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Sample records for active chronic sarcoidosis

  1. Sarcoidosis

    MedlinePlus

    ... Favorite Name: Category: Share: Yes No, Keep Private Sarcoidosis Share | Sarcoidosis is characterized by granulomas (a mass of red, ... kidney), and endocrine systems. Signs and symptoms of sarcoidosis are variable because of its ability to affect ...

  2. Sarcoidosis

    MedlinePlus

    ... page from the NHLBI on Twitter. What Is Sarcoidosis? Español Sarcoidosis (sar-koy-DO-sis) is a ... Content: NEXT >> Featured Video Living With and Managing Sarcoidosis 05/18/2011 This video—presented by the ...

  3. Sarcoidosis and chronic hepatitis C: treatment with prednisone and colchicine*

    PubMed Central

    Pereira, Eduardo Guimarães; Guimarães, Tais Ferreira; Bottino, Caroline Bertolini; D’Acri, Antonio Macedo; Lima, Ricardo Barbosa; Martins, Carlos José

    2016-01-01

    Sarcoidosis is a disease which still has uncertain etiology. Possible environmental causes are cited in the literature, like organic and inorganic particles and infectious agents. Recent studies have demonstrated the occurrence of sarcoidosis in patients with chronic C hepatitis; however, this association remains without statistical or causal evidence. In this report a case of sarcoidosis associated with chronic hepatitis C will be described, with subcutaneous lesions, considered rare, and good response to treatment with colchicine and prednisone. The hepatitis C virus was isolated in sarcoid tissue and the association between the two diseases will be discussed. PMID:27192527

  4. Sarcoidosis and chronic hepatitis C: treatment with prednisone and colchicine.

    PubMed

    Pereira, Eduardo Guimarães; Guimarães, Tais Ferreira; Bottino, Caroline Bertolini; D'Acri, Antonio Macedo; Lima, Ricardo Barbosa; Martins, Carlos José

    2016-04-01

    Sarcoidosis is a disease which still has uncertain etiology. Possible environmental causes are cited in the literature, like organic and inorganic particles and infectious agents. Recent studies have demonstrated the occurrence of sarcoidosis in patients with chronic C hepatitis; however, this association remains without statistical or causal evidence. In this report a case of sarcoidosis associated with chronic hepatitis C will be described, with subcutaneous lesions, considered rare, and good response to treatment with colchicine and prednisone. The hepatitis C virus was isolated in sarcoid tissue and the association between the two diseases will be discussed. PMID:27192527

  5. Sarcoidosis

    MedlinePlus

    Sarcoidosis is a disease that leads to inflammation, usually in your lungs, skin, or lymph nodes. It starts as tiny, grain-like lumps, called granulomas. Sarcoidosis can affect any organ in your body. No ...

  6. Sarcoidosis and chronic beryllium disease: similarities and differences.

    PubMed

    Mayer, Annyce S; Hamzeh, Nabeel; Maier, Lisa A

    2014-06-01

    Chronic beryllium disease (CBD) is a granulomatous lung disease that may be pathologically and clinically indistinguishable from pulmonary sarcoidosis, except through use of immunologic testing, such as the beryllium lymphocyte proliferation test (BeLPT). Similar to sarcoidosis, the pulmonary manifestations of CBD are variable and overlap with other respiratory diseases. Definitive diagnosis of CBD is established by evidence of immune sensitization to beryllium and diagnostic bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. However, the diagnosis of CBD can also be established on a medically probable basis in beryllium-exposed patients with consistent radiographic imaging and clinical course. Beryllium workers exposed too much higher levels of beryllium in the past demonstrated a much more fulminant disease than is usually seen today. Some extrapulmonary manifestations similar to sarcoidosis were noted in these historic cohorts, although with a narrower spectrum. Extrapulmonary manifestations of CBD are rare today. Since lung-predominant sarcoidosis can very closely resemble CBD, CBD is still misdiagnosed as sarcoidosis when current or past exposure to beryllium is not recognized and no BeLPT is obtained. This article describes the similarities and differences between CBD and sarcoidosis, including clinical and diagnostic features that can help physicians consider CBD in patients with apparent lung-predominant sarcoidosis. PMID:25007084

  7. Sarcoidosis

    MedlinePlus

    Sarcoidosis is a disease in which inflammation occurs in the lymph nodes, lungs, liver, eyes, skin, or ... The exact cause of sarcoidosis is unknown. What is known is that when a person has the disease, tiny clumps of abnormal tissue (granulomas) form ...

  8. Sarcoidosis

    MedlinePlus

    ... the elbow Sarcoidosis on the nose and forehead Respiratory system References Judson MA, Morgenthau AS, Baughman RP. Sarcoidosis. In: Broaddus VC, Mason RJ, Ernst JD, et al, eds. Murray and Nadel's Textbook of Respiratory Medicine . 6th ed. Philadelphia, PA: Elsevier Saunders; 2016: ...

  9. Tracheo-oesophageal fistula in a patient with chronic sarcoidosis.

    PubMed

    Darr, A; Mohamed, S; Eaton, D; Kalkat, M S

    2015-10-01

    Sarcoidosis is a common multisystem granulomatous condition of unknown aetiology, predominantly involving the respiratory system. Tracheal stenosis has been described but we believe that we present the first case of a tracheo-oesophageal fistula secondary to chronic sarcoidosis. A 57-year-old woman with sarcoidosis, a known tracheal stricture and a Polyflex(®) stent in situ presented with stridor. Bronchoscopy confirmed in-stent stenosis, by exuberant granulation tissue. The stent was removed and the granulation tissue was resected accordingly. Postoperatively, the patient was noticed to have an incessant cough and video fluoroscopy raised the suspicion of a tracheo-oesophageal fistula. A repeat bronchoscopy demonstrated marked granulation tissue, accompanied by a fistulous connection with the oesophagus at the mid-lower [middle of the lower] third of the trachea. Three Polyflex(®) stents were sited across the entire length of the trachea. Sarcoidosis presents with varying clinical manifestations and disease progression. Tracheal involvement appears to be a rare phenomenon and usually results in stenosis. To date, there has been little or no documented literature describing the formation of a tracheo-oesophageal fistula resulting from sarcoidosis. Early reports documented the presence of sarcoidosis induced weakening in the tracheal wall, a process termed tracheal dystonia. Weaknesses are more apparent in the membranous aspect of the trachea. Despite the rare nature of such pathology, this case report highlights the need to consider the presence of a tracheo-oesophageal fistula in sarcoidosis patients presenting with repeat aspiration in the absence of an alternate pathology. PMID:26274763

  10. [Sarcoidosis].

    PubMed

    Frye, B C; Schupp, J C; Köhler, T C; Voll, R E; Müller-Quernheim, J

    2016-05-01

    Sarcoidosis is a rare granulomatous disease mainly affecting lymph nodes and the lungs but joints, bones, muscles and other organs can also be affected. Sarcoidosis therefore represents an important differential diagnosis to various rheumatic diseases. For the diagnosis and differential diagnostic clarification, bronchoscopy including endobronchial ultrasound-guided fine needle aspiration of mediastinal and hilar lymph nodes represent the main procedures. Because of the high spontaneous remission rate initiating a therapy requires a therapeutic goal defined by sarcoidosis-associated functional organ impairment, especially for acute sarcoidosis. Cortisone represents the most commonly administered medication whereas methotrexate and azathioprine are well-established second-line medications. Antibodies which neutralize tumor necrosis factors (TNF) are a potential third-line therapy. PMID:27146405

  11. Sarcoidosis.

    PubMed

    Martires, Kathryn; Shvartsbeyn, Marianna; Brinster, Nooshin; Ramachandran, Sarika; Franks, Andrew G

    2015-01-01

    We present a 28-year-old man with a one-year history of cutaneous lesions in old scars and tattoos with concomitant subcutaneous nodules and myopathy. A skin biopsy specimen showed cutaneous sarcoidosis. We discuss the multiple aspects of this case, which represent unique presentations of this systemic disease as well as review isomorphic and isotopic responses. PMID:26990326

  12. Pulmonary granulomatous reaction: talc pneumoconiosis or chronic sarcoidosis?

    PubMed Central

    Tukiainen, P; Nickels, J; Taskinen, E; Nyberg, M

    1984-01-01

    A chronic pulmonary granulomatous reaction was associated with an almost identical clinical picture in two patients exposed to talc. In both patients lung biopsy showed the deposition of talc particles and a heavy granulomatous reaction. At the time of diagnosis the Kveim test result was negative in both patients, urinary calcium excretion was normal, and there were no extrapulmonary manifestations and no response to steroid treatment. These findings point against sarcoidosis. The serum angiotensin-converting enzyme level, however, was raised in both patients. It was concluded that the patient who was exposed to talc in the rubber industry had a true talc pneumoconiosis. The other patient, who was exposed to cosmetic talcum powder, suffered from chronic sarcoidosis with talc deposition in the lungs, since an enlarged axillar lymph node containing granulomatous inflammation was discovered after two years' follow up. These cases show that it may be extremely difficult to differentiate between chronic sarcoidosis and talc pneumoconiosis even after careful clinical and histological analysis. Images PMID:6691939

  13. Reliability and Convergent Validity of the Cutaneous Sarcoidosis Activity and Morphology Instrument for Assessing Cutaneous Sarcoidosis

    PubMed Central

    Chu, Emily Y.; Kim, Ellen J.; Payne, Aimee S.; Takeshita, Junko; Vittorio, Carmela C.; Wanat, Karolyn A.; Werth, Victoria P.; Gelfand, Joel M.

    2013-01-01

    Objective To assess the reliability and convergent validity of two outcome instruments for assessing cutaneous sarcoidosis: Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) and Sarcoidosis Activity and Severity Index (SASI). Design Cross-sectional study evaluating cutaneous sarcoidosis disease severity using CSAMI, SASI, and Physician's Global Assessment (PGA) as reference. Setting Cutaneous sarcoidosis clinic. Participants 8 dermatologists evaluated 11 patients with cutaneous sarcoidosis. Main Outcome Measures Primary outcomes: Inter- and intra-rater reliability and convergent validity. Secondary outcomes: Correlation with quality of life measures and time required for completion. Results All instruments demonstrated good to excellent intra-rater reliability. Inter-rater reliability was excellent for CSAMI Activity scores (intraclass correlation coefficient [ICC], 0.82; 95% CI, 0.66-0.94), and fair to poor for CSAMI Damage (0.42; 0.21-0.72), modified Facial SASI (0.40; 0.17-0.72), and PGA scores (0.40; 0.18-0.70). CSAMI Activity, Damage, and modified Facial SASI scores all demonstrated convergent validity with statistically significant correlations with PGA scores. Trends for correlations were seen between CSAMI scores and specific Skindex-29 quality of life domains. While CSAMI required longer time to complete than SASI, both were scored within adequate time for use in clinical trials. Conclusions CSAMI appears to be a reliable and valid outcome instrument to measure cutaneous sarcoidosis and may capture a wide range of body surface and cutaneous morphologies. Future research is necessary to demonstrate its sensitivity to change and to confirm its correlation with quality of life measures. PMID:23677081

  14. Etiologies of Sarcoidosis.

    PubMed

    Chen, Edward S; Moller, David R

    2015-08-01

    Since sarcoidosis was first described more than a century ago, the etiologic determinants causing this disease remain uncertain. Studies suggest that genetic, host immunologic, and environmental factors interact together to cause sarcoidosis. Immunologic characteristics of sarcoidosis include non-caseating granulomas, enhanced local expression of T helper-1 (and often Th17) cytokines and chemokines, dysfunctional regulatory T-cell responses, dysregulated Toll-like receptor signaling, and oligoclonal expansion of CD4+ T cells consistent with chronic antigenic stimulation. Multiple environmental agents have been suggested to cause sarcoidosis. Studies from several groups implicate mycobacterial or propionibacterial organisms in the etiology of sarcoidosis based on tissue analyses and immunologic responses in sarcoidosis patients. Despite these studies, there is no consensus on the nature of a microbial pathogenesis of sarcoidosis. Some groups postulate sarcoidosis is caused by an active viable replicating infection while other groups contend there is no clinical, pathologic, or microbiologic evidence for such a pathogenic mechanism. The authors posit a novel hypothesis that proposes that sarcoidosis is triggered by a hyperimmune Th1 response to pathogenic microbial and tissue antigens associated with the aberrant aggregation of serum amyloid A within granulomas, which promotes progressive chronic granulomatous inflammation in the absence of ongoing infection. PMID:25771769

  15. Gallium-67 activity in bronchoalveolar lavage fluid in sarcoidosis

    SciTech Connect

    Trauth, H.A.; Heimes, K.; Schubotz, R.; von Wichert, P.

    1986-01-01

    Roentgenograms and gallium-67 scans and gallium-67 counts of BAL fluid samples, together with differential cell counts, have proved to be useful in assessing activity and lung involvement in sarcoidosis. In active pulmonary sarcoidosis gallium-67 scans are usually positive. Quantitation of gallium-67 uptake in lung scans, however, may be difficult. Because gallium-67 uptake and cell counts in BAL fluid may be correlated, we set out to investigate gallium-67 activity in BAL fluid recovered from patient of different groups. Sixteen patients with recently diagnosed and untreated sarcoidosis, nine patients with healthy lungs, and five patients with CFA were studied. Gallium-67 uptake of the lung, gallium-67 activity in the lavage fluid, SACE and LACE levels, and alpha 1-AT activity were measured. Significantly more gallium-67 activity was found in BAL fluid from sarcoidosis patients than in that from CFA patients (alpha = .001) or patients with healthy lungs (alpha = .001). Gallium-67 activity in BAL fluid could be well correlated with the number of lymphocytes in BAL fluid, but poorly with the number of macrophages. Subjects with increased levels of SACE or serum alpha 1-AT showed higher lavage gallium-67 activity than did normals, but no correlation could be established. High gallium-67 activity in lavage fluid may be correlated with acute sarcoidosis or physiological deterioration; low activity denotes change for the better. The results show that gallium-67 counts in BAL fluid reflects the intensity of gallium-67 uptake and thus of activity of pulmonary sarcoidosis.

  16. Elevated MicroRNA-33 in Sarcoidosis and a Carbon Nanotube Model of Chronic Granulomatous Disease.

    PubMed

    Barna, Barbara P; McPeek, Matthew; Malur, Anagha; Fessler, Michael B; Wingard, Christopher J; Dobbs, Larry; Verbanac, Kathryn M; Bowling, Mark; Judson, Marc A; Thomassen, Mary Jane

    2016-06-01

    We established a murine model of multiwall carbon nanotube (MWCNT)-induced chronic granulomatous disease, which resembles human sarcoidosis pathology. At 60 days after oropharyngeal MWCNT instillation, bronchoalveolar lavage (BAL) cells from wild-type mice exhibit an M1 phenotype with elevated proinflammatory cytokines and reduced peroxisome proliferator-activated receptor γ (PPARγ)-characteristics also present in human sarcoidosis. Based upon MWCNT-associated PPARγ deficiency, we hypothesized that the PPARγ target gene, ATP-binding cassette (ABC) G1, a lipid transporter with antiinflammatory properties, might also be repressed. Results after MWCNT instillation indicated significantly repressed ABCG1, but, surprisingly, lipid transporter ABCA1 was also repressed, suggesting a possible second pathway. Exploration of potential regulators revealed that microRNA (miR)-33, a lipid transporter regulator, was strikingly elevated (13.9 fold) in BAL cells from MWCNT-instilled mice but not sham control mice. Elevated miR-33 was also detected in murine granulomatous lung tissue. In vitro studies confirmed that lentivirus-miR-33 overexpression repressed both ABCA1 and ABCG1 (but not PPARγ) in cultured murine alveolar macrophages. BAL cells of patients with sarcoidosis also displayed elevated miR-33 together with reduced ABCA1 and ABCG1 messenger RNA and protein compared with healthy control subjects. Moreover, miR-33 was elevated within sarcoidosis granulomatous tissue. The findings suggest that alveolar macrophage miR-33 is up-regulated by proinflammatory cytokines and may perpetuate chronic inflammatory granulomatous disease by repressing antiinflammatory functions of ABCA1 and ABCG1 lipid transporters. The results also suggest two possible pathways for transporter dysregulation in granulomatous disease-one associated with intrinsic PPARγ status and the other with miR-33 up-regulation triggered by environmental challenges, such as MWCNT. PMID:26641802

  17. Association of inflammatory bowel disease risk loci with sarcoidosis, and its acute and chronic subphenotypes.

    PubMed

    Fischer, A; Nothnagel, M; Franke, A; Jacobs, G; Saadati, H R; Gaede, K I; Rosenstiel, P; Schürmann, M; Müller-Quernheim, J; Schreiber, S; Hofmann, S

    2011-03-01

    Sarcoidosis is a complex granulomatous inflammatory disorder that shares several clinical and pathogenic features with inflammatory bowel disease (IBD). Postulating a common genetic basis of inflammatory diseases, we tested 106 single-nucleotide polymorphisms (SNPs) that are known or have been suggested to be associated with IBD for a potential association with sarcoidosis and its acute and chronic subphenotypes. We genotyped 1,996 German sarcoidosis patients, comprising 648 acutely and 1,161 chronically affected individuals, 2,622 control subjects, and 342 German trios with affected offspring using SNPlex™ technology. The nonsynonymous SNP rs11209026 (Arg381Gln) in the interleukin (IL)-23 receptor (IL23R) gene was associated with chronic sarcoidosis (OR 0.63; p = 5.58×10(-5)), which was supported by the result of a transmission disequilibrium test analysis in the independent family sample (OR 0.50; p = 0.031). Marker rs12035082 located at chromosome 1q24.3 was found to be associated with the acute subphenotype (OR 1.36; p = 6.80×10(-7)) and rs916977 (HERC2 locus; OR 1.30; p = 4.49×10(-5)) was associated with sarcoidosis. Our results highlight the potential importance of the IL-23 signalling pathway for the development of chronic sarcoidosis. The finding links sarcoidosis pathogenesis to other inflammatory conditions and may contribute to new hypotheses on disease mechanisms. PMID:20650992

  18. Atherosclerotic Vessel Changes in Sarcoidosis.

    PubMed

    Tuleta, I; Pingel, S; Biener, L; Pizarro, C; Hammerstingl, C; Öztürk, C; Schahab, N; Grohé, C; Nickenig, G; Schaefer, C; Skowasch, D

    2016-01-01

    Sarcoidosis is a systemic granulomatous disease. Atherosclerosis is a chronic inflammatory vessel disease. The aim of our present study was to investigate whether sarcoidosis could be associated with increased risk of atherosclerotic vessel changes. Angiological analysis and blood tests were performed in 71 sarcoidosis patients and 12 matched controls in this prospective cross-sectional study. Specifically, angiological measurements comprised ankle brachial index (ABI), central pulse wave velocity (cPWV), pulse wave index (PWI), and duplex sonography of central and peripheral arteries. Sarcoidosis activity markers (angiotensin converting enzyme, soluble interleukin-2 receptor) and cardiovascular risk parameters such as cholesterol, lipoprotein(a), C-reactive protein, interleukin 6, fibrinogen, d-dimer, and blood count were analyzed in blood. We found no relevant differences in ABI, cPWV, and plaque burden between the sarcoidosis and control groups (1.10 ± 0.02 vs. 1.10 ± 0.02, 6.7 ± 0.5 vs. 6.1 ± 1.2, 53.7 % vs. 54.5 %, respectively). However, PWI was significantly higher in sarcoidosis patients (146.2 ± 6.8) compared with controls (104.9 ± 8.8), irrespectively of the activity of sarcoidosis and immunosuppressive medication. Except for increased lipoprotein(a) and d-dimer in sarcoidosis, the remaining cardiovascular markers were similar in both groups. We conclude that sarcoidosis is associated with increased pulse wave index, which may indicate an early stage of atherosclerosis. PMID:26820732

  19. Search for chronic beryllium disease among sarcoidosis patients in Ontario, Canada.

    PubMed

    Ribeiro, Marcos; Fritscher, Leandro G; Al-Musaed, Ahmed M; Balter, Meyer S; Hoffstein, Victor; Mazer, Bruce D; Maier, Lisa A; Liss, Gary M; Tarlo, Susan M

    2011-06-01

    Chronic beryllium disease (CBD) is clinically similar to other granulomatous diseases such as sarcoidosis. It is often misdiagnosed if a thorough occupational history is not taken. When appropriate, a beryllium lymphocyte proliferation tests (BeLPT) need to be performed. We aimed to search for CBD among currently diagnosed pulmonary sarcoidosis patients and to identify the occupations and exposures in Ontario leading to CBD. Questionnaire items included work history and details of possible exposure to beryllium. Participants who provided a history of previous work with metals underwent BeLPTs and an ELISPOT on the basis of having a higher pretest probability of CBD. Among 121 sarcoid patients enrolled, 87 (72%) reported no known previous metal dust or fume exposure, while 34 (28%) had metal exposure, including 17 (14%) with beryllium exposure at work or home. However, none of these 34 who underwent testing had positive test results. Self-reported exposure to beryllium or metals was relatively common in these patients with clinical sarcoidosis, but CBD was not confirmed using blood assays in this population. PMID:21400234

  20. Venous thromboembolism and sarcoidosis: co-incidence or coexistence?

    PubMed Central

    Geremek, Marcin; Puscinska, Elzbieta; Sliwinski, Pawel

    2016-01-01

    The association between venous thromboembolism (VTE) and sarcoidosis has been reported recently, nevertheless the true incidence of co-incident sarcoidosis and VTE is unknown. Sarcoidosis as a chronic disease of immune dysregulation might be associated with an increased risk of VTE. The mechanisms responsible for VTE development are not clear and may be influenced by several factors: activity of inflammation, clinical characteristics of sarcoidosis and comorbidities. Pulmonary embolism (PE) as a potentially fatal condition should be considered in all of the patients with sarcoidosis in whom worsening of the respiratory status is diagnosed. A high plasma D-dimers (DD) level may be suggestive of VTE, nevertheless elevated plasma DD should be interpreted with caution, in the context of the active inflammatory process. If sarcoidosis appears to be one of risk factors for VTE development, further investigations are needed to define the pro-thrombotic phenotype of this disease. PMID:26862313

  1. [Life quality in patients with sarcoidosis and isolated skin syndrome in chronic dermatoses].

    PubMed

    Guryleva, M E

    2003-01-01

    Seventeen patients, including 3 (17.6%) males and 14 (82.4%) females, who had respiratory sarcoidosis with the skin syndrome as erythema nodosum, were examined; their mean age was 41.65 +/- 2.63 years. The histological verification of the diagnosis was 94%. Among 77 patients with chronic dermatoses with the isolated skin syndrome (psoriasis, acne vulgaris, atopic dermatitis, neurodermitis, lichen ruber planus, seborrheal pemphigns, eczema), there were 33 (42.9%) males and 44 (57.1%) females, whose mean age was 36.64 +/- 1.3 years. Comparative analysis of life quality (LQ) in these two groups by using the WHOQOL-100 questionnaire revealed differences in two indices that reflect the level of independence and social relations (p < or = 0.05). In terms of independence, the impact of the disease on LQ was more pronounced in patients with sarcoidosis, its negative effect being in 75% of the criteria rated. Thus, poorer LQ may be stated in patients with skin lesion than in those with the isolated skin syndrome in chronic dermatoses. PMID:14524097

  2. [Asymptomatic chronic intrahepatic cholestasis and multiple hypodense nodules in the liver and the spleen: manifestations of a case of sarcoidosis].

    PubMed

    Guilarte López-Mañas, J; Bellot García, V; Gallego Rojo, F J; Casado Caballero, F J; Ardoy Ibáñez, F M; Ortego Centeno, N; Caballero Plasencia, A M

    1996-01-01

    Sarcoidosis is a systemic granulomatous disease of unknown etiology which may present multiple clinical manifestations. Liver involvement is observed among 21-79% of the cases. Nonetheless, hepatic sarcoidosis is usually asymptomatic and the finding of cholestasis is an infrequent complication. In the last few years, the presence of multiple hypodense nodules in the liver and spleen has been described in 5-15% of these patients following the application of dynamic intravenous techniques in abdominal CT scan. Although the histopathologic study of these nodules suggests that their formation is due to the coalescence of the microscopic granulomas, the cause of this aggregation remains unknown. A case of hepatic sarcoidosis presenting chronic cholestasis and whose abdominal tomographic study with intravenous contrast demonstrated the existence of hypodense lesions in the liver and spleen suggesting malignant disseminated disease is reported. PMID:8963906

  3. Cutaneous Sarcoidosis: An Uncommon Side Effect of Pegylated Interferon and Ribavirin Use for Chronic Hepatitis C

    PubMed Central

    Martins, Elson Vidal; Gaburri, Ana Karla; Gaburri, Debora; Sementilli, Angelo

    2009-01-01

    The treatment of chronic hepatitis C (CHC) has evolved in the past 15 years and combination of pegylated interferon plus ribavirin is its current standard therapy. However, several side effects are commonly observed and frequently lead to transient or definitive interruption of treatment. Although sarcoidosis in its systemic or cutaneous form is a very rare side effect in such circumstances, some cases have been reported even with conventional interferon. This brief review of the literature and description of a case of sarcoidosis occurring in a tattoo and a scar patient's face, during treatment with pegylated interferon alpha-2b plus ribavirin, is an educative report directed in special to dermatologists. The lesion improved after drug interruption and recurred after retreatment with pegylated interferon alpha-2a. We conclude that this side effect must call the attention of doctors to seek for the diagnosis and therapy as soon as possible in such circumstances. No differences were noticed neither with alpha-2a nor alpha-2b pegylated interferon employment. PMID:21103255

  4. Sarcoidosis Quiz

    MedlinePlus

    ... Share this page from the NHLBI on Twitter. Sarcoidosis Quiz Sarcoidosis is a disease of unknown cause that leads ... various organs in the body. The outcome of sarcoidosis varies. The disease leads to organ damage in ...

  5. Activated alveolar macrophage and lymphocyte alveolitis in extrathoracic sarcoidosis without radiological mediastinopulmonary involvement

    SciTech Connect

    Wallaert, B.; Ramon, P.; Fournier, E.C.; Prin, L.; Tonnel, A.B.; Voisin, C.

    1986-01-01

    Cellular characteristics of BAL were investigated in 18 patients with proved extrathoracic sarcoidosis (that is, sarcoidosis that affected the skin, eyes, parotid glands, stomach, nose, kidneys, or meninges) without clinical or radiological mediastinopulmonary involvement. Computed tomography of the thorax was performed on five patients: four patients were normal, and one had enlarged lymph nodes (these enlargements were not detectable on the patient's chest roentgenogram). The results of pulmonary function tests were normal in all patients. The total BAL cell count did not differ significantly between controls and patients. Abnormal percentages of alveolar lymphocytes (from 18 to 87%) were noted in 15 out of 18 patients. SACE levels were normal in 15 patients. No pulmonary gallium uptake was detected. The chemiluminescence of AM's, whether spontaneous or PMA induced, was increased in five out of seven patients. The percentages of T3+ lymphocytes in sarcoidosis patients did not significantly differ from those in controls. The T4+:T8+ ratio was normal in four patients and slightly increased in one. Follow-up of patients showed that alveolar lymphocytosis is as lasting as extrathoracic involvement. Our data demonstrate increased percentages of lymphocytes and activated AM's in the BAL of patients with extrathoracic sarcoidosis. This may be due to the initial involvement of the respiratory tract in extrathoracic sarcoidosis or to the diffusion of activated macrophages and lymphocytes from an extrathoracic site into the lung.

  6. Possible role of L-selectin in T lymphocyte alveolitis in patients with active pulmonary sarcoidosis.

    PubMed

    Kaseda, M; Kadota, J; Mukae, H; Kawamoto, S; Shukuwa, T; Iwashita, T; Matsubara, Y; Ishimatsu, Y; Yoshinaga, M; Abe, K; Kohno, S

    2000-07-01

    A number of adhesion molecules participate in the recruitment of inflammatory cells to the site of inflammation, and selectins together with their ligands are important in the early transient adhesion phase. In this study, we evaluated the role of L-selectin in T lymphocyte alveolitis in patients with active pulmonary sarcoidosis. We measured serum and bronchoalveolar lavage fluid (BALF) concentrations of soluble (s)L-selectin using an ELISA. Serum and BALF concentrations of sL-selectin were significantly elevated in patients with sarcoidosis compared with control healthy subjects and idiopathic pulmonary fibrosis (IPF) patients (P < 0.05 and P < 0. 01, respectively). The lymphocyte surface marker was also examined in peripheral blood and BALF by flow cytometric analysis. The percentage of CD3+CD62L+ cells (L-selectin-bearing T lymphocytes) was significantly lower in peripheral blood of sarcoidosis than in that of healthy subjects (P < 0.01). In contrast, the percentage of CD3+CD62L- cells (L-selectin-negative T lymphocytes) in BALF of patients with sarcoidosis was significantly higher than in healthy subjects (P < 0.05) and IPF patients (P < 0.01). Furthermore, there was a significant correlation between serum concentrations of sL-selectin and the number of L-selectin-negative T lymphocytes in BALF (r = 0.535, P < 0.01). Our results suggest that L-selectin may be involved in T lymphocyte alveolitis in patients with active pulmonary sarcoidosis. PMID:10886252

  7. Possible role of l-selectin in T lymphocyte alveolitis in patients with active pulmonary sarcoidosis

    PubMed Central

    Kaseda, M; Kadota, J; Mukae, H; Kawamoto, S; Shukuwa, T; Iwashita, T; Matsubara, Y; Ishimatsu, Y; Yoshinaga, M; Abe, K; Kohno, S

    2000-01-01

    A number of adhesion molecules participate in the recruitment of inflammatory cells to the site of inflammation, and selectins together with their ligands are important in the early transient adhesion phase. In this study, we evaluated the role of l-selectin in T lymphocyte alveolitis in patients with active pulmonary sarcoidosis. We measured serum and bronchoalveolar lavage fluid (BALF) concentrations of soluble (s)l-selectin using an ELISA. Serum and BALF concentrations of sl-selectin were significantly elevated in patients with sarcoidosis compared with control healthy subjects and idiopathic pulmonary fibrosis (IPF) patients (P < 0·05 and P < 0·01, respectively). The lymphocyte surface marker was also examined in peripheral blood and BALF by flow cytometric analysis. The percentage of CD3+CD62L+ cells (l-selectin-bearing T lymphocytes) was significantly lower in peripheral blood of sarcoidosis than in that of healthy subjects (P < 0·01). In contrast, the percentage of CD3+CD62L− cells (l-selectin-negative T lymphocytes) in BALF of patients with sarcoidosis was significantly higher than in healthy subjects (P < 0·05) and IPF patients (P < 0·01). Furthermore, there was a significant correlation between serum concentrations of sl-selectin and the number of l-selectin-negative T lymphocytes in BALF (r = 0·535, P < 0·01). Our results suggest that l-selectin may be involved in T lymphocyte alveolitis in patients with active pulmonary sarcoidosis. PMID:10886252

  8. Diagnosis of sarcoidosis

    SciTech Connect

    Sharma, O.P.

    1983-07-01

    During the last decade, many biochemical and immunologic advances have been made in the treatment and understanding of sarcoidosis. These studies have helped us to understand the basic mechanisms involved in granuloma formation, and many clinicians have used the information to diagnose and assess the activity of sarcoidosis. Further studies are needed to clearly establish the role of these advances in the everyday management of patients with sarcoidosis.

  9. Radioaerosol lung clearance in patients with active pulmonary sarcoidosis

    SciTech Connect

    Jacobs, M.P.; Baughman, R.P.; Hughes, J.; Fernandez-Ulloa, M.

    1985-05-01

    Pulmonary radioaerosol clearance rate of /sup 99m/Tc diethylenetriamine pentacetate (DTPA) in 14 patients with untreated sarcoidosis was compared with /sup 67/Ga lung scan and increased lymphocytes in the bronchoalveolar lavage (BAL) fluid. Nine healthy nonsmoking subjects had a mean DTPA clearance rate of 1.18%/min (range, 0.54 to 1.60%/min). Eight of 14 patients with sarcoidosis had clearance rates greater than 1.60%/min. Of those 8 patients with abnormal DTPA clearance, 4 had positive gallium scans, 4 had more than 17% lymphocytes in the BAL fluid, and 3 had both tests positive. To study the cause of abnormal DTPA clearance, 23 subjects (including 3 normal controls, all 14 patients with sarcoidosis, and 6 patients with localized disease on chest roentgenogram) underwent both DTPA clearance studies and BAL for quantitation of the amount of albumin in lung fluid. There was a positive correlation between the rate of DTPA clearance and the albumin concentration in lung fluid (r = 0.87, p less than 0.01).

  10. Pathogenesis of Sarcoidosis

    PubMed Central

    Gundy, Karl Van; Sharma, Om P.

