-onset Still's disease (AOSD), by comparing serum calprotectin concentrations in patients with AOSD (n = 46), rheumatoid arthritis (RA, n = 34), primary Sjögren syndrome (pSS, n = 40), systemic lupus erythematosus (SLE, n = 39), osteoarthritis (OA, n = 20), and healthy controls (HCs, n = 49). Calprotectin concentrations were significantly higher in patients with AOSD (55.26 ± 18.00 ng/ml), compared to patients with RA (39.17 ± 18.90 ng/ml), pSS (35.31 ± 19.47 ng/ml), SLE (32.21 ± 25.01 ng/ml), OA (19.24 ± 10.67 ng/ml), and HCs (8.46 ± 5.17 ng/ml). All the differences were highly significant (p < 0.001). Using receiver-operating characteristic curve, the cut-off value of calprotectin was defined as 45.488 ng/ml, and its sensitivity and specificity for AOSD diagnosis were 63.0 and 80.1%, respectively. The positive rate of calprotectin was significantly higher in AOSD cases compared to patients with other diseases and healthy controls (p < 0.001). Serum calprotectin was positively correlated with ferritin (r = 0.294, p < 0.05), and concentration of hemoglobin was significantly lower in calprotectin-positive patients compared to negative patients in AOSD (103.49 ± 20.21 g/l vs 115.71 ± 15.59 g/l, t = -2.142, p = 0.038). These findings suggest that serum calprotectin may serve as a promising marker for the diagnosis of AOSD and monitor disease activity to a certain extent.

  10. Fever of unknown origin and leukemoid reaction as initial presentation of adult-onset Still's disease.

    PubMed

    Pardo-Cabello, Alfredo José; Manzano-Gamero, Victoria; Javier-Martínez, Rosario

    2014-01-01

    Adult Still's Disease has been reported as cause of Fever of Unknown Origin. Leukocytosis has been described as a common haematological abnormality in Adult Still's Disease. In some rare cases, leukemoid reaction has been reported associated to Still's Disease. We report the case of Adult Still's Disease presenting as Fever of Unknown Origin and leukemoid reaction in a patient with Down Syndrome. The patient needed high dosage of corticosteroids to control the disease and haematological findings.

  11. [Recurrent effusive pericarditis in the course of adult-onset Still's disease--case reports of two patients].

    PubMed

    Bilska, Anna; Wilińska, Ewelina; Szturmowicz, Monika; Wawrzyńska, Liliana; Fijałkowska, Anna; Oniszh, Karina; Swiatowiec, Andrzej; Wsół, Agnieszka; Torbicki, Adam

    2011-01-01

    Pericardial effusion is caused by various pathological agents. In differential diagnosis infectious as well as non-infectious factors have to be considered. Adult-onset Still disease (AOSD)--relatively uncommon systemic inflammatory disorder of unknown etiology--is among possible diagnosis. The disease typically affects patients in the age between 16-35 years and is characterized by spiking fever, arthralgia, evanescent salmon rash with other abnormalities including pharingitis, serositis (especially pleuritis and pericarditis) and leucocytosis as well as increased serum levels of inflammatory indicators. We present two patients with recurrent pericardial effusion in the course of AOSD.

  12. Combination Immunosuppressive Therapy Including Rituximab for Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis in Adult-Onset Still's Disease

    PubMed Central

    Schäfer, Eva Johanna; Jung, Wolfram

    2016-01-01

    Hemophagocytic lymphopcytosis (HLH) is a life-threatening condition. It can occur either as primary form with genetic defects or secondary to other conditions, such as hematological or autoimmune diseases. Certain triggering factors can predispose individuals to the development of HLH. We report the case of a 25-year-old male patient who was diagnosed with HLH in the context of adult-onset Still's disease (AOSD) during a primary infection with Epstein-Barr virus (EBV). During therapy with anakinra and dexamethasone, he was still symptomatic with high-spiking fevers, arthralgia, and sore throat. His laboratory values showed high levels of ferritin and C-reactive protein. His condition improved after the addition of rituximab and cyclosporine to his immunosuppressive regimen with prednisolone and anakinra. This combination therapy led to a sustained clinical and serological remission of his condition. While rituximab has been used successfully for HLH in the context of EBV-associated lymphoma, its use in autoimmune diseases is uncommon. We hypothesize that the development of HLH was triggered by a primary EBV infection and that rituximab led to elimination of EBV-infected B-cells, while cyclosporine ameliorated the cytokine excess. We therefore propose that this combination immunosuppressive therapy might be successfully used in HLH occurring in the context of autoimmune diseases. PMID:28018698

  13. Retrospective study of 61 patients with adult-onset Still's disease admitted with fever of unknown origin in China.

    PubMed

    Chen, Pei-Dong; Yu, Sheng-Lei; Chen, Shu; Weng, Xin-Hua

    2012-01-01

    Adult-onset Still's disease (AOSD), as a category of connective tissue diseases, has about 5∼9% of fever of unknown origin (FUO) cases. Diagnosis of AOSD was challenging because of its nonspecific characteristics. The present study analyzed clinical manifestations and laboratory findings in a series of patients with AOSD from eastern China. Medical records of 61 patients admitted with FUO and with a discharge diagnosis of AOSD were retrospectively evaluated and analyzed with special focus on clinical manifestations and laboratory findings. Compared with previous reports, most features of our patients had a similar incidence rate. Rash (79%), arthralgia (80%), and sore throat (84%) were the most frequent clinical manifestations in our series. Leukocytosis (80%), elevated ESR (98%) and CRP (100%), negative ANA (90%) and RF (93%), and high ferritin level (94%) were the most sensitive laboratory findings in our patients. AOSD was not a rare reason of FUO in eastern China. Fever, arthralgia, rash, sore throat, leukocytosis, neutrophilia, elevated ESR and CRP, negative ANA and RF, and high ferritin level were the most common clinical features in our series. The lack of highly specific characteristic makes the diagnosis of AOSD difficult compared with other diseases in FUO.

  14. Clinical characteristics and follow-up analysis of adult-onset Still's disease complicated by hemophagocytic lymphohistiocytosis.

    PubMed

    Zhang, Yun; Yang, Yingyun; Bai, Yujia; Yang, Dan; Xiong, Yangyang; Zeng, Xuejun

    2016-05-01

    We evaluated clinical characteristics and prognosis for adult-onset Still's disease (AOSD) complicated by hemophagocytic lymphohistiocytosis (HLH). We retrospectively identified cases of AOSD with (n = 10) and without (n = 305) HLH complications. We reviewed their medical records, completed follow-up through outpatient clinic and telephone interviews, and analyzed their clinical symptoms, signs, laboratory test results, treatments, and prognosis. More AOSD patients with HLH developed hepatomegaly, bleeding, serositis, and neurologic symptoms than those without HLH, and they more commonly presented with leukopenia, thrombocytopenia, severe anemia, severe liver function abnormalities, decreased fibrinogen, elevated immunoglobulin, and bone marrow hemophagocytosis. The ten patients with AOSD complicated by HLH were treated with high-dose steroids or pulse steroid therapy, and eight of them also received cytotoxic drugs, while biological agents showed poor response. Follow-up results indicated that AOSD patients overall had good prognosis, while those with HLH showed worse prognosis, including higher relapse and readmission rates and increased mortality. In patients with AOSD, unexplained decreased blood cells, severe liver dysfunction, and/or hemophagocytosis in the bone marrow should be considered as signs of HLH complication. Patients with AOSD complicated by HLH have worse prognosis and higher relapse rates compared to AOSD patients without HLH complications. Thus, these patients should undergo frequent and careful follow-up.

  15. A series of 22 patients with adult-onset Still's disease presenting with fever of unknown origin. A difficult diagnosis?

    PubMed

    Baxevanos, Gerasimos; Tzimas, Thomas; Pappas, Georgios; Akritidis, Nikolaos

    2012-01-01

    Adult-onset Still's disease (AOSD) remains a perplexing, difficult to diagnose clinical entity, with clinical characteristics that are often broad and encountered in numerous other clinical entities. This vague clinical presentation is depicted in the commonly used diagnostic criteria, as the ones by Yamaguchi and Fautrel. The authors sought to investigate how diagnostic criteria apply in a series of 22 new cases of AOSD patients presenting with fever of unknown origin (FUO) and diagnosed at the Internal Medicine Department of Hatzikosta General Hospital of Ioannina, Greece. The aims of the study were: (1) to study the incidence of AOSD and (2) to retrospectively apply different classifications to the data of these patients in search of a more efficient way of diagnosing these patients in the future. The annual incidence of AOSD was estimated at two new cases per 10(5). The clinical manifestations of the patients are discussed, with an emphasis on specific manifestations being considered as criteria by Yamaguchi and Fautrel classifications. Four patients exhibited markedly increased serum D: -dimers, a finding of which the potential pathophysiologic implications are discussed. Serum ferritin levels have additive values, both for diagnostic and cost-reduction purposes in cases presenting as FUO; serum ferritin values are not included in any diagnostic set of criteria at present. The finding of high levels of D-dimers in AOSD needs further studies.

  16. Efficacy of Anakinra in Refractory Adult-Onset Still's Disease: Multicenter Study of 41 Patients and Literature Review.

    PubMed

    Ortiz-Sanjuán, Francisco; Blanco, Ricardo; Riancho-Zarrabeitia, Leyre; Castañeda, Santos; Olivé, Alejandro; Riveros, Anne; Velloso-Feijoo, María L; Narváez, Javier; Jiménez-Moleón, Inmaculada; Maiz-Alonso, Olga; Ordóñez, Carmen; Bernal, José A; Hernández, María V; Sifuentes-Giraldo, Walter A; Gómez-Arango, Catalina; Galíndez-Agirregoikoa, Eva; Blanco-Madrigal, Juan; Ortiz-Santamaria, Vera; del Blanco-Barnusell, Jordi; De Dios, Juan R; Moreno, Mireia; Fiter, Jordi; de los Riscos, Marina; Carreira, Patricia; Rodriguez-Valls, María J; González-Vela, M Carmen; Calvo-Río, Vanesa; Loricera, Javier; Palmou-Fontana, Natalia; Pina, Trinitario; Llorca, Javier; González-Gay, Miguel A

    2015-09-01

    Adult-onset Still's disease (AOSD) is often refractory to standard therapy. Anakinra (ANK), an interleukin-1 receptor antagonist, has demonstrated efficacy in single cases and small series of AOSD. We assessed the efficacy of ANK in a series of AOSD patients. Multicenter retrospective open-label study. ANK was used due to lack of efficacy to standard synthetic immunosuppressive drugs and in some cases also to at least 1 biologic agent. Forty-one patients (26 women/15 men) were recruited. They had a mean age of 34.4 ± 14 years and a median [interquartile range (IQR)] AOSD duration of 3.5 [2-6] years before ANK onset. At that time the most common clinical features were joint manifestations 87.8%, fever 78%, and cutaneous rash 58.5%. ANK yielded rapid and maintained clinical and laboratory improvement. After 1 year of therapy, the frequency of joint and cutaneous manifestations had decreased to 41.5% and to 7.3% respectively, fever from 78% to 14.6%, anemia from 56.1% to 9.8%, and lymphadenopathy from 26.8% to 4.9%. A dramatic improvement of laboratory parameters was also achieved. The median [IQR] prednisone dose was also reduced from 20 [11.3-47.5] mg/day at ANK onset to 5 [0-10] at 12 months. After a median [IQR] follow-up of 16 [5-50] months, the most important side effects were cutaneous manifestations (n = 8), mild leukopenia (n = 3), myopathy (n = 1), and infections (n = 5). ANK is associated with rapid and maintained clinical and laboratory improvement, even in nonresponders to other biologic agents. However, joint manifestations are more refractory than the systemic manifestations.

  17. Adult-Onset Still’s Disease: Still a Serious Health Problem (a Case Report and Literature Review)

    PubMed Central

    Agha-Abbaslou, Mojgan; Bensaci, Ana Maria; Dike, Oluchi; Poznansky, Mark C.; Hyat, Arooj

    2017-01-01

    Patient: Female, 53 Final Diagnosis: Adult-onset Still’s Disease Symptoms: Abdominal pain • fever Medication: — Clinical Procedure: — Specialty: Rheumatology Objective: Rare disease Background: Adult-onset Still’s Disease (AOSD) is a rare systemic inflammatory disease accompanied by a triad of spiking fever, maculopapular exanthema, and arthralgia. To date, there is no definite laboratory or imaging test available for diagnosing AOSD, and the diagnosis is one of exclusion, which can be very challenging. Case Report: We report on the case of a 53-year-old female who presented with fever, arthralgia, and abdominal pain. Her initial laboratory tests showed elevated AST and ALT, and normal leukocytes with bandemia. During her hospitalization, we evaluated the patient for other potential differential diagnoses. After an extensive workup, the patient was diagnosed with AOSD based on Yamaguchi criteria. Her serum ferritin levels were measured and found to be markedly elevated, which is a non-specific finding in AOSD patients. Conclusions: This case highlights the important role of a detailed history and physical examination for timely diagnosis of AOSD to prevent complications and improve patient’s prognosis. PMID:28154368

  18. When uncommon and common coalesce: adult onset Still's disease associated with breast augmentation as part of autoimmune syndrome induced by adjuvants (ASIA).

    PubMed

    Dagan, A; Kogan, M; Shoenfeld, Y; Segal, G

    2016-06-01

    Adult onset Still's disease (AOSD) is an uncommon, multisystemic, auto-inflammatory disorder, while breast augmentation is a very common cosmetic procedure. We describe a case in which these two coalesce, AOSD, manifested with pleuritis and pericarditis, developed after breast mammoplasty. The pathogenetic, missing link, behind the development of AOSD following mammoplasty, is thought to be the autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA). We reviewed other cases of AOSD associated with breast mammoplasty published to date and the literature regarding AOSD and ASIA syndrome. The review is followed by a short debate of whether silicone implants should be explanted in similar, future cases.

  19. Iron Deficiency Anemia in Adult Onset Still's Disease with a Serum Ferritin of 26,387 μg/L.

    PubMed

    Patel, Sheetal; Monemian, Seyed; Khalid, Ayesha; Dosik, Harvey

    2011-01-01

    Serum ferritin rises in the anemia of chronic inflammation reflecting increased iron storage and other changes mediated by inflammation. When iron deficiency coexists, the ferritin may not always decline into the subnormal range. We describe the rare interaction of iron deficiency with the extreme hyperferritinemia characteristic of adult onset Still's disease. The combination has clinical relevance and allows deductions about the presence of serum ferritin at 26,387 μg/L despite obvious iron depletion. The diagnosis of iron deficiency anemia was delayed and became fully obvious when her Still's disease remitted and serum ferritin decreased to 6.5 μg/L. The coexistence of iron deficiency should be considered when evaluating a patient with anemia of chronic inflammation even when the ferritin level is elevated several hundredfold. Further insights on ferritin metabolism in Still's disease are suggested by the likelihood that the patient's massive hyperferritinemia in the acute phase of Still's disease was almost entirely of the iron-free apoferritin form.

  20. [Adult-onset rare diseases].

    PubMed

    Pfliegler, György; Kovács, Erzsébet; Kovács, György; Urbán, Krisztián; Nagy, Valéria; Brúgós, Boglárka

    2014-03-02

    The present paper is focusing on rare diseases manifesting in late childhood or adulthood. A part of these syndromes are not of genetic origin, such as relatively or absolutely rare infections, autoimmune diseases, tumours, or diseases due to rare environmental toxic agents. In addition, even a large proportion of genetic disorders may develop in adulthood or may have adult forms as well, affecting are almost each medical specialization. Examples are storage disorders (e.g. adult form of Tay-Sachs disease, Gaucher-disease), enzyme deficiencies (e.g. ornithin-transcarbamylase deficiency of the urea cycle disorders), rare thrombophilias (e.g. homozygous factor V. Leiden mutation, antithrombin deficiency), or some rare monogenic disorders such as Huntington-chorea and many others. It is now generally accepted that at least half of the 6-8000 "rare diseases" belong either to the scope of adult-care (e.g. internal medicine, neurology), or to "age-neutral" specialities such as ophtalmology, dermatology etc.).

  1. Adult Still's disease

    MedlinePlus

    Still's disease - adult; AOSD ... than 1 out of 100,000 people develop adult-onset Still's disease each year. It affects women more often than men. The cause of adult Still's disease is unknown. No risk factors for ...

  2. Refractory Coats’ Disease of Adult Onset

    PubMed Central

    Beselga, D.; Campos, A.; Mendes, S.; Carvalheira, F.; Castro, M.; Castanheira, D.

    2012-01-01

    Purpose We present the case of an 18-year-old Caucasian male with a unilateral macular star and retinal vascular anomalies compatible with adult onset Coats’ disease. Methods Diagnosis was based on fundoscopic, fluorescein angiography and optical coherence tomography findings. Results The patient presented to our emergency department with complaints of low vision in his left eye (LE) detected 10 days before. The best-corrected visual acuity in the LE was 20/50. Fundoscopy of the LE evidenced a complete macular star. Optical coherence tomography showed increased retinal thickness, infiltration of the retinal wall, and detachment of the neuroepithelium. Angiography revealed no appreciable diffusion in the macula. Above the superior temporal (ST) arcade, anomalies in the retinal vasculature were found, with interruption of the peripheral vessels and vessels which were ‘sausage’-like. After 1 month, the LE vision evolved to hand movements. Laser photocoagulation was performed in the ST quadrant. Intravitreal injection of bevacizumab 1.25 mg/0.05 ml and photodynamic therapy were performed without any significant changes, progression of ST serous detachment of the neuroepithelium, and finally progression to macular fibrosis. Discussion Coats’ disease is usually diagnosed in childhood, but rare cases may occur in adults. Those cases usually have a more indolent course which was not observed in our patient. When there is macular involvement, prognosis is more guarded, despite treatment. PMID:22548045

  3. Clinicopathological features of adult-onset neuronal intranuclear inclusion disease

    PubMed Central

    Sone, Jun; Mori, Keiko; Inagaki, Tomonori; Katsumata, Ryu; Takagi, Shinnosuke; Yokoi, Satoshi; Araki, Kunihiko; Kato, Toshiyasu; Nakamura, Tomohiko; Koike, Haruki; Takashima, Hiroshi; Hashiguchi, Akihiro; Kohno, Yutaka; Kurashige, Takashi; Kuriyama, Masaru; Takiyama, Yoshihisa; Tsuchiya, Mai; Kitagawa, Naoyuki; Kawamoto, Michi; Yoshimura, Hajime; Suto, Yutaka; Nakayasu, Hiroyuki; Uehara, Naoko; Sugiyama, Hiroshi; Takahashi, Makoto; Kokubun, Norito; Konno, Takuya; Katsuno, Masahisa; Tanaka, Fumiaki; Iwasaki, Yasushi; Yoshida, Mari

    2016-01-01

    Neuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous system, and also in the visceral organs. NIID has been considered to be a heterogeneous disease because of the highly variable clinical manifestations, and ante-mortem diagnosis has been difficult. However, since we reported the usefulness of skin biopsy for the diagnosis of NIID, the number of NIID diagnoses has increased, in particular adult-onset NIID. In this study, we studied 57 cases of adult-onset NIID and described their clinical and pathological features. We analysed both NIID cases diagnosed by post-mortem dissection and by ante-mortem skin biopsy based on the presence of characteristic eosinophilic, hyaline and ubiquitin-positive intanuclear inclusion: 38 sporadic cases and 19 familial cases, from six families. In the sporadic NIID cases with onset age from 51 to 76, dementia was the most prominent initial symptom (94.7%) as designated ‘dementia dominant group’, followed by miosis, ataxia and unconsciousness. Muscle weakness and sensory disturbance were also observed. It was observed that, in familial NIID cases with onset age less than 40 years, muscle weakness was seen most frequently (100%), as designated ‘limb weakness group’, followed by sensory disturbance, miosis, bladder dysfunction, and dementia. In familial cases with more than 40 years of onset age, dementia was most prominent (100%). Elevated cerebrospinal fluid protein and abnormal nerve conduction were frequently observed in both sporadic and familial NIID cases. Head magnetic resonance imaging showed high intensity signal in corticomedullary junction in diffusion-weighted image in both sporadic and familial NIID cases, a strong clue to the diagnosis. All of the dementia dominant cases presented with this type of leukoencephalopathy on head magnetic resonance imaging. Both sporadic and

  4. [Kimura's disease: an unrecognized cause of adult-onset nephrotic syndrome with minimal change disease].

    PubMed

    Shehwaro, N; Langlois, A-L; Gueutin, V; Debchi, L; Charlotte, F; Rouvier, P; Rottembourg, J; Izzedine, H

    2014-02-01

    Kimura's disease (KD) is an angiolymphoid proliferative disorder of soft tissue with eosinophilia, with a predilection for head and neck regions in young Oriental men. Kidney disease is thought to be rare in KD. About a case of adult-onset nephrotic syndrome with minimal change disease, we comment Kimura's disease and its associated kidney damage. Kimura disease should be suspected and included in the diagnosis of adult-onset nephrotic syndrome with minimal change disease.

  5. Adult onset Still’s disease with dermatopathic lymphadenopathy

    PubMed Central

    Qureshi, Ahmad Z.; AlSheef, Mohammad; Qureshi, Waqas T.; Amjad, Waseem

    2016-01-01

    Adult onset Still’s disease (AOSD) is a chronic inflammatory disorder involving multiple systems. The symptoms mimic those of lymphomas, therefore, the diagnosis of lymphoma needs to be excluded prior to establishing the diagnosis of AOSD. Another similar condition is dermatopathic lymphadenopathy (DL). In DL, the histopathological appearance of lymph node biopsy may also mimic AOSD. The DL is associated with several systemic pathologies, such as malignant lymphomas, and rarely AOSD. We present a case of a 43-year-old male presented with 3 months history of fatigue, fever, and lymphadenopathy. Initial work-up satisfactorily met the criteria for diagnosis of AOSD. But considering the well-known association of DL with hematological malignancies, detailed pathological studies were considered, including tumor markers to rule out the possibility of malignancy. The patient was started on steroids and showed remarkable recovery within 2 weeks. Evaluation of malignant lymphomas in a patient with DL is important, in order to diagnose AOSD and rule out hematological malignancy. PMID:27761568

  6. Adult-Onset Esophageal Crohn’s Disease

    PubMed Central

    Kasarala, George; Durrett, Sam

    2016-01-01

    Crohn’s disease (CD) is an idiopathic inflammatory bowel disease that can involve any part of the gastrointestinal tract. Esophageal involvement is rarely seen in adults, especially at the initial diagnosis of CD. Esophageal symptoms as primary manifestations of the disease are extremely rare. We report a case of a CD with esophageal involvement at the time of her initial diagnosis of CD. PMID:27761477

  7. Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers.

    PubMed

    Guerrero-Bosagna, Carlos; Covert, Trevor R; Haque, Md M; Settles, Matthew; Nilsson, Eric E; Anway, Matthew D; Skinner, Michael K

    2012-12-01

    The endocrine disruptor vinclozolin has previously been shown to promote epigenetic transgenerational inheritance of adult onset disease in the rat. The current study was designed to investigate the transgenerational actions of vinclozolin on the mouse. Transient exposure of the F0 generation gestating female during gonadal sex determination promoted transgenerational adult onset disease in F3 generation male and female mice, including spermatogenic cell defects, testicular abnormalities, prostate abnormalities, kidney abnormalities and polycystic ovarian disease. Pathology analysis demonstrated 75% of the vinclozolin lineage animals developed disease with 34% having two or more different disease states. Interestingly, the vinclozolin induced transgenerational disease was observed in the outbred CD-1 strain, but not the inbred 129 mouse strain. Analysis of the F3 generation sperm epigenome identified differential DNA methylation regions that can potentially be utilized as epigenetic biomarkers for transgenerational exposure and disease.

  8. Adult-Onset Asthma to Coronary Heart Disease and Stroke

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Asthma has been associated with atherosclerotic disease in several studies with some evidence that this association may be limited to women. However, most previous studies have failed to account for the heterogeneity of asthma subtypes. We previously reported increased carotid intima medial thickne...

  9. Dioxin (TCDD) induces epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.

    PubMed

    Manikkam, Mohan; Tracey, Rebecca; Guerrero-Bosagna, Carlos; Skinner, Michael K

    2012-01-01

    Environmental compounds can promote epigenetic transgenerational inheritance of adult-onset disease in subsequent generations following ancestral exposure during fetal gonadal sex determination. The current study examined the ability of dioxin (2,3,7,8-tetrachlorodibenzo[p]dioxin, TCDD) to promote epigenetic transgenerational inheritance of disease and DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to dioxin during fetal day 8 to 14 and adult-onset disease was evaluated in F1 and F3 generation rats. The incidences of total disease and multiple disease increased in F1 and F3 generations. Prostate disease, ovarian primordial follicle loss and polycystic ovary disease were increased in F1 generation dioxin lineage. Kidney disease in males, pubertal abnormalities in females, ovarian primordial follicle loss and polycystic ovary disease were increased in F3 generation dioxin lineage animals. Analysis of the F3 generation sperm epigenome identified 50 differentially DNA methylated regions (DMR) in gene promoters. These DMR provide potential epigenetic biomarkers for transgenerational disease and ancestral environmental exposures. Observations demonstrate dioxin exposure of a gestating female promotes epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.

  10. Sandhoff disease mimicking adult-onset bulbospinal neuronopathy.

    PubMed Central

    Thomas, P K; Young, E; King, R H

    1989-01-01

    A 32 year old male is described with an onset of upper limb postural tremor in adolescence followed by muscle cramps. Progressive proximal amyotrophy and weakness in the limbs developed late in the third decade. Examination disclosed, in addition, bilateral facial weakness and mild dysarthria. Enzyme studies revealed hexosaminidase A and B deficiency, indicating a diagnosis of Sandhoff disease. Intra-axonal membranocytoplasmic bodies were present in a rectal biopsy. The presentation, which resembled that of X-linked bulbospinal neuronopathy, widens the clinical spectrum for disorders related to G(M2) gangliosidosis. Images PMID:2795083

  11. Adult onset Hallervorden-Spatz disease with psychotic symptoms.

    PubMed

    del Valle-López, Pilar; Pérez-García, Rosa; Sanguino-Andrés, Rosa; González-Pablos, Emilio

    2011-01-01

    Hallervorden-Spatz disease is a rare neurological disorder characterized by pyramidal and extrapyramidal manifestations, dysarthria and dementia. Its onset is usually in childhood and most patients have a fatal outcome in few years. A high percentage of cases are hereditary with a recessive autosomal pattern. In the majority of the patients reported, a mutation of the gene that encodes the pantothenate kinase (PANK2) located in the 20p13-p12.3 chromosome that causes iron storage in the basal ganglia of the brain has been found. Its diagnosis is based on clinical symptoms as well as specific MRI imaging findings. The most common psychiatric features are cognitive impairment as well as depressive symptoms. There are few documented cases with psychotic disorders. We present the case of a patient with late onset Hallervorden-Spatz disease and psychotic symptoms that preceded the development of neurological manifestations. The pathophysiology and the treatment of psychotic symptomatology are presented and discussed. Key words: Psicosis, Hallervorden-Spatz, late onset, Basal ganglia.

  12. Genetic architecture differences between pediatric and adult-onset inflammatory bowel diseases in the Polish population

    PubMed Central

    Ostrowski, Jerzy; Paziewska, Agnieszka; Lazowska, Izabella; Ambrozkiewicz, Filip; Goryca, Krzysztof; Kulecka, Maria; Rawa, Tomasz; Karczmarski, Jakub; Dabrowska, Michalina; Zeber-Lubecka, Natalia; Tomecki, Roman; Kluska, Anna; Balabas, Aneta; Piatkowska, Magdalena; Paczkowska, Katarzyna; Kierkus, Jaroslaw; Socha, Piotr; Lodyga, Michal; Rydzewska, Grazyna; Klopocka, Maria; Mierzwa, Grazyna; Iwanczak, Barbara; Krzesiek, Elzbieta; Bak-Drabik, Katarzyna; Walkowiak, Jaroslaw; Klincewicz, Beata; Radwan, Piotr; Grzybowska-Chlebowczyk, Urszula; Landowski, Piotr; Jankowska, Agnieszka; Korczowski, Bartosz; Starzynska, Teresa; Albrecht, Piotr; Mikula, Michal

    2016-01-01

    Most inflammatory bowel diseases (IBDs) are classic complex disorders represented by common alleles. Here we aimed to define the genetic architecture of pediatric and adult-onset IBDs for the Polish population. A total of 1495 patients were recruited, including 761 patients with Crohn’s disease (CD; 424 pediatric), 734 patients with ulcerative colitis (UC; 390 pediatric), and 934 healthy controls. Allelotyping employed a pooled-DNA genome-wide association study (GWAS) and was validated by individual genotyping. Whole exome sequencing (WES) was performed on 44 IBD patients diagnosed before 6 years of age, 45 patients diagnosed after 40 years of age, and 18 healthy controls. Altogether, out of 88 selected SNPs, 31 SNPs were replicated for association with IBD. A novel BRD2 (rs1049526) association reached significance of P = 5.2 × 10−11 and odds ratio (OR) = 2.43. Twenty SNPs were shared between pediatric and adult patients; 1 and 7 were unique to adult-onset and pediatric-onset IBD, respectively. WES identified numerous rare and potentially deleterious variants in IBD-associated or innate immunity-associated genes. Deleterious alleles in both groups were over-represented among rare variants in affected children. Our GWAS revealed differences in the polygenic architecture of pediatric- and adult-onset IBD. A significant accumulation of rare and deleterious variants in affected children suggests a contribution by yet unexplained genetic components. PMID:28008999

  13. Pesticide methoxychlor promotes the epigenetic transgenerational inheritance of adult-onset disease through the female germline.

    PubMed

    Manikkam, Mohan; Haque, M Muksitul; Guerrero-Bosagna, Carlos; Nilsson, Eric E; Skinner, Michael K

    2014-01-01

    Environmental compounds including fungicides, plastics, pesticides, dioxin and hydrocarbons can promote the epigenetic transgenerational inheritance of adult-onset disease in future generation progeny following ancestral exposure during the critical period of fetal gonadal sex determination. This study examined the actions of the pesticide methoxychlor to promote the epigenetic transgenerational inheritance of adult-onset disease and associated differential DNA methylation regions (i.e. epimutations) in sperm. Gestating F0 generation female rats were transiently exposed to methoxychlor during fetal gonadal development (gestation days 8 to 14) and then adult-onset disease was evaluated in adult F1 and F3 (great-grand offspring) generation progeny for control (vehicle exposed) and methoxychlor lineage offspring. There were increases in the incidence of kidney disease, ovary disease, and obesity in the methoxychlor lineage animals. In females and males the incidence of disease increased in both the F1 and the F3 generations and the incidence of multiple disease increased in the F3 generation. There was increased disease incidence in F4 generation reverse outcross (female) offspring indicating disease transmission was primarily transmitted through the female germline. Analysis of the F3 generation sperm epigenome of the methoxychlor lineage males identified differentially DNA methylated regions (DMR) termed epimutations in a genome-wide gene promoters analysis. These epimutations were found to be methoxychlor exposure specific in comparison with other exposure specific sperm epimutation signatures. Observations indicate that the pesticide methoxychlor has the potential to promote the epigenetic transgenerational inheritance of disease and the sperm epimutations appear to provide exposure specific epigenetic biomarkers for transgenerational disease and ancestral environmental exposures.

  14. Familial Adult-onset Alexander Disease: Clinical and Neuroradiological Findings of Three Cases

    PubMed Central

    ELMALI, Ayşe Deniz; ÇETİNÇELİK, Ümran; IŞLAK, Civan; UZUN ADATEPE, Nurten; KARAALİ SAVRUN, Feray; YALÇINKAYA, Cengiz

    2016-01-01

    The adult-onset Alexander disease (AOAD) dramatically differs from the early onset AD with respect to clinical and neuroradiological findings. Herein we report the detailed clinical and neuroradiological findings of a Turkish family with AOAD. In all three cases, magnetic resonance imaging revealed marked atrophy of the mesencephalon, bulbus, and cervical spinal cord accompanied with signal abnormalities in the same regions along with supratentorial white matter. Basal ganglia were affected in two cases. Molecular genetic analysis revealed heterozygous mutation in the 8th exon of the glial fibrillary acidic protein gene M451I (c.1245G>A), leading to the diagnosis of AOAD in all cases. PMID:28360791

  15. Chinese new immigrant mothers' perception about adult-onset non-communicable diseases prevention during childhood.

    PubMed

    Wang, Linda Dong Ling; Lam, Wendy Wing Tak; Wu, Joseph Tsz Kei; Fielding, Richard

    2015-12-01

    Many non-communicable diseases (NCDs) are largely preventable via behaviour change and healthy lifestyle, which may be best established during childhood. This study sought insights into Chinese new immigrant mothers' perceptions about adult-onset NCDs prevention during childhood. Twenty-three semi-structured interviews were carried out with new immigrant mothers from mainland China who had at least one child aged 14 years or younger living in Hong Kong. Interviews were audio taped, transcribed and analysed using a Grounded Theory approach. The present study identified three major themes: perceived causes of adult NCDs, beliefs about NCDs prevention and everyday health information practices. Unhealthy lifestyle, contaminated food and environment pollution were perceived as the primary causes of adult NCDs. Less than half of the participants recognized that parents had responsibility for helping children establish healthy behaviours from an early age to prevent diseases in later life. Most participants expressed helplessness about chronic diseases prevention due to lack of knowledge of prevention, being perceived as beyond individual control. Many participants experienced barriers to seeking health information, the most common sources of health information being interpersonal conversation and television. Participants' everyday information practice was passive and generally lacked awareness regarding early prevention of adult-onset NCDs. Updated understanding of this issue has notable implications for future health promotion interventions.

  16. Limited diagnostic value of procalcitonin in early diagnosis of adult onset Still’s disease

    PubMed Central

    Wysocki, Jacek

    2016-01-01

    A 17-year-old female patient was referred to the Infectious Diseases Ward because of fever lasting for 14 days. On admission to the hospital the patient was in a generally good state, without any abnormalities on physical examination. Laboratory investigation revealed elevated inflammatory markers. Diagnostic imaging comprising chest X-ray, abdominal ultrasonography, and echocardiography showed no abnormalities. During the hospitalization, there occurred episodes of fever with skin rash and musculoskeletal pain of the lower limbs. Procalcitonin concentrations continued to increase. C-reactive protein concentrations decreased during therapy, starting from 191 mg/l. On the 23rd day of the disease, edema of the feet, ankles, and knees appeared. On the basis of the clinical picture and after excluding other possible causes of fever, the patient was diagnosed with adult onset Still’s disease. The procalcitonin concentration was normalized after 5 days of steroid therapy. The patient was discharged under ambulatory rheumatologic supervision. PMID:27826176

  17. Adult-onset Still’s disease: current challenges and future prospects

    PubMed Central

    Siddiqui, Mariam; Putman, Michael S; Dua, Anisha B

    2016-01-01

    Adult-onset Still’s disease (AOSD) – a multi-systemic inflammatory condition characterized by high fevers, polyarthritis, an evanescent rash, and pharyngitis – has been a challenging condition to diagnose expediently and treat effectively. Questions remain regarding the underlying pathophysiology and etiology of AOSD. Pathognomonic diagnostic tests and reliable biomarkers remain undiscovered. Over the past decade, important progress has been made. Diagnostic criteria employing glycosylated ferritin have improved specificity. More important, novel biologic therapies have offered important clues to AOSD’s underlying pathophysiology. Cytokine-specific biologic therapies have been instrumental in providing more effective treatment for disease refractory to conventional treatment. While IL-1 therapy has demonstrated efficacy in refractory disease, novel therapies targeting IL-6 and IL-18 show great promise and are currently under investigation. PMID:27843366

  18. Acute pneumonitis in a patient with adult-onset disease after toclizumab treatment with good response to anakinra.

    PubMed

    Sangüesa Gómez, Clara; Flores Robles, Bryan Josué; Jara Chinarro, Beatriz; Espinosa Malpartida, María; Barbadillo Mateos, Carmen

    Pulmonary involvement in the form of acute pneumonitis in adult-onset Still's disease (AOSD) is an uncommon manifestation, with few cases reported in the literature. We report the case of a 61-year-old male with 3 years of AOSD evolution, treated with methotrexate (MTX) and half-dose corticosteroids, which debuted with symptoms of fever, dyspnea and dry cough after 3 weeks of receiving the first dose of tocilizumab (TCZ). In the follow-up study showed leukocytosis with left shift, elevated serum ferritin and C-reactive protein standard. The chest CT scan showed ground-glass pattern predominantly in central and upper lobes and the BAL shows an increase in the percentage of lymphocyte with normal subpopulations and negative cultures. MTX and TCM were suspended, prednisone was increased to 30mg/day and within a week Anakinra 100mg/day SC was iniciated, noting in a few days a progressive clinical, analytical and radiological improvement.

  19. The ocular motor features of adult-onset alexander disease: a case and review of the literature.

    PubMed

    Pfeffer, Gerald; Abegg, Mathias; Vertinsky, A Talia; Ceccherini, Isabella; Caroli, Francesco; Barton, Jason J S

    2011-06-01

    A 51-year-old Chinese man presented with gaze-evoked nystagmus, impaired smooth pursuit and vestibular ocular reflex cancellation, and saccadic dysmetria, along with a family history suggestive of late-onset autosomal dominant parkinsonism. MRI revealed abnormalities of the medulla and cervical spinal cord typical of adult-onset Alexander disease, and genetic testing showed homozygosity for the p.D295N polymorphic allele in the gene encoding the glial fibrillary acidic protein. A review of the literature shows that ocular signs are frequent in adult-onset Alexander disease, most commonly gaze-evoked nystagmus, pendular nystagmus, and/or oculopalatal myoclonus, and less commonly ptosis, miosis, and saccadic dysmetria. These signs are consistent with the propensity of adult-onset Alexander disease to cause medullary abnormalities on neuroimaging.

  20. A new structural approach to genomic discovery of disease: example of adult-onset diabetes.

    PubMed

    Sirovich, Lawrence

    2016-12-01

    This paper reports on an investigation of disease discovery from genomic data, by methods which depart substantially from customary practices found in the investigation of genome-wide association studies. Such data in general are composed of the genomic content from two contrasting phenotypes, e.g., disease versus control populations, and the analysis proceeds under the hypothesis that populational dissimilarities might reveal disease risk alleles. The proposed suite of new methods is in part based on information theory (Shannon in Bell Syst Tech J 27:379-423, 1948a; Bell Syst Tech J 27:623-656, 1948b; Jaynes in Phys Rev 106:620-630, 1957), and strong evidence will be given of the effectiveness of this new approach. The methodology extends naturally and successfully to predicting genomic disposition to disease arising from large collections of weakly contributing genomic loci. Evidence will be advanced that the example of adult-onset diabetes ("type 2 diabetes") is such a candidate disease, and in this case, probably for the first time, it can be demonstrated that disease prediction is possible. Another novel element of this study is the search and identification of potential beneficial genomic loci that may counter a disease. The generality of the methodology suggests that it might extend to other diseases.

  1. Ethical and legal dilemmas arising during predictive testing for adult-onset disease: the experience of Huntington disease.

    PubMed Central

    Huggins, M; Bloch, M; Kanani, S; Quarrell, O W; Theilman, J; Hedrick, A; Dickens, B; Lynch, A; Hayden, M

    1990-01-01

    The goal of predictive testing is to modify the risk for currently healthy individuals to develop a genetic disease in the future. Such testing using polymorphic DNA markers has had major application in Huntington disease. The Canadian Collaborative Study of Predictive Testing for Huntington Disease has been guided by major principles of medical ethics, including autonomy, beneficence, confidentiality, and justice. Numerous ethical and legal dilemmas have arisen in this program, challenging these principles and occasionally casting them into conflict. The present report describes these dilemmas and offers our approach to resolving them. These issues will have relevance to predictive-testing programs for other adult-onset disorders. PMID:1971997

  2. Patient fibroblasts-derived induced neurons demonstrate autonomous neuronal defects in adult-onset Krabbe disease

    PubMed Central

    Choi, Won Jun; Oh, Ki-Wook; Nahm, Minyeop; Xue, Yuanchao; Choi, Jae Hyeok; Choi, Ji Young; Kim, Young-Eun; Chung, Ki Wha; Fu, Xiang-Dong; Ki, Chang-Seok; Kim, Seung Hyun

    2016-01-01

    Krabbe disease (KD) is an autosomal recessive neurodegenerative disorder caused by defective β-galactosylceramidase (GALC), a lysosomal enzyme responsible for cleavage of several key substrates including psychosine. Accumulation of psychosine to the cytotoxic levels in KD patients is thought to cause dysfunctions in myelinating glial cells based on a comprehensive study of demyelination in KD. However, recent evidence suggests myelin-independent neuronal death in the murine model of KD, thus indicating defective GALC in neurons as an autonomous mechanism for neuronal cell death in KD. These observations prompted us to generate induced neurons (iNeurons) from two adult-onset KD patients carrying compound heterozygous mutations (p.[K563*];[L634S]) and (p.[N228_S232delinsTP];[G286D]) to determine the direct contribution of autonomous neuronal toxicity to KD. Here we report that directly converted KD iNeurons showed not only diminished GALC activity and increased psychosine levels, as expected, but also neurite fragmentation and abnormal neuritic branching. The lysosomal-associated membrane proteins 1 (LAMP1) was expressed at higher levels than controls, LAMP1-positive vesicles were significantly enlarged and fragmented, and mitochondrial morphology and its function were altered in KD iNeurons. Strikingly, we demonstrated that psychosine was sufficient to induce neurite defects, mitochondrial fragmentation, and lysosomal alterations in iNeurons derived in healthy individuals, thus establishing the causal effect of the cytotoxic GALC substrate in KD and the autonomous neuronal toxicity in KD pathology. PMID:27780934

  3. Muscle MRI Findings in Childhood/Adult Onset Pompe Disease Correlate with Muscle Function

    PubMed Central

    Figueroa-Bonaparte, Sebastián; Segovia, Sonia; Llauger, Jaume; Belmonte, Izaskun; Pedrosa, Irene; Alejaldre, Aída; Mayos, Mercè; Suárez-Cuartín, Guillermo; Gallardo, Eduard; Illa, Isabel; Díaz-Manera, Jordi

    2016-01-01

    Objectives Enzyme replacement therapy has shown to be effective for childhood/adult onset Pompe disease (AOPD). The discovery of biomarkers useful for monitoring disease progression is one of the priority research topics in Pompe disease. Muscle MRI could be one possible test but the correlation between muscle MRI and muscle strength and function has been only partially addressed so far. Methods We studied 34 AOPD patients using functional scales (Manual Research Council scale, hand held myometry, 6 minutes walking test, timed to up and go test, time to climb up and down 4 steps, time to walk 10 meters and Motor Function Measure 20 Scale), respiratory tests (Forced Vital Capacity seated and lying, Maximun Inspiratory Pressure and Maximum Expiratory Pressure), daily live activities scales (Activlim) and quality of life scales (Short Form-36 and Individualized Neuromuscular Quality of Life questionnaire). We performed a whole body muscle MRI using T1w and 3-point Dixon imaging centered on thighs and lower trunk region. Results T1w whole body muscle MRI showed a homogeneous pattern of muscle involvement that could also be found in pre-symptomatic individuals. We found a strong correlation between muscle strength, muscle functional scales and the degree of muscle fatty replacement in muscle MRI analyzed using T1w and 3-point Dixon imaging studies. Moreover, muscle MRI detected mild degree of fatty replacement in paraspinal muscles in pre-symptomatic patients. Conclusion Based on our findings, we consider that muscle MRI correlates with muscle function in patients with AOPD and could be useful for diagnosis and follow-up in pre-symptomatic and symptomatic patients under treatment. Take home message Muscle MRI correlates with muscle function in patients with AOPD and could be useful to follow-up patients in daily clinic. PMID:27711114

  4. Adult-onset Atopic Dermatitis

    PubMed Central

    Kanwar, Amrinder Jit

    2016-01-01

    Adult-onset atopic dermatitis is still an under recognized condition as there are only few studies regarding this entity. As compared to childhood onset atopic dermatitis, clinical features of adult onset atopic dermatitis are still not categorized. Adult atopic dermatitis can present for the first time in adult age with atypical morphology or may progress from childhood onset. This article reviews the characteristic clinical features of adult atopic dermatitis, associated risk factors and management. PMID:27904186

  5. Novel case of Trevor’s disease: Adult onset and later recurrence

    PubMed Central

    Khalsa, Amrit S; Kumar, Neil S; Chin, Matthew A; Lackman, Richard D

    2017-01-01

    Dysplasia epiphysealis hemimelica (DEH), or Trevor’s disease, is an osteocartilaginous epiphyseal overgrowth typically occurring in children. The literature reports 6 adult cases and none describe recurrence requiring additional procedures. We present a new-onset proximal tibial DEH in an adult recurring approximately 3 years after open excision. A 39-year-old female presented with a history of right knee pain, swelling, and instability. Physical examination revealed a firm proximal tibial mass. Computed tomography (CT) imaging showed an exophytic, lobulated, sclerotic mass involving the anterolateral margin of the lateral tibial plateau. Magnetic resonance imaging was suggestive of an osteochondroma. The patient underwent curettage of the lesion due to its periarticular location. Histology revealed benign and reactive bone and cartilage consistent with periosteal chondroma. Two and a half years later, the patient presented with a firm, palpable mass larger than the initial lesion. CT revealed a lateral tibial plateau sclerotic mass consistent with recurrent intra-articular DEH. A complete excision was performed and histology showed sclerotic bone with overlying cartilage consistent with exostosis. DEH is a rare epiphyseal osteocartilaginous outgrowth frequently occurring in the long bones of children less than 8 years old. DEH resembles an osteochondroma due to its pediatric presentation and similar histologic appearance. Adult-onset cases comprise less than 1% of reported cases. Recurrence rate after surgical intervention is unknown. Only 1 such case, occurring in a child, has been described. Clinicians contemplating operative treatment for DEH should note the potential for recurrence and consider complete excision. A follow-up period of several years may be warranted to identify recurrent lesions. PMID:28144583

  6. Stroke prevention by direct revascularization for patients with adult-onset moyamoya disease presenting with ischemia.

    PubMed

    Kim, Tackeun; Oh, Chang Wan; Kwon, O-Ki; Hwang, Gyojun; Kim, Jeong Eun; Kang, Hyun-Seung; Cho, Won-Sang; Bang, Jae Seung

    2016-06-01

    . CONCLUSIONS Direct or combined revascularization for patients with adult-onset moyamoya disease presenting with ischemia can prevent further stroke.

  7. Adult-onset Alexander disease: a series of eleven unrelated cases with review of the literature.

    PubMed

    Pareyson, Davide; Fancellu, Roberto; Mariotti, Caterina; Romano, Silvia; Salmaggi, Andrea; Carella, Francesco; Girotti, Floriano; Gattellaro, Grazietta; Carriero, Maria Rita; Farina, Laura; Ceccherini, Isabella; Savoiardo, Mario

    2008-09-01

    Alexander disease (AD) in its typical form is an infantile lethal leucodystrophy, characterized pathologically by Rosenthal fibre accumulation. Following the identification of glial fibrillary acidic protein (GFAP) gene as the causative gene, cases of adult-onset AD (AOAD) are being described with increasing frequency. AOAD has a different clinical and neuroradiological presentation with respect to early-onset AD, as abnormalities are mainly concentrated in the brainstem-spinal cord junction. We report detailed clinical and genetic data of 11 cases of AOAD, observed over a 4-year period, and a review of the previously reported 25 cases of genetically confirmed AOAD. In our series, onset occurred as late as age 62, and up to 71 in an affected deceased relative. Most cases appeared sporadic, but family history may be misleading. The most frequent symptoms were related to bulbar dysfunction-with dysarthria, dysphagia, dysphonia (seven patients)-, pyramidal involvement (seven patients) and cerebellar ataxia (seven patients). Four patients had palatal myoclonus. Sleep disorders were also observed (four cases). Bulbar symptoms, however, were infrequent at onset and two symptomatic patients had an almost pure pyramidal involvement. Two subjects were asymptomatic. Misdiagnosis at presentation was frequent and MRI was instrumental in suggesting the correct diagnosis by showing, in all cases, mild to severe atrophy of the medulla oblongata extending caudally to the cervical spinal cord. In ten patients, molecular studies revealed six novel missense mutations and three previously reported changes in GFAP. The last typical patient carried no definitely pathogenic mutation, but a missense variant (p.D157N), supposedly a rare polymorphism. Revision of the literature and the present series indicate that the clinical picture is not specific, but AOAD must be considered in patients of any age with lower brainstem signs. When present, palatal myoclonus is strongly suggestive

  8. Inadvertent Skipping of Steroids in Septic Shock Leads to a Diagnosis of Adult Onset Still’s Disease

    PubMed Central

    Sethuraman, Vinoth K; Balasubramanian, Kavitha; Aghoram, Rajeswari

    2017-01-01

    Adult onset Still’s disease is uncommon in middle-aged and elderly individuals and can rarely present with shock; shock is usually associated with disseminated intravascular coagulation, multiorgan dysfunction syndrome or acute respiratory distress syndrome. We report a post-menopausal woman with arthritis, fever, pneumonitis and hypotension which was managed as septic shock. Steroids were inadvertently missed during the second day of hospitalization in the intensive care unit. Persistence of hypotension on inotropes, with normal renal, hepatic and neurological function and recurrence of fever when steroids were skipped, led to suspicion of an inflammatory disorder. A diagnosis of Still’s disease may be entertained in postmenopausal women with polyarthritis, rash, and fever with leukocytosis. Sepsis is mimicked, and multiple antibiotics use is common before the diagnosis of such an entity is made. Shock is rare in adult onset Still’s disease and is not necessarily associated with disseminated intravascular coagulation, acute respiratory distress syndrome, or multiorgan dysfunction. PMID:28191382

  9. Adult onset motor neuron disease: worldwide mortality, incidence and distribution since 1950.

    PubMed Central

    Chancellor, A M; Warlow, C P

    1992-01-01

    This review examines the commonly held premise that, apart from the Western Pacific forms, motor neuron disease (MND), has a uniform worldwide distribution in space and time; the methodological problems in studies of MND incidence; and directions for future epidemiological research. MND is more common in men at all ages. Age-specific incidence rises steeply into the seventh decade but the incidence in the very elderly is uncertain. A rise in mortality from MND over recent decades has been demonstrated wherever this has been examined and may be real rather than due to improved case ascertainment. Comparison of incidence studies in different places is complicated by non-standardised methods of case ascertainment and diagnosis but there appear to be differences between well studied populations. In developed countries in the northern hemisphere there is a weak positive correlation between standardised, age-specific incidence and distance from the equator. There is now strong evidence for an environmental factor as the cause of the Western Pacific forms of MND. A number of clusters of sporadic MND have been reported from developed countries, but no single agent identified as responsible. Images PMID:1479386

  10. Inhibition of GSK-3 Ameliorates Aβ Pathology in an Adult-Onset Drosophila Model of Alzheimer's Disease

    PubMed Central

    Killick, Richard; Augustin, Hrvoje; Gandy, Carina; Allen, Marcus J.; Hardy, John; Lovestone, Simon; Partridge, Linda

    2010-01-01

    Aβ peptide accumulation is thought to be the primary event in the pathogenesis of Alzheimer's disease (AD), with downstream neurotoxic effects including the hyperphosphorylation of tau protein. Glycogen synthase kinase-3 (GSK-3) is increasingly implicated as playing a pivotal role in this amyloid cascade. We have developed an adult-onset Drosophila model of AD, using an inducible gene expression system to express Arctic mutant Aβ42 specifically in adult neurons, to avoid developmental effects. Aβ42 accumulated with age in these flies and they displayed increased mortality together with progressive neuronal dysfunction, but in the apparent absence of neuronal loss. This fly model can thus be used to examine the role of events during adulthood and early AD aetiology. Expression of Aβ42 in adult neurons increased GSK-3 activity, and inhibition of GSK-3 (either genetically or pharmacologically by lithium treatment) rescued Aβ42 toxicity. Aβ42 pathogenesis was also reduced by removal of endogenous fly tau; but, within the limits of detection of available methods, tau phosphorylation did not appear to be altered in flies expressing Aβ42. The GSK-3–mediated effects on Aβ42 toxicity appear to be at least in part mediated by tau-independent mechanisms, because the protective effect of lithium alone was greater than that of the removal of tau alone. Finally, Aβ42 levels were reduced upon GSK-3 inhibition, pointing to a direct role of GSK-3 in the regulation of Aβ42 peptide level, in the absence of APP processing. Our study points to the need both to identify the mechanisms by which GSK-3 modulates Aβ42 levels in the fly and to determine if similar mechanisms are present in mammals, and it supports the potential therapeutic use of GSK-3 inhibitors in AD. PMID:20824130

  11. Adult onset retinoblastoma

    PubMed Central

    Sengupta, Sabyasachi; Pan, Utsab; Khetan, Vikas

    2016-01-01

    Retinoblastoma (RB) is the most common primary malignant intraocular tumor of childhood presenting usually before 5 years of age. RB in adults older than 20 years is extremely rare. A literature search using PubMed/PubMed Central, Scopus, Google Scholar, EMBASE, and Cochrane databases revealed only 45 cases till date. Over the past decade, there has been a significant increase in the number of such reports, indicating heightened level of suspicion among ophthalmologists. Compared to its pediatric counterpart, adult onset RB poses unique challenges in diagnosis and treatment. This article summarizes available literature on adult onset RB and its clinical and pathologic profile, genetics, association with retinocytoma, diagnostics, treatment, and outcomes. PMID:27609158

  12. Adult onset asymmetric upper limb tremor misdiagnosed as Parkinson’s disease: A clinical and electrophysiological study

    PubMed Central

    Schwingenschuh, Petra; Ruge, Diane; Edwards, Mark J; Terranova, Carmen; Katschnig, Petra; Carrillo, Fatima; Silveira-Moriyama, Laura; Schneider, Susanne A; Kägi, Georg; Dickson, John; Lees, Andrew J; Quinn, Niall; Mir, Pablo; Rothwell, John C; Bhatia, Kailash P

    2010-01-01

    different from controls. Taken together, these results may help differentiate these SWEDDs patients from PD and support our hypothesis that adult-onset dystonia is the underlying diagnosis in this sub-group of patients with SWEDDs. PMID:20131394

  13. Adult-onset mitochondrial myopathy.

    PubMed Central

    Fernandez-Sola, J.; Casademont, J.; Grau, J. M.; Graus, F.; Cardellach, F.; Pedrol, E.; Urbano-Marquez, A.

    1992-01-01

    Mitochondrial diseases are polymorphic entities which may affect many organs and systems. Skeletal muscle involvement is frequent in the context of systemic mitochondrial disease, but adult-onset pure mitochondrial myopathy appears to be rare. We report 3 patients with progressive skeletal mitochondrial myopathy starting in adult age. In all cases, the proximal myopathy was the only clinical feature. Mitochondrial pathology was confirmed by evidence of ragged-red fibres in muscle histochemistry, an abnormal mitochondrial morphology in electron microscopy and by exclusion of other underlying diseases. No deletions of mitochondrial DNA were found. We emphasize the need to look for a mitochondrial disorder in some non-specific myopathies starting in adult life. Images Figure 1 Figure 2 PMID:1589382

  14. Phenotypes, Risk Factors, and Mechanisms of Adult-Onset Asthma

    PubMed Central

    Ilmarinen, Pinja; Tuomisto, Leena E.; Kankaanranta, Hannu

    2015-01-01

    Asthma is a heterogeneous disease with many phenotypes, and age at disease onset is an important factor in separating the phenotypes. Genetic factors, atopy, and early respiratory tract infections are well-recognized factors predisposing to childhood-onset asthma. Adult-onset asthma is more often associated with obesity, smoking, depression, or other life-style or environmental factors, even though genetic factors and respiratory tract infections may also play a role in adult-onset disease. Adult-onset asthma is characterized by absence of atopy and is often severe requiring treatment with high dose of inhaled and/or oral steroids. Variety of risk factors and nonatopic nature of adult-onset disease suggest that variety of mechanisms is involved in the disease pathogenesis and that these mechanisms differ from the pathobiology of childhood-onset asthma with prevailing Th2 airway inflammation. Recognition of the mechanisms and mediators that drive the adult-onset disease helps to develop novel strategies for the treatment. The aim of this review was to summarize the current knowledge on the pathogenesis of adult-onset asthma and to concentrate on the mechanisms and mediators involved in establishing adult-onset asthma in response to specific risk factors. We also discuss the involvement of these mechanisms in the currently recognized phenotypes of adult-onset asthma. PMID:26538828

  15. TLR4 Endogenous Ligand S100A8/A9 Levels in Adult-Onset Still’s Disease and Their Association with Disease Activity and Clinical Manifestations

    PubMed Central

    Kim, Hyoun-Ah; Han, Jae Ho; Kim, Woo-Jung; Noh, Hyun Jin; An, Jeong-Mi; Yim, Hyunee; Jung, Ju-Yang; Kim, You-Sun; Suh, Chang-Hee

    2016-01-01

    S100A8/A9 has been suggested as a marker of disease activity in patients with adult-onset Still’s disease (AOSD). We evaluated the clinical significance of S100A8/A9 as a biomarker and its pathogenic role in AOSD. Blood samples were collected prospectively from 20 AOSD patients and 20 healthy controls (HCs). Furthermore, skin and lymph node biopsy specimens of AOSD patients were investigated for S100A8/A9 expression levels via immunohistochemistry. Peripheral blood mononuclear cells (PBMCs) of active AOSD patients and HCs were investigated for S100A8/A9 cell signals. S100A8/A9, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels in active AOSD patients were higher than those of HCs. S100A8/A9 levels correlated positively with IL-1β, TNF-α and C-reactive protein. The inflammatory cells expressing S100A8/A9 were graded from one to three in skin and lymph node biopsies of AOSD patients. The grading for S100A8/A9 was more intense in the skin lesions with karyorrhexis, mucin deposition, and neutrophil infiltration. Like lipopolysaccharide (LPS), S100A8/A9 induced phosphorylation of p38 and c-Jun amino-terminal kinase (JNK) in PBMCs, suggesting that S100A8/A9 activates Toll-like receptor 4 signaling pathways. These findings suggest that S100A8/A9 may be involved in the inflammatory response with induction of proinflammatory cytokines and may serve as a clinicopathological marker for disease activity in AOSD. PMID:27537874

  16. Highly Expression of CD11b and CD32 on Peripheral Blood Mononuclear Cells from Patients with Adult-Onset Still’s Disease

    PubMed Central

    Kim, Hyoun-Ah; Choi, Bunsoon; Suh, Chang-Hee; Han, Mi Hwa; Jung, Ju-Yang; Sayeed, Hasan M.; Kim, Ye Won; Sohn, Seonghyang

    2017-01-01

    Background: We investigated the potential role of several pattern-recognition receptors (PRRs; CD11b, CD11c, CD32, CD206, CD209, and dectin-1) in adult-onset Still’s disease (AOSD). Methods: The study included 13 untreated AOSD patients, 19 rheumatoid arthritis (RA) patients (as a disease control), and 19 healthy controls (HCs). The PRRs were quantified in peripheral blood using flow cytometry. The serum levels of interleukin-17 (IL-17), IL-18, and IL-23 were measured by enzyme-linked immunosorbent assay. Results: Significantly higher mean frequencies of cells presenting CD11b and CD32 from whole blood were observed in patients with AOSD than in patients with RA or HC. The levels of IL-17, IL-18, and IL-23 were elevated in AOSD patients compared to HCs. CD11b frequencies from whole cells correlated with systemic scores, lactate dehydrogenase (LDH) levels, aspartate transaminase levels, interleukin-23 (IL-23) levels, and IL-18. Frequencies of CD209 from granulocytes were significantly correlated with systemic scores, and the erythrocyte sedimentation rate and levels of C-reactive protein, ferritin, LDH, IL-23, and interleukin-18 (IL-18). Conclusions: Elevated frequencies of circulating CD11b-positive cells and positive correlations with disease activity markers suggest that circulating CD11b-positive cells contribute to the pathogenesis of AOSD. PMID:28106835

  17. An autopsied case of adult-onset bulbospinalform Alexander disease with a novel S393R mutation in the GFAP gene.

    PubMed

    Iwasaki, Yasushi; Saito, Yufuko; Mori, Keiko; Ito, Masumi; Mimuro, Maya; Aiba, Ikuko; Saito, Kozo; Mizuta, Ikuko; Yoshida, Tomokatsu; Nakagawa, Masanori; Yoshida, Mari

    2015-01-01

    A 50-year-old Japanese man with no apparent family history noticed diplopia. He gradually showed gait disturbance and dysuria. Abducens disorder of eye movement with nystagmus, tongue atrophy with fasciculation, spastic tetraparesis, and sensory disturbance were also observed. MRI showed severe atrophy of the medulla oblongata to the cervical cord ("tadpole appearance"). Tracheotomy and gastrostomy were performed 7 years after onset due to the development of bulbar palsy. Death occurred following respiratory failure after 11 years total disease duration. The brain weighed 1,380 g. The cerebrum, cerebellum, midbrain, and upper pons were preserved from atrophy, but the medulla oblongata to the cervical cord showed severe atrophy. A few Rosenthal fibers were observed in the cerebral white matter, basal ganglia, and cerebellum, whereas numerous Rosenthal fibers were observed in the medulla oblongata to the cervical cord. Myelin loss with relatively preserved axons was extensively observed from the middle of the pons to the spinal cord. The clinicopathological diagnosis was adult-onset bulbospinal-form Alexander disease. Glial fibrillary acidic protein (GFAP) gene analysis revealed a novel mutation of S393R. Expression patterns of S393R mutant GFAP using adrenal carcinoma-derived cells (SW13 cells) showed a decreased number of filamentous structures and abnormal aggregates.