    1987-01-01

    Sarcoidosis is a multisystem granulomatous disease of unknown etiology. The organs that are involved by sarcoidosis include the lungs in which the granuloma is seen in more than 90% of patients to the pituitary, which is only rarely affected. There are many hypotheses as to the cause of sarcoidosis. Some of them rely on the similarities seen between sarcoidosis and the other granuloma-forming diseases such as tuberculosis, berylliosis, pine pollen inhalation and acute and chronic bacterial and viral infections, while others find similarities between sarcoidosis and immune reactions observed in autoimmune disorders. Still other explanations implicate a genetic predisposition or a still-unknown agent as the underlying cause of the granuloma formation. Images PMID:3310401

  11. Extensive upper respiratory tract sarcoidosis.

    PubMed

    Soares, Mafalda Trindade; Sousa, Carolina; Garanito, Luísa; Freire, Filipe

    2016-01-01

    Sarcoidosis is a chronic granulomatous disease of unknown aetiology. It can affect any part of the organism, although the lung is the most frequently affected organ. Upper airway involvement is rare, particularly if isolated. Sarcoidosis is a diagnosis of exclusion, established by histological evidence of non-caseating granulomas and the absence of other granulomatous diseases. The authors report a case of a man with sarcoidosis manifesting as a chronic inflammatory stenotic condition of the upper respiratory tract and trachea. PMID:27090537

  12. Recent advances in sarcoidosis.

    PubMed

    Morgenthau, Adam S; Iannuzzi, Michael C

    2011-01-01

    Sarcoidosis, a systemic granulomatous disease of undetermined etiology, is characterized by a variable clinical presentation and course. During the past decade, advances have been made in the study of sarcoidosis. The multicenter ACCESS (A Case Control Etiologic Study of Sarcoidosis) trial recruited > 700 subjects with newly diagnosed sarcoidosis and matched control subjects. Investigators were unable to identify a single cause of sarcoidosis, but ACCESS paved the way for subsequent etiologic studies. The Mycobacterium tuberculosis catalase-peroxidase protein has been identified as a potential sarcoidosis antigen. Genetic aspects of the disease have been elucidated further. Genome-wide scans have identified candidate genes. Gene expression analyses have defined cytokine dysregulation in sarcoidosis more clearly. Although the criteria for diagnosis have not changed, sarcoidosis remains a diagnosis of exclusion best supported by a tissue biopsy specimen that demonstrates noncaseating granulomas in a patient with compatible clinical and radiologic features of the disease. Endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal lymph nodes has facilitated diagnosis, often eliminating the need for more invasive procedures, such as mediastinoscopy. PET scanning has proven valuable in locating occult sites of active disease. Currently, no reliable prognostic biomarkers have been identified. The tumor necrosis factor inhibitors, a relatively new class of agents, have been used in patients with refractory disease. It is unclear whether phosphodiesterase-5 inhibitors, prostaglandin analogs, or endothelin antagonists should be used for the treatment of sarcoidosis-associated pulmonary hypertension. PMID:21208877

  13. [Cutaneous manifestations of sarcoidosis].

    PubMed

    Descamps, V; Bouscarat, F

    2016-01-01

    Sarcoidosis is a systemic granulomatous disorder of unknown aetiology. Its dermatological manifestations are extremely polymorphous. They are normally classed as either specific lesions, comprising granulomas, which are generally chronic, or non-specific lesions, principally acute erythema nodosum. These signs are seen in around 25% of sarcoidosis patients. The disease may be heralded by a skin disorder. Diagnosis of cutaneous sarcoidosis provides the clinician with three problems: screening for a visceral site of the disease, determination of the prognosis, and long-term management with regular monitoring coupled with suitable therapy in the event of cosmetic or functional impairment. PMID:26804434

  14. Cardiac Sarcoidosis

    MedlinePlus

    ... is Cardiac Sarcoidosis? Sarcoidosis is a poorly understood disease that commonly affects the lungs. It can also involve the lymph nodes, liver, spleen, eyes, skin, bones, salivary glands and heart. ...

  15. Musculoskeletal involvement in sarcoidosis*, **

    PubMed Central

    Nessrine, Akasbi; Zahra, Abourazzak Fatima; Taoufik, Harzy

    2014-01-01

    Sarcoidosis is a multisystem inflammatory disorder of unknown cause. It most commonly affects the pulmonary system but can also affect the musculoskeletal system, albeit less frequently. In patients with sarcoidosis, rheumatic involvement is polymorphic. It can be the presenting symptom of the disease or can appear during its progression. Articular involvement is dominated by nonspecific arthralgia, polyarthritis, and Löfgren's syndrome, which is defined as the presence of lung adenopathy, arthralgia (or arthritis), and erythema nodosum. Skeletal manifestations, especially dactylitis, appear mainly as complications of chronic, multiorgan sarcoidosis. Muscle involvement in sarcoidosis is rare and usually asymptomatic. The diagnosis of rheumatic sarcoidosis is based on X-ray findings and magnetic resonance imaging findings, although the definitive diagnosis is made by anatomopathological study of biopsy samples. Musculoskeletal involvement in sarcoidosis is generally relieved with nonsteroidal anti-inflammatory drugs or corticosteroids. In corticosteroid-resistant or -dependent forms of the disease, immunosuppressive therapy, such as treatment with methotrexate or anti-TNF-α, is employed. The aim of this review was to present an overview of the various types of osteoarticular and muscle involvement in sarcoidosis, focusing on their diagnosis and management. PMID:24831403

  16. Psoriasiform Sarcoidosis

    PubMed Central

    Vega, Miriam L.; Abrahams, Jennifer

    2016-01-01

    Background: Psoriasiform lesions are an established, but rare, manifestation of sarcoidosis. Only 0.9 percent of patients with cutaneous sarcoidosis develop this form of the disease. Observation: The authors present a case of a 61-year-old woman with a history of pulmonary sarcoidosis who presented to their dermatology clinic with thick plaques resembling psoriasis. Biopsy of one of the lesions revealed sarcoidal granulomas in association with psoriasiform changes. Conclusion: Psoriasiform lesions are a rare manifestation of sarcoidosis. The authors theorize that the co-expression of TNF-α in both entities is a possible explanation of the psoriasiform expression of sarcoidosis. PMID:27462388

  17. Platelet-activating factor in bronchoalveolar lavage from patients with sarcoidosis.

    PubMed

    Scappaticci, E; Libertucci, D; Bottomicca, F; Da Col, R; Silvestro, L; Tetta, C; Camussi, G

    1992-08-01

    Platelet-activating factor (PAF), a lipid mediator of inflammation and anaphylaxis, may play a role in several physiopathologic alterations of the lung. A lipid compound with physicochemical and biologic characteristics similar to synthetic PAF was extracted and purified from bronchoalveolar lavage (BAL) fluid of 15 of 34 patients with sarcoidosis. PAF was quantitated by a bioassay on washed rabbit platelets. The specificity of platelet aggregation was assessed by using two different PAF receptor antagonists. The incidence of detectable amounts of PAF in BAL fluid of sarcoid patients was statistically significant (chi 2 = 4.064, p = 0.044) when compared with the 14 normal control subjects. The results demonstrated an increased production of PAF in the lower respiratory tract of patients with sarcoidosis. The presence of PAF in BAL fluid, however, did not correlate with radiologic stage, intensity of alveolitis, gallium scanning positivity, angiotensin-converting enzyme serum level, or lung function tests. Therefore, a direct relationship between presence of PAF in BAL fluid and activity of lung disease in patients with sarcoidosis was not directly established. PMID:1336939

  18. Gastric sarcoidosis: case report and literature review.

    PubMed

    Liang, David B; Price, Jennifer Cohen; Ahmed, Haitham; Farmer, Nicole; Montgomery, Elizabeth A; Giday, Samuel A

    2010-04-01

    Sarcoidosis involving the gastrointestinal tract is extremely rare. Clinically recognizable gastrointestinal system involvement occurs in 0.1% to 0.9% of patients with sarcoidosis. We encountered a 22-year-old African American female admitted to Johns Hopkins Hospital (Baltimore, Maryland) for a 2-week history of fever, chills, eye pain, and abdominal pain. Her abdominal CT scan showed multiple subcentimeter retroperitoneal lymph nodes. An upper endoscopy was performed and discovered an antral nodule that measured about 7 mm and antral gastritis in which biopsies showed active chronic necrotizing granulomatous gastritis. Biopsies of the antral polyp showed focal intestinal metaplasia and active chronic necrotizing granulomatous pattern. Stains for Helicobacter pylori, acid fast, and fungi were negative. A small-bowel series showed no abnormality. Ophthalmologic evaluation revealed panuveitis with bilateral optic disc edema. The patient was later prescribed 60 mg of prednisone by mouth once a day and subsequently her abdominal pain and fever resolved during follow-up 2 months later. This literature review demonstrates the importance in the diagnosis, pathophysiology, clinical manifestations, types of gastric sarcoidosis, major endoscopic findings, and management of gastric sarcoidosis. PMID:20437743

  19. Granulomatous Lithiasic Cholecystitis in Sarcoidosis

    PubMed Central

    Handra-Luca, Adriana

    2016-01-01

    Gallbladder granulomas are exceedingly rare, reported in association with tuberculosis or sarcoidosis. Here we report a case of gallbladder granulomatous cholecystitis occurring in the context of sarcoidosis. A 70-years old man presented with abdominal pain, nausea and vomiting. The medical history revealed sarcoidosis diagnosed more than 20-years previously. 2-years previously the patient showed renal lithiasis, hypercalcemia and, increased angiotensin converting enzyme. The imaging features suggested thoraco-abdominal sarcoidosis. Prednisone was given at 1.2 mg/kg/day initially, than decreased, being at 2.5 mg/day at present. The ultrasound examination showed gallbladder lithiasis. A cholecystectomy was performed. Microscopy showed subacute and chronic cholecystitis with several epithelioid and giant cell granulomas some of them perineural. In conclusion, we report a case of granulomatous cholecystitis occurring in the course of treated sarcoidosis. The perineural location of granulomas may give further insights into the pathogenesis of gallbladder dysmotility. PMID:27162601

  20. Sarcoidosis Presenting Addison's Disease.

    PubMed

    Takahashi, Kentaro; Kagami, Shin-Ichiro; Kawashima, Hirotoshi; Kashiwakuma, Daisuke; Suzuki, Yoshio; Iwamoto, Itsuo

    2016-01-01

    We herein describe a second Japanese case of sarcoidosis presenting Addison's disease. A 52-year-old man was diagnosed with sarcoidosis based on clinical and laboratory findings, including bilateral hilar lymphadenopathy and elevated levels of serum angiotensin-converting enzyme and lysozyme, as well as the presence of noncaseating epithelioid granulomas. The patient also exhibited general fatigue, pigmentation, weight loss, hypotension and hyponatremia, suggestive of chronic adrenocortical insufficiency. An endocrine examination confirmed primary adrenocortical insufficiency. This case suggests the direct involvement of sarcoid granuloma in the adrenal glands. PMID:27150885

  1. Morbidity and Mortality in Sarcoidosis

    PubMed Central

    Gerke, Alicia K.

    2015-01-01

    Purpose of Review Chronic sarcoidosis is a complex disease with numerous comorbid conditions and can be fatal in some cases. Recognizing causes of morbidity and mortality is important to effectively select treatments, manage symptoms, and improve outcomes. The purpose of this review is to examine emerging knowledge on morbidity and mortality in sarcoidosis. Recent Findings Approximately one to five percent of patients with sarcoidosis die from complications of sarcoidosis. Recent population studies indicate that mortality may be increasing over the past decade. The reasons behind these trends are unclear, but could include increasing incidence, detection rates, severity of disease, or age of the population. Morbidity of sarcoidosis is reflected by a trend of increased hospitalizations over recent years and increased use of healthcare resources. Morbidity can be caused by organ damage from granulomatous inflammation, treatment complications, and psychosocial effects of the disease. Recent studies are focused on morbidity related to cardiopulmonary complications, bone health, and aging within the sarcoidosis population. Last, sarcoidosis is associated with autoimmune diseases, pulmonary embolism, and malignancy; however, the underlying mechanisms linking diseases continue to be debated. Summary Morbidity in sarcoidosis is significant and multifactorial. Mortality is infrequent, but may be increasing over the years. PMID:25029298

  2. A natural herbal remedy modulates angiogenic activity of bronchoalveolar lavage cells from sarcoidosis patients

    PubMed Central

    Radomska-Leśniewska, Dorota M.; Skopińska-Różewska, Ewa; Demkow, Urszula; Jóźwiak, Jarosław; Sobiecka, Małgorzata

    2016-01-01

    Sarcoidosis is a systemic inflammatory disease with abnormally high angiogenic activity of inflammatory cells. Reumaherb preparation consisting of three herbs: Echinacea purpurea, Harpagophytum procumbens, and Filipendula ulmaria, and it exerts anti-inflammatory, antioxidant, and analgesic activity and stimulates regenerative and immunological processes. The aim of this paper was to estimate the effect of Reumaherb on immunological angiogenesis induced by bronchoalveolar lavage (BAL) cells collected from six patients with sarcoidosis and grafted into Balb/c mice skin. After grafting, the animals were fed for three days with 0.6 or 1.2 mg of Reumaherb (calculated from recommended human daily dose) daily, suspended in 40 µl of water, or 40 µl of water alone (control group). A significant reduction of newly formed blood vessels was obtained in four cases for 1.2 mg and in three cases for 0.6 mg daily dose of this remedy. Thus, we hypothesise that Reumaherb promotes anti-angiogenic activity and may potentially be used in diseases associated with excessive blood vessel formation. PMID:27095919

  3. Severe Sarcoidosis.

    PubMed

    Kouranos, Vasileios; Jacob, Joe; Wells, Athol U

    2015-12-01

    In sarcoidosis, reduction in mortality and the prevention of disability due to major organ involvement are treatment goals. Thus, it is important to recognize severe disease and identify patients at higher risk of progression to severe disease. In this article, fibrotic lung disease and cardiac sarcoidosis are reviewed as the major contributors to sarcoidosis mortality and morbidity. In the absence of a standardized definition of severe pulmonary disease, a multidisciplinary approach to clinical staging is suggested, based on symptoms, pulmonary function tests, and imaging findings at presentation, integrated with the duration of disease and longitudinal disease behavior during early follow-up. PMID:26593144

  4. Cardiac sarcoidosis

    PubMed Central

    Smedema, J.P.; Zondervan, P.E.; van Hagen, P.; ten Cate, F.J.; Bresser, P.; Doubell, A.F.; Pattynama, P.; Hoogsteden, H.C.; Balk, A.H.M.M.

    2002-01-01

    Sarcoidosis is a multi-system granulomatous disorder of unknown aetiology. Symptomatic cardiac involvement occurs in approximately 5% of patients. The prevalence of sarcoidosis in the Netherlands is unknown, but estimated to be approximately 20 per 100,000 population (3200 patients). We report on five patients who presented with different manifestations of cardiac sarcoidosis, and give a brief review on the current management of this condition. Magnetic Resonance Imaging (MRI) can be of great help in diagnosing this condition as well as in the follow-up of the response to therapy. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6 PMID:25696121

  5. Pulmonary Sarcoidosis: Diagnosis and Treatment.

    PubMed

    Carmona, Eva M; Kalra, Sanjay; Ryu, Jay H

    2016-07-01

    Sarcoidosis is a chronic granulomatous disease of unknown cause that is seen worldwide and occurs mainly in patients between the ages of 20 and 60 years. It can be difficult to diagnose because it can mimic many other diseases including lymphoproliferative disorders and granulomatous infections and because there is no specific test for diagnosis, which depends on correlation of clinicoradiologic and histopathologic features. This review will focus on recent discoveries regarding the pathogenesis of sarcoidosis, common clinical presentations, diagnostic evaluation, and indications for treatment. This review is aimed largely at general practitioners and emphasizes the importance of differentiating pulmonary sarcoidosis from its common imitators. PMID:27378039

  6. Role of a functional polymorphism in the F2R gene promoter in sarcoidosis

    PubMed Central

    Platé, Manuela; Lawson, Phillippa J.; Hill, Michael R.; Marshall, Richard P.; Booth, Helen L.; Kumari, Meena; Laurent, Geoffrey J.; Hurst, John R.

    2015-01-01

    Sarcoidosis is a multisystem granulomatous disease of unknown aetiology characterized by increased inflammation, and results from gene–environment interactions. Proteinase‐activated receptor‐1 mediates the interplay between coagulation and inflammation. The rs2227744G > A promoter single nucleotide polymorphism has been linked to inflammation, cardiovascular disease and chronic obstructive pulmonary disease exacerbations. Using a case‐control study (184 cases with sarcoidosis and 368 controls), we show that the rs2227744A allele significantly associates with protection from sarcoidosis (P = 0.003, OR = 0.68 (0.52–0.88)). PMID:26278396

  7. Multisystemic Sarcoidosis Presenting as Pretibial Leg Ulcers.

    PubMed

    Wollina, Uwe; Baunacke, Anja; Hansel, Gesina

    2016-09-01

    Sarcoidosis is a multisystemic disease of unknown etiology. Up to 30% of patients develop cutaneous manifestations, either specific or nonspecific. Ulcerating sarcoidosis leading to leg ulcers is a rare observation that may lead to confusions with other, more common types of chronic leg ulcers. We report the case of a 45-year-old female patient with chronic multisystemic sarcoidosis presenting with pretibial leg ulcers. Other etiology could be excluded. Histology revealed nonspecific findings. Therefore, the diagnosis of nonspecific leg ulcers in sarcoidosis was confirmed. Treatment consisted of oral prednisolone and good ulcer care. Complete healing was achieved within 6 months. Sarcoidosis is a rare cause of leg ulcers and usually sarcoid granulomas can be found. Our patient illustrates that even in the absence of sarcoid granulomas, leg ulcers can be due to sarcoidosis. PMID:27272316

  8. Progressive kidney failure as the sole manifestation of extrapulmonary sarcoidosis.

    PubMed

    Sethi, Supreet; Relia, Nitin; Syal, Gaurav; Kaushik, Chhavi; Gokden, Neriman; Malik, Ahmad B

    2013-09-01

    Sarcoidosis is a chronic multisystem disorder characterized by an accumulation of T lymphocytes and mononuclear phagocytes, non-caseating epitheliod granulomas and derangement of normal tissue architecture in affected organs. Sarcoidosis can affect any organ system, however approximately 90% of patients with sarcoidosis have pulmonary, lymph node, cutaneous or ocular manifestations. Renal involvement in sarcoidosis is rare and clinically significant renal dysfunction even less common. We present a case of isolated renal sarcoidosis which manifested with progressively worsening renal function and hypercalcemia. A systematic diagnostic approach with pertinent laboratory studies, imaging and renal biopsy elucidated the diagnosis of renal sarcoidosis without any evidence of systemic involvement. PMID:24079056

  9. Assessing the activity of sarcoidosis: quantitative /sup 67/Ga-citrate imaging

    SciTech Connect

    Fajman, W.A.; Greenwald, L.V.; Staton, G.; Check, I.J.; Pine, J.; Gilman, M.; Scheidt, K.A.; McClees, E.C.

    1984-04-01

    Three different methods of quantitating /sup 67/Ga-citrate lung images - a visual index, a computer-assisted index, and the total-lung-to-background ratio - were compared in 71 studies of patients with biopsy-proven sarcoidosis. Fifty consecutive cases were analyzed independently by two different observers using all three methods. In these studies, each index was correlated with the cell differential in the bronchoalveolar lavage fluid. The total-lung-to-background ratio proved to be the simplest to perform; correlated best with the original visual index and the percentage of lymphocytes obtained in bronchoalveolar lavage fluid. Sensitivity for detecting active disease was 84% compared with 64% and 58% for the visual and computer-assisted indices, respectively, with no sacrifice in specificity.

  10. [Kidney involvement in sarcoidosis].

    PubMed

    Kornev, B M; Potapova, A V

    1991-01-01

    Variants of renal damage in sarcoidosis demonstrate the diversity of clinical manifestations common to this systemic disease and serve distinctive reference points in the choice of the treatment policy. A well-defined relationship between hypercalciuria associated with sarcoidosis and risk of calcium nephropathy development is, one the one hand, a reliable criterion for the disease activity and, on the other one, the basis for administration of drug the therapy permitting one to control its level (corticosteroids and drugs of the 4-aminoquinoline series). Other variants of renal damage in sarcoidosis, excluding amyloidosis, form the basis for corticosteroid administration even in cases of the presence of renal failure, demonstrating that so-called "dramatic therapy" produces a remarkable beneficial effect characterized by the disappearance of the signs of renal failure. PMID:1948730

  11. Consequences of Sarcoidosis.

    PubMed

    Drent, Marjolein; Strookappe, Bert; Hoitsma, Elske; De Vries, Jolanda

    2015-12-01

    Sarcoidosis is a multisystem disorder of unknown cause(s). Less specific disabling symptoms, including fatigue and physical impairments, may have a major influence on the daily activities and the social and professional lives of the patients, resulting in a reduced quality of life. A multidisciplinary approach focusing on somatic and psychosocial aspects is recommended. Patients self-perceived knowledge about the importance of exercise and lifestyle should be improved. Developing the most appropriate therapeutic approach for sarcoidosis requires careful consideration of the possible impact of fatigue, small fiber neuropathy related symptoms, pain, cognitive functioning, and coping strategies. Personalized medicine and appropriate communication are beneficial. PMID:26593145

  12. The Evaluation of Cardiac Sarcoidosis with 18F-FDG PET.

    PubMed

    Al-Faham, Zaid; Jolepalem, Prashant; Oliver Wong, Ching Yee

    2016-06-01

    Cardiac involvement in sarcoidosis is associated with poor prognosis. (18)F-FDG PET can detect the presence of cardiac sarcoidosis, assess disease activity, and serve as a means to monitor treatment response in patients with cardiac sarcoidosis. PMID:26271805

  13. Musculoskeletal and cutaneous sarcoidosis: exuberant case report.

    PubMed

    Haddad, Natalie; Oliveira Filho, Jayme de; Nasser, Kassila da Rosa; Corbett, Ana Maria França; Tebet, Ana Carolina Franco; Reis, Mariana Lacerda Junqueira

    2014-01-01

    Sarcoidosis is a multisystem granulomatous disease of unknown cause. The osteoarticular involvement in sarcoidosis is rare and is often associated with cutaneous and long-standing chronic multisystem disease. More common in black women, osseous sarcoidosis is difficult to diagnose, with an incidence of 3 to 13%. The most characteristic radiological clinical picture evidences rounded, well-defined cysts, with no periosteal reaction and without peripheral sclerosis. The small bones of hands and feet are the most frequently involved sites. This report aims to demonstrate a rare case of osteoarticular sarcoidosis with characteristic clinical presentation, and highlight the importance of detecting osteoarticular involvement in this pathology. PMID:25054759

  14. Cardiac Sarcoidosis.

    PubMed

    Birnie, David H; Nery, Pablo B; Ha, Andrew C; Beanlands, Rob S B

    2016-07-26

    Clinically manifest cardiac involvement occurs in perhaps 5% of patients with sarcoidosis. The 3 principal manifestations of cardiac sarcoidosis (CS) are conduction abnormalities, ventricular arrhythmias, and heart failure. An estimated 20% to 25% of patients with pulmonary/systemic sarcoidosis have asymptomatic cardiac involvement (clinically silent disease). In 2014, the first international guideline for the diagnosis and management of CS was published. In patients with clinically manifest CS, the extent of left ventricular dysfunction seems to be the most important predictor of prognosis. There is controversy in published reports as to the outcome of patients with clinically silent CS. Despite a paucity of data, immunosuppression therapy (primarily with corticosteroids) has been advocated for the treatment of clinically manifest CS. Device therapy, primarily with implantable cardioverter-defibrillators, is often recommended for patients with clinically manifest disease. PMID:27443438

  15. Cutaneous Sarcoidosis.

    PubMed

    Wanat, Karolyn A; Rosenbach, Misha

    2015-12-01

    The skin is the second most common organ affected in sarcoidosis, which can affect patients of all ages and races, with African American women having the highest rates of sarcoidosis in the United States. The cutaneous manifestations are protean and can reflect involvement of sarcoidal granulomas within the lesion or represent reactive non-specific inflammation, as seen with erythema nodosum. Systemic work-up is necessary in any patient with cutaneous involvement of sarcoidal granulomas, and treatment depends on other organ involvement and severity of clinical disease. Skin-directed therapies are first line for mild disease, and immunomodulators or immunosuppressants may be necessary. PMID:26593142

  16. [Morphological, immunohistochemical and radiological manifestation of lung tissue remodeling at lung sarcoidosis].

    PubMed

    Kogan, E A; Kichigina, O N; Demura, S A; Osipenko, V I

    2012-01-01

    Sarcoidosis is a group of diseases with chronic immune inflammation and granulomas formation in the lung, lymph nodes, and others organs. Under progress of disease remodeling of the lung tissue occurs and at 20-25% of patient with sarcoidosis lung fibrosis is developed. We studied biopsies from 50 patients with sarcoidosis and 10 biopsies of pathological intact lung tissue as a control group. Roentgenologic, morphologic and immunohistochemical methods with using of mono- and polyclonal antibody to MMP 1, 2, 9 and TIMP-1, PCNA, aSMA, apo-CAS were realized. The expression levels of growth factors, apoptosis, MMPs, TIMPs were different in various clinic-morphological courses of sarcoidosis. As a rule under sarcoidosis deep remodeling of lung tissue didn't occur in spite of granulomatous inflammation. Granulomatous process, alveolitis (bronchiolitis) and sclerotic changes resulted in alteration of the lung. Cells of sarcoidosis granulomas, produced low level of MMPs and TIMP can't induce evident fibrosis and so hypertension is absent or becomes apparent in the slight form. It apparently can be link with localization of pathologic process in lung tissue without any alterations in the bronchoalveolar zone. Alveolitis under sarcoidosis conditions is notable for low activity of inflammation and doesn't result in interstitial fibrosis developing. PMID:22937579

  17. Administering the Sarcoidosis Health Questionnaire to sarcoidosis patients in Serbia

    PubMed Central

    Mihailović-Vučinić, Violeta; Gvozdenović, Branislav; Stjepanović, Mihailo; Vuković, Mira; Marković-Denić, Ljiljana; Milovanović, Aleksandar; Videnović-Ivanov, Jelica; Žugić, Vladimir; Škodrić-Trifunović, Vesna; Filipović, Snežana; Omčikus, Maja

    2016-01-01

    Objective: The aim of this study was to use a Serbian-language version of the disease-specific, self-report Sarcoidosis Health Questionnaire (SHQ), which was designed and originally validated in the United States, to assess health status in sarcoidosis patients in Serbia, as well as validating the instrument for use in the country. Methods: This was a cross-sectional study of 346 patients with biopsy-confirmed sarcoidosis. To evaluate the health status of the patients, we used the SHQ, which was translated into Serbian for the purposes of this study. We compared SHQ scores by patient gender and age, as well as by disease duration and treatment. Lower SHQ scores indicate poorer health status. Results: The SHQ scores demonstrated differences in health status among subgroups of the sarcoidosis patients evaluated. Health status was found to be significantly poorer among female patients and older patients, as well as among those with chronic sarcoidosis or extrapulmonary manifestations of the disease. Monotherapy with methotrexate was found to be associated with better health status than was monotherapy with prednisone or combination therapy with prednisone and methotrexate. Conclusions: The SHQ is a reliable, disease-specific, self-report instrument. Although originally designed for use in the United States, the SHQ could be a useful tool for the assessment of health status in various non-English-speaking populations of sarcoidosis patients. PMID:27167430

  18. How Is Sarcoidosis Treated?

    MedlinePlus

    ... page from the NHLBI on Twitter. How Is Sarcoidosis Treated? Not everyone who has sarcoidosis needs treatment. ... Content: NEXT >> Featured Video Living With and Managing Sarcoidosis 05/18/2011 This video—presented by the ...

  19. What Causes Sarcoidosis?

    MedlinePlus

    ... page from the NHLBI on Twitter. What Causes Sarcoidosis? The cause of sarcoidosis isn't known. More ... Content: NEXT >> Featured Video Living With and Managing Sarcoidosis 05/18/2011 This video—presented by the ...

  20. Living with Sarcoidosis

    MedlinePlus

    ... page from the NHLBI on Twitter. Living With Sarcoidosis Sarcoidosis has no cure, but you can take ... Content: NEXT >> Featured Video Living With and Managing Sarcoidosis 05/18/2011 This video—presented by the ...

  1. How Is Sarcoidosis Diagnosed?

    MedlinePlus

    ... page from the NHLBI on Twitter. How Is Sarcoidosis Diagnosed? Your doctor will diagnose sarcoidosis based on ... Content: NEXT >> Featured Video Living With and Managing Sarcoidosis 05/18/2011 This video—presented by the ...

  2. Subcutaneous sarcoidosis: a clinical analysis of nine patients.

    PubMed

    Ando, Masaru; Miyazaki, Eishi; Hatano, Yutaka; Nishio, Suehiro; Torigoe, Chihiro; Yamasue, Mari; Mukai, Yutaka; Nureki, Shin-Ichi; Kadota, Jun-Ichi

    2016-09-01

    Subcutaneous sarcoidosis is the specific subset of cutaneous sarcoidosis frequently associated with systemic disease. However, the disease activity, severity, and prognosis have not yet been elucidated due to the limited number of reported cases. The purpose of this study was to identify the clinical, laboratory, and prognostic differences between subcutaneous sarcoidosis and other type of cutaneous sarcoidosis. All patients with sarcoidosis diagnosed histopathologically from 2000 to 2012 at our institution were enrolled. The clinical, laboratory, chest X-ray, and pulmonary function test results were retrospectively evaluated in the patients with cutaneous sarcoidosis. In the 130 patients with sarcoidosis, cutaneous sarcoidosis was diagnosed in 37 patients (28.4 %), and 9 (6.9 %) of these patients had subcutaneous sarcoidosis. The serum levels of soluble interleukin-2 receptor (sIL-2R) were significantly elevated in the group of patients with subcutaneous sarcoidosis in comparison to the patients with other types of cutaneous sarcoidosis, whereas there was no significant difference in the severity score between the two groups. Following a 2-year observation period, three patients were in remission, five patients demonstrated stable disease, and one patient had progressive disease. Subcutaneous sarcoidosis may be associated with the disease activity, although it was not found to be associated with the disease severity and it was not a predictive factor for the prognosis. Furthermore, the prevalence of subcutaneous sarcoidosis may be higher than that in previously reported series. PMID:27449952

  3. Assessment of activity in Sarcoidosis. Sensitivity and specificity of 67Gallium scintigraphy, serum ACE levels, chest roentgenography, and blood lymphocyte subpopulations

    SciTech Connect

    Klech, H.; Kohn, H.; Kummer, F.; Mostbeck, A.

    1982-12-01

    The value of different factors are examined to assess activity in 60 patients with biopsy-proven sarcoidosis. In patients with active sarcoidosis (n . 35), /sup 67/Ga scans proved to be the most sensitive method (94 percent sensitivity), followed by serum angiotensin I converting enzyme (S-ACE) levels, chest x-ray films, and lymphocyte assays. In patients with peripheral pulmonary lesions, chest x-ray films failed in 32 percent of cases to document activity (68 percent sensitivity) whereas /sup 67/Ga scans and S-ACE levels remained to give reliable results. Despite poor specificity, negative /sup 67/Ga scans together with normal ACE levels have a high predictive value for exclusion of active sarcoidosis. In patients with peripheral pulmonary lesions, chest roentgenography is of doubtful value for staging lung involvement and assessment of activity including monitoring and control of therapy.

  4. A case of childhood sarcoidosis.

    PubMed

    Hunt, S J; O'toole, E; Philips, W; Hardman, C; Wakelin, S H; Walters, S

    2002-09-01

    Cutaneous sarcoidosis is rare in children. We report a case of a 5-year-old Bangladeshi girl who presented with fever, a papular eruption on the lower limbs and trunk, malaise, anorexia and weight loss. There was multisystem involvement with marked hepatosplenomegaly, generalized lymphadenopathy, parotid fullness and chronic uveitis. Pulmonary infiltrates were seen on the chest X-ray. Histology of a skin biopsy showed naked noncaseating granulomata and PCR for Mycobacterium tuberculosis was negative. A clinical diagnosis of sarcoidosis was made. The patient was treated with oral prednisolone (2 mg/kg per day). An excellent clinical response with resolution of the rash and improvement of extracutaneous signs was noted within 3 months and she remains well on low-dose prednisolone on alternate days. We discuss the presentation and management of sarcoidosis in children, and highlight the potential difficulty in differentiating this from disseminated tuberculosis. PMID:12372081

  5. Sarcoidosis and the heart: A review of the literature

    PubMed Central

    Ipek, Emrah; Demirelli, Selami; Ermis, Emrah; Inci, Sinan

    2015-01-01

    Summary Sarcoidosis is a chronic multisystem disorder without any defined etiology. Cardiac sarcoidosis (CS) is detected in 2–7% of patients with sarcoidosis and more than 20% of the cases of sarcoidosis are clinically silent. Cardiac involvement in systemic sarcoidosis (SS) and isolated cardiac sarcoidosis (iCS) are associated with arrhythmia and severe heart failure (HF) and have a poor prognosis. Early diagnosis of CS and prompt initiation of corticosteroid therapy with or without other immunosuppressants is crucial. Electrocardiography, Holter monitoring, and Doppler echocardiography with speckle tracking imaging can serve as the initial steps to diagnosis of CS. Cardiac magnetic resonance (CMR) imaging and positron emission tomography (PET) are promising techniques for both diagnosis and follow-up of CS. This review discusses the main aspects of cardiac involvement in sarcoidosis. PMID:26668777

  6. Current and emerging pharmacological treatments for sarcoidosis: a review

    PubMed Central

    Beegle, Scott H; Barba, Kerry; Gobunsuy, Romel; Judson, Marc A

    2013-01-01

    The treatment of sarcoidosis is not standardized. Because sarcoidosis may never cause significant symptoms or organ dysfunction, treatment is not mandatory. When treatment is indicated, oral corticosteroids are usually recommended because they are highly likely to be effective in a relative short period of time. However, because sarcoidosis is often a chronic condition, long-term treatment with corticosteroids may cause significant toxicity. Therefore, corticosteroid sparing agents are often indicated in patients requiring chronic therapy. This review outlines the indications for treatment, corticosteroid treatment, and corticosteroid sparing treatments for sarcoidosis. PMID:23596348

  7. Microglial Activation & Chronic Neurodegeneration

    PubMed Central

    Lull, Melinda E.; Block, Michelle L.

    2010-01-01

    Microglia, the resident innate immune cells in the brain, have long been implicated in the pathology of neurodegenerative diseases. Accumulating evidence points to activated microglia as a chronic source of multiple neurotoxic factors, including TNFα, NO, IL1-β, and reactive oxygen species (ROS), driving progressive neuron damage. Microglia can become chronically activated by either a single stimulus (ex. LPS or neuron damage) or multiple stimuli exposures to result in cumulative neuronal loss over time. While the mechanisms driving these phenomena are just beginning to be understood, reactive microgliosis (the microglial response to neuron damage) and ROS have been implicated as key mechanisms of chronic and neurotoxic microglial activation, particularly in the case of Parkinson’s Disease. Here, we review the mechanisms of neurotoxicity associated with chronic microglial activation and discuss the role of neuronal death and microglial ROS driving the chronic and toxic microglial phenotype. PMID:20880500

  8. Sarcoidosis: radiographic manifestations in the nails and distal phalanges.

    PubMed

    Albers, Brittany K; Sluzevich, Jason C; Garner, Hillary W

    2016-05-01

    Sarcoidosis is a granulomatous disease which can affect multiple organ systems. Clinical and radiologic manifestations depend on the organ system involved and the chronicity of disease. Nail involvement in sarcoidosis is rare, but is clinically relevant as it indicates chronic systemic disease. Nail abnormalities can be identified radiographically, and when seen in patients with known or suspected sarcoidosis, should prompt careful evaluation of the underlying bone for osseous involvement. We describe a case of sarcoidosis with radiographic findings in the nails and distal phalangeal tufts, which were indicative of nail and osseous sarcoid involvement and strongly supported the presence of chronic systemic disease. Although the nail findings resolved clinically and on radiographs after treatment, the osseous findings showed only minimal improvement. To our knowledge, the radiographic findings of nail sarcoidosis have not been previously addressed in the literature. PMID:26768259

  9. Tenth international conference on sarcoidosis and other granulomatous disorder

    SciTech Connect

    Johns, C.J.

    1986-01-01

    This book contains papers divided among three sections: Basic Mechanisms of Sarcoidosis; Other Granulomatous Disorders; and Clinical Studies of Sarcoidosis. Some of the paper titles are: Radionuclides in Detecting Active Granuloma Formation: Gallium-67 Scintigraphy and Histopathology with Autoradiographic; a European Survey on the Usefulness of /sup 67/Ga Lung Scans in Assessing Sarcoidosis: Experience in 14 Research Centers in Seven Different Countries; and Reassessing the Standard Chest Radiograph for Intraparenchymal Activity.

  10. Rheumatologic Manifestations of Sarcoidosis

    PubMed Central

    Sweiss, Nadera J.; Patterson, Karen; Sawaqed, Ray; Jabbar, Umair; Korsten, Peter; Hogarth, Kyle; Wollman, Robert; Garcia, Joe G.N.; Niewold, Timothy B.; Baughman, Robert P.

    2012-01-01

    Sarcoidosis is a systemic, clinically heterogeneous disease characterized by the development of granulomas. Any organ system can be involved, and patients may present with any number of rheumatologic symptoms. There are no U.S. Food and Drug Administration–approved therapies for the treatment of sarcoidosis. Diagnosing sarcoidosis becomes challenging, particularly when its complications cause patients’ symptoms to mimic other conditions, including polymyositis, Sjögren syndrome, or vasculitis. This review presents an overview of the etiology of and biomarkers associated with sarcoidosis. We then provide a detailed description of the rheumatologic manifestations of sarcoidosis and present a treatment algorithm based on current clinical evidence for patients with sarcoid arthritis. The discussion will focus on characteristic findings in patients with sarcoid arthritis, osseous involvement in sarcoidosis, and sarcoid myopathy. Arthritic conditions that sometimes coexist with sarcoidosis are described as well. We present two cases of sarcoidosis with rheumatologic manifestations. Our intent is to encourage a multidisciplinary, translational approach to meet the challenges and difficulties in understanding and treating sarcoidosis. PMID:20665396

  11. Sarcoidosis simulating syringomas.

    PubMed

    Rocha, Diego Santos; Presotto, Carolina; Bringel, Daniela Martins; Bomm, Lislaine; Balassiano, Eli; Alves, Maria de Fátima Guimarães Scotelaro

    2012-01-01

    Sarcoidosis is a granulomatous disease of unknown etiology. The skin is commonly affected. Cutaneous manifestations can mimic other diseases and autoimmune disorders. The dermatologist plays a critical role in elucidating the clinical diagnosis and assisting other specialists in the investigation of a systemic disease. We report a patient with typical cutaneous manifestation of sarcoidosis with pulmonary involvement. PMID:22570040

  12. Sarcoidosis presenting with chylothorax.

    PubMed Central

    Jarman, P. R.; Whyte, M. K.; Sabroe, I.; Hughes, J. M.

    1995-01-01

    A patient in whom chylothorax was the presenting feature of sarcoidosis is reported. Mediastinal lymphadenopathy was shown by computed tomographic scanning. Obstruction of the thoracic duct by enlarged lymph nodes or fibrosis is the probable cause of chylothorax in this case. The association of chylothorax and sarcoidosis is extremely rare. Images PMID:8553312

  13. Systemic and lung protein changes in sarcoidosis. Lymphocyte counts, gallium uptake values, and serum angiotensin-converting enzyme levels may reflect different aspects of disease activity

    SciTech Connect

    Check, I.J.; Kidd, M.R.; Staton, G.W. Jr.

    1986-01-01

    BAL lymphocyte percentages, quantitated gallium-67 lung uptake, and SACE levels have all been proposed as measures of disease activity in sarcoidosis. We analyzed 32 paired sera and BAL fluids from sarcoidosis patients by high-resolution agarose electrophoresis to look for protein changes characteristic of systemic or local inflammation and compared the results with those from the above tests. Nine patients (group 1) had serum inflammatory protein changes and increased total protein, albumin, beta 1-globulin (transferrin), and gamma-globulin levels in fluid recovered by BAL. Thirteen patients (group 2) had normal protein levels in sera but abnormal protein levels in BAL specimens. Ten patients (group 3) had normal protein levels in sera and in BAL specimens. Patients in groups 1 and 2 had a disproportionate increase in beta 1-globulin (transferrin) and gamma-globulin levels in their BAL specimens. The BAL lymphocyte percentage changes paralleled the BAL protein level changes, suggesting relationships among the immunoregulatory role of these cells, increased local immunoglobulin synthesis, and the pathogenesis of altered alveolar permeability. Gallium-67 uptake was highest in patients with serum inflammatory protein changes. Thus, systemic inflammation may facilitate pulmonary gallium-67 uptake, possibly by changes in BAL fluid or serum transferrin saturation and/or kinetics. SACE levels showed no relationship to changes in the levels of serum or BAL proteins. These data suggest that the various proposed measures of disease activity reflect different aspects of inflammation in sarcoidosis.

  14. Tuberculosis or sarcoidosis: Opposite ends of the same disease spectrum?

    PubMed

    Agrawal, Rupesh; Kee, Ae Ra; Ang, Leslie; Tun Hang, Yeo; Gupta, Vishali; Kon, Onn Min; Mitchell, Donald; Zierhut, Manfred; Pavesio, Carlos

    2016-05-01

    Tuberculosis and sarcoidosis are chronic systemic diseases that have similar pulmonary and extra-pulmonary manifestations. Multiple studies have found an epidemiological, molecular, and immunological link between the two. It has been suggested that mycobacterium tuberculosis could be a common pathophysiologic mechanism for tuberculosis and sarcoidosis, and that both clinical entities can trigger similar immunological response in patients. Due to this close association, together with possible coexistence in the same patient, the diagnosis of one disease from another may be difficult. In our paper, we suggest that tuberculosis and sarcoidosis are two ends of the same spectrum. Given the pathophysiological and clinical link between the two, we also propose a classification system for tuberculosis and sarcoidosis: Sarcoidosis (S); Sarcoid-Tuberculous (ST); Tuberculous Sarcoid (TS) and Tuberculosis (TB). More research and clinical trials should first be done to affirm the link between the two disease entities. PMID:27156614

  15. Budd-Chiari Syndrome: An Unusual Presentation of Multisystemic Sarcoidosis

    PubMed Central

    Bacha, Dhouha; Romdhane, Hayfa; Cheikh, Myriam; Nejma, Houda Ben; BelHadj, Najet

    2015-01-01

    Sarcoidosis is a multisystem granulomatous disease of unknown origin. All organs may be affected. Liver involvement is common but it is rarely symptomatic. Only a few cases of Budd-Chiari syndrome (BCS) secondary to a hepatic sarcoidosis have been described so far. We describe a case of multisystemic sarcoidosis presenting with BCS. A 42-year old female was referred to our department for chronic and anicteric cholestasis. Laboratory and imaging investigations disclosed features of chronic BCS associated with multisystemic sarcoidosis. The positive diagnosis was based on microscopic features, which showed hepatic, gastric and cutaneous non-caseating granulomas. Screening for an underlying thrombophilic disorder was negative. The diagnosis of BCS complicating hepatic sarcoidosis was the most likely. She was put on corticosteroids and anticoagulation therapy. To our knowledge, few cases of sarcoidosis-related BCS have been reported in the literature. In addition to being an uncommon presentation of sarcoidosis, this case illustrates the importance of recognizing an unusual cause of BCS and its therapeutic difficulties. PMID:26900444

  16. Cardiac sarcoidosis - silent destroyer.

    PubMed

    Martusewicz-Boros, Magdalena M; Piotrowska-Kownacka, Dorota; Wiatr, Elżbieta; Roszkowski-Śliż, Kazimierz

    2016-01-01

    We report a case of histologically proven pulmonary sarcoidosis and cardiac involvement in a 53-year old woman with progression leading to the heart failure documented in cardiovascular magnetic resonsnce studies. PMID:27537722

  17. Foundation for Sarcoidosis Research

    MedlinePlus

    ... Clinical Trials Fail: FSR’s New Initiative to Bridge Gap between Industry Leaders, Researchers, and Patients Guest post ... 1 2 3 … 10 Next → Foundation for Sarcoidosis Research 1820 W. Webster Ave Suite 304 Chicago, Illinois ...

  18. Altered Cyclooxygenase-2 Expression in Pulmonary Sarcoidosis is not Related to Clinical Classifications.

    PubMed

    Kiszałkiewicz, Justyna; Piotrowski, Wojciech J; Pastuszak-Lewandoska, Dorota; Górski, Paweł; Antczak, Adam; Górski, Witold; Domańska-Senderowska, Daria; Migdalska-Sęk, Monika; Czarnecka, Karolina H; Nawrot, Ewa; Brzeziańska-Lasota, Ewa

    2016-08-01

    Elevated COX-2 activity is associated with the development of chronic lung diseases leading to bronchial obstruction, including sarcoidosis. The aim of the study was to examine expression pattern of COX-2 messenger RNA (mRNA). Expression was performed by q-PCR method in bronchoalveolar lavage (BAL) cells and peripheral blood (PB) lymphocytes in sarcoidosis patients (n = 61) and control group (n = 30). Analysis of COX-2 mRNA expression level in BAL fluid and PB revealed downregulation in sarcoidosis and control groups. In PB lymphocytes, the statistically significant difference between patients and controls was observed (P = 0.003, Mann-Whitney U test), with higher expression in patients. There were no statistically significant differences between patients without and with parenchymal involvement (stages I vs. II-IV), between patients with acute vs. insidious onset of disease and between patients with abnormal vs. normal spirometry (P > 0.05, Mann-Whitney U test). Results suggest that expression of COX-2 mRNA in patients with pulmonary sarcoidosis is not related to clinical classifications. PMID:27188849

  19. Imaging of cardiac sarcoidosis.

    PubMed

    Erthal, Fernanda; Juneau, Daniel; Lim, Siok P; Dwivedi, Girish; Nery, Pablo B; Birnie, David; Beanlands, Rob S

    2016-09-01

    Sarcoidosis is a multisystem inflammatory disease. Cardiac involvement is described in up to 50% of the cases. The disease spectrum is wide and cardiac manifestations ranges from being asymptomatic to heart failure, arrhythmias and sudden cardiac death. The diagnosis of cardiac sarcoidosis can be challenging due to its non-specific nature and the focal involvement of the heart. In this review, we discuss the utility of a stepwise approach with multimodality cardiac imaging in the diagnosis and management of CS. PMID:27225318

  20. Sarcoidosis of the liver and bile ducts.

    PubMed

    Ishak, K G

    1998-05-01

    In sarcoidosis, granulomas are frequently present in multiple organs, including the liver. Typically, epithelioid granulomas (noncaseating) are scattered throughout the liver, but confluent granulomas can be present in cases with severe hepatic involvement. The characteristic inclusions in giant cells (for example, Schaumann bodies and asteroid bodies) are not seen in all cases and are not pathognomonic. The granulomas of sarcoidosis may heal without a trace, but confluent granulomas can result in extensive, irregular scarring. Occlusion of intrahepatic portal vein branches by the granulomatous inflammation probably accounts for the development of portal hypertension in some cases. A granulomatous cholangitis leading to ductopenia seems to be the underlying pathogenetic mechanism of the chronic cholestatic syndrome of sarcoidosis. Recognition of this syndrome is important in the differential diagnosis of other chronic cholestatic diseases, such as primary biliary cirrhosis or primary sclerosing cholangitis. Other rare complications of sarcoidosis are the Budd-Chiari syndrome and obstructive jaundice attributable to hepatic hilar lymphadenopathy or strictures of the bile ducts. PMID:9581591

  1. Nail Sarcoidosis with and without Systemic Involvement: Report of Two Cases.

    PubMed

    Noriega, Leandro; Criado, Paulo; Gabbi, Tatiana; Avancini, João; Di Chiacchio, Nilton

    2015-09-01

    The most commonly seen nail change in sarcoidosis, often associated with chronic systemic disease, is onychodystrophy. Imaging of hands, feet and chest is of paramount importance when nail sarcoidosis is suspected, for evaluation of bone cysts and pulmonary involvement, respectively. We report 2 cases of sarcoidosis that developed nail involvement - one with pulmonary disease, and the other without any evidence of systemic involvement, which is very rare. PMID:27170939

  2. Nail Sarcoidosis with and without Systemic Involvement: Report of Two Cases

    PubMed Central

    Noriega, Leandro; Criado, Paulo; Gabbi, Tatiana; Avancini, João; Di Chiacchio, Nilton

    2015-01-01

    The most commonly seen nail change in sarcoidosis, often associated with chronic systemic disease, is onychodystrophy. Imaging of hands, feet and chest is of paramount importance when nail sarcoidosis is suspected, for evaluation of bone cysts and pulmonary involvement, respectively. We report 2 cases of sarcoidosis that developed nail involvement – one with pulmonary disease, and the other without any evidence of systemic involvement, which is very rare. PMID:27170939

  3. Sickle cell anemia patient with sarcoidosis-associated inguinal lymph node and lung infiltration.

    PubMed Central

    Güvenç, Birol; Unsal, Cagatay; Hanta, Ismail; Unsal, Aydan; Güvenç, Hakan

    2005-01-01

    Sarcoidosis is a chronic, systemic inflammatory disease of unknown etiology, characterized by noncaseating granulomatous infiltration of any organ. Sickle cell anemia (SCA) is the homozygoid form of sickle cell disease (SCD), which includes a group of genetic disorders characterized by production of an abnormal hemoglobin S (HbS). There are a few case reports with coexistence of sarcoidosis and SCA. We reported a 47-year-old female with SCA and sarcoidosis. Images Fig. 1 PMID:16035582

  4. Elevated IL-8 and MCP-1 in the bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis.

    PubMed

    Car, B D; Meloni, F; Luisetti, M; Semenzato, G; Gialdroni-Grassi, G; Walz, A

    1994-03-01

    The potential for interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) to induce neutrophil and mononuclear phagocyte accumulation in the lungs of patients with pulmonary sarcoidosis and idiopathic pulmonary fibrosis (IPF) was investigated. Bronchoalveolar lavage (BAL) fluids from 12 patients with IPF and 15 with sarcoidosis were concentrated by reversed-phase chromatography, and their IL-8 and MCP-1 concentrations assessed by enzyme-linked immunosorbent assay (ELISA), chemotaxis, and enzyme-releasing assays with monocytes and neutrophils. ELISA revealed significantly elevated concentrations of MCP-1 (20.1 ng/mg albumin) in the BAL fluids of patients with pulmonary sarcoidosis and those with IPF (41.8 ng/mg) in comparison to 11 normal individuals (4.24 ng/mg) and 15 patients with chronic bronchitis (CB) (5.16 ng/mg). Similarly, the chemotactic activity for monocytes (MCP-1 equivalent) was strongly increased in patients with sarcoidosis (86.03 ng/mg) as well as in those with IPF (54.47 ng/mg). The chemoattractant activity of normal individuals and CB patients was 7- or 3-fold lower, respectively. Patients with IPF and sarcoidosis also had elevated IL-8 levels (15.5 and 26.0 ng/mg, respectively; normals: 2.14 ng/mg; and CB patients: 4.23 ng/mg) and greater neutrophil chemotaxis (60.25 and 49.68 ng/mg, respectively; normals: 0.35 ng/mg; and CB patients: 11.06 ng/mg). These data suggest that increased levels of both MCP-1 and IL-8 may be characteristic for sarcoidosis or IPF. It appears likely that both of these chemoattractants contribute to the influx of monocytes and neutrophils into the pulmonary alveolus and interstitium in these diseases. PMID:8118632

  5. A clinically unsuspected nasopharyngeal sarcoidosis.

    PubMed

    Tuğrul, Selahattin; Göktaş, Seda Sezen; Özücer, Berke; Sönmez, Fatma Cavide; Özturan, Orhan

    2016-01-01

    Sarcoidosis is a multi-system disease which rarely involves the upper respiratory tract, leading to hoarseness, dysphagia, laryngeal paralysis, and upper airway obstruction. The Waldeyer's ring involvement in sarcoidosis is also very rare. In this article, we report a 32-year-old male case in whom a nasopharyngeal mass was detected based on the Waldeyer's ring involvement due to sarcoidosis. PMID:27107604

  6. [Systemic sarcoidosis: a diagnostic challenge in pediatrics. Case report].

    PubMed

    Díaz Angarita, Tomás; Morales Camacho, William; Lozano Neira, Laura; Plata Ortiz, Jessica; Zárate Taborda, Linda

    2016-10-01

    Sarcoidosis is a granulomatous inflammatory disease of unknown etiology, evidenced most often in young adults, which can compromise several organs, mainly lung, lymph nodes, eyes and skin. The presence of the disease in pediatric population is rare. Denomination in pediatrics is made based on age and clinical manifestations of the patient. The aim of this report is to present a case of systemic sarcoidosis in a pediatric patient without lung involvement with severe extrapulmonary manifestations. Fifteen year old patient who debuted with nonspecific symptoms (emesis, weight loss). Radiographic studies without lung involvement but with findings suggestive of Langerhans cell histiocytosis; however, histopathological report (bone and lymph) showed the presence of chronic granulomatous nonnecrotizing disease, sarcoidosis type. Childhood sarcoidosis is a rare and difficult entity to diagnose, mainly by the lack of specific biomarkers for diagnosis. PMID:27606655

  7. Sarcoidosis and Autoimmunity: From Genetic Background to Environmental Factors.

    PubMed

    Bindoli, Sara; Dagan, Amir; Torres-Ruiz, José J; Perricone, Carlo; Bizjak, Mojca; Doria, Andrea; Shoenfeld, Yehuda

    2016-01-01

    Sarcoidosis is a chronic multisystem disease with variable course resulting from the interaction between environmental factors and the immune system of individuals genetically predisposed. The evidence linking sarcoidosis with environmental triggers such as metals is increasing. We describe the case of a 44 year old female with a history. of smoking since age 30 and previous mercury dental filling who presented at physical examination with numerous subcutaneous nodules. Laboratory data showed accelerated erythrocyte sedimentation rate and high titer of anti-U1 ribonucleoprotein antibodies (U1 RNP). Skin biopsy and chest X-ray suggested the diagnosis of sarcoidosis. In this report we illustrate the different causes involved in the onset of sarcoidosis. PMID:27228643

  8. Cryptococcal meningitis complicating sarcoidosis

    PubMed Central

    Leonhard, Sonja E.; Fritz, Daan; van de Beek, Diederik; Brouwer, Matthijs C.

    2016-01-01

    Abstract Background: Cryptococcal meningitis is an uncommon but severe complication of sarcoidosis. Methods: We present 2 patients with cryptococcal meningitis complicating sarcoidosis and compared findings with 38 cases reported in the literature. Results: When analyzing our patients and 38 cases reported in the literature, we found that median age of sarcoidosis patients with cryptococcal meningitis was 39 years (range 30–48); 27 of 33 reported cases (82%) had a history of sarcoidosis. Only 16 of 40 patients (40%) received immunomodulating therapy at the time of diagnosis of cryptococcal meningitis. The diagnosis of cryptococcal meningitis was delayed in 17 of 40 patients (43%), mainly because of the initial suspicion of neurosarcoidosis. Cerebrospinal fluid (CSF) examination showed mildly elevated white blood cell count (range 23–129/mm3). Twenty-nine of 32 cases (91%) had a positive CSF culture for Cryptococcus neoformans and 25 of 27 cases (93%) had a positive CSF C neoformans antigen test. CD4 counts were low in all patients in whom counts were performed (84–228/mL). Twelve patients had an unfavorable outcome (32%), of which 7 died (19%) and 24 patients (65%) had a favorable outcome. The rate of unfavorable outcome in patients with a delayed diagnosis was 7 of 17 (41%) compared to 5 of 28 (21%) in patients in whom diagnosis was not delayed. Conclusion: Cryptococcal meningitis is a rare but life-threatening complication of sarcoidosis. Patients were often initially misdiagnosed as neurosarcoidosis, which resulted in considerable treatment delay and worse outcome. CSF cryptococcal antigen tests are advised in patients with sarcoidosis and meningitis. PMID:27583871

  9. Who Is at Risk for Sarcoidosis?

    MedlinePlus

    ... NHLBI on Twitter. Who Is at Risk for Sarcoidosis? Sarcoidosis affects people of all ages and races. ... Content: NEXT >> Featured Video Living With and Managing Sarcoidosis 05/18/2011 This video—presented by the ...

  10. Computed tomography in pulmonary sarcoidosis

    SciTech Connect

    Lynch, D.A.; Webb, W.R.; Gamsu, G.; Stulbarg, M.; Golden, J.

    1989-05-01

    We studied the high resolution CT (HRCT) scans of 15 patients with biopsy-proven sarcoidosis and correlated the findings with pulmonary function tests (12 patients), 67Ga scans (10 patients), bronchoalveolar lavage (five patients), recent transbronchial biopsy (six patients), and recent open lung biopsy (three patients). The HRCT features included small nodules, thickened interlobular septa, patchy focal increase in lung density, honeycombing, and central conglomeration of vessels and bronchi. Active alveolitis was present by gallium scanning criteria in 5 of 10 cases. By bronchoalveolar lavage criteria, activity was present in three of five cases. Patchy increase in density may correlate with active alveolitis as seen on /sup 67/Ga scanning. High resolution CT was better than chest X-radiography for demonstration of patchy increase in density and for distinguishing nodules from septal thickening. Both nodules and patchy density were partly reversible following therapy. Nodular densities seen on CT correlated with the presence of granulomata on histology. Resting pulmonary function tests correlated poorly with presence and extent of lung disease on HRCT. The presence on HRCT of focal fine nodules, patchy focal increase in lung density, and central crowding of bronchi and vessels should suggest the diagnosis of sarcoidosis. In some patients, HRCT can identify unsuspected parenchymal lung disease and document the reversible components of sarcoid lung disease.

  11. Pulmonary hypertension complicating pulmonary sarcoidosis.

    PubMed

    Huitema, M P; Grutters, J C; Rensing, B J W M; Reesink, H J; Post, M C

    2016-06-01

    Pulmonary hypertension (PH) is a severe complication of sarcoidosis, with an unknown prevalence. The aetiology is multifactorial, and the exact mechanism of PH in the individual patient is often difficult to establish. The diagnostic work-up and treatment of PH in sarcoidosis is complex, and should therefore be determined by a multidisciplinary expert team in a specialised centre. It is still a major challenge to identify sarcoidosis patients at risk for developing PH. There is no validated algorithm when to refer a patient suspected for PH, and PH analysis itself is difficult. Until present, there is no established therapy for PH in sarcoidosis. Besides optimal treatment for sarcoidosis, case series evaluating new therapeutic options involving PH-targeted therapy are arising for a subgroup of patients. This review summarises the current knowledge regarding the aetiology, diagnosis and possible treatment options for PH in sarcoidosis. PMID:27194118

  12. Sarcoidosis: Immunopathogenesis and Immunological Markers

    PubMed Central

    Loke, Wei Sheng Joshua; Herbert, Cristan; Thomas, Paul S.

    2013-01-01

    Sarcoidosis is a multisystem granulomatous disorder invariably affecting the lungs. It is a disease with noteworthy variations in clinical manifestation and disease outcome and has been described as an “immune paradox” with peripheral anergy despite exaggerated inflammation at disease sites. Despite extensive research, sarcoidosis remains a disease with undetermined aetiology. Current evidence supports the notion that the immune response in sarcoidosis is driven by a putative antigen in a genetically susceptible individual. Unfortunately, there currently exists no reliable biomarker to delineate the disease severity and prognosis. As such, the diagnosis of sarcoidosis remains a vexing clinical challenge. In this review, we outline the immunological features of sarcoidosis, discuss the evidence for and against various candidate etiological agents (infective and noninfective), describe the exhaled breath condensate, a novel method of identifying immunological biomarkers, and suggest other possible immunological biomarkers to better characterise the immunopathogenesis of sarcoidosis. PMID:26464848

  13. Cough in Sarcoidosis.

    PubMed

    Tully, Timothy; Birring, Surinder S

    2016-02-01

    Sarcoidosis is a granulomatous disorder that frequently affects the lungs. Cough is commonly reported by patients and can significantly reduce health-related quality of life. The mechanism of cough is unknown but airway inflammation, mechanical distortion from pulmonary fibrosis and disruption of the vagus nerve are possible. Recent evidence suggests cough reflex hypersensitivity may also be an important mechanism and predictor of the frequency of cough. The investigation of cough should evaluate common causes such as asthma, gastro-oesophageal reflux and rhinitis. In patients with suspected cough due to sarcoidosis, a trial of corticosteroids should be considered. The severity of cough should be evaluated with validated outcome measures such as visual analogue scales, cough severity diary, health-related quality of life questionnaires such as the Leicester Cough Questionnaire and objective cough monitors. Future studies are needed to identify targets for therapeutic development. PMID:26349475

  14. [Ocular Manifestations in Sarcoidosis].

    PubMed

    Walscheid, K; Tappeiner, C; Heiligenhaus, A

    2016-05-01

    Sarcoidosis is an inflammatory multi-organ disease of unknown pathogenesis, characterised by non-necrotising granulomata. Sarcoidosis predominantly manifests in the lung, but any other organ may be affected. Ocular involvement is present in about 25 to 50 % of patients. The most common ocular manifestation is uveitis, especially of the anterior eye segment. If ocular sarcoidosis is suspected, interdisciplinary assessment of the patient is mandatory, including laboratory tests, chest X-ray, assessment by a specialist in internal medicine and, ideally, histological evidence of granuloma formation in a tissue specimen. Other (infectious) causes of granulomatous inflammation need to be excluded, especially tuberculosis or syphilis. For the ophthalmological assessment, detection of granulomatous lesions is of particular importance, especially by visualising chorioretinal granuloma by fluorescein and indocyanin green angiography. Cystoid macular oedema and glaucoma are the most frequent complications limiting visual acuity. Corticosteroids, which can be administered either locally or systemically, are the mainstay of therapy. Depending on the clinical course and the development of ocular complications, systemic steroid-sparing immunosuppressive medication may be indicated. PMID:27187879

  15. [Lung sarcoidosis: Clinical features and therapeutic issues].

    PubMed

    Uzunhan, Y; Jeny, F; Crockett, F; Piver, D; Kambouchner, M; Valeyre, D; Nunes, H

    2016-09-01

    Sarcoidosis is a granulomatous disease of unknown cause. This proteiform disease is characterized by an almost constant and often predominant lung involvement. The natural history of disease is difficult to predict at presentation. Diagnosis is based on a compatible clinical and radiological presentation and evidence of non-caseating granulomas. Exclusion of alternative diseases is also required according to clinical presentation. Biopsy samples of superficial lesions should be considered before other sites like per-endoscopic bronchial biopsies or endobronchial ultrasound-guided transbronchial needle aspiration. Therapeutic strategy for lung disease has to take into account the possible spontaneous resolution observed in newly diagnosed patients. Corticosteroids are the first choice when a treatment is decided, which concerns half of patients. Second and third line therapy are based respectively on immunosuppressive drugs and anti-TNFα drugs. Sarcoidosis mortality and morbidity are mainly linked to advanced pulmonary sarcoidosis - lung fibrosis, pulmonary hypertension, bronchial stenosis and chronic pulmonary aspergillosis. "Non anti-inflammatory" treatments have to be considered as well. Clinicians have an essential role in treatment indication, end-point targets and evaluation of response to treatment during follow-up and in finding the best benefice to risk balance. Progress made on pharmacogenetics may offer more personalized treatments for the patients. PMID:26897112

  16. Beryllium-induced lung disease exhibits expression profiles similar to sarcoidosis.

    PubMed

    Li, Li; Silveira, Lori J; Hamzeh, Nabeel; Gillespie, May; Mroz, Peggy M; Mayer, Annyce S; Fingerlin, Tasha E; Maier, Lisa A

    2016-06-01

    A subset of beryllium-exposed workers develop beryllium sensitisation (BeS) which precedes chronic beryllium disease (CBD). We conducted an in-depth analysis of differentially expressed candidate genes in CBD.We performed Affymetrix GeneChip 1.0 ST array analysis on peripheral blood mononuclear cells (PBMCs) from 10 CBD, 10 BeS and 10 beryllium-exposed, nondiseased controls stimulated with BeSO4 or medium. The differentially expressed genes were validated by high-throughput real-time PCR in this group and in an additional group of cases and nonexposed controls. The functional roles of the top candidate genes in CBD were assessed using a pharmacological inhibitor. CBD gene expression data were compared with whole blood and lung tissue in sarcoidosis from the Gene Expression Omnibus.We confirmed almost 450 genes that were significantly differentially expressed between CBD and controls. The top enrichment of genes was for JAK (Janus kinase)-STAT (signal transducer and activator of transcription) signalling. A JAK2 inhibitor significantly decreased tumour necrosis factor-α and interferon-γ production. Furthermore, we found 287 differentially expressed genes overlapped in CBD/sarcoidosis. The top shared pathways included cytokine-cytokine receptor interactions, and Toll-like receptor, chemokine and JAK-STAT signalling pathways.We show that PBMCs demonstrate differentially expressed gene profiles relevant to the immunnopathogenesis of CBD. CBD and sarcoidosis share similar differential expression of pathogenic genes and pathways. PMID:27103383

  17. Cutaneous sarcoidosis and polycythemia vera.

    PubMed

    Pascual, J C; Belinchón, I; Albares, P; Vergara, G; Betlloch, I; Bañuls, J

    2004-11-01

    Polycythemia vera is classified with myelogenous leukaemia, agnogenic myeloid metaplasia and primary thrombocythemia as a myeloproliferative syndrome. Cutaneous symptoms have been reported with polycythemia vera, including facial plethora, aquagenic pruritus, urticaria, purpura, Sweet's syndrome and pyoderma gangrenosum. However, polycythemia vera associated with systemic sarcoidosis has been rarely reported. An unusual case of polycythemia vera associated with cutaneous sarcoidosis is described. PMID:15482300

  18. Granuloma Formation in Pulmonary Sarcoidosis

    PubMed Central

    Broos, Caroline E.; van Nimwegen, Menno; Hoogsteden, Henk C.; Hendriks, Rudi W.; Kool, Mirjam; van den Blink, Bernt

    2013-01-01

    Sarcoidosis is a granulomatous disorder of unknown cause, affecting multiple organs, but mainly the lungs. The exact order of immunological events remains obscure. Reviewing current literature, combined with careful clinical observations, we propose a model for granuloma formation in pulmonary sarcoidosis. A tight collaboration between macrophages, dendritic cells, and lymphocyte subsets, initiates the first steps toward granuloma formation, orchestrated by cytokines and chemokines. In a substantial part of pulmonary sarcoidosis patients, granuloma formation becomes an on-going process, leading to debilitating disease, and sometimes death. The immunological response, determining granuloma sustainment is not well understood. An impaired immunosuppressive function of regulatory T cells has been suggested to contribute to the exaggerated response. Interestingly, therapeutical agents commonly used in sarcoidosis, such as glucocorticosteroids and anti-TNF agents, interfere with granuloma integrity and restore the immune homeostasis in autoimmune disorders. Increasing insight into their mechanisms of action may contribute to the search for new therapeutical targets in pulmonary sarcoidosis. PMID:24339826

  19. [Cardiac sarcoidosis - clinical manifestation and diagnosis].