  18. ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43.

    PubMed

    Arnold, Eveline S; Ling, Shuo-Chien; Huelga, Stephanie C; Lagier-Tourenne, Clotilde; Polymenidou, Magdalini; Ditsworth, Dara; Kordasiewicz, Holly B; McAlonis-Downes, Melissa; Platoshyn, Oleksandr; Parone, Philippe A; Da Cruz, Sandrine; Clutario, Kevin M; Swing, Debbie; Tessarollo, Lino; Marsala, Martin; Shaw, Christopher E; Yeo, Gene W; Cleveland, Don W

    2013-02-19

    Transactivating response region DNA binding protein (TDP-43) is the major protein component of ubiquitinated inclusions found in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) with ubiquitinated inclusions. Two ALS-causing mutants (TDP-43(Q331K) and TDP-43(M337V)), but not wild-type human TDP-43, are shown here to provoke age-dependent, mutant-dependent, progressive motor axon degeneration and motor neuron death when expressed in mice at levels and in a cell type-selective pattern similar to endogenous TDP-43. Mutant TDP-43-dependent degeneration of lower motor neurons occurs without: (i) loss of TDP-43 from the corresponding nuclei, (ii) accumulation of TDP-43 aggregates, and (iii) accumulation of insoluble TDP-43. Computational analysis using splicing-sensitive microarrays demonstrates alterations of endogenous TDP-43-dependent alternative splicing events conferred by both human wild-type and mutant TDP-43(Q331K), but with high levels of mutant TDP-43 preferentially enhancing exon exclusion of some target pre-mRNAs affecting genes involved in neurological transmission and function. Comparison with splicing alterations following TDP-43 depletion demonstrates that TDP-43(Q331K) enhances normal TDP-43 splicing function for some RNA targets but loss-of-function for others. Thus, adult-onset motor neuron disease does not require aggregation or loss of nuclear TDP-43, with ALS-linked mutants producing loss and gain of splicing function of selected RNA targets at an early disease stage.

  19. Heterogeneity and frequency of movement disorders in juvenile and adult-onset Niemann-Pick C disease.

    PubMed

    Anheim, Mathieu; Lagha-Boukbiza, Ouhaïd; Fleury-Lesaunier, Marie-Céline; Valenti-Hirsch, Maria-Paola; Hirsch, Edouard; Gervais-Bernard, Hélène; Broussolle, Emmanuel; Thobois, Stéphane; Vanier, Marie T; Latour, Philippe; Tranchant, Christine

    2014-01-01

    Niemann-Pick type C disease (NPC) is a recessive neurolipidosis. We report five adolescent and adult NPC cases to underscore the frequency and heterogeneity of movement disorders in NPC. Clinical, morphologic, biochemical and genetic study was performed in the five patients. Disease onset was between 8 and 50 years. Movement disorders were present in all cases, were heterogeneous and often combined [cerebellar ataxia (5/5), myoclonus (3/5), dystonia (2/5), chorea (1/5) and tremor (1/5)] and were the first sign in 4/5. Two patients were reported to have no vertical supranuclear gaze palsy (VSGP) at the first examination. Two patients experienced acute neuropsychiatric signs leading to death in one case due to myoclonic storm. Filipin staining was always positive. Two NPC1 mutations were identified in three patients, only one in two siblings. NPC should be considered in case of unexplained movement disorders, even when VSGP or cataplexy are not reported. Filipin staining remains a strong support for the diagnosis. Treatment with miglustat should be considered which is currently the only approved disease-specific treatment of NPC in children and adults.

  20. Metabolic Disturbances in Adult-Onset Still’s Disease Evaluated Using Liquid Chromatography/Mass Spectrometry-Based Metabolomic Analysis

    PubMed Central

    Chen, Der-Yuan; Hsieh, Chia-Wei; Chen, Hsin-Hua; Hung, Wei-Ting

    2016-01-01

    Objective Liquid chromatography/mass spectrometry (LC/MS)-based comprehensive analysis of metabolic profiles with metabolomics approach has potential diagnostic and predictive implications. However, no metabolomics data have been reported in adult-onset Still’s disease (AOSD). This study investigated the metabolomic profiles in AOSD patients and examined their association with clinical characteristics and disease outcome. Methods Serum metabolite profiles were determined on 32 AOSD patients and 30 healthy controls (HC) using ultra-performance liquid chromatography (UPLC)/MS analysis, and the differentially expressed metabolites were quantified using multiple reactions monitoring (MRM)/MS analysis in 44 patients and 42 HC. Pure standards were utilized to confirm the presence of the differentially expressed metabolites. Results Eighteen differentially expressed metabolites were identified in AOSD patents using LC/MS-based analysis, of which 13 metabolites were validated by MRM/MS analysis. Among them, serum levels of lysoPC(18:2), urocanic acid and indole were significantly lower, and L-phenylalanine levels were significantly higher in AOSD patients compared with HC. Moreover, serum levels of lysoPC(18:2), PhePhe, uridine, taurine, L-threonine, and (R)-3-Hydroxy-hexadecanoic acid were significantly correlated with disease activity scores (all p<0.05) in AOSD patients. A different clustering of metabolites was associated with a different disease outcome, with significantly lower levels of isovalerylsarcosine observed in patients with chronic articular pattern (median, 77.0AU/ml) compared with monocyclic (341.5AU/ml, p<0.01) or polycyclic systemic pattern (168.0AU/ml, p<0.05). Conclusion Thirteen differentially expressed metabolites identified and validated in AOSD patients were shown to be involved in five metabolic pathways. Significant associations of metabolic profiles with disease activity and outcome of AOSD suggest their involvement in AOSD pathogenesis. PMID

  1. Adult Onset Asthma and Periocular Xanthogranuloma (AAPOX), a Rare Entity With a Strong Link to IgG4-Related Disease: An Observational Case Report Study.

    PubMed

    London, Jonathan; Martin, Antoine; Soussan, Michael; Badelon, Isabelle; Gille, Thomas; Uzunhan, Yurdagul; Giroux-Leprieur, Bénédicte; Warzocha, Ursula; Régent, Alexis; Galatoire, Olivier; Dhote, Robin; Abad, Sébastien

    2015-10-01

    Adult onset asthma and periocular xanthogranuloma (AAPOX) is a rare non-Langerhans histiocytosis characterized histopathologically by a periocular infiltration of foamy histiocytes and Touton giant cells. Benign hyperplasia with plasma cell infiltration is classically described in eyelids or lymph nodes of AAPOX patients. It is also a characteristic feature of IgG4-related disease (IgG4-RD), a new entity defined by an IgG4-bearing plasma cell infiltration of organs.To determine if AAPOX syndrome shares clinical, biological, and histopathological characteristics with IgG4-RD, we used the comprehensive clinical diagnostic criteria for IgG4-RD in a retrospective case series of three consecutive patients with histologically-proven AAPOX. Patients who were diagnosed with AAPOX at a French academic referral center for orbital inflammation between November 1996 and March 2013 were enrolled. Biopsies from ocular adnexa or other organs were systematically reexamined. For each patient, clinical and serological data, radiologic findings, and treatment were retrospectively analyzed.Two AAPOX patients fulfilled all of the diagnostic criteria for a definite IgG4-RD. One patient who lacked the serological criteria fulfilled the criteria of a probable IgG4-RD.These 3 cases of AAPOX patients fulfilled the IgG4-RD comprehensive clinical diagnostic criteria. To our knowledge, this is the first observational case report study to clearly show a strong relationship between IgG4-RD and AAPOX syndrome.

  2. Observational clinical study of 22 adult-onset Pompe disease patients undergoing enzyme replacement therapy over 5years.

    PubMed

    Stepien, Karolina M; Hendriksz, Christian J; Roberts, Mark; Sharma, Reena

    2016-04-01

    Pompe disease is an autosomal recessive disease resulting from deficiency of the acid alpha-glucosidase (GAA). The late-onset Pompe Disease (LOPD) patients develop muscular and respiratory complications later in life. We describe a retrospective observational cohort study including 22 patients with LOPD. The cohort was assessed at baseline before Enzyme Replacement Therapy (ERT) with alglucosidase alpha (20mg/kg biweekly) was commenced and subsequently relevant information was collected at 2, 4 and 5years later. The median age of the patients at study entry was 44years (16-64years), with median disease duration of 11.5years (4-31years). At baseline, 10 patients (45%) could walk without support, 12 (55%) could walk with unilateral or bilateral support including 3/12 were wheelchair bound. Mean predicted FVC % was 55.7 (95% CI 45-66) of predicted normal at baseline and showed no significant change after 5years (54.6 (95% CI 43-66)), (all p=0.9815). Mean FVC % supine was 41.8 (95% CI 33.8-49) of predicted normal at baseline and remained significantly unchanged at 5years (48.4 (95% CI 37-59.6)), (all p=0.8680). The overnight non-invasive ventilator dependence increased by 18.2% as compared with baseline and requirement of mobility aids increased during this period by 5.2% as compared with the baseline. Mean walking distance at 6min walk test was 411.5 (95% CI 338-485) at baseline, 266.5 (95% CI 187-346) m at 2years, 238.6 (95% CI 162-315) m at 4years and 286.8 (95% CI 203-370) m at 5years (p=0.1981; ANOVA was completed only for 14 patients). A gradual decline in FVC% predicted was noted only in four cases and a decline in FVC% supine in two other. Only one patient showed a decline in both pulmonary function tests. In all remaining cases (17/22) respiratory function remains stable. In conclusion overall pulmonary function tests and mobility remained stable for 5years in majority of patients on ERT. However, in some patients they continued to decline in spite of ERT

  3. Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu-Hakola disease: lesion staging and dynamic changes of axons and microglial subsets.

    PubMed

    Oyanagi, Kiyomitsu; Kinoshita, Michiaki; Suzuki-Kouyama, Emi; Inoue, Teruhiko; Nakahara, Asa; Tokiwai, Mika; Arai, Nobutaka; Satoh, Jun-Ichi; Aoki, Naoya; Jinnai, Kenji; Yazawa, Ikuru; Arai, Kimihito; Ishihara, Kenji; Kawamura, Mitsuru; Ishizawa, Keisuke; Hasegawa, Kazuko; Yagisita, Saburo; Amano, Naoji; Yoshida, Kunihiro; Terada, Seishi; Yoshida, Mari; Akiyama, Haruhiko; Mitsuyama, Yoshio; Ikeda, Shu-Ichi

    2016-09-08

    The brains of 10 Japanese patients with adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) encompassing hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD) and eight Japanese patients with Nasu-Hakola disease (N-HD) and five age-matched Japanese controls were examined neuropathologically with special reference to lesion staging and dynamic changes of microglial subsets. In both diseases, the pathognomonic neuropathological features included spherically swollen axons (spheroids and globules), axon loss and changes of microglia in the white matter. In ALSP, four lesion stages based on the degree of axon loss were discernible: Stage I, patchy axon loss in the cerebral white matter without atrophy; Stage II, large patchy areas of axon loss with slight atrophy of the cerebral white matter and slight dilatation of the lateral ventricles; Stage III, extensive axon loss in the cerebral white matter and dilatation of the lateral and third ventricles without remarkable axon loss in the brainstem and cerebellum; Stage IV, devastated cerebral white matter with marked dilatation of the ventricles and axon loss in the brainstem and/or cerebellum. Internal capsule and pontine base were relatively well preserved in the N-HD, even at Stage IV, and the swollen axons were larger with a higher density in the ALSP. Microglial cells immunopositive for CD68, CD163 or CD204 were far more obvious in ALSP, than in N-HD, and the shape and density of the cells changed in each stage. With progression of the stage, clinical symptoms became worse to apathetic state, and epilepsy was frequently observed in patients at Stages III and IV in both diseases. From these findings, it is concluded that (i) shape, density and subsets of microglia change dynamically along the passage of stages and (ii) increase of IBA-1-, CD68-, CD163- and CD204-immunopositive cells precedes loss of axons in ALSP.

  4. ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43

    PubMed Central

    Arnold, Eveline S.; Ling, Shuo-Chien; Huelga, Stephanie C.; Lagier-Tourenne, Clotilde; Polymenidou, Magdalini; Ditsworth, Dara; Kordasiewicz, Holly B.; McAlonis-Downes, Melissa; Platoshyn, Oleksandr; Parone, Philippe A.; Da Cruz, Sandrine; Clutario, Kevin M.; Swing, Debbie; Tessarollo, Lino; Marsala, Martin; Shaw, Christopher E.; Yeo, Gene W.; Cleveland, Don W.

    2013-01-01

    Transactivating response region DNA binding protein (TDP-43) is the major protein component of ubiquitinated inclusions found in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) with ubiquitinated inclusions. Two ALS-causing mutants (TDP-43Q331K and TDP-43M337V), but not wild-type human TDP-43, are shown here to provoke age-dependent, mutant-dependent, progressive motor axon degeneration and motor neuron death when expressed in mice at levels and in a cell type-selective pattern similar to endogenous TDP-43. Mutant TDP-43-dependent degeneration of lower motor neurons occurs without: (i) loss of TDP-43 from the corresponding nuclei, (ii) accumulation of TDP-43 aggregates, and (iii) accumulation of insoluble TDP-43. Computational analysis using splicing-sensitive microarrays demonstrates alterations of endogenous TDP-43–dependent alternative splicing events conferred by both human wild-type and mutant TDP-43Q331K, but with high levels of mutant TDP-43 preferentially enhancing exon exclusion of some target pre-mRNAs affecting genes involved in neurological transmission and function. Comparison with splicing alterations following TDP-43 depletion demonstrates that TDP-43Q331K enhances normal TDP-43 splicing function for some RNA targets but loss-of-function for others. Thus, adult-onset motor neuron disease does not require aggregation or loss of nuclear TDP-43, with ALS-linked mutants producing loss and gain of splicing function of selected RNA targets at an early disease stage. PMID:23382207

  5. Adult-onset food allergy.

    PubMed

    Kivity, Shmuel

    2012-01-01

    The prevalence of food allergy is increasing in both the pediatric and adult populations. While symptom onset occurs mostly during childhood, there are a considerable number of patients whose symptoms first begin to appear after the age of 18 years. The majority of patients with adult-onset food allergy suffer from the pollen-plant allergy syndromes. Many of them manifest their allergy after exercise and consuming food to which they are allergic. Eosinophilic esophagitis, an eosinophilic inflammation of the esophagus affecting individuals of all ages, recently emerged as another allergic manifestation, with both immediate and late response to the ingested food. This review provides a condensed update of the current data in the literature on adult-onset allergy.

  6. An atypical presentation of adult-onset Still’s disease complicated by pulmonary hypertension and macrophage activation syndrome treated with immunosuppression: a case-based review of the literature

    PubMed Central

    Manson, Daniel K.; Horn, Evelyn M.; Haythe, Jennifer

    2016-01-01

    Abstract Pulmonary arterial hypertension (PAH) is a known complication of rheumatologic diseases, but it is only rarely associated with adult-onset Still’s disease (AOSD). We describe the case of a 30-year-old woman who presented in a pulmonary hypertension crisis and was found to have underlying AOSD with PAH and nonspecific interstitial pneumonia (NSIP) with a course complicated by macrophage activation syndrome (MAS). She dramatically improved with steroids, cyclosporine A, and anakinra, with total resolution of the MAS and significant improvement of her pulmonary arterial pressures. While there are only select case reports of AOSD associated with PAH, this is the first reported case of (1) AOSD complicated by both PAH and MAS and (2) AOSD complicated by biopsy-proven NSIP. Clinically, this case highlights the efficacy of immunosuppressive agents in the treatment of PAH and MAS from underlying AOSD and supports their use in this setting. PMID:27162622

  7. Functional and Structural Analyses of CYP1B1 Variants Linked to Congenital and Adult-Onset Glaucoma to Investigate the Molecular Basis of These Diseases

    PubMed Central

    Chakrabarti, Saikat; Ray, Kunal

    2016-01-01

    Glaucoma, the leading cause of irreversible blindness, appears in various forms. Mutations in CYP1B1 result in primary congenital glaucoma (PCG) by an autosomal recessive mode of inheritance while it acts as a modifier locus for primary open angle glaucoma (POAG). We investigated the molecular basis of the variable phenotypes resulting from the defects in CYP1B1 by using subclones of 23 CYP1B1 mutants reported in glaucoma patients, in a cell based system by measuring the dual activity of the enzyme to metabolize both retinol and 17β-estradiol. Most variants linked to POAG showed low steroid metabolism while null or very high retinol metabolism was observed in variants identified in PCG. We examined the translational turnover rates of mutant proteins after the addition of cycloheximide and observed that the levels of enzyme activity mostly corroborated the translational turnover rate. We performed extensive normal mode analysis and molecular-dynamics-simulations-based structural analyses and observed significant variation of fluctuation in certain segmental parts of the mutant proteins, especially at the B-C and F-G loops, which were previously shown to affect the dynamic behavior and ligand entry/exit properties of the cytochrome P450 family of proteins. Our molecular study corroborates the structural analysis, and suggests that the pathologic state of the carrier of CYP1B1 mutations is determined by the allelic state of the gene. To our knowledge, this is the first attempt to dissect biological activities of CYP1B1 for correlation with congenital and adult onset glaucomas. PMID:27243976

  8. The Scottish Motor Neuron Disease Register: a prospective study of adult onset motor neuron disease in Scotland. Methodology, demography and clinical features of incident cases in 1989.

    PubMed Central

    1992-01-01

    The Scottish Motor Neuron Disease Register (SMNDR) is a prospective, collaborative, population based study of motor neuron disease (MND) in Scotland. The register started in January 1989 with the aim of studying the clinical and epidemiological features of MND by prospectively identifying incident patients. It is based on a system of registration by recruitment from multiple sources, followed by the collection of complete clinical data and follow up, mainly through general practitioners. In this report the register's methodology and the demography and incidence data for the first year of study are presented. One hundred and fourteen newly diagnosed patients were identified in 1989 giving a crude incidence for Scotland of 2.24/100,000/year. Standardised incidence ratios showed a non-significant trend towards lower rates in north eastern regions and island areas. PMID:1640227

  9. Hyperferritinemic syndrome: Still's disease and catastrophic antiphospholipid syndrome triggered by fulminant Chikungunya infection: a case report of two patients.

    PubMed

    Betancur, Juan-Felipe; Navarro, Erika-Paola; Echeverry, Alex; Moncada, Pablo A; Cañas, Carlos A; Tobón, Gabriel J

    2015-11-01

    There are four medical conditions characterized by high levels of ferritin, the macrophage activation syndrome (MAS), adult onset Still' s disease (AOSD), catastrophic antiphospholipid syndrome (CAPS), and septic shock, that share similar clinical and laboratory features, suggesting a common pathogenic mechanism. This common syndrome entity is termed "the hyperferritinemic syndrome." Here, we describe two different cases of hyperferritinemic syndrome triggered by Chikungunya fever virus infection: a 21-year-old female with SLE and a 32-year-old male patient who developed AOSD after the coinfection of dengue and Chikungunya viruses.

  10. Etiopathogenesis and Therapeutic Approach to Adult Onset Acne

    PubMed Central

    Kaur, Sarabjit; Verma, Poonam; Sangwan, Ankita; Dayal, Surabhi; Jain, Vijay Kumar

    2016-01-01

    Acne vulgaris is usually considered as a skin disorder that primarily affects adolescents reaching a peak at the age of 14–17 years in females and 16–19 years in males. However, recent epidemiologic studies have shown that a significant number of female patients aged >25 years experience acne. As it is regarded as a disease of teenagers, adults are more apprehensive and experience social anxiety. Hence, adult onset acne has become a matter of concern. PMID:27512185

  11. Adult onset pigmentary orthochromatic leukodystrophy with ovarian dysgenesis.

    PubMed

    Verghese, J; Weidenheim, K; Malik, S; Rapin, I

    2002-11-01

    Pigmentary type of orthochromatic leukodystrophy (POLD) is an adult-onset leukodystrophy, characterized pathologically by the presence of glial and microglial cytoplasmic pigment inclusions. The complete phenotype, genotype and pathogenetic mechanisms in POLD have not been elucidated. We followed for 18 years a woman with autopsy-proven POLD, who presented with 'frontal' dementia and spasticity. Her further course was marked by progressive mutism, apraxia and seizures. Her sister had died of the same disease after a much more rapidly progressing course. These sisters had primary infertility with pathologic evidence of streak ovaries. Diagnosis was confirmed in both cases by post-mortem examination. POLD is a rare cause of adult-onset leukodystrophy presenting with dementia. Ovarian dysgenesis is extremely rare in the absence of demonstrable chromosomal abnormalities and extends the clinical spectrum of POLD.

  12. Interleukin 6 SNP rs1800797 associates with the risk of adult-onset asthma.

    PubMed

    Lajunen, T K; Jaakkola, J J K; Jaakkola, M S

    2016-04-01

    Interleukin 6 (IL6) is an inflammatory cytokine that has been suggested to have an important role in the pathogenesis of asthma. IL6 single-nucleotide polymorphisms (SNPs) have been associated with levels of IL6, and with childhood and prevalent adult asthma. A recent study also suggested that IL6 SNPs associate especially with atopic asthma. However, association of IL6 SNPs with adult-onset asthma has not been studied. In a population-based study of 467 incident adult-onset asthma cases and 613 disease-free controls from South Finland, we analyzed association of 6 tagging SNPs of the IL6 locus with the risk of adult-onset asthma and with atopy. Asthma was clinically diagnosed, and atopy was defined based on Phadiatop test. IL6 SNP rs1800797 associated with the risk of adult-onset asthma in a log additive model, with adjusted odds ratio (aOR) 1.31 (95% confidence interval 1.09-1.57), and especially with the risk of atopic adult-onset asthma when compared with non-atopic controls, aOR 1.46 (95% CI 1.12-1.90). This is the first study to show an association of IL6 with adult-onset asthma, and especially with atopic adult-onset asthma.

  13. Adult Onset Vitiligo: Multivariate Analysis Suggests the Need for a Thyroid Screening

    PubMed Central

    Lazzeri, L.; Cammi, A.; Dragoni, F.

    2016-01-01

    Background. There are limited epidemiological studies evaluating the effect of age at onset on disease features in vitiligo. Objectives. To identify factors associated with adult onset vitiligo in comparison with childhood onset vitiligo. Patients and Methods. We retrospectively collected medical records of 191 patients. Such records included clinical examination, personal and familial medical history, laboratory evaluations, concomitant vitiligo treatment and drug assumption. Results. 123 patients with a disease onset after the age of 40 (adult onset vitiligo) were compared with 68 patients who developed vitiligo before the age of 12 (childhood onset vitiligo). Multivariate analysis revealed that personal history of thyroid diseases (P = 0.04; OR 0.4), stress at onset (P = 0.002; OR = 0.34), personal history of autoimmune thyroid disease (ATD) (P = 0.003; OR = 0.23), and thyroid nodules (P = 0.001; OR 0.90) were independently associated with adult onset vitiligo, whereas family history of dermatological diseases (P = 0.003; OR = 2.87) and Koebner phenomenon (P < 0.001; OR = 4.73) with childhood onset vitiligo. Moreover, in the adult onset group, concomitant thyroid disease preceded vitiligo in a statistically significant number of patients (P = 0.014). Conclusions. Childhood onset and adult onset vitiligo have different clinical features. In particular, ATD and thyroid nodules were significantly associated with adult onset vitiligo, suggesting that a thyroid screening should be recommended in this group of patients. PMID:27747240

  14. Adult Onset Vitiligo: Multivariate Analysis Suggests the Need for a Thyroid Screening.

    PubMed

    Lazzeri, L; Colucci, R; Cammi, A; Dragoni, F; Moretti, S

    2016-01-01

    Background. There are limited epidemiological studies evaluating the effect of age at onset on disease features in vitiligo. Objectives. To identify factors associated with adult onset vitiligo in comparison with childhood onset vitiligo. Patients and Methods. We retrospectively collected medical records of 191 patients. Such records included clinical examination, personal and familial medical history, laboratory evaluations, concomitant vitiligo treatment and drug assumption. Results. 123 patients with a disease onset after the age of 40 (adult onset vitiligo) were compared with 68 patients who developed vitiligo before the age of 12 (childhood onset vitiligo). Multivariate analysis revealed that personal history of thyroid diseases (P = 0.04; OR 0.4), stress at onset (P = 0.002; OR = 0.34), personal history of autoimmune thyroid disease (ATD) (P = 0.003; OR = 0.23), and thyroid nodules (P = 0.001; OR 0.90) were independently associated with adult onset vitiligo, whereas family history of dermatological diseases (P = 0.003; OR = 2.87) and Koebner phenomenon (P < 0.001; OR = 4.73) with childhood onset vitiligo. Moreover, in the adult onset group, concomitant thyroid disease preceded vitiligo in a statistically significant number of patients (P = 0.014). Conclusions. Childhood onset and adult onset vitiligo have different clinical features. In particular, ATD and thyroid nodules were significantly associated with adult onset vitiligo, suggesting that a thyroid screening should be recommended in this group of patients.

  15. Reviewing Dengue: Still a Neglected Tropical Disease?

    PubMed Central

    Horstick, Olaf; Tozan, Yesim; Wilder-Smith, Annelies

    2015-01-01

    Dengue is currently listed as a “neglected tropical disease” (NTD). But is dengue still an NTD or not? Classifying dengue as an NTD may carry advantages, but is it justified? This review considers the criteria for the definition of an NTD, the current diverse lists of NTDs by different stakeholders, and the commonalities and differences of dengue with other NTDs. We also review the current research gaps and research activities and the adequacy of funding for dengue research and development (R&D) (2003–2013). NTD definitions have been developed to a higher precision since the early 2000s, with the following main features: NTDs are characterised as a) poverty related, b) endemic to the tropics and subtropics, c) lacking public health attention, d) having poor research funding and shortcomings in R&D, e) usually associated with high morbidity but low mortality, and f) often having no specific treatment available. Dengue meets most of these criteria, but not all. Although dengue predominantly affects resource-limited countries, it does not necessarily only target the poor and marginalised in those countries. Dengue increasingly attracts public health attention, and in some affected countries it is now a high profile disease. Research funding for dengue has increased exponentially in the past two decades, in particular in the area of dengue vaccine development. However, despite advances in dengue research, dengue epidemics are increasing in frequency and magnitude, and dengue is expanding to new areas. Specific treatment and a highly effective vaccine remain elusive. Major research gaps exist in the area of integrated surveillance and vector control. Hence, although dengue differs from many of the NTDs, it still meets important criteria commonly used for NTDs. The current need for increased R&D spending, shared by dengue and other NTDs, is perhaps the key reason why dengue should continue to be considered an NTD. PMID:25928673

  16. Similarity of HLA-DQ profiles in adult-onset type 1 insulin-dependent diabetic patients with and without extra-pancreatic auto-immune disease.

    PubMed

    Gu, X F; Larger, E; Clauser, E; Assan, R

    1992-01-01

    Some insulin-dependent diabetic patients present with auto-immune diseases involving extra pancreatic tissues (type 1b diabetes mellitus). The genetic specificity of this syndrome, as opposed to insulin dependent diabetes mellitus (IDDM) free of such associations (Type 1a IDDM) is not clearly established. We have analyzed the HLA-DQB1 and DQA1, loci, after PCR amplification of genomic DNA, in 44 Type 1b IDDM patients, 78 Type 1a IDDM patients and 105 control subjects. No essential difference in HLA-DQ profiles appeared between Type 1b and Type 1a IDDM patients. Both diabetic groups displayed a significant enrichment in DQB1 alleles negative for aspartate at position 57 (Type 1b: 83%; Type 1a: 89%; controls 48%; p < 0.001 vs both patient groups) and in DQB1 Asp 57 negative homozygosity: 71% of Type 1b; 80% of Type 1a; 25% of controls (p < 0.01). This enrichment in DQB1 Asp 57 negative alleles was accounted for by DQB1* 0201 in the Type 1b group, and by DQB1 % 0201 and 0302 in the Type 1a patients. Conversely, alleles DQB1* 0602 and 0301 (DQB1 Asp 57 positive) were protective. Both diabetic groups also displayed a significant enrichment in DQA1 alleles positives for arginine at position 52 (65% of Type 1b; 76% of Type 1a; 50% of control subjects; p < 0.01 and 0.001, respectively, vs controls), and in DQA1 Arg 52 positive homozygotes (48% of Type 1b, 58% of Type 1a, 22% of control subjects; p < 0.01). All differences between diabetic groups and the control group were more pronounced in the case of Type 1a than of Type 1b patients. The HLA-DQ genes shared by Type 1a and Type 1b patients must therefore be closely associated with islet autoimmunity. Genetic differences between Type 1a and Type 1b syndromes, if any, must be investigated in other MHC and non-MHC regions of the genome.

  17. Season of Birth and Risk for Adult Onset Glioma

    PubMed Central

    Efird, Jimmy T.

    2010-01-01

    Adult onset glioma is a rare cancer which occurs more frequently in Caucasians than African Americans, and in men than women. The etiology of this disease is largely unknown. Exposure to ionizing radiation is the only well established environmental risk factor, and this factor explains only a small percentage of cases. Several recent studies have reported an association between season of birth and glioma risk. This paper reviews the plausibility of evidence focusing on the seasonal interrelation of farming, allergies, viruses, vitamin D, diet, birth weight, and handedness. To date, a convincing explanation for the occurrence of adult gliomas decades after a seasonal exposure at birth remains elusive. PMID:20623001

  18. Adult-onset opsoclonus-myoclonus syndrome.

    PubMed

    Klaas, James P; Ahlskog, J Eric; Pittock, Sean J; Matsumoto, Joseph Y; Aksamit, Allen J; Bartleson, J D; Kumar, Rajeev; McEvoy, Kathleen F; McKeon, Andrew

    2012-12-01

    BACKGROUND Little is known about adult-onset opsoclonus-myoclonus syndrome (OMS) outside of individual case reports. OBJECTIVE To describe adult-onset OMS. DESIGN Review of medical records (January 1, 1990, through December 31, 2011), prospective telephone surveillance, and literature review (January 1, 1967, through December 31, 2011). SETTING Department of Neurology, Mayo Clinic, Rochester, Minnesota. PATIENTS Twenty-one Mayo Clinic patients and 116 previously reported patients with adult-onset OMS. MAIN OUTCOME MEASURES Clinical course and longitudinal outcomes. RESULTS The median age at onset of the 21 OMS patients at the Mayo Clinic was 47 years (range, 27-78 years); 11 were women. Symptoms reported at the first visit included dizziness, 14 patients; balance difficulties, 14; nausea and/or vomiting, 10; vision abnormalities, 6; tremor/tremulousness, 4; and altered speech, 2. Myoclonus distribution was extremities, 15 patients; craniocervical, 8; and trunk, 4. Cancer was detected in 3 patients (breast adenocarcinoma, 2; and small cell lung carcinoma, 1); a parainfectious cause was assumed in the remainder of the patients. Follow-up of 1 month or more was available for 19 patients (median, 43 months; range, 1-187 months). Treatment (median, 6 weeks) consisted of immunotherapy and symptomatic therapy in 16 patients, immunotherapy alone for 2, and clonazepam alone for 1. Of these 19 patients, OMS remitted in 13 and improved in 3; 3 patients died (neurologic decline, 1; cancer, 1; and myocardial infarction, 1). The cause of death was of paraneoplastic origin in 60 of 116 literature review patients, with the most common carcinomas being lung (33 patients) and breast (7); the most common antibody was antineuronal nuclear antibody type 2 (anti-Ri, 15). Other causes were idiopathic in origin, 38 patients; parainfectious, 15 (human immunodeficiency virus, 7); toxic/metabolic, 2; and other autoimmune, 1. Both patients with N -methyl-D-aspartate receptor antibody had

  19. [Human hantavirus diseases - still neglected zoonoses?].

    PubMed

    Vrbovská, V; Chalupa, P; Straková, P; Hubálek, Z; Rudolf, I

    2015-10-01

    Hantavirus disease is the most common rodent-borne viral infection in the Czech Republic, with a mean annual incidence of 0.02 cases per 100 000 population and specific antibodies detected in 1% of the human population. Four hantaviruses (Puumala, Dobrava-Belgrade, Tula, and Seewis) circulate in this country, of which Puumala virus (responsible for a mild form of hemorrhagic fever with renal syndrome called nephropathia epidemica) and Dobrava-Belgrade virus (causing haemorrhagic fever with renal syndrome) have been proven to cause human disease. The aim of this study is to provide a comprehensive review of the hantaviruses occurring in the Czech Republic, based on the literature published during the past three decades, including their geographical distribution and clinical symptoms. The recent detection of Tula virus in an immunocompromised person as well as reports of Seoul virus infections in Europe highlight the possible emergence of neglected hantavirus infections in the foreseeable future.

  20. Iron hypothesis of cardiovascular disease: still controversial.

    PubMed

    Aursulesei, Viviana; Cozma, A; Krasniqi, A

    2014-01-01

    Iron hypothesis has been a controversial subject for over 30 years as many studies support its role as a risk factor for cardiovascular disease, while other studies found no evidence to support it. The conflicting results are accounted for by the non-homogeneity of trial design in terms of population inclusion criteria and different endpoints, non-uniform use of parameters for assessing iron role, and incomplete understanding of the mechanisms of action. The nature of iron is dual, being of crucial importance for the human body, but also toxic as "free iron" induces oxidative stress. Under physiological conditions, there are efficient and complex mechanisms against iron-induced oxidative stress, which could be reproduced for creating new, intelligent antioxidants. Iron depletion improves the cardiovascular prognosis only if serum concentration is at the lowest limit of normal ranges. However, low iron levels and the type of dietary iron intake correlate with atherosclerotic cardiovascular disease, influence the ischemic endpoints in the elderly, and exert negative impact on heart failure prognosis. So far, the causal relation and involved mechanisms are not fully elucidated. Iron overload is a difficult and frequent condition, involving the cardiovascular system by specific pathogenic pathways, therefore determining a particular form of restrictive cardiomyopathy and vaso-occlusive arterial damage.

  1. Mapping a gene for adult-onset primary open-angle glaucoma to chromosome 3q.

    PubMed Central

    Wirtz, M K; Samples, J R; Kramer, P L; Rust, K; Topinka, J R; Yount, J; Koler, R D; Acott, T S

    1997-01-01

    Glaucoma is the third-leading cause of blindness in the world, affecting >13.5 million people. Adult-onset primary open-angle glaucoma (POAG) is the most common form of glaucoma in the United States. We present a family in which adult-onset POAG is inherited as an autosomal dominant trait. Twelve affected family members were identified from 44 at-risk individuals. The disease-causing gene was mapped to chromosome 3q21-24, with analysis of recombinant haplotypes suggesting a total inclusion region of 11.1 cM between markers D3S3637 and D3S1744. This is the first report of mapping of an adult-onset POAG gene to chromosome 3q, gene symbol GLC1C. PMID:9012402

  2. Update on differences between childhood-onset and adult-onset systemic lupus erythematosus

    PubMed Central

    2013-01-01

    Systemic lupus erythematosus (SLE) is a complex autoimmune disease and occurs worldwide in both children and adults. The estimated annual incidence among children is 2.22/100,000 and among adults is 23.2/100,000 in the United States. There is increasing understanding about differences in disease manifestations, medication use, and disease severity between those with childhood-onset SLE as compared with adult-onset SLE. Children have a more fulminant disease onset and course than adults with SLE, resulting in two to three times higher mortality. In future years, we anticipate more insight into the genetics between childhood-onset SLE and adult-onset SLE to help delineate the best therapies for both subsets of patients. PMID:23998441

  3. Adult-onset hypophosphatemic osteomalacia associated with Sjogren syndrome

    PubMed Central

    Shen, Guohua; Zhang, Yuwei; Hu, Shuang; Liu, Bin; Kuang, Anren

    2017-01-01

    Abstract Rationale: Hypophosphatemic osteomalacia (HO) is a metabolic bone disease, exhibiting different etiologies such as genetic mutation, tumor induction, dysimmunity, or renal disease. Sjogren's syndrome (SS) is a connective tissue disorder commonly involving exocrine glands; however kidney involvement is also encountered, leading to abnormal phosphorus metabolism, even HO. Patient concerns: A 47-year-old female patient presented progressively worsening pain in the chest wall, back and bilateral lower extremities as well as muscle weakness was referred to our department. Diagnoses, interventions and outcomes: Due to the laboratory test results, radiographic findings and pathologic results, she was diagnosed with adult-onset HO associated with SS. She was then treated with alkalinization, steroids, neutral phosphate, calcium supplements together with activated vitamin D. So far, she recovered uneventfully with relieved pain and increased serum phosphorus level. Lessons: HO may be secondary to renal tubular acidosis of SS patients, and it might be a diagnostic challenge when the kidney involvement in SS is latent and precede the typical sicca symptoms. PMID:28353596

  4. Meniere's disease: Still a mystery disease with difficult differential diagnosis.

    PubMed

    Vassiliou, A; Vlastarakos, P V; Maragoudakis, P; Candiloros, D; Nikolopoulos, T P

    2011-01-01

    One hundred and forty-six years after its first description, the differential diagnosis of Meniere's disease remains very challenging. The aim of the present study is to review the current knowledge on the advantages and disadvantages of the new diagnostic methods for Meniere's disease. The importance of accurate diagnosis for primary healthcare systems is also discussed. An extensive search of the literature was performed in Medline and other available database sources. Information from electronic links and related books were also included. Controlled clinical studies, prospective cohort studies, retrospective cohort studies, cross-sectional studies, case reports, written guidelines, systematic reviews, and books were selected. The typical clinical triad of symptoms from the vestibular and cochlear systems (recurrent vertigo, fluctuating sensorineural hearing loss and tinnitus) is usually the key for clinical diagnosis. Glycerol dehydration test and electrocochleography are the main diagnostic tests in current practice, while vestibular evoked myogenic potentials may be used in disease staging. Imagine techniques are not specific enough to set alone the diagnosis of Meniere's disease, although they may be necessary to exclude other pathologies. Recently developed 3D MRI protocols can delineate the perilymphatic/endolymphatic spaces of the inner ear and aid diagnosis. Meniere's disease is a continuous problem for the patients and affects their quality of life. Taking into account the frequent nature of the disease in certain countries, efforts for reliable diagnosis, prompt referral, and successful management are undoubtedly cost-effective for healthcare systems.

  5. Periocular xanthogranulomas associated with severe adult-onset asthma.

    PubMed Central

    Jakobiec, F A; Mills, M D; Hidayat, A A; Dallow, R L; Townsend, D J; Brinker, E A; Charles, N C

    1993-01-01

    This article describes six patients who presented, usually bilaterally, with yellow-orange, elevated, indurated, and nonulcerated xanthomatous eyelid lesions, typically extending into the anterior orbital fat, and sometimes involving the extraocular muscles and the lacrimal gland. Because the eyelids remained intact and because the process did not reach the deep orbital and perioptic connective tissues, visual acuity was well preserved. There is cosmetic morbidity and occasionally motility restriction with advancing involvement of the extraocular muscles. All patients had variably severe adult-onset asthma that required treatment with systemic prednisone and inhalants. No evidence of Erdheim-Chester disease was found in any patient, but the appearance in one patient, after 25 years of follow-up, of a separate subcutaneous necrobiotic xanthogranulomatous lesion in the mandibular region with an associated paraproteinemia, suggests that at least some of our cases might be a mild form of necrobiotic xanthogranuloma. For this reason, we would suggest repeated periodic serum protein immunoelectrophoretic studies as well as evaluation for lymphoma. Therapy probably should consist of low doses of periorbital radiotherapy coupled with high doses of corticosteroids. Should this not be successful, then systemic administration of corticosteroids with chemotherapeutic agents might be efficacious, as in necrobiotic xanthogranuloma. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 FIGURE 10 FIGURE 11 FIGURE 12 FIGURE 13 FIGURE 14 FIGURE 15 FIGURE 16 FIGURE 17 FIGURE 18 FIGURE 19 PMID:8140711

  6. Niemann-Pick type C: focus on the adolescent/adult onset form.

    PubMed

    Di Lazzaro, Vincenzo; Marano, Massimo; Florio, Lucia; De Santis, Stefano

    2016-11-01

    Niemann-Pick disease type C (NP-C) is an inherited sphingolipidosis characterized by progressive neurological deterioration and early mortality. The symptomatology and disease progression of NP-C are markedly affected by the age at onset of neurological manifestations, and categorization into early-infantile, late-infantile, juvenile, adolescent/adult neurological onset forms can aid evaluation of disease course and responses to therapy. Here, we review current information on the detection, diagnosis, monitoring and treatment of NP-C, with a focus on the adolescent/adult-onset form. A recent analysis indicated that the combined incidence of NP-C related to NPC1 gene mutations (NPC1) and NP-C related to NPC2 gene mutations (NPC2) is approximately 1 case in every 89 000 live births. In particular, late-onset phenotypes might well provide a greater contribution to the overall incidence than has previously been reported. Some neuropathological features in NP-C are held in common with other advanced age-onset diseases such as Alzheimer's disease. Visceral symptoms such as splenomegaly are frequently asymptomatic in patients with adolescent/adult-onset NP-C, and are only occasionally detected during routine ultrasound assessments. In contrast, most patients with adolescent/adult-onset exhibit some degree of slowly progressive, non-disease-specific movement disorders (e.g. cerebellar ataxia), and/or more pathognomonic neurological signs such as vertical supranuclear gaze palsy. An increasing number of adolescent/adult-onset cases have been reported following initial recognition of cognitive impairment and/or psychiatric signs. The recent development and implementation of new clinical screening tools (e.g. the NP-C suspicion index) and biomarkers (e.g. plasma oxysterols) should help identify patients who warrant further investigation and possible treatment.

  7. Guinea worm cause of adult onset asthmatic attack, a radiological diagnosis.

    PubMed

    Marchie, T T

    1999-01-01

    A case report of a fifty years old Hausa male from Sokoto town, Nigeria an endemic region of guinea worm infestation, who presented with sudden adult onset of asthmatic attack and was evaluated radiologically and the diagnosis of acute obstructive airway disease was confirmed. It was noted, that there were associated calcified chain of guinea worms in the lung parenchyma. A rare association of acute asthmatic attack. Patient responded there-after to an anti-asthmatic regime of management.

  8. Adult-onset acute rheumatic fever.

    PubMed

    Nakashima, Dainari; Ueda, Kohei; Tsukuda, Kyozo; Utsu, Noriaki; Kohki, Shimazu; Fushimi, Hiroaki; Miyakoshi, Kazuho

    2012-01-01

    A 62-year-old man was hospitalized for acute rheumatic fever. He had previously suffered from rheumatic fever at 15 years of age. The rheumatic fever was complicated by carditis, which caused valve disease that required surgical treatment. The incidence of rheumatic fever has decreased in most developed countries with improvements in sanitary conditions. The low incidence of this disease makes a timely and accurate diagnosis difficult. Due to the fact that both the first occurrence and recurrence of acute rheumatic fever can occur in the elderly and adults, this potential disease should not be overlooked when making a differential diagnosis.

  9. Adult-onset amenorrhea: a study of 262 patients.

    PubMed

    Reindollar, R H; Novak, M; Tho, S P; McDonough, P G

    1986-09-01

    A series of 262 patients with amenorrhea of adult onset are reported. Hypothalamic suppression followed by inappropriate positive feedback, and then hyperprolactinemia and ovarian failure are the most frequently encountered etiologies. Other etiologies are diverse and numerically less frequent. Amenorrhea after use of oral contraceptives, or postpill amenorrhea, occurred in 77 (29%) of all patients. The average age of presentation, prior menstrual history, associated morbidity, and subsequent reproductive potential of each diagnostic group are reported. Adult-onset amenorrhea has a less significant impact on future wellbeing than was reported for a similar-sized group of patients whose amenorrhea developed as a result of pubertal aberrancy.

  10. Effects of diabetes mellitus on bone mass in juvenile and adult-onset diabetes.

    PubMed

    Levin, M E; Boisseau, V C; Avioli, L V

    1976-01-29

    To assess the influence of diabetes mellitus on bone metabolism, we measured skeletal mass in the forearms of 35 patients with juvenile diabetes on insulin and 101 stable patients with adult-onset diabetes, on diet alone, insulin, or oral hypoglycemic agents. There was a significant loss of bone mass in both juvenile and adult-onset diabetes (P less than 0.01) as compared to controls matched for age and sex. The decrease was already present in patients with diabetes of less than five years' duration. Bone loss and duration of the diabetes did not correlate; the greatest decrease in bone mass was observed in the patients receiving oral agents. These data are consistent with the hypothesis that the loss of skeletal tissue in diabetes reflects the underlying disease since it occurs early and is not related to severity as evidenced by the need for insulin, to duration, or to treatment with insulin or diet alone.

  11. Mapping a gene for adult-onset primary open-angle glaucoma to chromosome 3q

    SciTech Connect

    Wirtz, M.K.; Samples, J.R.; Kramer, P.L.

    1997-02-01

    Glaucoma is the third-leading cause of blindness in the world, affecting >13.5 million people. Adult-on-set primary open-angle glaucoma (POAG) is the most common form of glaucoma in the United States. We present a family in which adult-onset POAG is inherited as an autosomal dominant trait. Twelve affected family members were identified from 44 at-risk individuals. The disease-causing gene was mapped to chromosome 3q21-24, with analysis of recombinant haplotypes suggesting a total inclusion region of 11.1 cM between markers D3S3637 and D3S1744. This is the first report of mapping of an adult-onset POAG gene to chromosome 3q, gene symbol GLC1C. 57 refs., 3 figs., 3 tabs.

  12. Clinical profile of patients with adult-onset eosinophilic asthma

    PubMed Central

    Storm, Huib; Amelink, Marijke; de Nijs, Selma B.; Eichhorn, Edwin; Reitsma, Bennie H.; Bel, Elisabeth H.D.; ten Brinke, Anneke

    2016-01-01

    Adult-onset eosinophilic asthma is increasingly recognised as a severe and difficult-to-treat subtype of asthma. In clinical practice, early recognition of patients with this asthma subtype is important because it may have treatment implications. Therefore, physicians need to know the distinct characteristics of this asthma phenotype. The objective of the present study was to determine the characteristic profile of patients with adult-onset eosinophilic asthma. 130 patients with adult-onset (>18 years of age) asthma and high blood eosinophil counts (≥0.3×109 L−1) were compared with 361 adult-onset asthma patients with low (<0.3×109 L−1) blood eosinophils. Measurements included a series of clinical, functional and imaging parameters. Patients with high blood eosinophils were more often male, had less well controlled asthma and higher exacerbation rates, despite the use of higher doses of inhaled corticosteroids. They had higher levels of total IgE without more sensitisation to common inhaled allergens. In addition, these patients had worse lung function, and more often showed fixed airflow limitation, air trapping, nasal polyposis and abnormalities on sinus computed tomography scanning. Chronic rhinosinusitis, air trapping and male sex were three independent factors associated with blood eosinophilia (adjusted OR 3.8 (95% CI 1.7–8.1), 3.0 (95% CI 1.1–8.1) and 2.4 (95% CI 1.3–4.4), respectively). Patients with adult-onset asthma with elevated blood eosinophils exhibit a distinct profile, which can readily be recognised in clinical practice. PMID:27730197

  13. Clinical profile of patients with adult-onset eosinophilic asthma.

    PubMed

    de Groot, Jantina C; Storm, Huib; Amelink, Marijke; de Nijs, Selma B; Eichhorn, Edwin; Reitsma, Bennie H; Bel, Elisabeth H D; Ten Brinke, Anneke

    2016-04-01

    Adult-onset eosinophilic asthma is increasingly recognised as a severe and difficult-to-treat subtype of asthma. In clinical practice, early recognition of patients with this asthma subtype is important because it may have treatment implications. Therefore, physicians need to know the distinct characteristics of this asthma phenotype. The objective of the present study was to determine the characteristic profile of patients with adult-onset eosinophilic asthma. 130 patients with adult-onset (>18 years of age) asthma and high blood eosinophil counts (≥0.3×10(9) L(-1)) were compared with 361 adult-onset asthma patients with low (<0.3×10(9) L(-1)) blood eosinophils. Measurements included a series of clinical, functional and imaging parameters. Patients with high blood eosinophils were more often male, had less well controlled asthma and higher exacerbation rates, despite the use of higher doses of inhaled corticosteroids. They had higher levels of total IgE without more sensitisation to common inhaled allergens. In addition, these patients had worse lung function, and more often showed fixed airflow limitation, air trapping, nasal polyposis and abnormalities on sinus computed tomography scanning. Chronic rhinosinusitis, air trapping and male sex were three independent factors associated with blood eosinophilia (adjusted OR 3.8 (95% CI 1.7-8.1), 3.0 (95% CI 1.1-8.1) and 2.4 (95% CI 1.3-4.4), respectively). Patients with adult-onset asthma with elevated blood eosinophils exhibit a distinct profile, which can readily be recognised in clinical practice.

  14. Epidemiology of adult-onset hydrocephalus: institutional experience with 2001 patients.

    PubMed

    Bir, Shyamal C; Patra, Devi Prasad; Maiti, Tanmoy K; Sun, Hai; Guthikonda, Bharat; Notarianni, Christina; Nanda, Anil

    2016-09-01

    OBJECTIVE Adult-onset hydrocephalus is not commonly discussed in the literature, especially regarding its demographic distribution. In contrast to pediatric hydrocephalus, which is related to a primary CSF pathway defect, its development in adults is often secondary to other pathologies. In this study, the authors investigated the epidemiology of adult-onset hydrocephalus as it pertains to different etiologies and in reference to age, sex, and race distributions. METHODS The authors retrospectively reviewed the clinical notes of 2001 patients with adult-onset hydrocephalus who presented to Louisiana State University Health Sciences Center within a 25-year span. Significant differences between the groups were analyzed by a chi-square test; p < 0.05 was considered significant. RESULTS The overall mean (± SEM) incidence of adult hydrocephalus in this population was 77 ± 30 per year, with a significant increase in incidence in the past decade (55 ± 3 [1990-2003] vs 102 ± 6 [2004-2015]; p < 0.0001). Hydrocephalus in a majority of the patients had a vascular etiology (45.5%) or was a result of a tumor (30.2%). The incidence of hydrocephalus in different age groups varied according to various pathologies. The incidence was significantly higher in males with normal-pressure hydrocephalus (p = 0.03) or head injury (p = 0.01) and higher in females with pseudotumor cerebri (p < 0.0001). In addition, the overall incidence of hydrocephalus was significantly higher in Caucasian patients (p = 0.0002) than in those of any other race. CONCLUSIONS Knowledge of the demographic variations in adult-onset hydrocephalus is helpful in achieving better risk stratification and better managing the disease in patients. For general applicability, these results should be validated in a large-scale meta-analysis based on a national population database.

  15. Lifetime Increased Risk of Adult Onset Atopic Dermatitis in Adolescent and Adult Patients with Food Allergy

    PubMed Central

    Yu, Hsu-Sheng; Tu, Hung-Pin; Hong, Chien-Hui; Lee, Chih-Hung

    2016-01-01

    Food allergy can result in life-threatening anaphylaxis. Atopic dermatitis (AD) causes intense itching and impaired quality of life. Previous studies have shown that patients with classical early-onset AD tend to develop food allergy and that 10% of adults with food allergies have concomitant AD. However, it is not known whether late-onset food allergy leads to adult-onset AD, a recently recognized disease entity. Using an initial cohort of one-million subjects, this study retrospectively followed-up 2851 patients with food allergy (age > 12 years) for 14 years and compared them with 11,404 matched controls. While 2.8% (81) of the 2851 food allergy patients developed AD, only 2.0% (227) of the 11,404 controls developed AD. Multivariate regression analysis showed that food allergy patients were more likely to develop AD (adjusted hazard ratio = 2.49, p < 0.0001). Controls had a 1.99% risk of developing AD, while food allergy patients had a significantly higher risk (7.18% and 3.46% for patients with ≥3 and <3 food allergy claims, respectively) of developing adult-onset AD. This is the first study to describe the chronological and dose-dependent associations between food allergy in adolescence and the development of adult-onset AD. PMID:28035995

  16. Iron: Protector or Risk Factor for Cardiovascular Disease? Still Controversial

    PubMed Central

    Muñoz-Bravo, Carlos; Gutiérrez-Bedmar, Mario; Gómez-Aracena, Jorge; García-Rodríguez, Antonio; Fernández-Crehuet Navajas, Joaquín

    2013-01-01

    Iron is the second most abundant metal in the Earth’s crust. Despite being present in trace amounts, it is an essential trace element for the human body, although it can also be toxic due to oxidative stress generation by the Fenton reaction, causing organic biomolecule oxidation. This process is the basis of numerous pathologies, including cardiovascular diseases (CVD). The relationship between iron and cardiovascular disease was proposed in 1981 by Jerome Sullivan. Since then, numerous epidemiological studies have been conducted to test this hypothesis. The aim of this review is to present the main findings of the chief epidemiological studies published during the last 32 years, since Sullivan formulated his iron hypothesis, suggesting that this element might act as a risk factor for cardiovascular disease. We have analyzed 55 studies, of which 27 supported the iron hypothesis, 20 found no evidence to support it and eight were contrary to the iron hypothesis. Our results suggest that there is not a high level of evidence which supports the hypothesis that the iron may be associated with CVD. Despite the large number of studies published to date, the role of iron in cardiovascular disease still generates a fair amount of debate, due to a marked disparity in results. PMID:23857219

  17. Adult-onset idiopathic chondrolysis of the hip.

    PubMed

    Yapp, Liam Z; McClymont, Liusaidh; Beggs, Ian; Gaston, Paul; Salter, Donald M

    2017-05-01

    We report the case of a 23-year-old man diagnosed with adult-onset idiopathic chondrolysis of the hip. Chondrolysis of the hip is a disorder most frequently seen in children who have suffered with slipped capital femoral epiphyses. Idiopathic chondrolysis of the hip is extremely rare and to our knowledge, its onset has never been documented in adults aged over 20. With reference to the available medical literature, we summarise the current clinical management of this unusual but important cause of young adult hip pain.

  18. Compound heterozygote mutations in SPG7 in a family with adult-onset primary lateral sclerosis

    PubMed Central

    Yang, Yi; Lynch, David R.; Lukas, Thomas; Ahmeti, Kreshnik; Sleiman, Patrick M.A.; Ryan, Eanna; Schadt, Kimberly A.; Newman, Jordan H.; Deng, Han-Xiang; Siddique, Nailah

    2016-01-01

    Objective: To identify the genetic defect for adult-onset primary lateral sclerosis (PLS) in a family with 5 patients. Methods: Whole-exome sequencing was performed to identify the shared genetic variants in 3 affected members in a PLS family with 5 affected individuals. Sanger sequencing was used for validation of the variants and for cosegregation analysis. Mitochondrial activity for both patients and unaffected siblings was measured using a SeaHorse metabolic analyzer. Results: Whole-exome sequencing and subsequent cosegregation analysis demonstrated that compound heterozygous missense variants L695P and I743T in SPG7 were the only mutations cosegregating with the disease in an autosomal recessive fashion in this family. The parents and siblings are genetically heterozygous and clinically unaffected. Functional studies suggested that the PLS-associated SPG7 mutants affect mitochondrial function when glucose is reduced. Conclusions: Compound heterozygote mutations in SPG7 are associated with adult-onset PLS, extending the spectrum of SPG7-linked neurologic diseases. Patients with the PLS phenotype should have genetic testing for paraplegin, especially when the condition is familial. PMID:27123479

  19. Predictive Medicine: Recombinant DNA Technology and Adult-Onset Genetic Disorders

    PubMed Central

    Hayden, Michael

    1988-01-01

    Genetic factors are of great importance in common adult-onset disorders such as atherosclerosis, cancer, and neuro-degenerative diseases. Advances in DNA technology now allow identification of persons at high-risk of developing some of these diseases. This advance is leading to predictive medicine. In some genetic disorders, such as those leading to atherosclerosis and cancer, identification of high-risk individuals allows intervention which alters the natural history of the disorder. In other diseases, for which there is no treatment, such as Huntington's disease, the application of this technology provides information that relieves uncertainty and may affect quality of life, but does not alter the course of the illness. General implementation of predictive testing programs awaits the results of pilot projects, which will demonstrate the needs, appropriate levels of support, and guidelines for delivery of such testing. PMID:21253100

  20. Yellow fever in China is still an imported disease.

    PubMed

    Chen, Jun; Lu, Hongzhou

    2016-05-23

    Yellow fever is a vector-borne disease endemic to tropical regions of Africa and South America. A recent outbreak in Angola caused hundreds of deaths. Six cases of yellow fever imported from Angola were reported recently in China. This raised the question of whether it will spread in China and how it can be prevented. This article discusses the possibility of yellow fever transmission in China and the strategies to counter it.

  1. Olestra? The Jury's Still Out

    NASA Astrophysics Data System (ADS)

    Doyle, Ellin

    1997-04-01

    Although it has been more than a year since the FDA approved the use of olestra in certain foods, this fat substitute, a mixture of sucrose polyesters, is still controversial. It would seem that a fat substitute that is heat stable and has an acceptable flavor and texture would be welcomed enthusiastically in a country where increasing numbers of people, young and old, exceed their ideal body weight. Obesity and diets containing high levels of fat have been linked to numerous health problems, including cardiovascular diseases, certain types of cancer, and adult-onset diabetes; they may also exacerbate some chronic problems such as arthritis in joints of the lower extremities. Nevertheless, some scientists and consumer groups question olestra's safety and usefulness.

  2. Distinguishing adult-onset asthma from COPD: a review and a new approach

    PubMed Central

    Abramson, Michael J; Perret, Jennifer L; Dharmage, Shyamali C; McDonald, Vanessa M; McDonald, Christine F

    2014-01-01

    Adult-onset asthma and chronic obstructive pulmonary disease (COPD) are major public health burdens. This review presents a comprehensive synopsis of their epidemiology, pathophysiology, and clinical presentations; describes how they can be distinguished; and considers both established and proposed new approaches to their management. Both adult-onset asthma and COPD are complex diseases arising from gene–environment interactions. Early life exposures such as childhood infections, smoke, obesity, and allergy influence adult-onset asthma. While the established environmental risk factors for COPD are adult tobacco and biomass smoke, there is emerging evidence that some childhood exposures such as maternal smoking and infections may cause COPD. Asthma has been characterized predominantly by Type 2 helper T cell (Th2) cytokine-mediated eosinophilic airway inflammation associated with airway hyperresponsiveness. In established COPD, the inflammatory cell infiltrate in small airways comprises predominantly neutrophils and cytotoxic T cells (CD8 positive lymphocytes). Parenchymal destruction (emphysema) in COPD is associated with loss of lung tissue elasticity, and small airways collapse during exhalation. The precise definition of chronic airflow limitation is affected by age; a fixed cut-off of forced expiratory volume in 1 second/forced vital capacity leads to overdiagnosis of COPD in the elderly. Traditional approaches to distinguishing between asthma and COPD have highlighted age of onset, variability of symptoms, reversibility of airflow limitation, and atopy. Each of these is associated with error due to overlap and convergence of clinical characteristics. The management of chronic stable asthma and COPD is similarly convergent. New approaches to the management of obstructive airway diseases in adults have been proposed based on inflammometry and also multidimensional assessment, which focuses on the four domains of the airways, comorbidity, self-management, and

  3. A novel mouse model that recapitulates adult-onset glycogenosis type 4

    PubMed Central

    Orhan Akman, H.; Emmanuele, Valentina; Kurt, Yasemin Gülcan; Kurt, Bülent; Sheiko, Tatiana; DiMauro, Salvatore; Craigen, William J.

    2015-01-01

    Glycogen storage disease type IV (GSD IV) is a rare autosomal recessive disorder caused by deficiency of the glycogen-branching enzyme (GBE). The diagnostic hallmark of the disease is the accumulation of a poorly branched form of glycogen known as polyglucosan (PG). The disease is clinically heterogeneous, with variable tissue involvement and age at onset. Complete loss of enzyme activity is lethal in utero or in infancy and affects primarily the muscle and the liver. However, residual enzyme activity as low as 5–20% leads to juvenile or adult onset of a disorder that primarily affects the central and peripheral nervous system and muscles and in the latter is termed adult polyglucosan body disease (APBD). Here, we describe a mouse model of GSD IV that reflects this spectrum of disease. Homologous recombination was used to knock in the most common GBE1 mutation p.Y329S c.986A > C found in APBD patients of Ashkenazi Jewish decent. Mice homozygous for this allele (Gbe1ys/ys) exhibit a phenotype similar to APBD, with widespread accumulation of PG. Adult mice exhibit progressive neuromuscular dysfunction and die prematurely. While the onset of symptoms is limited to adult mice, PG accumulates in tissues of newborn mice but is initially absent from the cerebral cortex and heart muscle. Thus, PG is well tolerated in most tissues, but the eventual accumulation in neurons and their axons causes neuropathy that leads to hind limb spasticity and premature death. This mouse model mimics the pathology and pathophysiologic features of human adult-onset branching enzyme deficiency. PMID:26385640

  4. Disease patterns in vasculitis-still a mystery.

    PubMed

    Hoffman, Gary S

    2008-01-01

    In the field of autoimmunity, much has been learned from studying circulating and tissue bound immune-reactive cells, cytokines and antibodies. However, what has brought those cells to the site of injury, for most forms of vasculitis remains a mystery. Might the etiology of at least certain forms of vasculitis be related to generation of neoantigens in the native vessel, making that vessel the target of a pathogenic immune response? How might one explain organ targeting and patterns of disease that are so critical to the diagnostic process? Embryologists have demonstrated great diversity in the vasculature of different organs. Unique quantitative and qualitative features become apparent in vascular territories as early as the third week of gestation. These differences are later amplified by the effects of further development, aging, infection, spontaneous mutations and other co-morbidities. Based on data from these observations a testable hypothesis would be that many forms of vasculitis may begin with emergence of new antigens within affected vessel walls and the resulting immune response may in fact be a normal reaction to perceived foreign protein(s).

  5. Adult-onset nemaline myopathy in a dog presenting with persistent atrial standstill and primary hypothyroidism.

    PubMed

    Nakamura, R K; Russell, N J; Shelton, G D

    2012-06-01

    A nine-year-old neutered female mixed breed dog presented for evaluation following a five-day history of lethargy, inappetence, weakness, abdominal distension and generalised muscle atrophy. Persistent vatrial standstill with a junctional rhythm was identified on electrocardiogram. Echocardiogram identified moderate dilation of all cardiac chambers and mild thickening of the mitral and tricuspid valves. Serology was negative for Neospora caninum and Toxoplasma gondii. Permanent pacemaker implantation was performed in addition to endomyocardial and skeletal muscle biopsies. Cryosections from the biceps femoris muscle showed numerous nemaline rod bodies while endomyocardial biopsies were possibly consistent with end-stage myocarditis. Rod bodies have rarely been reported in the veterinary literature. To the authors' knowledge, this is the first report of adult-onset nemaline rod myopathy and hypothyroidism with concurrent cardiac disease in a dog.

  6. Case report: An adult-onset type II citrin deficiency patient in the emergency department

    PubMed Central

    TANG, LUJIA; CHEN, LIANG; WANG, HAIRONG; DAI, LIHUA; PAN, SHUMING

    2016-01-01

    Mutations in the solute carrier family 25 (SLC25A13) gene may result in neonatal intrahepatic cholestasis caused by citrin deficiency and/or adult-onset type II citrullinemia. These conditions are inherited in an autosomal recessive manner. The current case report describes a 43-year-old man who presented with sudden delirium and upper limb weakness. Upon admission, the patient was fully conscious and alert but later lost consciousness subsequent to a sudden convulsive seizure. Hyperammonemia was detected and analysis of the SLC25A13 gene identified an 851del4 mutation. Thus, the possibility of genetic disease should be considered as a potential cause of the symptoms of patients with altered states of consciousness, such as delirium and loss of consciousness, in cases where the cause of the disturbance is unknown. PMID:27347070

  7. Clinical Value of NPHS2 Analysis in Early- and Adult-Onset Steroid-Resistant Nephrotic Syndrome

    PubMed Central

    Santín, Sheila; Tazón-Vega, Bárbara; Silva, Irene; Cobo, María Ángeles; Giménez, Isabel; Ruíz, Patricia; García-Maset, Rafael; Ballarín, José

    2011-01-01

    Summary Background and objectives To date, very few cases with adult-onset focal segmental glomerulosclerosis (FSGS) carrying NPHS2 variants have been described, all of them being compound heterozygous for the p.R229Q variant and one pathogenic mutation. Design, setting, participants, & measurements Mutation analysis was performed in 148 unrelated Spanish patients, of whom 50 presented with FSGS after 18 years of age. Pathogenicity of amino acid substitutions was evaluated through an in silico scoring system. Haplotype analysis was carried out using NPHS2 single nucleotide polymorphism and microsatellite markers. Results Compound heterozygous or homozygous NPHS2 pathogenic mutations were identified in seven childhood-onset steroid-resistant nephrotic syndrome (SRNS) cases. Six additional cases with late childhood- and adult-onset SRNS were compound heterozygotes for p.R229Q and one pathogenic mutation, mostly p.A284V. p.R229Q was more frequent among SRNS cases relative to controls (odds ratio = 2.65; P = 0.02). Significantly higher age at onset of the disease and slower progression to ESRD were found in patients with one pathogenic mutation plus the p.R229Q variant in respect to patients with two NPHS2 pathogenic mutations. Conclusions NPHS2 analysis has a clinical value in both childhood- and adult-onset SRNS patients. For adult-onset patients, the first step should be screening for p.R229Q and, if positive, for p.A284V. These alleles are present in conserved haplotypes, suggesting a common origin for these substitutions. Patients carrying this specific NPHS2 allele combination did not respond to corticoids or immunosuppressors and showed FSGS, average 8-year progression to ESRD, and low risk for recurrence of FSGS after kidney transplant. PMID:20947785

  8. Warming up Improves Speech Production in Patients with Adult Onset Myotonic Dystrophy

    ERIC Educational Resources Information Center

    de Swart, B.J.M.; van Engelen, B.G.M.; Maassen, B.A.M.

    2007-01-01

    This investigation was conducted to study whether warming up decreases myotonia (muscle stiffness) during speech production or causes adverse effects due to fatigue or exhaustion caused by intensive speech activity in patients with adult onset myotonic dystrophy. Thirty patients with adult onset myotonic dystrophy (MD) and ten healthy controls…

  9. Nephrin mutations cause childhood- and adult-onset focal segmental glomerulosclerosis.

    PubMed

    Santín, Sheila; García-Maset, Rafael; Ruíz, Patricia; Giménez, Isabel; Zamora, Isabel; Peña, Antonia; Madrid, Alvaro; Camacho, Juan A; Fraga, Gloria; Sánchez-Moreno, Ana; Cobo, Maria Angeles; Bernis, Carmen; Ortiz, Alberto; de Pablos, Augusto Luque; Pintos, Guillem; Justa, Maria Luisa; Hidalgo-Barquero, Emilia; Fernández-Llama, Patricia; Ballarín, José; Ars, Elisabet; Torra, Roser

    2009-12-01

    Mutations in the NPHS1 gene cause congenital nephrotic syndrome of the Finnish type presenting before the first 3 months of life. Recently, NPHS1 mutations have also been identified in childhood-onset steroid-resistant nephrotic syndrome and milder courses of disease, but their role in adults with focal segmental glomerulosclerosis remains unknown. Here we developed an in silico scoring matrix to evaluate the pathogenicity of amino-acid substitutions using the biophysical and biochemical difference between wild-type and mutant amino acid, the evolutionary conservation of the amino-acid residue in orthologs, and defined domains, with the addition of contextual information. Mutation analysis was performed in 97 patients from 89 unrelated families, of which 52 presented with steroid-resistant nephrotic syndrome after 18 years of age. Compound heterozygous or homozygous NPHS1 mutations were identified in five familial and seven sporadic cases, including one patient 27 years old at onset of the disease. Substitutions were classified as 'severe' or 'mild' using this in silico approach. Our results suggest an earlier onset of the disease in patients with two 'severe' mutations compared to patients with at least one 'mild' mutation. The finding of mutations in a patient with adult-onset focal segmental glomerulosclerosis indicates that NPHS1 analysis could be considered in patients with later onset of the disease.

  10. Dominant-Negative Effects of Adult-Onset Huntingtin Mutations Alter the Division of Human Embryonic Stem Cells-Derived Neural Cells

    PubMed Central

    Lopes, Carla; Aubert, Sophie; Bourgois-Rocha, Fany; Barnat, Monia; Rego, Ana Cristina; Déglon, Nicole

    2016-01-01

    Mutations of the huntingtin protein (HTT) gene underlie both adult-onset and juvenile forms of Huntington’s disease (HD). HTT modulates mitotic spindle orientation and cell fate in mouse cortical progenitors from the ventricular zone. Using human embryonic stem cells (hESC) characterized as carrying mutations associated with adult-onset disease during pre-implantation genetic diagnosis, we investigated the influence of human HTT and of an adult-onset HD mutation on mitotic spindle orientation in human neural stem cells (NSCs) derived from hESCs. The RNAi-mediated silencing of both HTT alleles in neural stem cells derived from hESCs disrupted spindle orientation and led to the mislocalization of dynein, the p150Glued subunit of dynactin and the large nuclear mitotic apparatus (NuMA) protein. We also investigated the effect of the adult-onset HD mutation on the role of HTT during spindle orientation in NSCs derived from HD-hESCs. By combining SNP-targeting allele-specific silencing and gain-of-function approaches, we showed that a 46-glutamine expansion in human HTT was sufficient for a dominant-negative effect on spindle orientation and changes in the distribution within the spindle pole and the cell cortex of dynein, p150Glued and NuMA in neural cells. Thus, neural derivatives of disease-specific human pluripotent stem cells constitute a relevant biological resource for exploring the impact of adult-onset HD mutations of the HTT gene on the division of neural progenitors, with potential applications in HD drug discovery targeting HTT-dynein-p150Glued complex interactions. PMID:26863614

  11. Genetics Home Reference: adult-onset leukoencephalopathy with axonal spheroids and pigmented glia

    MedlinePlus

    ... it causes a severe decline in thinking and reasoning abilities (dementia). Over time, motor skills are affected, ... Schmahmann JD. Adult onset leukodystrophy with neuroaxonal spheroids: clinical, neuroimaging and neuropathologic observations. Brain Pathol. 2009 Jan; ...

  12. Adult-onset nemaline rods in a patient treated for suspected dermatomyositis: study with two-dimensional electrophoresis

    SciTech Connect

    Danon, M.J.; Giometti, C.S.; Manaligod, J.R.; Perurena, O.H.; Skosey, J.L.

    1981-12-01

    A 65-year-old woman with progressive muscle weakness and a diffuse rash of three years' duration was examined. Muscle tissue was studied with histochemical techniques, phase-contrast microscopy, electron microscopy, and two-dimensional electrophoresis. Histochemical studies showed numerous nemaline rods, with a normal ratio of types I and II fibers. Two-dimensional electrophoresis revealed abnormalities in the myosin light chain and tropomyosin protein patterns when compared with normal and diseased muscle biopsy samples, including those from two patients with adult-onset dermatomyositis.

  13. Juvenile versus adult-onset ankylosing spondylitis -- clinical, radiographic, and social outcomes. a systematic review.

    PubMed

    Jadon, Deepak R; Ramanan, Athimalaipet V; Sengupta, Raj

    2013-11-01

    Ankylosing spondylitis (AS) has 2 main modes of onset: juvenile-onset AS (JoAS) and adult-onset AS (AoAS). It is not known whether JoAS is a subtype of AS, or AS modulated by early age of onset and longer disease duration. We performed a systematic review of the literature, identifying 12 articles and 1 abstract directly comparing JoAS and AoAS cohorts, with observational study design. Patients with JoAS appear to have more peripheral joint involvement both clinically and radiographically (especially knees and ankles) and more root joint involvement (hips and shoulders); they are more likely to proceed to hip arthroplasty and often initially present with peripheral rather than axial symptoms. Patients with AoAS appear to have more axial symptoms and radiographic disease, particularly in the lumbar spine, and worse axial metrology. In terms of other characteristics, more evidence is needed to confidently state whether JoAS and AoAS are different.

  14. Young-onset parkinsonism in a Hong Kong Chinese man with adult-onset Hallervorden-Spatz syndrome.

    PubMed

    Mak, Chloe Miu; Sheng, Bun; Lee, Hencher Han-chih; Lau, Kwok-kwong; Chan, Wing-tak; Lam, Ching-wan; Chan, Yan-wo

    2011-04-01

    Neurodegeneration with brain iron accumulation (NBIA) is a heterogeneous group of disorders varied in genetic etiologies, clinical presentations, and radiological features. NBIA is an iron homeostasis disorder with progressive iron accumulation in the central nervous systems and is clinically characterized by extrapyramidal movement abnormalities, retinal pigmentary changes, and cognitive impairment. Panthothenate kinase-associated neurodegeneration (Hallervorden-Spatz disease) is the commonest disorder of NBIA with a prevalence of one-three per million. Clinically, it is classified into early-onset childhood, atypical late-onset, and adult-onset type. Adult-onset type is rarer. We report the first case of adult-onset panthothenate kinase-associated neurodegeneration in Hong Kong in a 28-year-old Chinese man who presented with pure young-onset parkinsonism. Magnetic resonance imaging (MRI) of the brain showed the presence of eye-of-the-tiger sign. Two compound heterozygous mutations PANK2 NM_153638.2: c.445G > T; NP_705902.2: p.E149X and PANK2 NM_153638.2: c.1133A > G; NP_705902.2: p.D378G were detected. Parkinsonism per se is a very heterogeneous phenotypic group. In view of the readily available genetic analysis of PANK2, panthothenate kinase-associated neurodegeneration should be considered in adult patients with young-onset parkinsonism with or without the eye-of-the-tiger sign. The exact diagnosis offers a different management approach and genetic counseling. NBIA is likely under- or misdiagnosed in Hong Kong Chinese.

  15. Variation in genes related to cochlear biology is strongly associated with adult-onset deafness in border collies.

    PubMed

    Yokoyama, Jennifer S; Lam, Ernest T; Ruhe, Alison L; Erdman, Carolyn A; Robertson, Kathryn R; Webb, Aubrey A; Williams, D Colette; Chang, Melanie L; Hytönen, Marjo K; Lohi, Hannes; Hamilton, Steven P; Neff, Mark W

    2012-09-01

    Domestic dogs can suffer from hearing losses that can have profound impacts on working ability and quality of life. We have identified a type of adult-onset hearing loss in Border Collies that appears to have a genetic cause, with an earlier age of onset (3-5 years) than typically expected for aging dogs (8-10 years). Studying this complex trait within pure breeds of dog may greatly increase our ability to identify genomic regions associated with risk of hearing impairment in dogs and in humans. We performed a genome-wide association study (GWAS) to detect loci underlying adult-onset deafness in a sample of 20 affected and 28 control Border Collies. We identified a region on canine chromosome 6 that demonstrates extended support for association surrounding SNP Chr6.25819273 (p-value = 1.09 × 10(-13)). To further localize disease-associated variants, targeted next-generation sequencing (NGS) of one affected and two unaffected dogs was performed. Through additional validation based on targeted genotyping of additional cases (n = 23 total) and controls (n = 101 total) and an independent replication cohort of 16 cases and 265 controls, we identified variants in USP31 that were strongly associated with adult-onset deafness in Border Collies, suggesting the involvement of the NF-κB pathway. We found additional support for involvement of RBBP6, which is critical for cochlear development. These findings highlight the utility of GWAS-guided fine-mapping of genetic loci using targeted NGS to study hereditary disorders of the domestic dog that may be analogous to human disorders.

  16. A nonsense mutation of human XRCC4 is associated with adult-onset progressive encephalocardiomyopathy

    PubMed Central

    Bee, Leonardo; Nasca, Alessia; Zanolini, Alice; Cendron, Filippo; d'Adamo, Pio; Costa, Rodolfo; Lamperti, Costanza; Celotti, Lucia; Ghezzi, Daniele; Zeviani, Massimo

    2015-01-01

    We studied two monozygotic twins, born to first cousins, affected by a multisystem disease. At birth, they both presented with bilateral cryptorchidism and malformations. Since early adulthood, they developed a slowly progressive neurological syndrome, with cerebellar and pyramidal signs, cognitive impairment, and depression. Dilating cardiomyopathy is also present in both. By whole-exome sequencing, we found a homozygous nucleotide change in XRCC4 (c.673C>T), predicted to introduce a premature stop codon (p.R225*). XRCC4 transcript levels were profoundly reduced, and the protein was undetectable in patients' skin fibroblasts. XRCC4 plays an important role in non-homologous end joining of DNA double-strand breaks (DSB), a system that is involved in repairing DNA damage from, for example, ionizing radiations. Gamma-irradiated mutant cells demonstrated reduction, but not abolition, of DSB repair. In contrast with embryonic lethality of the Xrcc4 KO mouse, nonsense mutations in human XRCC4 have recently been associated with primordial dwarfism and, in our cases, with adult-onset neurological impairment, suggesting an important role for DNA repair in the brain. Surprisingly, neither immunodeficiency nor predisposition to malignancy was reported in these patients. PMID:25872942

  17. Genes and Pathways Involved in Adult Onset Disorders Featuring Muscle Mitochondrial DNA Instability

    PubMed Central

    Ahmed, Naghia; Ronchi, Dario; Comi, Giacomo Pietro

    2015-01-01

    Replication and maintenance of mtDNA entirely relies on a set of proteins encoded by the nuclear genome, which include members of the core replicative machinery, proteins involved in the homeostasis of mitochondrial dNTPs pools or deputed to the control of mitochondrial dynamics and morphology. Mutations in their coding genes have been observed in familial and sporadic forms of pediatric and adult-onset clinical phenotypes featuring mtDNA instability. The list of defects involved in these disorders has recently expanded, including mutations in the exo-/endo-nuclease flap-processing proteins MGME1 and DNA2, supporting the notion that an enzymatic DNA repair system actively takes place in mitochondria. The results obtained in the last few years acknowledge the contribution of next-generation sequencing methods in the identification of new disease loci in small groups of patients and even single probands. Although heterogeneous, these genes can be conveniently classified according to the pathway to which they belong. The definition of the molecular and biochemical features of these pathways might be helpful for fundamental knowledge of these disorders, to accelerate genetic diagnosis of patients and the development of rational therapies. In this review, we discuss the molecular findings disclosed in adult patients with muscle pathology hallmarked by mtDNA instability. PMID:26251896

  18. The distinction between juvenile and adult-onset primary open-angle glaucoma

    SciTech Connect

    Wiggs, J.L.; Haines, J.L.; Damji, K.F.

    1996-01-01

    Because of the significant differences between the juvenile and adult forms of open-angle glaucoma, especially with regard to inheritance, prevalence, severity, and age of onset, we read with interest the recent publication by Morissette et al., describing a pedigree with a phenotype that overlaps the distinctive features of juvenile-onset open-angle glaucoma (JOAG) and adult-onset primary open-angle glaucoma (usually abbreviated as POAG or COAG). These authors conclude that a gene mapped to human chromosome 1q21-q31 (GLC1A) can be responsible for both juvenile and adult forms of open-angle glaucoma. The implications of such a result could be extremely important, in light of the high prevalence of the adult form of the disease. However, while the data presented in this report suggest that variable expressivity of the GLC1A gene may lead to a broader range of onset for this form of juvenile glaucoma, these data do not identify the GLC1A gene as an important cause of POAG. To prevent misleading interpretations of this and similar studies, we wish to clarify the distinction between the juvenile and adult forms of open-angle glaucoma. 8 refs.

  19. Genes and Pathways Involved in Adult Onset Disorders Featuring Muscle Mitochondrial DNA Instability.

    PubMed

    Ahmed, Naghia; Ronchi, Dario; Comi, Giacomo Pietro

    2015-08-05

    Replication and maintenance of mtDNA entirely relies on a set of proteins encoded by the nuclear genome, which include members of the core replicative machinery, proteins involved in the homeostasis of mitochondrial dNTPs pools or deputed to the control of mitochondrial dynamics and morphology. Mutations in their coding genes have been observed in familial and sporadic forms of pediatric and adult-onset clinical phenotypes featuring mtDNA instability. The list of defects involved in these disorders has recently expanded, including mutations in the exo-/endo-nuclease flap-processing proteins MGME1 and DNA2, supporting the notion that an enzymatic DNA repair system actively takes place in mitochondria. The results obtained in the last few years acknowledge the contribution of next-generation sequencing methods in the identification of new disease loci in small groups of patients and even single probands. Although heterogeneous, these genes can be conveniently classified according to the pathway to which they belong. The definition of the molecular and biochemical features of these pathways might be helpful for fundamental knowledge of these disorders, to accelerate genetic diagnosis of patients and the development of rational therapies. In this review, we discuss the molecular findings disclosed in adult patients with muscle pathology hallmarked by mtDNA instability.

  20. Mutated CTSF in adult-onset neuronal ceroid lipofuscinosis and FTD

    PubMed Central

    van der Zee, Julie; Mariën, Peter; Crols, Roeland; Van Mossevelde, Sara; Dillen, Lubina; Perrone, Federica; Engelborghs, Sebastiaan; Verhoeven, Jo; D'aes, Tine; Ceuterick-De Groote, Chantal; Sieben, Anne; Versijpt, Jan; Cras, Patrick; Martin, Jean-Jacques

    2016-01-01

    Objective: To investigate the molecular basis of a Belgian family with autosomal recessive adult-onset neuronal ceroid lipofuscinosis (ANCL or Kufs disease [KD]) with pronounced frontal lobe involvement and to expand the findings to a cohort of unrelated Belgian patients with frontotemporal dementia (FTD). Methods: Genetic screening in the ANCL family and FTD cohort (n = 461) was performed using exome sequencing and targeted massive parallel resequencing. Results: We identified a homozygous mutation (p.Ile404Thr) in the Cathepsin F (CTSF) gene cosegregating in the ANCL family. No other mutations were found that could explain the disease in this family. All 4 affected sibs developed motor symptoms and early-onset dementia with prominent frontal features. Two of them evolved to akinetic mutism. Disease presentation showed marked phenotypic variation with the onset ranging from 26 to 50 years. Myoclonic epilepsy in one of the sibs was suggestive for KD type A, while epilepsy was not present in the other sibs who presented with clinical features of KD type B. In a Belgian cohort of unrelated patients with FTD, the same heterozygous p.Arg245His mutation was identified in 2 patients who shared a common haplotype. Conclusions: A homozygous CTSF mutation was identified in a recessive ANCL pedigree. In contrast to the previous associations of CTSF with KD type B, our findings suggest that CTSF genetic testing should also be considered in patients with KD type A as well as in early-onset dementia with prominent frontal lobe and motor symptoms. PMID:27668283

  1. Adult-onset leukoencephalopathy with neuroaxonal spheroids and pigmented glia: report of five cases and a new mutation.

    PubMed

    Kleinfeld, Kirk; Mobley, Bret; Hedera, Peter; Wegner, Adam; Sriram, Subramaniam; Pawate, Siddharama

    2013-02-01

    The objective of this work is to report on a series of five patients with adult-onset leukoencephalopathy with neuroaxonal spheroids and pigmented glia (ALSP). ALSP is a rare adult-onset leukodystrophy, which encompasses hereditary diffuse leukoencephalopathy with axonal spheroids and pigmentary orthochromatic leukodystrophy. This was a retrospective chart review and literature review. Five previously healthy women presented with a rapidly progressive neurological disorder at ages 39, 37, 40, 30, and 47, respectively. All five individuals were initially diagnosed as suffering from multiple sclerosis. The clinical courses of the five patients were dominated by progressive spastic quadriparesis (patient 5, newly diagnosed, has paraparesis at this time) and dementia. Brain magnetic resonance imaging (MRI) showed diffuse cerebral atrophy, corpus callosal atrophy, and diffuse T2 hyperintensities in the subcortical and periventricular white matter with no gadolinium enhancing lesions. Three patients showed involvement of pyramidal tracts from motor cortex to the brainstem. Cerebrospinal fluid was normal in all cases. Diagnosis of ALSP was established by biopsy (two cases) and autopsy (two cases). Histopathology showed the presence of neuroaxonal spheroids in all four cases and pigmented glia in three. In the fifth case, diagnosis was established by genetic analysis alone that showed a disease-causing mutation in the colony-stimulating factor 1 receptor (CSF1R) gene. Genetic analysis was done in three patients with available DNA, and identified the disease-causing mutation in all three, including a novel mutation F828S. ALSP may be suspected in adults with rapid to subacute progression of neurological disease when (1) MRI shows corpus callosal atrophy on a background of generalized brain atrophy and diffuse white matter disease without postcontrast enhancement, (2) CSF studies are normal, and (3) studies for systemic inflammatory diseases and specific leukodystrophies are

  2. B-cell populations discriminate between pediatric- and adult-onset multiple sclerosis

    PubMed Central

    Schwarz, Alexander; Balint, Bettina; Korporal-Kuhnke, Mirjam; Jarius, Sven; von Engelhardt, Kathrin; Fürwentsches, Alexandra; Bussmann, Cornelia; Ebinger, Friedrich; Haas, Jürgen

    2016-01-01

    Objective: To comparatively assess the B-cell composition in blood and CSF of patients with pediatric-onset multiple sclerosis (pedMS) and adult-onset multiple sclerosis (adMS). Methods: In this cross-sectional study, we obtained blood and CSF samples from 25 patients with pedMS (8–18 years) and 40 patients with adMS (23–65 years) and blood specimens from 66 controls (1–55 years). By using multicolor flow cytometry, we identified naive, transitional, isotype class-switched memory, nonswitched memory, and double-negative memory B-cell subsets as well as plasmablasts (PB) and terminally differentiated plasma cells (PC). Flow cytometric data were compared to concentrations of B-cell-specific cytokines in serum and CSF as determined by ELISA. Results: Frequencies of circulating naive B-cells decreased with higher age in controls but not in patients with multiple sclerosis (MS). B-cell patterns in CSF differed between pedMS and adMS with an acute relapse: in pedMS-derived CSF samples, high frequencies of nonswitched memory B cells and PB were present, whereas class-switched memory B cells and PC dominated in the CSF of patients with adMS. In pedMS, PB were also elevated in the periphery. Accumulation of PB in the CSF correlated with high intrathecal CXCL-13 levels and augmented intrathecal synthesis of immunoglobulin G and immunoglobulin M. Conclusions: We demonstrate distinct changes in intrathecal B-cell homeostasis in patients with pedMS during active disease, which differ from those in adults by an expansion of plasmablasts in blood and CSF and similarly occur in prototypic autoantibody-driven autoimmune disorders. This emphasizes the particular importance of activated B-lymphocyte subsets for disease progression in the earliest clinical stages of MS. PMID:28053999

  3. Is Adolescent-Onset First-Episode Psychosis Different from Adult Onset?

    ERIC Educational Resources Information Center

    Ballageer, Trevor; Malla, Ashok; Manchanda, Rahul; Takhar, Jatinder; Haricharan, Raj

    2005-01-01

    Objective: To examine whether first-episode psychosis patients with onset during adolescence (ages 15-18) differ significantly from those with young-adult onset (ages 19-30). Method: Consecutive patients presenting with first-episode psychosis (N = 242) were assessed for demographic and illness characteristics such as duration of untreated…

  4. Adult-Onset Antisocial Behavior Trajectories: Associations with Adolescent Family Processes and Emerging Adulthood Functioning

    ERIC Educational Resources Information Center

    Mata, Andrea D.; van Dulmen, Manfred H. M.

    2012-01-01

    Guided by conceptual and empirical work on emerging adulthood, this study investigated the role of closeness to mother and father and behavioral autonomy during adolescence on the development of adult-onset antisocial behavior. Using data from the National Longitudinal Study of Adolescent Health (Add Health), we identified four aggressive…

  5. Parental smoking in pregnancy and the risks of adult-onset hypertension.

    PubMed

    de Jonge, Layla L; Harris, Holly R; Rich-Edwards, Janet W; Willett, Walter C; Forman, Michele R; Jaddoe, Vincent W V; Michels, Karin B

    2013-02-01

    Fetal exposure to parental smoking may lead to developmental adaptations and promote various diseases in later life. This study evaluated the associations of parental smoking during pregnancy with the risk of hypertension in the daughter in adulthood, and assessed whether these associations are explained by birth weight or body weight throughout life. We used data on 33086 participants of the Nurses' Health Study II and the Nurses' Mothers' Cohort. Cox proportional hazards models were used to examine the associations of maternal and paternal smoking during pregnancy with the nurse daughter, with self-reported physician-diagnosed hypertension from 1989 until 2007. Overall, 8575 (25.9%) mothers and 18874 (57.0%) fathers smoked during pregnancy. During follow-up, 7825 incident cases of adult-onset hypertension were reported. Both maternal and paternal smoking of ≥ 15 cigarettes/d during pregnancy were associated with increased risks of hypertension (rate ratio, 1.19; 95% CI, 1.09-1.29; and rate ratio, 1.18; 95% CI, 1.12-1.25, respectively) in the age-adjusted models. Further adjustment for birth weight did not affect the effect estimates appreciably, whereas additional adjustment for body shape and weight until age 18, or current body mass index, attenuated the associations with both maternal and paternal smoking (rate ratio, 1.07; 95% CI, 0.98-1.16; and rate ratio, 1.06; 95% CI, 1.01-1.12, respectively). The associations of parental smoking during pregnancy with the risk of hypertension in the offspring were largely explained by body weight throughout life, suggesting that these associations may not reflect direct intrauterine mechanisms.

  6. Meniere’s disease: Still a mystery disease with difficult differential diagnosis

    PubMed Central

    Vassiliou, A.; Vlastarakos, P. V.; Maragoudakis, P.; Candiloros, D.; Nikolopoulos, T. P.

    2011-01-01

    One hundred and forty-six years after its first description, the differential diagnosis of Meniere’s disease remains very challenging. The aim of the present study is to review the current knowledge on the advantages and disadvantages of the new diagnostic methods for Meniere’s disease. The importance of accurate diagnosis for primary healthcare systems is also discussed. An extensive search of the literature was performed in Medline and other available database sources. Information from electronic links and related books were also included. Controlled clinical studies, prospective cohort studies, retrospective cohort studies, cross-sectional studies, case reports, written guidelines, systematic reviews, and books were selected. The typical clinical triad of symptoms from the vestibular and cochlear systems (recurrent vertigo, fluctuating sensorineural hearing loss and tinnitus) is usually the key for clinical diagnosis. Glycerol dehydration test and electrocochleography are the main diagnostic tests in current practice, while vestibular evoked myogenic potentials may be used in disease staging. Imagine techniques are not specific enough to set alone the diagnosis of Meniere’s disease, although they may be necessary to exclude other pathologies. Recently developed 3D MRI protocols can delineate the perilymphatic/endolymphatic spaces of the inner ear and aid diagnosis. Meniere’s disease is a continuous problem for the patients and affects their quality of life. Taking into account the frequent nature of the disease in certain countries, efforts for reliable diagnosis, prompt referral, and successful management are undoubtedly cost-effective for healthcare systems. PMID:21633608

  7. [The Brill-Zinsser disease still occurs in Croatia: retrospective analysis of 25 hospitalized patients].

    PubMed

    Turcinov, Drago; Kuzman, Ilija; Puljiz, Ivan

    2002-10-01

    The article presents epidemiological, clinical, laboratory and therapeutic characteristics of Brill-Zinsser disease (BZD). A total of 25 cases of BZD were retrospectively analyzed during the period from January 1, 1980 through December 31, 2000, and etiology was confirmed by rickettsial complement-fixation test (CFT). The majority of cases 15 (60%) quoted history of primary attack of epidemic typhus during or after the World War II. During the course of the disease in our patients different organic systems were involved. Aseptic meningitis was verified in 21 (84%) patients, rash in 17 (68%), liver lesion in 14 (56%), pneumonitis in 7 (28%), myopericarditis in 7 (28%) and 5 (20%) had renal lesion. Not a single clinical symptom or finding of disease has a diagnostic particularity. However, long term fever, headache, rash and aseptic meningitis, or information of infestation with lice in childhood, or a history of epidemic typhus should arouse a suspicion of this disease, which still occurs in Croatia.

  8. Adult-onset focal expression of mutated human tau in the hippocampus impairs spatial working memory of rats.

    PubMed

    Mustroph, Martina L; King, Michael A; Klein, Ronald L; Ramirez, Julio J

    2012-07-15

    Tauopathy in the hippocampus is one of the earliest cardinal features of Alzheimer's disease (AD), a condition characterized by progressive memory impairments. In fact, density of tau neurofibrillary tangles (NFTs) in the hippocampus strongly correlates with severity of cognitive impairments in AD. In the present study, we employed a somatic cell gene transfer technique to create a rodent model of tauopathy by injecting a recombinant adeno-associated viral vector with a mutated human tau gene (P301L) into the hippocampus of adult rats. The P301L mutation is causal for frontotemporal dementia with parkinsonism-17 (FTDP-17), but it has been used for studying memory effects characteristic of AD in transgenic mice. To ascertain if P301L-induced mnemonic deficits are persistent, animals were tested for 6 months. It was hypothesized that adult-onset, spatially restricted tau expression in the hippocampus would produce progressive spatial working memory deficits on a learned alternation task. Rats injected with the tau vector exhibited persistent impairments on the hippocampal-dependent task beginning at about 6 weeks post-transduction compared to rats injected with a green fluorescent protein vector. Histological analysis of brains for expression of human tau revealed hyperphosphorylated human tau and NFTs in the hippocampus in experimental animals only. Thus, adult-onset, vector-induced tauopathy spatially restricted to the hippocampus progressively impaired spatial working memory in rats. We conclude that the model faithfully reproduces histological and behavioral findings characteristic of dementing tauopathies. The rapid onset of sustained memory impairment establishes a preclinical model particularly suited to the development of potential tauopathy therapeutics.

  9. [Multi-organ failure as first clinical sign of macrophage activation syndrome in childhood Still's disease].

    PubMed

    López-Sánchez, M; Rubio-López, I; Obeso-González, T; Teja-Barbero, J L; Santidrián-Miguel, J P; Peiro-Callizo, E

    2010-10-01

    Macrophage activation syndrome is a form of secondary haemophagocytic lymphohistiocytosis seen in the context of rheumatic diseases. It is seen most frequently in association with systemic onset juvenile arthritis or childhood Still's disease. Hemophagocytosis is part of a sepsis-like clinical syndrome caused by hypercytokinemia due to a highly stimulated but ineffective immune response. Coagulopathy and hemorrhages, decreased white cell count, elevated levels of aspartate aminotransferase, fever, rash, hepatosplenomegaly and central nervous system dysfunction are some of diagnostic criteria of macrophage activation syndrome, but it is very difficult to diagnose due to the lack of specific clinical signs. We report a 8-year-old child who was admitted to the ICU with lethargy, fever, acute respiratory failure, coagulopathy, metabolic acidosis and multiorgan failure. Septic shock was suspected, but he was diagnosed with macrophage activation syndrome and treated with corticosteroids and intravenous immunoglobulin and later discharged from the ICU.

  10. [Biological treatment of rare inflammatory rheumatic diseases].

    PubMed

    Baslund, Bo

    2008-06-09

    The current status of the use of biological medicine in the treatment of adult onset morbus still, Wegeners granulomatosis and systemic lupus erythematosus (SLE) is reviewed. The need for controlled trials is emphasized. Anti-CD20 treatment for SLE patients with kidney involvement and patients with Wegeners granulomatosis seems promising. Anti-TNF and IL1 receptor antagonist can control disease activity in most patients with adult morbus still.

  11. Clinical Characteristics of Pediatric-Onset and Adult-Onset Multiple Sclerosis in Hispanic Americans.

    PubMed

    Langille, Megan M; Islam, Talat; Burnett, Margaret; Amezcua, Lilyana

    2016-07-01

    Multiple sclerosis can affect pediatric patients. Our aim was to compare characteristics between pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanic Americans. This was a cross-sectional analysis of 363 Hispanic American multiple scleroses cases; demographic and clinical characteristics were analyzed. A total of 110 Hispanic patients presented with multiple sclerosis before age 18 and 253 as adult multiple sclerosis. The most common presenting symptoms for both was optic neuritis. Polyfocal symptoms, seizures, and cognitive symptoms at presentation were more prevalent in pediatric-onset multiple sclerosis (P ≤ .001). Transverse myelitis was more frequent in adult-onset multiple sclerosis (P ≤ .001). Using multivariable analysis, pediatric-onset multiple sclerosis (adjusted odds ratio, 0.3OR 95% confidence interval 0.16-0.71, P = .004) and being US born (adjusted odds ratio, 0.553, 95% confidence interval 0.3-1.03, P = .006) were less likely to have severe ambulatory disability. Results suggest that pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanics have differences that could be important for treatment and prognosis.

  12. The Genetic Link between Parkinson's Disease and the Kynurenine Pathway Is Still Missing

    PubMed Central

    Török, Nóra; Török, Rita; Szolnoki, Zoltán; Somogyvári, Ferenc; Klivényi, Péter; Vécsei, László

    2015-01-01

    Background. There is substantial evidence that the kynurenine pathway (KP) plays a role in the normal physiology of the brain and is involved in the pathology of neurodegenerative disorders such as Huntington's disease and Parkinson's disease (PD). Objective. We set out to investigate the potential roles in PD of single nucleotide polymorphisms (SNPs) from one of the key enzymes of the KP, kynurenine 3-monooxygenase (KMO). Methods. 105 unrelated, clinically definitive PD patients and 131 healthy controls were enrolled to investigate the possible effects of the different alleles of KMO. Fluorescently labeled TaqMan probes were used for allele discrimination. Results. None of the four investigated SNPs proved to be associated with PD or influenced the age at onset of the disease. Conclusions. The genetic link between the KP and PD is still missing. The investigated SNPs presumably do not appear to influence the function of KMO and probably do not contain binding sites for regulatory proteins of relevance in PD. This is the first study to assess the genetic background behind the biochemical alterations of the kynurenine pathway in PD, directing the attention to this previously unexamined field. PMID:25785227

  13. Dengue is still an imported disease in China: a case study in Guangzhou.

    PubMed

    Sang, Shaowei; Chen, Bin; Wu, Haixia; Yang, Zhicong; Di, Biao; Wang, Lihua; Tao, Xiaoyan; Liu, Xiaobo; Liu, Qiyong

    2015-06-01

    Dengue virus and its four serotypes (DENV 1-4) infect approximately 390 million people worldwide each year, with most cases in tropical and subtropical regions. Because of repeated introduction of DENV from epidemic regions and suitable weather conditions, many regions have shifted from hypo-endemicity to hyper-endemicity over recent decades. Since the first dengue outbreak in 1978, it is crucial to understand the current situation in China over nearly 40 years. The purpose of the study was to examine whether dengue in China was endemic or not, which is essential for relevant dengue control and prevention strategy implementation in China. The study, combining epidemiological characteristics of dengue from the disease notification system, phylogenetic and phylogeographic analyses, showed that all four serotypes had been detected in Guangzhou, China, which was dominated by DENV 1-2. The Maximum Likelihood tree analytic results showed that the virus detected in Guangzhou localized in different clades, except of virus of 2002 and 2003 clustered together. There existed the mutual introductions between Guangzhou and Southeast Asia. Most of the viruses were imported from Southeast Asia and the sources of outbreaks in Guangzhou mainly originated from Thailand, Indonesia, and the Philippines. The study indicates that dengue in China still remains as an imported disease, with the possibility of localization.

  14. [Periodontal disease and occlusal trauma: a still debated controversy? A review of the literature].

    PubMed

    Sbordone, L; Bortolaia, C

    2002-03-01

    In the "Glossary of Periodontics Terms" written by the American Academy of Periodontology, the occlusal trauma is defined as "an injury to the attachment apparatus as a result of excessive occlusal forces". Nowadays, the effects of occlusal trauma on tooth support tissues, the onset and the progression of periodontal disease are still debated: many commonplaces have been disproved, but some doubts and not yet clear points remain, even owing to the difficult diagnosis of the presence and the real clinical impact of a traumatic occlusion. Then, ethical reasons prevent researchers from prospective clinical trials. At the beginning of the last century occlusal trauma has been supposed to be an etiologic factor of "alveolar pyorrhea", but several studies attending more strict scientific criteria failed to prove such correlation. On the basis of the bacterial genesis of periodontal disease, researchers started evaluating the possible effects of occlusal discrepancies on incidence, progression and treatment outcomes of periodontitis, but all the results underlined the more relevant role played by micro-organisms. The present review of the literature runs through this controversy again, analysing the most significant studies published.

  15. Non-motor symptoms in patients with adult-onset focal dystonia: Sensory and psychiatric disturbances.

    PubMed

    Conte, Antonella; Berardelli, Isabella; Ferrazzano, Gina; Pasquini, Massimo; Berardelli, Alfredo; Fabbrini, Giovanni

    2016-01-01

    Dystonia is characterized by the presence of involuntary muscle contractions that cause abnormal movements and posture. Adult onset focal dystonia include cervical dystonia, blepharospasm, arm dystonia and laryngeal dystonia. Besides motor manifestations, patients with focal dystonia frequently also display non-motor signs and symptoms. In this paper, we review the evidence of sensory and psychiatric disturbances in adult patients with focal dystonia. Clinical studies and neurophysiological investigations consistently show that the sensory system is involved in dystonia. Several studies have also demonstrated that neuropsychiatric disorders, particularly depression and anxiety, are more frequent in patients with focal dystonia, whereas data on obsessive compulsive disorders are more contrasting.

  16. Adult onset primary focal dystonia of the foot: an orthopaedic intervention.

    PubMed

    Logan, Loretta; Resseque, Barbara; Dontamsetti, Monica Sakshi

    2016-03-30

    A 54-year-old woman presented to a foot centre with a chief symptom of cramping in her toes, which, she believed, was of a secondary cause originating from a bunion. She was treated conservatively; however, she returned a month later as the symptoms had progressed to painful cramping of toes, toe-curling and instability while walking, due to involuntary movement of her toes. It was believed that the patient presented with a rare case of primary adult onset focal foot dystonia. This case report explains dystonia further in detail and delves into the different treatment and management options available today, including the unique orthopaedic intervention provided for this patient.

  17. Adult-onset opsoclonus-myoclonus syndrome due to West Nile Virus treated with intravenous immunoglobulin.

    PubMed

    Hébert, Julien; Armstrong, David; Daneman, Nick; Jain, Jennifer Deborah; Perry, James

    2017-02-01

    A 63-year-old female with no significant past medical history was presented with a 5-day history of progressive opsoclonus-myoclonus, headaches, and fevers. Her workup was significant only for positive West-Nile Virus serum serologies. She received a 2-day course of intravenous immunoglobulin (IvIG). At an 8-week follow up, she had a complete neurological remission. Adult-onset opsoclonus-myoclonus syndrome is a rare condition for which paraneoplastic and infectious causes have been attributed. To our knowledge, this is the first case reported of opsoclonus-myoclonus secondary to West-Nile Virus treated with intravenous immunoglobulin monotherapy.

  18. Adult onset leukodystrophy with neuroaxonal spheroids and demyelinating plaque-like lesions.

    PubMed

    Martinez-Saez, Elena; Shah, Sachit; Costa, Carme; Fleminger, Simon; Connor, Stephen; Bodi, Istvan

    2012-06-01

    Adult onset leukodystrophy with neuroaxonal spheroids is an uncommon cause of dementia. Both hereditary (autosomal dominant) and sporadic cases have been described. A 41-year-old African woman presented with inappropriate behavior and personality change consistent with frontal lobe dysfunction. MRI demonstrated diffuse frontoparietal white matter signal abnormality and volume loss, as well as focal enhancing white matter lesions, while CT scan showed white matter calcifications. She had been gradually deteriorating over the last 5 years, diagnosed as having progressive demyelinating illness. She died of recurrent chest infections. There was no familial history. The brain showed prominent symmetrical white matter changes with greyish discolorization mainly affecting the frontal and parietal lobes, with less involvement of the temporal lobe and only mildly affecting the occipital white matter. Histology revealed deep white matter atrophy with many neuroaxonal spheroids labelled by neurofilament and β-amyloid precursor protein. In addition, scattered inactive demyelinating plaque-like lesions were found in the periventricular areas, brainstem and the cervical spinal cord. This case had typical features of an adult onset leukodystrophy with neuroaxonal spheroids. However, we also demonstrated demyelinating plaque-like lesions, which has not been previously described. The possibility of a demyelinating origin contributing to the changes may be considered in the pathogenesis of this condition.

  19. Genes Interacting with Occupational Exposures to Low Molecular Weight Agents and Irritants on Adult-Onset Asthma in Three European Studies

    PubMed Central

    Rava, Marta; Ahmed, Ismail; Kogevinas, Manolis; Le Moual, Nicole; Bouzigon, Emmanuelle; Curjuric, Ivan; Dizier, Marie-Hélène; Dumas, Orianne; Gonzalez, Juan R.; Imboden, Medea; Mehta, Amar J.; Tubert-Bitter, Pascale; Zock, Jan-Paul; Jarvis, Deborah; Probst-Hensch, Nicole M.; Demenais, Florence; Nadif, Rachel

    2016-01-01

    Background: The biological mechanisms by which cleaning products and disinfectants—an emerging risk factor—affect respiratory health remain incompletely evaluated. Studying genes by environment interactions (G × E) may help identify new genes related to adult-onset asthma. Objectives: We identified interactions between genetic polymorphisms of a large set of genes involved in the response to oxidative stress and occupational exposures to low molecular weight (LMW) agents or irritants on adult-onset asthma. Methods: Our data came from three large European cohorts: Epidemiological Family-based Study of the Genetics and Environment of Asthma (EGEA), Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults (SAPALDIA), and European Community Respiratory Health Survey in Adults (ECRHS). A candidate pathway–based strategy identified 163 genes involved in the response to oxidative stress and potentially related to exposures to LMW agents/irritants. Occupational exposures were evaluated using an asthma job-exposure matrix and job-specific questionnaires for cleaners and healthcare workers. Logistic regression models were used to detect G × E interactions, adjusted for age, sex, and population ancestry, in 2,599 adults (mean age, 47 years; 60% women, 36% exposed, 18% asthmatics). p-Values were corrected for multiple comparisons. Results: Ever exposure to LMW agents/irritants was associated with current adult-onset asthma [OR = 1.28 (95% CI: 1.04, 1.58)]. Eight single nucleotide polymorphism (SNP) by exposure interactions at five loci were found at p < 0.005: PLA2G4A (rs932476, chromosome 1), near PLA2R1 (rs2667026, chromosome 2), near RELA (rs931127, rs7949980, chromosome 11), PRKD1 (rs1958980, rs11847351, rs1958987, chromosome 14), and PRKCA (rs6504453, chromosome 17). Results were consistent across the three studies and after accounting for smoking. Conclusions: Using a pathway-based selection process, we identified novel genes potentially involved

  20. [Sinusoidal obstruction disease (SOS), previous hepatic venoocclusive disease (VOD)--still serious complication after hematopoietic stem cell transplantation].

    PubMed

    Gozdzik, Jolanta; Krasowska-Kwiecień, Aleksandra; Wedrychowicz, Anna

    2008-01-01

    Hepatic venocclusive disease (VOD) lastly named sinusoidal obstruction syndrome (SOS) is a serious toxicity associated with high dose therapy used to prepare patients for stem cell transplantation. A sizable proportion of patients who develop VOD/SOS die. It is clear that injury to endothelial cells and hepatocytes in zone 3 of the liver acinus is the initial event in the pathogenesis of VOD/SOS. Although clinical presentation and diagnostic criteria are well known, the cause of VOD/SOS, its prevention and treatment remain still unclear. Currently treatment of VOD/SOS has largely consisted of supportive measures designed to maintain intravascular volume and decrease interstitial edema. Other treatments used with various measures of success have included substitution of antitrombine and glutamine or aggressive fibrinolitic and antithrombotic therapy. Despite these treatments, the outcome remains fairly dismal.

  1. The Phospholipase D2 Knock Out Mouse Has Ectopic Purkinje Cells and Suffers from Early Adult-Onset Anosmia

    PubMed Central

    Zhang, Qifeng; Smethurst, Elizabeth; Segonds-Pichon, Anne; Schrewe, Heinrich; Wakelam, Michael J. O.

    2016-01-01

    Phospholipase D2 (PLD2) is an enzyme that produces phosphatidic acid (PA), a lipid messenger molecule involved in a number of cellular events including, through its membrane curvature properties, endocytosis. The PLD2 knock out (PLD2KO) mouse has been previously reported to be protected from insult in a model of Alzheimer's disease. We have further analysed a PLD2KO mouse using mass spectrophotometry of its lipids and found significant differences in PA species throughout its brain. We have examined the expression pattern of PLD2 which allowed us to define which region of the brain to analyse for defect, notably PLD2 was not detected in glial-rich regions. The expression pattern lead us to specifically examine the mitral cells of olfactory bulbs, the Cornus Amonis (CA) regions of the hippocampus and the Purkinje cells of the cerebellum. We find that the change to longer PA species correlates with subtle architectural defect in the cerebellum, exemplified by ectopic Purkinje cells and an adult-onset deficit of olfaction. These observations draw parallels to defects in the reelin heterozygote as well as the effect of high fat diet on olfaction. PMID:27658289

  2. Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia linked CSF1R mutation: Report of four Korean cases.

    PubMed

    Kim, Eun-Joo; Shin, Jin-Hong; Lee, Jeong Hee; Kim, Jong Hun; Na, Duk L; Suh, Yeon-Lim; Hwang, Sun Jae; Lee, Jae-Hyeok; Lee, Young Min; Shin, Myung-Jun; Lee, Myung Jun; Kim, Seong-Jang; Yoon, Uicheul; Park, Do Youn; Jung, Dae Soo; Ahn, Jae Woo; Sung, Suk; Huh, Gi Yeong

    2015-02-15

    We describe detailed clinical, biochemical, neuroimaging and neuropathological features in adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), encompassing hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD), linked to colony-stimulating factor 1 receptor (CSF1R) mutations in four Korean cases. Clinical, biochemical, neuroimaging and neuropathological findings were obtained by direct evaluation and from previous medical records. The genetic analysis of the CSF1R gene was done in two autopsy-confirmed ALSP cases and two cases where ALSP was suspected based on the clinical and neuroimaging characteristics. We identified two known mutations: c.2342C>T (p.A781V) in one autopsy-proven HDLS and clinically ALSP-suspected case and c.2345G>A (p.R782H) in another autopsy-proven POLD case. We also found a novel mutation (c.2296A>G; p.M766V) in a patient presenting with hand tremor, stuttering and hesitant speech, and abnormal behavior whose father died from a possible diagnosis of spinocerebellar ataxia. To the best of our knowledge, this is the first documented ALSP-linked CSF1R mutation in Korea and supports the suggestion that HDLS and POLD, with pathological characteristics that are somewhat different but which are caused by CSF1R mutations, are the same spectrum of disease, ALSP.

  3. Adult onset leukodystrophy with neuroaxonal spheroids and pigmented glia: report of a family, historical perspective, and review of the literature.

    PubMed

    Marotti, Jonathan D; Tobias, Sharon; Fratkin, Jonathan D; Powers, James M; Rhodes, C Harker

    2004-06-01

    We present a two-generation family consisting of a father and two daughters, who had an adult-onset leukodystrophy characterized by widespread destruction of cerebral white matter with neuroaxonal spheroids. The mode of inheritance appears to be autosomal dominant. All three patients presented with a variety of motor and cognitive symptoms, including frontal lobe signs, 4-7 years before death. Each followed a chronic course until death at ages 39, 46, and 51. At autopsy, the white matter loss was widespread but most prominent in the cerebrum with descending corticospinal tract degeneration and relative sparing of subcortical U-fibers. Pigmented glial cells were present, most of which appear to be macrophages, but inconstantly Prussian blue-positive. This disease is consistent with published reports of hereditary diffuse leukoencephalopathy with spheroids (HDLS). However, a review of the literature and a personal review of the neuropathology of the original case of the pigmentary type of orthochromatic leukodystrophy (POLD) reveal overlapping clinical and neuropathologic features between these two previously distinct entities, suggesting a common pathogenetic and perhaps etiological relationship between the two.

  4. Congenital encephalomyopathy and adult-onset myopathy and diabetes mellitus: Different phenotypic associations of a new heteroplasmic mtDNA tRNA glutamic acid mutation

    SciTech Connect

    Hanna, M.G.; Nelson, I.; Sweeney, M.G.; Cooper, J.M.; Watkins, P.J.; Morgan-Hughes, J.A.; Harding, A.E.

    1995-05-01

    We report the clinical, biochemical, and molecular genetic findings in a family with an unusual mitochondrial disease phenotype harboring a novel mtDNA tRNA glutamic acid mutation at position 14709. The proband and his sister presented with congenital myopathy and mental retardation and subsequently developed cerebellar ataxia. Other family members had either adult-onset diabetes mellitus with muscle weakness or adult-onset diabetes mellitus alone. Ragged-red and cytochrome c oxidase (COX)-negative fibers were present in muscle biopsies. Biochemical studies of muscle mitochondria showed reduced complex I and IV activities. The mtDNA mutation was heteroplasmic in blood and muscle in all matrilineal relatives analyzed. Primary myoblast, but not fibroblast, cultures containing high proportions of mutant mtDNA exhibited impaired mitochondrial translation. These observations indicate that mtDNA tRNA point mutations should be considered in the differential diagnosis of congenital myopathy. In addition they illustrate the diversity of phenotypes associated with this mutation in the same family and further highlight the association between mtDNA mutations and diabetes mellitus. 43 refs., 4 figs., 1 tab.

  5. Vapor, Dust and Smoke Exposure in relation to adult-onset asthma and chronic respiratory symptoms: The Singapore Chinese Health Study

    PubMed Central

    LeVan, Tricia D.; Koh, Woon-Puay; Lee, Hin-Peng; Koh, David; Yu, Mimi C.; London, Stephanie J.

    2006-01-01

    Occupational factors contribute to a significant fraction of respiratory disease and symptoms. We evaluated the role of occupational exposures on asthma, chronic bronchitis, and respiratory symptoms in a population-based cohort, the Singapore Chinese Health Study. History of occupations, occupational exposures, and respiratory conditions were collected by interviews with 52,325 Singaporeans born 1918–1953. Exposure to dusts, from cotton, wood, metal, mineral and/or asbestos, was associated with non-chronic cough and/or phlegm (OR = 1.19, 95% CI = 1.08, 1.30), chronic bronchitis (OR = 1.26, 95% CI = 1.01, 1.57) and adult-onset asthma (OR = 1.14, 95% CI = 1.00, 1.30). Cotton dust was the major component contributing to respiratory symptoms. Vapor exposure, from chemical solvents, dyes, cooling oils, paints, wood preservatives and/or pesticides, was associated with non-chronic cough or phlegm (OR = 1.14, 95% CI = 1.03, 1.27), chronic dry cough (OR = 1.55, 95% CI = 1.19, 2.01) and adult-onset asthma (OR = 1.34, 95% CI = 1.15, 1.56). Chemical solvents, cooling oils and pesticides were the major sources contributing to respiratory symptoms. These data support the role of occupational exposures in the etiology of respiratory illness in a population-based cohort in Singapore with a low prevalence of atopic illness. PMID:16707657

  6. A common gene for juvenile and adult-onset primary open-angle glaucomas confined on chromosome 1q

    SciTech Connect

    Morissette, J.; Plante, M.; Raymond, V.

    1995-06-01

    Primary open-angle glaucoma (POAG), which causes progressive loss of the visual fields, was subdivided into two groups according to age at onset: (1) chronic open-angle glaucoma (COAG) diagnosed after 40 years and (2) juvenile open-angle glaucoma (JOAG) diagnosed between 3 years of age and early adulthood. A JOAG gene (GLC1A) was recently mapped to chromosome 1q. We studied 142 members of a huge multigenerational French Canadian family affected with autosomal dominant POAG. Either JOAG or COAG was diagnosed with ocular hypertension (OHT), which may lead to POAG. To localize a common disease gene that might be responsible for both glaucoma subsets, we performed linkage analysis considering JOAG and COAG under the same phenotypic category. JOAG/COAG was tightly linked to seven microsatellite markers on chromosome 1q23-q25; a maximum lod score of 6.62 was obtained with AF-M278ye5. To refine the disease locus, we exploited a recombination mapping strategy based on a unique founder effect. The same characteristic haplotype, composed of 14 markers spanning 12 cM between loci D1S196 and D1S212, was recognized in all persons affected by JOAG, COAG, or OHT, but it did not occur in unaffected spouses and in normal family members >35 years of age, except for three obligatory carriers. Key combination events confined the disease region within a 9-cM interval between loci D1S445 and D1S416/D1S480. These observations demonstrate that the GLC1A gene is responsible for both adult-onset and juvenile glaucomas and suggest that the JOAG and COAG categories within this family may be part of a clinical continuum artificially divided at age 40 years. 49 refs., 4 figs., 2 tabs.

  7. [A case of adult-onset type II citrullinemia in an elderly patient].

    PubMed

    Kitaoka, Mayuko; Sakaeda, Hiroshi; Suzuki, Mika; Miki, Toshifumi; Saito, Junko; Chikamori, Masayasu; Tomita, Hideharu; Ichikawa, Hiromoto; Yoshimoto, Kaori; Takamatsu, Masahiro; Okada, Mitsuo; Aono, Rei; Enzan, Hideaki; Miyamoto, Takako

    2013-03-01

    A 72-year-old man presented with consciousness disturbance. The results of brain magnetic resonance imaging and cerebrospinal fluid examination were normal, but triphasic waves were noted on electroencephalography. His plasma ammonia level was elevated due to which encephalopathy secondary to hyperammonemia was suspected. However, his liver function was normal, and no evidence of cirrhosis or portal-systemic shunt was noted. The patient's medical history revealed that he had a tendency to excessively consume pulse products since childhood, and an amino acid analysis showed elevation of citrulline and arginine levels. Thus, we diagnosed the patient with an extremely rare case of adult-onset type II citrullinemia, which was triggered by cessation of the intake of pulse foods (soybeans and peanuts) due to dental problems.

  8. Adult-onset intradural spinal teratoma in the lumbar spine: A case report.

    PubMed

    Arai, Yasuhisa; Takahashi, Masaki; Takeda, Koutarou; Shitoto, Katsuo

    2000-12-01

    Intradural spinal teratoma is a very rare tumour that can be associated with dysraphic defects. We report a case of adult-onset intradural spinal teratoma in the lumbar spine. The patient was a 54-year-old female who had chief complaints of a gait disturbance. X-rays showed an enlargement of the interpedicular distance at L3/L4 and spina bifida distal to L4. MRI showed a spindle-shaped tumour between L2 and L5. We performed laminotomy using an ultrasonic surgical knife. Pathological diagnosis of the resected tumour was matured teratoma. The diagnosis of matured teratoma was made because the tumour had no epithelium and a layered structure including prostate tissue, matured fat, cartilage and sweat gland.

  9. Occupational exposures and uncontrolled adult-onset asthma in the European Community Respiratory Health Survey II.

    PubMed

    Le Moual, Nicole; Carsin, Anne-Elie; Siroux, Valérie; Radon, Katja; Norback, Dan; Torén, Kjell; Olivieri, Mario; Urrutia, Isabel; Cazzoletti, Lucia; Jacquemin, Bénédicte; Benke, Geza; Kromhout, Hans; Mirabelli, Maria C; Mehta, Amar J; Schlünssen, Vivi; Sigsgaard, Torben; Blanc, Paul D; Kogevinas, Manolis; Antó, Josep M; Zock, Jan-Paul

    2014-02-01

    Occupational exposure is a well-recognised modifiable risk factor for asthma, but the relationship between occupational exposure and asthma control has not been studied. We aimed to study this association among working-age adults from the European Community Respiratory Health Survey (ECRHS). Data were available for 7077 participants (mean age 43 years, 45% never-smokers, 5867 without asthma and 1210 with current asthma). Associations between occupational exposure to specific asthmagens and asthma control status (33% with uncontrolled asthma, based on the Global Initiative for Asthma guidelines) were evaluated using logistic and multinomial regressions, adjusted for age, sex and smoking status, with study areas included as a random effect. Statistically significant positive associations were observed between uncontrolled adult-onset asthma and both past 12-month and 10-year exposure to any occupational asthmagens (OR (95% CI) 1.6 (1.0-2.40) and 1.7 (1.2-2.5), respectively); high (1.7 (1.0-2.8) and 1.9 (1.3-2.9), respectively) and low (1.6 (1.0-2.7) and 1.8 (1.2-2.7), respectively) molecular weight agents; and cleaning agents (2.0 (1.1-3.6) and 2.3 (1.4-3.6), respectively), with stronger associations for long-term exposures. These associations were mainly explained by the exacerbation domain of asthma control and no associations were observed between asthmagens and partly controlled asthma. These findings suggest that occupational exposure to asthmagens is associated with uncontrolled adult-onset asthma. Occupational risk factors should be quickly identified to prevent uncontrolled asthma.

  10. With current gene markers, presymptomatic diagnosis of heritable disease is still a family affair

    SciTech Connect

    Not Available

    1987-09-04

    In the last four years, genes or genetic markers have been identified for a host of disorders including Huntington's disease, cystic fibrosis, Duchenne muscular dystrophy, polycystic kidney disease, bipolar depressive disorder, retinoblastoma, Alzheimer's disease, and schizophrenia. Such discoveries have made it possible to diagnose in utero some 30 genetic diseases during the first trimester of pregnancy. Yet, while these newly discovered gene markers may be revolutionizing prenatal and presymptomatic diagnosis, they are in many respects halfway technology. Such was the opinion of several speakers at a conference sponsored by the American Medical Association in Washington, DC. At the conference, entitled DNA Probes in the Practice of Medicine, geneticists emphasized that gene markers - stretches of DNA that are usually inherited in tandem with a disease gene - are usually not sufficient for presymptomatic diagnosis of genetic disease in an individual.