    PubMed

    Błaut-Jurkowska, Justyna; Podolec, Piotr; Olszowska, Maria

    2016-08-01

    Sarcoidosis is a multisystem inflammatory disease defined histologically by the formation of noncaseating granulomas. The etiology of sarcoidosis remains unknown. Heart involvement in the course of sarcoidosis concerns about 5% of patients. The most common manifestation of cardiac sarcoidosis are conduction abnormalities, arrhythmias and heart failure. The diagnostic algorithm includes performing a clinical history, a 12-lead electrocardiogram (ECG) and an echocardiogram. If any of the initial screening investigations yields an abnormality, diagnostics should be continue using advanced imaging techniques: cardiovascular magnetic resonance (CMR) or fluorodeoxyglucose positron emission tomography (FDG-PET). Nowadays endomyocardial biopsy is not performed routinely.The clinical picture of cardiac sarcoidosis is highly variable. Screening for cardiac sarcoidosis should be performed in all patients diagnosed with extracardiac sarcoidosis. Cardiac sarcoidosis should also be suspected in young patients without a diagnosis of sarcoidosis who present with conduction abnormalities of unknown etiology, because cardiac sarcoidosis may be the first or the only manifestation of the disease. PMID:27591449

  20. [Cardiac sarcoidosis - clinical manifestation and diagnosis].

    PubMed

    Błaut-Jurkowska, Justyna; Podolec, Piotr; Olszowska, Maria

    2016-07-01

    Sarcoidosis is a multisystem inflammatory disease defined histologically by the formation of noncaseating granulomas. The etiology of sarcoidosis remains unknown. Heart involvement in the course of sarcoidosis concerns about 5% of patients. The most common manifestation of cardiac sarcoidosis are conduction abnormalities, arrhythmias and heart failure. The diagnostic algorithm includes performing a clinical history, a 12-lead electrocardiogram (ECG) and an echocardiogram. If any of the initial screening investigations yields an abnormality, diagnostics should be continue using advanced imaging techniques: cardiovascular magnetic resonance (CMR) or fluorodeoxyglucose positron emission tomography (FDG-PET). Nowadays endomyocardial biopsy is not performed routinely.The clinical picture of cardiac sarcoidosis is highly variable. Screening for cardiac sarcoidosis should be performed in all patients diagnosed with extracardiac sarcoidosis. Cardiac sarcoidosis should also be suspected in young patients without a diagnosis of sarcoidosis who present with conduction abnormalities of unknown etiology, because cardiac sarcoidosis may be the first or the only manifestation of the disease. PMID:27590654

  1. Blockade of the Programmed Death-1 Pathway Restores Sarcoidosis CD4+ T-Cell Proliferative Capacity

    PubMed Central

    Braun, Nicole A.; Celada, Lindsay J.; Herazo-Maya, Jose D.; Abraham, Susamma; Shaginurova, Guzel; Sevin, Carla M.; Grutters, Jan; Culver, Daniel A.; Dworski, Ryszard; Sheller, James; Massion, Pierre P.; Polosukhin, Vasiliy V.; Johnson, Joyce E.; Kaminski, Naftali; Wilkes, David S.; Oswald-Richter, Kyra A.

    2014-01-01

    Rationale: Effective therapeutic interventions for chronic, idiopathic lung diseases remain elusive. Normalized T-cell function is an important contributor to spontaneous resolution of pulmonary sarcoidosis. Up-regulation of inhibitor receptors, such as programmed death-1 (PD-1) and its ligand, PD-L1, are important inhibitors of T-cell function. Objectives: To determine the effects of PD-1 pathway blockade on sarcoidosis CD4+ T-cell proliferative capacity. Methods: Gene expression profiles of sarcoidosis and healthy control peripheral blood mononuclear cells were analyzed at baseline and follow-up. Flow cytometry was used to measure ex vivo expression of PD-1 and PD-L1 on systemic and bronchoalveolar lavage–derived cells of subjects with sarcoidosis and control subjects, as well as the effects of PD-1 pathway blockade on cellular proliferation after T-cell receptor stimulation. Immunohistochemistry analysis for PD-1/PD-L1 expression was conducted on sarcoidosis, malignant, and healthy control lung specimens. Measurements and Main Results: Microarray analysis demonstrates longitudinal increase in PDCD1 gene expression in sarcoidosis peripheral blood mononuclear cells. Immunohistochemistry analysis revealed increased PD-L1 expression within sarcoidosis granulomas and lung malignancy, but this was absent in healthy lungs. Increased numbers of sarcoidosis PD-1+ CD4+ T cells are present systemically, compared with healthy control subjects (P < 0.0001). Lymphocytes with reduced proliferative capacity exhibited increased proliferation with PD-1 pathway blockade. Longitudinal analysis of subjects with sarcoidosis revealed reduced PD-1+ CD4+ T cells with spontaneous clinical resolution but not with disease progression. Conclusions: Analogous to the effects in other chronic lung diseases, these findings demonstrate that the PD-1 pathway is an important contributor to sarcoidosis CD4+ T-cell proliferative capacity and clinical outcome. Blockade of the PD-1 pathway may be a

  2. Unilateral Eyelid Edema as Initial Sign of Orbital Sarcoidosis.

    PubMed

    Petrarolha, Sílvia Miguéis Picado; Rodrigues, Bruna Suda; Filho, Flávio David Haddad; Dedivitis, Rogério Aparecido; Petrarolha, Samuel Brunini; Morais, Pedro Martins Tavares Scianni

    2016-01-01

    Introduction. Sarcoidosis is a rare multisystemic granulomatous inflammatory disease of unknown etiology affecting the respiratory system, skin, and eyes. Sarcoidosis outside the lacrimal gland is rare. The case study concerns a patient with a final diagnosis of orbital sarcoidosis. Case Report. A 37-year-old male patient went to the ophthalmic emergency room complaining of pain in the left eye, diplopia, and decreased visual acuity. An external eye examination showed hard and cold edema of the lower eyelid, ocular motility with limitation of adduction, and discreet ipsilateral proptosis. Magnetic resonance of the orbit showed left eye proptosis and thickening and increase of soft tissues associated with heterogeneous impregnation of contrast in the infralateral region of the left eyelid. A biopsy of the lesion showed a chronic inflammatory process, with numerous compact nonnecrotizing granulomas surrounded by lamellar hyaline collagen, providing histological confirmation of sarcoidosis. Discussion. A biopsy of the orbital tumor is essential for the diagnosis of sarcoidosis, in addition to the search for systemic findings such as hilar adenopathy or parenchymal lung disease found in 90% of patients. PMID:27298746

  3. Colonic sarcoidosis: Unusual onset of a systemic disease

    PubMed Central

    Erra, Paola; Crusco, Sonia; Nugnes, Loredana; Pollio, Anna Maria; Di Pilla, Gianni; Biondi, Giuseppe; Vigliardi, Giovanni

    2015-01-01

    Sarcoidosis is a multisystem chronic inflammatory condition of unknown etiology that has the potential to involve every tissue in the body. Sarcoidosis in the gastrointestinal system, and particularly the colon, is very rare. Here, we report the case of a 57-year-old man with no previous diagnosis of sarcoidosis who presented with new onset of abdominal pain and constipation. A colonoscopy revealed that the abdominal pain was caused by an obstructing lesion in the cecum-ascending colon and lacked a clear histologic diagnosis. Radiologic investigation revealed concentric wall thickening of the cecum-ascending colon with multiple satellite lymphadenopathies, highly suggestive of a malignancy. The patient underwent a laparotomy and a right hemicolectomy was performed. A diagnosis of colonic sarcoidosis was made after the resected specimen was examined. Additionally, a chest computed tomography scan revealed lung involvement with atypical radiologic features in the absence of respiratory symptoms. Only histologic examination of the surgical specimen can yield a diagnosis of gastrointestinal sarcoidosis due to the non-specificity of endoscopic and radiologic findings. PMID:25805948

  4. Unilateral Eyelid Edema as Initial Sign of Orbital Sarcoidosis

    PubMed Central

    Filho, Flávio David Haddad; Dedivitis, Rogério Aparecido; Petrarolha, Samuel Brunini

    2016-01-01

    Introduction. Sarcoidosis is a rare multisystemic granulomatous inflammatory disease of unknown etiology affecting the respiratory system, skin, and eyes. Sarcoidosis outside the lacrimal gland is rare. The case study concerns a patient with a final diagnosis of orbital sarcoidosis. Case Report. A 37-year-old male patient went to the ophthalmic emergency room complaining of pain in the left eye, diplopia, and decreased visual acuity. An external eye examination showed hard and cold edema of the lower eyelid, ocular motility with limitation of adduction, and discreet ipsilateral proptosis. Magnetic resonance of the orbit showed left eye proptosis and thickening and increase of soft tissues associated with heterogeneous impregnation of contrast in the infralateral region of the left eyelid. A biopsy of the lesion showed a chronic inflammatory process, with numerous compact nonnecrotizing granulomas surrounded by lamellar hyaline collagen, providing histological confirmation of sarcoidosis. Discussion. A biopsy of the orbital tumor is essential for the diagnosis of sarcoidosis, in addition to the search for systemic findings such as hilar adenopathy or parenchymal lung disease found in 90% of patients. PMID:27298746

  5. Childhood sarcoidosis: Louisiana experience.

    PubMed

    Gedalia, Abraham; Khan, Tahir A; Shetty, Avinash K; Dimitriades, Victoria R; Espinoza, Luis R

    2016-07-01

    A retrospective chart review was conducted to detect patients with sarcoidosis seen by pediatric rheumatology service from the period of 1992 to 2013 at Children's hospital of New Orleans. Twenty-seven patients were identified. The average duration of symptoms before diagnosis was 5 (range 1-120) months. Five patients had onset before the age of 5 years and were diagnosed with early-onset sarcoidosis. The most common manifestations at presentation were constitutional symptoms (62 %) followed by ocular (38 %). During the course of illness, 19/27 (70 %) had multiorgan involvement. Common manifestations included uveitis/iritis (77 %), fever (50 %), hilar adenopathy (42 %), arthritis (31 %), peripheral lympadenopathy (31 %), hepatosplenomegaly (31 %), parenchymal lung disease (27 %), and skin rash (19 %). Unusual manifestations included granulomatous bone marrow disease (3 cases), hypertension (2), abdominal aortic aneurysm (large vessel vasculitis; 1), granulomatous hepatitis (1), nephrocalcinosis (1), membranous nephropathy (1), refractory granulomatous interstitial nephritis with recurrence in transplanted kidney (1), CNS involvement (2), parotid gland enlargement (1), and sensorineural hearing loss (1). Biopsy specimen was obtained in 21/27 (77 %) patients, and demonstration of noncaseating granuloma associated with negative stains for mycobacteria and fungi was seen in 18 patients. Elevated angiotensin-converting enzyme level was seen in 74 % of patients. Treatment with oral prednisone was initiated in symptomatic patients with significant clinical improvement. Low-dose methotrexate (MTX) 10-15 mg/m(2)/week orally, as steroid-sparing agent, was administered in 14 patients. Other immunomodulators included cyclophosphamide (2 patients), etanercept (2), infliximab (2), mycophenolate mofetil (1), and tacrolimus (1). Childhood sarcoidosis is prevalent in Louisiana. Most of the affected children present with a multisystem disease associated with

  6. Extrapulmonary sites of radiogallium accumulation in sarcoidosis

    SciTech Connect

    Sulavik, S.B.; Palestro, C.J.; Spencer, R.P.; Swyer, A.J.; Goldsmith, S.J.; Tierstein, A.S. )

    1990-12-01

    In an effort to detect extrapulmonary sites of radiogallium accumulation in cases of sarcoidosis, 145 separate Ga-67 citrate studies of 114 patients with biopsy-proven sarcoidosis were examined. The most characteristic extrapulmonary radiogallium uptake pattern was the panda sign in 47 patients (41%). The most common site of prominent extrapulmonary radiogallium uptake was the lacrimal glands in 101 patients (88%). Second most common was activity in one or more superficial lymph node regions such as the cervical, axillary, femoral, or inguinal in 19 patients (17%). Other extrapulmonary sites included breast uptake in 6 out of 80 women (8%), prominent splenic and nasal uptake in 9 (8%) patients, periportal accumulation in 7 (6%), and cutaneous/subcutaneous activity in 4 (4%). Because many of these individuals were receiving corticosteroids, the natural (untreated) prevalence of extrapulmonary findings may be even higher. Although the sensitivity and specificity of extrapulmonary radiogallium accumulation has still to be determined, many of the sites may be accessible to biopsy both for diagnostic purposes and to follow the effects of medications. It is therefore suggested that whole-body imaging be performed when radiogallium is administered to patients with suspected or known sarcoidosis.

  7. Sarcoidosis in celiac disease: A page written by genetic variants in IL-18 miRNAs target site?

    PubMed

    Mormile, Raffaella

    2016-05-01

    Sarcoidosis is a chronic idiopathic granulomatous disease. Interleukin-18 (IL-18) has been strongly implicated in the pathogenesis of sarcoidosis. Sarcoidosis shows characteristic microRNAs (miRNAs) profiles. MiRNAs have recently emerged as a new class of modulators of gene expression. MiRNAs are involved in susceptibility to a number of autoimmune diseases promoting and inhibiting the gene expression of different Th1 pro-inflammatory cytokines including IL18. Sarcoidosis has been connected with a variety of autoimmune disorders including celiac disease (CD). CD is a chronic, immune-mediated condition of the small intestine caused by permanent intolerance to dietary gluten. IL-18 has been reported to play an important role in inducing and maintaining inflammation after gluten exposure. MiRNAs expression is significantly altered in CD patients. We hypothesize that sarcoidosis and CD may be the result of common genetic variants in IL-18 miRNA target site. PMID:27063085

  8. Radioisotope scanning in osseous sarcoidosis

    SciTech Connect

    Rohatgi, P.K.

    1980-01-01

    Technetium-99m (/sup 99m/Tc)-labeled pyrophosphate or diphosphonate compounds and gallium-67 citrate (/sup 67/Ga) are two radionuclide scanning agents that are in widespread use in clinical practice. Technetium-99m pyrophosphate is used extensively for bone scanning to detect metastatic bone disease, benign bone tumors, osteomyelitis, benign hypertrophic osteoarthropathy, and Paget's disease. Only two reports describe abnormal /sup 99m/Tc/ pyrophosphate bone scans in four patients with osseous sarcoidosis. Gallium-67 scans are used primarily to localize neoplastic or inflammatory lesions anywhere in the body. In recent years /sup 67/Ga scans have also been used to detect the presence of both pulmonary and extrapulmonary sarcoidosis, but there are no reports describing abnormal uptake of gallium in patients with osseous sarcoidosis. This report describes experience with radioisotope scanning in two patients with osseous sarcoidosis.

  9. Husband and wife with sarcoidosis: possible environmental factors involved

    PubMed Central

    2013-01-01

    Sarcoidosis is a granulomatous multisystem disorder of unclear etiology that involves any organ, most commonly the lung and the lymph nodes. It is hypothesized that the disease derives from the interaction between single or multiple environmental factors and genetically determined host factors. Multiple potential etiologic agents for sarcoidosis have been proposed without any definitive demonstration of causality. We report the case of two patients, husband (57 years old) and wife (55 years old), both suffering from sarcoidosis. They underwent a lymph node biopsy by mediastinoscopy which showed a “granulomatous epithelioid giant cell non-necrotising chronic lymphadenitis”. They had lived up to 3 years ago in the country in a farm, in contact with organic dusts, animals such as dogs, chickens, rabbits, pigeons; now they have lived since about 3 years in an urban area where there are numerous chemical industries and stone quarries. The aim of this case report was to focus on environmental factors that might be related to the pathogenesis of the sarcoidosis. PMID:23351275

  10. Ultrasound findings in cutaneous sarcoidosis

    PubMed Central

    Dybiec, Ewa; Pietrzak, Aldona; Kieszko, Robert; Kanitakis, Jean

    2015-01-01

    The diagnosis of cutaneous sarcoidosis relies mainly on the patient's history, presence of characteristic skin lesions and histological examination that shows a granulomatous, non-necrotizing dermal infiltration. The aim of the study was to assess the ultrasonographic features of cutaneous lesions of sarcoidosis before and after treatment. A 38-year-old woman with systemic sarcoidosis and specific cutaneous lesions was treated with systemic steroids followed by hydroxychloroquine. Ultrasonographic examination of the cutaneous sarcoidosis lesions was performed with a Philips iU 22 and Siemens Acuson S 2000 device, with the use of linear 15 MHz and 17 MHz transducers. Histological examination of skin lesions showed characteristic, naked, non-necrotizing granulomas in the upper dermis. Ultrasound examination revealed well-demarcated, hypoechogenic changes. Power-Doppler scan revealed increased vascularity within the lesions and the surrounding tissue. Clinical improvement of the skin lesions was confirmed by ultrasound examination, which showed a decrease in their size and normalization of dermal echogenicity and vascularity. Ultrasound examination can show cutaneous sarcoidosis lesions and their regression after appropriate treatment. PMID:25821428

  11. Direct quantitation of thoracic gallium-67 uptake in sarcoidosis

    SciTech Connect

    Bourguet, P.; Delaval, P.; Herry, J.Y.

    1986-10-01

    A method of direct quantitation of /sup 67/Ga uptake in the lung is described. The attenuation coefficient requires calculation and is obtained simply for each patient by transmission using a planar radionuclide source. The validity of the method was tested with a phantom (error less than 10%). Forty-three patients with pulmonary and/or mediastinal sarcoidosis were classified. The different groups of patients as defined clinically and radiographically (controls, nonactive, and active sarcoidosis) were well-differentiated (p less than 0.001).

  12. Cardiac Sarcoidosis Masked by Malignant Lymphoma.

    PubMed

    Tobita, Takashige; Hattori, Hidetoshi; Serizawa, Naoki; Suzuki, Tsuyoshi; Uto, Kenta; Momose, Mitsuru; Kameyama, Kaori; Shiga, Tsuyoshi; Okamoto, Shinichiro; Hagiwara, Nobuhisa

    2016-08-01

    There is an association between sarcoidosis and lymphoma, termed "sarcoidosis-lymphoma syndrome." Sarcoidosis is generally detected before lymphoma, but it could present after or even concurrently with the diagnosis of lymphoma. We describe a patient presenting with ventricular tachycardia and lymphadenopathy. A diagnosis of Hodgkin lymphoma was made histologically. The patient responded to treatment, but had persistent (18)F-fluoro-deoxyglucose uptake in the lymph nodes and heart on follow-up positron emission tomography. Second biopsies of lymph node and endomyocardial both confirmed sarcoidosis. This finding suggests that we should maintain a high degree of suspicion for cardiac sarcoidosis in lymphoma patients. PMID:27094123

  13. Spontaneous release of interleukin 2 by lung T lymphocytes in active pulmonary sarcoidosis is primarily from the Leu3+DR+ T cell subset.

    PubMed Central

    Saltini, C; Spurzem, J R; Lee, J J; Pinkston, P; Crystal, R G

    1986-01-01

    The inflammation within the lower respiratory tract of individuals with pulmonary sarcoidosis is dominated by large numbers of helper T lymphocytes that proliferate and spontaneously release interleukin 2 (IL-2). To identify the lymphocyte subpopulation that releases IL-2 in this disorder, lung lymphocytes recovered by bronchoalveolar lavage were characterized using the monoclonal antibodies Leu4 (T lymphocyte), Leu3 (helper/inducer), Leu2 (suppressor/cytotoxic), and anti-HLA-DR, and separated by panning and flow cytometry. The majority of the IL-2 spontaneously released by T cells in the sarcoid lung was contributed by the Leu3+ cell population (Leu3+65 +/- 23 IL-2 units released/10(6) cells per 24 h; Leu2+ 9 +/- 8, P less than 0.04). Further characterization of the lung Leu3+ T cells in sarcoid demonstrated that 30 +/- 3% were expressing HLA-DR molecules on their surface compared with 6 +/- 1% in normals (P less than 0.01). Importantly, the subpopulation of Leu3+ lung T lymphocytes expressing a high intensity of HLA-DR molecules on their surface was responsible for the majority of the release of IL-2 in the sarcoid lung (Leu3+ high-intensity DR 42 +/- 17 U/10(6) cells per 24 h, Leu3+ low-intensity DR 8 +/- 1 U/10(6) cells per 24 h; P less than 0.01). Thus, the spontaneous release of IL-2 in the lung of sarcoid patients appears to be localized to a subset of Leu3+ high-intensity DR ("activated" lung helper/inducer) T lymphocytes. Because the sarcoid lung is characterized by markedly increased numbers of these cells, it is likely that this compartmentalized T cell population plays a major role in sustaining the exaggerated localized immune processes of this disorder. PMID:3486888

  14. Immunogenetics of Disease-Causing Inflammation in Sarcoidosis.

    PubMed

    Grunewald, Johan; Spagnolo, Paolo; Wahlström, Jan; Eklund, Anders

    2015-08-01

    Sarcoidosis is a systemic inflammatory disorder characterised by tissue infiltration by mononuclear phagocytes and lymphocytes with associated non-caseating granuloma formation. Originally described as a disorder of the skin, sarcoidosis can involve any organ with wide-ranging clinical manifestations and disease course. Recent studies have provided new insights into the mechanisms involved in disease pathobiology, and we now know that sarcoidosis has a clear genetic basis largely involving human leukocyte antigen (HLA) genes. In contrast to Mendelian-monogenic disorders--which are generally due to specific and relatively rare mutations often leading to a single amino acid change in an encoded protein--sarcoidosis results from genetic variations relatively common in the general population and involving multiple genes, each contributing an effect of varying magnitude. However, an individual may have the necessary genetic profile and yet the disease will not develop unless an environmental or infectious factor is encountered. Genetics appears also to contribute to the huge variability in clinical phenotype and disease behaviour. Moreover, it has been established that sarcoidosis granulomatous inflammation is a highly polarized T helper 1 immune response that starts with an antigenic stimulus followed by T cell activation via a classic HLA class II-mediated pathway. A complex network of lymphocytes, macrophages, and cytokines is pivotal in the orchestration and evolution of the granulomatous process. Despite these advances, the aetiology of sarcoidosis remains elusive and its pathogenesis incompletely understood. As such, there is an urgent need for a better understanding of disease pathogenesis, which hopefully will translate into the development of truly effective therapies. PMID:25791751

  15. Steroid Refractory Autoimmune Haemolytic Anaemia Secondary to Sarcoidosis Successfully Treated with Rituximab and Mycophenolate Mofetil.

    PubMed

    Green, Sarah; Partridge, Erica; Idedevbo, Edore; Borg, Anton

    2016-01-01

    Autoimmune haemolytic anaemia is not a well-recognised complication of sarcoidosis. We describe the case of a 30-year-old female who presented with acute warm haemolytic anaemia and widespread lymphadenopathy. Sarcoidosis was diagnosed on lymph node biopsy and further investigation. The haemolytic anaemia responded only to a high dose of steroids. Evidence regarding treatment of steroid refractory autoimmune haemolysis secondary to sarcoidosis is lacking. Based on the emergent evidence that both disorders share common immunopathogenic mechanisms involving Th1 and Th17 lymphocytes, our patient was given rituximab and mycophenolate mofetil to successfully suppress the haemolysis and sarcoid activity. PMID:27563474

  16. Steroid Refractory Autoimmune Haemolytic Anaemia Secondary to Sarcoidosis Successfully Treated with Rituximab and Mycophenolate Mofetil

    PubMed Central

    Idedevbo, Edore; Borg, Anton

    2016-01-01

    Autoimmune haemolytic anaemia is not a well-recognised complication of sarcoidosis. We describe the case of a 30-year-old female who presented with acute warm haemolytic anaemia and widespread lymphadenopathy. Sarcoidosis was diagnosed on lymph node biopsy and further investigation. The haemolytic anaemia responded only to a high dose of steroids. Evidence regarding treatment of steroid refractory autoimmune haemolysis secondary to sarcoidosis is lacking. Based on the emergent evidence that both disorders share common immunopathogenic mechanisms involving Th1 and Th17 lymphocytes, our patient was given rituximab and mycophenolate mofetil to successfully suppress the haemolysis and sarcoid activity. PMID:27563474

  17. MRI and FDG PET/CT imaging manifestations of cardiac sarcoidosis.

    PubMed

    Lu, Yang; Sweiss, Nadera J

    2015-12-01

    A 52-year-old man had biopsy-proven sarcoidosis of mediastinal lymph nodes. Cardiac sarcoidosis was confirmed on cardiac MRI with typical imaging features as delayed gadolinium enhancement. Follow-up FDG PET/CT with a 3-day pretest diet modification showed suppression of overall myocardial uptake of FDG but with multifocal abnormal FDG uptake in the myocardium regions corresponding to the previous MRI findings. Additional noncardiac active sarcoidosis involving multiple organ and lymph nodes were also visualized on FDG PET/CT. PMID:26544904

  18. What Are the Signs and Symptoms of Sarcoidosis?

    MedlinePlus

    ... Twitter. What Are the Signs and Symptoms of Sarcoidosis? Many people who have sarcoidosis have no signs ... symptom is more common in women than men. Sarcoidosis Signs and Symptoms The illustration shows the major ...

  19. [Hypercalcemia revealing sarcoidosis in a child].

    PubMed

    Kinné, M; Filleron, A; Salet, R; Saumet, L; Baron Joly, S; Tran, T A

    2016-05-01

    Sarcoidosis is a systemic granulomatosis disease with a classic triad of presentation: typical clinical and radiological signs, presence of tuberculoid granuloma without caseum in histopathology, and exclusion of other causes of granulomatosis, especially tuberculosis. Sarcoidosis is rare in the general population, and even more so in children. In the literature, few cases of sarcoidosis associated with hypercalcemia have been reported in children. We report here the case of a 14-year-old boy with bone marrow and lymph node sarcoidosis suspected, based on poor general condition with hypercalcemia. The patient was treated with hydration, diuretics, and bisphosphonates with good results. We also performed a literature review of published cases of hypercalcemia since 1990 with a diagnosis of sarcoidosis in children, comparing 23 cases (including ours) on clinical and epidemiological, biological, imaging, and histopathological diagnosis. When hypercalcemia is present in the initial clinical presentation, the diagnosis of sarcoidosis is usually made in younger children. Classical locations of the lesions, including lung, skin, and lymph nodes, were highly suggestive of sarcoidosis. Corticosteroids are commonly used to treat sarcoidosis lesions including hypercalcemia. In conclusion, sarcoidosis in children remains difficult to diagnose because the disease is rare and it is common to have nonspecific symptoms in the clinical picture (with diagnosis delayed between 3 months and several years). The classic triad is not always present. Sarcoidosis should be systematically considered and investigated in case of hypercalcemia of unknown cause in children. PMID:27021884

  20. Gallium scan in intracerebral sarcoidosis

    SciTech Connect

    Makhija, M.C.; Anayiotos, C.P.

    1981-07-01

    Sarcoidosis involving the nervous system probably occurs in about 4% of patients. The usefulness of brain scintigraphy in these cases has been suggested. In this case of cerebral sarcoid granuloma, gallium imaging demonstrated the lesion before treatment and showed disappearance of the lesion after corticosteroid treatment, which correlated with the patient's clinical improvement.