  11. From NAFLD to Cardiovascular Disease. Is it (Still) the Metabolic Syndrome?

    PubMed Central

    MUNTEANU, MIHAI ALEXANDRU; MIRCEA, PETRU ADRIAN

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in developed countries. The incidence of NAFLD in the general population is 30–38% deppending on the geographical area and the diagnostic method used. NAFLD is considered to be the liver manifestation of the metabolic syndrome. A better understanding of the natural evolution would have practical consequences related mainly to the need of early and aggressive diagnosis, active monitoring and therapeutic solutions. Cardiovascular disease appears to be the main cause of death in these patients. The mechanisms linking NAFLD with cardiovascular disease are not fully understood yet, but attention was focused primarily on insulin resistance. The visceral adipose tissue, the epicardial adipose tissue, the systemic inflammatory response syndrome, the lipid profile, the procoagulants factors, the oxidative stress, and type 2 diabetes mellitus, they all might play a role in the link between NAFLD and cardiovascular disease. Currently, there isn’t any medication specifically recommended for the treatment of NAFLD. Although the mechanisms underlying the association between NAFLD and cardiovascular disease are not fully known, attention must be paid to this association, given that these patients are more likely to die due to heart disease rather than liver disease. PMID:26528002

  12. Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia Caused by a Novel R782G Mutation in CSF1R

    PubMed Central

    Foulds, Nicola; Pengelly, Reuben J.; Hammans, Simon R.; Nicoll, James A. R.; Ellison, David W.; Ditchfield, Adam; Beck, Sarah; Ennis, Sarah

    2015-01-01

    We report a new family with autosomal dominant inheritance of a late onset rapidly progressive leukodystrophy in which exome sequencing has revealed a novel mutation p.R782G in the Colony-Stimulating Factor 1 Receptor gene (CSF1R). Neuropathology of two affected family members showed cerebral white matter degeneration with axonal swellings and pigmented macrophages. The few recently reported families with CSF1R mutations had been previously labelled “hereditary diffuse leukencephalopathy with axonal spheroids” (HDLS) and “pigmentary orthochromatic leukodystrophy” (POLD), disorders which now appear to form a disease continuum. The term “adult-onset leukoencephalopathy with axonal spheroids and pigmented glia” (ALSP) has been proposed to encompass this spectrum. As CSF1R regulates microglia this mutation implies that dysregulation of microglia is the primary cause of the disease. PMID:25975230

  13. Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia Caused by a Novel R782G Mutation in CSF1R.

    PubMed

    Foulds, Nicola; Pengelly, Reuben J; Hammans, Simon R; Nicoll, James A R; Ellison, David W; Ditchfield, Adam; Beck, Sarah; Ennis, Sarah

    2015-05-15

    We report a new family with autosomal dominant inheritance of a late onset rapidly progressive leukodystrophy in which exome sequencing has revealed a novel mutation p.R782G in the Colony-Stimulating Factor 1 Receptor gene (CSF1R). Neuropathology of two affected family members showed cerebral white matter degeneration with axonal swellings and pigmented macrophages. The few recently reported families with CSF1R mutations had been previously labelled "hereditary diffuse leukencephalopathy with axonal spheroids" (HDLS) and "pigmentary orthochromatic leukodystrophy" (POLD), disorders which now appear to form a disease continuum. The term "adult-onset leukoencephalopathy with axonal spheroids and pigmented glia" (ALSP) has been proposed to encompass this spectrum. As CSF1R regulates microglia this mutation implies that dysregulation of microglia is the primary cause of the disease.

  14. Care of the injured worldwide: trauma still the neglected disease of modern society.

    PubMed

    Sakran, Joseph V; Greer, Sarah E; Werlin, Evan; McCunn, Maureen

    2012-09-15

    Traditionally, surgical diseases including emergency and injury care have garnered less attention and support internationally when compared to other medical specialties. Over the past decade however, healthcare professionals have increasingly advocated for the need to address the global burden of non-communicable diseases. Surgical disease, including traumatic injury, is among the top causes of death and disability worldwide and the subsequent economic burden is substantial, falling disproportionately on low- and middle-income countries (LMICs). The future of global health in these regions depends on a redirection of attention to diseases managed within surgical, anesthesia and emergency specialties. Increasing awareness of these disparities, as well as increasing focus in the realms of policy and advocacy, is crucial. While the barriers to providing quality trauma and emergency care worldwide are not insurmountable, we must work together across disciplines and across boundaries in order to negotiate change and reduce the global burden of surgical disease.

  15. Does cyclophosphamide still have a role in the treatment of severe inflammatory eye disease?

    PubMed

    Wakefield, Denis

    2014-08-01

    Cyclophosphamide is a highly effective immunosuppressive drug that has proven efficacy in the treatment of patients with severe inflammatory eye disease. It has the advantage of being able to be used either orally or intravenously, has a potent steroid-sparing effect, and is effective in inducing disease remission. The major limitations to the use of this alkylating agent are its frequent side effects. With the increasing availability of alternate forms of therapy it is time to review the therapeutic regimen for cyclophosphamide use in patients with inflammatory eye disease.

  16. [Curative treatment of Alzheimer's disease is still missing--is amyloid plaque hypothesis the wrong starting point?].

    PubMed

    Tanila, Heikki

    2015-01-01

    For more than a quarter century, the research of and drug development for Alzheimer's diseases have been governed by the amyloid plaque hypothesis, whereby deranged metabolism of the amyloid precursor protein leads to the formation of extracellular amyloid plaques, which in turn causes the activation of microglial cells, destruction of neurons and a progressive memory disease. The ending of three extensive clinical trials in disappointment has raised the question whether the amyloid plaque hypothesis is the correct starting point in the development of curative treatment for Alzheimer's disease at all. Two commencing new trials with patients that are still symptomless will be the final challenge for the hypothesis.

  17. [Scurvy, an old disease still in the news: two case reports].

    PubMed

    Pailhous, S; Lamoureux, S; Caietta, E; Bosdure, E; Chambost, H; Chabrol, B; Bresson, V

    2015-01-01

    Scurvy is the clinical manifestation of a deficiency in vitamin C, which is present in fresh fruits and vegetables. It is historically linked to the era of great maritime expeditions. Manifestations are misleading in children, in contrast with adults: bone disease and hemorrhagic syndrome are the earliest and most frequent manifestations due to a collagen biosynthesis defect. Scurvy is an old, potentially fatal disease but is easily curable with ascorbic acid. It can be prevented with vitamin C treatment in pediatric populations with unusual eating habits. We describe two cases of pediatric scurvy in two 7-year-old boys who had dietary restrictions stemming from developmental disorders.

  18. Juvenile recurrent respiratory papillomatosis: still a mystery disease with difficult management.

    PubMed

    Stamataki, Sofia; Nikolopoulos, Thomas P; Korres, Stavros; Felekis, Dimitrios; Tzangaroulakis, Antonios; Ferekidis, Eleftherios

    2007-02-01

    Juvenile recurrent respiratory papillomatosis (RRP) is the most common benign neoplastic disease of the larynx in children and adolescents and has a significant impact on patients and the health care system with a cost ranging from $60,000 to $470,000 per patient. The aim of this paper is to review the current literature on RRP and summarize the recent advances. RRP is caused by human papillomavirus (HPV; mainly by types 6 and 11). Patients suffer from wart-like growths in the aerodigestive tract. The course of the disease is unpredictable. Although spontaneous remission is possible, pulmonary spread and malignant transformation have been reported. Surgical excision, including new methods like the microdebrider, aims to secure an adequate airway and improve and maintain an acceptable voice. Repeated recurrences are common and thus overenthusiastic attempts to eradicate the disease may cause serious complications. When papillomas recur, old and new adjuvant methods may be tried. In addition, recent advances in immune system research may allow us to improve our treatment modalities and prevention strategies. A new vaccine is under trial to prevent HPV infection in women; the strongest risk factor for juvenile RRP is a maternal history of genital warts (transmitted from mother to child during delivery). Better understanding of the etiology of the disease and the knowledge of all available therapies is crucial for the best management of the affected patients.

  19. mHealth Interventions to Counter Noncommunicable Diseases in Developing Countries: Still an Uncertain Promise.

    PubMed

    Beratarrechea, Andrea; Moyano, Daniela; Irazola, Vilma; Rubinstein, Adolfo

    2017-02-01

    mHealth constitutes a promise for health care delivery in low- and middle-income countries (LMICs) where health care systems are unprepared to combat the threat of noncommunicable diseases (NCDs). This article assesses the impact of mHealth on NCD outcomes in LMICs. A systematic review identified controlled studies evaluating mHealth interventions that addressed NCDs in LMICs. From the 1274 abstracts retrieved, 108 articles were selected for full text review and 20 randomized controlled trials were included from 14 LMICs. One-way SMS was the most commonly used mobile function to deliver reminders, health education, and information. mHealth interventions in LMICs have positive but modest effects on chronic disease outcomes.

  20. Early Pathogenesis in the Adult-Onset Neurodegenerative Disease Amyotrophic Lateral Sclerosis

    PubMed Central

    van Zundert, Brigitte; Izaurieta, Pamela; Fritz, Elsa; Alvarez, Francisco J.

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a devastating paralytic disorder caused by dysfunction and degeneration of motor neurons starting in adulthood. Most of our knowledge about the pathophysiological mechanisms of ALS comes from transgenic mice models that emulate a subgroup of familial ALS cases (FALS), with mutations in the gene encoding superoxide dismutase (SOD1). In the more than 15 years since these mice were generated, a large number of abnormal cellular mechanisms underlying motor neuron degeneration have been identified, but to date this effort has led to few improvements in therapy, and no cure. Here, we consider that this surfeit of mechanisms is best interpreted by current insights that suggest a very early initiation of pathology in motor neurons, followed by a diversity of secondary cascades and compensatory mechanisms that mask symptoms for decades, until trauma and/or aging overloads their protective function. This view thus posits that adultonset ALS is the consequence of processes initiated during early development. In fact, motor neurons in neonatal mutant SOD mice display important alterations in their intrinsic electrical properties, synaptic inputs and morphology that are accompanied by subtle behavioral abnormalities. We consider evidence that human mutant SOD1 protein in neonatal hSOD1G93A mice instigates motor neuron degeneration by increasing persistent sodium currents and excitability, in turn altering synaptic circuits that control excessive motor neuron firing and leads to excitotoxicity. We also discuss how therapies that are aimed at suppressing abnormal neuronal activity might effectively mitigate or prevent the onset of irreversible neuronal damage in adulthood. PMID:22740507

  1. Adult-onset hypogonadism: evaluation and role of testosterone replacement therapy

    PubMed Central

    Davidiuk, Andrew J.

    2016-01-01

    Testosterone deficiency (TD) has become a growing concern in the field of men’s sexual health, with an increasing number of men presenting for evaluation of this condition. Given the increasing demand for testosterone replacement therapy (TRT), a panel of experts met in August of 2015 to discuss the treatment of men who present for evaluation in the setting of low or normal gonadotropin levels and the associated signs and symptoms of hypogonadism. This constellation of factors can be associated with elements of both primary and secondary hypogonadism. Because this syndrome commonly occurs in men who are middle-aged and older, it was termed adult-onset hypogonadism (AOH). AOH can be defined by the following elements: low levels of testosterone, associated signs and symptoms of hypogonadism, and low or normal gonadotropin levels. Although there are significant benefits of TRT for patients with AOH, candidates also need to understand the potential risks. Patients undergoing TRT will need to be monitored regularly because there are potential complications that can develop with long-term use. This review is aimed at providing a deeper understanding of AOH, discussing the benefits and risks of TRT, and outlining each modality of TRT in use for AOH. PMID:28078213

  2. Effects of Aging and Adult-Onset Hearing Loss on Cortical Auditory Regions

    PubMed Central

    Cardin, Velia

    2016-01-01

    Hearing loss is a common feature in human aging. It has been argued that dysfunctions in central processing are important contributing factors to hearing loss during older age. Aging also has well documented consequences for neural structure and function, but it is not clear how these effects interact with those that arise as a consequence of hearing loss. This paper reviews the effects of aging and adult-onset hearing loss in the structure and function of cortical auditory regions. The evidence reviewed suggests that aging and hearing loss result in atrophy of cortical auditory regions and stronger engagement of networks involved in the detection of salient events, adaptive control and re-allocation of attention. These cortical mechanisms are engaged during listening in effortful conditions in normal hearing individuals. Therefore, as a consequence of aging and hearing loss, all listening becomes effortful and cognitive load is constantly high, reducing the amount of available cognitive resources. This constant effortful listening and reduced cognitive spare capacity could be what accelerates cognitive decline in older adults with hearing loss. PMID:27242405

  3. A search for the primary abnormality in adult-onset type II citrullinemia

    SciTech Connect

    Kobayashi, Keiko; Shaheen, Nazma; Saheki, Takeyori ); Kumashiro, Ryukichi; Tanikawa, Kyuichi ); O'Brien, W.E.; Beaudet, A.L. )

    1993-11-01

    Deficiency of argininosuccinate synthetase (ASS) causes citrullinemia in human beings. Type II citrullinemia is found in most patients with adult-onset citrullinemia in Japan, and ASS deficiency is found specifically in the liver. Previous studies have shown that the decrease of hepatic ASS activity is caused by a decrease in enzyme protein with normal kinetic properties and that there were no apparent abnormalities in the amount, translational activity, and gross structure of hepatic ASS mRNA. In the present work, the authors show by sequencing analysis that there was no mutation in the ASS mRNA from two patients with type II citrullinemia. The authors also report RFLP analysis of a consanguineous family with type II citrullinemia, by using three DNA polymorphisms located within the ASS gene locus. In spite of having consanguineous parents, the patient was not a homozygous haplotype for the ASS gene. The RFLP analysis of 16 affected patients from consanguineous parents showed that 5 of 16 patients had the heterozygous pattern for one of the three DNA probes and that the frequency of the heterozygous haplotype was not different from the control frequency. These results suggest that the primary defect of type II citrullinemia is not within the ASS gene locus. 29 refs., 1 fig., 3 tabs.

  4. Adult-onset NREM parasomnia with hypnopompic hallucinatory pain: a case report.

    PubMed

    Mantoan, Laura; Eriksson, Sofia H; Nisbet, Angus P; Walker, Matthew C

    2013-02-01

    We report the case of a 43-year-old woman presenting with nocturnal episodes of pain and screaming during sleep starting at age 30. There was no childhood or family history of parasomnia. The events had gradually become more frequent over the years, occurring in the first half of the night within 2 h of sleep onset. There were no triggers, and she had partial amnesia for the events. A diagnosis of adult-onset sleep terrors was made on clinical grounds and supported polysomnographically. Seizures and periodic limb movements were excluded as triggering factors. There was some mild sleep disordered breathing (predominantly non-desaturating hypopnea with a propensity for REM sleep of debatable significance). Imaging of the brain and spine and neurophysiological investigations ruled out lesions, entrapments, or neuropathies as possible causes of pain. Treatment (clonazepam, paroxetine, or gabapentin) was poorly tolerated and made no difference to the nocturnal episodes, while trazodone worsened them. This is the first report of hypnopompic psychic pain in association with a NREM parasomnia. We hypothesize that the pain may represent a sensory hallucination analogous to the more commonly recognized visual NREM parasomnia-associated hypnopompic visual hallucinations and that, as such, it may arise during arousal of the sensory neocortex as confabulatory response.

  5. Irritable bowel syndrome: A disease still searching for pathogenesis, diagnosis and therapy

    PubMed Central

    Bellini, Massimo; Gambaccini, Dario; Stasi, Cristina; Urbano, Maria Teresa; Marchi, Santino; Usai-Satta, Paolo

    2014-01-01

    Irritable bowel syndrome (IBS) is the most frequently diagnosed functional gastrointestinal disorder in primary and secondary care. It is characterised by abdominal discomfort, pain and changes in bowel habits that can have a serious impact on the patient’s quality of life. The pathophysiology of IBS is not yet completely clear. Genetic, immune, environmental, inflammatory, neurological and psychological factors, in addition to visceral hypersensitivity, can all play an important role, one that most likely involves the complex interactions between the gut and the brain (gut-brain axis). The diagnosis of IBS can only be made on the basis of the symptoms of the Rome III criteria. Because the probability of organic disease in patients fulfilling the IBS criteria is very low, a careful medical history is critical and should pay particular attention to the possible comorbidities. Nevertheless, the severity of the patient’s symptoms or concerns sometimes compels the physician to perform useless and/or expensive diagnostic tests, transforming IBS into a diagnosis of exclusion. The presence of alarming symptoms (fever, weight loss, rectal bleeding, significant changes in blood chemistry), the presence of palpable abdominal masses, any recent onset of symptoms in patient aged over 50 years, the presence of symptoms at night, and a familial history of celiac disease, colorectal cancer and/or inflammatory bowel diseases all warrant investigation. Treatment strategies are based on the nature and severity of the symptoms, the degree of functional impairment of the bowel habits, and the presence of psychosocial disorders. This review examines and discusses the pathophysiological aspects and the diagnostic and therapeutic approaches available for patients with symptoms possibly related to IBS, pointing out controversial issues and the strengths and weaknesses of the current knowledge. PMID:25083055

  6. Chronic disease and the shifting focus of public health: is prevention still a political lightweight?

    PubMed

    Mayes, Rick; Oliver, Thomas R

    2012-04-01

    Why is it so politically difficult to obtain government investment in public health initiatives that are aimed at addressing chronic disease? This article examines the structural disadvantage faced by those who advocate for public health policies and practices to reduce chronic disease related to people's unhealthy lifestyles and physical environments. It identifies common features that make it difficult to establish and maintain initiatives to prevent or reduce costly illness and physical suffering: (1) public health benefits are generally dispersed and delayed; (2) benefactors of public health are generally unknown and taken for granted; (3) the costs of many public health initiatives are concentrated and generate opposition from those who would pay them; and (4) public health often clashes with moral values or social norms. The article concludes by discussing the importance of a new paradigm, "health in all policies," that targets the enormous health and economic burdens associated with chronic conditions and asserts a need for new policies, practices, and participation beyond the confines of traditional public health agencies and services.

  7. Vitamin C in human health and disease is still a mystery? An overview.

    PubMed

    Naidu, K Akhilender

    2003-08-21

    this vitamin/nutraceutical in human biology and health is still a mystery in view of many beneficial claims and controversies.

  8. Relapsing macrophage activating syndrome in a 15-year-old girl with Still's disease: a case report

    PubMed Central

    2009-01-01

    Introduction Macrophage activating syndrome is a severe, potentially life-threatening condition that may accompany Still's disease. It is characterized by fever, hepatosplenomegaly, lymphadenopathy, severe cytopenia, serious liver dysfunction, coagulopathy and neurologic involvement. The principal treatment for patients with this syndrome includes etoposide 150 mg/2 M twice a week for two weeks, dexamethasone 10 mg/2 M for two weeks and cyclosporine 3 mg/kg to 5 mg/kg for a longer period. Cases of relapse of macrophage activating syndrome are relatively rare. Case presentation We describe the case of a 15-year-old Iraqi girl with Still's disease who developed macrophage activating syndrome with acute respiratory distress syndrome that required resuscitation and mechanical ventilation. Following intensive treatment, including high dose steroids and cyclosporine, the patient improved significantly. Two weeks after cyclosporine was discontinued, however, she was readmitted with an acute relapse of macrophage activating syndrome manifested by spiking fever, arthralgias, maculopapular rash and leukocytosis. This time the patient recovered following the reintroduction of treatment with cyclosporine and the addition of mycophenolate mofetil (Cellcept). Conclusion We believe that cyclosporine is a cornerstone for the treatment of Still's disease. We recommend continuing this medication for several weeks following the patient's clinical recovery in order to prevent macrophage activating syndrome relapses. PMID:20062775

  9. Mast Cells are Important Modifiers of Autoimmune Disease: With so Much Evidence, Why is There Still Controversy?

    PubMed

    Brown, Melissa A; Hatfield, Julianne K

    2012-01-01

    There is abundant evidence that mast cells are active participants in events that mediate tissue damage in autoimmune disease. Disease-associated increases in mast cell numbers accompanied by mast cell degranulation and elaboration of numerous mast cell mediators at sites of inflammation are commonly observed in many human autoimmune diseases including multiple sclerosis, rheumatoid arthritis, and bullous pemphigoid. In animal models, treatment with mast cell stabilizing drugs or mast cell ablation can result in diminished disease. A variety of receptors including those engaged by antibody, complement, pathogens, and intrinsic danger signals are implicated in mast cell activation in disease. Similar to their role as first responders in infection settings, mast cells likely orchestrate early recruitment of immune cells, including neutrophils, to the sites of autoimmune destruction. This co-localization promotes cellular crosstalk and activation and results in the amplification of the local inflammatory response thereby promoting and sustaining tissue damage. Despite the evidence, there is still a debate regarding the relative role of mast cells in these processes. However, by definition, mast cells can only act as accessory cells to the self-reactive T and/or antibody driven autoimmune responses. Thus, when evaluating mast cell involvement using existing and somewhat imperfect animal models of disease, their importance is sometimes obscured. However, these potent immune cells are undoubtedly major contributors to autoimmunity and should be considered as important targets for therapeutic disease intervention.

  10. [Adult-onset ataxia-telangiectasia. A clinical and therapeutic observation].

    PubMed

    Gazulla, J; Benavente, I; Sarasa Barrio, M

    2006-10-01

    A case of adult-onset ataxia-telangiectasia (AT) is presented, with debut at the age of 18 years and survival into the fourth decade. The clinical picture included cerebellar ataxia, distal weakness and hypopalesthesia in the lower limbs, oculomotor apraxia, dysarthria, and conjunctival telangiectasiae. Carcinoembrionic antigen was raised in plasma. MR imaging showed atrophy of the cerebellar vermis and thinning of the spinal cord. Deficiencies of gamma-aminobutyric acid and glutamate have been found in the cerebellar cortex in a case of AT. These were attributed to the loss of Purkinje cells and granule cells. In spite of some ataxias having improved with the gabaergic drugs gabapentin and tiagabine, the administration of gabapentin, acetazolamide and a placebo, did not benefit this patient. Pregabalin, 225 mg/day, ameliorated the ataxia unexpectedly, with further improvement after the addition of tiagabine. The authors suggest that the beneficial effect observed might have been due, either to the higher affinity of pregabalin towards alpha2-delta, a subtype of the alpha2-delta subunit which forms part of the voltage-gated calcium channel; either to the profusion of this subtype in the Purkinje cell layer, or to its larger capacity to let calcium into the neuron; or to the combination of these. These differences with gabapentin could explain the higher power of pregabalin in the stimulation of the cerebellar structures, thus justifying the improvement of ataxia in this case of AT. A synergistic effect with pregabalin is proposed as the cause of the improvement obtained with the addition of tiagabine.

  11. Adult onset asthma and interaction between genes and active tobacco smoking: The GABRIEL consortium

    PubMed Central

    Postma, D. S.; Moffatt, M. F.; Jarvis, D.; Ramasamy, A.; Wjst, M.; Omenaas, E. R.; Bouzigon, E.; Demenais, F.; Nadif, R.; Siroux, V.; Polonikov, A. V.; Solodilova, M.; Ivanov, V. P.; Curjuric, I.; Imboden, M.; Kumar, A.; Probst-Hensch, N.; Ogorodova, L. M.; Puzyrev, V. P.; Bragina, E. Yu; Freidin, M. B.; Nolte, I. M.; Farrall, A. M.; Cookson, W. O. C. M.; Strachan, D. P.; Koppelman, G. H.; Boezen, H. M.

    2017-01-01

    Background Genome-wide association studies have identified novel genetic associations for asthma, but without taking into account the role of active tobacco smoking. This study aimed to identify novel genes that interact with ever active tobacco smoking in adult onset asthma. Methods We performed a genome-wide interaction analysis in six studies participating in the GABRIEL consortium following two meta-analyses approaches based on 1) the overall interaction effect and 2) the genetic effect in subjects with and without smoking exposure. We performed a discovery meta-analysis including 4,057 subjects of European descent and replicated our findings in an independent cohort (LifeLines Cohort Study), including 12,475 subjects. Results First approach: 50 SNPs were selected based on an overall interaction effect at p<10−4. The most pronounced interaction effect was observed for rs9969775 on chromosome 9 (discovery meta-analysis: ORint = 0.50, p = 7.63*10−5, replication: ORint = 0.65, p = 0.02). Second approach: 35 SNPs were selected based on the overall genetic effect in exposed subjects (p <10−4). The most pronounced genetic effect was observed for rs5011804 on chromosome 12 (discovery meta-analysis ORint = 1.50, p = 1.21*10−4; replication: ORint = 1.40, p = 0.03). Conclusions Using two genome-wide interaction approaches, we identified novel polymorphisms in non-annotated intergenic regions on chromosomes 9 and 12, that showed suggestive evidence for interaction with active tobacco smoking in the onset of adult asthma. PMID:28253294

  12. Hereditary leukoencephalopathy with axonal spheroids: a spectrum of phenotypes from CNS vasculitis to parkinsonism in an adult onset leukodystrophy series

    PubMed Central

    Jaunmuktane, Zane; Sheerin, Una-Marie; Phadke, Rahul; Brandner, Sebastian; Milonas, Ionnis; Dean, Andrew; Bajaj, Nin; McNicholas, Nuala; Costello, Daniel; Cronin, Simon; McGuigan, Chris; Rossor, Martin; Fox, Nick; Murphy, Elaine; Chataway, Jeremy; Houlden, Henry

    2016-01-01

    Background Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) is a hereditary, adult onset leukodystrophy which is characterised by the presence of axonal loss, axonal spheroids and variably present pigmented macrophages on pathological examination. It most frequently presents in adulthood with dementia and personality change. HDLS has recently been found to be caused by mutations in the colony stimulating factor-1 receptor (CSF1R) gene. Methods In this study, we sequenced the CSF1R gene in a cohort of 48 patients from the UK, Greece and Ireland with adult onset leukodystrophy of unknown cause. Results Five pathogenic mutations were found, including three novel mutations. The presentations ranged from suspected central nervous system (CNS) vasculitis to extrapyramidal to cognitive phenotypes. The case histories and imaging are presented here, in addition to neuropathological findings from two cases with novel mutations. Conclusion We estimate that CSF1R mutations account for 10% of idiopathic adult onset leukodystrophies and that genetic testing for CSF1R mutations is essential in adult patients presenting with undefined CNS vasculitis or a leukodystrophy with prominent neuropsychiatric signs or dementia. PMID:25935893

  13. Adult Still's Disease

    MedlinePlus

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  14. Intrathecal antibody production against Epstein-Barr and other neurotropic viruses in pediatric and adult onset multiple sclerosis.

    PubMed

    Pohl, Daniela; Rostasy, Kevin; Jacobi, Christian; Lange, Peter; Nau, Roland; Krone, Bernd; Hanefeld, Folker

    2010-02-01

    Epstein-Barr virus (EBV) has been implicated in the pathogenesis of multiple sclerosis (MS). Recent reports proposed an increased EBV-targeted humoral immune response in MS, which appears to be more pronounced in pediatric patients. However, little is known about the CNS-derived antibody production against EBV in patients with MS. The objective of this study was to assess the frequency and intensity of intrathecal antibody production against EBV as compared to other neurotropic viruses in pediatric and adult onset MS. In cohorts of 43 childhood, 50 adult onset MS patients, 20 children and 12 adults with other CNS disorders, paired CSF and serum samples were studied. Frequency and intensity of intrathecal antibody production against EBV as compared to measles, rubella, varicella zoster (VZV) and herpes simplex virus (HSV) were analyzed by determination of virus-specific CSF-to-serum Antibody Indices (AI). Intrathecally synthesized EBV antibodies were detectable in 26% pediatric and 10% adult onset MS patients, compared to frequencies ranging in both groups from 10 to 60% for the other viruses. Median AIs for EBV were lower than those for all other viruses, with more than twofold higher median AI for measles, rubella and VZV. The EBV-targeted humoral immune response in the CNS is only part of the intrathecal polyspecific antibody production in MS, directed against various neurotropic viruses. Our results do not rule out the possibility that EBV is involved in the pathogenesis of MS by triggering diverse cellular immune mechanisms, but they argue against a direct pathogenic role of EBV-targeted humoral immune response within the CNS.

  15. Obesity-related abnormalities couple environmental triggers with genetic susceptibility in adult-onset T1D.

    PubMed

    Nguyen, K Hoa; Ande, Sudharsana R; Mishra, Suresh

    2016-01-29

    The incidence of adult-onset T1D in low-risk non-HLA type has increased several folds, whereas the contemporaneous incidence in high-risk HLA-type remains stable. Various factors behind this selective increase in T1D in young adults remain unclear. Obesity and its associated abnormalities appear to be an important determinant; however, the underlying mechanism involved is not understood. Recently, we have developed two novel transgenic obese mice models, Mito-Ob and m-Mito-Ob, by expressing a pleiotropic protein prohibitin (PHB) and a phospho mutant form of PHB (Y114F-PHB or m-PHB) from the aP2 gene promoter, respectively. Both mice models develop obesity in a sex-neutral manner, independent of diet; but obesity associated chronic low-grade inflammation and insulin resistance in a male sex-specific manner. Interestingly, on a high fat diet (HFD) only male m-Mito-Ob mice displayed marked mononuclear cell infiltration in pancreas and developed insulitis that mimic adult-onset T1D. Male Mito-Ob mice that share the metabolic phenotype of male m-Mito-Ob mice, and female m-Mito-Ob that harbor m-PHB similar to male m-Mito-Ob mice, did not develop insulitis. Thus, insulitis development in male m-Mito-Ob in response to HFD requires both, obesity-related abnormalities and m-PHB. Collectively, this data provides a proof-of-concept that obesity-associated abnormalities couple environmental triggers with genetic susceptibility in adult-onset T1D and reveals PHB as a potential susceptibility gene for T1D.

  16. Solitary, adult-onset, intraosseous myofibroma of the finger: report of a case and review of literature.

    PubMed

    Ma, Yihong; Siegal, Gene P; Wei, Shi

    2015-09-01

    Myofibroma is a rare benign neoplasm of myofibroblastic origin. It typically occurs in the skin and subcutaneous tissues of the head and neck in infants and young children as multicentric lesions known as infantile myofibromatosis. Intraosseous myofibromas are very rare and are typically destructive lesions that predominantly affect craniofacial bones in the setting of myofibromatosis. Solitary, intraosseous myofibromas in adults are exceedingly rare. Herein, we report a myofibroma involving the middle phalanx of the right index finger in a 58-year-old man who presented with a pathologic fracture. Twelve other cases of adult-onset, intraosseous myofibroma were compiled from the English language literature and integrated with this report.

  17. Multistage still

    SciTech Connect

    Franco, J.; Saravia, L.R.; Esteban, S.

    1999-07-01

    A new design for a passive atmospheric multiple effect solar distillation unit is proposed. Inclined glass surfaces with a 4{degree} slope and placed one over the other in an isolated box are used. The cold salty water is fed only in the upper stage and flows along each surface, falling from one stage to the next by gravity and reaching finally a heated tray at the bottom. Vapor condenses below each surface and produces the water evaporation in the upper side of the same surface. For heating the bottom of the still a simple 1.3 m{sup 2} solar collector with a fresnel type concentrator is used. The collector is separated from the still and heat is transported from one unit to the other using a 4 kg aluminium slab, which is placed in the absorber and it is heated at a temperature about 350 C. The slab is then placed below the tray in an isolated box. Four slabs are used and they are changed periodically when the slab temperature drops below approximately 180 C. Several slabs can be used for heat storage if several collectors are built, allowing the use of the still during some hours at night, improving its daily productivity. Experiments have been performed with a prototype and the results are discussed and compared with the values obtained with another electrically heated prototype.

  18. GC-MS metabolomic analysis reveals significant alterations in cerebellar metabolic physiology in a mouse model of adult onset hypothyroidism.

    PubMed

    Constantinou, Caterina; Chrysanthopoulos, Panagiotis K; Margarity, Marigoula; Klapa, Maria I

    2011-02-04

    Although adult-onset hypothyroidism (AOH) has been connected to neural activity alterations, including movement, behavioral, and mental dysfunctions, the underlying changes in brain metabolic physiology have not been investigated in a systemic and systematic way. The current knowledge remains fragmented, referring to different experimental setups and recovered from various brain regions. In this study, we developed and applied a gas chromatography-mass spectrometry (GC-MS) metabolomics protocol to obtain a holistic view of the cerebellar metabolic physiology in a Balb/cJ mouse model of prolonged adult-onset hypothyroidism induced by a 64-day treatment with 1% potassium perchlorate in the drinking water of the animals. The high-throughput analysis enabled the correlation between multiple parallel-occurring metabolic phenomena; some have been previously related to AOH, while others implicated new pathways, designating new directions for further research. Specifically, an overall decline in the metabolic activity of the hypothyroid compared to the euthyroid cerebellum was observed, characteristically manifested in energy metabolism, glutamate/glutamine metabolism, osmolytic/antioxidant capacity, and protein/lipid synthesis. These alterations provide strong evidence that the mammalian cerebellum is metabolically responsive to AOH. In light of the cerebellum core functions and its increasingly recognized role in neurocognition, these findings further support the known phenotypic manifestations of AOH into movement and cognitive dysfunctions.

  19. Mutations in zebrafish lrp2 result in adult-onset ocular pathogenesis that models myopia and other risk factors for glaucoma.

    PubMed

    Veth, Kerry N; Willer, Jason R; Collery, Ross F; Gray, Matthew P; Willer, Gregory B; Wagner, Daniel S; Mullins, Mary C; Udvadia, Ava J; Smith, Richard S; John, Simon W M; Gregg, Ronald G; Link, Brian A

    2011-02-01

    The glaucomas comprise a genetically complex group of retinal neuropathies that typically occur late in life and are characterized by progressive pathology of the optic nerve head and degeneration of retinal ganglion cells. In addition to age and family history, other significant risk factors for glaucoma include elevated intraocular pressure (IOP) and myopia. The complexity of glaucoma has made it difficult to model in animals, but also challenging to identify responsible genes. We have used zebrafish to identify a genetically complex, recessive mutant that shows risk factors for glaucoma including adult onset severe myopia, elevated IOP, and progressive retinal ganglion cell pathology. Positional cloning and analysis of a non-complementing allele indicated that non-sense mutations in low density lipoprotein receptor-related protein 2 (lrp2) underlie the mutant phenotype. Lrp2, previously named Megalin, functions as an endocytic receptor for a wide-variety of bioactive molecules including Sonic hedgehog, bone morphogenic protein 4, retinol-binding protein, vitamin D-binding protein, and apolipoprotein E, among others. Detailed phenotype analyses indicated that as lrp2 mutant fish age, many individuals--but not all--develop high IOP and severe myopia with obviously enlarged eye globes. This results in retinal stretch and prolonged stress to retinal ganglion cells, which ultimately show signs of pathogenesis. Our studies implicate altered Lrp2-mediated homeostasis as important for myopia and other risk factors for glaucoma in humans and establish a new genetic model for further study of phenotypes associated with this disease.

  20. Mutations in Zebrafish lrp2 Result in Adult-Onset Ocular Pathogenesis That Models Myopia and Other Risk Factors for Glaucoma

    PubMed Central

    Veth, Kerry N.; Willer, Jason R.; Collery, Ross F.; Gray, Matthew P.; Willer, Gregory B.; Wagner, Daniel S.; Mullins, Mary C.; Udvadia, Ava J.; Smith, Richard S.; John, Simon W. M.; Gregg, Ronald G.; Link, Brian A.

    2011-01-01

    The glaucomas comprise a genetically complex group of retinal neuropathies that typically occur late in life and are characterized by progressive pathology of the optic nerve head and degeneration of retinal ganglion cells. In addition to age and family history, other significant risk factors for glaucoma include elevated intraocular pressure (IOP) and myopia. The complexity of glaucoma has made it difficult to model in animals, but also challenging to identify responsible genes. We have used zebrafish to identify a genetically complex, recessive mutant that shows risk factors for glaucoma including adult onset severe myopia, elevated IOP, and progressive retinal ganglion cell pathology. Positional cloning and analysis of a non-complementing allele indicated that non-sense mutations in low density lipoprotein receptor-related protein 2 (lrp2) underlie the mutant phenotype. Lrp2, previously named Megalin, functions as an endocytic receptor for a wide-variety of bioactive molecules including Sonic hedgehog, Bone morphogenic protein 4, retinol-binding protein, vitamin D-binding protein, and apolipoprotein E, among others. Detailed phenotype analyses indicated that as lrp2 mutant fish age, many individuals—but not all—develop high IOP and severe myopia with obviously enlarged eye globes. This results in retinal stretch and prolonged stress to retinal ganglion cells, which ultimately show signs of pathogenesis. Our studies implicate altered Lrp2-mediated homeostasis as important for myopia and other risk factors for glaucoma in humans and establish a new genetic model for further study of phenotypes associated with this disease. PMID:21379331

  1. Maturity of judgement in decision making for predictive testing for nontreatable adult-onset neurogenetic conditions: a case against predictive testing of minors.

    PubMed

    Richards, F H

    2006-11-01

    International guidelines developed to minimize harm from predictive testing for adult-onset, nontreatable neurogenetic conditions such as Huntington disease (HD) state that such testing should not be available to minors. Some authors have proposed that predictive testing for these conditions should be available to minors at the request of parents and/or of younger adolescents themselves. They highlight the lack of empirical evidence that predictive testing of minors causes harm and suggest that refusing to test minors may be detrimental. The current study focuses on the context of predictive test requests by adolescents younger than 18 years, and presents arguments and evidence that the risk of potential harm from testing such young people is sufficiently high to justify continued caution in this area. A study based on a model of psychosocial maturity found that the 3 factors involved in maturity of judgement in decision making - responsibility, temperance and perspective - continue to develop into late adolescence. There is also evidence that the prefrontal areas of the brain, which are involved in executive functions such as decision making, are not fully developed until early adulthood. Combined with evidence of adverse long-term effects, from research with adults who have undergone predictive testing, these findings constitute grounds for retaining a minimum age of 18 years for predictive testing for nontreatable conditions. Further research on assessment of maturity will assist with reaching a consensus on this issue.

  2. Molecular basis of adult-onset and chronic G sub M2 gangliosidoses in patients of Ashkenazi Jewish origin: Substitution of serine for glycine at position 269 of the. alpha. -subunit of. beta. -hexosaminidase

    SciTech Connect

    Paw, B.H.; Kaback, M.M.; Neufeld, E.F. )

    1989-04-01

    Chronic and adult-onset G{sub M2} gangliosidoses are neurological disorders caused by marked deficiency of the A isoenzyme of {beta}-hexosaminidase; they occur in the Ashkenazi Jewish population, though less frequently than classic (infantile) Tay-Sachs disease. Earlier biosynthetic studies had identified a defective {alpha}-subunit that failed to associate with the {beta}-subunit. The authors have now found a guanosine to adenosine transition at the 3{prime} end of exon 7, which causes substitution of serine for glycine at position 269 of the {alpha}-subunit. An RNase protection assay was used to localize the mutation to a segment of mRNA from fibroblasts of a patient with the adult-onset disorder. That segment of mRNA (after reverse transcription) and a corresponding segment of genomic DNA were amplified by the polymerase chain reaction and sequenced by the dideoxy method. The sequence analysis, together with an assay based on the loss of a ScrFI restriction site, showed that the patient was a compound heterozygote who had inherited the 269 (Gly {yields} Ser) mutation from his father and an allelic null mutation from his mother. The 269 (Gly {yields} Ser) mutation, in compound heterozygosity with a presumed null allele, was also found in fetal fibroblasts with an association-defective phenotype and in cells from five patients with chronic G{sub M2} gangliosidosis.

  3. A Case of Adult-Onset Acute Rheumatic Fever With Long-Lasting Atrioventricular Block Requiring Permanent Pacemaker Implantation.

    PubMed

    Oba, Yusuke; Watanabe, Hiroaki; Nishimura, Yoshioki; Ueno, Shuichi; Nagashima, Takao; Imai, Yasushi; Shimpo, Masahisa; Kario, Kazuomi

    2015-01-01

    A 45-year-old hypertensive Japanese woman presented with epigastric pain on inspiration, fever, complete atrioventricular block and polyarthritis. Her antistreptolysin O levels were markedly elevated. A diagnosis of rheumatic fever was made according to the modified Jones criteria. She was prescribed loxoprofen sodium, which was partially effective for her extracardiac clinical symptoms. However, she had syncope due to complete atrioventricular block with asystole longer than 10 seconds. Consequently, we implanted a permanent pacemaker. Although we prescribed prednisolone, the efficacy of which was limited for the patient's conduction disturbance, the complete atrioventricular block persisted. In our systematic review of 12 similar cases, the duration of complete heart block was always transient and there was no case requiring a permanent pacemaker. We thus encountered a very rare case of adult-onset acute rheumatic fever with persistent complete atrioventricular block necessitating permanent pacemaker implantation.

  4. Autosomal recessive cerebellar ataxia of adult onset due to STUB1 mutations.

    PubMed

    Depondt, Chantal; Donatello, Simona; Simonis, Nicolas; Rai, Myriam; van Heurck, Roxane; Abramowicz, Marc; D'Hooghe, Marc; Pandolfo, Massimo

    2014-05-13

    Autosomal recessive ataxias affect about 1 person in 20,000. Friedreich ataxia accounts for one-third of the cases in Caucasians; the others are due to a growing list of very rare molecular defects, including mild forms of metabolic diseases. In nearly 50%, the genetic cause remains undetermined.

  5. Distinct Muscle Biopsy Findings in Genetically Defined Adult-Onset Motor Neuron Disorders.

    PubMed

    Jokela, Manu; Huovinen, Sanna; Raheem, Olayinka; Lindfors, Mikaela; Palmio, Johanna; Penttilä, Sini; Udd, Bjarne

    2016-01-01

    The objective of this study was to characterize and compare muscle histopathological findings in 3 different genetic motor neuron disorders. We retrospectively re-assessed muscle biopsy findings in 23 patients with autosomal dominant lower motor neuron disease caused by p.G66V mutation in CHCHD10 (SMAJ), 10 X-linked spinal and bulbar muscular atrophy (SBMA) and 11 autosomal dominant c9orf72-mutated amyotrophic lateral sclerosis (c9ALS) patients. Distinct large fiber type grouping consisting of non-atrophic type IIA muscle fibers were 100% specific for the late-onset spinal muscular atrophies (SMAJ and SBMA) and were never observed in c9ALS. Common, but less specific findings included small groups of highly atrophic rounded type IIA fibers in SMAJ/SBMA, whereas in c9ALS, small group atrophies consisting of small-caliber angular fibers involving both fiber types were more characteristic. We also show that in the 2 slowly progressive motor neuron disorders (SMAJ and SBMA) the initial neurogenic features are often confused with considerable secondary "myopathic" changes at later disease stages, such as rimmed vacuoles, myofibrillar aggregates and numerous fibers reactive for fetal myosin heavy chain (dMyHC) antibodies. Based on our findings, muscle biopsy may be valuable in the diagnostic work-up of suspected motor neuron disorders in order to avoid a false ALS diagnosis in patients without clear findings of upper motor neuron lesions.

  6. Distinct Muscle Biopsy Findings in Genetically Defined Adult-Onset Motor Neuron Disorders

    PubMed Central

    Jokela, Manu; Huovinen, Sanna; Raheem, Olayinka; Lindfors, Mikaela; Palmio, Johanna; Penttilä, Sini; Udd, Bjarne

    2016-01-01

    The objective of this study was to characterize and compare muscle histopathological findings in 3 different genetic motor neuron disorders. We retrospectively re-assessed muscle biopsy findings in 23 patients with autosomal dominant lower motor neuron disease caused by p.G66V mutation in CHCHD10 (SMAJ), 10 X-linked spinal and bulbar muscular atrophy (SBMA) and 11 autosomal dominant c9orf72-mutated amyotrophic lateral sclerosis (c9ALS) patients. Distinct large fiber type grouping consisting of non-atrophic type IIA muscle fibers were 100% specific for the late-onset spinal muscular atrophies (SMAJ and SBMA) and were never observed in c9ALS. Common, but less specific findings included small groups of highly atrophic rounded type IIA fibers in SMAJ/SBMA, whereas in c9ALS, small group atrophies consisting of small-caliber angular fibers involving both fiber types were more characteristic. We also show that in the 2 slowly progressive motor neuron disorders (SMAJ and SBMA) the initial neurogenic features are often confused with considerable secondary “myopathic” changes at later disease stages, such as rimmed vacuoles, myofibrillar aggregates and numerous fibers reactive for fetal myosin heavy chain (dMyHC) antibodies. Based on our findings, muscle biopsy may be valuable in the diagnostic work-up of suspected motor neuron disorders in order to avoid a false ALS diagnosis in patients without clear findings of upper motor neuron lesions. PMID:26999347

  7. Sex-specific associations of low birth weight with adult-onset diabetes and measures of glucose homeostasis: Brazilian Longitudinal Study of Adult Health

    PubMed Central

    Yarmolinsky, James; Mueller, Noel T; Duncan, Bruce B; Chor, Dóra; Bensenor, Isabela M; Griep, Rosane H; Appel, Lawrence J; Barreto, Sandhi M; Schmidt, Maria Inês

    2016-01-01

    Emerging evidence suggests sex differences in the early origins of adult metabolic disease, but this has been little investigated in developing countries. We investigated sex-specific associations between low birth weight (LBW; <2.5 kg) and adult-onset diabetes in 12,525 participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Diabetes was defined by self-reported information and laboratory measurements. In confounder-adjusted analyses, LBW (vs. 2.5–4 kg) was associated with higher prevalence of diabetes in women (Prevalence Ratio (PR) 1.54, 95% CI: 1.32–1.79), not in men (PR 1.06, 95% CI: 0.91–1.25; Pheterogeneity = 0.003). The association was stronger among participants with maternal diabetes (PR 1.60, 95% CI: 1.35–1.91), than those without (PR 1.15, 95% CI: 0.99–1.32; Pheterogeneity = 0.03). When jointly stratified by sex and maternal diabetes, the association was observed for women with (PR 1.77, 95% CI: 1.37–2.29) and without (PR 1.45, 95% CI: 1.20–1.75) maternal diabetes. In contrast, in men, LBW was associated with diabetes in participants with maternal diabetes (PR 1.45, 95% CI: 1.15–1.83), but not in those without (PR 0.92, 95% CI: 0.74–1.14). These sex-specific findings extended to continuous measures of glucose homeostasis. LBW was associated with higher diabetes prevalence in Brazilian women, and in men with maternal diabetes, suggesting sex-specific intrauterine effects on adult metabolic health. PMID:27845438

  8. Changing Paradigms in Detection of Dysplasia and Management of Patients With Inflammatory Bowel Disease: Is Colectomy Still Necessary?

    PubMed

    Velayos, Fernando; Kathpalia, Priya; Finlayson, Emily

    2017-02-01

    This review chronicles the evolution of dysplasia detection and management in inflammatory bowel disease since 1925, the year the first case report of colitis-related colorectal cancer was published. We conclude that colorectal cancer prevention and dysplasia management for patients with inflammatory bowel disease has changed since this first case report, from somewhat hopeless to hopeful.

  9. Adult-onset demyelinating neuropathy associated with FBLN5 gene mutation.

    PubMed

    Cheng, Si; Lv, He; Zhang, Wei; Wang, Zhaoxia; Shi, Xin; Liang, Wei; Yuan, Yun

    2017-03-23

    Rare forms of autosomal-dominant Charcot-Marie-Tooth disease (AD-CMT) may be associated with mutations in Fibulin-5 (FBLN5) as AD-CMT is genetically heterogeneous. Here, we report the first pathological study of an Asian family. The proband was a 46-year-old man with slowly progressive distal numbness and weakness for 12 years. He had a history of diabetes mellitus for 12 years. His mother was 81 years old and had mild polyneuropathy. His 16-year-old daughter was asymptomatic. The nerve conduction velocities (NCVs) and compound muscular action potential (CMAP) amplitudes were moderately to severely reduced in the proband, and moderately reduced in his daughter and mother. A sensory response could not be elicited in the proband and was moderately to severely decreased in the daughter and mother. Nerve ultrasound indicated a general enlargement of the peripheral nerves in the proband, daughter, and mother. A sural nerve biopsy from the proband demonstrated a pronounced depletion of myelinated fibers, thin myelinated fibers, and onion-bulb formations. A reported heterozygous mutation of c.1117C>T in FBLN5 was identified in the proband, mother, and daughter. These findings confirm a novel subtype of AD-CMT 1 due to a mutation in the FBLN5 gene.
.

  10. Adult-onset type 1 diabetes patients display decreased IGRP-specific Tr1 cells in blood.

    PubMed

    Chujo, Daisuke; Nguyen, Thien-Son; Foucat, Emile; Blankenship, Derek; Banchereau, Jacques; Nepom, Gerald T; Chaussabel, Damien; Ueno, Hideki

    2015-12-01

    The breakdown of immune tolerance against islet antigens causes type 1 diabetes (T1D). The antigens associated with adult-onset T1D (AT1D) remain largely undefined. It is possible that AT1D patients display a unique type of CD4(+) T cells specific for a certain islet antigen. Here we analyzed the cytokine production profiles of CD4(+) helper T (Th) cells that are specific for three islet antigens; GAD65, preproinsulin, and IGRP in patients with AT1D, juvenile-onset T1D (JT1D), and age-, gender- and human leukocyte antigen (HLA)-matched control adults. While IGRP-specific Th cells in AT1D patients were dominantly Th1 cells, IGRP-specific Th cells in control adults and JT1D patients were dominantly Th2 and T regulatory type 1 (Tr1) cells. Notably, the frequency of IGRP-specific Tr1 cells was significantly lower in AT1D patients than in control adults and JT1D patients. In conclusion, our study suggests that IGRP-specific Th cells play a unique pathogenic role in AT1D.

  11. Adult-onset presentation of a hyperornithinemia-hyperammonemia-homocitrullinuria patient without prior history of neurological complications.

    PubMed

    Tezcan, Kamer; Louie, Kristal T; Qu, Yong; Velasquez, Jorge; Zaldivar, Frank; Rioseco-Camacho, Natalia; Camacho, José Angel

    2012-01-01

    The Hyperornithinemia-Hyperammonemia-Homocitrullinuria (HHH) syndrome is a disorder of the urea cycle and ornithine degradation pathway caused by mutations in the mitochondrial ornithine transporter, ORNT1 (SLC25A15). In general, the majority of patients with HHH syndrome come to medical attention during infancy or early school years with symptoms such as learning disabilities, changes in cognitive development, spasticity, or liver dysfunction. In this report, we describe a 35-year-old male of Indian descent who was diagnosed with HHH syndrome after he presented to the emergency room with gastroenteritis, disorientation, and slurred speech. Molecular analysis revealed that this patient was heterozygous for two ORNT1 mutations, p.[Gly220Arg(+)Arg275X] (c.[658G>A(+)823C>T]) that had been previously reported in homozygous probands who presented during the first year of life. Cellular studies revealed that the ORNT1 p.Gly220Arg mutation was nonfunctional but targeted to the mitochondria. Given that this patient was a successful college graduate on a vegetarian diet without a prior history of learning or neurological impairment, additional factors such as gene redundancy, environmental, and epigenetic factors may have contributed to the delay in onset of presentation and lack of any previous symptoms. To the best of our knowledge, this is the first reported case of an adult-onset HHH syndrome presentation without a prior history of neurological or cognitive deficiency.

  12. Rituximab Treatment for PR3-ANCA-Positive Membranoproliferative Glomerulonephritis Associated with Adult-Onset Periodic Fever Syndrome

    PubMed Central

    Hamano, Yoshitomo; Yoshizawa, Hiromichi; Sugase, Taro; Miki, Takuya; Ohtani, Naoko; Hanawa, Shiho; Takeshima, Eri; Morishita, Yoshiyuki; Saito, Osamu; Takemoto, Fumi; Muto, Shigeaki; Yumura, Wako; Kusano, Eiji

    2012-01-01

    We report the case of a 36-year-old Japanese woman with nephrotic syndrome due to membranoproliferative glomerulonephritis (MPGN) Type I diagnosed after a 5-year history of periodic fever syndrome (PFS). Hypocomplementemia and elevation of anti-proteinase 3 anti-neutrophil cytoplasmic autoantibody (PR3-ANCA) were observed. HIV, and hepatitis B and C serology were negative. Nephrotic syndrome and periodic fever did not respond to oral steroid and intravenous steroid pulse therapies combined with cyclosporine, dipyridamole, warfarin and losartan. We tried immunotherapy using rituximab, a human-mouse chimeric monoclonal antibody directed against the CD20 antigen on mature B cells. This therapeutic approach led to improvement of renal function and remission of nephrotic syndrome and hypocomplementemia. However, it did not have a beneficial effect on periodic fever. Suspecting adult-onset hereditary PFS, we analyzed her genetic alteration of MEFV and TNFRSF1A genes. A rare genotype in intron 6 of TNFRSF1A was revealed. The etiological relationship between periodic fever and MPGN is discussed. Rituximab is a hopeful choice of induction therapy for refractory MPGN. PMID:23197963

  13. Snippets From the Past: Cohort Analysis of Disease Rates—Another Piece in a Seemingly Still Incomplete Puzzle

    PubMed Central

    Morabia, Alfredo

    2014-01-01

    For almost a century, epidemiologists have stratified age-specific disease rates by year of birth to better understand the distribution of a disease in a population and its evolution across time. In the present article, I review the contributions of John Brownlee, Kristian Feyer Andvord, and Wade Hampton Frost and, to accentuate the similarities of their approaches, redraw their original graphs of age-specific death rates of tuberculosis organized either by year of death or year of birth. In addition, this article reports on an apparently universally forgotten publication in the American Journal of Hygiene published in 1929, which both upsets the conventional history of the earliest reports of disease rates stratified by birth cohorts and challenges the theory that Frost discovered cohort analysis independently and gave it its name. PMID:24920785

  14. Adult-onset cerebello-brainstem dominant form of X-linked adrenoleukodystrophy presenting as multiple system atrophy: Case report and literature review

    PubMed Central

    Ogaki, Kotaro; Koga, Shunsuke; Aoki, Naoya; Lin, Wenlang; Suzuki, Kinuko; Ross, Owen A.; Dickson, Dennis W.

    2015-01-01

    X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder and is caused by ABCD1 mutations. A cerebello-brainstem dominant form that mainly involves the cerebellum and brainstem is summarized in a review of the literature, with autopsy confirmed cases exceedingly rare. We report a 69-year-old white man who was diagnosed with this rare disorder and describe neuropathologic, ultrastructural and genetic analyses. He did not have adrenal insufficiency or a family history of X-ALD or Addison’s disease. His initial symptom was temporary loss of eyesight at age 34 years. His major symptoms were chronic and progressive gait disorder, weakness in his lower extremities, and spasticity, as well as autonomic failure and cerebellar ataxia suggesting possible multiple system atrophy (MSA). He also had seizures, hearing loss, and sensory disturbances. His brain MRI showed no obvious atrophy or significant white matter pathology in cerebrum, brainstem or cerebellum. He died at age 69 years with a diagnosis of multiple system atrophy. Microscopic analysis showed mild, patchy myelin rarefaction with perivascular clusters of PAS-positive, CD68-positive macrophages in the white matter most prominent in the cerebellum and occipital lobe, but also affecting optic tract and internal capsule. Electron microscopy of cerebellar white matter showed cleft-like trilamellar cytoplasmic inclusions in macrophages typical of X-ALD, which prompted genetic analysis that revealed a novel ABCD1 mutation, p.R163G. Given the relatively mild pathological findings and long disease duration, it is likely that the observed pathology was the result of a slow and indolent disease process. We described a patient who had sporadic cerebello-brainstem dominant form of X-ALD with long clinical course, mild pathological findings, and an ABCD1 p.R163G substitution. We also review a total of 34 cases of adult-onset cerebello-brainstem dominant form of X-ALD. Although rare, X-ALD should be

  15. Phenotypic characterization of a Csf1r haploinsufficient mouse model of adult-onset leukodystrophy with axonal spheroids and pigmented glia (ALSP)

    PubMed Central

    Chitu, Violeta; Gokhan, Solen; Gulinello, Maria; Branch, Craig A.; Patil, Madhuvati; Basu, Ranu; Stoddart, Corrina; Mehler, Mark F.; Stanley, E. Richard

    2014-01-01

    Mutations in the colony stimulating factor-1 receptor (CSF1R) that abrogate the expression of the affected allele or lead to the expression of mutant receptor chains devoid of kinase activity have been identified in both familial and sporadic cases of ALSP. To determine the validity of the Csf1r heterozygous mouse as a model of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) we performed behavioral, radiologic, histopathologic, ultrastructural and cytokine expression studies of young and old Csf1r+/− and control Csf1r+/+ mice. Six to 8-month old Csf1r+/− mice exhibit cognitive deficits, and by 9-11 months develop sensorimotor deficits and in male mice, depression and anxiety-like behavior. MRIs of one year-old Csf1r+/− mice reveal lateral ventricle enlargement and thinning of the corpus callosum. Ultrastructural analysis of the corpus callosum uncovers dysmyelinated axons as well as neurodegeneration, evidenced by the presence of axonal spheroids. Histopathological examination of 11-week-old mice reveals increased axonal and myelin staining in the cortex, increase of neuronal cell density in layer V and increase of microglial cell densities throughout the brain, suggesting that early developmental changes contribute to disease. By 10-months of age, the neuronal cell density normalizes, oligodendrocyte precursor cells increase in layers II-III and V and microglial densities remain elevated without an increase in astrocytes. Also, the age-dependent increase in CSF-1R+ neurons in cortical layer V is reduced. Moreover, the expression of Csf2, Csf3, Il27 and Il6 family cytokines is increased, consistent with microglia-mediated inflammation. These results demonstrate that the inactivation of one Csf1r allele is sufficient to cause an ALSP-like disease in mice. The Csf1r+/− mouse is a model of ALSP that will allow the critical events for disease development to be determined and permit rapid evaluation of therapeutic approaches

  16. Food-borne diseases - the challenges of 20 years ago still persist while new ones continue to emerge.

    PubMed

    Newell, Diane G; Koopmans, Marion; Verhoef, Linda; Duizer, Erwin; Aidara-Kane, Awa; Sprong, Hein; Opsteegh, Marieke; Langelaar, Merel; Threfall, John; Scheutz, Flemming; van der Giessen, Joke; Kruse, Hilde

    2010-05-30

    The burden of diseases caused by food-borne pathogens remains largely unknown. Importantly data indicating trends in food-borne infectious intestinal disease is limited to a few industrialised countries, and even fewer pathogens. It has been predicted that the importance of diarrhoeal disease, mainly due to contaminated food and water, as a cause of death will decline worldwide. Evidence for such a downward trend is limited. This prediction presumes that improvements in the production and retail of microbiologically safe food will be sustained in the developed world and, moreover, will be rolled out to those countries of the developing world increasingly producing food for a global market. In this review evidence is presented to indicate that the microbiological safety of food remains a dynamic situation heavily influenced by multiple factors along the food chain from farm to fork. Sustaining food safety standards will depend on constant vigilance maintained by monitoring and surveillance but, with the rising importance of other food-related issues, such as food security, obesity and climate change, competition for resources in the future to enable this may be fierce. In addition the pathogen populations relevant to food safety are not static. Food is an excellent vehicle by which many pathogens (bacteria, viruses/prions and parasites) can reach an appropriate colonisation site in a new host. Although food production practices change, the well-recognised food-borne pathogens, such as Salmonella spp. and Escherichia coli, seem able to evolve to exploit novel opportunities, for example fresh produce, and even generate new public health challenges, for example antimicrobial resistance. In addition, previously unknown food-borne pathogens, many of which are zoonotic, are constantly emerging. Current understanding of the trends in food-borne diseases for bacterial, viral and parasitic pathogens has been reviewed. The bacterial pathogens are exemplified by those well

  17. Metabolic programming effects initiated in the suckling period predisposing for adult-onset obesity cannot be reversed by calorie restriction

    PubMed Central

    Srinivasan, Malathi; Mahmood, Saleh

    2013-01-01

    Neonatal rats reared on high-carbohydrate (HC) milk formula developed chronic hyperinsulinemia and adult-onset obesity due to programming of islets and the hypothalamic energy circuitry. In this study, calorie restriction by pair-feeding was imposed on HC male rats (HC/PF) to normalize food intake similar to that of mother-fed (MF) rats from weaning until postnatal day 140. A group of HC/PF rats was switched over to ad libitum feeding (HC/PF/AL) from days 90 to 140. Pair-feeding reduced body weight gains and serum insulin and leptin levels in HC/PF rats compared with HC rats, but these parameters were restored to HC levels in the HC/PF/AL rats after ad libitum feeding. Interestingly, the heightened insulin secretory response of isolated islets from adult HC/PF and HC/PF/ AL rats to glucose, acetylcholine, and oxymetazoline were not significantly different from the responses of islets from HC rats. Similarly, the expression of neuropeptide Y and proopiomelanocortin in the hypothalamus was not significantly different among HC, HC/PF, and HC/PF/AL rats. Expression of the leptin receptor in the hypothalami from the HC, HC/PF, and HC/PF/AL rats mirrored that of serum leptin, whereas suppressor of cytokine signaling 3 (Socs3) expression remained high in these three groups. The results indicate that, although calorie restriction resulted in reduction in body weight gain and normalized the serum hormonal pattern, the programed predisposition for the hypersecretory capacity of islets and the hypothalamic hyperphagic response in the HC rats could not be permanently overcome by the pair-feeding imposed on HC rats. PMID:23249696

  18. Recent trends in the distribution of causative diseases of fever of unknown origin.

    PubMed

    Shang, Jin; Yan, Libo; Du, Lingyao; Liang, Lingbo; Zhou, Qiaoling; Liang, Tao; Bai, Lang; Tang, Hong

    2017-03-01

    Fever of unknown origin is a challenging diagnostic problem and the aim of this research was to analyze trends in the distribution of its causative diseases. This retrospective study makes a comparison between two different clinical series of patients from two different periods: 227 from period 1 (1998-2002) and 602 from period 2 (2008-2012). There were fewer infections (31.72% vs.16.45%) and more miscellaneous causes (5.29% vs. 13.12%) in the period 2 series, whereas no significant differences in autoimmune diseases, malignancies and undiagnosed cases were found. Adult onset Still's disease and lymphoma occupied the largest proportion in autoimmune diseases (75.00%) and malignancies (89.81%), respectively. Interestingly, the autoimmune diseases group, instead of infections, was found to be the leading category of the causative diseases in fever of unknown origin, which is contrary to previous reports. Further, adult onset Still's disease and lymphoma were suggested to be valued more highly in view of the large and rising proportions found in this study. These trends could support the diagnosis and treatment of fever of unknown origin better in the future.

  19. Compensatory stepping in Parkinson's disease is still a problem after deep brain stimulation randomized to STN or GPi

    PubMed Central

    St George, R. J.; Carlson-Kuhta, P.; King, L. A.; Burchiel, K. J.

    2015-01-01

    The effects of deep brain stimulation (DBS) on balance in people with Parkinson's disease (PD) are not well established. This study examined whether DBS randomized to the subthalamic nucleus (STN; n = 11) or globus pallidus interna (GPi; n = 10) improved compensatory stepping to recover balance after a perturbation. The standing surface translated backward, forcing subjects to take compensatory steps forward. Kinematic and kinetic responses were recorded. PD-DBS subjects were tested off and on their levodopa medication before bilateral DBS surgery and retested 6 mo later off and on DBS, combined with off and on levodopa medication. Responses were compared with PD-control subjects (n = 8) tested over the same timescale and 17 healthy control subjects. Neither DBS nor levodopa improved the stepping response. Compensatory stepping in the best-treated state after surgery (DBS+DOPA) was similar to the best-treated state before surgery (DOPA) for the PD-GPi group and the PD-control group. For the PD-STN group, there were more lateral weight shifts, a delayed foot-off, and a greater number of steps required to recover balance in DBS+DOPA after surgery compared with DOPA before surgery. Within the STN group five subjects who did not fall during the experiment before surgery fell at least once after surgery, whereas the number of falls in the GPi and PD-control groups were unchanged. DBS did not improve the compensatory step response needed to recover from balance perturbations in the GPi group and caused delays in the preparation phase of the step in the STN group. PMID:26108960

  20. Rearranged Anaplastic Lymphoma Kinase (ALK) Gene in Adult-Onset Papillary Thyroid Cancer Amongst Atomic Bomb Survivors

    PubMed Central

    Mukai, Mayumi; Takahashi, Keiko; Hayashi, Yuzo; Nakachi, Kei; Kusunoki, Yoichiro

    2012-01-01

    rearrangements, being observed in 6 of 10 PTC cases with ALK rearrangements versus 2 of 15 cases with no ALK rearrangements. The six radiation-exposed cases of PTC harboring both ALK rearrangements and solid/trabecular-like architecture were associated with higher radiation doses and younger ages at the time of the A-bombing and at diagnosis compared to the other 19 PTC with no detectable gene alterations. Conclusion Our findings suggest that ALK rearrangements are involved in the development of radiation-induced adult-onset PTC. PMID:23050789

  1. Calprotectin in rheumatic diseases: a review.

    PubMed

    Kopeć-Mędrek, Magdalena; Widuchowska, Małgorzata; Kucharz, Eugeniusz J

    2016-01-01

    Calprotectin also known as MRP8/14 or S100A8/A9 is a heterodimeric complex of two S100 calcium-binding proteins: myeloid-related protein 8 (MRP-8 or S100A8) and MRP-14 (or S100A9). At present, according to many authors, it is considered that calprotectin MRP8/14 is a potentially more sensitive biomarker of disease activity in rheumatoid disease than conventional inflammatory indices such as the erythrocyte sedimentation rate, C-reactive protein and others. A review of the literature on concentration of calprotectin in patients with some rheumatic diseases (rheumatoid arthritis, juvenile idiopathic arthritis, adult-onset Still's disease, systemic vasculitis, polymyalgia rheumatica, ankylosis spondylitis, systemic lupus erythematosus, and primary Sjögren's syndrome) is presented.

  2. Increased Expression of the Large Conductance, Calcium-Activated K+ (BK) Channel in Adult-Onset Neuronal Ceroid Lipofuscinosis

    PubMed Central

    Donnelier, Julien; Braun, Samuel T.; Dolzhanskaya, Natalia; Ahrendt, Eva; Braun, Andrew P.; Velinov, Milen; Braun, Janice E. A.

    2015-01-01

    Cysteine string protein (CSPα) is a presynaptic J protein co-chaperone that opposes neurodegeneration. Mutations in CSPα (i.e., Leu115 to Arg substitution or deletion (Δ) of Leu116) cause adult neuronal ceroid lipofuscinosis (ANCL), a dominantly inherited neurodegenerative disease. We have previously demonstrated that CSPα limits the expression of large conductance, calcium-activated K+ (BK) channels in neurons, which may impact synaptic excitability and neurotransmission. Here we show by western blot analysis that expression of the pore-forming BKα subunit is elevated ~2.5 fold in the post-mortem cortex of a 36-year-old patient with the Leu116∆ CSPα mutation. Moreover, we find that the increase in BKα subunit level is selective for ANCL and not a general feature of neurodegenerative conditions. While reduced levels of CSPα are found in some postmortem cortex specimens from Alzheimer’s disease patients, we find no concomitant increase in BKα subunit expression in Alzheimer’s specimens. Both CSPα monomer and oligomer expression are reduced in synaptosomes prepared from ANCL cortex compared with control. In a cultured neuronal cell model, CSPα oligomers are short lived. The results of this study indicate that the Leu116∆ mutation leads to elevated BKα subunit levels in human cortex and extend our initial work in rodent models demonstrating the modulation of BKα subunit levels by the same CSPα mutation. While the precise sequence of pathogenic events still remains to be elucidated, our findings suggest that dysregulation of BK channels may contribute to neurodegeneration in ANCL. PMID:25905915

  3. 38 CFR 3.309 - Disease subject to presumptive service connection.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... Coccidioidomycosis. Diabetes mellitus. Encephalitis lethargica residuals. Endocarditis. (This term covers all forms... other acneform disease consistent with chloracne Type 2 diabetes (also known as Type II diabetes mellitus or adult-onset diabetes) Hodgkin's disease Chronic lymphocytic leukemia Multiple myeloma...

  4. Adult-onset deficiency in growth hormone and insulin-like growth factor-I alters oligodendrocyte turnover in the corpus callosum.

    PubMed

    Hua, Kun; Forbes, M Elizabeth; Lichtenwalner, Robin J; Sonntag, William E; Riddle, David R

    2009-08-01

    Growth hormone (GH) and insulin-like growth factor-I (IGF-I) provide trophic support during development and also appear to influence cell structure, function and replacement in the adult brain. Recent studies demonstrated effects of the GH/IGF-I axis on adult neurogenesis, but it is unclear whether the GH/IGF-I axis influences glial turnover in the normal adult brain. In the current study, we used a selective model of adult-onset GH and IGF-I deficiency to evaluate the role of GH and IGF-I in regulating glial proliferation and survival in the adult corpus callosum. GH/IGF-I-deficient dwarf rats of the Lewis strain were made GH/IGF-I replete via twice daily injections of GH starting at postnatal day 28 (P28), approximately the age at which GH pulse amplitude increases in developing rodents. GH/IGF-I deficiency was initiated in adulthood by removing animals from GH treatment. Quantitative analyses revealed that adult-onset GH/IGF-I deficiency decreased cell proliferation in the white matter and decreased the survival of newborn oligodendrocytes. These findings are consistent with the hypothesis that aging-related changes in the GH/IGF-I axis produce deficits in ongoing turnover of oligodendrocytes, which may contribute to aging-related cognitive changes and deficits in remyelination after injury.

  5. Limbic encephalitis associated with anti-voltage-gated potassium channel complex antibodies as a cause of adult-onset mesial temporal lobe epilepsy.

    PubMed

    Toyota, Tomoko; Akamatsu, Naoki; Tsuji, Sadatoshi; Nishizawa, Shigeru

    2014-06-01

    Recently, some reports have indicated that limbic encephalitis associated with anti-voltage-gated potassium channel complex antibodies (VGKC-Ab) is a cause of adult-onset mesial temporal lobe epilepsy (MTLE). We report a 53-year-old woman who had her first epileptic seizure at the age of 50 years old. Examination by 3-Tesla brain MRI revealed left hippocampal high signal intensity and swelling on fluid-attenuated inversion recovery (FLAIR) and T2-weighted imaging at 2 months after her first seizure. The patient received intravenous methylprednisolone and carbamazepine 300 mg/day. One month later, MRI revealed improvement of her left hippocampal abnormalities. Thereafter, she had no seizures, however, three years after her first seizure, EEG revealed a seizure pattern in the left temporal region. Brain MRI revealed left hippocampal high signal intensity and brain fluorodeoxyglucose positron emission tomography revealed hypermetabolism. Her serum VGKC-Ab levels were 118 pM(normal < 100 pM). Intravenous methylprednisolone therapy was reinitiated. Two months later, her hippocampal abnormalities had improved and 3 months later her VGKC-Ab levels decreased to 4.4 pM. Remission of the epileptic seizures was also observed. This MTLE in the middle age was considered as limbic encephalitis associated with anti- VGKC-Ab. In cases of unexplained adult-onset MTLE, limbic encephalitis associated with anti-VGKC-Ab, which responds well to immunotherapy, should be considered in the differential diagnosis.

  6. A case of adult-onset reducing body myopathy presenting a novel clinical feature, asymmetrical involvement of the sternocleidomastoid and trapezius muscles.

    PubMed

    Fujii, Takayuki; Hayashi, Shintaro; Kawamura, Nobutoshi; Higuchi, Masa-Aki; Tsugawa, Jun; Ohyagi, Yasumasa; Hayashi, Yukiko K; Nishino, Ichizo; Kira, Jun-Ichi

    2014-08-15

    We herein report a 32-year-old woman with adult-onset reducing body myopathy (RBM) who had a mutation in the four-and-a-half LIM domain 1 gene (FHL1) and showed a marked asymmetrical involvement of sternocleidomastoid and trapezius muscles. At 30 years of age she noticed bilateral foot drop, and over the next two years developed difficulty raising her right arm. At 32 years of age she was admitted to our hospital for a diagnostic evaluation. Neurological examination showed moderate weakness and atrophy of her right sternocleidomastoid muscle, right trapezius muscle, and bilateral upper proximal muscles. There were severe weakness and atrophy of her bilateral tibialis anterior muscles. Her deep tendon reflexes were hypoactive in her upper extremities. Her serum creatine kinase level was mildly increased. Muscle biopsy specimens from the left tibialis anterior muscle revealed marked variation in fiber size, some necrotic or regenerating fibers, and reducing bodies. Gene analysis of FHL1 demonstrated a mutation: a heterozygous missense mutation of c.377G>A (p. C126T) in FHL1. Compared with previous adult-onset RBM cases harboring mutations in FHL1, our case was characterized by asymmetrical atrophy of the sternocleidomastoid and trapezius muscles.

  7. Radiation risk of individual multifactorial diseases in offspring of the atomic-bomb survivors: a clinical health study.

    PubMed

    Tatsukawa, Yoshimi; Cologne, John B; Hsu, Wan-Ling; Yamada, Michiko; Ohishi, Waka; Hida, Ayumi; Furukawa, Kyoji; Takahashi, Norio; Nakamura, Nori; Suyama, Akihiko; Ozasa, Kotaro; Akahoshi, Masazumi; Fujiwara, Saeko; Shore, Roy

    2013-06-01

    There is no convincing evidence regarding radiation-induced heritable risks of adult-onset multifactorial diseases in humans, although it is important from the standpoint of protection and management of populations exposed to radiation. The objective of the present study was to examine whether parental exposure to atomic-bomb (A-bomb) radiation led to an increased risk of common polygenic, multifactorial diseases-hypertension, hypercholesterolaemia, diabetes mellitus, angina pectoris, myocardial infarction or stroke-in the first-generation (F1) offspring of A-bomb survivors. A total of 11,951 F1 offspring of survivors in Hiroshima or Nagasaki, conceived after the bombing, underwent health examinations to assess disease prevalence. We found no evidence that paternal or maternal A-bomb radiation dose, or the sum of their doses, was associated with an increased risk of any multifactorial diseases in either male or female offspring. None of the 18 radiation dose-response slopes, adjusted for other risk factors for the diseases, was statistically significantly elevated. However, the study population is still in mid-life (mean age 48.6 years), and will express much of its multifactorial disease incidence in the future, so ongoing longitudinal follow-up will provide increasingly informative risk estimates regarding hereditary genetic effects for incidence of adult-onset multifactorial disease.

  8. [Heart and Steinert's disease].

    PubMed

    Fayssoil, A; Nardi, O

    2011-08-01

    Myotonic dystrophy type 1 (Steinert disease) is an autosomal dominant disease characterized by myotonia and multiorgan damage. This latter is the most frequent of the adult-onset muscular dystrophies. Heart involvement is often associated, including cardiomyopathies, atrioventricular block, atrial and ventricular arrhythmias.

  9. Adult-onset deficiency of acyl CoA:monoacylglycerol acyltransferase 2 protects mice from diet-induced obesity and glucose intolerance[S

    PubMed Central

    Banh, Taylor; Nelson, David W.; Gao, Yu; Huang, Ting-Ni; Yen, Mei-I; Yen, Chi-Liang E.

    2015-01-01

    Acyl-CoA:monoacylglycerol acyltransferase (MGAT) 2 catalyzes triacylglycerol (TAG) synthesis, required in intestinal fat absorption. We previously demonstrated that mice without a functional MGAT2-coding gene (Mogat2−/−) exhibit increased energy expenditure and resistance to obesity induced by excess calories. One critical question raised is whether lacking MGAT2 during early development is required for the metabolic phenotypes in adult mice. In this study, we found that Mogat2−/− pups grew slower than wild-type littermates during the suckling period. To determine whether inactivating MGAT2 in adult mice is sufficient to confer resistance to diet-induced obesity, we generated mice with an inducible Mogat2-inactivating mutation. Mice with adult-onset MGAT2 deficiency (Mogat2AKO) exhibited a transient decrease in food intake like Mogat2−/− mice when fed a high-fat diet and a moderate increase in energy expenditure after acclimatization. They gained less weight than littermate controls, but the difference was smaller than that between wild-type and Mogat2−/− mice. The moderate reduction in weight gain was associated with reduced hepatic TAG and improved glucose tolerance. Similar protective effects were also observed in mice that had gained weight on a high-fat diet before inactivating MGAT2. These findings suggest that adult-onset MGAT2 deficiency mitigates metabolic disorders induced by high-fat feeding and that MGAT2 modulates early postnatal nutrition and may program metabolism later in life. PMID:25535286

  10. The potential of disease management for neuromuscular hereditary disorders.

    PubMed

    Chouinard, Maud-Christine; Gagnon, Cynthia; Laberge, Luc; Tremblay, Carmen; Côté, Charlotte; Leclerc, Nadine; Mathieu, Jean

    2009-01-01

    Neuromuscular hereditary disorders require long-term multidisciplinary rehabilitation management. Although the need for coordinated healthcare management has long been recognized, most neuromuscular disorders are still lacking clinical guidelines about their long-term management and structured evaluation plan with associated services. One of the most prevalent adult-onset neuromuscular disorders, myotonic dystrophy type 1, generally presents several comorbidities and a variable clinical picture, making management a constant challenge. This article presents a healthcare follow-up plan and proposes a nursing case management within a disease management program as an innovative and promising approach. This disease management program and model consists of eight components including population identification processes, evidence-based practice guidelines, collaborative practice, patient self-management education, and process outcomes evaluation (Disease Management Association of America, 2004). It is believed to have the potential to significantly improve healthcare management for neuromuscular hereditary disorders and will prove useful to nurses delivering and organizing services for this population.

  11. A systematic review of the off-label use of biological therapies in systemic autoimmune diseases.

    PubMed

    Ramos-Casals, Manuel; Brito-Zerón, Pilar; Muñoz, Sandra; Soto, María-José

    2008-11-01

    In 2006, the Study Group on Autoimmune Diseases (GEAS) of the Spanish Society of Internal Medicine created the BIOGEAS project, a multicenter study devoted to collecting data on the use of biological agents in adult patients with systemic autoimmune diseases (SAD). The information source is a periodic surveillance of reported cases by a MEDLINE search (last update before this writing: December 31, 2007). The analysis included a total of 19 SAD and 6 biological agents. By December 31, 2007, the Registry included 1370 patients with SAD who had been treated with biological agents (562 received infliximab, 463 rituximab, 285 etanercept, 42 anakinra, and 18 adalimumab). SAD included Sjögren syndrome (SS; 215 cases), Wegener granulomatosis (261 cases), sarcoidosis (219 cases), systemic lupus erythematosus (SLE; 172 cases), Behçet disease (173 cases), adult-onset Still disease (118 cases), cryoglobulinemia (88 cases), and other diseases (80 cases). The higher rate of therapeutic response was found for the use of rituximab in patients with SLE (90%), SS (91%), antiphospholipid syndrome (92%), and cryoglobulinemia (87%); infliximab in sarcoidosis (99%), adult-onset Still disease (90%), and polychondritis (86%); and etanercept in Behçet disease (96%). Results from controlled trials showed lack of efficacy for the use of infliximab in SS and etanercept in SS, Wegener granulomatosis, and sarcoidosis. In addition, an excess of side effects (>50% of reported cases) was observed for the use of infliximab in inflammatory myopathies and sarcoidosis, and for the use of etanercept in polymyositis. Sufficient data are not yet available to evaluate fully the efficacy and safety of adalimumab and anakinra in patients with SAD. In conclusion, current scientific evidence on the use of biological therapies in patients with SAD is mainly based on uncontrolled, observational data. The best results have been observed in the use of rituximab for SS, SLE, and cryoglobulinemia; infliximab for

  12. Vaginal contraceptives still evolving.

    PubMed

    Pearson, R M

    1986-01-01

    The effort to develop vaginal contraceptives began in the distant past and is still underway today. 1000 years ago, South American Indians inserted into the vagina bark strips impregnated with quinine. In medieval times women used vaginal inserts of cloth soaked in honey or vinegar. Quinine pessaries were introduced into Europe in the late 1800s, and in the early 1900s investigators began to study the effects of various chemicals on sperm motility. Following World War II, surfactant spermicides which disrupt the sperm membrane were developed and marketed. Many of these preparations contained nonoxynol-9. Currently, the D-isomer of propranolol is being examined as a spermicidal contraceptive, and several bacteriocides, e.g., benzalkonium and chlorhexidine, are being developed as spermicides which reduce the penetrability of cervical mucus. Other chemicals being investigated act by inhibiting the acrosome reaction. Advantages of vaginal contraceptives are that they are inexpensive, reversible, and relatively safe and easy to use. Generally they require no medical intervention or supervision. In addition, spermicides may kill or inhibit the growth of organisms responsible for sexually transmitted diseases. Disadvantages of spermicides are that they are generally less effective than many other methods, some interfere with sexual spontaneity, they may cause local irritations, and some women find them messy to use. Recently, concerns were expressed about the possible teratogenic effects of sperimicides. Most of these concerns proved to be unfounded. Given the many new avenues of research, the major disadvantage of sperimicides, i.e., their high failure rates, may be minimized in the near future.

  13. Similar L-dopa-stimulated motor activity in mice with adult-onset 6-hydroxydopamine-induced symmetric dopamine denervation and in transcription factor Pitx3 null mice with perinatal-onset symmetric dopamine denervation.

    PubMed

    Li, Li; Sagot, Ben; Zhou, Fu-Ming

    2015-07-30

    The transcription factor Pitx3 null mutant (Pitx3Null) mice have a constitutive perinatal-onset and symmetric bilateral dopamine (DA) loss in the striatum. In these mice l-3,4-dihydroxyphenylalanine (l-dopa) induces apparently normal horizontal movements (walking) but also upward movements consisting of the vertical body trunk and waving paws that are absent in normal animals and in animals with the classic unilateral 6-hydroxydopamine (6-OHDA) lesion-induced DA denervation. Thus, a concern is that the perinatal timing of the DA loss and potential developmental abnormalities in Pitx3Null mice may underlie these upward movements, thus reducing the usefulness as a DA denervation model. Here we show that in normal wild-type (Pitx3WT) mice with adult-onset symmetric, bilateral 6-OHDA-induced DA lesion in the dorsal striatum, l-dopa induces normal horizontal movements and upward movements that are qualitatively identical to those in Pitx3Null mice. Furthermore, after unilateral 6-OHDA lesion of the residual DA innervation in the striatum in Pitx3Null mice, l-dopa induces contraversive rotation that is similar to that in Pitx3WT mice with the classic unilateral 6-OHDA lesion. These results indicate that in Pitx3Null mice, the bilateral symmetric DA denervation in the dorsal striatum is sufficient for expressing the l-dopa-induced motor phenotype and the perinatal timing of their DA loss is not a determining factor, providing further evidence that Pitx3Null mice are a convenient and suitable mouse model to study the consequences of DA loss and dopaminergic replacement therapy in Parkinson's disease.

  14. A multicentre comparative trial of sodium valproate and carbamazepine in adult onset epilepsy. Adult EPITEG Collaborative Group.

    PubMed Central

    Richens, A; Davidson, D L; Cartlidge, N E; Easter, D J

    1994-01-01

    The long-term efficacy and safety of sodium valproate and carbamazepine in adult outpatients with newly diagnosed primary generalised or partial and secondarily generalised seizures were compared in a randomised, open, multicentre study at 22 neurology outpatient clinics. Patients were randomised to oral sodium valproate (Epilim EC enteric coated 200 mg tablets twice daily, n = 149) or oral carbamazepine (100 mg twice daily increasing to 200 mg twice daily in week 2, n = 151) and followed up for three years. If clinically necessary, dosages were regularly increased until seizures were controlled or toxicity developed. Sodium valproate and carbamazepine controlled both primary generalised and partial seizures equally effectively overall. Significantly more patients on sodium valproate than carbamazepine (126/140 (90%) v 105/141 (75%), p = 0.001) remained on randomised treatment for at least six months. Skin rashes occurred significantly more often in carbamazepine recipients than in sodium valproate recipients (11.2% v 1.7%, p < 0.05) and carbamazepine was associated with a higher withdrawal rate because of adverse events (15% v 5% on sodium valproate) in the first six months of treatment. There was no difference between the drugs in the rate of withdrawal because of poor seizure control at any stage, regardless of seizure type. At the end of the three year trial period, over 70% of the available patients were still on randomised treatment or had recently stopped treatment after achieving full seizure control. Sodium valproate and carbamazepine were both associated with a high degree of overall seizure control regardless of seizure type and both have good long-term tolerability in adult patients with newly diagnosed epilepsy. Recommendations are made for a higher initial dosage regime for sodium valproate in partial seizures. PMID:8006647

  15. Imaging of connective tissue diseases of the head and neck.

    PubMed

    Abdel Razek, Ahmed Abdel Khalek

    2016-06-01

    We review the imaging appearance of connective tissue diseases of the head and neck. Bilateral sialadenitis and dacryoadenitis are seen in Sjögren's syndrome; ankylosis of the temporo-mandibular joint with sclerosis of the crico-arytenoid joint are reported in rheumatoid arthritis and lupus panniculitis with atypical infection are reported in patients with systemic lupus erythematosus. Relapsing polychondritis shows subglottic stenosis, prominent ear and saddle nose; progressive systemic sclerosis shows osteolysis of the mandible, fibrosis of the masseter muscle with calcinosis of the subcutaneous tissue and dermatomyositis/polymyositis shows condylar erosions and autoimmune thyroiditis. Vascular thrombosis is reported in antiphospholipid antibodies syndrome; cervical lymphadenopathy is seen in adult-onset Still's disease, and neuropathy with thyroiditis reported in mixed connective tissue disorder. Imaging is important to detect associated malignancy with connective tissue disorders. Correlation of the imaging findings with demographic data and clinical findings are important for the diagnosis of connective tissue disorders.

  16. Adult-onset congenital thrombotic thrombocytopenic purpura caused by a novel compound heterozygous mutation of the ADAMTS13 gene.

    PubMed

    Krabbe, Johannes G; Kemna, Evelien W M; Strunk, Annuska L M; Jobse, Pieter A; Kramer, P A; Dikkeschei, L D; van den Heuvel, L P W J; Fijnheer, Rob; Verdonck, Leo F

    2015-10-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease, characterized by microangiopathic hemolytic anaemia and thrombocytopenia, resulting in neurologic and/or renal abnormalities. We report a 49-year-old patient with a history of thrombotic events, renal failure, and thrombocytopenia. Blood analysis demonstrated no ADAMTS13 activity in the absence of antibodies against ADAMTS13. The complete ADAMTS13 gene was sequenced, and two mutations were identified: one mutation on exon 24 (Arg1060Asp), which had previously been described, and a mutation on exon 27 (Met1260IlefsX34), which has not been reported. For these mutations, compound heterozygosity appears to be necessary to cause TTP, as family members of the patient display only one of the mutations and all displayed normal ADAMTS13 activity.

  17. Biallelic Mutation of ARHGEF18, Involved in the Determination of Epithelial Apicobasal Polarity, Causes Adult-Onset Retinal Degeneration.

    PubMed

    Arno, Gavin; Carss, Keren J; Hull, Sarah; Zihni, Ceniz; Robson, Anthony G; Fiorentino, Alessia; Hardcastle, Alison J; Holder, Graham E; Cheetham, Michael E; Plagnol, Vincent; Moore, Anthony T; Raymond, F Lucy; Matter, Karl; Balda, Maria S; Webster, Andrew R

    2017-02-02

    Mutations in more than 250 genes are implicated in inherited retinal dystrophy; the encoded proteins are involved in a broad spectrum of pathways. The presence of unsolved families after highly parallel sequencing strategies suggests that further genes remain to be identified. Whole-exome and -genome sequencing studies employed here in large cohorts of affected individuals revealed biallelic mutations in ARHGEF18 in three such individuals. ARHGEF18 encodes ARHGEF18, a guanine nucleotide exchange factor that activates RHOA, a small GTPase protein that is a key component of tight junctions and adherens junctions. This biological pathway is known to be important for retinal development and function, as mutation of CRB1, encoding another component, causes retinal dystrophy. The retinal structure in individuals with ARHGEF18 mutations resembled that seen in subjects with CRB1 mutations. Five mutations were found on six alleles in the three individuals: c.808A>G (p.Thr270Ala), c.1617+5G>A (p.Asp540Glyfs(∗)63), c.1996C>T (p.Arg666(∗)), c.2632G>T (p.Glu878(∗)), and c.2738_2761del (p.Arg913_Glu920del). Functional tests suggest that each disease genotype might retain some ARHGEF18 activity, such that the phenotype described here is not the consequence of nullizygosity. In particular, the p.Thr270Ala missense variant affects a highly conserved residue in the DBL homology domain, which is required for the interaction and activation of RHOA. Previously, knock-out of Arhgef18 in the medaka fish has been shown to cause larval lethality which is preceded by retinal defects that resemble those seen in zebrafish Crumbs complex knock-outs. The findings described here emphasize the peculiar sensitivity of the retina to perturbations of this pathway, which is highlighted as a target for potential therapeutic strategies.

  18. A large genomic deletion leads to enhancer adoption by the lamin B1 gene: a second path to autosomal dominant adult-onset demyelinating leukodystrophy (ADLD)

    DOE PAGES

    Giorgio, E.; Robyr, D.; Spielmann, M.; ...

    2015-02-20

    Chromosomal rearrangements with duplication of the lamin B1 (LMNB1) gene underlie autosomal dominant adult-onset demyelinating leukodystrophy (ADLD), a rare neurological disorder in which overexpression of LMNB1 causes progressive central nervous system demyelination. However, we previously reported an ADLD family (ADLD-1-TO) without evidence of duplication or other mutation in LMNB1 despite linkage to the LMNB1 locus and lamin B1 overexpression. By custom array-CGH, we further investigated this family and report here that patients carry a large (~660 kb) heterozygous deletion that begins 66 kb upstream of the LMNB1 promoter. Lamin B1 overexpression was confirmed in further ADLD-1-TO tissues and in amore » postmortem brain sample, where lamin B1 was increased in the frontal lobe. Through parallel studies, we investigated both loss of genetic material and chromosomal rearrangement as possible causes of LMNB1 overexpression, and found that ADLD-1-TO plausibly results from an enhancer adoption mechanism. The deletion eliminates a genome topological domain boundary, allowing normally forbidden interactions between at least three forebrain-directed enhancers and the LMNB1 promoter, in line with the observed mainly cerebral localization of lamin B1 overexpression and myelin degeneration. Finally, this second route to LMNB1 overexpression and ADLD is a new example of the relevance of regulatory landscape modifications in determining Mendelian phenotypes.« less

  19. A large genomic deletion leads to enhancer adoption by the lamin B1 gene: a second path to autosomal dominant adult-onset demyelinating leukodystrophy (ADLD)

    PubMed Central

    Giorgio, Elisa; Robyr, Daniel; Spielmann, Malte; Ferrero, Enza; Di Gregorio, Eleonora; Imperiale, Daniele; Vaula, Giovanna; Stamoulis, Georgios; Santoni, Federico; Atzori, Cristiana; Gasparini, Laura; Ferrera, Denise; Canale, Claudio; Guipponi, Michel; Pennacchio, Len A.; Antonarakis, Stylianos E.; Brussino, Alessandro; Brusco, Alfredo

    2015-01-01

    Chromosomal rearrangements with duplication of the lamin B1 (LMNB1) gene underlie autosomal dominant adult-onset demyelinating leukodystrophy (ADLD), a rare neurological disorder in which overexpression of LMNB1 causes progressive central nervous system demyelination. However, we previously reported an ADLD family (ADLD-1-TO) without evidence of duplication or other mutation in LMNB1 despite linkage to the LMNB1 locus and lamin B1 overexpression. By custom array-CGH, we further investigated this family and report here that patients carry a large (∼660 kb) heterozygous deletion that begins 66 kb upstream of the LMNB1 promoter. Lamin B1 overexpression was confirmed in further ADLD-1-TO tissues and in a postmortem brain sample, where lamin B1 was increased in the frontal lobe. Through parallel studies, we investigated both loss of genetic material and chromosomal rearrangement as possible causes of LMNB1 overexpression, and found that ADLD-1-TO plausibly results from an enhancer adoption mechanism. The deletion eliminates a genome topological domain boundary, allowing normally forbidden interactions between at least three forebrain-directed enhancers and the LMNB1 promoter, in line with the observed mainly cerebral localization of lamin B1 overexpression and myelin degeneration. This second route to LMNB1 overexpression and ADLD is a new example of the relevance of regulatory landscape modifications in determining Mendelian phenotypes. PMID:25701871

  20. A large genomic deletion leads to enhancer adoption by the lamin B1 gene: a second path to autosomal dominant adult-onset demyelinating leukodystrophy (ADLD)

    SciTech Connect

    Giorgio, E.; Robyr, D.; Spielmann, M.; Ferrero, E.; Di Gregorio, E.; Imperiale, D.; Vaula, G.; Stamoulis, G.; Santoni, F.; Atzori, C.; Gasparini, L.; Ferrera, D.; Canale, C.; Guipponi, M.; Pennacchio, L. A.; Antonarakis, S. E.; Brussino, A.; Brusco, A.

    2015-02-20

    Chromosomal rearrangements with duplication of the lamin B1 (LMNB1) gene underlie autosomal dominant adult-onset demyelinating leukodystrophy (ADLD), a rare neurological disorder in which overexpression of LMNB1 causes progressive central nervous system demyelination. However, we previously reported an ADLD family (ADLD-1-TO) without evidence of duplication or other mutation in LMNB1 despite linkage to the LMNB1 locus and lamin B1 overexpression. By custom array-CGH, we further investigated this family and report here that patients carry a large (~660 kb) heterozygous deletion that begins 66 kb upstream of the LMNB1 promoter. Lamin B1 overexpression was confirmed in further ADLD-1-TO tissues and in a postmortem brain sample, where lamin B1 was increased in the frontal lobe. Through parallel studies, we investigated both loss of genetic material and chromosomal rearrangement as possible causes of LMNB1 overexpression, and found that ADLD-1-TO plausibly results from an enhancer adoption mechanism. The deletion eliminates a genome topological domain boundary, allowing normally forbidden interactions between at least three forebrain-directed enhancers and the LMNB1 promoter, in line with the observed mainly cerebral localization of lamin B1 overexpression and myelin degeneration. Finally, this second route to LMNB1 overexpression and ADLD is a new example of the relevance of regulatory landscape modifications in determining Mendelian phenotypes.

  1. A large genomic deletion leads to enhancer adoption by the lamin B1 gene: a second path to autosomal dominant adult-onset demyelinating leukodystrophy (ADLD).

    PubMed

    Giorgio, Elisa; Robyr, Daniel; Spielmann, Malte; Ferrero, Enza; Di Gregorio, Eleonora; Imperiale, Daniele; Vaula, Giovanna; Stamoulis, Georgios; Santoni, Federico; Atzori, Cristiana; Gasparini, Laura; Ferrera, Denise; Canale, Claudio; Guipponi, Michel; Pennacchio, Len A; Antonarakis, Stylianos E; Brussino, Alessandro; Brusco, Alfredo

    2015-06-01

    Chromosomal rearrangements with duplication of the lamin B1 (LMNB1) gene underlie autosomal dominant adult-onset demyelinating leukodystrophy (ADLD), a rare neurological disorder in which overexpression of LMNB1 causes progressive central nervous system demyelination. However, we previously reported an ADLD family (ADLD-1-TO) without evidence of duplication or other mutation in LMNB1 despite linkage to the LMNB1 locus and lamin B1 overexpression. By custom array-CGH, we further investigated this family and report here that patients carry a large (∼660 kb) heterozygous deletion that begins 66 kb upstream of the LMNB1 promoter. Lamin B1 overexpression was confirmed in further ADLD-1-TO tissues and in a postmortem brain sample, where lamin B1 was increased in the frontal lobe. Through parallel studies, we investigated both loss of genetic material and chromosomal rearrangement as possible causes of LMNB1 overexpression, and found that ADLD-1-TO plausibly results from an enhancer adoption mechanism. The deletion eliminates a genome topological domain boundary, allowing normally forbidden interactions between at least three forebrain-directed enhancers and the LMNB1 promoter, in line with the observed mainly cerebral localization of lamin B1 overexpression and myelin degeneration. This second route to LMNB1 overexpression and ADLD is a new example of the relevance of regulatory landscape modifications in determining Mendelian phenotypes.

  2. Co-existing spinal intradural ependymal cyst and sacral Tarlov cyst in adult-onset tethered cord syndrome with syringomyelia: Case report and literature review

    PubMed Central

    Rai, Hamid H.; Khan, Muhammad F.; Enam, Syed Ather; Hashmi, Imtiaz

    2016-01-01

    Background: Synchronous spinal intradural ependymal cysts and sacral Tarlov cysts in adult onset tethered cord syndrome are extremely rare. Case Description: A 23-year-old male presented with back pain radiating into both lower extremities, accompanied by acute onset of gait difficulty and sphincter dysfunction. Magnetic resonance imaging identified a low lying conus medullaris, syringomyelia with septations extending from T12 to S1, a tethered cord, and a thickened filum terminale with a sacral Tarlov cyst. The patient underwent a L3-4 laminectomy for decompression of syringomyelia and excision/biopsy of a space occupying lesion along with S1-2 laminectomy for cord untethering and Tarlov cyst fenestration. Postoperative histopathology confirmed that the lesion was an ependymal cyst. Clinically, patient showed marked improvement in the neurological status. Conclusion: Simultaneous decompressive laminectomy of L3-4 and S1-2 effectively decompressed the syringomyelia while allowing for excision/biopsy of a space occupying lesion at the former and untethering and Tarlov cyst fenestration at the latter levels. PMID:27843691

  3. Is Information Still Relevant?

    ERIC Educational Resources Information Center

    Ma, Lia

    2013-01-01

    Introduction: The term "information" in information science does not share the characteristics of those of a nomenclature: it does not bear a generally accepted definition and it does not serve as the bases and assumptions for research studies. As the data deluge has arrived, is the concept of information still relevant for information…

  4. Encaustic Still Life.

    ERIC Educational Resources Information Center

    Mathes, Len

    2002-01-01

    Presents an art lesson used in an advanced high school art class where students used the encaustic painting technique by melting wax and combining various pigments. Explains that the students painted a still-life of flowers in the style of Vincent van Gogh. (CMK)

  5. Epigenetic transgenerational actions of vinclozolin on the development of disease and cancer.

    PubMed

    Skinner, Michael K; Anway, Matthew D

    2007-08-01

    Exposure to an environmental endocrine disruptor (e.g., vinclozolin) during embryonic gonadal sex determination appears to alter the male germ line epigenome and subsequently promotes transgenerational adult onset disease. The epigenetic mechanism involves the induction of new imprinted-like genes/DNA sequences in the germ line that appear to transmit disease phenotypes. The disease phenotypes include testis abnormalities, prostate disease, kidney disease, immune abnormalities, and tumor development. This epigenetic transgenerational disease mechanism provides a unique perspective from which to view inheritable adult onset disease states, such as cancer, and ultimately offers new insights into novel diagnostic and therapeutic strategies.

  6. Localization of a locus (GLC1B) for adult-onset primary open angle glaucoma to the 2cen-q13 region

    SciTech Connect

    Stoilova, D.; Trifan, O.C.; Sarfarazi, M.

    1996-08-15

    Primary open angle glaucoma (GLC1) is a common ocular disorder with a characteristic degeneration of the optic nerve and visual field defects that is often associated with an elevated intraocular pressure. The severe but rare juvenile-onset type has previously been mapped to 1q21-q31, and its genetic heterogeneity has been established. Herein, we present a new locus (GLC1B) for one form of GLC1 on chromosome 2cen-q13 with a clinical presentation of low to moderate intraocular pressure, onset in late 40s, and a good response to medical treatment. Two-point and haplotype analyses of affected and unaffected meioses in six families provided maximum linkage information with D2S417, GATA112EO3, D2S113, D2S373, and D2S274 (lod scores ranging from 3.11 to 6.48) within a region of 8.5 cM that is flanked by D2S2161 and D2S2264. Analysis of affected meioses alone revealed no recombination with an additional two markers (D2S2264 and D2S135) in a region of 11.2 cM that is flanked by D2S2161 and D2S176. Analysis of unaffected meioses identified only one healthy 86-year-old male who has inherited the entire affected haplotype and, hence, is a gene carrier for this condition. Eight additional families with similar and/or different clinical presentation did not show any linkage to this region and, therefore, provided evidence for genetic heterogeneity of adult-onset primary open angle glaucoma. 63 refs., 2 figs., 2 tabs.

  7. Digital Electronic Still Camera

    NASA Technical Reports Server (NTRS)

    Holland, Samuel D.; Yeates, Herbert D.

    1993-01-01

    Digital electronic still camera part of electronic recording, processing, tansmitting, and displaying system. Removable hard-disk drive in camera serves as digital electronic equivalent of photographic film. Images viewed, analyzed, or transmitted quickly. Camera takes images of nearly photographic quality and stores them in digital form. Portable, hand-held, battery-powered unit designed for scientific use. Camera used in conjunction with playback unit also serving as transmitting unit if images sent to remote station. Remote station equipped to store, process, and display images. Digital image data encoded with error-correcting code at playback/transmitting unit for error-free transmission to remote station.

  8. [Why still whooping cough?].

    PubMed

    Guiso, Nicole

    2005-06-30

    Whooping cough is a human respiratory infection, dramatic for newborns and elderly, by the bacteria Bordetella pertussis and parapertussis. Intensive vaccination of children allowed an important decrease of mortality and morbidity. However, generalization of vaccination conducted to a change in the transmission of the disease due to the short duration of vaccinal immunity and the lack of vaccinal or natural boosters. The disease affects now adolescents and adults who contaminate new-borns too young to be vaccinated. For this reason, many countries including France, decided to add vaccine boosters for adolescents and young adults.

  9. Surgery for rheumatic mitral valve disease in sub-saharan African countries: why valve repair is still the best surgical option.

    PubMed

    Mvondo, Charles Mve; Pugliese, Marta; Giamberti, Alessandro; Chelo, David; Kuate, Liliane Mfeukeu; Boombhi, Jerome; Dailor, Ellen Marie

    2016-01-01

    Rheumatic valve disease, a consequence of acute rheumatic fever, remains endemic in developing countries in the sub-Saharan region where it is the leading cause of heart failure and cardiovascular death, involving predominantly a young population. The involvement of the mitral valve is pathognomonic and mitral surgery has become the lone therapeutic option for the majority of these patients. However, controversies exist on the choice between valve repair or prosthetic valve replacement. Although the advantages of mitral valve repair over prosthetic valve replacement in degenerative mitral disease are well established, this has not been the case for rheumatic lesions, where the use of prosthetic valves, specifically mechanical devices, even in poorly compliant populations remains very common. These patients deserve more accurate evaluation in the choice of the surgical strategy which strongly impacts the post-operative outcomes. This report discusses the factors supporting mitral repair surgery in rheumatic disease, according to the patients' characteristics and the effectiveness of the current repair techniques compared to prosthetic valve replacement in developing countries.

  10. Adult onset-hypothyroidism: alterations in hippocampal field potentials in the dentate gyrus are largely associated with anaesthesia-induced hypothermia.

    PubMed

    Sánchez-Huerta, K; Pacheco-Rosado, J; Gilbert, M E

    2015-01-01

    Thyroid hormone (TH) is essential for a number of physiological processes and is particularly critical during nervous system development. The hippocampus is strongly implicated in cognition and is sensitive to developmental hypothyroidism. The impact of TH insufficiency in the foetus and neonate on hippocampal synaptic function has been fairly well characterised. Although adult onset hypothyroidism has also been associated with impairments in cognitive function, studies of hippocampal synaptic function with late onset hypothyroidism have yielded inconsistent results. In the present study, we report hypothyroidism induced by the synthesis inhibitor propylthiouracil (10 p.p.m., 0.001%, minimum of 4 weeks), resulted in marginal alterations in excitatory postsynaptic potential (EPSP) and population spike (PS) amplitude in the dentate gyrus measured in vivo. No effects were seen in tests of short-term plasticity, and a minor enhancement of long-term potentiation of the EPSP slope was observed. The most robust synaptic alteration evident in hypothyroid animals was an increase in synaptic response latency, which was paralleled by a failure to maintain normal body temperature under anaesthesia, despite warming on a heating pad. Latency shifts could be reversed in hypothyroid animals by increasing the external heat source and, conversely, synaptic delays could be induced in control animals by removing the heat source, with a consequent drop in body and brain temperature. Thermoregulation is TH- dependent, and anaesthesia necessary for surgical procedures posed a thermoregulatory challenge that was differentially met in control and hypothyroid animals. Minor increases in field potential EPSP slope, decreases in PS amplitudes and increased latencies are consistent with previous reports of hypothermia in naive control rats. We conclude that failures in thyroid-dependent temperature regulation rather than direct action of TH in synaptic physiology are responsible for the

  11. Sex-comparative study of mouse cerebellum physiology under adult-onset hypothyroidism: The significance of GC-MS metabolomic data normalization in meta-analysis.

    PubMed

    Maga-Nteve, Christoniki; Vasilopoulou, Catherine G; Constantinou, Caterina; Margarity, Marigoula; Klapa, Maria I

    2017-01-15

    A systematic data quality validation and normalization strategy is an important component of the omic profile meta-analysis, ensuring comparability of the profiles and exclusion of experimental biases from the derived biological conclusions. In this study, we present the normalization methodology applied on the sets of cerebellum gas chromatography-mass spectrometry metabolic profiles of 124days old male and female animals in an adult-onset-hypothyroidism (AOH) mouse model before combining them into a sex-comparative analysis. The employed AOH model concerns the monitoring of the brain physiology of Balb/cJ mice after eight-week administration of 1%w/v KClO4 in the drinking water, initiated on the 60th day of their life. While originating from the same animal study, the tissues of the two sexes were processed and their profiles acquired and analyzed at different time periods. Hence, the previously published profile set of male mice was first re-annotated based on the presently available resources. Then, after being validated as acquired under the same analytical conditions, both profiles sets were corrected for derivatization biases and filtered for low-confidence measurements based on the same criteria. The final normalized 73-metabolite profiles contribute to the currently few available omic datasets of the AOH effect on brain molecular physiology, especially with respect to sex differentiation. Multivariate statistical analysis indicated one (unknown) and three (succinate, benzoate, myristate) metabolites with significantly higher and lower, respectively, cerebellum concentration in the hypothyroid compared to the euthyroid female mice. The respective numbers for the males were two and 24. Comparison of the euthyroid cerebellum metabolic profiles between the two sexes indicated 36 metabolites, including glucose, myo- and scyllo-inositol, with significantly lower concentration in the females versus the males. This implies that the female mouse cerebellum has been

  12. Localization of the fourth locus (GLC1E) for adult-onset primary open-angle glaucoma to the 10p15-p14 region.

    PubMed Central

    Sarfarazi, M; Child, A; Stoilova, D; Brice, G; Desai, T; Trifan, O C; Poinoosawmy, D; Crick, R P

    1998-01-01

    One of the major causes of blindness is primary open-angle glaucoma, which affects millions of elderly people worldwide. Genetic studies have so far mapped three loci for the adult-onset form of this condition to the 2cen-q13, 3q21-q24, and 8q23 regions. Herein, we report the localization of a fourth locus, to the 10p15-p14 region, in one large British family with a classical form of normal-tension open-angle glaucoma. Of the 42 meioses genotyped in this pedigree, 39 subjects (16 affected) inherited a haplotype compatible with their prior clinical designation, whereas the remaining 3 were classified as unknown. Although a maximum LOD score of 10.00 at a recombination fraction of straight theta=.00 was obtained with D10S1216, 21 other markers provided significant values, varying between 3.77 and 9.70. When only the affected meioses of this kindred were analyzed, LOD scores remained statistically significant, ranging from 3.16 (D10S527) to 3.57 (D10S506). Two critical recombinational events in the affected subjects positioned this new locus to a region of approximately 21 cM, flanked by D10S1729 and D10S1664. However, an additional recombination in a 59-year-old unaffected female suggests that this locus resides between D10S585 (or D10S1172) and D10S1664, within a genetic distance of 5-11 cM. However, the latter minimum region must be taken cautiously, because the incomplete penetrance has previously been documented for this group of eye conditions. A partial list of genes that positionally are considered as candidates includes NET1, PRKCT, ITIH2, IL2RA, IL15RA, IT1H2, hGATA3, the mRNA for open reading frame KIAA0019, and the gene for D123 protein. PMID:9497264

  13. Experiences of t-PA use in moderate-to-severe hepatic veno-occlusive disease after hematopoietic SCT: is it still reasonable to use t-PA?

    PubMed

    Yoon, J-H; Min, W-S; Kim, H-Je; Kim, J-H; Shin, S-H; Yahng, S-A; Lee, S-E; Cho, B-S; Eom, K-S; Kim, Y-J; Lee, S; Min, C-K; Cho, S-G; Kim, D-W; Lee, J-W; Park, C-W

    2013-11-01

    Hepatic veno-occlusive disease (VOD) remains one of the most severe complications of hematopoietic SCT (HSCT). Anticoagulation and thrombolytic therapies using tissue-plasminogen activator (t-PA) have been used, but are reported to be ineffective and are associated with significant bleeding complications. We analyzed 56 moderate-to-severe post HSCT hepatic VOD cases treated with t-PA. We analyzed clinical outcomes according to the maximal daily dose of t-PA (t-PAmax) and the severity of VOD. Patients were stratified by t-PAmax10 mg (n=37) vs t-PAmax>10 mg (n=19). A higher t-PAmax was associated with increased mortality. Bleeding complications were more likely at higher t-PAmax in both moderate and severe VOD (P=0.036, 0.063), especially if patients had concomitant use of anticoagulants (36.4% vs 13.3%). In moderate VOD, the response rate was 86.4% for t-PAmax10 mg/day and 80% for t-PAmax>10 mg compared with 33.3% and 7.1%, respectively, for severe VOD (P=0.106). The 5-year OS in moderate and severe VOD was 49% and 7%, respectively, and it was 32% for t-PAmax10 mg and 18% for t-PAmax>10 mg. Our data demonstrate that lower bleeding complications and bleeding-related deaths may result from strict limitations on the t-PAmax without concomitant use of anticoagulation therapy. However, the overall response and survival outcomes should be re-evaluated by a well-validated study in the future.

  14. Geriatric Pulsar Still Kicking

    NASA Astrophysics Data System (ADS)

    2009-02-01

    's clearly fading as it ages, it is still more than holding its own with the younger generations." It's likely that two forms of X-ray emission are produced in J0108: emission from particles spiraling around magnetic fields, and emission from heated areas around the neutron star's magnetic poles. Measuring the temperature and size of these heated regions can provide valuable insight into the extraordinary properties of the neutron star surface and the process by which charged particles are accelerated by the pulsar. The younger, bright pulsars commonly detected by radio and X-ray telescopes are not representative of the full population of objects, so observing objects like J0108 helps astronomers see a more complete range of behavior. At its advanced age, J0108 is close to the so-called "pulsar death line," where its pulsed radiation is expected to switch off and it will become much harder, if not impossible, to observe. "We can now explore the properties of this pulsar in a regime where no other pulsar has been detected outside the radio range," said co-author Oleg Kargaltsev of the University of Florida. "To understand the properties of 'dying pulsars,' it is important to study their radiation in X-rays. Our finding that a very old pulsar can be such an efficient X-ray emitter gives us hope to discover new nearby pulsars of this class via their X-ray emission." The Chandra observations were reported by Pavlov and colleagues in the January 20, 2009, issue of The Astrophysical Journal. However, the extreme nature of J0108 was not fully apparent until a new distance to it was reported on February 6 in the PhD thesis of Adam Deller from Swinburne University in Australia. The new distance is both larger and more accurate than the distance used in the Chandra paper, showing that J0108 was brighter in X-rays than previously thought. "Suddenly this pulsar became the record holder for its ability to make X-rays," said Pavlov, "and our result became even more interesting without us

  15. Managing juvenile Huntington's disease.

    PubMed

    Quarrell, Oliver W J; Nance, Martha A; Nopoulos, Peggy; Paulsen, Jane S; Smith, Jonathan A; Squitieri, Ferdinando

    2013-06-01

    Huntington's disease (HD) is a well-recognized progressive neurodegenerative disorder that follows an autosomal dominant pattern of inheritance. Onset is insidious and can occur at almost any age, but most commonly the diagnosis is made between the ages of 35 and 55 years. Onset ≤20 years of age is classified as juvenile HD (JHD). This age-based definition is arbitrary but remains convenient. There is overlap between the clinical pathological and genetic features seen in JHD and more traditional adult-onset HD. Nonetheless, the frequent predominance of bradykinesia and dystonia early in the course of the illness, more frequent occurrence of epilepsy and myoclonus, more widespread pathology, and larger genetic lesion means that the distinction is still relevant. In addition, the relative rarity of JHD means that the clinician managing the patient is often doing so for the first time. Management is, at best, symptomatic and supportive with few or no evidence-based guidelines. In this article, the authors will review what is known of the condition and present some suggestions based on their experience.

  16. Chikungunya Fever Presenting as a Systemic Disease with Fever. Arthritis and Rash: Our Experience in Israel.

    PubMed

    Tanay, Amir

    2016-01-01

    Chikungunya fever (CHIK-F) has been increasingly documented among Western travelers returning from areas with chikungunya virus transmission, which are also popular tourist sites. We present three Israeli travelers who developed fever, maculopapular rash and long-standing arthralgias while visiting northern Indian states not known to be involved in the chikungunya fever epidemic. We also present an epidemiological review of the chikungunya epidemic over the past decades. Rare systemic manifestations of this disorder, like catastrophic antiphospholipid syndrome (CAPS) and adult-onset Still's syndrome, are discussed. The present era of international travel poses a new diagnostic and epidemiologic challenge that demands increased awareness to the possibility of an exotic tropical infectious disease.

  17. Still hope for schistosomiasis vaccine

    PubMed Central

    Ricciardi, Alessandra; Ndao, Momar

    2015-01-01

    Schistosomiasis is a parasitic disease caused by helminths belonging to the Schistosoma genus. Approximately 700 million people are at risk of infection and 200 million people are currently infected. Schistosomiasis is the most important helminth infection, and treatment relies solely on the drug praziquantel. Worries of praziquantel resistance as well as high disease burden are only some of the justifications which support the development of a vaccine against schistosomiasis. To date, only 2 schistosome vaccines have made it into clinical trials: Sh28GST (Bilhvax) and Sm14. However, there are several vaccine candidates, such as TSP-2, sm-p8, and Sm-Cathepsin B, which are generating promising results in pre-clinical studies. Schistosomiasis vaccine development has been an uphill battle, and there are still several hurdles to overcome in the future. Fortunately, the research groups involved in the research for vaccine development have not abandoned their work. Furthermore, in the last few years, schistosomiasis has garnered some additional attention on a global scale due to its significant impact on public health. PMID:26176659

  18. Still hope for schistosomiasis vaccine.

    PubMed

    Ricciardi, Alessandra; Ndao, Momar

    2015-01-01

    Schistosomiasis is a parasitic disease caused by helminths belonging to the Schistosoma genus. Approximately 700 million people are at risk of infection and 200 million people are currently infected. Schistosomiasis is the most important helminth infection, and treatment relies solely on the drug praziquantel. Worries of praziquantel resistance as well as high disease burden are only some of the justifications which support the development of a vaccine against schistosomiasis. To date, only 2 schistosome vaccines have made it into clinical trials: Sh28GST (Bilhvax) and Sm14. However, there are several vaccine candidates, such as TSP-2, sm-p8, and Sm-Cathepsin B, which are generating promising results in pre-clinical studies. Schistosomiasis vaccine development has been an uphill battle, and there are still several hurdles to overcome in the future. Fortunately, the research groups involved in the research for vaccine development have not abandoned their work. Furthermore, in the last few years, schistosomiasis has garnered some additional attention on a global scale due to its significant impact on public health.

  19. Adult Orbital Xanthogranulomatous Disease: A Review with Emphasis on Etiology, Systemic Associations, Diagnostic Tools, and Treatment.

    PubMed

    Kerstetter, Justin; Wang, Jun

    2015-07-01

    Adult orbital xanthogranulomatous diseases are rare entities and encompass a group of disorders with varying manifestations that are poorly understood. Taken as a group, there are non-Langerhans histiocytic disorders (type II) that are diagnosed histologically by the presence of foamy histiocytes, Touton giant cells, and varying degrees of fibrosis. Based on the accompanying systemic associations, there are 4 main categories of adult xanthogranulomatous disease: adult-onset xanthogranuloma, adult-onset asthma and periocular xanthogranuloma, necrobiotic xanthogranuloma, and Erdheim-Chester disease. Herein, we discuss the etiopathogenesis, systemic associations, methods of diagnosis, and treatment options for these disorders.

  20. Huntington Disease: A Case Study of Early Onset Presenting as Depression

    ERIC Educational Resources Information Center

    Duesterhus, Pia; Schimmelmann, Benno Graf; Wittkugel, Oliver; Schulte-Markwort, Michael

    2004-01-01

    Huntington disease is a dominantly inherited, neurodegenerative disease characterized by choreiform movement disturbances and dementia, usually with adult onset. The rare juvenile-onset Huntington disease differs from the adult phenotype. A case presenting twice, at age 10 with all the signs of a major depression and age 14 with mutism and…

  1. Siblings with the adult-onset slowly progressive type of pantothenate kinase-associated neurodegeneration and a novel mutation, Ile346Ser, in PANK2: clinical features and (99m)Tc-ECD brain perfusion SPECT findings.

    PubMed

    Doi, Hiroshi; Koyano, Shigeru; Miyatake, Satoko; Matsumoto, Naomichi; Kameda, Tomoaki; Tomita, Atsuko; Miyaji, Yosuke; Suzuki, Yume; Sawaishi, Yukio; Kuroiwa, Yoshiyuki

    2010-03-15

    Pantothenate kinase-associated neurodegeneration (PKAN), formerly known as Hallervorden-Spatz syndrome (HSS), is an autosomal recessive neurodegenerative disorder characterized by iron accumulation in the brain. Mutations in the pantothenate kinase 2 (PANK2) gene are known to be responsible for PKAN. Several studies have revealed correlations between clinical phenotypes and particular PANK2 mutations. The adult-onset slowly progressive type of PKAN with PANK2 mutations is very rare. In this report, we describe siblings with the adult-onset slowly progressive type of PKAN with a novel mutation, Ile346Ser, in PANK2. The siblings had the same mutation in PANK2 and had common clinical signs such as misalignment of teeth, a high arched palate, hollow feet, a slight cognitive decline, and an apparent executive dysfunction, although they showed different patterns of movement disorders. Thus, even if PKAN patients have identical mutations, it is likely that they will present with different types of movement disorders. Brain perfusion single photon emission computed tomography in both patients showed decreased regional cerebral blood flow in the bilateral frontoparietal lobes, the globus pallidus, the striatum, and around the ventriculus quartus. Cardiac uptake of [(123)I] meta-iodobenzylguanidine was normal in both patients. Analysis of genotype-phenotype correlations and the elucidation of mutational effects on pantothenate kinase 2 function, expression, and structure are important for understanding the mechanisms of PKAN.

  2. Wild Beasts of Still Life

    ERIC Educational Resources Information Center

    Lott, Debra

    2007-01-01

    This article describes a project with a transformative approach to color theory and still life. Students' use of an arbitrary color scheme can open their eyes, push their creativity and produce exciting paintings. Ordinary still-life objects will be transformed into dramatic, vibrant visuals. The Fauve style of painting is a great art history…

  3. A 12-week, randomized, parallel-group, proof-of-concept study of tulobuterol patch and salmeterol inhaler as add-on therapy in adult-onset mild-to-moderate asthma.

    PubMed

    Inoue, Hideki; Niimi, Akio; Matsumoto, Hisako; Ito, Isao; Oguma, Tsuyoshi; Otsuka, Kojiro; Takeda, Tomoshi; Nakaji, Hitoshi; Tajiri, Tomoko; Iwata, Toshiyuki; Nagasaki, Tadao; Mishima, Michiaki

    2017-01-01

    Patch formulation of tulobuterol has been used in asthma treatment as a long-acting β2 -agonist (LABA) through sustained skin absorption. Its treatment efficacy, especially in small airways, remains poorly understood. The study aim was to investigate LABA add-on effects of tulobuterol patch (TP) and salmeterol inhaler (SA) on pulmonary function, asthma control and health status. Patients who had adult-onset under-control asthma, despite taking inhaled corticosteroids, were enrolled in a randomized, open-label, parallel-group, proof-of-concept study of 12-week add-on treatment with TP (n=16) or SA (n=17). Spirometry, impulse oscillometry (IOS), exhaled nitric oxide levels, and clinical questionnaires of asthma control, health status (St. George's Respiratory Questionnaire: SGRQ), and symptoms were evaluated every 4 weeks. Add-on treatment of SA significantly improved the spirometric indices of small airway obstruction (forced expiratory flow between 25% and 75% of FVC: FEF25-75 , and maximum expiratory flow at 25% of FVC: MEF25 ) and IOS indices of whole respiratory resistance (resistance at 5 Hz) as compared to TP. In intra-group comparisons, add-on treatment of TP improved the scores of the asthma control test and the total SGRQ, as well as the symptom and impact components of the SGRQ. SA add-on treatment improved FEV1 and IOS parameters of resistance at 20 Hz and reactance at 5 Hz. Neither of the treatments improved exhaled nitric oxide levels. In conclusion, add-on treatment of TP improved asthma control and health status, whereas SA improved pulmonary function measures associated with large and small airway involvement among patients with adult-onset mild-to-moderate asthma.

  4. PRENATAL EXPOSURE TO LOW DOSE PFOA INDUCES LOW DEVELOPMENTAL BODY WEIGHT FOLLOWED BY ADULT ONSET OBESITY THAT IS BLUNTED IN OVARIECTOMIZED ANIMALS

    EPA Science Inventory

    The Barker hypothesis, or fetal origins of adult disease, proposes that individuals born to mothers who were pregnant during lean times develop a "thrifty" phenotype with a smaller body size and lowered metabolic rates, leading to a propensity for obesity and development of disor...