  1. Diagnosis and Management of Sarcoidosis.

    PubMed

    Soto-Gomez, Natalia; Peters, Jay I; Nambiar, Anoop M

    2016-05-15

    Sarcoidosis is a systemic disease of unknown etiology characterized by the presence of noncaseating granulomas in any organ, most commonly the lungs and intrathoracic lymph nodes. A diagnosis of sarcoidosis should be suspected in any young or middle-aged adult presenting with unexplained cough, shortness of breath, or constitutional symptoms, especially among blacks or Scandinavians. Diagnosis relies on three criteria: (1) a compatible clinical and radiologic presentation, (2) pathologic evidence of noncaseating granulomas, and (3) exclusion of other diseases with similar findings, such as infections or malignancy. An early and accurate diagnosis of sarcoidosis remains challenging, because initial presentations may vary, many patients are asymptomatic, and there is no single reliable diagnostic test. Prognosis is variable and depends on epidemiologic factors, mode of onset, initial clinical course, and specific organ involvement. The optimal treatment for sarcoidosis remains unclear, but corticosteroid therapy has been the mainstay of therapy for those with significantly symptomatic or progressive pulmonary disease or serious extrapulmonary disease. Refractory or complex cases may require immunosuppressive therapy. Despite aggressive treatment, some patients may develop life-threatening pulmonary, cardiac, or neurologic complications from severe, progressive disease. End-stage disease may ultimately require lung or heart transplantation for eligible patients. PMID:27175719

  2. Cardiac sarcoidosis: diagnosis and management.

    PubMed

    Dubrey, S W; Sharma, R; Underwood, R; Mittal, T

    2015-07-01

    Cardiac sarcoidosis is one of the most serious and unpredictable aspects of this disease state. Heart involvement frequently presents with arrhythmias or conduction disease, although myocardial infiltration resulting in congestive heart failure may also occur. The prognosis in cardiac sarcoidosis is highly variable, which relates to the heterogeneous nature of heart involvement and marked differences between racial groups. Electrocardiography and echocardiography often provide the first clue to the diagnosis, but advanced imaging studies using positron emission tomography and MRI, in combination with nuclear isotope perfusion scanning are now essential to the diagnosis and management of this condition. The identification of clinically occult cardiac sarcoidosis and the management of isolated and/or asymptomatic heart involvement remain both challenging and contentious. Corticosteroids remain the first treatment choice with the later substitution of immunosuppressive and steroid-sparing therapies. Heart transplantation is an unusual outcome, but when performed, the results are comparable or better than heart transplantation for other disease states. We review the epidemiology, developments in diagnostic techniques and the management of cardiac sarcoidosis. PMID:26130811

  3. Pulmonary arterial hypertension in patients with sarcoidosis: the Pulsar single center experience.

    PubMed

    Pabst, Stefan; Hammerstingl, Christoph; Grau, Natalie; Kreuz, Jens; Grohe, Christian; Juergens, Uwe R; Nickenig, Georg; Skowasch, Dirk

    2013-01-01

    Sarcoidosis is a systemic granulomatous disease with unknown etiology. Lungs and lymph nodes are commonly affected. Also, cases of pulmonary hypertension (PH) and pulmonary arterial hypertension (PAH) are described. However, the exact prevalence of PAH in patients with sarcoidosis is unclear. A 111 patients with proven sarcoidosis were recruited from January 2010 to October 2010. All patients were studied prospectively by transthoracic echocardiography (TTE) for the presence of PH. In assumed PH, a right heart catheterization (RHC) followed if there were no other reasons for PH. In 23 of the 111 patients (21%) PH was assumed in TTE. Three patients presented with severe mitral insufficiency III° and IV°, in eight patients PH was supposed to be caused by chronic heart failure or relevant diastolic dysfunction > II°, two patients declined undergoing RHC. Of the ten patients investigated with RHC, four showed a precapillary pulmonary arterial hypertension and in one patient a postcapillary hypertension was diagnosed. All four patients with precapillary PH had a radiologic stage III and IV. In three of the four patients a significantly reduced transfer factor for carbon monoxide (TLCO) <50% was found. All patients with precapillary PH had a chronic course of sarcoidosis lasting ≥13 years. This is the first study which prospectively investigated a large cohort of patients with sarcoidosis for the prevalence of PH and PAH. The prevalence of precapillary PH was found to be at least 3.6% (4/111) and therefore exceeds the prevalence of PAH in the normal population by far. A chronic and progressive lung involvement due to sarcoidosis seems to be the most evident risk factor for developing a sarcoidosis PH. PMID:22826080

  4. Orbital Granuloma Annulare as Presentation of Systemic Sarcoidosis

    PubMed Central

    Kang, Joann J.; Aakalu, Vinay K.; Lin, Amy; Setabutr, Pete

    2014-01-01

    Purpose: To report a unique case of an orbital mass with atypical histopathologic features that although overlap with other granulomatous disorders, likely represents orbital involvement of systemic sarcoidosis. Methods: Observational case report. Results: A 51-year-old woman presented with an orbital mass and was found to have mild proptosis and restriction of ocular motility. The remainder of her ophthalmic exam was unremarkable. Excisional biopsy revealed ill-defined granulomas with central necrosis, chronic inflammation and sclerotic collagen; several features consistent with granuloma annulare. Further systemic workup including laboratory and radiologic studies were compatible with a diagnosis of systemic sarcoidosis. Conclusion: Our case emphasizes the importance of a complete systemic workup with the detection of an orbital granuloma to ensure accurate diagnosis and appropriate management. PMID:23895369

  5. Orbital tumor revealing a systemic sarcoidosis.

    PubMed

    Hannanachi Sassi, Samia; Dhouib, Rim; Kanchal, Fatma; Doghri, Raoudha; Boujelbene, Nadia; Bouguila, Hedi; Mrad, Karima

    2015-01-01

    Ocular involvement is seen in approximately 25% of patients with sarcoidosis. Uveitis is the most common ocular manifestation, but sarcoidosis may involve any part of the eye. Orbital manifestations of sarcoidosis are uncommon with few series in the literature. A 65-year-old woman presented with redness of the right eye and painless, unilateral eyelid swelling. Orbital scanning revealed mass infiltrating the soft tissue of the inferior right orbital quadrant. Biopsy results showed nodular, noncaseating granulomas consistent with sarcoidosis. The complete systemic workup revealed systemic manifestations of sarcoidosis at the time of examination with hilar and mediastinal lymphadenopathies noted on CT scan. The orbital surgical treatment was followed by systemic prednisone therapy with good response. Although rare, orbital sarcoidosis must be considered in the evaluation of orbital tumors in elderly patients. A search for systemic findings should be undertaken and appropriate therapy should be instituted. PMID:25796029

  6. Sarcoidosis of the upper and lower airways.

    PubMed

    Morgenthau, Adam S; Teirstein, Alvin S

    2011-12-01

    Sarcoidosis is a systemic granulomatous disease of undetermined etiology characterized by a variable clinical presentation and disease course. Although clinical granulomatous inflammation may occur within any organ system, more than 90% of sarcoidosis patients have lung disease. Sarcoidosis is considered an interstitial lung disease that is frequently characterized by restrictive physiologic dysfunction on pulmonary function tests. However, sarcoidosis also involves the airways (large and small), causing obstructive airways disease. It is one of a few interstitial lung diseases that affects the entire length of the respiratory tract - from the nose to the terminal bronchioles - and causes a broad spectrum of airways dysfunction. This article examines airway dysfunction in sarcoidosis. The anatomical structure of the airways is the organizational framework for our discussion. We discuss sarcoidosis involving the nose, sinuses, nasal passages, larynx, trachea, bronchi and small airways. Common complications of airways disease, such as, atelectasis, fibrosis, bullous leions, bronchiectasis, cavitary lesions and mycetomas, are also reviewed. PMID:22082167

  7. Sarcoidosis and multiple myeloma: Concurrent presentation of an unusual association.

    PubMed

    Nair, Vidya; Prajapat, Deepak; Talwar, Deepak

    2016-01-01

    Literature on concurrent association of sarcoidosis with lymphoproliferative malignancies other than lymphoma e.g. multiple myeloma is meager. The rarity of the situation prompted us to report this patient who was a 51-year-old woman with a 2-years history of breathlessness, cough with expectoration, chest pain and backache. Initial evaluation revealed mild anemia, increased alkaline phosphatase with chest skiagram showing both lower zone non homogenous opacities with calcified hilar lymph nodes. CECT chest showed mediastinal with bilateral hilar lymphadenopathy, parenchymal fibrosis, traction bronchiectasis, ground glass opacities, septal and peribronchovascular thickening affecting mid and lower lung zones bilaterally. MRI Dorsolumbar spine was suggestive of marrow infiltrative disorder. EBUS FNA of intrathoracic nodes, EBB and TBLB confirmed sarcoidosis. PET CT revealed hyper metabolic activity in lung, multiple lymph nodes and lytic bone lesions. Serum protein electrophoresis and immunofixation revealed a monoclonal paraprotein, immunoglobulin IgG kappa type. Bone marrow biopsy revealed an increase in plasma cells (15%), but no granulomas. Diagnosis of Indolent or multiple myeloma with sarcoidosis was established. 12 cases of sarcoidosis and multiple myeloma have been reported in literature, and mostly preceding the onset of multiple myeloma by many years, in our case both were diagnosed concurrently. PMID:26933313

  8. An epidemiological perspective of the pathology and etiology of sarcoidosis.

    PubMed

    Sawahata, Michiru; Sugiyama, Yukihiko

    2016-01-01

    To update current knowledge on the pathology and etiology of sarcoidosis, here we review previous epidemiological research and discuss age-related differences and historical changes in the clinical characteristics of sarcoidosis we identified over the last four decades in Japan. Extrathoracic lymph node involvement was more common in young patients, while extrathoracic involvement of non-lymphatic organs and hypercalcemia were more common in older patients. Most patients in their 20s presented with bilateral hilar lymphadenopathy, but this was consistently less common among older patients. Over time, the distribution of age at diagnosis has shifted toward the older age group in the United States, Denmark, and Japan. In Japan, the incidence rate has been decreasing among young people, but there has consistently been a second peak among postmenopausal women. Age-related differences in the clinical presentation of sarcoidosis may reflect the pathways of causative antigens and the strengthening of immunoregulatory mechanisms with age. Internal and external environmental factors, such as exposure to diverse microorganisms, ovarian insufficiency, and active vitamin D deficiency, that may contribute to the onset of sarcoidosis must be identified in order to develop strategies for prevention and treatment. PMID:27537712

  9. Sarcoidosis and multiple myeloma: Concurrent presentation of an unusual association

    PubMed Central

    Nair, Vidya; Prajapat, Deepak; Talwar, Deepak

    2016-01-01

    Literature on concurrent association of sarcoidosis with lymphoproliferative malignancies other than lymphoma e.g. multiple myeloma is meager. The rarity of the situation prompted us to report this patient who was a 51-year-old woman with a 2-years history of breathlessness, cough with expectoration, chest pain and backache. Initial evaluation revealed mild anemia, increased alkaline phosphatase with chest skiagram showing both lower zone non homogenous opacities with calcified hilar lymph nodes. CECT chest showed mediastinal with bilateral hilar lymphadenopathy, parenchymal fibrosis, traction bronchiectasis, ground glass opacities, septal and peribronchovascular thickening affecting mid and lower lung zones bilaterally. MRI Dorsolumbar spine was suggestive of marrow infiltrative disorder. EBUS FNA of intrathoracic nodes, EBB and TBLB confirmed sarcoidosis. PET CT revealed hyper metabolic activity in lung, multiple lymph nodes and lytic bone lesions. Serum protein electrophoresis and immunofixation revealed a monoclonal paraprotein, immunoglobulin IgG kappa type. Bone marrow biopsy revealed an increase in plasma cells (15%), but no granulomas. Diagnosis of Indolent or multiple myeloma with sarcoidosis was established. 12 cases of sarcoidosis and multiple myeloma have been reported in literature, and mostly preceding the onset of multiple myeloma by many years, in our case both were diagnosed concurrently. PMID:26933313

  10. HIV-associated chronic immune activation

    PubMed Central

    Paiardini, Mirko; Müller-Trutwin, Michaela

    2013-01-01

    Summary Systemic chronic immune activation is considered today as the driving force of CD4+ T-cell depletion and acquired immunodeficiency syndrome (AIDS). A residual chronic immune activation persists even in HIV-infected patients in which viral replication is successfully inhibited by antiretroviral therapy, with the extent of this residual immune activation being associated with CD4+ T-cell loss. Unfortunately, the causal link between chronic immune activation and CD4+ T-cell loss has not been formally established. This article provides first a brief historical overview on how the perception of the causative role of immune activation has changed over the years and lists the different kinds of immune activation that have been observed to be characteristic for human immunodeficiency virus (HIV) infection. The mechanisms proposed to explain the chronic immune activation are multiple and are enumerated here, as well as the mechanisms proposed on how chronic immune activation could lead to AIDS. In addition, we summarize the lessons learned from natural hosts that know how to ‘show AIDS the door’, and discuss how these studies informed the design of novel immune modulatory interventions that are currently being tested. Finally, we review the current approaches aimed at targeting chronic immune activation and evoke future perspectives. PMID:23772616

  11. Cryptococcal meningitis in a patient with sarcoidosis

    PubMed Central

    Gibson, Maeghan

    2016-01-01

    Sarcoidosis is a multisystem granulomatous disease characterized by the presence of noncaseating granulomas. Case reports have previously described an association between sarcoidosis and cryptococcal infection, but many of these patients were receiving immunosuppression at the time of diagnosis or had limited cutaneous disease. We report a case of cryptococcal meningitis in a 65-year-old man with a new presentation of sarcoidosis who was not receiving immunosuppressive medications. PMID:27034573

  12. Imaging of Sarcoidosis: A Contemporary Review.

    PubMed

    Guidry, Carey; Fricke, Robert Gaines; Ram, Roopa; Pandey, Tarun; Jambhekar, Kedar

    2016-05-01

    Sarcoidosis is a systemic granulomatous disorder with a variety of clinical presentations and radiological appearances. Although it primarily affects the lungs and lymphatics, sarcoidosis potentially involves essentially every organ system. On imaging, sarcoidosis can mimic different disease entities, including primary and metastatic neoplasms, vasculitis, and other granulomatous infections. Definitive diagnosis often requires a combination of clinical, radiological, and histologic information. Imaging plays a crucial role in diagnosis and evaluating response to therapy. This review covers imaging findings in sarcoidosis within each organ system, with an emphasis on the use of imaging in the diagnosis and management of this condition. PMID:27153786

  13. Pulmonary sarcoidosis in a preschool patient.

    PubMed

    Shanthikumar, Shivanthan; Harrison, Jo

    2015-12-01

    Sarcoidosis is a rare disease, especially in the preschool age group where it usually presents with eye, joint, and skin involvement sparing the lungs. Multiple treatment regimes have been described with oral prednisolone being the usual first line treatment. We describe a case of a 4-year-old boy presenting with pulmonary sarcoidosis with no other organ involvement. The child was successfully managed with pulse intravenous methylprednisolone followed by oral prednisolone and has had a good outcome. This case reports a rare presentation of preschool sarcoidosis as well as the novel and successful use of pulse methylprednisolone in paediatric pulmonary sarcoidosis. PMID:26120005

  14. Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers

    PubMed Central

    Bloom, Chloe I.; Graham, Christine M.; Berry, Matthew P. R.; Rozakeas, Fotini; Redford, Paul S.; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A.; Wilkinson, Robert J.; Kendrick, Yvonne; Devouassoux, Gilles; Ferry, Tristan; Miyara, Makoto; Bouvry, Diane; Dominique, Valeyre; Gorochov, Guy; Blankenship, Derek; Saadatian, Mitra; Vanhems, Phillip; Beynon, Huw; Vancheeswaran, Rama; Wickremasinghe, Melissa; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Ho, Ling-pei; Lipman, Marc; O’Garra, Anne

    2013-01-01

    Rationale New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. Objectives To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. Methods We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. Measurements and Main Results An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Conclusions Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the

  15. Ga-67 uptake in the lung in sarcoidosis

    SciTech Connect

    Johnson, D.G.; Johnson, S.M.; Harris, C.C.; Piantadosi, C.A.; Blinder, R.A.; Coleman, R.E.

    1984-02-01

    Images were obtained with Ga-67 and bronchopulmonary lavage performed in 21 patients with sarcoidosis (31 studies). The Ga-67 index, a semiquantitative criterion, was compared to a quantitative computer index based on lung:liver activity ratios; accuracy in predicting active alveolitis (defined by lavage lymphocyte counts) was assessed and differences between 24- and 48-hour studies examined. Computer activity ratios correlated well with the Ga-67 index, which had a sensitivity of 64%, specificity of 71%, 82%, and 77%, respectively, for the computer scores. Scores at 24 and 48 hours were similar. These results suggest that (a) Ga-67 scanning is useful in staging activity in pulmonary sarcoidosis, (b) quantitative computer scores are accurate in predicting disease activity, and (c) scanning can be performed 24 or 48 hours after injection.

  16. Dual Inhibition of Rip2 and IRAK1/4 Regulates IL-1β and IL-6 in Sarcoidosis Alveolar Macrophages and Peripheral Blood Mononuclear Cells.

    PubMed

    Talreja, Jaya; Talwar, Harvinder; Ahmad, Nisar; Rastogi, Ruchi; Samavati, Lobelia

    2016-08-15

    Sarcoidosis is a multisystem granulomatous disease of unknown etiology that primarily affects the lungs. Our previous work indicates that activation of p38 plays a pivotal role in sarcoidosis inflammatory response. Therefore, we investigated the upstream kinase responsible for activation of p38 in sarcoidosis alveolar macrophages (AMs) and PBMCs. We identified that sustained p38 phosphorylation in sarcoidosis AMs and PBMCs is associated with active MAPK kinase 4 but not with MAPK kinase 3/6. Additionally, we found that sarcoidosis AMs exhibit a higher expression of IRAK1, IRAK-M, and receptor interacting protein 2 (Rip2). Surprisingly, ex vivo treatment of sarcoidosis AMs or PBMCs with IRAK1/4 inhibitor led to a significant increase in IL-1β mRNA expression both spontaneously and in response to TLR2 ligand. However, a combination of Rip2 and IRAK-1/4 inhibitors significantly decreased both IL-1β and IL-6 production in sarcoidosis PBMCs and moderately in AMs. Importantly, a combination of Rip2 and IRAK-1/4 inhibitors led to decreased IFN-γ and IL-6 and decreased percentage of activated CD4(+)CD25(+) cells in PBMCs. These data suggest that in sarcoidosis, both pathways, namely IRAK and Rip2, are deregulated. Targeted modulation of Rip2 and IRAK pathways may prove to be a novel treatment for sarcoidosis. PMID:27402699

  17. Physical Activity and Chronic Prostatitis/Chronic Pelvic Pain Syndrome

    PubMed Central

    Zhang, Ran; Chomistek, Andrea K.; Dimitrakoff, Jordan D.; Giovannucci, Edward L.; Willett, Walter C.; Rosner, Bernard A.; Wu, Kana

    2014-01-01

    Purpose Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent urologic disorder among men, but its etiology is still poorly understood. Our objective was to examine the relationship between physical activity and incidence of CP/CPPS in a large cohort of male health professionals. Methods We conducted a prospective cohort study among men in the Health Professionals Follow-up Study followed from 1986 to 2008. The study population included 20,918 men who completed all CP/CPPS questions on the 2008 questionnaire. Leisure-time physical activity, including type and intensity of activity, was measured by questionnaire in 1986. A National Institute of Health Chronic Prostatitis Symptom Index pain score was calculated based on the responses on the 2008 questionnaire. Participants with pain scores ≥ 8 were considered CP/CPPS cases (n=689). Results Higher leisure-time physical activity was associated with lower risk of CP/CPPS. The multivariable-adjusted odds ratio (OR) comparing >35.0 to ≤3.5 MET-h/wk of physical activity was 0.72 (95% confidence interval (CI): 0.56, 0.92, p for trend <0.001). Observed inverse associations between physical activity and CP/CPPS were similar for both moderate- and vigorous-intensity activities. Sedentary behavior, measured as time spent watching television, was not associated with risk of CP/CPPS (p for trend 0.64). Conclusions Findings from this study, the first large scale and most comprehensive study to date on this association, suggest that higher levels of leisure-time physical activity may lower risk of CP/CPPS in middle-aged and older men. PMID:25116086

  18. Systemic Sarcoidosis Unmasked by Cushing's Disease Surgical Treatment.

    PubMed

    Bongetta, Daniele; Zoia, Cesare; Lombardi, Francesco; Lovati, Elisabetta; Lucotti, Pietro; Gaetani, Paolo

    2016-01-01

    Diseases responsive to glucocorticoids, like sarcoidosis, are rarely masked by Cushing's syndrome. An ACTH secreting pituitary adenoma is a possible cause of Cushing's syndrome and its resection can make a subclinical sarcoidosis clear. Only few cases of sarcoidosis following the treatment of hypercortisolism are reported in literature. We report a case of sarcoidosis after the resection of an ACTH secreting pituitary adenoma. PMID:27525010

  19. Systemic Sarcoidosis Unmasked by Cushing's Disease Surgical Treatment

    PubMed Central

    Lombardi, Francesco; Lovati, Elisabetta; Gaetani, Paolo

    2016-01-01

    Diseases responsive to glucocorticoids, like sarcoidosis, are rarely masked by Cushing's syndrome. An ACTH secreting pituitary adenoma is a possible cause of Cushing's syndrome and its resection can make a subclinical sarcoidosis clear. Only few cases of sarcoidosis following the treatment of hypercortisolism are reported in literature. We report a case of sarcoidosis after the resection of an ACTH secreting pituitary adenoma. PMID:27525010

  20. Cutaneous sarcoidosis simulating porokeratosis of Mibelli.

    PubMed

    Elfatoiki, Fatima Zahra; Soussi, Wessal; Chiheb, Soumia; Jabri, Lamia; Benchikhi, Hakima

    2015-01-01

    We report a skin localization of systemic sarcoidosis, which presented with lesions that resemble porokeratosis of Mibelli. Skin biopsy showed non-caseating sarcoidal granuloma. Whereas cutaneous sarcoidosis is present in up to one-third of cases and may present with a wide variety of lesions, our presentation is uncommon. Partial remission was obtained with hydroxychloroquine and prednisone. PMID:26113926

  1. Cutaneous sarcoidosis simulating porokeratosis of Mibelli

    PubMed Central

    Elfatoiki, Fatima Zahra; Soussi, Wessal; Chiheb, Soumia; Jabri, Lamia; Benchikhi, Hakima

    2015-01-01

    We report a skin localization of systemic sarcoidosis, which presented with lesions that resemble porokeratosis of Mibelli. Skin biopsy showed non-caseating sarcoidal granuloma. Whereas cutaneous sarcoidosis is present in up to one-third of cases and may present with a wide variety of lesions, our presentation is uncommon. Partial remission was obtained with hydroxychloroquine and prednisone PMID:26113926

  2. Evaluation of Known or Suspected Cardiac Sarcoidosis.

    PubMed

    Blankstein, Ron; Waller, Alfonso H

    2016-03-01

    Sarcoidosis is a multisystem disorder of unknown cause, and cardiac sarcoidosis affects at least 25% of patients and accounts for substantial mortality and morbidity from this disease. Cardiac sarcoidosis may present with heart failure, left ventricular systolic dysfunction, AV block, atrial or ventricular arrhythmias, and sudden cardiac death. Cardiac involvement can be challenging to detect and diagnose because of the focal nature of the disease, as well as the fact that clinical criteria have limited diagnostic accuracy. Nevertheless, the diagnosis of cardiac sarcoidosis can be enhanced by integrating both clinical and imaging findings. This article reviews the various roles that different imaging modalities provide in the evaluation and management of patients with known or suspected cardiac sarcoidosis. PMID:26926267

  3. Biologic therapies in the treatment of sarcoidosis.

    PubMed

    Saketkoo, Lesley Ann; Baughman, Robert P

    2016-08-01

    Sarcoidosis is a disease of remarkable heterogeneity in organ manifestation, severity and natural history, characterized by the presence of non-caseating granulomas. The majority of cases are acute and self-limited or remit with short courses of glucocorticoids; however, a proportion progress to a life-threatening obliterative fibrotic type associated with significant disability related to pulmonary, cardiac, ocular or central nervous system involvement. Biologic agents have been demonstrated in the successful treatment of refractory organ-threatening sarcoidosis; and though sarcoidosis remains elusive in predictability of progression, strong evidence suggests an indisputably efficacious role for these agents in efforts to stave morbidity and mortality related to sarcoidosis. This paper provides a review of sarcoidosis mechanistic etiopathogenesis to highlight the hypothetical underpinnings of the utility and concerns of current biologic treatments in current use and the potential future applications of newer agents and those under development. PMID:27117719

  4. Impaired monocytic IL-10 production in sarcoidosis and potential link to abnormalities in iNKT cells

    PubMed Central

    Crawshaw, Anjali; Kendrick, Yvonne R; McMichael, Andrew J; Ho, Ling-Pei

    2016-01-01

    Sarcoidosis is a multi-system granulomatous disorder characterised by marked TH1-biased T cell expansion. The cause of T cell over-activity is unknown. We hypothesized that a cellular source for IL-10 might be defective, resulting in loss of regulation of T cell activity. Focusing on IL-10-producing monocytes, we first showed that monocytes isolated from blood of corticosteroid-naïve sarcoidosis patients (n=51) produced less IL-10 compared to controls, and were less able to suppress T cell proliferation. In addition, monocytic IL-10 production correlated negatively with disease activity. We then questioned if defects in iNKT cells (known to be reduced in sarcoidosis), might be responsible for this reduced IL-10 production since iNKT cells can interact with monocytes. We found that monocytic IL-10 production were higher where there were greater numbers of circulating iNKT cells. In vitro, iNKT cells enhanced monocytic IL-10 production. Defective IL-10 production and T cell suppression by sarcoidosis monocytes can be restored by co-culture with iNKT cells, in a CD1d-requiring and contact-dependent process. We suggest that reduced iNKT cell numbers in sarcoidosis may lead to impaired monocytic IL-10 production and unchecked T cell expansion in sarcoidosis. The findings provide fresh insight into sarcoidosis disease mechanism, and interaction between iNKT cells and monocytes. PMID:24723379

  5. Clinical management of pulmonary sarcoidosis.

    PubMed

    Zhou, Ying; Lower, Elyse E; Li, Huiping; Baughman, Robert P

    2016-05-01

    Sarcoidosis is a multisystem disease for which diagnosis relies on the integration of clinical, radiologic, laboratory, and pathologic information. Assessment of clinical features is an important part of the disease evaluation. Computer Tomography provides information not available on routine chest roentgenogram which can assist diagnosing and establishing extent of disease. Monitoring for pulmonary and extra-pulmonary disease facilitates disease management. Patients with quality of life affecting symptoms or threatened end organ damage require systemic treatment which can be recommended in a stepwise fashion. Here, we provide guidance for the initial assessment, disease monitoring, and treatment recommendations for pulmonary and extra pulmonary disease. PMID:26959110

  6. Active "itch fibers" in chronic pruritus.

    PubMed

    Schmelz, M; Hilliges, M; Schmidt, R; Ørstavik, K; Vahlquist, C; Weidner, C; Handwerker, H O; Torebjörk, H E

    2003-08-26

    An itch-specific neuronal pathway was recently discovered in healthy humans and animals. Here the authors report that activity in this specific pathway coincides with itch under pathophysiologic conditions in a patient with chronic pruritus. Microneurographic recordings from the symptomatic area revealed spontaneous activity in six single C-fiber afferents that had the characteristic features of "itch fibers." Itch may be caused by activity in a specific subpopulation of C-fiber afferents. PMID:12939442

  7. Expression Profile of Six RNA-Binding Proteins in Pulmonary Sarcoidosis

    PubMed Central

    Novosadova, Eva; Hagemann-Jensen, Michael; Kullberg, Susanna; Kolek, Vitezslav; Grunewald, Johan; Petrek, Martin

    2016-01-01

    Background Sarcoidosis is characterised by up-regulation of cytokines and chemokine ligands/receptors and proteolytic enzymes. This pro-inflammatory profile is regulated post-transcriptionally by RNA-binding proteins (RBPs). We investigated in vivo expression of six RBPs (AUF1, HuR, NCL, TIA, TIAR, PCBP2) and two inhibitors of proteolytic enzymes (RECK, PTEN) in pulmonary sarcoidosis and compared it to the expression in four control groups of healthy individuals and patients with other respiratory diseases: chronic obstructive pulmonary disease (COPD), asthma and idiopathic interstitial pneumonias (IIPs). Methods RT-PCR was used to quantify the mRNAs in bronchoalveolar (BA) cells obtained from 50 sarcoidosis patients, 23 healthy controls, 30 COPD, 19 asthmatic and 19 IIPs patients. Flow cytometry was used to assess intracellular protein expression of AUF1 and HuR in peripheral blood T lymphocytes (PBTLs) obtained from 9 sarcoidosis patients and 6 healthy controls. Results Taking the stringent conditions for multiple comparisons into consideration, we consistently observed in the primary analysis including all patients regardless of smoking status as well as in the subsequent sub-analysis limited for never smokers that the BA mRNA expression of AUF1 (p<0.001), TIA (p<0.001), NCL (p<0.01) and RECK (p<0.05) was decreased in sarcoidosis compared to healthy controls. TIA mRNA was also decreased in sarcoidosis compared to both obstructive pulmonary diseases (COPD and asthma; p<0.001) but not compared to IIPs. There were several positive correlations between RECK mRNA and RBP mRNAs in BA cells. Also sarcoidosis CD3+, CD4+ and CD8+ PBTLs displayed lower mean fluorescence intensity of AUF1 (p≤0.02) and HuR (p≤0.03) proteins than control healthy PBTLs. Conclusion mRNA expressions of three RBPs (AUF1, TIA and NCL) and their potential target mRNA encoding RECK in BA cells and additionally protein expression of AUF1 and HuR in PBTLs were down-regulated in our sarcoidosis

  8. Assessment of gallium-67 scanning in pulmonary and extrapulmonary sarcoidosis

    SciTech Connect

    Israel, H.L.; Gushue, G.F.; Park, C.H.

    1986-01-01

    Gallium-67 scans have been widely employed in patients with sarcoidosis as a means of indicating alveolitis and the need for corticosteroid therapy. Observation of 32 patients followed 3 or more years after gallium scans showed no correlation between findings and later course: of 10 patients with pulmonary uptake, 7 recovered with minor residuals; of 18 patients with mediastinal of extrathoracic uptake, 10 had persistent or progressive disease; of 4 patients with negative initial scans, 2 had later progression. The value of gallium-67 scans as an aid to diagnosis was studied in 40 patients with extrapulmonary sarcoidosis. In 12 patients, abnormal lacrimal, nodal, or pulmonary uptake aided in selection of biopsy sites. Gallium-67 scans and serum ACE levels were compared in 97 patients as indices of clinical activity. Abnormal gallium-67 uptake was observed in 96.3% of the tests in active disease, and ACE level elevation occurred in 56.3%. In 24 patients with inactive or recovered disease, abnormal gallium-67 uptake occurred in 62.5% and ACE level elevation in 37.5%. Gallium-67 scans have a limited but valuable role in the diagnosis and management of sarcoidosis.

  9. Decreased fibrinolytic activity in juvenile chronic arthritis.

    PubMed Central

    Mussoni, L; Pintucci, G; Romano, G; De Benedetti, F; Massa, M; Martini, A

    1990-01-01

    The basal fibrinolytic activity in 17 children with active juvenile chronic arthritis (JCA) was investigated. It was found that patients with JCA, and particularly those with the systemic form, show decreased plasma fibrinolytic activity and a marked increase in plasminogen activator inhibitor. Additionally, it was found that patients with systemic JCA, but not those with the polyarticular or pauciarticular form, have increased circulating levels of tissue-type plasminogen activator, and endothelial cell protein, suggesting possible endothelial cell participation in systemic JCA. PMID:2125408

  10. Sarcoidosis and mechanisms of unexpected death.

    PubMed

    Byard, Roger W; Manton, Nicholas; Tsokos, Michael

    2008-03-01

    Sarcoidosis is a multisystem disease of uncertain etiology characterized by multifocal areas of discrete and confluent granulomatous inflammation that may rarely be responsible for sudden and unexpected death. Two cases are reported to demonstrate disparate pathological features in fatal cases, one involving cardiac sarcoidosis, and the other neurosarcoidosis with hypothalamic infiltration. Sarcoidosis in individuals dying suddenly may be completely unrelated to the death, contributory or causal. Cardiovascular causes of sudden death in sarcoidosis include arrhythmias associated with cardiomyopathy and ischemia, ventricular rupture, and cor pulmonale due to pulmonary hypertension; respiratory causes include hemorrhage and upper airway obstruction; central nervous system causes include arrhythmias from infiltration of autonomic centers, epilepsy, and obstructive hydrocephalus from brainstem involvement; and gastrointestinal deaths may be due to hemorrhage from esophageal varices associated with portal hypertension. The diagnosis relies on the demonstration of typical noncaseating granulomas and the exclusion of other infective and environmental diseases with similar histopathological findings. PMID:18366580

  11. [Hypercalcemia in sarcoidosis--case report, prevalence, pathophysiology and therapeutic options].

    PubMed

    Ackermann, D

    2007-05-01

    Hypercalcemia is a highly prevalent complication of sarcoidosis. A medical history of a patient with sarcoidosis is shown as case report. Depending on the population studied about 2-63% of sarcoidosis patients show hypercalcemia. The major difference in the prevalence of hypercalcemia may be in part due to the undulating course of subacute sarcoidosis, so hypercalcemia may be missed when serum calcium is not frequently measured. Hypercalciuria appears to be twice as prevalent then hypercalcemia and should be looked for in every sarcoidosis patient. Hypercalcemia in sarcoidosis is due to the uncontrolled synthesis of 1,25-dihydroxyvitamin D3 by macrophages. 1,25-dihydroxyvitamin D3 leads to an increased absorption of calcium in the intestine and to an increased resorption of calcium in the bone. Immunoregulatory properties have been ascribed to 1,25-dihydroxyvitamin D3. It is an important inhibitor of interleukin-2 and of interferon-gamma-synthesis, two cytokines that are important in granuloma formation in sarcoidosis. It is thought that 1,25-dihydroxyvitamin D3 counterregulates uncontrolled granuloma formation. Treatment of hypercalcemia depends on the serum level of hypercalcemia and its persistence. Generally sarcoidotic patients should be advised to avoid sun exposition to reduce vitamin D3 synthesis in the skin, to omit fish oils that are rich of vitamin D and to produce more than two liters urine a day by adapting fluid intake. Although severe hypercalcemia seems to be rare, glucocorticosteroid treatment should be started if corrected total calcium level rises beyond 3 mmol/l. If hypercalcemia is symptomatic, treatment should be started even at lower levels. Glucocorticosteroids act by inhibition of the overly 1alpha-hydroxylase activity of macrophages. Alternatively, treatment with chloroquine or ketoconazole can be established. If isolated hypercalciuria without hypercalcemia is present with evidence for recurrent nephrolithiasis, patients can be treated

  12. Sarcoidosis in Melanoma Patients: Case Report and Literature Review

    PubMed Central

    Beutler, Bryce D.; Cohen, Philip R.

    2015-01-01

    Sarcoidosis is a systemic inflammatory disease characterized by the development of noncaseating granulomas in multiple organ systems. Many hematologic malignancies and solid tumors, including melanoma, have been associated with sarcoidosis. We describe the clinical and pathologic findings of a 54-year-old man with melanoma-associated sarcoidosis. In addition, we not only review the literature describing characteristics of other melanoma patients with sarcoidosis, but also the features of melanoma patients with antineoplastic therapy-associated sarcoidosis. Sarcoidosis has been described in 80 melanoma patients; sufficient information for analysis was provided in 39 of these individuals. In 43.6% of individuals (17 out of 39), sarcoidosis was directly associated with melanoma; in 56.4% of oncologic patients (22 out of 39), sarcoidosis was induced by antineoplastic therapy that had been administered for the treatment of their metastatic melanoma. The discovery of melanoma preceded the development of sarcoidosis in 12 of the 17 (70.5%) individuals who did not receive systemic treatment. Pulmonary and/or cutaneous manifestations of sarcoidosis were common among both groups of patients. Most patients did not require treatment for sarcoidosis. Melanoma patients—either following antineoplastic therapy or without systemic treatment—may be at an increased risk to develop sarcoidosis. In antineoplastic therapy naive melanoma patients, a common etiologic factor—such as exposure to ultraviolet light—may play a role in their developing melanoma and sarcoidosis. PMID:26083934

  13. Chromosome abnormalities in chronic active hepatitis

    PubMed Central

    Stefanescu, D. T.; Moanga, M.; Teodorescu, M.; Brucher, J.

    1972-01-01

    An investigation on human peripheral blood lymphocyte chromosomes in chronic active hepatitis was carried out. A higher percentage of chromatid and chromosome lesions was recorded in all patients studied as compared with control groups—normal individuals, healthy subjects who had suffered from acute viral hepatitis, patients with alcoholic liver disease, and patients with mechanical jaundice due to cancer. The possible origin of these abnormalities is discussed. PMID:5076805

  14. [An original revealing mode of sarcoidosis: Sweet's syndrome].

    PubMed

    Bricha, Myriem; Sqalli, Fatimazzahra; Hammi, Sanae; Bourkadi, Jamal Eddine

    2016-01-01

    Sweet's syndrome is a neutrophilic dermatosis which usually presents as an idiopathic disorder. The combination of Sweet's syndrome and sarcoidosis is rare. We report the clinical case of a Sweet's syndrome revealing sarcoidosis. PMID:27279949

  15. Parotid gland biopsy and /sup 67/Ga imaging correlation in systemic sarcoidosis

    SciTech Connect

    Brantley, S.D.; Orzel, J.A.; Weiland, F.L.; Bower, J.H.