  5. SARS: Down But Still a Threat

    DTIC Science & Technology

    2003-08-01

    economic and political impact. • Although SARS has killed far fewer people than die each year from more common maladies such as pneumonia, influenza...is not necessarily authoritative. DI Cartography Center/MPG 764135AI 8-03 All of these diseases, except cholera , dengue, and diphtheria, are... Cholera O1 Dengue/Dengue Hemorrhagic Fever Cholera O139 Dengue 9 Discussion SARS: Down But Still a Threat The Global Health Challenge

  6. Sternalis muscle: a mystery still.

    PubMed

    Loukas, Marios; Bowers, Maggi; Hullett, Joel

    2004-05-01

    Despite intensive anatomical research during the last century, anatomical structures or variations of these structures may still cause confusion or even iatrogenic injury. A matter of debate is the sternalis muscle. We present a review of the literature of the sternalis muscle with special emphasis on its clinical anatomy.

  7. A Beautiful Britto Still Life

    ERIC Educational Resources Information Center

    Coy, Mary

    2012-01-01

    Romero Britto is a wonderful artist for young students to study when learning the building blocks of art and design. Colorful, linear, and full of bold patterns, Britto's work blends a contemporary cubist style and pop art commercial appeal. Themes of this contemporary artist's work include animals, flowers, still life, and people in joyful…

  8. Why Are Chimps Still Chimps?

    ERIC Educational Resources Information Center

    Johnson, Norman A.; Smith, James J.; Pobiner, Briana; Schrein, Caitlin

    2012-01-01

    Teachers may be posed with such questions as, "If we evolved from chimps, why are there still chimps?" We provide teachers with answers to this and related questions in the context of the latest genetic, fossil, and behavioral evidence. We also provide references they can use to further students' understanding of human evolution and evolution in…

  9. Clinical neurogenetics: huntington disease.

    PubMed

    Bordelon, Yvette M

    2013-11-01

    Huntington disease (HD) is an autosomal dominant, adult-onset, progressive neurodegenerative disease characterized by the triad of abnormal movements (typically chorea), cognitive impairment, and psychiatric problems. It is caused by an expanded CAG repeat in the gene encoding the protein huntingtin on chromosome 4 and causes progressive atrophy of the striatum as well as cortical and other extrastriatal structures. Genetic testing has been available since 1993 to confirm diagnosis in affected adults and for presymptomatic testing in at-risk individuals. This review covers HD signs, symptoms, and pathophysiology; current genetic testing issues; and current and future treatment strategies.

  10. Imagers for digital still photography

    NASA Astrophysics Data System (ADS)

    Bosiers, Jan; Dillen, Bart; Draijer, Cees; Manoury, Erik-Jan; Meessen, Louis; Peters, Inge

    2006-04-01

    This paper gives an overview of the requirements for, and current state-of-the-art of, CCD and CMOS imagers for use in digital still photography. Four market segments will be reviewed: mobile imaging, consumer "point-and-shoot cameras", consumer digital SLR cameras and high-end professional camera systems. The paper will also present some challenges and innovations with respect to packaging, testing, and system integration.

  11. Managing juvenile Huntington’s disease

    PubMed Central

    Quarrell, Oliver W. J.; Nance, Martha A.; Nopoulos, Peggy; Paulsen, Jane S.; Smith, Jonathan A.; Squitieri, Ferdinando

    2013-01-01

    SUMMARY Huntington’s disease (HD) is a well-recognized progressive neurodegenerative disorder that follows an autosomal dominant pattern of inheritance. Onset is insidious and can occur at almost any age, but most commonly the diagnosis is made between the ages of 35 and 55 years. Onset ≤20 years of age is classified as juvenile HD (JHD). This age-based definition is arbitrary but remains convenient. There is overlap between the clinical pathological and genetic features seen in JHD and more traditional adult-onset HD. Nonetheless, the frequent predominance of bradykinesia and dystonia early in the course of the illness, more frequent occurrence of epilepsy and myoclonus, more widespread pathology, and larger genetic lesion means that the distinction is still relevant. In addition, the relative rarity of JHD means that the clinician managing the patient is often doing so for the first time. Management is, at best, symptomatic and supportive with few or no evidence-based guidelines. In this article, the authors will review what is known of the condition and present some suggestions based on their experience. PMID:24416077

  12. Solar stills for agricultural purposes

    NASA Technical Reports Server (NTRS)

    Selcuk, M. K.; Tran, V. V.

    1975-01-01

    Basic concepts of using desalinated water for agricultural purposes are outlined. A mathematical model describing heat and mass transfer in a system combining a solar still with a greenhouse, its solution, and test results of a small-scale unit built at the Middle East Technical University, Ankara, Turkey, are discussed. The unit was employed to demonstrate the technical feasibility of the system. Further development and modifications are necessary for larger-scale operations. The basis of an optimization study which is underway at the Brace Research Institute of McGill University in Montreal, Canada, aimed at finding the best combination of design and operation parameters is also presented.

  13. Is asthma prevalence still increasing?

    PubMed

    Lundbäck, Bo; Backman, Helena; Lötvall, Jan; Rönmark, Eva

    2016-01-01

    Increased awareness of asthma in society and altered diagnostic practices makes evaluation of data on prevalence change difficult. In most parts of the world the asthma prevalence seems to still be increasing. The increase is associated with urbanization and has been documented particularly among children and teenagers in urban areas of middle- and low-level income countries. Use of validated questionnaires has enabled comparisons of studies. Among adults there are few studies based on representative samples of the general population which allow evaluation of time trends of prevalence. This review focuses mainly on studies of asthma prevalence and symptoms among adults. Parallel with increased urbanization, we can assume that the increase in asthma prevalence in most areas of the world will continue. However, in Australia and North-West Europe studies performed, particularly among children and adolescents, indicate that the increase in asthma prevalence may now be leveling off.

  14. [Orthostatic tremor: unsteadiness while standing still].

    PubMed

    Wiendels, Natalie J; Tromp, Selma C

    2012-01-01

    We present three patients with histories of the typical unsteady feeling in the legs while standing still which disappears when walking or sitting down. An orthostatic tremor is a disorder that is difficult to recognise because patients describe balance disturbances rather than tremors. Clinical findings include a fine tremor in the legs which may be invisible but can be heard on auscultation and felt on palpation of the leg muscles. The diagnosis is confirmed by EMG which reveals a pathognomonic tremor of 13-18 Hz while the patient is standing upright. Its pathophysiology is unknown but a disorder related to proprioceptive feedback has been suggested. The tremor can be associated with Parkinson's disease, Graves' disease, and cerebellar or pontine lesions which should be excluded by laboratory investigations and MRI. There is little evidence available on effective treatments, but clonazepam seems to be the first drug of choice, followed by gabapentin. Levodopa can be tried in patients with parkinsonism.

  15. Is acute appendicitis still misdiagnosed?

    PubMed Central

    Danys, Donatas; Poskus, Tomas; Mikalauskas, Saulius; Poskus, Eligijus; Jotautas, Valdemaras; Beisa, Virgilijus; Strupas, Kestutis

    2016-01-01

    Abstract Objective The optimal diagnostics and treatment of acute appendicitis continues to be a challenge. A false positive diagnosis of appendicitis may lead to an unnecessary operation, which has been appropriately termed negative appendectomy. The aim of our study was to identify the effectiveness of preoperative investigations in preventing negative appendectomy. Methods A retrospective study was performed on adult patients who underwent operation for suspected acute appendicitis from 2008 to 2013 at Vilnius University Hospital Santariskiu Klinikos. Patients were divided into two groups: group A underwent an operation, where appendix was found to be normal (non-inflamed); group B underwent an appendectomy for inflamed appendix. Groups were compared for preoperative data, investigations, treatment results and pathology findings. Results 554 patients were included in the study. Preoperative laboratory tests results of hemoglobin, hematocrit concentrations and white blood cell count were significantly higher in group B (p<0.001). Ultrasonography was performed for 78 % of patients in group A and 74 % in group B and did not provide any statistically significant results. Comparing Alvarado score results, there were more patients with Alvarado score less than 7 in group A than in group B. In our large series we could find only four independent risk factors, and they could only account for 24 % of cases. Conclusions In summary, acute appendicitis is still often misdiagnosed and the ratio of negative appendectomies remains rather high. Additional investigations such as observation and computed tomography should be used to prevent this.

  16. Unusual sequelae of adult-onset dermatomyositis

    PubMed Central

    Naffaa, Mohammad Ebrahim; Bishara, Rema; Braun-Moscovici, Yolanda; Balbir-Gurman, Alexandra

    2014-01-01

    A 44-year-old woman diagnosed with dermatomyositis 5 years ago based on progressive proximal muscle weakness, elevated creatine kinase, typical findings on electromyography and muscle biopsy. Despite the treatment, in contrast to improvement in her muscle symptoms, the heliotrope rash of her eyelids persisted. After several years, the patient developed multiple limited skin retraction lesions with hyperpigmentation on both lower limbs. Palpation of these lesions revealed dry, cold and very firm skin on both thighs and calves, particularly in the distal areas. X-ray and ultrasound imaging of the calves showed multiple subcutaneous calcifications in the distal muscles. PMID:25085949

  17. Adult-onset deficiency in growth hormone and insulin-like growth factor-I decreases survival of dentate granule neurons: insights into the regulation of adult hippocampal neurogenesis.

    PubMed

    Lichtenwalner, Robin J; Forbes, M Elizabeth; Sonntag, William E; Riddle, David R

    2006-02-01

    Insulin-like growth factor-I (IGF-I), long thought to provide critical trophic support during development, also has emerged as a candidate for regulating ongoing neuronal production in adulthood. Whether and how IGF-I influences each phase of neurogenesis, however, remains unclear. In the current study, we used a selective model of growth hormone (GH) and plasma IGF-I deficiency to evaluate the role of GH and IGF-I in regulating cell proliferation, survival, and neuronal differentiation in the adult dentate gyrus. GH/IGF-I-deficient dwarf rats of the Lewis strain were made GH/IGF-I replete throughout development via twice daily injections of GH, and then GH/IGF-I deficiency was initiated in adulthood by removing animals from GH treatment. Bromodeoxyuridine (BrdU) labeling revealed no effect of GH/IGF-I deficiency on cell proliferation, but adult-onset depletion of GH and plasma IGF-I significantly reduced the survival of newly generated cells in the dentate gyrus. Colabeling for BrdU and markers of immature and mature neurons revealed a selective effect of GH/IGF-I deficiency on the survival of more mature new neurons. The number of BrdU-labeled cells expressing the immature neuronal marker TUC-4 did not differ between GH/IGF-I-deficient and -replete animals, but the number expressing only the marker of maturity NeuN was lower in depleted animals. Taken together, results from the present study suggest that, under conditions of short-term GH/IGF-I deficiency during adulthood, dentate granule cells continue to be produced, to commit to a neuronal fate, and to begin the process of neuronal maturation, whereas survival of the new neurons is impaired.

  18. Role of CYP1B1, MYOC, OPTN and OPTC genes in adult-onset primary open-angle glaucoma: predominance of CYP1B1 mutations in Indian patients

    PubMed Central

    Basavaraj, Manjunath G.; Gupta, Santosh K.; Qamar, Imteyaz; Ali, Abdullah Mahmood; Bajaj, Vineeta; Ramesh, T.K.; Prakash, D. Ravi; Shetty, Jyoti S.; Dorairaj, Syril K.

    2007-01-01

    Purpose Mutations in the CYP1B1, MYOC, OPTN, and WDR36 genes result in glaucoma. Given its expression in the optic nerve, it is likely a mutation in the OPTC gene is also involved in initiating glaucoma. This study was designed to evaluate the involvement of the CYP1B1, MYOC, OPTN, and OPTC genes in the etiology of adult-onset primary open-angle glaucoma (POAG) found in 251 Indian patients. Methods Blood samples were obtained from individuals for DNA isolation. A combination of polymerase chain reaction-single strand conformation polymorphism, allele-specific PCR, and DNA sequencing techniques were used to detect mutations in four genes. Four microsatellite markers from the CYP1B1 candidate region and three intragenic CYP1B1 single nucleotide polymorphisms (SNPs) were used to determine the origin of the most common CYP1B1 mutations. Results Three previously known mutations (Pro193Leu, Glu229Lys, and Arg368His) and one novel (Met292Lys) mutation were found in the CYP1B1 gene. Frequencies of the most common mutations, Glu229Lys and Arg368His, in patients were 5.12% and 3.98%, respectively. The Glu229Lys and Arg368His mutations were also found in normal controls at frequencies of 5% and 2%, respectively, suggesting that these mutations might be polymorphic variants in our population. The absence of allele sharing for D2S177, D2S1346, D2S2974, and D2S2331 markers and three intragenic CYP1B1 SNPs in patients suggested multiple origins for the Glu229Lys and Arg368His variants. Two of 251 (0.8%) patients had the Gln48His mutation in MYOC. There was no difference in the frequency of a MYOC -83G>A promoter polymorphism between patients and controls. A novel OPTN mutation, Thr202Arg, was detected in one of 251 (0.4%) patients. The OPTN variant Met98Lys was detected in similar frequencies in patients and controls. No mutation was detected in OPTC. Taken together, 3.59% (9/251) of our POAG patients had mutations in the CYP1B1, MYOC, and OPTN genes. Conclusions This is the

  19. Feline infectious peritonitis: still an enigma?

    PubMed

    Kipar, A; Meli, M L

    2014-03-01

    Feline infectious peritonitis (FIP) is one of the most important fatal infectious diseases of cats, the pathogenesis of which has not yet been fully revealed. The present review focuses on the biology of feline coronavirus (FCoV) infection and the pathogenesis and pathological features of FIP. Recent studies have revealed functions of many viral proteins, differing receptor specificity for type I and type II FCoV, and genomic differences between feline enteric coronaviruses (FECVs) and FIP viruses (FIPVs). FECV and FIP also exhibit functional differences, since FECVs replicate mainly in intestinal epithelium and are shed in feces, and FIPVs replicate efficiently in monocytes and induce systemic disease. Thus, key events in the pathogenesis of FIP are systemic infection with FIPV, effective and sustainable viral replication in monocytes, and activation of infected monocytes. The host's genetics and immune system also play important roles. It is the activation of monocytes and macrophages that directly leads to the pathologic features of FIP, including vasculitis, body cavity effusions, and fibrinous and granulomatous inflammatory lesions. Advances have been made in the clinical diagnosis of FIP, based on the clinical pathologic findings, serologic testing, and detection of virus using molecular (polymerase chain reaction) or antibody-based methods. Nevertheless, the clinical diagnosis remains challenging in particular in the dry form of FIP, which is partly due to the incomplete understanding of infection biology and pathogenesis in FIP. So, while much progress has been made, many aspects of FIP pathogenesis still remain an enigma.

  20. 32 CFR 705.10 - Still photography.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 5 2010-07-01 2010-07-01 false Still photography. 705.10 Section 705.10... AND OFFICIAL RECORDS PUBLIC AFFAIRS REGULATIONS § 705.10 Still photography. (a) Policy and procedures...) Basic policy and procedures for still photos are set forth in the Manual of Naval Photography,...

  1. Gaining insight into the health effects of soy but a long way still to go: commentary on the fourth International Symposium on the Role of Soy in Preventing and Treating Chronic Disease.

    PubMed

    Messina, Mark; Gardner, Christoper; Barnes, Stephen

    2002-03-01

    Research into the health effects of soyfoods and soybean constituents has increased at a phenomenal pace over the past decade. This research includes a wide range of areas, such as cancer, coronary heart disease, osteoporosis, cognitive function, menopausal symptoms and renal function. Importantly, there are an increasing number of clinical studies being conducted in this field, which was quite evident from the findings presented at the Fourth International Symposium on the Role of Soy in Preventing and Treating Chronic Disease, November 4-7, 2001, in San Diego, California. There is no doubt that progress in understanding the health effects of soy is being made, but much of the data are frustratingly inconsistent. For example, there were conflicting results presented at the symposium on the role of isoflavones in bone health. Similarly, presentations painted an unclear picture of the role of isoflavones in cholesterol reduction. The relatively short duration and small sample size of many of the human studies in this field likely contribute to the inconsistent results. Although there are some controversies regarding the safety of soy for certain subsets of the population, special sessions at the symposium on breast cancer and cognitive function did much to alleviate concerns that soy could have detrimental effects in these areas. Furthermore, published data and new research presented at this meeting suggest that the consumption of even 10 g (typical of Asian intake) of isoflavone-rich soy protein per day may be associated with health benefits. If this modest amount of soy protein were to be incorporated in the American diet, it would represent only approximately 15% of total U. S. protein intake.

  2. Measles: Still a Significant Health Threat.

    PubMed

    Lindberg, Claire; Lanzi, Maria; Lindberg, Kristen

    2015-01-01

    Measles (Rubeola), although considered eradicated in the United States, still causes periodic outbreaks. Vaccine refusal leads to vulnerable pockets of individuals who may become infected once the virus is imported from countries where it is endemic. In turn, these individuals may spread the virus to young infants and to other vulnerable individuals. Many healthcare providers are not familiar with this disease or with the factors that contribute to the risk of spread. Measles causes a serious febrile illness that may lead to pneumonia, blindness, deafness, neurological disorders, and even death. Patients with measles need supportive care and administration of oral vitamin A. The measles vaccine is highly effective and considered extremely safe, but misinformation about the safety of this and other vaccines has decreased immunization coverage in some areas of the country. Mandatory immunization laws exist in every state and have been upheld by courts including the United States Supreme Court, but laws and exemptions vary among states. Nurses can play a strong role in care of patients with measles, case identification, and prevention of transmission. Most importantly, because nurses hold positions of trust in their communities, they should be tireless frontline advocates for immunization. The purpose of this article is to provide information on measles, its transmission, signs and symptoms, treatment, prevention, and relevant laws and regulations.

  3. Is the incidence of heart attack still decreasing in Australia? Developing reliable methods for monitoring trends in myocardial infarction and coronary heart disease (AUS-MOCHA): a study protocol

    PubMed Central

    Nedkoff, Lee; Knuiman, Matthew; Hobbs, Michael S T; Hung, Joseph; Mathur, Sushma; Beilby, John; Reynolds, Anna; Briffa, Tom G; Lopez, Derrick

    2016-01-01

    Introduction Accurate monitoring of acute coronary heart disease (CHD) is essential for understanding the effects of primary and secondary prevention and for planning of healthcare services. The ability to reliably monitor acute CHD has been affected by new diagnostic tests for myocardial infarction (MI) and changing clinical classifications and management of CHD. Our study will develop new and reliable methods for monitoring population trends in incidence, outcomes and health service usage for acute CHD and chest pain. Methods and analysis The study cohort of all CHD will be identified from the Western Australian Data Linkage System using state-wide data sets for emergency department presentation, hospitalisations and mortality data for 2002–2014. This core linked data set will be supplemented with data from hospital medical record reviews, pathology data and hospital pharmacy dispensing databases. The consistency over time of the coding of the different subgroups of CHD/chest pain (ST-elevation MI, non-ST elevation MI, unstable angina, stable angina, other CHD, non-CHD chest pain) in linked data will be assessed using these data sources, and an algorithm developed detailing groups in which temporal trends can be reliably measured. This algorithm will be used for measurement of trends in incidence and outcomes of acute CHD, and to develop further methods for monitoring acute CHD using unlinked and linked data with varying availability of hospitalisation history. Ethics and dissemination Ethics approval has been obtained from the Human Research Ethics Committees of the WA Department of Health (#2016/23) and The University of Western Australia (RA/4/1/7230). Findings will be disseminated via publication in peer-reviewed journals, and presentation at national and international conferences. There will also be a strong platform for dissemination of new monitoring methods via collaboration with the Australian Institute of Health and Welfare which will assist with

  4. Unsupervised Pedestrian Detection in Still Images

    DTIC Science & Technology

    2013-09-01

    Unsupervised Pedestrian Detection in Still Images by Prudhvi Gurram , Shuowen Hu, Christopher Reale, and Alex Chan ARL-TR...Research Laboratory Adelphi, MD 20783-1197 ARL-TR-6615 September 2013 Unsupervised Pedestrian Detection in Still Images Prudhvi Gurram ...Pedestrian Detection in Still Images 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Prudhvi Gurram , Shuowen Hu

  5. Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations.

    PubMed

    Manikkam, Mohan; Tracey, Rebecca; Guerrero-Bosagna, Carlos; Skinner, Michael K

    2013-01-01

    Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1-F3) following ancestral exposure during fetal gonadal sex determination. The current study was designed to determine if a mixture of plastic derived endocrine disruptor compounds bisphenol-A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP) at two different doses promoted epigenetic transgenerational inheritance of adult onset disease and associated DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to either the "plastics" or "lower dose plastics" mixture during embryonic days 8 to 14 of gonadal sex determination and the incidence of adult onset disease was evaluated in F1 and F3 generation rats. There were significant increases in the incidence of total disease/abnormalities in F1 and F3 generation male and female animals from plastics lineages. Pubertal abnormalities, testis disease, obesity, and ovarian disease (primary ovarian insufficiency and polycystic ovaries) were increased in the F3 generation animals. Kidney and prostate disease were only observed in the direct fetally exposed F1 generation plastic lineage animals. Analysis of the plastics lineage F3 generation sperm epigenome previously identified 197 differential DNA methylation regions (DMR) in gene promoters, termed epimutations. A number of these transgenerational DMR form a unique direct connection gene network and have previously been shown to correlate with the pathologies identified. Observations demonstrate that a mixture of plastic derived compounds, BPA and phthalates, can promote epigenetic transgenerational inheritance of adult onset disease. The sperm DMR provide potential epigenetic biomarkers for transgenerational disease and/or ancestral environmental exposures.

  6. Still Life with Fruit and Seashell

    ERIC Educational Resources Information Center

    Gojeski, Laura

    2011-01-01

    Henri Matisse's painting, "Sideboard," opens the door to the author's first-grade students' lesson on still life. This lesson is about the process of designing, the act of making decisions, and the knowledge of one's own preferences. In this article, the author describes how the students made still life with fruit and seashells.

  7. Apprentice Still Photographic Specialist (AFSC 23132).

    ERIC Educational Resources Information Center

    Air Univ., Gunter AFS, Ala. Extension Course Inst.

    This four-volume student text is designed for use by Air Force personnel enrolled in a self-study extension course for apprentice still photographic specialists. Covered in the individual volumes are general subjects (career ladder progression, security, photographic safety, and photographic laboratory administration); still photographic…

  8. Spinocerebellar ataxia type 13 mutation that is associated with disease onset in infancy disrupts axonal pathfinding during neuronal development.

    PubMed

    Issa, Fadi A; Mock, Allan F; Sagasti, Alvaro; Papazian, Diane M

    2012-11-01

    Spinocerebellar ataxia type 13 (SCA13) is an autosomal dominant disease caused by mutations in the Kv3.3 voltage-gated potassium (K(+)) channel. SCA13 exists in two forms: infant onset is characterized by severe cerebellar atrophy, persistent motor deficits and intellectual disability, whereas adult onset is characterized by progressive ataxia and progressive cerebellar degeneration. To test the hypothesis that infant- and adult-onset mutations have differential effects on neuronal development that contribute to the age at which SCA13 emerges, we expressed wild-type Kv3.3 or infant- or adult-onset mutant proteins in motor neurons in the zebrafish spinal cord. We characterized the development of CaP (caudal primary) motor neurons at ∼36 and ∼48 hours post-fertilization using confocal microscopy and 3D digital reconstruction. Exogenous expression of wild-type Kv3.3 had no significant effect on CaP development. In contrast, CaP neurons expressing the infant-onset mutation made frequent pathfinding errors, sending long, abnormal axon collaterals into muscle territories that are normally innervated exclusively by RoP (rostral primary) or MiP (middle primary) motor neurons. This phenotype might be directly relevant to infant-onset SCA13 because interaction with inappropriate synaptic partners might trigger cell death during brain development. Importantly, pathfinding errors were not detected in CaP neurons expressing the adult-onset mutation. However, the adult-onset mutation tended to increase the complexity of the distal axonal arbor. From these results, we speculate that infant-onset SCA13 is associated with marked changes in the development of Kv3.3-expressing cerebellar neurons, reducing their health and viability early in life and resulting in the withered cerebellum seen in affected children.

  9. Stigmatization toward irritable bowel syndrome and inflammatory bowel disease in an online cohort

    PubMed Central

    Taft, T. H.; Bedell, A.; Naftaly, J.; Keefer, L.

    2017-01-01

    Background Stigma is associated with many negative health outcomes. Research has examined perceived and internalized stigma in individuals with irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), but less has been done to evaluate levels of enacted stigma associated with these conditions. The aim of this study was to evaluate the presence of enacted stigma toward IBS and IBD in the general population compared to an adult-onset asthma (AOA) control group. Methods Participants were recruited via social media and a research-dedicated website and completed all measures online. Participants were randomized to one of six clinical vignettes: (i) IBD male, (ii) IBD female, (iii) IBS male, (iv) IBS female, (v) AOA male, or (vi) AOA female. Participants read the assigned vignette and then completed measures of emotional empathy, level of familiarity, and enacted stigma. Key Results Participants reported higher levels of enacted stigma toward IBS compared to both IBD and AOA. No differences in stigma were found between IBD and AOA. Higher levels of familiarity were most strongly correlated with reduced IBD-related stigma, with weaker but still significant correlations between level of familiarity and IBS and AOA. Higher levels of emotional empathy were associated with reduced stigma for IBD, IBS, and AOA. Conclusions & Inferences Individuals with IBS experience greater levels of enacted stigma compared to IBD and AOA. This finding is consistent with previous research that has shown greater levels of perceived and internalized stigma in IBS compared to IBD. PMID:27501483

  10. Helicobacter and disease: still more questions than answers

    PubMed Central

    Kandel, Gabor

    2000-01-01

    Since the causative role of Helicobacter pylori in peptic ulcer and gastritis was established, a number of advances have been made. Helicobacter virulence factors have been identified, the changes it causes in gastric acid secretion has been elucidated, and the entire genome of H. pylori has been mapped. Multiple lines of evidence indicate a strong link between the bacterium and noncardia gastric cancer. The infection can be confidently diagnosed by noninvasive serologic tests and the urea breath test. Triple therapy is almost always curative, and the infection almost never recurs in Canadian adults, but eradicating the bacteria in the absence of peptic ulcer only rarely leads to resolution of dyspepsia. New studies suggest that treating Helicobacter may increase the risk of peptic esophagitis and adenocarcinoma of the esophagus and cardia. PMID:11045091

  11. Catatonia as an internal medicine disease: infrequent or still underdiagnosed?

    PubMed

    Proenca, Margarida; Marques, Filipa; Cardoso, Débora; Fonseca, Cândida

    2016-04-22

    Catatonia is a motor and behavioural syndrome with multiple psychiatric, general medical and neurological aetiologies that might be simultaneously present. B12 deficiency is a rare, treatable cause of catatonia, not always easy to rule out. The authors present a case of a woman with catatonia associated with severe cyanocobalamin deficiency, admitted to an internal medicine ward. The benign course was related to an adequate and early diagnosis.

  12. Amyloid myopathy: characteristic features of a still underdiagnosed disease.

    PubMed

    Chapin, John E; Kornfeld, Mario; Harris, Alexis

    2005-02-01

    A 62-year-old man with progressive proximal weakness underwent extensive evaluation including muscle biopsy without a clear diagnosis being established. A repeat muscle biopsy including Congo red-stained sections revealed infiltration of blood-vessel walls and endomysium with amyloid protein, as well as an unusual pattern of pathologic changes to muscle fibers. From a review of 79 cases of amyloid myopathy reported in the English-language literature, the characteristic features of this disorder are described. Congo red-stained sections of muscle biopsy viewed under fluorescent or polarized optics, and serum or urine protein immunoelectrophoresis, play an important role in the evaluation of myopathy. Amyloid myopathy should be a consideration in adults with progressive neuromuscular weakness of uncertain cause.

  13. Drinking Water: Health Hazards Still Not Resolved

    ERIC Educational Resources Information Center

    Wade, Nicholas

    1977-01-01

    Despite the suggested link between cancer deaths and drinking obtained from the Mississippi River, New Orleans still treats its water supply in the same manner as before the Environmental Defense Fund's epidemiological study. (BT)

  14. Cardiology Still a Man's Field, Survey Finds

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_162700.html Cardiology Still a Man's Field, Survey Finds Women less ... Dr. Claire Duvernoy, chair of the Women in Cardiology Council at the American College of Cardiology (ACC). ...

  15. Zika Still a Threat During Winter Months

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_162518.html Zika Still a Threat During Winter Months Public health ... doesn't necessarily mean the end of the Zika threat in the United States, a public health ...

  16. Pap Smear: Still Necessary After Hysterectomy?

    MedlinePlus

    ... Pap tests still needed after removal of the uterus (hysterectomy)? Answers from Sandhya Pruthi, M.D. It ... If you had a partial hysterectomy — when the uterus is removed but the lower end of the ...

  17. Evolution of disease phenotype in adult and pediatric onset Crohn’s disease in a population-based cohort

    PubMed Central

    Lovasz, Barbara Dorottya; Lakatos, Laszlo; Horvath, Agnes; Szita, Istvan; Pandur, Tunde; Mandel, Michael; Vegh, Zsuzsanna; Golovics, Petra Anna; Mester, Gabor; Balogh, Mihaly; Molnar, Csaba; Komaromi, Erzsebet; Kiss, Lajos Sandor; Lakatos, Peter Laszlo

    2013-01-01

    AIM: To investigate the evolution of disease phenotype in adult and pediatric onset Crohn’s disease (CD) populations, diagnosed between 1977 and 2008. METHODS: Data of 506 incident CD patients were analyzed (age at diagnosis: 28.5 years, interquartile range: 22-38 years). Both in- and outpatient records were collected prospectively with a complete clinical follow-up and comprehensively reviewed in the population-based Veszprem province database, which included incident patients diagnosed between January 1, 1977 and December 31, 2008 in adult and pediatric onset CD populations. Disease phenotype according to the Montreal classification and long-term disease course was analysed according to the age at onset in time-dependent univariate and multivariate analysis. RESULTS: Among this population-based cohort, seventy-four (12.8%) pediatric-onset CD patients were identified (diagnosed ≤ 17 years of age). There was no significant difference in the distribution of disease behavior between pediatric (B1: 62%, B2: 15%, B3: 23%) and adult-onset CD patients (B1: 56%, B2: 21%, B3: 23%) at diagnosis, or during follow-up. Overall, the probability of developing complicated disease behaviour was 49.7% and 61.3% in the pediatric and 55.1% and 62.4% in the adult onset patients after 5- and 10-years of follow-up. Similarly, time to change in disease behaviour from non stricturing, non penetrating (B1) to complicated, stricturing or penetrating (B2/B3) disease was not significantly different between pediatric and adult onset CD in a Kaplan-Meier analysis. Calendar year of diagnosis (P = 0.04), ileal location (P < 0.001), perianal disease (P < 0.001), smoking (P = 0.038) and need for steroids (P < 0.001) were associated with presence of, or progression to, complicated disease behavior at diagnosis and during follow-up. A change in disease location was observed in 8.9% of patients and it was associated with smoking status (P = 0.01), but not with age at diagnosis. CONCLUSION: Long

  18. Flash photography by digital still camera

    NASA Astrophysics Data System (ADS)

    Yamamoto, Yoshitaka

    2001-04-01

    Recently, the number of commercially produced digital still cameras has increases rapidly. However, detailed performance of digital still camera had not been evaluated. One of the purposes of this paper is to devise the method of evaluating the performance of a new camera. Another purpose is to show possibility of taking a picture of a scientific high quality photograph with a camera on the market, and taking a picture of a high-speed phenomenon.

  19. Genetic testing of children for diseases that have onset in adulthood: the limits of family interests.

    PubMed

    Hardart, George E; Chung, Wendy K

    2014-10-01

    Two recent policy statements, one from the American Academy of Pediatrics and one from the American College of Medical Genetics, reach very different conclusions about the question of whether children should be tested for adult-onset genetic conditions. The American Academy of Pediatrics policy begins with the presumption that genetic testing for children should be driven by the best interest of the child. It recognizes the importance of preserving the child's open future, recommending that genetic testing for adult-onset diseases be deferred. The American College of Medical Genetics, by contrast, recommended testing children for at least some adult conditions, although it should be noted they have recently modified this recommendation. They justified this recommendation by arguing that it, in fact, was in the best interests of the child and family to receive this information. In this article, we analyze these 2 different positions and suggest ways that the seeming conflicts between them might be reconciled.

  20. Landsat still contributing to environmental research

    USGS Publications Warehouse

    Loveland, Thomas R.; Cochrane, Mark A.; Henebry, Geoffrey M.

    2008-01-01

    Landsat data have enabled continuous global monitoring of both human-caused and other land cover disturbances since 1972. Recently degraded performance and intermittent service of the Landsat 7 and Landsat 5 sensors, respectively, have raised concerns about the condition of global Earth observation programs. However, Landsat imagery is still useful for landscape change detection and this capability should continue into the foreseeable future.

  1. 32 CFR 705.10 - Still photography.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 5 2011-07-01 2011-07-01 false Still photography. 705.10 Section 705.10 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY UNITED STATES NAVY REGULATIONS... to cooperate, but will instead seek the assistance of appropriate civil authorities and/or...

  2. 32 CFR 705.10 - Still photography.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 5 2012-07-01 2012-07-01 false Still photography. 705.10 Section 705.10 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY UNITED STATES NAVY REGULATIONS... to cooperate, but will instead seek the assistance of appropriate civil authorities and/or...

  3. 32 CFR 705.10 - Still photography.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... on taking photos by the general public, given in § 705.5 apply also to media representatives. (b) Basic policy and procedures for still photos are set forth in the Manual of Naval Photography, OPNAVINST... material has been photographed. In such cases, all unclassified photos will be returned promptly to...

  4. 32 CFR 705.10 - Still photography.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... on taking photos by the general public, given in § 705.5 apply also to media representatives. (b) Basic policy and procedures for still photos are set forth in the Manual of Naval Photography, OPNAVINST... material has been photographed. In such cases, all unclassified photos will be returned promptly to...

  5. STS-83 Pilot Susan Still suits up

    NASA Technical Reports Server (NTRS)

    1997-01-01

    STS-83 Pilot Susan L. Still gives a thumbs-up as she is assisted into her launch/entry suit in the Operations and checkout (O&C) Building. She is the second woman to fly in this capacity on a Space Shuttle. Still is a lieutenant colonel in the Navy and has more than 2,000 flight hours in 30 different types of aircraft. She also holds a master's degree in aerospace engineering. Still will assist Halsell with all phases of the space flight and will have primary responsibility to take action in the event of an emergency. After Columbia reaches orbit, Still will be busy with the many and varied tasks associated with monitoring and maintaining the orbiter. She and six fellow crew members will shortly depart the O&C and head for Launch Pad 39A, where the Space Shuttle Columbia will lift off during a launch window that opens at 2:00 p.m. EST, April 4.

  6. STS-94 Pilot Susan Still suits up

    NASA Technical Reports Server (NTRS)

    1997-01-01

    STS-94 Pilot Susan L. Still waves as she is assisted into her launch/entry suit in the Operations and Checkout (O&C) Building. She is the second woman to fly in this capacity on a Space Shuttle. Still is a lieutenant colonel in the Navy and has more than 2,000 flight hours in 30 different types of aircraft. She also holds a masters degree in aerospace engineering. Still will assist Halsell with all phases of the space flight and will have primary responsibility to take action in the event of an emergency. After Columbia reaches orbit, Still will be busy with the many and varied tasks associated with monitoring and maintaining the orbiter. She and six fellow crew members will shortly depart the O&C and head for Launch Pad 39A, where the Space Shuttle Columbia will lift off during a launch window that opens at 1:50 a.m. EDT, July 1. The launch window was opened 47 minutes early to improve the opportunity to lift off before Florida summer rain showers reached the space center.

  7. Mathematics from Still and Moving Images

    ERIC Educational Resources Information Center

    Pierce, Robyn; Stacey, Kaye; Ball, Lynda

    2005-01-01

    Digital photos and digital movies offer an excellent way of bringing real world situations into the mathematics classroom. The technologies surveyed here are feasible for everyday classroom use and inexpensive. Examples are drawn from the teaching of Cartesian coordinates, linear functions, ratio and Pythagoras' theorem using still images, and…

  8. Still Foreign after All These Years

    ERIC Educational Resources Information Center

    McNeill, David

    2007-01-01

    Paul Snowden's appointment as a dean to the School of International Liberal Studies at Waseda University was considered so unusual that he compared it to the first moonwalk. Snowden's new position was the highest position reached by a non-Japanese at Waseda, Japan's top private university. Waseda's embrace of foreigners is still considered an…

  9. Canadian Adult Education: Still a Movement

    ERIC Educational Resources Information Center

    Nesbit, Tom

    2011-01-01

    Writing recently in this journal, two of Canada's veteran adult educators contemplated the "death" of the Canadian adult education movement. I disagree and argue that adult education in Canada is as vital an activity as ever and one that still fully justifies being called a movement. Specifically, Selman and Selman (2009) list five…

  10. Avian Mycobacteriosis: Still Existing Threat to Humans

    PubMed Central

    Ulmann, Vit

    2016-01-01

    The nontuberculous mycobacteria are typically environmental organisms residing in soil and water. These microorganisms can cause a wide range of clinical diseases; pulmonary disease is most frequent, followed by lymphadenitis in children, skin and soft tissue disease, and rare extra pulmonary or disseminated infections. Mycobacterium avium complex is the second most common cause of pulmonary mycobacterioses after M. tuberculosis. This review covers the clinical and laboratory diagnosis of infection caused by the members of this complex and particularities for the treatment of different disease types and patient populations. PMID:27556033

  11. Efficacy and safety of liposomal amphotericin B for deep mycosis in patients with connective tissue disease.

    PubMed

    Kotani, Takuya; Takeuchi, Tohru; Makino, Shigeki; Hata, Kenichiro; Yoshida, Shuzo; Nagai, Koji; Wakura, Daisuke; Isoda, Kentaro; Hanafusa, Toshiaki

    2013-08-01

    The efficacy and safety of liposomal amphotericin B (L-AMB) in the treatment of invasive fungal infections (IFIs) were retrospectively evaluated for patients with connective tissue diseases (CTDs) during treatment with immunosuppressive therapy. Subjects were 13 patients with CTDs complicated by IFI, on the basis of clinical symptoms, imaging findings, and microbiological and histological examinations. All patients were treated with L-AMB. Efficacy and safety were evaluated before and after administration of L-AMB. Underlying diseases were systemic lupus erythematosus for 4 patients, rheumatoid arthritis for 3, microscopic polyangiitis for 2, adult-onset Still disease for 1, dermatomyositis for 1, and mixed connective tissue disease for 1. Eight patients were resistant to other antifungal drugs. Prednisolone was given to 11 patients and the median dose was 10 mg/day. Immunosuppressants were used for 8 patients. The median duration of administration of L-AMB was 8.5 days (range 4-38 days). In proven and probable diagnosis patients (n = 5), the treatment was effective for 3 patients and ineffective for 2 (efficacy rate 60 %). Serum 1,3-β-D-glucan antigenemia (BG) levels decreased after treatment in the 2 patients who were positive for BG. Serum Aspergillus galactomannan antigen levels decreased in 3 of 4 patients with Aspergillus infection. No patient died of IFI. Regarding potential adverse reactions, there were no significant changes in serum creatinine and potassium levels. L-AMB is effective and well-tolerated for treatment of IFI in patients with CTDs.

  12. Livewire based single still image segmentation

    NASA Astrophysics Data System (ADS)

    Zhang, Jun; Yang, Rong; Liu, Xiaomao; Yue, Hao; Zhu, Hao; Tian, Dandan; Chen, Shu; Li, Yiquan; Tian, Jinwen

    2011-11-01

    In the application of the video contactless measurement, the quality of the image taken from underwater is not very well. It is well known that automatic image segmental method cannot provide acceptable segmentation result with low quality single still image. Snake algorithm can provide better result in this case with the aiding of human. However, sometimes the segmental result of Snake may far from the initial segmental contour drawn by user. Livewire algorithm can keep the location of the seed points that user selected nailed from the beginning to the end. But the contour may have burrs when the image's noise is quite high and the contrast is low. In this paper, we modified the cost function of Livewire algorithm and proposed a new segmentation method that can be used for single still image segmentation with high noise and low contrast.

  13. Challenges Still to Be Appropriately Addressed

    NASA Astrophysics Data System (ADS)

    Maurette, Michel

    This section includes a heteroclite set of questions and comments of colleagues, which have still to be fully answered. Progress in science occurs not only with a few spectacular achievements that are generally cleverly advertised by funding agencies and the prestigious journals, but also by incessant questioning. They remain in the shadow for a while because you have to wait for an answer that might never come.

  14. Guidelines for presymptomatic testing for Huntington's disease: past, present and future in France.

    PubMed

    Clément, S; Gargiulo, M; Feingold, J; Durr, A

    2015-01-01

    Huntington's disease was the first adult onset neurological disease for which presymptomatic genetic testing became possible. It served as a model for the approach which constituted a radical change in medical practice and provided an important framework for multi-step, multidisciplinary, counselling for at risk persons. We will review the historical context of guidelines and good clinical practices, the experiences of our team which covers more than 20 years of presymptomatic testing for Huntington's disease in France, and explore the impact of the new French legislation for the future of presymptomatic testing of diseases for which neither preventive measures nor curative treatments are yet available.

  15. Experimental study of a solar still

    NASA Astrophysics Data System (ADS)

    Hassoun, Z. Sari; Aliane, K.; Berrezoug, H. I.

    2016-07-01

    This work concerns the study of a solar distiller. Particular attention is paid to the different operating characteristics such as: temperature, global and internal efficiency, performance and the performance factor during the distillation process. We have also established the overall heat balance in transition. A series of tests was carried out during the summer under the sea water to see the evolution of different parameters of the distiller. The daily output of solar still is 1.8litre / day. All the dissolved solids (TDS), conductivity and pH of the water were measured.

  16. Electronic Still Camera Project on STS-48

    NASA Technical Reports Server (NTRS)

    1991-01-01

    On behalf of NASA, the Office of Commercial Programs (OCP) has signed a Technical Exchange Agreement (TEA) with Autometric, Inc. (Autometric) of Alexandria, Virginia. The purpose of this agreement is to evaluate and analyze a high-resolution Electronic Still Camera (ESC) for potential commercial applications. During the mission, Autometric will provide unique photo analysis and hard-copy production. Once the mission is complete, Autometric will furnish NASA with an analysis of the ESC s capabilities. Electronic still photography is a developing technology providing the means by which a hand held camera electronically captures and produces a digital image with resolution approaching film quality. The digital image, stored on removable hard disks or small optical disks, can be converted to a format suitable for downlink transmission, or it can be enhanced using image processing software. The on-orbit ability to enhance or annotate high-resolution images and then downlink these images in real-time will greatly improve Space Shuttle and Space Station capabilities in Earth observations and on-board photo documentation.

  17. Chronic postsurgical pain: still a neglected topic?

    PubMed Central

    Kissin, Igor; Gelman, Simon

    2012-01-01

    Background Surgical injury can frequently lead to chronic pain. Despite the obvious importance of this problem, the first publications on chronic pain after surgery as a general topic appeared only a decade ago. This study tests the hypothesis that chronic postsurgical pain was, and still is, represented insufficiently. Methods We analyzed the presentation of this topic in journal articles covered by PubMed and in surgical textbooks. The following signs of insufficient representation in journal articles were used: (1) the lack of journal editorials on chronic pain after surgery, (2) the lack of journal articles with titles clearly indicating that they are devoted to chronic postsurgical pain, and (3) the insufficient representation of chronic postsurgical pain in the top surgical journals. Results It was demonstrated that insufficient representation of this topic existed in 1981–2000, especially in surgical journals and textbooks. Interest in this topic began to increase, however, mostly regarding one specific surgery: herniorrhaphy. It is important that the change in the attitude toward chronic postsurgical pain spreads to other groups of surgeries. Conclusion Chronic postsurgical pain is still a neglected topic, except for pain after herniorrhaphy. The change in the attitude toward chronic postsurgical pain is the important first step in the approach to this problem. PMID:23152698

  18. Niemann-Pick disease type C.

    PubMed

    Vanier, Marie T

    2010-06-03

    Niemann-Pick C disease (NP-C) is a neurovisceral atypical lysosomal lipid storage disorder with an estimated minimal incidence of 1/120,000 live births. The broad clinical spectrum ranges from a neonatal rapidly fatal disorder to an adult-onset chronic neurodegenerative disease. The neurological involvement defines the disease severity in most patients but is typically preceded by systemic signs (cholestatic jaundice in the neonatal period or isolated spleno- or hepatosplenomegaly in infancy or childhood). The first neurological symptoms vary with age of onset: delay in developmental motor milestones (early infantile period), gait problems, falls, clumsiness, cataplexy, school problems (late infantile and juvenile period), and ataxia not unfrequently following initial psychiatric disturbances (adult form). The most characteristic sign is vertical supranuclear gaze palsy. The neurological disorder consists mainly of cerebellar ataxia, dysarthria, dysphagia, and progressive dementia. Cataplexy, seizures and dystonia are other common features. NP-C is transmitted in an autosomal recessive manner and is caused by mutations of either the NPC1 (95% of families) or the NPC2 genes. The exact functions of the NPC1 and NPC2 proteins are still unclear. NP-C is currently described as a cellular cholesterol trafficking defect but in the brain, the prominently stored lipids are gangliosides. Clinical examination should include comprehensive neurological and ophthalmological evaluations. The primary laboratory diagnosis requires living skin fibroblasts to demonstrate accumulation of unesterified cholesterol in perinuclear vesicles (lysosomes) after staining with filipin. Pronounced abnormalities are observed in about 80% of the cases, mild to moderate alterations in the remainder ("variant" biochemical phenotype). Genotyping of patients is useful to confirm the diagnosis in the latter patients and essential for future prenatal diagnosis. The differential diagnosis may include

  19. [Do We Still Need Electrophysiology in Ophthalmology?

    PubMed

    Tegetmeyer, H

    2016-12-01

    Electrophysiological methods in clinical ophthalmology include the full-field electroretinogram (ERG) for assessment of outer and middle retinal layers, pattern ERG (PERG) for assessment of ganglion cell function, the electrooculogram (EOG) for assessment of retinal pigment epithelium function, as well as visual evoked potentials (VEP) for assessment of the visual pathway, including the optic nerve and visual cortex. Multifocal recording techniques for ERG and VEP are used for tests within selected areas of the visual field. Technical progress in ocular imaging, especially optical coherence tomography (OCT) and fundus autofluorescence (FAF), allows high-resolution imaging of subtle morphological changes of the retina and posterior fundus. Typical retinal diseases may then be diagnosed at an early stage, without conventional electrophysiological investigations (e.g. x-linked retinoschisis, Stargardt disease, vitelliform macular dystrophy). OCT outclasses electrophysiological methods in the quantification of optic atrophies. With newly developed optic techniques, peripheral retinal structures (wide angle optics) and subtle structures up to the photoreceptor level (adaptive optics) can be imaged with increasing quality. However, differentiation of central retinal disorders (e.g. macular dystrophy) from generalised retinal diseases requires electrophysiological diagnostic testing. The same applies to discrimination between different functional disorders in generalised retinal diseases (e.g. enhanced S-cone syndrome, congenital stationary night blindness, achromatopsia).

  20. "Hu's line" still holds effective for China.

    PubMed

    1992-02-01

    The population distribution data of the 1990 census showed no significant change in the geographic distribution of population in China since 1933. In 1935 a population geographer drew up China's 1st population map based on 1933 population figures of 458 million. A demarcation line called Hu's Line, which is still valid today, indicated regional distribution of population from Aihui (now Heihe City in the northeast Heilongjiang Province) to Tengchong (in the southwest Yunnan Province). The territory to the east of the line accounted for 36% of the total national area while the territory to the west of the line represented 64%. The population in the territory to the east of the line accounted for 96% while those living on the west only for 4% of the people. In 1990 China, had 1.16 billion people (including Taiwan, Hong Kong, Macao), with 94.2% in the east and 5.8% in the west. There was only a 1.8% change in the proportions after 56 years caused by migration to the west from 1949 to 1982 and a higher total fertility rate in the west. From 1933 the formerly densely populated areas become even denser by 1990. In the Yangtze River Delta and Qiantang River Plain population density increased form 500 persons/sq km in 1933 to 750 in 1990; in the Huang (River) Huai (River) Hai (River) Big Plain, it increased from 300 to 700 and in the deltas of the China's southeast coastal areas, from 400 to 700. Eastern China consists of plains and hilly land which account for 25.2% of the country's territory and 79.1% of population. But the immense 1.49 million sq km of desert, gobi, and desertified land (15.6% of the territory) in the west is still uninhabited as in 1933. The rural population still comprises 73.77% of the total. The East possesses 82% of the national railways, 85% of highways, and 99% of navigable rivers. 16 of 17 megacities with more than 2 million population are located in the East.

  1. Food-borne botulism: still actual topic

    PubMed Central

    Brola, Waldemar; Fudala, Malgorzata; Gacek, Szymon; Gruenpeter, Pawel

    2013-01-01

    Even though since the mid-1990s the number of food-borne botulism cases has systematically decreased and it now occurs in Poland relatively rarely, it is still a real epidemiological problem. There are about 30 cases of botulism in Poland a year, which ranks Poland the first among the European Union. In most cases the symptomatology of botulism is typical, however it does not always fully coincide with the one described in medical manuals which emphasise the dramatic clinical course of botulism with its frequent fatal consequences. Diagnosis of botulism may be difficult because of its rare prevalence and a variable clinical course, especially in old patients. Authors of this paper describe two cases of botulism and diagnostic problems associated with it. PMID:23391950

  2. Solar 'hot spots' are still hot

    NASA Technical Reports Server (NTRS)

    Bai, Taeil

    1990-01-01

    Longitude distributions of solar flares are not random but show evidence for active zones (or hot spots) where flares are concentrated. According to a previous study, two hot spots in the northern hemisphere, which rotate with a synodic period of about 26.72 days, produced the majority of major flares, during solar cycles 20 and 21. The more prominent of these two hot spots is found to be still active during the rising part of cycle 22, producing the majority of northern hemisphere major flares. The synodic rotation period of this hot spot is 26.727 + or - 0.007 days. There is also evidence for hot spots in the southern hemisphere. Two hot spots separated by 180 deg are found to rotate with a period of 29.407 days, with one of them having persisted in the same locations during cycles 19-22 and the other, during cycles 20-22.

  3. Does ageism still exist in nurse education?

    PubMed

    Coleman, Deborah

    2015-06-01

    Worldwide demographic changes mean that older people represent a significant group of patients for nurses everywhere. Ageism is increasingly recognised as an issue among healthcare professionals and evidence suggests that problems with quality of care remain. Nursing curricula have to address the needs of an ageing population in a variety of settings, reflect the importance of therapeutic care and explore nursing students' attitudes, in order to provide them with the appropriate skills to meet the needs of older people. This article debates the main factors influencing gerontological content in nursing curricula and suggests that ageism is still evident in nurse education. A variety of strategies are identified to assist in developing appropriate curriculum content.

  4. Food-borne botulism: still actual topic.

    PubMed

    Brola, Waldemar; Fudala, Malgorzata; Gacek, Szymon; Gruenpeter, Pawel

    2013-02-06

    Even though since the mid-1990s the number of food-borne botulism cases has systematically decreased and it now occurs in Poland relatively rarely, it is still a real epidemiological problem. There are about 30 cases of botulism in Poland a year, which ranks Poland the first among the European Union. In most cases the symptomatology of botulism is typical, however it does not always fully coincide with the one described in medical manuals which emphasise the dramatic clinical course of botulism with its frequent fatal consequences. Diagnosis of botulism may be difficult because of its rare prevalence and a variable clinical course, especially in old patients. Authors of this paper describe two cases of botulism and diagnostic problems associated with it.

  5. Taenia solium in Europe: Still endemic?

    PubMed

    Devleesschauwer, Brecht; Allepuz, Alberto; Dermauw, Veronique; Johansen, Maria V; Laranjo-González, Minerva; Smit, G Suzanne A; Sotiraki, Smaragda; Trevisan, Chiara; Wardrop, Nicola A; Dorny, Pierre; Gabriël, Sarah

    2017-01-01

    The pork tapeworm, Taenia solium, causes an important economic and health burden, mainly in rural or marginalized communities of sub-Saharan Africa, Asia, and Latin-America. Although improved pig rearing conditions seem to have eliminated the parasite in most Western European countries, little is known about the true endemicity status of T. solium throughout Europe. Three recent reviews indicate that autochthonous human T. solium taeniasis/cysticercosis may be possible in Europe, but that current peer-reviewed literature is biased towards Western Europe. Officially reported data on porcine cysticercosis are highly insufficient. Favourable conditions for local T. solium transmission still exist in eastern parts of Europe, although the ongoing integration of the European Union is speeding up modernisation and intensification of the pig sector. Further evidence is urgently needed to fill the gaps on the European T. solium endemicity map. We urge to make human cysticercosis notifiable and to improve the reporting of porcine cysticercosis.

  6. Vinyl chloride: still a cause for concern.

    PubMed Central

    Kielhorn, J; Melber, C; Wahnschaffe, U; Aitio, A; Mangelsdorf, I

    2000-01-01

    Vinyl chloride (VC) is both a known carcinogen and a regulated chemical, and its production capacity has almost doubled over the last 20 years, currently 27 million tons/year worldwide. According to recent reports it is still a cause for concern. VC has been found as a degradation product of chloroethylene solvents (perchloroethylene and trichloroethylene) and in landfill gas and groundwater at concentrations up to 200 mg/m(3) and 10 mg/L, respectively. Worldwide occupational exposure to VC still seems to be high in some countries (e.g., averages of approximately 1,300 mg/m(3) until 1987 in one factory), and exposure may also be high in others where VC is not regulated. By combining the most relevant epidemiologic studies from several countries, we observed a 5-fold excess of liver cancer, primarily because of a 45-fold excess risk from angiosarcoma of the liver (ASL). The number of ASL cases reported up to the end of 1998 was 197 worldwide. The average latency for ASL is 22 years. Some studies show a small excess risk for hepatocellular carcinoma, and others suggest a possible risk of brain tumors among highly exposed workers. Lung cancer, lymphomas, or leukemia do not seem to be related to VC exposure according to recent results. The mutation spectra observed in rat and human liver tumors (ASL and/or hepatocellular carcinoma) that are associated with exposure to VC are clearly distinct from those observed in sporadic liver tumors or hepatic tumors that are associated with other exposures. In rats, the substitution mutations found at A:T base pairs in the ras and p53 genes are consistent with the promutagenic properties of the DNA adduct 1,N(6)-ethenoadenine formed from VC metabolites. Risk assessments derived from animal studies seem to overestimate the actual risk of cancer when comparing estimated and reported cases of ASL. Images Figure 1 Figure 2 PMID:10905993

  7. Neurocysticercosis is still prevalent in Mexico.

    PubMed

    Fleury, Agnès; Sciutto, Edda; Larralde, Carlos

    2012-01-01

    In this work, we report the published cases of human and porcine cysticercosis, as well as Taenia solium taeniasis diagnosed in Mexico during the last 10 years. Numerical data allow us to state that this disease remains as a public health problem in our country. Whereas efficient tools have been developed for the diagnosis and prevention of cysticercosis, we strongly recommend further measures allowing the control and eventual eradication of this parasite in Mexico.

  8. PERIORAL DERMATITIS: STILL A THERAPEUTIC CHALLENGE.

    PubMed

    Mokos, Zrinka Bukvić; Kummer, Ana; Mosler, Elvira Lazić; Čeović, Romana; Basta-Juzbašić, Aleksandra

    2015-06-01

    Perioral dermatitis is a common and often chronic dermatosis. In its classic form, it primarily affects women aged 15 to 45 years, but there are also variants including lupus-like and granulomatous perioral dermatitis, where granulomatous form is more common in childhood and affects mostly prepubescent boys. The etiopathogenesis of the disease remains unclear, but there is a frequent finding of prolonged use of topical products, especially corticosteroids, in the treatment of rosacea and seborrheic dermatitis, preceding the clinical manifestation of perioral dermatitis. Other causes important for the occurrence of the disease include various skin irritants, as well as other physical and hormonal factors, which all share the epidermal barrier dysfunction as an underlying main pathogenic factor. Clinical presentation of papulovesicular eruption in the perioral region with a typical narrow spared zone around the edge of the lips is characteristic. Therapeutic approach should be individually addressed, depending on the severity of clinical presentation and patient's age, with special attention to patient's education and continuous psychological support. In mild forms of perioral dermatitis, 'zero therapy' is the treatment of choice. In the initial treatment period, patients with steroid-induced perioral dermatitis should be closely followed up because the rebound phenomenon usually develops after cessation of previous topical treatment. In moderate disease, treatment includes topical metronidazole, erythromycin, and pimecrolimus, whereas in more severe cases the best validated choice is oral tetracycline in a subantimicrobial dose until complete remission is achieved. Systemic isotretinoin should be considered as a therapeutic option for patients refractory to all standard therapies.

  9. Neonatal pain management: still in search for the Holy Grail.

    PubMed

    Allegaert, Karel; van den Anker, John N

    2016-07-01

    Inadequate pain management but also inappropriate use of analgesics in early infancy has negative effects on neurodevelopmental outcome. As a consequence, neonatal pain management is still in search for the Holy Grail. At best, effective pain management is based on prevention, assessment, and treatment followed by a re-assessment of the pain to determine if additional treatment is still necessary. Unfortunately, epidemiological observations suggest that neonates are undergoing painful procedures very frequently, unveiling the need for effective preventive, non-pharmacological strategies. In addition, assessment is still based on validated, multimodal, but subjective pain assessment tools. Finally, in neonatal intensive care units, there is a shift in clinical practices (e.g., shorter intubation and ventilation), and this necessitates the development and validation of new pharmacological treatment modalities. To illustrate this, a shift in the use of opioids to paracetamol has occurred and short-acting agents (remifentanil, propofol) are more commonly administered to neonates. In addition to these new modalities and as part of a more advanced approach of the developmental pharmacology of analgesics, pharmacogenetics also emerged as a tool for precision medicine in neonates. To assure further improvement of neonatal pain management the integration of pharmacogenetics with the usual covariates like weight, age and/or disease characteristics is needed.

  10. Calprotectin in rheumatic diseases: a review

    PubMed Central

    Widuchowska, Małgorzata; Kucharz, Eugeniusz J.

    2016-01-01

    Calprotectin also known as MRP8/14 or S100A8/A9 is a heterodimeric complex of two S100 calcium-binding proteins: myeloid-related protein 8 (MRP-8 or S100A8) and MRP-14 (or S100A9). At present, according to many authors, it is considered that calprotectin MRP8/14 is a potentially more sensitive biomarker of disease activity in rheumatoid disease than conventional inflammatory indices such as the erythrocyte sedimentation rate, C-reactive protein and others. A review of the literature on concentration of calprotectin in patients with some rheumatic diseases (rheumatoid arthritis, juvenile idiopathic arthritis, adult-onset Still’s disease, systemic vasculitis, polymyalgia rheumatica, ankylosis spondylitis, systemic lupus erythematosus, and primary Sjögren’s syndrome) is presented. PMID:28115781

  11. Object analysis of the Stilling tables.

    PubMed

    Lakowski, R

    1976-01-01

    The CIE space that is occupied by the Stilling tables was found to be similar to that occupied by the Ishihara plates [LAKOWSKI, 1965] with the notable exceptions of a single table that extends into the blue area and two others that extend further into the green (fig. 4). Spectrophotometric curves show that the inks used are similar to those in other PIC plates, i.e. they have reflectance curves with broad-band characteristics. All tables are of the vanishing type and there is an attempt to differentiate between protan and deutan defects. Colorimetrically, tables I, II, VII and VIII have figure and background colours aligned mainly along the deutan isochromatic lines and only table III is a clear protan plate. Tables V, VI, IX, X and XI are ambiguous in design, i.e. they would be confused by most colour-deficient persons. Of the tables designed to detect blue-yellow deficiencies (tables V, VI, XI and XII), only the colours in table XII are aligned along tetartan confusion lines, while the other three tables are indefinite in their design. Thus the usefulness of these plates for detecting acquired dyschromatopsias is limited.

  12. Louisiana gas play still a hit

    SciTech Connect

    Brown, D.

    1991-12-01

    Despite the mature look of the oil and gas development in south Louisiana, many deeper oil and gas prospects are still untouched. Most wells in this area are relatively shallow and were stopped before they were actually reached pressured reservoirs. This paper discusses the success of the Miami Fee natural gas field which was drilled based on the reinterpretation of existing seismic data. Plains Resources Inc. of Houston recently completed its Miami Fee No. 1 well in Cameron Parish, Louisiana, about 25 miles southwest of the West Chalkley gas field discovery. Plains' new well produced from lower Oligocene sands between 15,300 and 15,632 feet, flowing 23.3 million cubic feet of gas and 1,353 barrels of condensate per day on a 3/8-inch choke in a four-point test. To help locate this field the company used an inversion technique to formulate crude sonic logs in areas between reflected boundaries, reprocessing some six-fold seismic data from as far back as 1968.

  13. Quality criterion for digital still camera

    NASA Astrophysics Data System (ADS)

    Bezryadin, Sergey

    2007-02-01

    The main quality requirements for a digital still camera are color capturing accuracy, low noise level, and quantum efficiency. Different consumers assign different priorities to the listed parameters, and camera designers need clearly formulated methods for their evaluation. While there are procedures providing noise level and quantum efficiency estimation, there are no effective means for color capturing accuracy estimation. Introduced in this paper criterion allows to fill this gap. Luther-Ives condition for correct color reproduction system became known in the beginning of the last century. However, since no detector system satisfies Luther-Ives condition, there are always stimuli that are distinctly different for an observer, but which detectors are unable to distinguish. To estimate conformity of a detector set with Luther-Ives condition and calculate a measure of discrepancy, an angle between detector sensor sensitivity and Cohen's Fundamental Color Space may be used. In this paper, the divergence angle is calculated for some typical CCD sensors and a demonstration provided on how this angle might be reduced with a corrective filter. In addition, it is shown that with a specific corrective filter Foveon sensors turn into a detector system with a good Luther-Ives condition compliance.

  14. Why do we still find anonymous ESTs?

    PubMed

    Cirera, S; Winterø, A K; Fredholm, M

    2000-08-01

    During recent years, there has been an exponential rise in the number of sequences accessible in the public databases. Despite this, a high percentage of partial sequences of cDNA (ESTs) submitted to the databases remain unrecognized (anonymous ESTs). This lack of similarities could be explained by several hypotheses: i) a different part of the transcript is present in the GenBank; ii) the transcript represents a novel gene not yet isolated in other species; iii) alternative splicing of the same gene in different species; iv) inaccurate sequence data; and/or v) the sequence of the transcript has diverged to the extent that it is not recognized as an ortholog. In the present study we selected a sample of 20 ESTs from a pool of 656 anonymous pig small intestine ESTs in order to investigate the possible cause for the lack of similarities with database entries. To test the significant hypotheses we carried out total sequencing of each insert along with zoo-blot and Northern-blot analysis. Extended analyses of the 20 ESTs showed significant matches to seven existing database entries, whereas 13 still did not show significant hits. The results are discussed in the context of the hypothesis listed above.

  15. Working memory still needs verbal rehearsal.

    PubMed

    Lucidi, Annalisa; Langerock, Naomi; Hoareau, Violette; Lemaire, Benoît; Camos, Valérie; Barrouillet, Pierre

    2016-02-01

    The causal role of verbal rehearsal in working memory has recently been called into question. For example, the SOB-CS (Serial Order in a Box-Complex Span) model assumes that there is no maintenance process for the strengthening of items in working memory, but instead a process of removal of distractors that are involuntarily encoded and create interference with memory items. In the present study, we tested the idea that verbal working memory performance can be accounted for without assuming a causal role of the verbal rehearsal process. We demonstrate in two experiments using a complex span task and a Brown-Peterson paradigm that increasing the number of repetitions of the same distractor (the syllable ba that was read aloud at each of its occurrences on screen) has a detrimental effect on the concurrent maintenance of consonants whereas the maintenance of spatial locations remains unaffected. A detailed analysis of the tasks demonstrates that accounting for this effect within the SOB-CS model requires a series of unwarranted assumptions leading to undesirable further predictions contradicted by available experimental evidence. We argue that the hypothesis of a maintenance mechanism based on verbal rehearsal that is impeded by concurrent articulation still provides the simplest and most compelling account of our results.

  16. Renal biopsy: Still a landmark for the nephrologist

    PubMed Central

    Visconti, Luca; Cernaro, Valeria; Ricciardi, Carlo Alberto; Lacava, Viviana; Pellicanò, Vincenzo; Lacquaniti, Antonio; Buemi, Michele; Santoro, Domenico

    2016-01-01

    Renal biopsy was performed for the first time more than one century ago, but its clinical use was routinely introduced in the 1950s. It is still an essential tool for diagnosis and choice of treatment of several primary or secondary kidney diseases. Moreover, it may help to know the expected time of end stage renal disease. The indications are represented by nephritic and/or nephrotic syndrome and rapidly progressive acute renal failure of unknown origin. Nowadays, it is performed mainly by nephrologists and radiologists using a 14-18 gauges needle with automated spring-loaded biopsy device, under real-time ultrasound guidance. Bleeding is the major primary complication that in rare cases may lead to retroperitoneal haemorrhage and need for surgical intervention and/or death. For this reason, careful evaluation of risks and benefits must be taken into account, and all procedures to minimize the risk of complications must be observed. After biopsy, an observation time of 12-24 h is necessary, whilst a prolonged observation may be needed rarely. In some cases it could be safer to use different techniques to reduce the risk of complications, such as laparoscopic or transjugular renal biopsy in patients with coagulopathy or alternative approaches in obese patients. Despite progress in medicine over the years with the introduction of more advanced molecular biology techniques, renal biopsy is still an irreplaceable tool for nephrologists. PMID:27458561

  17. Clinical and immunological aspects and outcome of a Brazilian cohort of 414 patients with systemic lupus erythematosus (SLE): comparison between childhood-onset, adult-onset, and late-onset SLE.

    PubMed

    das Chagas Medeiros, M M; Bezerra, M Campos; Braga, F N Holanda Ferreira; da Justa Feijão, M R Melo; Gois, A C Rodrigues; Rebouças, V C do Rosário; de Carvalho, T M Amorim Zaranza; Carvalho, L N Solon; Ribeiro, Át Mendes

    2016-04-01

    The clinical expression of systemic lupus erythematosus (SLE) is influenced by genetic and environmental factors and therefore varies between ethnicities. Information on the epidemiology of SLE in Brazil is scarce and practically limited to studies conducted in socioeconomically developed regions (South and Southeast). The objective of this study was to describe the clinical and immunological aspects and outcome of a cohort of patients with SLE treated at a university hospital in northeastern Brazil and compare patterns related to age at onset: childhood (cSLE), adult (aSLE), and late (lSLE). A random sample of 414 records (women: 93.5%) were reviewed. The mean age at SLE onset and the mean disease duration were 28.9 ± 10.9 years and 10.2 ± 6.6 years, respectively. Most patients had aSLE (n = 338; 81.6%), followed by cSLE (n = 60; 14.5%) and lSLE (n = 16; 3.9%). The female/male ratio was 6.5:1 in cSLE and 16.8:1 in aSLE; in lSLE, all patients were female (p = 0.05). During follow-up, the cSLE group presented higher rates of nephritis (70% vs. 52.9% vs. 12.5%; p = 0.0001) and leuko/lymphopenia (61.7% vs. 43.8% vs. 56.2%; p = 0.02). No significant differences were found for anti-dsDNA, anti-Sm, and antiphospholipid antibodies. Treatment with immunosuppressants was significantly more common, and higher doses of prednisone were used, in cSLE. The prevalence of cardiovascular diseases were more frequent in lSLE (p = 0.03). No significant differences were found between the three groups with regard to mean damage accrual (SDI), remission, and mortality. Although cSLE presented higher rates of nephritis and leuko/lymphopenia, more frequent use of immunosuppressants and higher prednisone doses than aSLE and lSLE, the three groups did not differ significantly with regard to damage accrual, remission, and mortality.

  18. Neuropathic Pain Treatment: Still a Challenge

    PubMed Central

    Nascimento, Osvaldo J.M.; Pessoa, Bruno L.; Orsini, Marco; Ribeiro, Pedro; Davidovich, Eduardo; Pupe, Camila; Filho, Pedro Moreira; Dornas, Ricardo Menezes; Masiero, Lucas; Bittencourt, Juliana; Bastos, Victor Hugo

    2016-01-01

    Neuropathic pain (NP) is the result of a series of conditions caused by diseases or lesions to the somatosensory system. Due to the better understanding of NP pathophysiology previously unexplored therapies have been used with encouraging results. In this group, acetyl-L-carnitine, alpha-lipoic-acid, cannabinoids, clonidine, EMA401, botulinum toxin type A and new voltage-gated sodium channel blockers, can be included. Besides, changing paradigms may occur with the advent of optogenetics and a better understanding of epigenetic regulation. We reviewed the published literature on the pharmacological treatment of NP. Despite the interesting results, randomized controlled trials are demanded the majority of the therapies previously mentioned. In spite of several studies for the relief of NP, pain control continues being a challenge. PMID:27441065

  19. Inflammatory bowel disease and celiac disease: overlaps and differences.

    PubMed

    Pascual, Virginia; Dieli-Crimi, Romina; López-Palacios, Natalia; Bodas, Andrés; Medrano, Luz María; Núñez, Concepción

    2014-05-07

    Recent findings demonstrate the common genetic basis for many immune-mediated diseases, and consequently, the partially shared pathogenesis. We collected these findings and reviewed the extension of these overlaps to other disease characteristics. Two autoimmune diseases were selected that also share the specific target organ, the bowel. The etiology and immunopathogenesis of both conditions characterized by chronic intestinal inflammation, inflammatory bowel disease (IBD) and celiac disease (CeD), are not completely understood. Both are complex diseases with genetics and environment contributing to dysregulation of innate and adaptive immune responses, leading to chronic inflammation and disease. CeD constitutes a particular disease because the main environmental and genetic triggers are largely known. IBD comprises two main clinical forms, Crohn's disease and ulcerative colitis, which most likely involve a complex interplay between some components of the commensal microbiota and other environmental factors in their origin. These multifactorial diseases encompass a broad spectrum of clinical phenotypes and ages of onset, although the clinical presentation often differs depending on childhood or adult onset, with greater heterogeneity commonly observed in adults.

  20. Inflammatory bowel disease and celiac disease: Overlaps and differences

    PubMed Central

    Pascual, Virginia; Dieli-Crimi, Romina; López-Palacios, Natalia; Bodas, Andrés; Medrano, Luz María; Núñez, Concepción

    2014-01-01

    Recent findings demonstrate the common genetic basis for many immune-mediated diseases, and consequently, the partially shared pathogenesis. We collected these findings and reviewed the extension of these overlaps to other disease characteristics. Two autoimmune diseases were selected that also share the specific target organ, the bowel. The etiology and immunopathogenesis of both conditions characterized by chronic intestinal inflammation, inflammatory bowel disease (IBD) and celiac disease (CeD), are not completely understood. Both are complex diseases with genetics and environment contributing to dysregulation of innate and adaptive immune responses, leading to chronic inflammation and disease. CeD constitutes a particular disease because the main environmental and genetic triggers are largely known. IBD comprises two main clinical forms, Crohn’s disease and ulcerative colitis, which most likely involve a complex interplay between some components of the commensal microbiota and other environmental factors in their origin. These multifactorial diseases encompass a broad spectrum of clinical phenotypes and ages of onset, although the clinical presentation often differs depending on childhood or adult onset, with greater heterogeneity commonly observed in adults. PMID:24803796

  1. Avian colibacillosis: still many black holes.

    PubMed

    Guabiraba, Rodrigo; Schouler, Catherine

    2015-08-01

    Avian pathogenic Escherichia coli (APEC) strains cause severe respiratory and systemic diseases, threatening food security and avian welfare worldwide. Intensification of poultry production and the quick expansion of free-range production systems will increase the incidence of colibacillosis through greater exposure of birds to pathogens and stress. Therapy is mainly based on antibiotherapy and current vaccines have poor efficacy. Serotyping remains the most frequently used diagnostic method, only allowing the identification of a limited number of APEC strains. Several studies have demonstrated that the most common virulence factors studied in APEC are all rarely present in the same isolate, showing that APEC strains constitute a heterogeneous group. Different isolates may harbor different associations of virulence factors, each one able to induce colibacillosis. Despite its economical relevance, pathogenesis of colibacillosis is poorly understood. Our knowledge on the host response to APEC is based on very descriptive studies, mostly restricted to bacteriological and histopathological analysis of infected organs such as lungs. Furthermore, only a small number of APEC isolates have been used in experimental studies. In the present review, we discuss current knowledge on APEC diversity and virulence, including host response to infection and the associated inflammatory response with a focus on pulmonary colibacillosis.

  2. Smallpox: can we still learn from the journey to eradication?

    PubMed Central

    Smith, Kendall A.

    2013-01-01

    One of the most celebrated achievements of immunology and modern medicine is the eradication of the dreaded plague smallpox. From the introduction of smallpox vaccination by Edward Jenner, to its popularization by Louis Pasteur, to the eradication effort led by Donald Henderson, this story has many lessons for us today, including the characteristics of the disease and vaccine that permitted its eradication, and the obviousness of the vaccine as a vector for other intractable Infectious diseases. The disease itself, interpreted in the light of modern molecular immunology, is an obvious immunopathological disease, which occurs after a latent interval of 1-2 weeks, and manifests as a systemic cell-mediated delayed type hypersensitivity (DTH) syndrome. The vaccine that slayed this dragon was given the name vaccinia, and was thought to have evolved from cowpox virus, but is now known to be most closely related to a poxvirus isolated from a horse. Of interest is the fact that of the various isolates of orthopox viruses, only variola, vaccinia and monkeypox viruses can infect humans. In contrast to the systemic disease of variola, vaccinia only replicates locally at the site of inoculation, and causes a localized DTH response that usually peaks after 7-10 days. This difference in the pathogenicity of variola vs. vaccinia is thought to be due to the capacity of variola to circumvent innate immunity, which allows it to disseminate widely before the adaptive immune response occurs. Thus, the fact that vaccinia virus is attenuated compared to variola, but is still replication competent, makes for its remarkable efficacy as a vaccine, as the localized infection activates all of the cells and molecules of both innate and adaptive immunity. Accordingly vaccinia itself, and not modified replication incompetent vaccina, is the hope for use as a vector in the eradication of additional pathogenic microbes from the globe. PMID:23760373

  3. Smallpox: can we still learn from the journey to eradication?

    PubMed

    Smith, Kendall A

    2013-05-01

    One of the most celebrated achievements of immunology and modern medicine is the eradication of the dreaded plague smallpox. From the introduction of smallpox vaccination by Edward Jenner, to its popularization by Louis Pasteur, to the eradication effort led by Donald Henderson, this story has many lessons for us today, including the characteristics of the disease and vaccine that permitted its eradication, and the obviousness of the vaccine as a vector for other intractable Infectious diseases. The disease itself, interpreted in the light of modern molecular immunology, is an obvious immunopathological disease, which occurs after a latent interval of 1-2 weeks, and manifests as a systemic cell-mediated delayed type hypersensitivity (DTH) syndrome. The vaccine that slayed this dragon was given the name vaccinia, and was thought to have evolved from cowpox virus, but is now known to be most closely related to a poxvirus isolated from a horse. Of interest is the fact that of the various isolates of orthopox viruses, only variola, vaccinia and monkeypox viruses can infect humans. In contrast to the systemic disease of variola, vaccinia only replicates locally at the site of inoculation, and causes a localized DTH response that usually peaks after 7-10 days. This difference in the pathogenicity of variola vs. vaccinia is thought to be due to the capacity of variola to circumvent innate immunity, which allows it to disseminate widely before the adaptive immune response occurs. Thus, the fact that vaccinia virus is attenuated compared to variola, but is still replication competent, makes for its remarkable efficacy as a vaccine, as the localized infection activates all of the cells and molecules of both innate and adaptive immunity. Accordingly vaccinia itself, and not modified replication incompetent vaccina, is the hope for use as a vector in the eradication of additional pathogenic microbes from the globe.

  4. Phenotypic convergence of Menkes and Wilson disease.

    PubMed

    Bansagi, Boglarka; Lewis-Smith, David; Pal, Endre; Duff, Jennifer; Griffin, Helen; Pyle, Angela; Müller, Juliane S; Rudas, Gabor; Aranyi, Zsuzsanna; Lochmüller, Hanns; Chinnery, Patrick F; Horvath, Rita

    2016-12-01

    Menkes disease is an X-linked multisystem disorder with epilepsy, kinky hair, and neurodegeneration caused by mutations in the copper transporter ATP7A. Other ATP7A mutations have been linked to juvenile occipital horn syndrome and adult-onset hereditary motor neuropathy.(1,2) About 5%-10% of the patients present with "atypical Menkes disease" characterized by longer survival, cerebellar ataxia, and developmental delay.(2) The intracellular copper transport is regulated by 2 P type ATPase copper transporters ATP7A and ATP7B. These proteins are expressed in the trans-Golgi network that guides copper to intracellular compartments, and in copper excess, it relocates copper to the plasma membrane to pump it out from the cells.(3)ATP7B mutations cause Wilson disease with dystonia, ataxia, tremor, and abnormal copper accumulation in the brain, liver, and other organs.(4).

  5. Unusual early-onset Huntingtons disease.

    PubMed

    Vargas, Antonio P; Carod-Artal, Francisco J; Bomfim, Denise; Vázquez-Cabrera, Carolina; Dantas-Barbosa, Carmela

    2003-06-01

    Huntington's disease is an autosomal dominant progressive neurodegenerative disorder characterized by involuntary movements, cognitive decline, and behavioral disorders leading to functional disability. In contrast to patients with adult onset, in which chorea is the major motor abnormality, children often present with spasticity, rigidity, and significant intellectual decline associated with a more rapidly progressive course. An unusual early-onset Huntington's disease case of an 11-year-old boy with severe hypokinetic/rigid syndrome appearing at the age of 2.5 years is presented. Clinical diagnosis was confirmed by polymerase chain reaction study of the expanded IT-15 allele with a compatible size of 102 cytosine-adenosine-guanosine repeats L-Dopa mildly ameliorated rigidity, bradykinesia, and dystonia. We conclude that Huntington's disease should be included in the differential diagnoses of regressive syndromes of early childhood.

  6. Environmentally induced epigenetic transgenerational inheritance of ovarian disease.

    PubMed

    Nilsson, Eric; Larsen, Ginger; Manikkam, Mohan; Guerrero-Bosagna, Carlos; Savenkova, Marina I; Skinner, Michael K

    2012-01-01

    The actions of environmental toxicants and relevant mixtures in promoting the epigenetic transgenerational inheritance of ovarian disease was investigated with the use of a fungicide, a pesticide mixture, a plastic mixture, dioxin and a hydrocarbon mixture. After transient exposure of an F0 gestating female rat during embryonic gonadal sex determination, the F1 and F3 generation progeny adult onset ovarian disease was assessed. Transgenerational disease phenotypes observed included an increase in cysts resembling human polycystic ovarian disease (PCO) and a decrease in the ovarian primordial follicle pool size resembling primary ovarian insufficiency (POI). The F3 generation granulosa cells were isolated and found to have a transgenerational effect on the transcriptome and epigenome (differential DNA methylation). Epigenetic biomarkers for environmental exposure and associated gene networks were identified. Epigenetic transgenerational inheritance of ovarian disease states was induced by all the different classes of environmental compounds, suggesting a role of environmental epigenetics in ovarian disease etiology.

  7. Environmentally Induced Epigenetic Transgenerational Inheritance of Ovarian Disease

    PubMed Central

    Nilsson, Eric; Larsen, Ginger; Manikkam, Mohan; Guerrero-Bosagna, Carlos; Savenkova, Marina I.; Skinner, Michael K.

    2012-01-01

    The actions of environmental toxicants and relevant mixtures in promoting the epigenetic transgenerational inheritance of ovarian disease was investigated with the use of a fungicide, a pesticide mixture, a plastic mixture, dioxin and a hydrocarbon mixture. After transient exposure of an F0 gestating female rat during embryonic gonadal sex determination, the F1 and F3 generation progeny adult onset ovarian disease was assessed. Transgenerational disease phenotypes observed included an increase in cysts resembling human polycystic ovarian disease (PCO) and a decrease in the ovarian primordial follicle pool size resembling primary ovarian insufficiency (POI). The F3 generation granulosa cells were isolated and found to have a transgenerational effect on the transcriptome and epigenome (differential DNA methylation). Epigenetic biomarkers for environmental exposure and associated gene networks were identified. Epigenetic transgenerational inheritance of ovarian disease states was induced by all the different classes of environmental compounds, suggesting a role of environmental epigenetics in ovarian disease etiology. PMID:22570695

  8. The Orion Nebula: Still Full of Surprises

    NASA Astrophysics Data System (ADS)

    2011-01-01

    This ethereal-looking image of the Orion Nebula was captured using the Wide Field Imager on the MPG/ESO 2.2-metre telescope at the La Silla Observatory, Chile. This nebula is much more than just a pretty face, offering astronomers a close-up view of a massive star-forming region to help advance our understanding of stellar birth and evolution. The data used for this image were selected by Igor Chekalin (Russia), who participated in ESO's Hidden Treasures 2010 astrophotography competition. Igor's composition of the Orion Nebula was the seventh highest ranked entry in the competition, although another of Igor's images was the eventual overall winner. The Orion Nebula, also known as Messier 42, is one of the most easily recognisable and best-studied celestial objects. It is a huge complex of gas and dust where massive stars are forming and is the closest such region to the Earth. The glowing gas is so bright that it can be seen with the unaided eye and is a fascinating sight through a telescope. Despite its familiarity and closeness there is still much to learn about this stellar nursery. It was only in 2007, for instance, that the nebula was shown to be closer to us than previously thought: 1350 light-years, rather than about 1500 light-years. Astronomers have used the Wide Field Imager on the MPG/ESO 2.2-metre telescope at ESO's La Silla Observatory in Chile to observe the stars within Messier 42. They found that the faint red dwarfs in the star cluster associated with the glowing gas radiate much more light than had previously been thought, giving us further insights into this famous object and the stars that it hosts. The data collected for this science project, with no original intention to make a colour image, have now been reused to create the richly detailed picture of Messier 42 shown here. The image is a composite of several exposures taken through a total of five different filters. Light that passed through a red filter as well as light from a filter that

  9. Where Does Human Plague Still Persist in Latin America?

    PubMed Central

    Schneider, Maria Cristina; Najera, Patricia; Aldighieri, Sylvain; Galan, Deise I.; Bertherat, Eric; Ruiz, Alfonso; Dumit, Elsy; Gabastou, Jean Marc; Espinal, Marcos A.

    2014-01-01

    Background Plague is an epidemic-prone disease with a potential impact on public health, international trade, and tourism. It may emerge and re-emerge after decades of epidemiological silence. Today, in Latin America, human cases and foci are present in Bolivia, Brazil, Ecuador, and Peru. Aims The objective of this study is to identify where cases of human plague still persist in Latin America and map areas that may be at risk for emergence or re-emergence. This analysis will provide evidence-based information for countries to prioritize areas for intervention. Methods Evidence of the presence of plague was demonstrated using existing official information from WHO, PAHO, and Ministries of Health. A geo-referenced database was created to map the historical presence of plague by country between the first registered case in 1899 and 2012. Areas where plague still persists were mapped at the second level of the political/administrative divisions (counties). Selected demographic, socioeconomic, and environmental variables were described. Results Plague was found to be present for one or more years in 14 out of 25 countries in Latin America (1899–2012). Foci persisted in six countries, two of which have no report of current cases. There is evidence that human cases of plague still persist in 18 counties. Demographic and poverty patterns were observed in 11/18 counties. Four types of biomes are most commonly found. 12/18 have an average altitude higher than 1,300 meters above sea level. Discussion Even though human plague cases are very localized, the risk is present, and unexpected outbreaks could occur. Countries need to make the final push to eliminate plague as a public health problem for the Americas. A further disaggregated risk evaluation is recommended, including identification of foci and possible interactions among areas where plague could emerge or re-emerge. A closer geographical approach and environmental characterization are suggested. PMID:24516682

  10. [Social medicine: does it still make sense in 2013?].

    PubMed

    Vu, Francis; Bischoff, Thomas; Wolff, Hans; Guessous, Idris; Dory, Elodie; Dubois-Arber, Françoise; Stringhini, Silvia; Bodenmann, Patrick

    2013-11-27

    Social medicine is a medicine that seeks to understand the impact of socio-economic conditions on human health and diseases in order to improve the health of a society and its individuals. In this field of medicine, determining the socio-economic status of individuals is generally not sufficient to explain and/or understand the underlying mechanisms leading to social inequalities in health. Other factors must be considered such as environmental, psychosocial, behavioral and biological factors that, together, can lead to more or less permanent damages to the health of the individuals in a society. In a time where considerable progresses have been made in the field of the biomedicine, does the practice of social medicine in a primary care setting still make sense?

  11. Typhoid intestinal perforation in developing countries: Still unavoidable deaths?

    PubMed Central

    Contini, Sandro

    2017-01-01

    Typhoid fever is a public health challenge mostly concentrated in impoverished, overcrowded areas of the developing world, with lack of safe drinking and sanitation. The most serious complication is typhoid intestinal perforation (TIP), observed in 0.8% to 39%, with a striking rate difference between high-income and low-middle-income countries. Although the mortality rate consequent to TIP in resource-poor countries is improved in the last decades, it is still fluctuating from 5% to 80%, due to surgical- and not surgical-related constraints. Huge economic costs and long timelines are required to provide a short- to middle-term solution to the lack of safe water and sanitation. Inherent limitations of the currently available diagnostic tools may lead to under-evaluation as well as over-evaluation of the disease, with consequent delayed treatment or inappropriate, excessive antibiotic use, hence increasing the likelihood of bacterial resistance. There is a need for immunization programs in populations at greatest risk, especially in sub-Saharan Africa. Uniform surgical strategies and guidelines, on the basis of sound or prospective surgical studies and adapted to the local realities, are still lacking. Major drawbacks of the surgical treatment are the frequent delays to surgery, either for late diagnosis or for difficult transports, and the unavailable appropriate intensive care units in most peripheral facilities. As a consequence, poor patient’s conditions at presentation, severe peritoneal contamination and unsuitable postoperative care are the foremost determinant of surgical morbidity and mortality. PMID:28373758

  12. 27 CFR 29.47 - Notice requirement; manufacture of stills.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...; manufacture of stills. 29.47 Section 29.47 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... Notice requirement; manufacture of stills. (a) General. When required by letter issued by the appropriate... manufactures any still, boiler (double or pot still), condenser, or other apparatus to be used for the...

  13. 27 CFR 29.47 - Notice requirement; manufacture of stills.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...; manufacture of stills. 29.47 Section 29.47 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... Notice requirement; manufacture of stills. (a) General. When required by letter issued by the appropriate... manufactures any still, boiler (double or pot still), condenser, or other apparatus to be used for the...

  14. 27 CFR 29.47 - Notice requirement; manufacture of stills.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...; manufacture of stills. 29.47 Section 29.47 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... Notice requirement; manufacture of stills. (a) General. When required by letter issued by the appropriate... manufactures any still, boiler (double or pot still), condenser, or other apparatus to be used for the...

  15. 27 CFR 29.47 - Notice requirement; manufacture of stills.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...; manufacture of stills. 29.47 Section 29.47 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... Notice requirement; manufacture of stills. (a) General. When required by letter issued by the appropriate... manufactures any still, boiler (double or pot still), condenser, or other apparatus to be used for the...

  16. 27 CFR 29.47 - Notice requirement; manufacture of stills.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...; manufacture of stills. 29.47 Section 29.47 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... Notice requirement; manufacture of stills. (a) General. When required by letter issued by the appropriate... manufactures any still, boiler (double or pot still), condenser, or other apparatus to be used for the...

  17. Parents' Attitudes Toward Pediatric Genetic Testing for Common Disease Risk

    PubMed Central

    Hensley Alford, Sharon; Emmons, Karen M.; Lipkus, Isaac M.; Wilfond, Benjamin S.; McBride, Colleen M.

    2011-01-01

    OBJECTIVE: To describe parents' attitudes toward pediatric genetic testing for common, adult-onset health conditions and to identify factors underlying these attitudes. PARTICIPANTS AND METHODS: Parents (n = 219) enrolled in a large, group-practice health plan were offered a “multiplex” genetic test for susceptibility to 8 common, adult-onset health conditions and completed an online survey assessing attitudes and beliefs about the risks and benefits of the test for their child, their willingness to consider having their child tested, and other psychosocial variables. RESULTS: Parents viewed the benefits of pediatric testing to outweigh its risks (positive decisional balance) and were moderately interested in pediatric testing. Variables associated with positive decisional balance included greater interest in knowing about gene-health associations in their child, anticipation of less difficulty understanding their child's genetic health risks, and more positive emotional reactions to learning about their child's decreased health risks (adjusted R2 = 0.33, P < .0001). Similarly, variables associated with greater parental willingness to test were being a mother (versus being a father), greater perceived risk of diseases in their child, greater interest in knowing about gene-health relationships in their child, anticipating less difficulty learning about their child's genetic health risks, anticipating more positive emotional reactions to learning about their child's decreased health risks, and positive decisional balance (adjusted R2 = 0.57, P < .0001). CONCLUSIONS: As genetic susceptibility testing for common, adult-onset health conditions proliferates, pediatricians should anticipate parents' interest in testing children and be prepared to facilitate informed decision making about such testing. PMID:21502235

  18. Juvenile Huntington's disease: a case report and literature review.

    PubMed

    Reyes Molón, L; Yáñez Sáez, R M; López-Ibor Alcocer, M I

    2010-01-01

    Huntington's disease is the most frequent neurodegenerative disease with a prevalence of fewer than 10 cases per 10,000 inhabitants; the juvenile form is responsible for less than 10% of all cases. Huntington's disease belongs to the group known as "triad syndromes," which evolve with cognitive, motor and neuropsychiatric manifestations. Around 30% of patients debut with behavioral symptoms, which are a major challenge for management by patients, families, and caregivers. Huntington's disease (HD) is reviewed and a case of juvenile onset is reported in this article. The characteristics of juvenile-onset Huntington's disease (HD) differ from those of adult-onset HD, as chorea does not occur, although bradykinesia, dystonia, and signs of cerebellar disorder, such as rigidity, are present, frequently in association with convulsive episodes and psychotic manifestations.

  19. Giant Intradural Mucocele in a Patient with Adult Onset Seizures

    PubMed Central

    Kechagias, E.; Georgakoulias, N.; Ioakimidou, C.; Kyriazi, S.; Kontogeorgos, G.; Seretis, A.

    2009-01-01

    A rare case of mucopyocele in a patient who presented with epileptic seizures is reported. The computed tomography scan (CT) and the magnetic resonance (MR) imaging revealed an intradural extension of a giant fronto-ethmoidal mucopyocele, eroding the cribriform plate and compressing both frontal lobes. The lesion was removed by craniotomy with elimination of the mass effect and reconstruction of the anterior skull base. An intracranial-intradural mucopyocele is an extremely rare cause of generalized convulsion as a presenting symptom, with only 6 cases reported in the literature. The total removal of the lesion associated with anterior fossa reconstruction is the treatment of choice. PMID:20847833

  20. Childhood adversities and adult-onset asthma: a cohort study

    PubMed Central

    Korkeila, Jyrki; Lietzen, Raija; Sillanmäki, Lauri H; Rautava, Päivi; Korkeila, Katariina; Kivimäki, Mika; Koskenvuo, Markku; Vahtera, Jussi

    2012-01-01

    Objectives Childhood adversities may be important determinants of later illnesses and poor health behaviour. However, large-scale prospective studies on the associations between childhood adversities and the onset of asthma in adulthood are lacking. Design Prospective cohort study with 7-year follow-up. Setting Nationally representative study. Data were collected from the Health and Social Support (HeSSup) survey and national registers. Participants The participants represent the Finnish population from the following age groups: 20–24, 30–34, 40–44, and 50–54 years at baseline in 1998 (24 057 survey participants formed the final cohort of this study). The occurrence of childhood adversities was assessed at baseline with a six-item survey scale. The analyses were adjusted for sociodemographic characteristics, behavioural health risks and common mental disorders. Primary and secondary outcomes The survey data were linked to data from national health registers on incident asthma during a 7-year follow-up to define new-onset asthma cases with verified diagnoses. Results A total of 12 126 (59%) participants reported that they encountered a childhood adversity. Of them 3677 (18% of all) endured three to six adversities. During a follow-up of 7 years, 593 (2.9%) participants were diagnosed with incident asthma. Those who reported three or more childhood adversities had a 1.6-fold (95% CI 1.31 to 2.01) greater risk of asthma compared to those without childhood adversities. This hazard attenuated but remained statistically significant after adjustment for conventional risk factors (HR 1.33; 95% CI 1.06 to 1.67). Conclusions Adults who report having encountered adversities in childhood may have an increased risk of developing asthma. PMID:23069774

  1. Adult Onset of Xanthelasmoid Mastocytosis: Report of a Rare Entity

    PubMed Central

    Nabavi, Nafiseh Sadat; Nejad, Masumeh Hosseini; Feli, Shahab; Bakhshoodeh, Behnoosh; Layegh, Pouran

    2016-01-01

    Xanthelasmoid or pseudoxanthomatous mastocytosis is an extremely rare variant of diffuse cutaneous mastocytosis. Herein, we describe an adult male with cutaneous mastocytosis showing multiple widespread yellowish ovoid papules like eruptive xanthoma. A 60-year-old male visited our outpatient clinic with a 1-year history of generalized yellowish, ovoid, and skin color papular eruption located on the trunk, groin, extremities, with the modest pruritus. Vital signs were stable, and Darier's sign was negative. No other subjective and objective signs were detected during the examination. No abnormality was detected in his diagnostic laboratory tests. Skin biopsy was taken, and histopathologic examination revealed proliferation of mast cells with ovoid and spindle nuclei with distinct cytoplasm borders around the capillaries, which was compatible with mastocytosis. Antihistamine was prescribed for pruritus control which was successful, but eruptions were persistent, and even 1-year phototherapy was not useful. PMID:27512209

  2. Epigenetic mechanisms in neurodevelopmental and neurodegenerative disease

    PubMed Central

    Jakovcevski, Mira; Akbarian, Schahram

    2013-01-01

    The exploration of brain epigenomes, which consist of various types of DNA methylation and covalent histone modifications, is providing new and unprecedented insights into the mechanisms of normal neural development, neurological disease and aging. Traditionally, chromatin defects in brain were considered static lesions of early development that occurred in the context of rare genetic syndromes but it is now clear that mutations and maladaptations of the epigenetic machinery cover a much wider continuum, including adult-onset neurodegenerative disease. Here, we describe how recent advances in neuroepigenetics have contributed to an improved mechanistic understanding of developmental and degenerative brain disorders, as well as how they could influence the development of future therapies for these conditions. PMID:22869198

  3. Sleepwalking in Parkinson's disease: a questionnaire-based survey.

    PubMed

    Oberholzer, Michael; Poryazova, Rositsa; Bassetti, Claudio L

    2011-07-01

    Sleepwalking (SW) corresponds to a complex sleep-associated behavior that includes locomotion, mental confusion, and amnesia. SW is present in about 10% of children and 2-3% of adults. In a retrospective series of 165 patients with Parkinson's disease (PD), we found adult-onset ("de novo") SW "de novo" in six (4%) of them. The aim of this study was to assess prospectively and systematically the frequency and characteristics of SW in PD patients. A questionnaire including items on sleep quality, sleep disorders, and specifically also SW and REM sleep behavior disorder (RBD), PD characteristics and severity, was sent to the members of the national PD patients organization in Switzerland. In the study, 36/417 patients (9%) reported SW, of which 22 (5%) had adult-onset SW. Patients with SW had significantly longer disease duration (p = 0.035), they reported more often hallucinations (p = 0.004) and nightmares (p = 0.003), and they had higher scores, suggestive for RBD in a validated questionnaire (p = 0.001). Patients with SW were also sleepier (trend to a higher Epworth Sleepiness Scale score, p = 0.055). Our data suggest that SW in PD patients is (1) more common than in the general population, and (2) is associated with RBD, nightmares, and hallucinations. Further studies including polysomnographic recordings are needed to confirm the results of this questionnaire-based analysis, to understand the relationship between SW and other nighttime wandering behaviors in PD, and to clarify the underlying mechanisms.

  4. Niemann–Pick type C disease – the tip of the iceberg? A review of neuropsychiatric presentation, diagnosis and treatment

    PubMed Central

    Evans, William R. H.; Hendriksz, Chris J.

    2017-01-01

    Niemann–Pick type C (NP-C) disease is a rare neurodegenerative lysosomal storage disorder. It is highly heterogeneous, and there is limited awareness of a substantial subgroup that has an attenuated adolescent/adult-onset disease. In these patients psychiatric features, often a psychosis, may dominate the initial impression, although often there is an associated ataxia and cognitive impairment. Typically, patients experience a substantial diagnostic delay. In this review we highlight the importance of early recognition and discuss the pathophysiology, neuropsychiatric presentation and recent changes in the investigation and work-up of these patients, and treatment options.

  5. U.S. Doctors Still Over-Prescribing Drugs

    MedlinePlus

    ... 162364.html U.S. Doctors Still Over-Prescribing Drugs: Survey More than 1 in 4 say antibiotics are ... doctors are still prescribing these treatments, a new survey of doctors reveals. Antibiotics are by far the ...

  6. 27 CFR 24.301 - Bulk still wine record.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Bulk still wine record. 24..., DEPARTMENT OF THE TREASURY LIQUORS WINE Records and Reports § 24.301 Bulk still wine record. A proprietor who produces or receives still wine in bond, (including wine intended for use as distilling material or...

  7. 27 CFR 24.301 - Bulk still wine record.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Bulk still wine record. 24..., DEPARTMENT OF THE TREASURY ALCOHOL WINE Records and Reports § 24.301 Bulk still wine record. A proprietor who produces or receives still wine in bond, (including wine intended for use as distilling material or...

  8. 27 CFR 24.193 - Conversion into still wine.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Conversion into still wine..., DEPARTMENT OF THE TREASURY LIQUORS WINE Production of Effervescent Wine § 24.193 Conversion into still wine. Sparkling wine or artificially carbonated wine may be dumped for use as still wine. The dumping process...

  9. 27 CFR 24.301 - Bulk still wine record.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Bulk still wine record. 24..., DEPARTMENT OF THE TREASURY LIQUORS WINE Records and Reports § 24.301 Bulk still wine record. A proprietor who produces or receives still wine in bond, (including wine intended for use as distilling material or...

  10. 27 CFR 24.301 - Bulk still wine record.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Bulk still wine record. 24..., DEPARTMENT OF THE TREASURY ALCOHOL WINE Records and Reports § 24.301 Bulk still wine record. A proprietor who produces or receives still wine in bond, (including wine intended for use as distilling material or...

  11. 27 CFR 24.193 - Conversion into still wine.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Conversion into still wine..., DEPARTMENT OF THE TREASURY ALCOHOL WINE Production of Effervescent Wine § 24.193 Conversion into still wine. Sparkling wine or artificially carbonated wine may be dumped for use as still wine. The dumping process...

  12. 27 CFR 24.193 - Conversion into still wine.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Conversion into still wine..., DEPARTMENT OF THE TREASURY LIQUORS WINE Production of Effervescent Wine § 24.193 Conversion into still wine. Sparkling wine or artificially carbonated wine may be dumped for use as still wine. The dumping process...

  13. 27 CFR 24.301 - Bulk still wine record.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Bulk still wine record. 24..., DEPARTMENT OF THE TREASURY LIQUORS WINE Records and Reports § 24.301 Bulk still wine record. A proprietor who produces or receives still wine in bond, (including wine intended for use as distilling material or...

  14. 27 CFR 24.193 - Conversion into still wine.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Conversion into still wine..., DEPARTMENT OF THE TREASURY LIQUORS WINE Production of Effervescent Wine § 24.193 Conversion into still wine. Sparkling wine or artificially carbonated wine may be dumped for use as still wine. The dumping process...

  15. 27 CFR 24.193 - Conversion into still wine.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Conversion into still wine..., DEPARTMENT OF THE TREASURY ALCOHOL WINE Production of Effervescent Wine § 24.193 Conversion into still wine. Sparkling wine or artificially carbonated wine may be dumped for use as still wine. The dumping process...

  16. 27 CFR 18.23 - Registry of stills.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Registry of stills. 18.23 Section 18.23 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... Registry of stills. The provisions of subpart C of part 29 of this chapter are applicable to stills...

  17. 27 CFR 22.66 - Registry of stills.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Registry of stills. 22.66... OF THE TREASURY ALCOHOL DISTRIBUTION AND USE OF TAX-FREE ALCOHOL Qualification Registry of Stills § 22.66 Registry of stills. The provisions of subpart C of part 29 of this chapter are applicable...

  18. 27 CFR 20.66 - Registry of stills.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Registry of stills. 20.66 Section 20.66 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... and Users Registry of Stills § 20.66 Registry of stills. The provisions of subpart C of part 29...

  19. 27 CFR 20.66 - Registry of stills.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Registry of stills. 20.66 Section 20.66 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... and Users Registry of Stills § 20.66 Registry of stills. The provisions of subpart C of part 29...

  20. 27 CFR 19.169 - Registry of stills.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Registry of stills. 19.169 Section 19.169 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... Registry of stills. The provisions of subpart C of part 29 of this chapter are applicable to stills...

  1. 27 CFR 18.23 - Registry of stills.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Registry of stills. 18.23 Section 18.23 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... Registry of stills. The provisions of subpart C of part 29 of this chapter are applicable to stills...

  2. 27 CFR 18.23 - Registry of stills.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Registry of stills. 18.23 Section 18.23 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... Registry of stills. The provisions of subpart C of part 29 of this chapter are applicable to stills...

  3. 27 CFR 18.23 - Registry of stills.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Registry of stills. 18.23 Section 18.23 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... Registry of stills. The provisions of subpart C of part 29 of this chapter are applicable to stills...

  4. 27 CFR 22.66 - Registry of stills.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Registry of stills. 22.66... OF THE TREASURY LIQUORS DISTRIBUTION AND USE OF TAX-FREE ALCOHOL Qualification Registry of Stills § 22.66 Registry of stills. The provisions of subpart C of part 29 of this chapter are applicable...

  5. 27 CFR 20.66 - Registry of stills.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Registry of stills. 20.66 Section 20.66 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... and Users Registry of Stills § 20.66 Registry of stills. The provisions of subpart C of part 29...

  6. 27 CFR 22.66 - Registry of stills.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Registry of stills. 22.66... OF THE TREASURY LIQUORS DISTRIBUTION AND USE OF TAX-FREE ALCOHOL Qualification Registry of Stills § 22.66 Registry of stills. The provisions of subpart C of part 29 of this chapter are applicable...

  7. 27 CFR 22.66 - Registry of stills.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Registry of stills. 22.66... OF THE TREASURY ALCOHOL DISTRIBUTION AND USE OF TAX-FREE ALCOHOL Qualification Registry of Stills § 22.66 Registry of stills. The provisions of subpart C of part 29 of this chapter are applicable...

  8. 27 CFR 20.66 - Registry of stills.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Registry of stills. 20.66 Section 20.66 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... and Users Registry of Stills § 20.66 Registry of stills. The provisions of subpart C of part 29...

  9. 27 CFR 20.66 - Registry of stills.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Registry of stills. 20.66 Section 20.66 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... and Users Registry of Stills § 20.66 Registry of stills. The provisions of subpart C of part 29...

  10. 27 CFR 18.23 - Registry of stills.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Registry of stills. 18.23 Section 18.23 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... Registry of stills. The provisions of subpart C of part 29 of this chapter are applicable to stills...

  11. 27 CFR 22.66 - Registry of stills.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Registry of stills. 22.66... OF THE TREASURY LIQUORS DISTRIBUTION AND USE OF TAX-FREE ALCOHOL Qualification Registry of Stills § 22.66 Registry of stills. The provisions of subpart C of part 29 of this chapter are applicable...

  12. A Case of Juvenile Huntington Disease in a 6-Year-Old Boy

    PubMed Central

    Sunwoo, Jun-Sang; Lee, Soon-Tae; Kim, Manho

    2010-01-01

    Huntington disease is a neurodegenerative disorder distinguished by the triad of dominant inheritance, choreoathetosis and dementia, usually with onset in the fourth and fifth decades. It is caused by an unstable cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the gene IT15 in locus 4p16.3. Juvenile HD that constitutes about 3% to 10% of all patients is clinically different from adult-onset form and characterized by a larger number of CAG repeats typically exceeding 60. We report a case of a 6-year-old boy with myoclonic seizure and 140 CAG repeats confirmed by molecular genetic analysis. PMID:24868381

  13. Fascia Research Congress evidence from the 100 year perspective of Andrew Taylor Still.

    PubMed

    Findley, Thomas W; Shalwala, Mona

    2013-07-01

    More than 100 years ago A.T. Still MD founded osteopathic medicine, and specifically described fascia as a covering, with common origins of layers of the fascial system despite diverse names for individual parts. Fascia assists gliding and fluid flow and is highly innervated. Fascia is intimately involved with respiration and with nourishment of all cells of the body, including those of disease and cancer. This paper reviews information presented at the first three International Fascia Research Congresses in 2007, 2009 and 2012 from the perspective of Dr Still, that fascia is vital for organism's growth and support, and it is where disease is sown.

  14. Diuretics: still essential drugs for the management of hypertension.

    PubMed

    Fuchs, Flávio Danni

    2009-06-01

    According to most current international guidelines for hypertension, diuretics are indicated for elderly and black patients, unless they have any of a long list of other preferential indications. These recommendations are mostly based on the results of corporate-sponsored and biased trials, which have unsuccessfully tried to demonstrate the existence of pleiotropic effects of newer agents. Metaregression analyses have shown that the benefits of treatments are directly proportional to the difference in blood pressure between trial arms. New analyses of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack (ALLHAT) trial demonstrated the superiority of chlorthalidone over other agents in the prevention of end-stage renal disease in diabetics and of cardiovascular events in newer cases of diabetes. Despite this evidence, patients continue to withdraw from effective therapies in recent trials. The use of diuretics has also been challenged by the results of the Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial, which employed hydrochlorothiazide, a diuretic with lower potency and duration of action than chlorthalidone. Diuretics are still essential drugs for hypertension management, but diuretics with higher potency and duration of action, such as chlorthalidone, should be preferred.

  15. Iron and ferroptosis: A still ill-defined liaison.

    PubMed

    Doll, Sebastian; Conrad, Marcus

    2017-03-09

    Ferroptosis is a recently described form of regulated necrotic cell death, which appears to contribute to a number of diseases, such as tissue ischemia/reperfusion injury, acute renal failure, and neurodegeneration. A hallmark of ferroptosis is iron-dependent lipid peroxidation, which can be inhibited by the key ferroptosis regulator glutathione peroxidase 4(Gpx4), radical trapping antioxidants and ferroptosis-specific inhibitors, such as ferrostatins and liproxstatins, as well as iron chelation. Although great strides have been made towards a better understanding of the proximate signals of distinctive lipid peroxides in ferroptosis, still little is known about the mechanistic implication of iron in the ferroptotic process. Hence, this review aims at summarizing recent advances in our understanding to what is known about enzymatic and nonenzymatic routes of lipid peroxidation, the involvement of iron in this process and the identification of novel players in ferroptotic cell death. Additionally, we review early works carried out long time before the term "ferroptosis" was actually introduced but which were instrumental in a better understanding of the role of ferroptosis in physiological and pathophysiological contexts. © 2017 IUBMB Life, 2017.

  16. Mixed connective tissue disease.

    PubMed

    Gunnarsson, Ragnar; Hetlevik, Siri Opsahl; Lilleby, Vibke; Molberg, Øyvind

    2016-02-01

    The concept of mixed connective tissue disease (MCTD) as a separate connective tissue disease (CTD) has persisted for more than four decades. High titers of antibodies targeting the U1 small nuclear ribonucleoprotein particle (U1 snRNP) in peripheral blood are a sine qua non for the diagnosis of MCTD, in addition to distinct clinical features including Raynaud's phenomenon (RP), "puffy hands," arthritis, myositis, pleuritis, pericarditis, interstitial lung disease (ILD), and pulmonary hypertension (PH). Recently, population-based epidemiology data from Norway estimated the point prevalence of adult-onset MCTD to be 3.8 per 100,000 and the mean annual incidence to be 2.1 per million per year, supporting the notion that MCTD is the least common CTD. Little is known about the etiology of MCTD, but recent genetic studies have confirmed that MCTD is a strongly HLA (​human leukocyte antigen)-linked disease, as the HLA profiles of MCTD differ distinctly from the corresponding profiles of ethnically matched healthy controls and other CTDs. In the first section of this review, we provide an update on the clinical, immunological, and genetic features of MCTD and discuss the relationship between MCTD and the other CTDs. Then we proceed to discuss the recent advances in therapy and our current understanding of prognosis and prognostic factors, especially those that are associated with the more serious pulmonary and cardiovascular complications of the disease. In the final section, we discuss some of the key, unresolved questions related to anti-RNP-associated diseases and indicate how these questions may be approached in future studies.

  17. Amyloid-beta immunotherapy: the hope for Alzheimer disease?

    PubMed Central

    2016-01-01

    Abstract Alzheimer disease (AD) is the most prevalent form of dementia of adult-onset, characterized by progressive impairment in cognition and memory. There is no cure for the disease and the current treatments are only symptomatic. Drug discovery is an expensive and time-consuming process; in the last decade no new drugs have been found for AD despite the efforts of the scientific community and pharmaceutical companies. The Aβ immunotherapy is one of the most promising approaches to modify the course of AD. This therapeutic strategy uses synthetic peptides or monoclonal antibodies (mAb) to decrease the Aβ load in the brain and slow the progression of the disease. Therefore, this article will discuss the main aspects of AD neuropathogenesis, the classical pharmacologic treatment, as well as the active and passive immunization describing drug prototypes evaluated in different clinical trials. PMID:28293044

  18. Amyloid-beta immunotherapy: the hope for Alzheimer disease?

    PubMed

    Barrera-Ocampo, Alvaro; Lopera, Francisco

    2016-12-30

    Alzheimer disease (AD) is the most prevalent form of dementia of adult-onset, characterized by progressive impairment in cognition and memory. There is no cure for the disease and the current treatments are only symptomatic. Drug discovery is an expensive and time-consuming process; in the last decade no new drugs have been found for AD despite the efforts of the scientific community and pharmaceutical companies. The Aβ immunotherapy is one of the most promising approaches to modify the course of AD. This therapeutic strategy uses synthetic peptides or monoclonal antibodies (mAb) to decrease the Aβ load in the brain and slow the progression of the disease. Therefore, this article will discuss the main aspects of AD neuropathogenesis, the classical pharmacologic treatment, as well as the active and passive immunization describing drug prototypes evaluated in different clinical trials.

  19. 7. PUMPING PLANT, SOUTHWEST AND SOUTHEAST SIDES, AND STILLING POND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. PUMPING PLANT, SOUTHWEST AND SOUTHEAST SIDES, AND STILLING POND - Outlook Irrigation District, Pumping Plant & Woodstave Pipe, Hudson Road & Snipes Lateral Road vicinity, Outlook, Yakima County, WA

  20. Ethical issues and policy analysis for genetic testing: Huntington's disease as a paradigm for diseases with a late onset.

    PubMed

    Lilani, Anjali

    2005-01-01

    This paper discusses the main ethical issues that arise when testing for genetic diseases with a late adult onset, such as Huntington's disease, take place. It is imperative to study genetic testing for HD and similar diseases because of the potential to influence future medical advances and the growing number of individuals who are considered pre-symptomatic. The main ethical issues are consent and privacy, prenatal testing and its implications, in addition to insurance discrimination. These issues are viewed from the perspective of genetic counselors, patients, the families of patients, and insurance companies. Policies put forth by the United States National Society of Genetic Counselors ("NSGC"), the Task Force on Genetic Testing, and the President's Council for Bioethics are also analyzed. Finally, new recommendations are proposed in order to ameliorate the ethical dilemmas encountered in genetic testing. These recommendations are largely based on existing policies and therefore involve amending current policies rather than revamping them.

  1. Pesticide and insect repellent mixture (permethrin and DEET) induces epigenetic transgenerational inheritance of disease and sperm epimutations.

    PubMed

    Manikkam, Mohan; Tracey, Rebecca; Guerrero-Bosagna, Carlos; Skinner, Michael K

    2012-12-01

    Environmental compounds are known to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a "pesticide mixture" (pesticide permethrin and insect repellent N,N-diethyl-meta-toluamide, DEET) promotes epigenetic transgenerational inheritance of disease and associated DNA methylation epimutations in sperm. Gestating F0 generation female rats were exposed during fetal gonadal sex determination and the incidence of disease evaluated in F1 and F3 generations. There were significant increases in the incidence of total diseases in animals from pesticide lineage F1 and F3 generation animals. Pubertal abnormalities, testis disease, and ovarian disease (primordial follicle loss and polycystic ovarian disease) were increased in F3 generation animals. Analysis of the pesticide lineage F3 generation sperm epigenome identified 363 differential DNA methylation regions (DMR) termed epimutations. Observations demonstrate that a pesticide mixture (permethrin and DEET) can promote epigenetic transgenerational inheritance of adult onset disease and potential sperm epigenetic biomarkers for ancestral environmental exposures.

  2. Adverse prenatal environment and kidney development: implications for programing of adult disease.

    PubMed

    Dorey, Emily S; Pantaleon, Marie; Weir, Kristy A; Moritz, Karen M

    2014-06-01

    The 'developmental origins of health and disease' hypothesis suggests that many adult-onset diseases can be attributed to altered growth and development during early life. Perturbations during gestation can be detrimental and lead to an increased risk of developing renal, cardiovascular, metabolic, and neurocognitive dysfunction in adulthood. The kidney has emerged as being especially vulnerable to insult at almost any stage of development resulting in a reduction in nephron endowment. In both humans and animal models, a reduction in nephron endowment is strongly associated with an increased risk of hypertension. The focus of this review is twofold: i) to determine the importance of specific periods during development on long-term programing and ii) to examine the effects of maternal perturbations on the developing kidney and how this may program adult-onset disease. Recent evidence has suggested that insults occurring around the time of conception also have the capacity to influence long-term health. Although epigenetic mechanisms are implicated in mediating these outcomes, it is unclear as to how these may impact on kidney development. This presents exciting new challenges and areas for research.

  3. Who Is Billy Still? Cue Sheet for Students.

    ERIC Educational Resources Information Center

    John F. Kennedy Center for the Performing Arts, Washington, DC.

    Designed to be used before and after attending a centennial performance of the music of African American composer William Grant Still, this cue sheet presents information about the performance. The cue sheet presents biographical information about Still and background information on the Lincoln Theatre in Washington, D.C., which had been closed…

  4. HST Solar Arrays photographed by Electronic Still Camera

    NASA Technical Reports Server (NTRS)

    1993-01-01

    This close-up view of one of two Solar Arrays (SA) on the Hubble Space Telescope (HST) was photographed with an Electronic Still Camera (ESC), and downlinked to ground controllers soon afterward. Electronic still photography is a technology which provides the means for a handheld camera to electronically capture and digitize an image with resolution approaching film quality.

  5. 27 CFR 19.79 - Registry of stills.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Registry of stills. 19.79 Section 19.79 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... Obtaining a Permit Requirements for Registering A Plant § 19.79 Registry of stills. Section 29.55 of...

  6. 27 CFR 19.79 - Registry of stills.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Registry of stills. 19.79 Section 19.79 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... Obtaining a Permit Requirements for Registering A Plant § 19.79 Registry of stills. Section 29.55 of...

  7. 27 CFR 19.79 - Registry of stills.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Registry of stills. 19.79 Section 19.79 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... Obtaining a Permit Requirements for Registering A Plant § 19.79 Registry of stills. Section 29.55 of...

  8. 27 CFR 19.79 - Registry of stills.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Registry of stills. 19.79 Section 19.79 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... Obtaining a Permit Requirements for Registering A Plant § 19.79 Registry of stills. Section 29.55 of...

  9. What Counselors Still Need to Know about Community Colleges

    ERIC Educational Resources Information Center

    Johnson, Anne Stansbury

    2012-01-01

    Many things have not changed since Esther Hugo's 2006 article on community colleges. For the most part, "open-door" means just that: "apply and you're in." The lenses community colleges use to see students are still complex; the purposes of community colleges are still many. Students of all ages come for transfer, career and vocational training,…

  10. 27 CFR 26.52 - Still wines containing carbon dioxide.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... carbon dioxide. 26.52 Section 26.52 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... ISLANDS Formulas for Products From Puerto Rico § 26.52 Still wines containing carbon dioxide. (a) General. Still wines may contain not more than 0.392 gram of carbon dioxide per 100 milliliters of wine;...

  11. 27 CFR 26.222 - Still wines containing carbon dioxide.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... carbon dioxide. 26.222 Section 26.222 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... ISLANDS Formulas for Products From the Virgin Islands § 26.222 Still wines containing carbon dioxide. (a) General. Still wines may contain not more than 0.392 gram of carbon dioxide per 100 milliliters of...

  12. 27 CFR 26.52 - Still wines containing carbon dioxide.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... carbon dioxide. 26.52 Section 26.52 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... ISLANDS Formulas for Products From Puerto Rico § 26.52 Still wines containing carbon dioxide. (a) General. Still wines may contain not more than 0.392 gram of carbon dioxide per 100 milliliters of wine;...

  13. 27 CFR 26.52 - Still wines containing carbon dioxide.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... carbon dioxide. 26.52 Section 26.52 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... ISLANDS Formulas for Products From Puerto Rico § 26.52 Still wines containing carbon dioxide. (a) General. Still wines may contain not more than 0.392 gram of carbon dioxide per 100 milliliters of wine;...

  14. 27 CFR 26.222 - Still wines containing carbon dioxide.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... carbon dioxide. 26.222 Section 26.222 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... ISLANDS Formulas for Products From the Virgin Islands § 26.222 Still wines containing carbon dioxide. (a) General. Still wines may contain not more than 0.392 gram of carbon dioxide per 100 milliliters of...

  15. 27 CFR 26.52 - Still wines containing carbon dioxide.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... carbon dioxide. 26.52 Section 26.52 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... ISLANDS Formulas for Products From Puerto Rico § 26.52 Still wines containing carbon dioxide. (a) General. Still wines may contain not more than 0.392 gram of carbon dioxide per 100 milliliters of wine;...

  16. 27 CFR 26.222 - Still wines containing carbon dioxide.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... carbon dioxide. 26.222 Section 26.222 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... ISLANDS Formulas for Products From the Virgin Islands § 26.222 Still wines containing carbon dioxide. (a) General. Still wines may contain not more than 0.392 gram of carbon dioxide per 100 milliliters of...

  17. 27 CFR 26.222 - Still wines containing carbon dioxide.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... carbon dioxide. 26.222 Section 26.222 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... ISLANDS Formulas for Products From the Virgin Islands § 26.222 Still wines containing carbon dioxide. (a) General. Still wines may contain not more than 0.392 gram of carbon dioxide per 100 milliliters of...

  18. 27 CFR 26.52 - Still wines containing carbon dioxide.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... carbon dioxide. 26.52 Section 26.52 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... ISLANDS Formulas for Products From Puerto Rico § 26.52 Still wines containing carbon dioxide. (a) General. Still wines may contain not more than 0.392 gram of carbon dioxide per 100 milliliters of wine;...

  19. 27 CFR 26.222 - Still wines containing carbon dioxide.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... carbon dioxide. 26.222 Section 26.222 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... ISLANDS Formulas for Products From the Virgin Islands § 26.222 Still wines containing carbon dioxide. (a) General. Still wines may contain not more than 0.392 gram of carbon dioxide per 100 milliliters of...

  20. Genetics Home Reference: Huntington disease

    MedlinePlus

    ... in personality and a decline in thinking and reasoning abilities. Individuals with the adult-onset form of ... and drooling. School performance declines as thinking and reasoning abilities become impaired. Seizures occur in 30 percent ...

  1. Unravelling the myotonic dystrophy type 1 clinical spectrum: A systematic registry-based study with implications for disease classification.

    PubMed

    De Antonio, M; Dogan, C; Hamroun, D; Mati, M; Zerrouki, S; Eymard, B; Katsahian, S; Bassez, G

    2016-10-01

    The broad clinical spectrum of myotonic dystrophy type 1 (DM1) creates particular challenges for both medical care and design of clinical trials. Clinical onset spans a continuum from birth to late adulthood, with symptoms that are highly variable in both severity and nature of the affected organ systems. In the literature, this complex phenotype is divided into three grades (mild, classic, and severe) and four or five main clinical categories (congenital, infantile/juvenile, adult-onset and late-onset forms), according to symptom severity and age of onset, respectively. However, these classifications are still under discussion with no consensus thus far. While some specific clinical features have been primarily reported in some forms of the disease, there are no clear distinctions. As a consequence, no modifications in the management of healthcare or the design of clinical studies have been proposed based on the clinical form of DM1. The present study has used the DM-Scope registry to assess, in a large cohort of DM1 patients, the robustness of a classification divided into five clinical forms. Our main aim was to describe the disease spectrum and investigate features of each clinical form. The five subtypes were compared by distribution of CTG expansion size, and the occurrence and onset of the main symptoms of DM1. Analyses validated the relevance of a five-grade model for DM1 classification. Patients were classified as: congenital (n=93, 4.5%); infantile (n=303, 14.8%); juvenile (n=628, 30.7%); adult (n=694, 34.0%); and late-onset (n=326, 15.9%). Our data show that the assumption of a continuum from congenital to the late-onset form is valid, and also highlights disease features specific to individual clinical forms of DM1 in terms of symptom occurrence and chronology throughout the disease course. These results support the use of the five-grade model for disease classification, and the distinct clinical profiles suggest that age of onset and clinical form may

  2. Prevalence of systemic autoimmune rheumatic diseases and clinical significance of ANA profile: data from a tertiary hospital in Shanghai, China.