    1987-03-01

    We correlated the results of parotid gland biopsy, chest roentgenograms, and gallium citrate scintigraphy in 24 patients evaluated for possible systemic sarcoidosis. Of 19 patients ultimately proven to have sarcoidosis, 11 (57.9 percent) had positive parotid gland biopsy. The yield of parotid gland biopsy in patients with abnormal gallium parotid activity was only marginally higher (64.7 percent). Abnormal parotid gland uptake of gallium citrate was seen in 17 of these 19 patients (89.5 percent) and was always associated with abnormal lung or perihilar activity. The parotid gland biopsy is a useful technique for obtaining the tissue diagnosis of sarcoidosis; however, gallium scintigraphy should not be performed to select patients as this will only marginally increase the biopsy yield.

  16. Chronic variable stress activates hematopoietic stem cells

    PubMed Central

    Courties, Gabriel; Dutta, Partha; Iwamoto, Yoshiko; Zaltsman, Alex; von zur Muhlen, Constantin; Bode, Christoph; Fricchione, Gregory L.; Denninger, John; Lin, Charles P.; Vinegoni, Claudio; Libby, Peter; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias

    2014-01-01

    Exposure to psychosocial stress is a risk factor for many diseases, including atherosclerosis1,2. While incompletely understood, interaction between the psyche and the immune system provides one potential mechanism linking stress and disease inception and progression. Known crosstalk between the brain and immune system includes the hypothalamic–pituitary–adrenal axis, which centrally drives glucocorticoid production in the adrenal cortex, and the sympathetic–adrenal–medullary axis, which controls stress–induced catecholamine release in support of the fight–or–flight reflex3,4. It remains unknown however if chronic stress changes hematopoietic stem cell activity. Here we show that stress increases proliferation of these most primitive progenitors, giving rise to higher levels of disease–promoting inflammatory leukocytes. We found that chronic stress induced monocytosis and neutrophilia in humans. While investigating the source of leukocytosis in mice, we discovered that stress activates upstream hematopoietic stem cells. Sympathetic nerve fibers release surplus noradrenaline, which uses the β3 adrenergic receptor to signal bone marrow niche cells to decrease CXCL12 levels. Consequently, elevated hematopoietic stem cell proliferation increases output of neutrophils and inflammatory monocytes. When atherosclerosis–prone ApoE−/− mice encounter chronic stress, accelerated hematopoiesis promotes plaque features associated with vulnerable lesions that cause myocardial infarction and stroke in humans. PMID:24952646

  17. Genotyping in the MHC locus: potential for defining predictive markers in sarcoidosis

    PubMed Central

    Seitzer, Ulrike; Gerdes, Johannes; Müller-Quernheim, Joachim

    2002-01-01

    In sarcoidosis, host genetic factors are discussed as contributing to disease susceptibility and course. Since tumor necrosis factor (TNF)-α is a central mediator of granuloma formation and since elevated TNF-α levels are found during active phases of sarcoidosis, genetic polymorphisms correlating with influences on TNF-α levels are of special interest. The complete sequencing of the MHC region and the increase in the number of identified gene polymorphisms in this locus associated with TNF-α production offer the opportunity of detecting new genes associated with sarcoidosis and perhaps of defining disease-associated haplotypes that bear the potential of serving as predictive markers for this disease. PMID:11806841

  18. Management of sarcoidosis in clinical practice.

    PubMed

    Jeny, Florence; Bouvry, Diane; Freynet, Olivia; Soussan, Michael; Brauner, Michel; Planes, Carole; Nunes, Hilario; Valeyre, Dominique

    2016-06-01

    Sarcoidosis is a systemic disease of unknown cause with very diverse presentation, outcome, severity and need for treatments. While some presentations may be very typical, for many patients, the presentation is nonspecific, with shared associations with other diseases at times being by far more frequent or misleading, which can be a cause of significant delay and often several consultations before a diagnosis of sarcoidosis can be confirmed. This is particularly the case when pulmonary manifestations are in the forefront. The diagnosis relies on three well-known criteria. In clinical practice, these criteria are not easily implemented, particularly by physicians without expertise in sarcoidosis, which can lead to a risk of either under- or over-diagnosis. Qualifying the presentation according to sarcoidosis diagnosis is essential. However, it is often not easy to classify the presentation as typical versus compatible or compatible versus inconsistent. Further investigations are needed before any other hypothesis is to be considered. It is important to detect events and to determine whether or not they are indicative of a flare of sarcoidosis. Eventually, treatment needs to be related to the correct indications. The evaluation of the efficacy and safety of treatments is crucial. To address such issues, we present five emblematic cases that illustrate this. PMID:27246591

  19. The Clinical Features of Sarcoidosis: A Comprehensive Review.

    PubMed

    Judson, Marc A

    2015-08-01

    Sarcoidosis has innumerable clinical manifestations, as the disease may affect every body organ. Furthermore, the severity of sarcoidosis involvement may range from an asymptomatic state to a life-threatening condition. This manuscript reviews a wide variety of common and less common clinical characteristics of sarcoidosis. These manifestations are presented organ by organ, although additional sections describe systemic and multiorgan presentations of sarcoidosis. The lung is the organ most commonly involved with sarcoidosis with at least 90 % of sarcoidosis patients demonstrating lung involvement in most series. The skin, eye, liver, and peripheral lymph node are the next most commonly clinically involved organs in most series, with the frequency of involvement ranging from 10 to 30 %. The actual frequency of sarcoidosis organ involvement is probably much higher as it is frequently asymptomatic and may avoid detection. This is particularly common with lung, liver, cardiac, and bone involvement. Cardiac sarcoidosis is present in 25 % of all sarcoidosis but only causes clinical problems in 5 % of them. Nevertheless, unlike sarcoidosis involvement of most other organs, it may be suddenly fatal. Therefore, it is important to screen for cardiac sarcoidosis in all sarcoidosis patients. All sarcoidosis patients should also be screened for eye involvement as asymptomatic patients may have eye involvement that may cause permanent vision impairment. Pulmonary fibrosis from sarcoidosis is usually slowly progressive but may be life-threatening because of the development of respiratory failure, pulmonary hypertension, or hemoptysis related to a mycetoma or bronchiectasis. Some manifestations of sarcoidosis are not organ-specific and probably are the result of a release of mediators from the sarcoid granuloma. Two such manifestations include small fiber neuropathy and fatigue syndromes, and they are observed in a large percentage of patients. PMID:25274450

  20. A functional proteomics approach to the comprehension of sarcoidosis.

    PubMed

    Landi, C; Bargagli, E; Carleo, A; Bianchi, L; Gagliardi, A; Cillis, G; Perari, M G; Refini, R M; Prasse, A; Bini, L; Rottoli, P

    2015-10-14

    Pulmonary sarcoidosis (Sar) is an idiopathic disease histologically typified by non-caseating epitheliod cell sarcoid granulomas. A cohort of 37 Sar patients with chronic persistent pulmonary disease was described in this study. BAL protein profiles from 9 of these Sar patients were compared with those from 8 smoker (SC) and 10 no-smoker controls (NSC) by proteomic approach. Principal Component Analysis was performed to clusterize the samples in the corresponding conditions highlighting a differential pattern profiles primarily in Sar than SC. Spot identification reveals thirty-four unique proteins involved in lipid, mineral, and vitamin Dmetabolism, and immuneregulation of macrophage function. Enrichment analysis has been elaborated by MetaCore, revealing 14-3-3ε, α1-antitrypsin, GSTP1, and ApoA1 as "central hubs". Process Network as well as Pathway Maps underline proteins involved in immune response and inflammation induced by complement system, innate inflammatory response and IL-6signalling. Disease Biomarker Network highlights Tuberculosis and COPD as pathologies that share biomarkers with sarcoidosis. In conclusion, Sar protein expression profile seems more similar to that of NSC than SC, conversely to other ILDs. Moreover, Disease Biomarker Network revealed several common features between Sar and TB, exhorting to orientate the future proteomics investigations also in comparative BALF analysis of Sar and TB. PMID:26342673

  1. Vertebral sarcoidosis: demonstration of bone involvement by computerized axial tomography

    SciTech Connect

    Dinerstein, S.L.; Kovarsky, J.

    1984-08-01

    A report is given of a rare case of vertebral sarcoidosis with negative conventional spinal x-ray films, yet with typical cystic lesions of the spine found incidentally during abdominal computerized axial tomography (CAT). The patient was a 28-year-old black man, who was admitted for evaluation of a 1 1/2-year history of diffuse myalgias, intermittent fever to 102 F orally, bilateral hilar adenopathy, and leukopenia. A technetium polyphosphate bone scan revealed diffuse areas of increased uptake over the sternum, entire vertebral column, and pelvis. Conventional x-ray films of the cervical, thoracic, and lumbar spine, and an AP view of the pelvis were all normal. Chest x-ray film revealed only bilateral hilar adenopathy. During the course of an extensive negative evaluation for infection, an abdominal CAT scan was done, showing multiple, small, sclerotic-rimmed cysts at multiple levels of the lower thoracic and lumbar spine. Bone marrow biopsy revealed only changes consistent with anemia of chronic disease. Mediastinal lymph node biopsy revealed noncaseating granulomas. A tentative diagnosis of sarcoidosis was made, and treatment with prednisone, isoniazid and rifampin was begun. Within two weeks of initiation of prednisone therapy, the patient was symptom-free. A repeat technetium polyphosphate bone scan revealed only a small residual area of mildly increased uptake over the upper thoracic vertebrae.

  2. Acetylcholinesterase activity in chronic renal failure.

    PubMed

    Prall, Y G; Gambhir, K K; Cruz, I A; Blassingale, J; Ampy, F R

    2000-01-21

    Twenty healthy subjects and 39 Chronic Renal Failure patients (CRF-patients) maintained on chronic hemodialysis were used in this investigation to study the changes in acetylcholinesterase (AChE) activity of red blood cells (RBCs). The CRF-patients were all undergoing hemodialysis treatment. AChE activity from the CRF-patients was determined before and after dialysis. An additional objective was to study the effect of chronic renal failure on human red blood cell aging. Blood samples were drawn from controls and CRF-patients in tubes containing EDTA or sodium heparin as an anticoagulant. Red blood cells were purified to avoid interference with monocytes, reticulocytes and leukocytes. The purified RBCs were subfractionated into young (y) (1.08-1.09), mid (m) (1.09-1.11) and old (o) (1.11-1.12) percoll density (g/mL) fractions using a discontinous percoll gradient. The mean +/- SD AChE per gram hemoglobin (U/g Hgb) activities in whole blood (WB), purified human red blood cells (PRBCs), young human red blood cells (y-RBCs), mid age human red blood cells (m-RBCs) and old human red blood cells (o-RBCs) in CRF-patients were 31.2+/-3.43, 29.3+/-3.26, 30.4+/-3.91, 25.1+/-5.25, 17.1+/-6.02 in females and 29.8+/-5.39, 28.8+/-5.29, 28.7+/-5.29, 23.7+/-5.39 and 16.0+/-5.60 in males. AChE activity from CRF-patients were higher than that found in the control subjects. The aging of human RBCs in both the controls and CRF-patients showed a progressive reduction in AChE activity. AChE activity of RBCs from female CRF-patients were significantly higher (p < 0.05) than that of the female control subjects. The RBCs isolated from male CRF-patients showed a higher AChE activity than control males, but a significant difference was only observed with the mid-age-cells. These studies further indicate that AChE activity remained insignificantly different in the various density based age subfractions of RBCs of both CRF-patients and controls. PMID:10698358

  3. Isolated muscular sarcoidosis causing fever of unknown origin: The value of gallium-67 imaging

    SciTech Connect

    Patel, N.; Krasnow, A.; Sebastian, J.L.; Collier, B.D.; Hellman, R.S.; Isitman, A.T. )

    1991-02-01

    An unusual case of a patient with a long-standing fever of unknown origin (FUO) is presented whose gallium-67 ({sup 67}Ga) images revealed increased activity only in the calf muscles bilaterally. Other imaging modalities also failed to show chest or other abnormal findings. Subsequent biopsy of the right gastrocnemius muscle revealed noncaseating granulomas consistent with the diagnosis of sarcoidosis. When using {sup 67}Ga to evaluate a patient with a FUO, imaging of the extremities should always be included. Also, when abnormal Ga-67 uptake is present in the extremities, sarcoidosis should be included in the differential diagnosis.

  4. Physical activity, nutrition, and chronic disease.

    PubMed

    Blair, S N; Horton, E; Leon, A S; Lee, I M; Drinkwater, B L; Dishman, R K; Mackey, M; Kienholz, M L

    1996-03-01

    Epidemiologic, animal, clinical, and metabolic studies demonstrate the independent roles of physical activity and nutrition in the prevention and treatment of several chronic diseases. Fewer data are available to describe the synergistic effects of exercise and diet, and questions remain as to whether and how these two lifestyle factors work together to promote health and prevent disease. This paper briefly reviews many of the known effects of physical activity and nutrition on the prevention and treatment of coronary heart disease, non-insulin-dependent diabetes mellitus, obesity, and osteoporosis as well as how exercise and diet may work together. A discussion of how to increase physical activity levels and how to improve dietary intake also is included. Finally, current exercise and dietary recommendations are summarized, as are directions for future research. PMID:8776222

  5. Pleural effusion and sarcoidosis: an unusual combination.

    PubMed

    Ferreiro, Lucía; San José, Esther; González-Barcala, Francisco Javier; Suárez-Antelo, Juan; Toubes, M Elena; Valdés, Luis

    2014-12-01

    Pleural involvement in sarcoidosis is uncommon and appears in several forms. To document the incidence and characteristics of pleural effusion in sarcoidosis patients, a review of the cases diagnosed in our centre between January 2001 and December 2012 was carried out. One hundred and ninety-five patients with sarcoidosis were identified; three (two men and one woman) presented with unilateral pleural effusion (1.5%): one in the right side and two in the left. Two were in stageii and one was in stageiv. The pleural fluid of the two patients who underwent thoracocentesis was predominantly lymphocytic. One of these patients presented chylothorax and the other had high CA-125levels. In general, these effusions are lymphocyte-rich, paucicellular, serous exudates (sometimes chylothorax) and contain proportionally higher levels of protein than LDH. Most cases are treated with corticosteroids, although it may resolve spontaneously. PMID:24565689

  6. Sarcoidosis in tuberculosis-endemic regions: India

    PubMed Central

    2013-01-01

    Sarcoidosis is a multisystem inflammatory disease of unknown etiology affecting multiple organs. Earlier reports suggested that sarcoidosis was a disease of the developed world. However, recent reports suggest that the disease is found in the developing countries as well. Clinical, radiological, and histopathological similarities with tuberculosis pose a great challenge in countries endemic for tuberculosis. Mantoux test, high resolution computed tomography, and transbronchial lymph node and lung biopsies are diagnostic modalities, which play an important role in the diagnosis of sarcoid. In this review, we look at the epidemiology of sarcoid in tuberculosis-endemic regions, the sarcoidosis-tuberculosis link, clinical profile, diagnostic modalities, dilemma in the diagnosis, and the treatment of this disease. PMID:23803558

  7. Sarcoidosis: a diagnostic challenge in atypical radiologic findings of unilateral lymphadenopathy

    PubMed Central

    Meillier, Andrew; Commodore, Marius

    2015-01-01

    Sarcoidosis is a chronic systemic disease with a wide array of clinical findings. Given that the clinical symptoms are not pathognomonic, chest radiographs have become essential to the initial diagnosis and choice of treatment modality. Diagnosis hinges on ruling out alternative diagnoses; sometimes, advanced radiologic techniques and histopathology are required. On this occasion, we present a case of a patient with generalized symptoms, no significant chest radiograph findings and lymphadenopathy where advanced imaging and pathology assisted in the diagnosis. PMID:26719811

  8. Right Heart Involvement in Patients with Sarcoidosis.

    PubMed

    Patel, Mita B; Mor-Avi, Victor; Murtagh, Gillian; Bonham, Catherine A; Laffin, Luke J; Hogarth, Douglas Kyle; Medvedofsky, Diego; Lang, Roberto M; Patel, Amit R

    2016-05-01

    The left ventricle (LV) is affected in 20-25% of patients with sarcoidosis and its involvement is associated with morbidity and mortality. However, effects of sarcoidosis on the right ventricle (RV) are not well documented. Our aims were to investigate the prevalence of RV dysfunction in patients with sarcoidosis and determine whether it is predominantly associated with direct cardiac involvement, severity of lung disease, or pulmonary hypertension (PH). We identified 50 patients with biopsy-proven extra-cardiac sarcoidosis and preserved LV function, who underwent echocardiography, pulmonary function (PF) testing, and cardiovascular magnetic resonance. RV function was quantified by free wall longitudinal strain. Tricuspid valve Doppler and estimated right atrial pressure were used to estimate systolic pulmonary artery pressure. Myocardial late gadolinium enhancement was considered diagnostic for cardiac sarcoidosis and assumed to involve both ventricles. Of the 50 patients, 28 (56%) had RV dysfunction, 4 with poorly defined PF status. Of the remaining 24 patients, 16 (67%) had lung disease, 8 (33%) had PH, and 10 (42%) had LV involvement. Ten patients had greater than one of these findings, and 4 had all 3. In contrast, in 4/24 patients (17%), RV dysfunction could not be explained by these mechanisms, despite severely reduced RV strain. In conclusion, RV dysfunction is common in patients with sarcoidosis and is usually associated with either direct LV involvement, lung disease, or PH, but may occur in the absence of these mechanisms, suggesting the possibility of isolated RV involvement and underscoring the need for imaging protocols that would include RV strain analysis. PMID:26773449

  9. An In Silico Modeling Approach to Understanding the Dynamics of Sarcoidosis

    PubMed Central

    Aguda, Baltazar D.; Marsh, Clay B.; Thacker, Michael; Crouser, Elliott D.

    2011-01-01

    Background Sarcoidosis is a polygenic disease with diverse phenotypic presentations characterized by an abnormal antigen-mediated Th1 type immune response. At present, progress towards understanding sarcoidosis disease mechanisms and the development of novel treatments is limited by constraints attendant to conducting human research in a rare disease in the absence of relevant animal models. We sought to develop a computational model to enhance our understanding of the pathological mechanisms of and predict potential treatments of sarcoidosis. Methodology/Results Based upon the literature, we developed a computational model of known interactions between essential immune cells (antigen-presenting macrophages, effector and regulatory T cells) and cytokine mediators (IL-2, TNFα, IFNγ) of granulomatous inflammation during sarcoidosis. The dynamics of these interactions are described by a set of ordinary differential equations. The model predicts bistable switching behavior which is consistent with normal (self-limited) and “sarcoidosis-like” (sustained) activation of the inflammatory components of the system following a single antigen challenge. By perturbing the influence of model components using inhibitors of the cytokine mediators, distinct clinically relevant disease phenotypes were represented. Finally, the model was shown to be useful for pre-clinical testing of therapies based upon molecular targets and dose-effect relationships. Conclusions/Significance Our work illustrates a dynamic computer simulation of granulomatous inflammation scenarios that is useful for the investigation of disease mechanisms and for pre-clinical therapeutic testing. In lieu of relevant in vitro or animal surrogates, our model may provide for the screening of potential therapies for specific sarcoidosis disease phenotypes in advance of expensive clinical trials. PMID:21637752

  10. Uptake of fluorine-18-fluorodeoxyglucose in sarcoidosis

    SciTech Connect

    Lewis, P.J.; Salama, A.

    1994-10-01

    Whole-body PET scanning was performed using {sup 18}F-fluorodeoxyglucose (FDG) in two patients with hilar lymphadenopathy in whom the clinical differential diagnosis was between sarcoidosis and lymphoma. Both patients were later proven to have sarcoidosis. Uptake of {sup 18}FDG was seen in both intra- and extrathoracic lesions as well as in associated erythema nodosum. One patient underwent a repeat scan after steroid therapy where a marked decrease in hilar uptake was seen. Fluorine-18-fluorodeoxyglucose uptake is observed in lymph nodes with sarcoid involvement. Further investigation is necessary to assess if quantitative differences exist between sarcoid and malignant lymphadenopathy. 30 refs., 3 figs.

  11. Plasma catecholamine activity in chronic lead poisoning

    SciTech Connect

    deCastro, F.J.

    1990-04-01

    Plasma catecholamines where measured in 15 children with chronic lead poisoning and 15 matched controls by radioimmunassay. The data suggest that plasma catecholamines (norepinephrine and epinphrine) were significantly elevated in chronic lead poisoning. Plasma catecholamine elevation may well be important in the clinical finding of hyperactivity and hypertension associated with chronic lead poisoning.

  12. Prolidase activity in chronic plaque psoriasis patients

    PubMed Central

    Aksoy, Nurten; Ozgöztas, Orhan; Sezen, Hatice; Yesilova, Yavuz; Turan, Enver

    2015-01-01

    Introduction Psoriasis is a chronic, inflammatory, T-cell-mediated and hyperproliferative skin disease characterized by erythematous, squamous, sharply circumscribed and infiltrated plaques. The metabolisms of the collagen proteins undergo considerable changes due to the acceleration of their turnovers as a result of increased prolidase activity in psoriasis patients. Aim To determine the level of prolidase activity in psoriasis patients and evaluate its relationship with the oxidative system. Material and methods The serum prolidase enzyme activity, total antioxidant levels and total oxidant levels of 40 psoriasis patients and a control group including 47 healthy individuals were analyzed by using their serum samples, and their oxidative stress indices were calculated. Results The prolidase levels (p < 0.01), total oxidant levels (p < 0.01) and oxidative stress index levels (p < 0.001) of the patient group were higher than the corresponding parameters in the control group. The total antioxidant level was low (p < 0.01). Although a positive correlation was found between the prolidase and total antioxidant levels and the total oxidant level, no correlation was found between prolidase and the oxidative stress index. Conclusions It has been determined that the activity of the prolidase enzyme increases due to the increased collage turnover in psoriasis patients. Increased serum oxidant levels and oxidative stress indices values may play a role in the pathogenesis of psoriasis. PMID:26015776

  13. Extrapulmonary localization of gallium in sarcoidosis

    SciTech Connect

    Rohatgi, P.K.; Singh, R.; Vieras, F.

    1987-01-01

    This paper describes the spectrum of extrapulmonary localization of gallium in patients with sarcoidosis. The usefulness of Ga-67 scintiscans in detecting clinically occult lesions, in directing clinicians to accessible sites for biopsy, and in following the course of extrapulmonary sites of involvement with therapy is emphasized.

  14. Sarcoidosis of the vagina treated with methotrexate.

    PubMed

    Şahin, N; Solak, A; Karaarslan, S; Doruk, S

    2016-06-01

    We describe the first case of mediolateral episiotomic sarcoidosis of the deep vaginal tissue, without involvement of the pulmonary parenchyma or pulmonary symptoms. A 68-year-old female was admitted with a vaginal mass that had developed about 1 month prior. On bimanual examination, we found a painful solid mass approximately 4 cm in diameter on the episiotomy line of the deep vaginal tissue. The patient underwent pelvic magnetic resonance imaging on suspicion of a malignancy, and a vaginal true-cut biopsy was performed. The biopsy specimen exhibited non-caseating, granulomatous inflammation and many multinucleated giant cells, strongly suggesting sarcoidosis. We had excluded other granulomatous diseases; a final diagnosis was made of stage-1 sarcoidosis in the deep vaginal mass. A 3-month course of methotrexate (2.5 mg/week) was commenced to treat a flare-up of rheumatoid arthritis. The vaginal mass resolved. To the best of our knowledge, this is the first case of sarcoidosis in a deep vaginal mass without pulmonary parenchymal or other solid-organ involvement. PMID:26624970

  15. [Multisystemic sarcoidosis. A clinical case report].

    PubMed

    Cerri, D; Carabelli, A; Vanotti, P; Candiani, F; Bertani, E; Peroni, G; Gelmetti, C

    1990-12-01

    Sarcoidosis is a granulomatous disorder of unknown etiology with a multi-disciplinary interest. However, a multiple organ involvement is not always clearly presented. A case of a 62-year-old woman with cutaneous, pulmonary, ocular, cardiac, bone and articular involvement is described. PMID:2075284

  16. The Circulating Treg/Th17 Cell Ratio Is Correlated with Relapse and Treatment Response in Pulmonary Sarcoidosis Patients after Corticosteroid Withdrawal

    PubMed Central

    Liu, Yongzhe; Qiu, Lan; Wang, Yanxun; Aimurola, Halimulati; Zhao, Yuyue; Li, Shan; Xu, Zuojun

    2016-01-01

    Objectives Pulmonary sarcoidosis is an immune-mediated disease, and some patients can be effectively treated with corticosteroids. However, nearly half of all sarcoidosis patients relapse after corticosteroid withdrawal. Different subsets of CD4+ helper T cells participate in the immunopathogenesis of sarcoidosis. Thus, the aims of our study were to investigate whether the circulating subsets of CD4+ helper T cells were associated with sarcoidosis relapse and with its remission after retreatment. Additionally, we identified a useful biomarker for predicting the relapse and remission of sarcoidosis patients. Methods Forty-two patients were enrolled in the present study who had previously been diagnosed with pulmonary sarcoidosis and treated with corticosteroids. The patients were allocated into either a stable group if they exhibited sustained remission (n = 22) or a relapse group if they experienced clinical or radiological recurrence after treatment withdrawal (n = 20). Peripheral blood cells were collected from these patients and analyzed to determine the frequencies of subsets of circulating CD4+ helper T cells by flow cytometry. The patients in the relapse group were retreated with corticosteroids and immunosuppressive agents and were then reevaluated to determine the frequencies of dynamic subsets of circulating CD4+ helper T cells after remission. Results The frequencies of circulating Tregs were significantly increased concomitant with a decrease in the circulating Th17 cell frequency in the relapsed patients compared with the stable patients. The Treg/Th17 ratio was negatively correlated with sarcoidosis activity and was sensitive to retreatment. In addition, the percentage of isolated CD45RO+Ki67+ Tregs was higher in the patients who were stable and in those who recovered after retreatment than in those who relapsed. Conclusions An imbalance between Tregs and Th17 cells is associated with pulmonary sarcoidosis relapse after corticosteroid withdrawal. The

  17. Old-scar mass and changing surgical perspective: Sarcoidosis

    PubMed Central

    Aktimur, Recep; Aktimur, Sude Hatun; Çolak, Elif; Alıcı, Ömer; Demirağ, Mehmet Derya

    2015-01-01

    Sarcoidosis is a systemic inflammatory disease of an unknown etiology. Skin is involved in 25% of all cases, and 29% of them present as a scar sarcoidosis. Asymptomatic old-scar masses are generally regarded as a foreign body reaction by surgeons and often result in excisional biopsy. We describe a case of a patient who developed sarcoidosis in a 34-year-old appendectomy scar and adjacent inguinal lymph nodes without any local or systemic symptom and radiologic finding. Surgeons should not underestimate the importance of such lesions as a simple condition. Scar sarcoidosis may resolve spontaneously, or the treatment with some topical agents is effective. Furthermore, scar sarcoidosis may be the initial manifestation of systemic sarcoidosis. PMID:25931946

  18. [The "sarcoidosis-lymphoma syndrome"--a lymphocyte dysregulation?].

    PubMed

    Linnenberg, H S; Medici, T C; Rhyner, K

    1992-06-01

    Sarcoidosis and malignant lymphoma can occur in the same patient; sarcoidosis appears first, the malignant lymphoma follows later. The case histories of three patients illustrate what Brinker first coined as the "sarcoidosis-lymphoma syndrome". In two patients a pulmonary sarcoidosis stage I was diagnosed over 30 years respectively 4 years prior to the histological diagnosis of highly malignant Non-Hodgkin lymphoma. The third patient suffered from generalized sarcoidosis with splenomegaly, , granulomatous hepatitis and interstitial lung disease, in addition to which a lymphoproliferative syndrome was diagnosed. Comparing the pathogenesis of malignant lymphoma and sarcoidosis, parallels such as T-cell dysfunction, which probably facilitates malignant transformation of B-cells, become apparent. In both diseases the transforming gene could be the Ebstein-Barr virus. PMID:1495911

  19. Solitary osseous sarcoidosis: a rare reason for pathologic fracture.

    PubMed

    Liu, Bin; Zhang, Xuan; Zhang, Wen; Wang, Ji-bo; Zhang, Feng-chun

    2012-08-01

    Sarcoidosis with osseous involvement as the initial manifestation is rare. Due to lack of other organ involvements, the diagnosis is somehow difficult to establish. We report a case with osseous sarcoidosis as the initial and major manifestation that developed spontaneous bone fracture. Our case emphasizes the importance of histological evidence and exclusion of other diseases i.e. rheumatoid arthritis, before making the diagnosis of osseous sarcoidosis. PMID:20364256

  20. Sarcoidosis Presenting as Isolated Gingival Enlargement: A Rare Case Entity

    PubMed Central

    Aggarwal, Jaihans; Chopra, Deepak; Bagga, Sukhchain; Sethi, Kanika

    2014-01-01

    Sarcoidosis is a non-caseating granulomatous disease . It is a multiorgan inflammatory disorder of unknown etiology. Conditions affecting skin or other organs frequently involve oral cavity and rarely manifest as gingival disease. Here we are reporting a rare case in which gingival hyperplasia was the initial symptom which finally led to the diagnosis of sarcoidosis. Oral mucous membrane needs to be examined carefully as it may constitute in presenting first sign of systemic sarcoidosis. PMID:25584337

  1. Venous Leg Ulcer in a Sarcoidosis Patient: A Case Report

    PubMed Central

    Ohn, Jungyoon; Byun, Sang Young; Kim, In Su

    2015-01-01

    Venous leg ulcers, the most common form of leg ulcers, are relevant to the pathogenicity of pericapillary fibrin cuff. Sarcoidosis, a multiorgan granulomatous disease, causes fibrin deposition in tissues. We report a case of a 50-year-old man with venous leg ulcers coexisting with sarcoidosis. On the basis of the histologic findings, we propose the hypothesis that sarcoidosis patients are prone to the development of venous leg ulcers. PMID:26719645

  2. Gene Regulatory Networks Activated during Chronic Tuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic tuberculosis represents a burden for most of world’s population. Several genes were found to be up-regulated at the late stage of chronic tuberculosis when DNA microarray protocol was used to analyze murine tuberculosis. Rv0348 is a potential transcriptional regulator that is highly expresse...

  3. Gallium-67 scanning to stage the alveolitis of sarcoidosis: correlation with clinical studies, pulmonary function studies, and bronchoalveolar lavage

    SciTech Connect

    Line, B.R.; Hunninghake, G.W.; Keogh, B.A.; Jones, A.E.; Johnston, G.S.; Crystal, R.G.

    1981-04-01

    Current concepts of the pathogenesis of sarcoidosis suggest that the alveolitis of this disorder is related to increased numbers of mononuclear phagocytes and activated T-lymphocytes within the lung. To determine if 67Ga scanning, a procedure commonly used in the evaluation of inflammation, would be useful in staging the alveolitis of sarcoidosis, we studied 41 patients with this disorder and correlated estimates of pulmonary 67Ga accumulation with clinical, roentgenographic, physiologic, and bronchoalveolar lavage studies in these patients. Although 65% of patients with sarcoidosis showed increased amounts of 67Ga accumulation in the lung compared with control subjects, only weak correlations (r less than +/- 0.42, all comparisons) were found between the degree of gallium uptake and the clinical, roentgenographic, or physiologic data. In contrast, there was a strong correlation of 67Ga uptake and the number of lymphocytes and T-lymphocytes recovered from the lungs of these patients by bronchoalveolar lavage (p less than 0.0001, r greater than or equal to 0.67, both comparisons). This data suggested that gallium uptake reflects the intensity of the T-lymphocytes mediated component of the alveolitis in sarcoidosis. Because 67Ga scans are noninvasive, simple to perform, and widely available, they should prove useful to stage the activity of sarcoidosis and to make decisions regarding therapy directed against the alveolitis of the disease.

  4. Gallium-67 scanning to stage the alveolitis of sarcoidosis: correlation with clinical studies, pulmonary function studies, and bronchoalveolar lavage

    SciTech Connect

    Line, B.R.; Hunninghake, G.W.; Keogh, B.A.; Jones, A.E.; Johnston, G.S.; Crystal, R.G.

    1981-04-01

    Current concepts of the pathogenesis of sarcoidosis suggest that the alveolitis of this disorder is related to increased numbers of mononuclear phagocytes and activated T-lymphocytes within the lung. To determine if 67Ga scanning, a procedure commonly used in the evaluation of inflammation, would be useful in staging the alveolitis of sarcoidosis, researchers studied 41 patients with this disorder and correlated estimates of pulmonary /sup 67/Ga accumulation with clinical, roentgenographic, physiologic, and bronchoalveolar lavage studies in these patients. Although 65% of patients with sarcoidosis showed increased amounts of /sup 67/Ga accumulation in the lung compared with control subjects, only weak correlations (r less than +/- 0.42, all comparisons) were found between the degree of gallium uptake and the clinical, roentgenographic, or physiologic data. In contrast, there was a strong correlation of /sup 67/Ga uptake and the number of lymphocytes and T-lymphocytes recovered from the lungs of these patients by bronchoalveolar lavage (p less than 0.0001, r greater than or equal to 0.67, both comparisons). This data suggested that gallium uptake reflects the intensity of the T-lymphocytes mediated component of the alveolitis in sarcoidosis. Because /sup 67/Ga scans are noninvasive, simple to perform, and widely available, they should prove useful to stage the activity of sarcoidosis and to make decisions regarding therapy directed against the alveolitis of the disease.

  5. Sarcoidosis as unusual cause of massive pleural effusion

    PubMed Central

    Joshi, Sharad; Periwal, Pallavi; Dogra, Vikas; Talwar, Deepak

    2015-01-01

    Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Pleural involvement is relatively rare. Development of pleural effusion in sarcoidosis needs to be evaluated for other causes, especially tuberculosis in endemic countries. Sarcoid pleural effusion responds to systemic corticosteroids. We are presenting case of 42 year old male patient of sarcoidosis who developed massive pleural effusion while on treatment with steroids, which was attributed to disease per se. Sarcoidosis as a cause of massive pleural effusion has not been mentioned before in published literature. PMID:26744683

  6. Vitamin-D status and mineral metabolism in two ethnic populations with sarcoidosis.

    PubMed

    Capolongo, Giovanna; Xu, Li Hao Richie; Accardo, Mariasofia; Sanduzzi, Alessandro; Stanziola, Anna Agnese; Colao, Annamaria; Agostini, Carlo; Zacchia, Miriam; Capasso, Giovambattista; Adams-Huet, Beverley; Moe, Orson W; Maalouf, Naim M; Sakhaee, Khashayar; Hsia, Connie C W

    2016-06-01

    Vitamin-D insufficiency and sarcoidosis are more common and severe in African Americans (AA) than Caucasians. In sarcoidosis, substrate-dependent extrarenal 1,25-dihydroxyvitamin-D (1,25-(OH)2D) production is thought to contribute to hypercalciuria and hypercalcemia, and vitamin-D repletion is often avoided. However, the anti-inflammatory properties of vitamin-D may also be beneficial. We prospectively examined serum vitamin-D levels, calcium balance, and the effects of vitamin-D repletion in 86 AA and Caucasian patients with biopsy-proven active sarcoidosis from the USA (US) and Italy (IT) in university-affiliated outpatient clinics. Clinical features, pulmonary function, and calciotropic hormones were measured. 16 patients with vitamin-D deficiency and normal serum ionized calcium (Ca(2+)) were treated with oral ergocalciferol (50,000 IU/week) for 12 weeks. Baseline mineral parameters were similar in US (93% AA) and IT (95% Caucasian) patients irrespective of glucocorticoid treatment. Pulmonary dysfunction was less pronounced in IT patients. Nephrolithiasis (in 11% US, 17% IT patients) was associated with higher urinary calcium excretion. Vitamin-D deficiency was not more prevalent in patients compared to the respective general populations. As serum 25-hydroxyvitamin-D (25-OHD) rose postrepletion, serum 1,25-(OH)2D, γ-globulins, and the previously elevated angiotensin converting enzyme (ACE) levels declined. Asymptomatic reversible increases in Ca(2+) or urinary calcium/creatinine (Ca/Cr) developed in three patients during repletion. In conclusion, Caucasian and AA patients show similar calcium and vitamin D profiles. The higher prevalence of hypercalciuria and nephrolithiasis in sarcoidosis is unrelated to endogenous vitamin-D levels. Vitamin-D repletion in sarcoidosis is generally safe, although calcium balance should be monitored. A hypothesis that 25-OHD repletion suppresses granulomatous immune activity is provided. PMID:27053725

  7. Unsuspected exposure to beryllium: potential implications for sarcoidosis diagnoses.

    PubMed

    Laczniak, Andrew N; Gross, Nathan A; Fuortes, Laurence J; Field, R William

    2014-01-01

    Exposure to Beryllium (Be) can cause sensitization (BeS) and chronic beryllium disease (CBD) in some individuals.  Even relatively low exposures may be sufficient to generate an asymptomatic, or in some cases a symptomatic, immune response. Since the clinical presentation of CBD is similar to that of sarcoidosis, it is helpful to have information on exposure to beryllium in order to reduce misdiagnosis. The purpose of this pilot study is to explore the occurrence of Be surface deposits at worksites with little or no previous reported use of commercially available Be products.  The workplaces chosen for this study represent a convenience sample of businesses in eastern Iowa. One hundred thirty-six surface dust samples were collected from 27 businesses for analysis of Be. The results were then divided into categories by the amount of detected Be according to U.S. Department of Energy guidelines as described in 10 CFR 850.30 and 10 CFR 850.31. Overall, at least one of the samples at 78% of the work sites tested contained deposited Be above the analytical limit of quantitation (0.035 µg beryllium per sample).  Beryllium was detected in 46% of the samples collected. Twelve percent of the samples exceeded 0.2 µg/100 cm² and 4% of the samples exceeded a Be concentration of 3 µg/100 cm². The findings from this study suggest that there may be a wider range and greater number of work environments that have the potential for Be exposure than has been documented previously.  These findings could have implications for the accurate diagnosis of sarcoidosis. PMID:25078645

  8. Gastrointestinal and hepatic manifestations of sarcoidosis.

    PubMed

    Ebert, Ellen C; Kierson, Malca; Hagspiel, Klaus D

    2008-12-01

    Sarcoidosis is a multisystem disease characterized by noncaseating granulomas in the affected organs, including skin, heart, nervous system, and joints. Diagnosis of sarcoidosis is generally based upon a compatible history, demonstration of granulomas in at least two different organs, negative staining and culture for acid fast bacilli, absence of occupational or domestic exposure to toxins, and lack of drug-induced disease. Involvement of the hollow organs is rare. Rather than being due to sarcoidosis, some reported mucosal lesions may simply have incidental granulomas. Extrinsic compression from lymphadenopathy can occur throughout the gastrointestinal tract. The stomach, particularly the antrum, is the most common extrahepatic organ to be involved, while the small bowel is the least common. Liver involvement frequently occurs and ranges from asymptomatic incidental granulomas to portal hypertension from granulomas in the portal triad, usually with relatively preserved liver function. CT scans show hepatosplenomegaly and adenopathy, followed in frequency by focal low-attenuation lesions of the liver and spleen. Ascites is usually a transudate from right heart failure (because of pulmonary hypertension) or portal hypertension (because of biliary cirrhosis). Rarely, an exudative ascites may occur from studding of the peritoneum with nodules. Pancreatic involvement presents as a mass, usually in the head or a diffusely firm, nodular organ. Corticosteroids should be instituted when organ function is threatened, usually lungs, eyes, and central nervous system. Their role in the treatment of hepatic sarcoidosis is unclear. The overall prognosis is good although most patients will have some permanent organ impairment. Cardiac and pulmonary diseases are the main causes of death. PMID:18853979

  9. Gallium-67 uptake in meningeal sarcoidosis

    SciTech Connect

    Ayres, J.G.; Hicks, B.H.; Maisey, M.N.

    1986-07-01

    A case of sarcoidosis limited to the central nervous system is described in which the diagnosis was suggested by high Ga-67 uptake in the cranial and spinal meninges. The diagnosis was confirmed by meningeal biopsy. Treatment with oral corticosteroids resulted in clinical improvement and marked reduction in Ga-67 uptake in the meninges. This is the first reported case of the central nervous system sarcoid diagnosed by Ga-67 imaging.

  10. Gene-environment interactions in sarcoidosis

    PubMed Central

    Culver, Daniel A.; Newman, Lee S.; Kavuru, Mani S.

    2007-01-01

    Susceptibility to most human diseases is polygenic, with complex interactions between functional polymorphisms of single genes governing disease incidence, phenotype, or both. In this context, the contribution of any discrete gene is generally modest for a single individual, but may confer substantial attributable risk on a population level. Environmental exposure can modify the effects of a polymorphism, either by providing a necessary substrate for development of human disease or because the effects of a given exposure modulate the effects of the gene. In several diseases, genetic polymorphisms have been shown to be context-dependent, i.e. the effects of a genetic variant are realized only in the setting of a relevant exposure. Since sarcoidosis susceptibility is dependent on both genetic and environmental modifiers, the study of gene-environment interactions may yield important pathogenetic information and will likely be crucial for uncovering the range of genetic susceptibility loci. However, the complexity of these relationships implies that investigations of gene-environment interactions will require the study of large cohorts with carefully-defined exposures and similar clinical phenotypes. A general principle is that the study of gene-environment interactions requires a sample size at least several-fold greater than for either factor alone. To date, the presence of environmental modifiers has been demonstrated for one sarcoidosis susceptibility locus, HLA-DQB1, in African-American families. This article reviews general considerations obtaining for the study of gene-environment interactions in sarcoidosis. It also describes the limited current understanding of the role of environmental influences on sarcoidosis susceptibility genes. PMID:17560304

  11. Clinical manifestations of sarcoidosis among inner-city African-American dwellers.

    PubMed Central

    Mutlu, Gökhan M.; Rubinstein, Israel

    2006-01-01

    OBJECTIVES: To characterize clinical, radiographic and physiological features of sarcoidosis among African Americans residing in inner-city Chicago. METHODS: This is a retrospective review of medical records of 75 African Americans with biopsy-proven sarcoidosis from internal medicine and pulmonary clinics at three inner-city, acute care hospitals in Chicago. RESULTS: The number of organs involved was 1.77 +/- 0.94 (mean +/- SD). The most common sites for tissue diagnosis were lung (49%), skin (19%) and lymph nodes (16%). Thirty-six (48%) patients had stage-2 and -3 disease on chest x-ray. Electrocardiographic changes and ocular involvement were detected in 23% and 21% of patients, respectively. Nineteen (25%) patients had obstructive defect (FEV1 1.71 +/- 0.78 L/s), 15 (20%) had a restrictive defect [TLC 4.1 +/- 1.2 L (63.9 +/- 9.2% predicted)]. Three patients had both restrictive and obstructive defect. Forced vital capacity and FEV1 declined by 0.26 L and 0.09 L/s per year, respectively, in patients with an obstructive defect. Most patients (91%) were treated with prednisone for 3.8 +/- 3.9 years (range 0-20 years). CONCLUSIONS: African Americans with sarcoidosis residing in inner-city Chicago express a high rate of chronic progressive disease necessitating corticosteroid therapy. Further studies are warranted to elucidate the reasons underlying this paradigm. PMID:16895285

  12. Sarcoidosis Occurring After Solid Cancer: A Nonfortuitous Association

    PubMed Central

    Grados, Aurélie; Ebbo, Mikael; Bernit, Emmanuelle; Veit, Véronique; Mazodier, Karin; Jean, Rodolphe; Coso, Diane; Aurran-Schleinitz, Thérèse; Broussais, Florence; Bouabdallah, Reda; Gravis, Gwenaelle; Goncalves, Anthony; Giovaninni, Marc; Sève, Pascal; Chetaille, Bruno; Gavet-Bongo, Florence; Weitten, Thierry; Pavic, Michel; Harlé, Jean-Robert; Schleinitz, Nicolas

    2015-01-01

    Abstract The association between cancer and sarcoidosis is controversial. Some epidemiological studies show an increase of the incidence of cancer in patients with sarcoidosis but only few cases of sarcoidosis following cancer treatment have been reported. We conducted a retrospective case study from internal medicine and oncology departments for patients presenting sarcoidosis after solid cancer treatment. We also performed a literature review to search for patients who developed sarcoidosis after solid cancer. We describe the clinical, biological, and radiological characteristics and outcome of these patients. Twelve patients were included in our study. Various cancers were observed with a predominance of breast cancer. Development of sarcoidosis appeared in the 3 years following cancer and was asymptomatic in half of the patients. The disease was frequently identified after a follow-up positron emission tomography computerized tomography evaluation. Various manifestations were observed but all patients presented lymph node involvement. Half of the patients required systemic therapy. With a median follow-up of 73 months, no patient developed cancer relapse. Review of the literature identified 61 other patients for which the characteristics of both solid cancer and sarcoidosis were similar to those observed in our series. This report demonstrates that sarcoidosis must be considered in the differential diagnosis of patients with a history of malignancy who have developed lymphadenopathy or other lesions on positron emission tomography computerized tomography. Histological confirmation of cancer relapse is mandatory in order to avoid unjustified treatments. This association should be consider as a protective factor against cancer relapse. PMID:26181571

  13. Cutaneous localization of Ga-67 in systemic sarcoidosis

    SciTech Connect

    Rohatgi, P.K.

    1981-03-01

    /sup 67/Ga scans have been used in patients with sarcoidosis to assess noninvasively the intensity of alveolitis and to detect areas of extrathoracic involvement. To the author's knowledge, this is the first report of the localization of gallium in cutaneous lesions of a patient with sarcoidosis.

  14. Recognition of distinctive patterns of gallium-67 distribution in sarcoidosis

    SciTech Connect

    Sulavik, S.B.; Spencer, R.P.; Weed, D.A.; Shapiro, H.R.; Shiue, S.T.; Castriotta, R.J. )

    1990-12-01

    Assessment of gallium-67 ({sup 67}Ga) uptake in the salivary and lacrimal glands and intrathoracic lymph nodes was made in 605 consecutive patients including 65 with sarcoidosis. A distinctive intrathoracic lymph node {sup 67}Ga uptake pattern, resembling the Greek letter lambda, was observed only in sarcoidosis (72%). Symmetrical lacrimal gland and parotid gland {sup 67}Ga uptake (panda appearance) was noted in 79% of sarcoidosis patients. A simultaneous lambda and panda pattern (62%) or a panda appearance with radiographic bilateral, symmetrical, hilar lymphadenopathy (6%) was present only in sarcoidosis patients. The presence of either of these patterns was particularly prevalent in roentgen Stages I (80%) or II (74%). We conclude that simultaneous (a) lambda and panda images, or (b) a panda image with bilateral symmetrical hilar lymphadenopathy on chest X-ray represent distinctive patterns which are highly specific for sarcoidosis, and may obviate the need for invasive diagnostic procedures.

  15. Gallium 67 citrate scanning and serum angiotensin converting enzyme levels in sarcoidosis

    SciTech Connect

    Gupta, R.G.; Bekerman, C.; Sicilian, L.; Oparil, S.; Pinsky, S.M.; Szidon, J.P.

    1982-09-01

    Gallium 67 citrate scans and serum angiotension converting enzyme (ACE) levels were obtained in 54 patients with sarcoidosis and analyzed in relation to clinical manifestation. /sup 67/Ga scans were abnormal in 97% of patients with clinically active disease (n = 30) and in 71% of patients with inactive disease (n = 24). Serum ACE levels were abnormally high (2 standard deviations above the control mean) in 73% of patients with clinically active disease and in 54% of patients with inactive disease. Serum ACE levels correlated significantly with /sup 67/Ga uptake score (r = .436; p < .005). The frequency of abnormal /sup 67/Ga scans and elevated serum ACE levels suggests that inflammatory activity with little or no clinical expression is common in sarcoidosis. Abnormal /sup 67/Ga scans were highly sensitive (97%) but had poor specificity (29%) to clinical disease activity. The accuracy of negative prediction of clinical activity by normal scans (87%) was better than the accuracy of positive prediction of clinical activity by abnormal scans (63%). /sup 67/Ga scans can be used to support the clinical identification of inactive sarcoidosis.

  16. Plasma thymic hormone activity in patients with chronic mucocutaneous candidiasis

    PubMed Central

    Kirkpatrick, C. H.; Greenberg, Lynn E.; Chapman, S. W.; Goldstein, G.; Lewis, Verna M.; Twomey, J. J.

    1978-01-01

    To further characterize the immunological abnormalities in patients with chronic mucocutaneous candidiasis, the thymic hormone activity in their plasma was measured. Of the sixteen patients in the study, seven had chronic diffuse candidiasis, five had candidiasis with endocrinopathies and four had candidiasis with thymoma. Only one patient, an anergic child with chronic diffuse candidiasis had severe deficiency of plasma thymic hormone activity. Two patients, a woman with candidiasis and multiple endocrinopathies and an elderly man with metastatic epithelial thymoma had supranormal values. These studies indicate that the immunological deficit in most patients with these forms of chronic mucocutaneous candidiasis is not due to deficiency of a thymic inductive activity and suggest that an intrinsic defect exists in the maturation of antigen-responsive lymphoid cells. PMID:743805

  17. FDG PET/CT Evidence of Effective Treatment of Cardiac Sarcoidosis With Adalimumab.

    PubMed

    Miller, Christina T; Sweiss, Nadera J; Lu, Yang

    2016-05-01

    A 53-year-old man with mediastinal lymph node biopsy and cardiac MRI-proven cardiac sarcoidosis (CS) received treatment with pacemaker and steroids. FDG PET/CT showed active CS despite treatment with prednisone and methotrexate. Addition of weekly adalimumab (Humira) injections was introduced for 3 months. Follow-up FDG PET/CT showed complete resolution of CS as well as improvement of other sarcoid lesions in the thoracic lymph nodes. PMID:26828145

  18. Vascular function and ocular involvement in sarcoidosis.

    PubMed

    Siasos, Gerasimos; Paraskevopoulos, Theodoros; Gialafos, Elias; Rapti, Aggeliki; Oikonomou, Evangelos; Zaromitidou, Marina; Mourouzis, Konstantinos; Siasou, Georgia; Gouliopoulos, Nikolaos; Tsalamandris, Sotiris; Vlasis, Konstantinos; Stefanadis, Christodoulos; Papavassiliou, Athanasios G; Tousoulis, Dimitris

    2015-07-01

    Ocular involvement occurs in sarcoidosis (Sar) patients mainly in the form of uveitis. This study was designed to determine if uveitis in Sar patients is associated with vascular impairment. We enrolled 82 Sar patients and 77, age and sex matched, control subjects (Cl). Sar patients were divided into those with ocular sarcoidosis (OS) and those without ocular sarcoidosis (WOS). Endothelial function was evaluated by flow-mediated dilation (FMD). Pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) as a measure of arterial wave reflections. Although there was no significant difference in sex, age and mean arterial pressure, patients with OS compared to WOS patients and Cl subjects had impaired FMD (p<0.001), increased AIx (p=0.02) and increased PWV (p=0.001). Interestingly, impaired FMD in Sar patients was independently, from possible covariates (age, sex, smoking habits, arterial hypertension, dyslipidemia), associated with increased odds of ocular involvement (odds ratio=1.69, p=0.001). More precisely ROC curve analysis revealed that FMD had a significant diagnostic ability for the detection of OS (AUC=0.77, p<0.001) with a sensitivity of 79% and a specificity of 68% for an FMD value below 6.00%. To conclude in the present study we have shown that ocular involvement in Sar patients is associated with impaired endothelial function and increased arterial stiffness. These results strengthen the vascular theory which considers uveitis a consequence of vascular dysfunction in Sar patients and reveals a possible clinical importance of the use of endothelial function tests. PMID:25937082

  19. ProKaSaRe Study Protocol: A Prospective Multicenter Study of Pulmonary Rehabilitation of Patients With Sarcoidosis

    PubMed Central

    Lingner, Heidrun; Großhennig, Anika; Flunkert, Kathrin; Buhr-Schinner, Heike; Heitmann, Rolf; Tönnesmann, Ulrich; van der Meyden, Jochen

    2015-01-01

    Background Available data assessing the efficacy of pulmonary rehabilitation for patients with chronic sarcoidosis are scant; for Germany, there are none at all. Objective To gain information about the benefit of in-house pulmonary rehabilitation for patients with chronic sarcoidosis and for the health care system, we intend to collect data in a prospective multicenter “real-life” cohort trial. Methods ProKaSaRe (Prospektive Katamnesestudie Sarkoidose in der pneumologischen Rehabilitation) [Prospective Catamnesis Study of Sarcoidosis in Pulmonary Rehabilitation] will assess a multimodal 3-week inpatient pulmonary rehabilitation program for adult patients with chronic sarcoidosis over a 1-year follow-up time. Defined specific clinical measurements and tests will be performed at the beginning and the end of the rehabilitation. In addition, questionnaires concerning health-related quality of life and the patients’ symptoms will be provided to all patients. Inclusion criteria will be referral to one of the 6 participating pulmonary rehabilitation clinics in Germany for sarcoidosis and age between 18 and 80 years. Patients will only be excluded for a lack of German language skills or the inability to understand and complete the study questionnaires. To rule out seasonal influences, the recruitment will take place over a period of 1 year. In total, at least 121 patients are planned to be included. A descriptive statistical analysis of the data will be performed, including multivariate analyses. The primary outcomes are specific health-related quality of life (St George’s Respiratory Questionnaire) and exercise capacity (6-minute walk test). The secondary outcomes are several routine lung function and laboratory parameters, dyspnea scores and blood gas analysis at rest and during exercise, changes in fatigue, psychological burden, and generic health-related quality of life (36-item Short Form Health Survey). Results Funding was obtained on October 12, 2010

  20. Predictors of objective cough frequency in pulmonary sarcoidosis.

    PubMed

    Sinha, Aish; Lee, Kai K; Rafferty, Gerrard F; Yousaf, Nadia; Pavord, Ian D; Galloway, James; Birring, Surinder S

    2016-05-01

    Cough is a common symptom of pulmonary sarcoidosis. This study aimed to quantify cough frequency, and investigate its relationship with cough reflex sensitivity, pulmonary function and health status.32 patients with pulmonary sarcoidosis were compared with 40 healthy controls. Cough reflex sensitivity to capsaicin, objective 24-h cough counts, cough-specific health status, cough severity and cough triggers were measured. The predictors of cough frequency in sarcoidosis were determined in a multivariate analysis.Objective cough frequency was significantly raised in patients with sarcoidosis compared with healthy controls (p<0.001) and patients with cough had an impaired health status. Patients with pulmonary sarcoidosis had a heightened cough reflex sensitivity compared with healthy controls (p<0.001). Only cough reflex sensitivity was significantly associated with objective cough frequency in multivariate analysis, explaining 42% of the variance (p<0.001). There was no association between cough frequency, lung function, number of organs involved, chest radiograph stage or serum angiotensin-converting enzyme levels.Cough is a common and significant symptom in patients with sarcoidosis. Ambulatory objective cough monitoring provides novel insights into the determinants of cough in sarcoidosis, suggesting that cough reflex sensitivity may be more important than lung function and other measures of disease severity, and this should be investigated further. PMID:26846840

  1. Sarcoidosis presenting as non-scarring non-scalp alopecia.

    PubMed

    Dan, Luke; Relic, John

    2016-08-01

    In this article we describe a 39-year-old man who presented with non-scarring non-scalp alopecia of his limbs as the initial presentation of sarcoidosis. Alopecia is a rare cutaneous manifestation of sarcoidosis. A literature review has found only one other example of sarcoidosis presenting as non-scarring non-scalp alopecia in an area other than the scalp in a patient who was otherwise asymptomatic. Several reported cases have described scarring alopecia of the scalp, which is the area of skin most commonly affected by sarcoidosis. There has been one documented case of sarcoidosis manifesting as total body non-scarring alopecia in a patient who had systemic symptoms of sarcoidosis. Other cases have presented rare cutaneous manifestations of sarcoidosis but in all these cases several other organ systems have been involved, and the patient has had systemic symptoms on presentation or the cutaneous presentation did not include non-scalp non-scarring alopecia. PMID:25823524

  2. Metabolomics connects aberrant bioenergetic, transmethylation, and gut microbiota in sarcoidosis

    PubMed Central

    Geamanu, Andreea; Gupta, Smiti V.; Bauerfeld, Christian

    2016-01-01

    Sarcoidosis is a systemic granulomatous disease of unknown etiology. Granulomatous inflammation in sarcoidosis may affect multiple organs, including the lungs, skin, CNS, and the eyes, leading to severe morbidity and mortality. The underlying mechanisms for sustained inflammation in sarcoidosis are unknown. We hypothesized that metabolic changes play a critical role in perpetuation of inflammation in sarcoidosis. 1H nuclear magnetic resonance (NMR)-based untargeted metabolomic analysis was used to identify circulating molecules in serum to discriminate sarcoidosis patients from healthy controls. Principal component analyses (PCA) were performed to identify different metabolic markers and explore the changes of associated biochemical pathways. Using Chenomx 7.6 NMR Suite software, we identified and quantified metabolites responsible for such separation in the PCA models. Quantitative analysis showed that the levels of metabolites, such as 3-hydroxybutyrate, acetoacetate, carnitine, cystine, homocysteine, pyruvate, and trimethylamine N-oxide were significantly increased in sarcoidosis patients. Interestingly, succinate, a major intermediate metabolite involved in the tricyclic acid cycle was significantly decreased in sarcoidosis patients. Application of integrative pathway analyses identified deregulation of butanoate, ketone bodies, citric cycle metabolisms, and transmethylation. This may be used for development of new drugs or nutritional modification. PMID:27489531

  3. A rare presentation of sarcoidosis with nasal bone involvement

    PubMed Central

    Uslu, Selen; Korkmaz, Hakan; Çetinkol, Yeliz

    2016-01-01

    Background: Sarcoidosis is a multisystem granulomatous inflammatory disease that is induced by infectious or noninfectious environmental antigens in a genetically susceptible host. Tuberculosis and sarcoidosis are two diseases with similar clinical and pathologic findings. The link between these two diseases has been extensively studied. Objective: Herein we describe a case of sarcoidosis associated with tuberculosis, treated for tuberculosis, and, 1 year, later presented with a nasal dorsal lump and skin lesions on the extremities. Methods: Case report with clinical description. Results: Our patient had a history of skin and cervical lymphadenopathy symptoms 1 year earlier and was treated with antituberculosis drugs in an outer medical center. Therapy had cured cervical lymphadenopathies, with no improvement in skin lesions. On appearance of the nasal dorsal lump, she presented to our outpatient clinic. We retrieved the previous specimens of the patient, which revealed coexistence of necrotizing granulomas with non-necrotizing granulomas, which was strongly indicative of the coexistence of tuberculosis and sarcoidosis. Radiologic, histopathologic, and microbiologic investigation revealed the diagnosis of sarcoidosis with nasal, cutaneous, and pulmonary involvement. Treatment with prednisolone and hydroxychloroquine resulted in dramatic improvement of nasal bone, pulmonary, and skin lesions within 2 weeks. Conclusion: The clinical presentation of sarcoidosis can be complex, and the differential diagnosis from tuberculosis can be challenging. Atypical clinical pictures also can cause delays in diagnosis and proper management. In patients with granulomatous lesions that are unresponsive to antituberculosis therapy, physicians must be alerted to the possibility of coexistent sarcoidosis. PMID:27103561

  4. Pulmonary alveolar proteinosis: another autoimmune disease associated with sarcoidosis?

    PubMed

    Boerner, Eda Burcu; Costabel, Ulrich; Wessendorf, Thomas Ernst; Theegarten, Dirk; Hetzel, Martin; Drent, Marjolein; Bonella, Francesco

    2016-01-01

    Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by the accumulation of surfactant phospholipids and lipoproteins within the alveoli.  Here we report on a female patient who was diagnosed with autoimmune PAP and successfully treated with whole lung lavage (WLL). 15 months after PAP diagnosis the patient developed marked fatigue. Additional tests revealed the diagnosis of sarcoidosis. We can only speculate that PAP and sarcoidosis in our patient are linked to each other based on the fact that other autoimmune disorders have also been associated with sarcoidosis. PMID:27055841

  5. CT of Hepatic Sarcoidosis: Small Nodular Lesions Simulating Metastatic Disease

    PubMed Central

    Ufuk, Furkan; Herek, Duygu

    2015-01-01

    Summary Background Sarcoidosis is a multisystemic inflammatory disease of unknown origin. The lymphoid system and the lungs are the most commonly involved organs. The frequency of signs or symptoms of hepatic involvement is very low. Case Report We present a case of symptomatic granulomatous liver disease secondary to sarcoidosis, mimicking a metastatic disease on ultrasonography and CT. Conclusions Hepatic involvement in sarcoidosis might be a perplexing diagnostic problem. The decisive CT finding with respect to the differential diagnosis was the absence of a mass effect and intact vascular architecture around the lesions. PMID:25908950

  6. [Lichenoid sarcoidosis on skin tattoos produced by traditional herbal treatments].

    PubMed

    Soyinka, F; Badejo, O; Laja, A O

    1981-01-01

    An unusual case of generalised sarcoidosis of the skin on tattoo marks done two years for "medicinal" purposes on a 56 year old woman is presented. The lesions were lichenoid and scaly in appearance with closely grouped papules. The old tattoo marks on the skin were not involved and areas of skin between the new tattoo marks were also spared. In addition, the sarcoidosis lesion were pruritic and burning. The circumstantial evidence indicated the medical agent applied on the tattoo wounds as the provocative factor for the development of sarcoidosis of the skin. PMID:7026927

  7. Optic neuropathy associated with systemic sarcoidosis

    PubMed Central

    Burton, Ben J.; Graham, Elizabeth M.; Plant, Gordon T.

    2016-01-01

    Objective: To identify and follow a series of 52 patients with optic neuropathy related to sarcoidosis. Methods: Prospective observational cohort study. Results: The disorder was more common in women and affected a wide age range. It was proportionately more common in African and Caribbean ethnic groups. Two clinical subtypes were identified: the more common was a subacute optic neuropathy resembling optic neuritis; a more slowly progressive optic neuropathy arose in the remaining 17%. Sixteen (31%) were bilateral. Concurrent intraocular inflammation was seen in 36%. Pain arose in only 27% of cases. An optic perineuritis was seen in 2 cases, and predominate involvement of the chiasm in one. MRI findings showed optic nerve involvement in 75% of cases, with adjacent and more widespread inflammation in 31%. Treatment with corticosteroids was helpful in those with an inflammatory optic neuropathy, but not those with mass lesions. Relapse of visual signs arose in 25% of cases, necessitating an increase or escalation of treatment, but relapse was not a poor prognostic factor. Conclusions: This is a large prospective study of the clinical characteristics and outcome of treatment in optic neuropathy associated with sarcoidosis. Patients who experience an inflammatory optic neuropathy respond to treatment but may relapse. Those with infiltrative or progressive optic neuropathies improve less well even though the inflammatory disorder responds to therapy. PMID:27536707

  8. Unmasking sarcoidosis following surgery for Cushing disease

    PubMed Central

    Diernaes, Jon E.F.; Bygum, Anette; Poulsen, Per L.

    2016-01-01

    ABSTRACT We present a patient with Cushing disease apparently suppressing sarcoidosis, which was unmasked following surgical resection of a pituitary adrenocorticotropin (ACTH)-producing microadenoma. Case report and a short review of the literature published in this area. A 46-year-old Caucasian woman presented with symptoms of hypercortisolism such as progressive weight gain, Cushingoid appearance, proximal myopathy, easy bruising, and amenorrhea. Blood testing including inferior petrosal sinus sampling uncovered an ACTH-producing microadenoma in the right aspect of the anterior pituitary gland for which the patient underwent transphenoidal resection. Maintenance corticosteroid therapy was implemented, and the signs and symptoms of Cushing disease began to resolve. Three months after surgery, multiple erythematous painful nodules developed on the patient's arms. Erythema nodosum (EN) was diagnosed clinically and a suspicion of underlying sarcoidosis was substantiated by lung imaging and elevated plasma interleukin (IL)-2 receptor. One month later, the lesions spontaneously resolved without therapy other than maintenance glucocorticoid replacement. Physicians should be aware that patients undergoing successful treatment of Cushing syndrome may have a flare-up or emergence of a corticosteroid-responsive disease. PMID:27375832

  9. Unmasking sarcoidosis following surgery for Cushing disease.

    PubMed

    Diernaes, Jon E F; Bygum, Anette; Poulsen, Per L

    2016-01-01

    We present a patient with Cushing disease apparently suppressing sarcoidosis, which was unmasked following surgical resection of a pituitary adrenocorticotropin (ACTH)-producing microadenoma. Case report and a short review of the literature published in this area. A 46-year-old Caucasian woman presented with symptoms of hypercortisolism such as progressive weight gain, Cushingoid appearance, proximal myopathy, easy bruising, and amenorrhea. Blood testing including inferior petrosal sinus sampling uncovered an ACTH-producing microadenoma in the right aspect of the anterior pituitary gland for which the patient underwent transphenoidal resection. Maintenance corticosteroid therapy was implemented, and the signs and symptoms of Cushing disease began to resolve. Three months after surgery, multiple erythematous painful nodules developed on the patient's arms. Erythema nodosum (EN) was diagnosed clinically and a suspicion of underlying sarcoidosis was substantiated by lung imaging and elevated plasma interleukin (IL)-2 receptor. One month later, the lesions spontaneously resolved without therapy other than maintenance glucocorticoid replacement. Physicians should be aware that patients undergoing successful treatment of Cushing syndrome may have a flare-up or emergence of a corticosteroid-responsive disease. PMID:27375832

  10. Diagnosis and treatment of cardiac sarcoidosis.

    PubMed

    Kusano, Kengo F; Satomi, Kazuhiro

    2016-02-01

    Sarcoidosis is a systemic granulomatous disease of unknown aetiology. The frequency of cardiac involvement (cardiac sarcoidosis (CS)) varies in the different geographical regions, but it has been reported that it is an absolutely important prognostic factor in this disease. Complete atrioventricular block is the most common, and ventricular tachycardia/ventricular fibrillation the second most common arrhythmia in this disease, both of which are associated with cardiac sudden death. Diagnosing CS is sometimes difficult because of the non-specific ECG and echocardiographic findings, and CS is sometimes misdiagnosed as dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy or an idiopathic ventricular aneurysm, and therefore, endomyocardial biopsy is important, but has a low sensitivity. Another problem is the recognition of isolated types of CS. Recently, MRI and (18)F-fluorodeoxyglucose positron emission tomography have been demonstrated to be useful tools for the non-invasive diagnosis of CS as well as therapeutic evaluation tools, but are still unsatisfactory. Treatment of CS is usually done by corticosteroid therapy to control inflammation, prevent fibrosis and protect from any deterioration of the cardiac function, but the long-term outcome is still in debate. Despite the advancement of non-pharmacological approaches for CS (pacing, defibrillators and catheter ablation) to improve the prognosis, there are still many issues remaining to resolve diagnosing and managing CS. Here, we attempt a review of the clinical evidence, with special focus on the current understanding of this disease and showing the current strategies and remaining problems of diagnosing and managing CS. PMID:26643814

  11. Abnormalities in iNKT cells are associated with impaired ability of monocytes to produce IL-10 and suppress T-cell proliferation in sarcoidosis.