    PubMed

    Yang, Zaixing; Ren, Yingpeng; Liu, Donghong; Lin, Feng; Liang, Yan

    2016-09-01

    It is necessary and useful to explore prevalence of various systemic autoimmune rheumatic diseases (SARDs) in patients with suspicion of having SARDs and to characterize antinuclear antibodies (ANA) profile for identifying different populations (SARDs and non-SARDs). A total of 5024 consecutive patients with available medical records were investigated, whose sera had been tested for ANA profile, including ANA, anti-dsDNA and anti-extractable nuclear antigen (ENA) antibodies, between 31 January 2012 and 26 March 2014. Only 594 (11.8%) patients were diagnosed with SARDs of those suspected with SARDs. The prevalence of systemic lupus erythematosus (SLE) was highest (3.2%), followed by rheumatoid arthritis (RA) (2.5%), primary Sjögren's syndrome (pSS) (1.7%), ankylosing spondylitis (AS) (1.5%), etc. Of females, SLE also showed the highest prevalence (6%), while of males, AS showed the highest prevalence (1.9%). The prevalence of most SARDs was closely associated with age, except mixed connective tissue disease (MCTD), and the variation characteristics among different age groups were different among various SARDs. The prevalence of ANA was significantly increased in most SARD patients [especially in SLE, systemic sclerosis (SSc) and MCTD]. For anti-ENA antibodies, in contrast to some autoantibodies associated with multiple SARDs (e.g. anti-SSA, SSB, nRNP), others were relatively specific for certain diseases, such as anti-dsDNA, Sm, histone, nucleosome and Rib-P for SLE, anti-SCL-70 for SSc and anti-Jo-1 for polymyositis/dermatomyositis (PM/DM). Of note, ANA profile appeared to be of little significance for AS, ANCA-associated vasculitis (AAV), polymyalgia rheumatic (PMR), adult-onset Still's disease (ASD) and Behcet's disease (BD). The younger were more likely to have the presence of anti-dsDNA, Sm, histone or Rib-P for SLE, and anti-SSA for RA or MCTD. No significant differences for frequencies of ANA and anti-ENA autoantibodies were found between sexes in most SARDs

  3. Adult Xanthogranulomatous Disease of the Orbit: Clinical Presentations, Evaluation, and Management.

    PubMed

    Ortiz Salvador, J M; Subiabre Ferrer, D; Pérez Ferriols, A

    2017-03-02

    Adult xanthogranulomatous disease of the orbit refers to a heterogeneous group of clinical syndromes with differing degrees of systemic involvement and distinct prognoses. The different syndromes all present clinically with progressively enlarging, yellowish lesions of the orbit. Histologically, the lesions are characterized by an inflammatory infiltrate of foam cells and Touton-type multinucleated giant cells. The xanthomatized histiocytes are CD68(+), S100(-), and CD1a(-). There are 4 clinical forms of xanthogranulomatous disease of the orbit: adult xanthogranulomatous disease of the orbit, adult onset asthma and periocular xanthogranuloma, necrobiotic xanthogranuloma, and Erdheim-Chester disease. The treatment of local lesions are treated with systemic corticosteroids and other immunosuppressors. Vemurafenib, tocilizumab, and sirolimus have shown promising results in systemic disease.

  4. Applications of the Wittig-Still rearrangement in organic synthesis.

    PubMed

    Rycek, Lukas; Hudlicky, Tomas

    2017-02-16

    This review traces the discovery of the Wittig-Still rearrangement and its applications in organic synthesis. Its relationship to Wittig rearrangements is discussed along with detailed analysis of E/Z- and diastereoselectivity. Modifications of the products arising from the Wittig-Still rearrangement are reviewed in the context of increased complexity in intermediates potentially useful in target oriented synthesis. Early applications of the Wittig-Still rearrangement to modifications of steroids are reviewed as are applications to various terpene and alkaloid natural product targets and miscellaneous compounds. To the best of our knowledge, the literature is covered through December 2016.

  5. Aberrant palmitoylation in Huntington disease.

    PubMed

    Sanders, Shaun S; Hayden, Michael R

    2015-04-01

    Huntington disease (HD) is an adult-onset neurodegenerative disease caused by a CAG expansion in the HTT gene. HD is characterized by striatal atrophy and is associated with motor, cognitive and psychiatric deficits. In the presence of the HD mutation, the interactions between huntingtin (HTT) and huntingtin interacting protein 14 (HIP14 or DHHC17) and HIP14-like (DHHC13, a HIP14 orthologue), palmitoyl acyltransferases for HTT, are disturbed, resulting in reduced palmitoylation of HTT. Genetic ablation of either Hip14 or Hip14l recapitulates many features of HD, including striatal atrophy and motor deficits. However, there are no changes in palmitoylation of HTT in either mouse model and, subsequently, the similarities between the phenotypes of these two mouse models and the HD mouse model are believed to result from underpalmitoylation of other HIP14 and HIP14L substrates. HTT acts as a modulator of HIP14 activity such that in the presence of the HD mutation, HIP14 is less active. Consequently, HIP14 substrates are less palmitoylated, leading to neuronal toxicity. This suggests that altered HIP14-HTT and HIP14L-HTT interactions in the presence of the HD mutation reduces palmitoylation and promotes mislocalization of HTT and other HIP14/HIP14L substrates. Ultimately, HD may be, in part, a disease of altered palmitoylation.

  6. Motor neurone disease: a practical update on diagnosis and management.

    PubMed

    Wood-Allum, Clare; Shaw, Pamela J

    2010-06-01

    Motor neurone disease (MND) is an adult-onset neurodegenerative disease which leads inexorably via weakness of limb, bulbar and respiratory muscles to death from respiratory failure three to five years later. Most MND is sporadic but approximately 10% is inherited. In exciting recent breakthroughs two new MND genes have been identified. Diagnosis is clinical and sometimes difficult--treatable mimics must be excluded before the diagnosis is ascribed. Riluzole prolongs life by only three to four months and is only available for the amyotrophic lateral sclerosis (ALS) form of MND. Management therefore properly focuses on symptom relief and the preservation of independence and quality of life. Malnutrition is a poor prognostic factor. In appropriate patients enteral feeding is recommended although its use has yet to be shown to improve survival. In ALS patients with respiratory failure and good or only moderately impaired bulbar function non-invasive positive pressure ventilation prolongs life and improves quality of life.

  7. Early onset polycystic kidney disease: how early is early?

    PubMed

    Birewar, Sonali; Zawada, Edward T

    2003-11-01

    We report a case of a six-month-old infant with autosomal dominant polycystic kidney disease. He was a full term baby with an uneventful pre and postnatal period. He was delivered by uncomplicated vaginal delivery without forceps or fetal distress. His father was recently diagnosed with adult onset autosomal dominant polycystic kidney disease (APKD) with creatinine clearance around 25%-30%. The parents requested renal ultrasound of the baby to screen for APKD. It revealed normal sized and normal shaped kidneys, but with multiple bilateral cysts in the renal cortices, each measuring about 5 mm-7 mm in diameter. Subsequent DNA analysis showed presence of PKD1 gene, present on chromosome 16. His renal function was within normal range. The baby needs to be regularly followed-up for the most common complications of APKD, including hypertension and renal insufficiency.

  8. Current Pharmacological Management in Juvenile Huntington’s Disease

    PubMed Central

    Robertson, Lisa; Santini, Helen; O'Donovan, Kirsty L; Squitieri, Ferdinando; Barker, Roger A; Rakowicz, Maria; Landwehrmeyer, G. Bernhard; Quarrell, Oliver

    2012-01-01

    Background: The clinical presentation of Juvenile Huntington’s Disease (JHD) can be very different from adult-onset HD with little evidence to guide symptomatic management. Aim: To survey the current use of pharmacological treatments for JHD. Methods: Patients were identified through the HD Association, Hospital Doctors and the European Huntington’s Disease Network REGISTRY study. Results: The most commonly prescribed agents were anti-psychotics (24/45), anti-depressants (17/45) and anti-parkinsonian medications (15/45). 5 patients were taking more than 8 medications. Conclusions: The most commonly prescribed group of medication was the anti-psychotic. Many patients were on multiple therapies, highlighting the need to rationalise medications. PMID:22474619

  9. Gene Therapy in Mouse Models of Huntington Disease

    PubMed Central

    Southwell, Amber L.; Patterson, Paul H.

    2011-01-01

    Huntingtin, the protein that when mutated causes Huntington disease (HD), has many known interactors and participates in diverse cellular functions. Mutant Htt (mHtt) engages in a variety of aberrant interactions that lead to pathological gain of toxic functions as well as loss of normal functions. The broad symptomatology of HD, including diminished voluntary motor control, cognitive decline, and psychiatric disturbances, reflects the multifaceted neuropathology. Although currently available therapies for HD focus on symptom management, the autosomal dominant cause and the adult onset make this disease an ideal candidate for genetic intervention. A variety of gene therapy approaches have been tested in mouse models of HD, ranging from those aimed at ameliorating downstream pathology or replacing lost neuronal populations to more upstream strategies to reduce mHtt levels. Here the authors review the results of these preclinical trials. PMID:21489966

  10. Some Melanoma Survivors Still Seek Out the Sun

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_163887.html Some Melanoma Survivors Still Seek Out the Sun 1 in ... Even after surviving the potentially deadly skin cancer melanoma, some people continue to go out in the ...

  11. 9. VIEW OF THE PRESSURE CULVERT STILLING BASIN, LOOKING NORTH. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. VIEW OF THE PRESSURE CULVERT STILLING BASIN, LOOKING NORTH. NOTE THE LEVEE TO THE RIGHT. - Wyoming Valley Flood Control System, Woodward Pumping Station, East of Toby Creek crossing by Erie-Lackawanna Railroad, Edwardsville, Luzerne County, PA

  12. Metformin Still Best as First Type 2 Diabetes Treatment

    MedlinePlus

    ... fullstory_162835.html Metformin Still Best as First Type 2 Diabetes Treatment American College of Physicians updated diabetes guidelines, ... is the first-line drug for people with type 2 diabetes, and that several other medications -- including newer ones -- ...

  13. Docs and Nukes--Still a Live Issue.

    PubMed

    Helfand, Ira; Sidel, Victor W

    2015-11-12

    Physicians have played a key role in warning governments and the public about the danger of nuclear war and the need to abolish nuclear weapons. That role is still needed: existing nuclear warheads pose an existential threat to humanity.

  14. Americans with High Blood Pressure Still Eating Too Much Salt

    MedlinePlus

    ... Blood Pressure Still Eating Too Much Salt Average sodium intake more than double the recommended daily limit ... did in 1999. Between 1999 and 2012, salt (sodium) consumption rose from about 2,900 milligrams a ...

  15. 5. Photocopy of Historic Construction Photograph. PUMPING PLANT AND STILLING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Photocopy of Historic Construction Photograph. PUMPING PLANT AND STILLING POND. (Original print, U. S. Bureau of Reclamation, Yakima, WA., ca. 1915) - Outlook Irrigation District, Pumping Plant & Woodstave Pipe, Hudson Road & Snipes Lateral Road vicinity, Outlook, Yakima County, WA

  16. Stille couplings catalytic in tin: a "Sn-F" approach.

    PubMed

    Maleczka, R E; Gallagher, W P

    2001-12-27

    A new tin recycling method for Stille couplings catalytic in tin is reported. PMHS made hypercoordinate by KF((aq)) allows Me(3)SnH to be efficiently recycled during a Pd(0)-catalyzed hydrostannation/Stille cascade. Relative to previously disclosed protocols, reaction times are shorter and because this process is believed to proceed through a Me(3)SnF intermediate the hazards and problems associated with trimethyltins are also diminished.[reaction: see text

  17. HST Solar Arrays photographed by Electronic Still Camera

    NASA Technical Reports Server (NTRS)

    1993-01-01

    This medium close-up view of one of two original Solar Arrays (SA) on the Hubble Space Telescope (HST) was photographed with an Electronic Still Camera (ESC), and downlinked to ground controllers soon afterward. This view shows the cell side of the minus V-2 panel. Electronic still photography is a technology which provides the means for a handheld camera to electronically capture and digitize an image with resolution approaching film quality.

  18. HST Solar Arrays photographed by Electronic Still Camera

    NASA Technical Reports Server (NTRS)

    1993-01-01

    This view, backdropped against the blackness of space shows one of two original Solar Arrays (SA) on the Hubble Space Telescope (HST). The scene was photographed with an Electronic Still Camera (ESC), and downlinked to ground controllers soon afterward. Electronic still photography is a technology which provides the means for a handheld camera to electronically capture and digitize an image with resolution approaching film quality.

  19. Small UAV-Acquired, High-resolution, Georeferenced Still Imagery

    SciTech Connect

    Ryan Hruska

    2005-09-01

    Currently, small Unmanned Aerial Vehicles (UAVs) are primarily used for capturing and down-linking real-time video. To date, their role as a low-cost airborne platform for capturing high-resolution, georeferenced still imagery has not been fully utilized. On-going work within the Unmanned Vehicle Systems Program at the Idaho National Laboratory (INL) is attempting to exploit this small UAV-acquired, still imagery potential. Initially, a UAV-based still imagery work flow model was developed that includes initial UAV mission planning, sensor selection, UAV/sensor integration, and imagery collection, processing, and analysis. Components to support each stage of the work flow are also being developed. Critical to use of acquired still imagery is the ability to detect changes between images of the same area over time. To enhance the analysts’ change detection ability, a UAV-specific, GIS-based change detection system called SADI or System for Analyzing Differences in Imagery is under development. This paper will discuss the associated challenges and approaches to collecting still imagery with small UAVs. Additionally, specific components of the developed work flow system will be described and graphically illustrated using varied examples of small UAV-acquired still imagery.

  20. Impacts of wind stilling on solar radiation variability in China.

    PubMed

    Lin, Changgui; Yang, Kun; Huang, Jianping; Tang, Wenjun; Qin, Jun; Niu, Xiaolei; Chen, Yingying; Chen, Deliang; Lu, Ning; Fu, Rong

    2015-10-14

    Solar dimming and wind stilling (slowdown) are two outstanding climate changes occurred in China over the last four decades. The wind stilling may have suppressed the dispersion of aerosols and amplified the impact of aerosol emission on solar dimming. However, there is a lack of long-term aerosol monitoring and associated study in China to confirm this hypothesis. Here, long-term meteorological data at weather stations combined with short-term aerosol data were used to assess this hypothesis. It was found that surface solar radiation (SSR) decreased considerably with wind stilling in heavily polluted regions at a daily scale, indicating that wind stilling can considerably amplify the aerosol extinction effect on SSR. A threshold value of 3.5 m/s for wind speed is required to effectively reduce aerosols concentration. From this SSR dependence on wind speed, we further derived proxies to quantify aerosol emission and wind stilling amplification effects on SSR variations at a decadal scale. The results show that aerosol emission accounted for approximately 20% of the typical solar dimming in China, which was amplified by approximately 20% by wind stilling.

  1. Impacts of wind stilling on solar radiation variability in China

    PubMed Central

    Lin, Changgui; Yang, Kun; Huang, Jianping; Tang, Wenjun; Qin, Jun; Niu, Xiaolei; Chen, Yingying; Chen, Deliang; Lu, Ning; Fu, Rong

    2015-01-01

    Solar dimming and wind stilling (slowdown) are two outstanding climate changes occurred in China over the last four decades. The wind stilling may have suppressed the dispersion of aerosols and amplified the impact of aerosol emission on solar dimming. However, there is a lack of long-term aerosol monitoring and associated study in China to confirm this hypothesis. Here, long-term meteorological data at weather stations combined with short-term aerosol data were used to assess this hypothesis. It was found that surface solar radiation (SSR) decreased considerably with wind stilling in heavily polluted regions at a daily scale, indicating that wind stilling can considerably amplify the aerosol extinction effect on SSR. A threshold value of 3.5 m/s for wind speed is required to effectively reduce aerosols concentration. From this SSR dependence on wind speed, we further derived proxies to quantify aerosol emission and wind stilling amplification effects on SSR variations at a decadal scale. The results show that aerosol emission accounted for approximately 20% of the typical solar dimming in China, which was amplified by approximately 20% by wind stilling. PMID:26463748

  2. Genetic/environmental determinants of adult chronic obstructive pulmonary disease and possible links with childhood wheezing.

    PubMed

    Smith, O O; Helms, P J

    2001-06-01

    Epidemiological evidence and similarities in underlying inflammatory mechanisms suggest that childhood respiratory conditions and adult onset chronic obstructive pulmonary disease (COPD) may have a common aetiology. The prevalence of COPD in the UK has been estimated to be 10% in males and 11% in females, and like asthma, is thought to have a polygenic contribution with a complex interplay between genetic and environmental factors. The only proven genetic factor so far identified in its pathogenesis is alpha1-antitrypsin deficiency, although this accounts for less than 1% of individuals with disease. Environmental exposures are significant but the observation that only 15% of smokers develop COPD and only some young children exposed in utero develop recurrent wheezing points to as yet undefined contributory genetic factors. The similarity in response to medication also suggests some features in common and a central question must be whether those adults who develop COPD had transient viral-associated wheeze (VAW) or non-specific bronchial hyperresponsiveness (BHR) in childhood? Similarities between some of the childhood wheezing syndromes and adult onset COPD invites a re-examination of possible links between the two conditions.

  3. Molecular diagnosis of putative Stargardt disease by capture next generation sequencing.

    PubMed

    Zhang, Xiao; Ge, Xianglian; Shi, Wei; Huang, Ping; Min, Qingjie; Li, Minghan; Yu, Xinping; Wu, Yaming; Zhao, Guangyu; Tong, Yi; Jin, Zi-Bing; Qu, Jia; Gu, Feng

    2014-01-01

    Stargardt Disease (STGD) is the commonest genetic form of juvenile or early adult onset macular degeneration, which is a genetically heterogeneous disease. Molecular diagnosis of STGD remains a challenge in a significant proportion of cases. To address this, seven patients from five putative STGD families were recruited. We performed capture next generation sequencing (CNGS) of the probands and searched for potentially disease-causing genetic variants in previously identified retinal or macular dystrophy genes. Seven disease-causing mutations in ABCA4 and two in PROM1 were identified by CNGS, which provides a confident genetic diagnosis in these five families. We also provided a genetic basis to explain the differences among putative STGD due to various mutations in different genes. Meanwhile, we show for the first time that compound heterozygous mutations in PROM1 gene could cause cone-rod dystrophy. Our findings support the enormous potential of CNGS in putative STGD molecular diagnosis.

  4. Thermal and Exergetic Analysis of a Solar Still

    NASA Astrophysics Data System (ADS)

    Chávez, S.; Terres, H.; Lizardi, A.; López, R.; Lara, A.

    2017-01-01

    In this work an energy and exergy analysis of solar distillation process is presented. The analysis is based on the experimental observation of the simple basin type solar stills for 4 different initial volumes (5.5, 6.5, 7.5 and 8.5 L). Energy and exergy balance equations have been written for all components of the solar still including glass cover, brine and absorber plate. The thermodynamic models for the energy and exergy analysis are presented on the critical heat transfer correlations in literatures for the simple basin type solar still. The results show that maximum values are reached in the energy efficiency of 45.6, 41.5, 35.7 and 31.8%, however exergetic efficiency for maximum values are 7.5, 7.2, 7 and 5.4%, corresponding to volumes 5.5, 6.5, 7.5 and 8.5 L respectively.

  5. Evaluating thermal performance of a single slope solar still

    NASA Astrophysics Data System (ADS)

    Badran, Omar O.; Abu-Khader, Mazen M.

    2007-08-01

    The distillation is one of the important methods of getting clean water from brackish and sea water using the free energy supply from the sun. An experimental work is conducted on a single slope solar still. The thermal performance of the single slope solar still is examined and evaluated through implementing the following effective parameters: (a) different insulation thicknesses of 1, 2.5 and 5 cm; (b) water depth of 2 and 3.5 cm; (c) solar intensity; (d) Overall heat loss coefficient (e) effective absorbtivity and transmissivity; and (f) ambient, water and vapor temperatures. Different effective parameters should be taken into account to increase the still productivity. A mathematical model is presented and compared with experimental results. The model gives a good match with experimental values.

  6. Multilingual artificial text detection and extraction from still images

    NASA Astrophysics Data System (ADS)

    Raza, Ahsen; Abidi, Ali; Siddiqi, Imran

    2013-01-01

    In this paper we present a novel method for multilingual artificial text extraction from still images. We propose a lexicon independent, block based technique that employs a combination of spatial transforms, texture, edge and, gradient based operations to detect unconstrained textual regions from still images. Finally, some morphological and geometrical constraints are applied for fine localization of textual content. The proposed method was evaluated on two standard and three custom developed datasets comprising a wide variety of images with artificial text occurrences in five different languages namely English, Urdu, Arabic, Chinese and Hindi.

  7. Advances in motor neurone disease.

    PubMed

    Bäumer, Dirk; Talbot, Kevin; Turner, Martin R

    2014-01-01

    Motor neurone disease (MND), the commonest clinical presentation of which is amyotrophic lateral sclerosis (ALS), is regarded as the most devastating of adult-onset neurodegenerative disorders. The last decade has seen major improvements in patient care, but also rapid scientific advances, so that rational therapies based on key pathogenic mechanisms now seem plausible. ALS is strikingly heterogeneous in both its presentation, with an average one-year delay from first symptoms to diagnosis, and subsequent rate of clinical progression. Although half of patients succumb within 3-4 years of symptom onset, typically through respiratory failure, a significant minority survives into a second decade. Although an apparently sporadic disorder for most patients, without clear environmental triggers, recent genetic studies have identified disease-causing mutations in genes in several seemingly disparate functional pathways, so that motor neuron degeneration may need to be understood as a common final pathway with a number of upstream causes. This apparent aetiological and clinical heterogeneity suggests that therapeutic studies should include detailed biomarker profiling, and consider genetic as well as clinical stratification. The most common mutation, accounting for 10% of all Western hemisphere ALS, is a hexanucleotide repeat expansion in C9orf72. This and several other genes implicate altered RNA processing and protein degradation pathways in the core of ALS pathogenesis. A major gap remains in understanding how such fundamental processes appear to function without obvious deficit in the decades prior to symptom emergence, and the study of pre-symptomatic gene carriers is an important new initiative.

  8. Books that Made a Difference (and Still Do)

    ERIC Educational Resources Information Center

    School Administrator, 2009

    2009-01-01

    At a time when traditional forms of print media are surrendering to electronic transmission, the full-length hardcover/softcover book still finds its way onto the reading lists of the nation's top-level education administrators. This article presents nine reflections by education leaders on a book whose message continues to resonate: John L. Barry…

  9. Blood Thinners: Can I Still Get Blood Clots?

    MedlinePlus

    ... get blood clots? If you're taking a blood thinner, is it still possible to get a blood clot? Answers from Rekha Mankad, M.D. Yes. Medications that are commonly called blood thinners — such as aspirin, warfarin (Coumadin, Jantoven), dabigatran ( ...

  10. The Bear Is Still Singing: Creating Lyrics with Social Studies

    ERIC Educational Resources Information Center

    Turner, Thomas

    2008-01-01

    In the author's article in the 1988 premiere issue of "Social Studies and the Young Learner," he suggested that chain songs and rounds, simple folk and summer camp standards, could be easily transformed with lyrics (written by the teacher or students) that contained useful, purposeful social studies content. He argued then, and still does, that…

  11. Still Not Equal: Expanding Educational Opportunity in Society

    ERIC Educational Resources Information Center

    Brown, M. Christopher, II, Ed.

    2007-01-01

    "Still Not Equal: Expanding Educational Opportunity in Society" addresses the successes and failures of "Brown v. Board of Education" and the Civil Rights Act of 1964, as well as the continuing challenge of expanding educational opportunity in the United States and across the Black diaspora. The educational, political, and social influence…

  12. Complete Genome Sequence of Bacillus megaterium Siphophage Stills

    PubMed Central

    Lee, Simon S.; Kongari, Rohit R.; Hernandez, Adriana C.

    2015-01-01

    Bacillus megaterium is a soil-dwelling bacterium frequently used in research as a model organism and in industry in protein production applications. Bacteriophages may be used to enhance the use of this bacterium. Here, we describe the complete genome of B. megaterium siphophage Stills and its core features. PMID:26251490

  13. The Current Women Superintendents in Texas: Still in the Minority

    ERIC Educational Resources Information Center

    Sampson, Pauline; Davenport, Marie

    2010-01-01

    The superintendent is the highest ranking administrator in a school district (Katz, 2005). Despite increasing trends of women advancing in the fields of business and government, the superintendent position in school districts still has relatively few women (Brunner & Grogan, 2007; Dana & Bourisaw, 2006; Glass, 2000; Grogan & Brunner,…

  14. 21. Photocopy of ca. 1951 view (when furnaces were still ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    21. Photocopy of ca. 1951 view (when furnaces were still in blast) looking north at central furnace complex with railroad cars of furnace charging materials in foreground and No. 2 Furnace at left. Photo marked on back 'David W. Corson from A. Devaney, N.Y.' - Sloss-Sheffield Steel & Iron, First Avenue North Viaduct at Thirty-second Street, Birmingham, Jefferson County, AL

  15. 27 CFR 24.114 - Registry of stills.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Registry of stills. 24.114 Section 24.114 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS WINE Establishment and Operations Application § 24.114 Registry of...

  16. 27 CFR 24.114 - Registry of stills.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Registry of stills. 24.114 Section 24.114 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL WINE Establishment and Operations Application § 24.114 Registry of...

  17. 27 CFR 24.114 - Registry of stills.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Registry of stills. 24.114 Section 24.114 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS WINE Establishment and Operations Application § 24.114 Registry of...

  18. 27 CFR 24.114 - Registry of stills.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Registry of stills. 24.114 Section 24.114 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL WINE Establishment and Operations Application § 24.114 Registry of...

  19. 27 CFR 24.114 - Registry of stills.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Registry of stills. 24.114 Section 24.114 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS WINE Establishment and Operations Application § 24.114 Registry of...

  20. Design and operation of a small-scale ethanol still

    SciTech Connect

    Floyd, J.E.

    1980-01-01

    A description is presented of a small-scale alcohol still utilizing beer derived from both corn and potato mash. Use was made of the ethanol in alcohol vehicles imported from Brazil. By-products (stillage) were successfully used as cattle feed. (DMC)

  1. Connecticut's Children: Still at Risk. 1995 Data Update.

    ERIC Educational Resources Information Center

    Cunningham, Michelle Doucette

    This 1995 update to "Connecticut's Children: Still at Risk" is the second annual report examining how children in the state are faring. The title indicates that Connecticut's children are at tremendous risk of failing to become productive adults. The update does not repeat much of the general information from the previous year's…

  2. 29. Coke oven byproduct building "XX" with ammonia stills; powerhouse ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    29. Coke oven by-product building "XX" with ammonia stills; powerhouse with 8 sisters (stacks) in background; conveyor #20 (with break) on right, pulevrized coal storage bunker on left. Looking north/northwest - Rouge Steel Company, 3001 Miller Road, Dearborn, MI

  3. GENERAL VIEW OF PUMPHOUSE FOUNDATIONS, ALSO SHOWING THREE PUMPS STILL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF PUMPHOUSE FOUNDATIONS, ALSO SHOWING THREE PUMPS STILL ON THE PAD, AND THE ELECTRICAL SUBSTATION IN LEFT MIDDLE DISTANCE - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Flame Deflector Water System, Test Area 1-120, north end of Jupiter Boulevard, Boron, Kern County, CA

  4. Bead Roller, at right, used for preparing flume sheeting (still ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Bead Roller, at right, used for preparing flume sheeting (still in use, 2004); on left is a pipe cutter. Facing southeast - Childs-Irving Hydroelectric Project, Childs System, Childs Powerhouse, Forest Service Road 708/502, Camp Verde, Yavapai County, AZ

  5. All Things Considered: Still Life with Glass and Lemon

    ERIC Educational Resources Information Center

    School Arts: The Art Education Magazine for Teachers, 2004

    2004-01-01

    This brief article presents describes Pablo Picasso's oil on canvas painting, "Still Life with Glass and Lemon, 1910." Composed of abstract, monochromatic shapes, this painting's original subject is surprisingly a glass and lemon. The artist, Pablo Picasso, developed this unique system of breaking down objects into their basic geometric parts with…

  6. Why STEM Fields Still Don't Draw More Women

    ERIC Educational Resources Information Center

    Coger, Robin N.; Cuny, Jan; Klawe, Maria; McGann, Matt; Purcell, Karen D.

    2012-01-01

    There have been many efforts in recent years to draw more women into STEM fields. While women have made gains, they are still far less likely than men to major in such fields, especially engineering and computer science. Why? This article presents the responses and the thoughts of a group of scholars and experts.

  7. Surgery in Pediatric Crohn's Disease: Indications, Timing and Post-Operative Management

    PubMed Central

    2017-01-01

    Pediatric onset Crohn's disease (CD) tends to have complicated behavior (stricture or penetration) than elderly onset CD at diagnosis. Considering the longer duration of the disease in pediatric patients, the accumulative chance of surgical treatment is higher than in adult onset CD patients. Possible operative indications include perianal CD, intestinal stricture or obstruction, abdominal abscess or fistula, intestinal hemorrhage, neoplastic changes and medically untreatable inflammation. Growth retardation is an operative indication only for pediatric patients. Surgery can affect a patient's clinical course, especially for pediatric CD patient who are growing physically and mentally, so the decision should be made by careful consideration of several factors. The complex and diverse clinical conditions hinder development of a systemized treatment algorithm. Therefore, timing of surgery in pediatric CD patients should be determined with individualized approach by an experienced and well organized multidisciplinary inflammatory bowel disease team. Best long-term outcomes will require proactive post-operative monitoring and therapeutic modifications according to the conditions.

  8. Performance of triple effect evacuated solar still system

    SciTech Connect

    Kawahara, Takashi; Toyoshima, Yoshinori; Nakaya, Akira; Narasaki, Yuzo; Kamiya, Ichiro; Sato, Haruki

    1999-07-01

    The authors developed a solar energy distillation system, still, and tested it on 36 days from 23 November 1996 to 23 October 1997 at Keio University in Yokohama. The system consists of a 7.76 m{sup 2} solar collector and 3.7 m{sup 2} solar cells. The still is self-sustainable for use at any place without any fossil energy supply. The maximum mass of water distilled was 13.59 kg/m{sup 2} day (105 kg/day in total mass) on 16 July 1997. the coefficient of performance for distillation was 1,49 of the input solar energy for the system and the energy consumption of a vacuum pump.

  9. Dynamic and still microcirculatory image analysis for quantitative microcirculation research

    NASA Astrophysics Data System (ADS)

    Ying, Xiaoyou; Xiu, Rui-juan

    1994-05-01

    Based on analyses of various types of digital microcirculatory image (DMCI), we summed up the image features of DMCI, the digitizing demands for digital microcirculatory imaging, and the basic characteristics of the DMCI processing. A dynamic and still imaging separation processing (DSISP) mode was designed for developing a DMCI workstation and the DMCI processing. Original images in this study were clinical microcirculatory images from human finger nail-bed and conjunctiva microvasculature, and intravital microvascular network images from animal tissue or organs. A series of dynamic and still microcirculatory image analysis functions were developed in this study. The experimental results indicate most of the established analog video image analysis methods for microcirculatory measurement could be realized in a more flexible way based on the DMCI. More information can be rapidly extracted from the quality improved DMCI by employing intelligence digital image analysis methods. The DSISP mode is very suitable for building a DMCI workstation.

  10. Mass and heat transfer model of Tubular Solar Still

    SciTech Connect

    Ahsan, Amimul; Fukuhara, Teruyuki

    2010-07-15

    In this paper, a new mass and heat transfer model of a Tubular Solar Still (TSS) was proposed incorporating various mass and heat transfer coefficients taking account of the humid air properties inside the still. The heat balance of the humid air and the mass balance of the water vapor in the humid air were formulized for the first time. As a result, the proposed model enabled to calculate the diurnal variations of the temperature, water vapor density and relative humidity of the humid air, and to predict the hourly condensation flux besides the temperatures of the water, cover and trough, and the hourly evaporation flux. The validity of the proposed model was verified using the field experimental results carried out in Fukui, Japan and Muscat, Oman in 2008. The diurnal variations of the calculated temperatures and water vapor densities had a good agreement with the observed ones. Furthermore, the proposed model can predict the daily and hourly production flux precisely. (author)

  11. Climate and floods still govern California levee breaks

    USGS Publications Warehouse

    Florsheim, J.L.; Dettinger, M.D.

    2007-01-01

    Even in heavily engineered river systems, climate still governs flood variability and thus still drives many levee breaks and geomorphic changes. We assemble a 155-year record of levee breaks for a major California river system to find that breaks occurred in 25% of years during the 20th Century. A relation between levee breaks and river discharge is present that sets a discharge threshold above which most levee breaks occurred. That threshold corresponds to small floods with recurrence intervals of ???2-3 years. Statistical analysis illustrates that levee breaks and peak discharges cycle (broadly) on a 12-15 year time scale, in time with warm-wet storm patterns in California, but more slowly or more quickly than ENSO and PDO climate phenomena, respectively. Notably, these variations and thresholds persist through the 20th Century, suggesting that historical flood-control effects have not reduced the occurrence or frequency of levee breaks. Copyright 2007 by the American Geophysical Union.

  12. Reverse engineering human neurodegenerative disease using pluripotent stem cell technology.

    PubMed

    Liu, Ying; Deng, Wenbin

    2016-05-01

    With the technology of reprogramming somatic cells by introducing defined transcription factors that enables the generation of "induced pluripotent stem cells (iPSCs)" with pluripotency comparable to that of embryonic stem cells (ESCs), it has become possible to use this technology to produce various cells and tissues that have been difficult to obtain from living bodies. This advancement is bringing forth rapid progress in iPSC-based disease modeling, drug screening, and regenerative medicine. More and more studies have demonstrated that phenotypes of adult-onset neurodegenerative disorders could be rather faithfully recapitulated in iPSC-derived neural cell cultures. Moreover, despite the adult-onset nature of the diseases, pathogenic phenotypes and cellular abnormalities often exist in early developmental stages, providing new "windows of opportunity" for understanding mechanisms underlying neurodegenerative disorders and for discovering new medicines. The cell reprogramming technology enables a reverse engineering approach for modeling the cellular degenerative phenotypes of a wide range of human disorders. An excellent example is the study of the human neurodegenerative disease amyotrophic lateral sclerosis (ALS) using iPSCs. ALS is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons (MNs), culminating in muscle wasting and death from respiratory failure. The iPSC approach provides innovative cell culture platforms to serve as ALS patient-derived model systems. Researchers have converted iPSCs derived from ALS patients into MNs and various types of glial cells, all of which are involved in ALS, to study the disease. The iPSC technology could be used to determine the role of specific genetic factors to track down what's wrong in the neurodegenerative disease process in the "disease-in-a-dish" model. Meanwhile, parallel experiments of targeting the same specific genes in human ESCs could also be performed to control

  13. Biafra Still Matters: Contested Humanitarian Airlift and American Foreign Policy

    DTIC Science & Technology

    2016-06-01

    i BIAFRA STILL MATTERS : CONTESTED HUMANITARIAN AIRLIFT AND AMERICAN FOREIGN POLICY BY MAJOR DAVID WALTER MYRICK A THESIS PRESENTED...Statehood described as rushing “to pontificate on matters which these men (western scholars) are incompetent to comprehend.”2 Okpaku attributes...design for a Nigerian Federation. Nigerian nationalists wavered back and forth on the matter of federation and were less zealous than many of their

  14. Dr Pugh and the myth of the illicit still.

    PubMed

    Paull, J D

    2014-07-01

    In her valuable history of the arrival of the news of etherisation in Australia and its implementation by many doctors and dentists, titled One Grand Chain, the late Dr Gwen Wilson asserted that the dentist and the doctor who pioneered etherisation in Australia, "Belisario and Pugh, …were charged by the authorities with possession of an illicit still." This paper examines the evidence for the truth or otherwise of this assertion, in relation to Dr Pugh.

  15. Digitalis reappraised: Still here today, but gone tomorrow?

    PubMed

    Opie, Lionel H

    2014-12-15

    Digoxin is one of the oldest of drugs acting on the heart and still one of the most frequently used. While in atrial fibrillation digoxin continues to have a valid role in the control of ventricular rate when added to beta-blockers and calcium antagonists, digoxin for heart failure is no longer a supportable option in view of the negative recent meta-analysis.

  16. V838 Mon: hot component still in deep eclipse

    NASA Astrophysics Data System (ADS)

    Kolka, I.; Liimets, T.; Kankare, E.; Pursimo, T.; Datson, J.

    2009-09-01

    We report on brightness measurements of the peculiar binary V838 Mon in the B,V,Rc bands in 2009. We have used the ALFOSC and MOSCA cameras at the Nordic Optical Telescope on La Palma. The B magnitudes listed below indicate that the hot B3V component of the binary is still in the deep eclipse which was first reported by Goranskij in ATel #1821.

  17. Nitroglycerine - The Saga in India: We Still Need Fostering It

    DTIC Science & Technology

    1996-08-01

    rather than explosive. But NG even now demands a lot of attention and caution in its manufacture . NG has never allowed its transport naked...handling, it is being slowly phased out especially in mining activities. However its use in propellants still continues and its manufacture and handling...production started in India some where around 1905 for use in the manufacturing "Cordite" the Nitro Cellulose (NC) - Nitro Glycerine double base

  18. Congenital mesenteric hernia in neonates: Still a dilemma

    PubMed Central

    Mandhan, Parkash; Alshahwani, Noora; Al-Balushi, Zainab; Arain, Anwar

    2015-01-01

    Congenital transmesenteric hernia in neonates is a rare cause of intestinal obstruction with devastating outcomes and still remains a challenge to diagnose pre-operatively. Patients are often managed with emergency surgical exploration and may need bowel resection. We present 2 neonates with small bowel obstruction secondary to strangulated transmesenteric hernia through a congenital defect in the small bowel mesentery, which were managed successfully. We have also reviewed the literature about congenital transmesenteric hernia in neonates. PMID:26612129

  19. Vygotsky in english: what still needs to be done.

    PubMed

    van der Veer, René; Yasnitsky, Anton

    2011-12-01

    At present readers of English have still limited access to Vygotsky's writings. Existing translations are marred by mistakes and outright falsifications. Analyses of Vygotsky's work tend to downplay the collaborative and experimental nature of his research. Several suggestions are made to improve this situation. New translations are certainly needed and new analyses should pay attention to the contextual nature of Vygotsky's thinking and research practice.

  20. Still-to-video face recognition in unconstrained environments

    NASA Astrophysics Data System (ADS)

    Wang, Haoyu; Liu, Changsong; Ding, Xiaoqing

    2015-02-01

    Face images from video sequences captured in unconstrained environments usually contain several kinds of variations, e.g. pose, facial expression, illumination, image resolution and occlusion. Motion blur and compression artifacts also deteriorate recognition performance. Besides, in various practical systems such as law enforcement, video surveillance and e-passport identification, only a single still image per person is enrolled as the gallery set. Many existing methods may fail to work due to variations in face appearances and the limit of available gallery samples. In this paper, we propose a novel approach for still-to-video face recognition in unconstrained environments. By assuming that faces from still images and video frames share the same identity space, a regularized least squares regression method is utilized to tackle the multi-modality problem. Regularization terms based on heuristic assumptions are enrolled to avoid overfitting. In order to deal with the single image per person problem, we exploit face variations learned from training sets to synthesize virtual samples for gallery samples. We adopt a learning algorithm combining both affine/convex hull-based approach and regularizations to match image sets. Experimental results on a real-world dataset consisting of unconstrained video sequences demonstrate that our method outperforms the state-of-the-art methods impressively.

  1. A liquid phase based C. elegans behavioral analysis system identifies motor activity loss in a nematode Parkinson's disease model.

    PubMed

    Zheng, Maohua; Gorelenkova, Olga; Yang, Jiong; Feng, Zhaoyang

    2012-03-15

    Motor activity of Caenorhabditis elegans is widely used to study the mechanisms ranging from basic neuronal functions to human neurodegenerative diseases. It may also serve as a paradigm to screen for potential therapeutic reagents treating these diseases. Here, we developed an automated, 96-well plate and liquid phase based system that quantifies nematode motor activity in real time. Using this system, we identified an adult-onset, ageing-associated motor activity loss in a transgenic nematode line expressing human pathogenic G2019S mutant LRRK2 (leucine-rich repeat kinase 2), the leading genetic cause of Parkinson's disease characterized by dopaminergic neurodegeneration associated motor deficient mainly in elder citizens. Thus, our system may be used as a platform to screen for potential therapeutic drugs treating Parkinson's disease. It can also be used to monitor motor activity of nematodes in liquid phase at similar scenario.

  2. The Story of CD4+CD28− T Cells Revisited: Solved or Still Ongoing?

    PubMed Central

    Maly, Kathrin

    2015-01-01

    CD4+CD28− T cells are a unique type of proinflammatory T cells characterised by blockade of costimulatory CD28 receptor expression at the transcriptional level, which is still reversible by IL-12. In healthy individuals older than 65 years, these cells may accumulate to up to 50% of total CD4+ T lymphocytes as in many immune-mediated diseases, immunodeficiency, and specific infectious diseases. Here we focus on CD4+CD28− T cells in chronic immune-mediated diseases, summarizing various phenotypic and functional characteristics, which vary depending on the underlying disease, disease activity, and concurrent treatment. CD4+CD28− T cells present as effector/memory cells with increased replicative history and oligoclonality but reduced apoptosis. As an alternative costimulatory signal instead of CD28, not only natural killer cell receptors and Toll-like receptors, but also CD47, CTLA-4, OX40, and 4-1BB have to be considered. The proinflammatory and cytotoxic capacities of these cells indicate an involvement in progression and maintenance of chronic immune-mediated disease. So far it has been shown that treatment with TNF-α blockers, abatacept, statins, and polyclonal antilymphocyte globulins (ATG) mediates reduction of the CD4+CD28− T cell level. The clinical relevance of targeting CD4+CD28− T cells as a therapeutic option has not been examined so far. PMID:25834833

  3. Evaluation of Skybox Video and Still Image products

    NASA Astrophysics Data System (ADS)

    d'Angelo, P.; Kuschk, G.; Reinartz, P.

    2014-11-01

    The SkySat-1 satellite lauched by Skybox Imaging on November 21 in 2013 opens a new chapter in civilian earth observation as it is the first civilian satellite to image a target in high definition panchromatic video for up to 90 seconds. The small satellite with a mass of 100 kg carries a telescope with 3 frame sensors. Two products are available: Panchromatic video with a resolution of around 1 meter and a frame size of 2560 × 1080 pixels at 30 frames per second. Additionally, the satellite can collect still imagery with a swath of 8 km in the panchromatic band, and multispectral images with 4 bands. Using super-resolution techniques, sub-meter accuracy is reached for the still imagery. The paper provides an overview of the satellite design and imaging products. The still imagery product consists of 3 stripes of frame images with a footprint of approximately 2.6 × 1.1 km. Using bundle block adjustment, the frames are registered, and their accuracy is evaluated. Image quality of the panchromatic, multispectral and pansharpened products are evaluated. The video product used in this evaluation consists of a 60 second gazing acquisition of Las Vegas. A DSM is generated by dense stereo matching. Multiple techniques such as pairwise matching or multi image matching are used and compared. As no ground truth height reference model is availble to the authors, comparisons on flat surface and compare differently matched DSMs are performed. Additionally, visual inspection of DSM and DSM profiles show a detailed reconstruction of small features and large skyscrapers.

  4. 26. EASTERNMOST HYDRAULIC RAM IN CENTER RANK (STILL OPERABLE), LOWER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    26. EASTERNMOST HYDRAULIC RAM IN CENTER RANK (STILL OPERABLE), LOWER LEVEL OF STAGE, LOOKING SOUTH. THE CENTER BANK OF RAMS MOVED SMALL SECTIONS OF STAGE IN THE CENTER OF EACH LARGE MOVABLE SECTION. THE WEST EDGE OF THIS SECTION HAS BEEN EXTENDED TO THE WEST EDGE OF THE LARGE SECTION WHICH ORIGINALLY SURROUNDED IT. THE SOUTH RAM FOR THE LARGE SECTION IS VISIBLE IN THE BACKGROUND. THE SMALL MOVABLE SECTIONS COULD NOT TILT BUT COULD BE LOWERED TO THE LOWER LEVEL OF THE STAGE WITH HINGED PANELS UNDER EACH LARGE SECTION FILLING THE VOID. - Auditorium Building, 430 South Michigan Avenue, Chicago, Cook County, IL

  5. [Surgical frontal lecture. Still important for teaching students?].

    PubMed

    Wierlemann, A; Baur, J; Germer, C T

    2013-10-01

    In times of manifold digital learning resources open to public access lectures in surgery still play a major role in medical training. It is a platform for discussion with the medical teacher and provides the opportunity to create a vivid learning experience by showing live operations via video streaming and inviting patients to the lectures. When then change in paradigm is achieved from pure knowledge transfer to cross-linkage of knowledge, the surgical lecture will be a major future keystone in medical education, where the lecturer can reach the students with his own passion for the field of expertise and get them interested in surgery.

  6. Solar-powered alcohol still. Final technical report

    SciTech Connect

    Montgomery, J.A. Jr.

    1984-01-01

    The objective of this study was to determine the feasibility of a solar alcohol still to purify ethanol from a concentration normally achieved in a fermentation process to that of reasonable purity (ideally 90 to 95%). Several designs were utilized with varying success. The possibility of distilling alcohol without the use of fossil fuels is very attractive. Although the purity of the alcohol achieved was somewhat less than desired, the concept is promising and further design modifications and/or repeated distillations may prove to be adequate to provide alcohol of useful purity. 24 references, 3 figures.

  7. Performance measurement of commercial electronic still picture cameras

    NASA Astrophysics Data System (ADS)

    Hsu, Wei-Feng; Tseng, Shinn-Yih; Chiang, Hwang-Cheng; Cheng, Jui-His; Liu, Yuan-Te

    1998-06-01

    Commercial electronic still picture cameras need a low-cost, systematic method for evaluating the performance. In this paper, we present a measurement method to evaluating the dynamic range and sensitivity by constructing the opto- electronic conversion function (OECF), the fixed pattern noise by the peak S/N ratio (PSNR) and the image shading function (ISF), and the spatial resolution by the modulation transfer function (MTF). The evaluation results of individual color components and the luminance signal from a PC camera using SONY interlaced CCD array as the image sensor are then presented.

  8. Novel BAC mouse model of Huntington’s disease with 225 CAG repeats exhibits an early widespread and stable degenerative phenotype

    PubMed Central

    Wegrzynowicz, Michal; Bichell, Terry Jo; Soares, Barbara D.; Loth, Meredith K.; McGlothan, Jennifer L.; Alikhan, Fatima S.; Hua, Kegang; Coughlin, Jennifer M.; Holt, Hunter K.; Jetter, Christopher S.; Mori, Susumu; Pomper, Martin G.; Osmand, Alexander P.; Guilarte, Tomás R.; Bowman, Aaron B.

    2015-01-01

    BACKGROUND Unusually large CAG repeat expansions (>60) in exon one of Huntingtin (HTT) are invariably associated with a juvenile-onset form of Huntington’s disease (HD), characterized by a more extensive and rapidly progressing neuropathology than the more prevalent adult-onset form. However, existing mouse models of HD that express the full-length Htt gene with CAG repeat lengths associated with juvenile HD (ranging between ~75 to ~150 repeats in published models) exhibit selective neurodegenerative phenotypes more consistent with adult-onset HD. OBJECTIVE To determine if a very large CAG repeat (>200) in full-length Htt elicits neurodegenerative phenotypes consistent with juvenile HD. METHODS Using a bacterial artificial chromosome (BAC) system, we generated mice expressing full-length mouse Htt with ~225 CAG repeats under control of the mouse Htt promoter. Mice were characterized using behavioral, neuropathological, biochemical and brain imaging methods. RESULTS BAC-225Q mice exhibit phenotypes consistent with a subset of features seen in juvenile-onset HD: very early motor behavior abnormalities, reduced body weight, widespread and progressive increase in Htt aggregates, gliosis, and neurodegeneration. Early striatal pathology was observed, including reactive gliosis and loss of dopamine receptors, prior to detectable volume loss. HD-related blood markers of impaired energy metabolism and systemic inflammation were also increased. Aside from an age-dependent progression of diffuse nuclear aggregates at 6 months of age to abundant neuropil aggregates at 12 months of age, other pathological and motor phenotypes showed little to no progression. CONCLUSIONS The HD phenotypes present in animals 3 to 12 months of age make the BAC-225Q mice a unique and stable model of full-length mutant Htt associated phenotypes, including body weight loss, behavioral impairment and HD-like neurodegenerative phenotypes characteristic of juvenile-onset HD and/or late-stage adult-onset

  9. Endomyocardial Fibrosis: Still a Mystery after 60 Years

    PubMed Central

    Bukhman, Gene; Ziegler, John; Parry, Eldryd

    2008-01-01

    The pathologist Jack N. P. Davies identified endomyocardial fibrosis in Uganda in 1947. Since that time, reports of this restrictive cardiomyopathy have come from other parts of tropical Africa, South Asia, and South America. In Kampala, the disease accounts for 20% of heart disease patients referred for echocardiography. We conducted a systematic review of research on the epidemiology and etiology of endomyocardial fibrosis. We relied primarily on articles in the MEDLINE database with either “endomyocardial fibrosis” or “endomyocardial sclerosis” in the title. The volume of publications on endomyocardial fibrosis has declined since the 1980s. Despite several hypotheses regarding cause, no account of the etiology of this disease has yet fully explained its unique geographical distribution. PMID:18301727

  10. Endomyocardial fibrosis: still a mystery after 60 years.

    PubMed

    Bukhman, Gene; Ziegler, John; Parry, Eldryd

    2008-02-27

    The pathologist Jack N. P. Davies identified endomyocardial fibrosis in Uganda in 1947. Since that time, reports of this restrictive cardiomyopathy have come from other parts of tropical Africa, South Asia, and South America. In Kampala, the disease accounts for 20% of heart disease patients referred for echocardiography. We conducted a systematic review of research on the epidemiology and etiology of endomyocardial fibrosis. We relied primarily on articles in the MEDLINE database with either "endomyocardial fibrosis" or "endomyocardial sclerosis" in the title. The volume of publications on endomyocardial fibrosis has declined since the 1980s. Despite several hypotheses regarding cause, no account of the etiology of this disease has yet fully explained its unique geographical distribution.

  11. Primary amputation: is there still a place for it?

    PubMed

    Setacci, F; Sirignano, P; De Donato, G; Galzerano, G; Cappelli, A; Palasciano, G; Setacci, C

    2012-02-01

    Diabetic foot (DF) continues to present a significant challenge to the vascular surgeon. Despite great advances in the treatment of DF, including open revascularization and endovascular techniques, significant numbers of amputations are still performed. The effect of aggressive revascularization on ultimate limb salvage rates continues to be debated. In the US the amputation rate has increased from 19 to 30 per 100000 persons years over the last two decades primarily due to an increase in diabetes and advancing age. Despite advances in cardiovascular treatment, in patients over 85 year of age an amputation rate of 140 per 100000 persons/year has been reported with a primary amputation (PA) still carrying an excessively high mortality rate of 13-17%. Amputation has been historically regarded as a life saving therapeutic measure. At the time the advances of surgical techniques in revascularization, diagnostic modalities and effectiveness in antimicrobial agents have unintentionally designated amputation to be the last treatment option. Nowadays we have a variety of therapeutic options to correct, modify, or circumvent the obstructive vascular pathology, such as angioplasty, atherectomy, stenting, stent graft and the traditional open surgical approach using endarterectomy, patch angioplasty, or bypass revascularization and even sympathectomy to enhance cutaneous perfusion to the toes. However it is understandable that many older patients who have received multiple limb preservation procedures have spent most of the remaining days of their lives in and out of the hospital or in a long-term care facility where high technical and sophisticated wound care techniques can be provided.

  12. Establishing imaging sensor specifications for digital still cameras

    NASA Astrophysics Data System (ADS)

    Kriss, Michael A.

    2007-02-01

    Digital Still Cameras, DSCs, have now displaced conventional still cameras in most markets. The heart of a DSC is thought to be the imaging sensor, be it Full Frame CCD, and Interline CCD, a CMOS sensor or the newer Foveon buried photodiode sensors. There is a strong tendency by consumers to consider only the number of mega-pixels in a camera and not to consider the overall performance of the imaging system, including sharpness, artifact control, noise, color reproduction, exposure latitude and dynamic range. This paper will provide a systematic method to characterize the physical requirements of an imaging sensor and supporting system components based on the desired usage. The analysis is based on two software programs that determine the "sharpness", potential for artifacts, sensor "photographic speed", dynamic range and exposure latitude based on the physical nature of the imaging optics, sensor characteristics (including size of pixels, sensor architecture, noise characteristics, surface states that cause dark current, quantum efficiency, effective MTF, and the intrinsic full well capacity in terms of electrons per square centimeter). Examples will be given for consumer, pro-consumer, and professional camera systems. Where possible, these results will be compared to imaging system currently on the market.

  13. Learning random networks for compression of still and moving images

    NASA Technical Reports Server (NTRS)

    Gelenbe, Erol; Sungur, Mert; Cramer, Christopher

    1994-01-01

    Image compression for both still and moving images is an extremely important area of investigation, with numerous applications to videoconferencing, interactive education, home entertainment, and potential applications to earth observations, medical imaging, digital libraries, and many other areas. We describe work on a neural network methodology to compress/decompress still and moving images. We use the 'point-process' type neural network model which is closer to biophysical reality than standard models, and yet is mathematically much more tractable. We currently achieve compression ratios of the order of 120:1 for moving grey-level images, based on a combination of motion detection and compression. The observed signal-to-noise ratio varies from values above 25 to more than 35. The method is computationally fast so that compression and decompression can be carried out in real-time. It uses the adaptive capabilities of a set of neural networks so as to select varying compression ratios in real-time as a function of quality achieved. It also uses a motion detector which will avoid retransmitting portions of the image which have varied little from the previous frame. Further improvements can be achieved by using on-line learning during compression, and by appropriate compensation of nonlinearities in the compression/decompression scheme. We expect to go well beyond the 250:1 compression level for color images with good quality levels.

  14. Multiscale turbulence effects in supersonic jets exhausting into still air

    NASA Technical Reports Server (NTRS)

    Abdol-Hamid, Khaled S.; Wilmoth, Richard G.

    1987-01-01

    A modified version of the multiscale turbulence model of Hanjalic has been applied to the problem of supersonic jets exhausting into still air. In particular, the problem of shock-cell decay through turbulent interaction with the mixing layer has been studied for both mildly interacting and strongly resonant jet conditions. The modified Hanjalic model takes into account the nonequilibrium energy transfer between two different turbulent spectral scales. The turbulence model was incorporated into an existing shock-capturing, parabolized Navier-Stokes computational model in order to perform numerical experiments. The results show that the two-scale turbulence model provides significant improvement over one-scale models in the prediction of plume shock structure for underexpanded supersonic (Mach 2) and sonic (Mach 1) jets. For the supersonic jet, excellent agreement with experiment was obtained for the centerline shock-cell pressure decay up to 40 jet radii. For the sonic jet, the agreement with experiment was not so good, but the two-scale model still showed significant improvement over the one-scale model. It is shown that by relating some of the coefficients in the turbulent-transport equations to the relative time scale for transfer of energy between scales the two-scale model can provide predictions that bound the measured shock-cell decay rate for the sonic jet.

  15. Heated Proteins are Still Active in a Functionalized Nanoporous Support

    SciTech Connect

    Chen, Baowei; Qi, Wen N.; Li, Xiaolin; Lei, Chenghong; Liu, Jun

    2013-07-08

    We report that even under the heated condition, the conformation and activity of a protein can be hoarded in a functionalized nanoporous support via non-covalent interaction, although the hoarded protein was not exhibiting the full protein activity, the protein released subsequently still maintained its native conformation and activity. Glucose oxidase (GOX) was spontaneously and largely entrapped in aminopropyl-functionalized mesoporous silica (NH2-FMS) at 20 oC via a dominant electrostatic interaction. Although FMS-GOX displayed 45% activity of the free enzyme in solution, the GOX released from FMS exhibited its 100% activity prior to the entrapment. Surprisingly, the released GOX from FMS still maintained 89% of its initial activity prior to the entrapment after FMS-GOX was incubated at 60 oC for 1 h prior to release, while the free GOX in solution lost nearly all activity under the same incubation. Intrinsic fluorescence emission of GOX and native electrophoresis demonstrated that the heating resulted in significant conformational changes and oligomeric structures of the free GOX, but FMS efficiently maintained the thermal stability of GOX therein and resisted the thermal denaturation and oligomeric aggregation.

  16. After Kyoto, science still probes global warming causes

    SciTech Connect

    Westbrook, G.

    1998-01-19

    The Kyoto meeting has come and gone. In the US, the treaty still has to be signed by President Bill Clinton and ratified by the Senate, an action that is most unlikely in view of last year`s 95-0 vote on the issue. In the short term 36 senators are up for reelection in November and therefore likely to come under intense pressure to change their positions, to support the Kyoto treaty, and to push for Senate action. Senators will need support, additional inputs, and overall reinforcement of their positions. One area that this writer believes still has much to offer in this context is the quality--more specifically, the lack of quality--of much of the scientific evidence behind this treaty. Part of that subject is the natural variability in the climate. Natural climate variability is based on cyclical forces, random events, and the Earth`s response to these two factors. These forces create the variability in the climate, the background noise above which any signal of anthropogenic warming must rise in order to be detected. A review of key climatic cycles is the subject of this article.

  17. Do we still need renal biopsy in lupus nephritis?

    PubMed

    Haładyj, Ewa; Cervera, Ricard

    2016-01-01

    The natural course of systemic lupus erythematosus (SLE) is characterized by periods of disease activity and remissions. Prolonged disease activity results in cumulative organ damage. Lupus nephritis is one of the most common and devastating manifestations of SLE. In the era of changing therapy to less toxic regimens, some authors have stated that if mycophenolate mofetil can be used for the induction and maintenance treatment in all histological classes of lupus nephritis, renal biopsy can be omitted. This article aims to answer the question of what brings the bigger risk: renal biopsy or its abandonment.

  18. Bestrophin 1 and retinal disease.

    PubMed

    Johnson, Adiv A; Guziewicz, Karina E; Lee, C Justin; Kalathur, Ravi C; Pulido, Jose S; Marmorstein, Lihua Y; Marmorstein, Alan D

    2017-01-30

    Mutations in the gene BEST1 are causally associated with as many as five clinically distinct retinal degenerative diseases, which are collectively referred to as the "bestrophinopathies". These five associated diseases are: Best vitelliform macular dystrophy, autosomal recessive bestrophinopathy, adult-onset vitelliform macular dystrophy, autosomal dominant vitreoretinochoroidopathy, and retinitis pigmentosa. The most common of these is Best vitelliform macular dystrophy. Bestrophin 1 (Best1), the protein encoded by the gene BEST1, has been the subject of a great deal of research since it was first identified nearly two decades ago. Today we know that Best1 functions as both a pentameric anion channel and a regulator of intracellular Ca(2+) signaling. Best1 is an integral membrane protein which, within the eye, is uniquely expressed in the retinal pigment epithelium where it predominantly localizes to the basolateral plasma membrane. Within the brain, Best1 expression has been documented in both glial cells and astrocytes where it functions in both tonic GABA release and glutamate transport. The crystal structure of Best1 has revealed critical information about how Best1 functions as an ion channel and how Ca(2+) regulates that function. Studies using animal models have led to critical insights into the physiological roles of Best1 and advances in stem cell technology have allowed for the development of patient-derived, "disease in a dish" models. In this article we review our knowledge of Best1 and discuss prospects for near-term clinical trials to test therapies for the bestrophinopathies, a currently incurable and untreatable set of diseases.

  19. Diverticulosis today: unfashionable and still under-researched

    PubMed Central

    Tursi, Antonio

    2016-01-01

    Diverticulosis of the colon is a widespread disease, and its prevalence is increasing especially in the developing world. The underlying pathological mechanisms that cause the formation of colonic diverticula remain unclear but are likely to be the result of complex interactions among age, diet, genetic factors, colonic motility, and changes in colonic structure. The large majority of patients remain asymptomatic throughout their life, one fifth of them become symptomatic (developing the so-called ‘diverticular disease’) while only a minority of these will develop acute diverticulitis. The factors predicting the development of symptoms remain to be identified. Again, it is generally recognized that diverticular disease occurrence is probably related to complex interactions among colonic motility, diet, lifestyle, and genetic features. Changes in intestinal microflora due to low-fiber diet and consequent low-grade inflammation are thought to be one of the mechanisms responsible for symptoms occurrence of both diverticular disease and acute diverticulitis. Current therapeutic approaches with rifaximin and mesalazine to treat the symptoms seem to be promising. Antibiotic treatment is currently advised only in acute complicated diverticulitis, and no treatment has currently proven effective in preventing the recurrence of acute diverticulitis. Further studies are required in order to clarify the reasons why diverticulosis occurs and the factors triggering occurrence of symptoms. Moreover, the reasons why rifaximin and mesalazine work in symptomatic diverticular disease but not in acute diverticulitis are yet to be elucidated. PMID:26929783

  20. Beating Breast Cancer but Still Paying a Price

    MedlinePlus

    ... are doing in terms of pain, sexual function, body image and emotional health," she said. The study involved 103 breast cancer survivors who were disease-free for at least three years. ... spread to other parts of the body at the start of the study. Women in ...