    PubMed

    Crawshaw, Anjali; Kendrick, Yvonne R; McMichael, Andrew J; Ho, Ling-Pei

    2014-07-01

    Sarcoidosis is a multisystem granulomatous disorder characterized by marked T-cell expansion of T helper 1 (Th1) cells. The cause of T-cell overactivity is unknown. We hypothesized that interleukin-10 (IL-10) production by a yet undefined cell type might be defective, resulting in loss of regulation of T-cell activity. Focusing on IL-10-producing monocytes, we first showed that monocytes isolated from the peripheral blood of corticosteroid-naïve sarcoidosis patients (n = 51) produced less IL-10 compared to controls, and were less able to suppress T-cell proliferation. In addition, monocytic IL-10 production correlated negatively with disease activity score. As invariant natural killer T (iNKT) cells are known to both interact with monocytes and be reduced in sarcoidosis patients, we then asked whether iNKT-specific defects might be responsible for this reduced IL-10 production. We found that greater numbers of circulating iNKT cells was associated with higher IL-10 production. Moreover, iNKT cells enhanced monocytic IL-10 production in vitro. Defective IL-10 production and T-cell suppression by sarcoidosis monocytes could be restored following their coculture with iNKT cells, in a CD1d- and cell contact-dependent process. We suggest that reduced iNKT-cell numbers in sarcoidosis may lead to impaired monocytic IL-10 production and unchecked T-cell expansion in sarcoidosis. These findings provide fresh insight into the mechanism of sarcoidosis disease, and interaction between iNKT cells and monocytes. PMID:24723379

  12. FoxP3+ regulatory T cells suppress early stages of granuloma formation but have little impact on sarcoidosis lesions.

    PubMed

    Taflin, Cécile; Miyara, Makoto; Nochy, Dominique; Valeyre, Dominique; Naccache, Jean-Marc; Altare, Frédéric; Salek-Peyron, Pascale; Badoual, Cécile; Bruneval, Patrick; Haroche, Julien; Mathian, Alexis; Amoura, Zahir; Hill, Gary; Gorochov, Guy

    2009-02-01

    Sarcoidosis is characterized by a disproportionate Th1 granulomatous immune response in involved organs. It is also associated with both peripheral and intratissular regulatory T cell (Treg) expansion. These cells exhibit powerful antiproliferative activity, yet do not completely inhibit the production of either tumor necrosis factor-alpha or interferon-gamma. The origin of the observed Treg amplification and, more importantly, its impact on the evolution of sarcoidosis remain unresolved issues. Here, we show that CD4(+)CD45RA(-)FoxP3(bright) Tregs proliferate and accumulate within granulomas. However, circulating and tissue Treg numbers are neither correlated with the dissemination of the disease nor correlated locally with the extent of granulomatous inflammation. Rather, we found a positive correlation between the presence of Tregs in renal granulomas and the degree of interstitial fibrosis (r = 0.46, P = 0.03, n = 20). Furthermore, Treg depletion accelerates in vitro granuloma growth in mononuclear cell cultures of healthy controls, but not in those from patients with active sarcoidosis. The results of this study show that although healthy Tregs suppress the initial steps of granuloma formation, they have no positive influence on sarcoidosis lesions. Our findings argue for a more preventive than curative effect of Tregs on inflammatory processes. PMID:19147826

  13. Chronic psychological stress activates BMP4-dependent extramedullary erythropoiesis.

    PubMed

    Vignjević, Sanja; Budeč, Mirela; Marković, Dragana; Dikić, Dragoslava; Mitrović, Olivera; Mojsilović, Slavko; Durić, Sanja Vranješ; Koko, Vesna; Cokić, Bojana Beleslin; Cokić, Vladan; Jovčić, Gordana

    2014-01-01

    Psychological stress affects different physiological processes including haematopoiesis. However, erythropoietic effects of chronic psychological stress remain largely unknown. The adult spleen contains a distinct microenvironment favourable for rapid expansion of erythroid progenitors in response to stressful stimuli, and emerging evidence suggests that inappropriate activation of stress erythropoiesis may predispose to leukaemic transformation. We used a mouse model to study the influence of chronic psychological stress on erythropoiesis in the spleen and to investigate potential mediators of observed effects. Adult mice were subjected to 2 hrs daily restraint stress for 7 or 14 consecutive days. Our results showed that chronic exposure to restraint stress decreased the concentration of haemoglobin in the blood, elevated circulating levels of erythropoietin and corticosterone, and resulted in markedly increased number of erythroid progenitors and precursors in the spleen. Western blot analysis revealed significantly decreased expression of both erythropoietin receptor and glucocorticoid receptor in the spleen of restrained mice. Furthermore, chronic stress enhanced the expression of stem cell factor receptor in the red pulp. Moreover, chronically stressed animals exhibited significantly increased expression of bone morphogenetic protein 4 (BMP4) in the red pulp as well as substantially enhanced mRNA expression levels of its receptors in the spleen. These findings demonstrate for the first time that chronic psychological stress activates BMP4-dependent extramedullary erythropoiesis and leads to the prolonged activation of stress erythropoiesis pathways. Prolonged activation of these pathways along with an excessive production of immature erythroid cells may predispose chronically stressed subjects to a higher risk of leukaemic transformation. PMID:24283209

  14. Clonal expansion of lung V delta 1+ T cells in pulmonary sarcoidosis.

    PubMed Central

    Forrester, J M; Newman, L S; Wang, Y; King, T E; Kotzin, B L

    1993-01-01

    Sarcoidosis is a multisystem disease of unknown etiology characterized by the presence of noncaseating granulomas in involved tissues. To investigate a potential role for gamma/delta T cells in the pathogenesis of pulmonary sarcoidosis, we studied lung and blood T cells from patients for preferential expression of particular gamma/delta T cell receptors. An abnormally high percentage of gamma/delta cells was found in the blood of some patients. However, the increased percentage did not reflect an increase in absolute number, and appeared to be secondary to a decrease in T cells expressing alpha/beta receptors. Furthermore, as in normals, the circulating gamma/delta cells in patients predominantly expressed V gamma 9/V delta 2 receptors, a subset that was not enriched at the site of disease. In contrast, in the lung, an increased percentage of gamma/delta cells expressing V delta 1 was found in a subset of patients. Importantly, these cells demonstrated evidence of prior activation by selectively expanding in vitro in the presence of interleukin 2. Furthermore, an analysis of junctional region sequences revealed their clonal nature. These clonal expansions of V delta 1+ cells in pulmonary sarcoidosis provide evidence for a disease process that involves specific recognition of a local antigen by T cells, and contributes new information regarding the nature of the as yet undefined antigenic stimulus. PMID:8423227

  15. Propionibacterium acnes isolated from lymph nodes of patients with sarcoidosis.

    PubMed

    de Brouwer, Bart; Veltkamp, Marcel; Wauters, Carla A; Grutters, Jan C; Janssen, Rob

    2015-01-01

    Propionibacterium acnes has been repeatedly suggested as a candidate causative agent of sarcoidosis. It is the only microorganism that has been isolated from sarcoid lesions by bacterial culture so far and this has been described in Japanese patients only. We report two non-Japanese patients in whom mediastinoscopy was performed in order to obtain lymph node tissue for histopathology, which was suggestive for sarcoidosis. Bacterial culture of these uncontaminated mediastinal lymph nodes revealed P. acnes in both patients. As shown in these two cases, P. acnes can be isolated from sterile biopsied sarcoid lymph nodes of non-Japanese patients and supports the belief that there is an etiologic link between P. acnes sarcoidosis. Further elucidation could provide an opening to novel strategies using antibiotics for treating sarcoidosis. PMID:26422574

  16. Myositis and eosinophilia in a patient with sarcoidosis.

    PubMed Central

    al-Saffar, Z. S.; Kelsey, C. R.; Kennet, R. P.; Webley, M.

    1994-01-01

    We present a patient with muscle manifestations of sarcoidosis associated with raised creatine kinase levels, eosinophilia and interstitial lung disease. She had significant improvement on prednisolone 30 mg per day. PMID:7824422

  17. Pulmonary sarcoidosis presenting with acute respiratory distress syndrome

    PubMed Central

    Arondi, Sabrina; Valsecchi, Alberto; Borghesi, Andrea; Monti, Stefano

    2016-01-01

    Sarcoidosis is a common disease that involve almost constantly the lung. Usually the onset is insidious, and symptoms are slowly ingravescent. Very rarely, as in the case here reported, sarcoidosis can cause an acute respiratory failure with acute respiratory distress syndrome (ARDS). A 20-year-old girl from Pakistan presented for acute fatigue, fever, and cough with a chest X-ray displayed the micronodular interstitial disease. Despite of anti-tuberculosis therapy, ARDS developed in a few days requiring continuous positive airway pressure treatment. Examinations on transbronchial specimens obtained by bronchoscopy permitted to reach the diagnosis of sarcoidosis and steroid therapy improved rapidly clinical conditions. This is the first case report reported in Europe that confirms the rare onset of sarcoidosis as ARDS. Steroid therapy allows to cure rapidly this severe complication. PMID:26933462

  18. An Isolated Mass in the Palm, Starting Manifestation of Sarcoidosis

    PubMed Central

    Ghorbanhoseini, Mohammad; Yazdi, Hamidreza; Naseh, Hossein; Hafezi, Poopak

    2016-01-01

    Sarcoidosis is a systemic disease that is characterized with noncaseating granulomatous nodules which present in multiple organs specially lungs (90%). Incidence of masses due to Sarcoidosis in upper extremity is low and most cases present in association with involvement of pulmonary hilary lymph nodes. In this article we present a rare case of Sarcoidosis which presented as a single soft tissue mass in hand without osseous or pulmonary hillary lymph node involvement. Incidence of involvement of musculoskeletal system is 1-5 %, mostly it occurs in small bones in hands and feet. In most cases involvement of soft tissue in extremities is accompanied with bone lesions. Those cases of soft tissue involvement are generally coincide with pulmonary lymph nodules. To the authors` knowledge, this is the first case of Sarcoidosis that presents without spreading in bones or pulmonary hilar lymph nodes. PMID:26894226

  19. Successful treatment of refractory midgut bleeding with ocreotide and corticosteroids in a dialysis patient with suspected sarcoidosis.

    PubMed

    Velasco, Nestor; Imtiaz, Toufeeq; Shah, Amir Ali; Koulaouzidis, Anastasios

    2016-01-01

    We present a case of severe and recurrent small-bowel bleeding, due to multiple intestinal angiodysplasias, in a female patient with chronic renal failure due to suspected sarcoidosis. Over the years, she required numerous admissions and >200 units of blood for symptomatic anaemia. However, following a small-bowel capsule endoscopy that revealed several small-bowel angiectasis, she was treated successfully with octreotide and corticosteroids. Her transfusion requirements and hospital admissions were reduced drastically. Moreover, hypercalcaemia and liver function tests also normalised after treatment and double-balloon enteroscopy confirmed the complete resolution of these angiodysplasias. This case presentation confirms the usefulness of octreotide in the management of small-bowel angiodysplasias in dialysis patients and highlights the additional benefit of corticosteroids in portal hypertension due to suspected sarcoidosis. PMID:27417989

  20. Study of Toll-like receptor gene loci in sarcoidosis

    PubMed Central

    Schürmann, M; Kwiatkowski, R; Albrecht, M; Fischer, A; Hampe, J; Müller-Quernheim, J; Schwinger, E; Schreiber, S

    2008-01-01

    Sarcoidosis is a multi-factorial systemic disease of granulomatous inflammation. Current concepts of the aetiology include interactions of unknown environmental triggers with an inherited susceptibility. Toll-like receptors (TLRs) are main components of innate immunity and therefore TLR genes are candidate susceptibility genes in sarcoidosis. Ten members of the human TLR gene family have been identified and mapped to seven chromosomal segments. The aim of this study was to investigate all known TLR gene loci for genetic linkage with sarcoidosis and to follow positive signals with different methods. We analysed linkage of TLR gene loci to sarcoidosis by use of closely flanking microsatellite markers in 83 families with 180 affected siblings. We found significant linkage between sarcoidosis and markers of the TLR4 gene locus on chromosome 9q (non-parametric linkage score 2·63, P = 0·0043). No linkage was found for the remaining TLR gene loci. We subsequently genotyped 1203 sarcoidosis patients from 997 families, 1084 relatives and 537 control subjects for four single nucleotide polymorphisms of TLR4, including Asp299Gly and Thr399Ile. This genotype data set was studied by case–control comparisons and transmission disequilibrium tests, but showed no significant results. In summary, TLR4 − w ith significant genetic linkage results − appears to be the most promising member of the TLR gene family for further investigation in sarcoidosis. However, our results do not confirm the TLR4 polymorphisms Asp299Gly and Thr399Ile as susceptibility markers. Our results rather point to another as yet unidentified variant within or close to TLR4 that might confer susceptibility to sarcoidosis. PMID:18422738

  1. Evidence for a genetic component in familial sarcoidosis

    SciTech Connect

    Rybicki, B.A.; Harrington, D.; Major, M.

    1994-09-01

    Sarcoidosis is a disease with reported familial clustering, but a putative hereditary component has not been established. We analyzed 33 sarcoid index cases with a positive family history and their 596 1st and 2nd degree relatives to determine if the distribution of disease was consistent with a genetic etiology. Prevalence of sarcoidosis was twice as high in 1st degree relatives of index cases compared to 2nd degree relatives (8.5% vs. 3.9%; p=0.016). Recurrence risk ratios (defined as the risk of disease in relatives divided by the population prevalence) were calculated in 2nd degree relatives after making an ascertainment correction. A single gene model fit the observed results better than a polygenic model for a range of sarcoidosis prevalance. A greater shared environment among siblings compared to parents and offspring did not appear to increase risk of sarcoidosis based on a higher prevalance of disease in the latter (7.1% vs. 10.7%; p=0.313). However, the age of diagnosis in affected parent-offspring pairs was more consistent with a combined genetic and environmental etiology than either component alone. In summary, these results suggest a genetic component, possibly a single gene, increases disease risk in family members of sarcoidosis cases. A segregation analysis is planned to more thoroughly evaluate the evidence for both genetic and non-genetic transmission of sarcoidosis in these families.

  2. Hepatic sarcoidosis: pathogenesis, clinical context, and treatment options.

    PubMed

    Syed, Umer; Alkhawam, Hassan; Bakhit, Mena; Companioni, Rafael A Ching; Walfish, Aron

    2016-09-01

    Sarcoidosis is typically characterized as a non-caseating granulomatous disease that has the ability to affect multiple different organ systems. Although extra-thoracic sarcoidosis can occur in the presence and also without lung involvement, isolated extra-pulmonary disease is rare. The liver is the third most commonly affected organ system after the lungs and lymph nodes. When discussing hepatic sarcoidosis it is important to keep in mind that many patients in this population may not present as one would typically expect since most of the patients are asymptomatic or have mild presentations. Therefore, the diagnosis can be difficult at times since no single laboratory or imaging study can definitively diagnose this systemic disease. In the rare case of some patients where there is difficulty in discerning between different pathologies, the use of image-guided tissue biopsy may be necessary to establish a diagnosis. At the current time, there are no clear guidelines for the management of hepatic sarcoidosis and are mostly dependent on a patient's clinical status at time of presentation. The current body of research in regard to treatment suggests steroids to be the mainstay of therapy. However, there is a role for additional immunosuppressive therapy in cases where the initial treatment is refractory to steroids. In this manuscript, we discussed the pathogenesis of liver sarcoidosis and context of its presentation. In addition, the differential diagnosis and imaging evaluation in this population is discussed. Finally, treatment options are reviewed in setting of previous studies for liver sarcoidosis. PMID:27175775

  3. The alveolitis of pulmonary sarcoidosis. Evaluation of natural history and alveolitis-dependent changes in lung function

    SciTech Connect

    Keogh, B.A.; Hunninghake, G.W.; Line, B.R.; Crystal, R.G.

    1983-08-01

    Current concepts of the pathogenesis of pulmonary sarcoidosis suggest that a mononuclear cell alveolitis, comprised of activated T-lymphocytes and activated alveolar macrophages, precedes and modulates the formation of granuloma and fibrosis. To evaluate the natural history of this alveolitis and determine the relationship it has to subsequent changes in lung function, 19 untreated patients with pulmonary sarcoidosis without extrapulmonary manifestations were studied with bronchoalveolar lavage, /sup 67/Ga scanning, and pulmonary function tests to evaluate lung T-cells, lung alveolar macrophages, and lung function, respectively. In patients with sarcoidosis, low intensity alveolitis (lung T-cells less than or equal to 28% of all lung effector cells and/or /sup 67/Ga scan negative) was much more common (80% of all observations) than high intensity alveolitis (lung T-cells greater than 28% and /sup 67/Ga scan positive, 20% of all observations). Conventional clinical, roentgenographic, or physiologic studies could not predict the alveolitis status. Interestingly, of the 51 alveolitis evaluations in the 19 patients, there were 24 occurrences (47%) where the alveolitis was ''split,'' i.e., /sup 67/Ga scans positive and T-cells low (39%) or /sup 67/Ga negative and T-cells high (8%). Most untreated patients with sarcoidosis without extrapulmonary symptoms may have some inflammatory processes ongoing in their alveolar structures. Overall, whenever a high intensity alveolitis episode occurred, it was followed by deterioration over the next 6 months in at least one lung function parameter. A low intensity alveolitis episode was followed by functional deterioration only 8% of the time. The alveolitis parameters (lavage and /sup 67/Ga scanning) clearly predicted prognosis. These observations should prove useful in understanding the natural history of pulmonary sarcoidosis, in staging patients with this disease, and in making rational therapy decisions.

  4. Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) Study. Sarcoidosis Protocol.

    PubMed

    Moller, David R; Koth, Laura L; Maier, Lisa A; Morris, Alison; Drake, Wonder; Rossman, Milton; Leader, Joseph K; Collman, Ronald G; Hamzeh, Nabeel; Sweiss, Nadera J; Zhang, Yingze; O'Neal, Scott; Senior, Robert M; Becich, Michael; Hochheiser, Harry S; Kaminski, Naftali; Wisniewski, Stephen R; Gibson, Kevin F

    2015-10-01

    Sarcoidosis is a systemic disease characterized by noncaseating granulomatous inflammation with tremendous clinical heterogeneity and uncertain pathobiology and lacking in clinically useful biomarkers. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study is an observational cohort study designed to explore the role of the lung microbiome and genome in these two diseases. This article describes the design and rationale for the GRADS study sarcoidosis protocol. The study addresses the hypothesis that distinct patterns in the lung microbiome are characteristic of sarcoidosis phenotypes and are reflected in changes in systemic inflammatory responses as measured by peripheral blood changes in gene transcription. The goal is to enroll 400 participants, with a minimum of 35 in each of 9 clinical phenotype subgroups prioritized by their clinical relevance to understanding of the pathobiology and clinical heterogeneity of sarcoidosis. Participants with a confirmed diagnosis of sarcoidosis undergo a baseline visit with self-administered questionnaires, chest computed tomography, pulmonary function tests, and blood and urine testing. A research or clinical bronchoscopy with a research bronchoalveolar lavage will be performed to obtain samples for genomic and microbiome analyses. Comparisons will be made by blood genomic analysis and with clinical phenotypic variables. A 6-month follow-up visit is planned to assess each participant's clinical course. By the use of an integrative approach to the analysis of the microbiome and genome in selected clinical phenotypes, the GRADS study is powerfully positioned to inform and direct studies on the pathobiology of sarcoidosis, identify diagnostic or prognostic biomarkers, and provide novel molecular phenotypes that could lead to improved personalized approaches to therapy for sarcoidosis. PMID:26193069

  5. "End-stage" pulmonary fibrosis in sarcoidosis.

    PubMed

    Teirstein, Alvin T; Morgenthau, Adam S

    2009-02-01

    Pulmonary fibrosis is an unusual "end stage" in patients with sarcoidosis. Fibrosis occurs in a minority of patients, and presents with a unique physiologic combination of airways dysfunction (obstruction) superimposed on the more common restrictive dysfunction. Imagin techniques are essential to the diagnosis, assessment and treatment of pulmonary fibrosis. Standard chest radiographs and CT scans may reveal streaks, bullae, cephalad retraction of the hilar areas, deviation of the trachea and tented diaphragm. Positive gallium and PET scans indicate residual reversible granulomatous disease and are important guides to therapy decisions. Treatment, usually with corticosteroids, is effective in those patients with positive scans, but fibrosis does not improve with any treatment. With severe functional impariment and patient disability, pulmonary hypertension and right heart failure may supervene for which the patient will require treatment. Oxygen, careful diuresis, sildenafil and bosentan may be salutary. These patients are candidates for lung transplantation. PMID:19170216

  6. Chronic active hepatitis experience of Groote Schuur Hospital, 1964 - 1977.

    PubMed

    Poreh, S; Kirsch, R E; Terblanche, J; Saunders, S J

    1980-06-14

    From 1964 to 1977, 54 patients with clinical, biochemical and histological criteria of chronic active hepatitis were seen at Groote Schuur Hospital, Cape Town. Our experience with this disease is reviewed, and the diagnosis and mangement are commented on. PMID:7404076

  7. Single Lesion of Sarcoidosis Presenting as Cicatricial Alopecia: A Rare Report from India

    PubMed Central

    Ghosh, Aparajita; Sengupta, Sujata; Coondoo, Arijit; Gharami, Ramesh Chandra

    2014-01-01

    Sarcoidosis affects different systems of the body including the skin where it can affect various cutaneous sites. Among these sites, the scalp is a very unusual location for lesions of sarcoidosis. Sarcoidosis of the scalp can very rarely be accompanied by cicatricial alopecia. We report here a rare case of sarcoidosis of scalp with cicatricial alopecia. To the best of our knowledge, this is the first such report from India. PMID:25191039

  8. Molecular Analysis of Sarcoidosis Granulomas Reveals Antimicrobial Targets.

    PubMed

    Rotsinger, Joseph E; Celada, Lindsay J; Polosukhin, Vasiliy V; Atkinson, James B; Drake, Wonder P

    2016-07-01

    Sarcoidosis is a granulomatous disease of unknown cause. Prior molecular and immunologic studies have confirmed the presence of mycobacterial virulence factors, such as catalase peroxidase and superoxide dismutase A, within sarcoidosis granulomas. Molecular analysis of granulomas can identify targets of known antibiotics classes. Currently, major antibiotics are directed against DNA synthesis, protein synthesis, and cell wall formation. We conducted molecular analysis of 40 sarcoidosis diagnostic specimens and compared them with 33 disease control specimens for the presence of mycobacterial genes that encode antibiotic targets. We assessed for genes involved in DNA synthesis (DNA gyrase A [gyrA] and DNA gyrase B), protein synthesis (RNA polymerase subunit β), cell wall synthesis (embCAB operon and enoyl reductase), and catalase peroxidase. Immunohistochemical analysis was conducted to investigate the locale of mycobacterial genes such as gyrA within 12 sarcoidosis specimens and 12 disease controls. Mycobacterial DNA was detected in 33 of 39 sarcoidosis specimens by quantitative real-time polymerase chain reaction compared with 2 of 30 disease control specimens (P < 0.001, two-tailed Fisher's test). Twenty of 39 were positive for three or more mycobacterial genes, compared with 1 of 30 control specimens (P < 0.001, two-tailed Fisher's test). Immunohistochemistry analysis localized mycobacterial gyrA nucleic acids to sites of granuloma formation in 9 of 12 sarcoidosis specimens compared with 1 of 12 disease controls (P < 0.01). Microbial genes encoding enzymes that can be targeted by currently available antimycobacterial antibiotics are present in sarcoidosis specimens and localize to sites of granulomatous inflammation. Use of antimicrobials directed against target enzymes may be an innovative treatment alternative. PMID:26807608

  9. Delayed diagnosis of sarcoidosis is common in Brazil*

    PubMed Central

    Rodrigues, Mauri Monteiro; Coletta, Ester Nei Aparecida Martins; Ferreira, Rimarcs Gomes; Pereira, Carlos Alberto de Castro

    2013-01-01

    OBJECTIVE: To determine the frequency of and the factors related to delayed diagnosis of sarcoidosis in Brazil. METHODS: We evaluated patients with a biopsy-proven diagnosis of sarcoidosis, using a questionnaire that addressed the following: time since symptom onset and since the first medical visit; and the number and specialty of the physicians visited. We divided the patients by the timeliness of the diagnosis-timely (< 6 months) and delayed (≥ 6 months)-comparing the two groups in terms of systemic and pulmonary symptoms; extrathoracic involvement; spirometric data; radiological staging; level of education; income; and tuberculosis (diagnosis and treatment). RESULTS: We evaluated 100 patients. The median number of physicians consulted was 3 (range, 1-14). In 11 cases, sarcoidosis was diagnosed at the first visit. In 54, the first physician seen was a general practitioner. The diagnosis of sarcoidosis was timely in 41 patients and delayed in 59. The groups did not differ in terms of gender; race; type of health insurance; level of education; income; respiratory/systemic symptoms; extrathoracic involvement; and radiological staging. In the delayed diagnosis group, FVC was lower (80.3 ± 20.4% vs. 90.5 ± 17.1%; p = 0.010), as was FEV1 (77.3 ± 19.9% vs. 86.4 ± 19.5%; p = 0.024), misdiagnosis with and treatment for tuberculosis (≥ 3 months) also being more common (24% vs. 7%, p = 0.032, and 20% vs. 0%; p = 0.002, respectively). CONCLUSIONS: The diagnosis of sarcoidosis is often delayed, even when the imaging is suggestive of sarcoidosis. Delayed diagnosis is associated with impaired lung function at the time of diagnosis. Many sarcoidosis patients are misdiagnosed with and treated for tuberculosis. PMID:24310626

  10. Hypocholesterolemia in chronic anemias with increased erythropoietic activity.

    PubMed

    Shalev, Hanna; Kapelushnik, Joseph; Moser, Asher; Knobler, Hilla; Tamary, Hannah

    2007-03-01

    Hypocholesterolemia of unknown etiology has been previously described in various chronic anemias. Few small studies also suggested that those patients have a lower incidence of atherosclerotic events. The aim of our study was to determine the extent of hypocholesterolemia in various types of anemias. We studied 59 patients with chronic anemias associated with high-erythropoietic activity (thalassemia intermedia, congenital dyserythropoietic anemia type I, congenital spherocytosis), 8 patients with low-erythropoietic activity anemias (acquired aplastic anemia, Fanconi anemia, and Diamond Blackfan anemia), and 20 healthy controls. Mean serum cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, hemoglobin, serum ferritin, soluble transferrin receptor (STR), and serum erythropoietin levels were determined in each patient. All patients with chronic anemia and increased erythropoietic activity had hypocholesterolemia, whereas none of those with low erythropoietic activity was hypocholesterolemic. Mean serum cholesterol, HDL cholesterol, and LDL cholesterol levels were found to be significantly lower in the high-erythropoietic activity group (80+/-19 mg/dl; 31+/-10 mg/dl; 35+/-14 mg/dl, respectively) compared with the control group (P<0.001; 0.001; 0.001, respectively) and the low-erythropoietic activity group (P<0.001; 0.001; 0.01, respectively). Significant inverse correlation (R2=0.507) was observed between serum cholesterol and STR levels, which in the absence of iron deficiency reflect bone marrow activity. Taken together, our results imply that hypocholesterolemia accompanies anemias with high-erythropoietic activity. We suggest that the high-erythropoitic activity-associated hypocholesterolemia is due to increased cholesterol requirements by the proliferating erythoid cells. Further studies are needed to elucidate the exact mechanism and the possible clinical consequences of this phenomenon. PMID

  11. [Radionuclide assessment of cardiac involvement in patients with sarcoidosis].

    PubMed

    Hiroe, M; Nagata, M; Sekiguchi, M; Ohta, Y; Kusakabe, K; Shigeta, A; Horie, T; Fujita, N; Hasumi, M; Toyosaki, T

    1990-01-01

    This study was aimed to determine whether nuclear methods were useful for examining cardiac pathology and for making a decision of corticosteroid therapy in patients with sarcoidosis. Thirty six patients were divided into two groups; GpA consisted of 19 patients with cardiac sarcoidosis and abnormal ECG findings, and GpB of 17 patients with sarcoidosis without ECG abnormalities. Cardiac uptake of 67Ga-citrate in 2 and 99mTc-PYP in one of GpA was observed and steroid therapy resulted in the disappearance of the uptake. 201Tl-CL cardiac tomograms disclosed perfusion defects in 10 of 14 patients (71%) in GpA, including defects with redistribution in 8 of the 10 pts, but only one case in GpB. Radionuclide ventriculography using 99mTc-RBC revealed abnormal response of left ventricular (LV) function to exercise and LV dysfunction in GpA. These data suggest that nuclear study is a useful tool for diagnosing cardiac sarcoidosis, evaluating therapeutic effectiveness and long-term follow-up in patients with sarcoidosis. PMID:2162435

  12. Chronic electrical stimulation homeostatically decreases spontaneous activity, but paradoxically increases evoked network activity

    PubMed Central

    Goel, Anubhuti

    2013-01-01

    Neural dynamics generated within cortical networks play a fundamental role in brain function. However, the learning rules that allow recurrent networks to generate functional dynamic regimes, and the degree to which these regimes are themselves plastic, are not known. In this study we examined plasticity of network dynamics in cortical organotypic slices in response to chronic changes in activity. Studies have typically manipulated network activity pharmacologically; we used chronic electrical stimulation to increase activity in in vitro cortical circuits in a more physiological manner. Slices were stimulated with “implanted” electrodes for 4 days. Chronic electrical stimulation or treatment with bicuculline decreased spontaneous activity as predicted by homeostatic learning rules. Paradoxically, however, whereas bicuculline decreased evoked network activity, chronic stimulation actually increased the likelihood that evoked stimulation elicited polysynaptic activity, despite a decrease in evoked monosynaptic strength. Furthermore, there was an inverse correlation between spontaneous and evoked activity, suggesting a homeostatic tradeoff between spontaneous and evoked activity. Within-slice experiments revealed that cells close to the stimulated electrode exhibited more evoked polysynaptic activity and less spontaneous activity than cells close to a control electrode. Collectively, our results establish that chronic stimulation changes the dynamic regimes of networks. In vitro studies of homeostatic plasticity typically lack any external input, and thus neurons must rely on “spontaneous” activity to reach homeostatic “set points.” However, in the presence of external input we propose that homeostatic learning rules seem to shift networks from spontaneous to evoked regimes. PMID:23324317

  13. Renal Failure Found during the Follow-up of Sarcoidosis: The Relevance of a Delay in the Diagnosis of Concurrent Hypercalcemia.

    PubMed

    Hishida, Erika; Masuda, Takahiro; Akimoto, Tetsu; Sato, Ryuta; Wakabayashi, Natsuko; Miki, Atsushi; Otani, Naoko; Imai, Toshimi; Sugase, Taro; Takeda, Shin-Ichi; Muto, Shigeaki; Nagata, Daisuke

    2016-01-01

    We herein present a case of relapsed sarcoidosis with a deteriorated renal function accompanied by hypercalcemia, nephrolithiasis, and a ureteral stone in a woman with a history of ocular sarcoidosis. The ocular involvement appeared to be well controlled for a long period of time with a topical ophthalmic steroid; however, we believe that the absence of apparent recrudescence could have led to the delay in our diagnosis of relapse of the disease during the follow-up period. The conundrums regarding longitudinal surveillance for both evaluating the disease activity and determining the necessity of therapeutics are also discussed. PMID:27432099

  14. Sarcoidosis patient with lupus pernio and infliximab-induced myositis: Response to Acthar gel

    PubMed Central

    Zhou, Ying; Lower, Elyse E.; Li, Huiping; Baughman, Robert P.

    2015-01-01

    Infliximab is an effective treatment for sarcoidosis patients with persistent disease despite glucocorticoids and immunosuppressive therapy. Patients receiving infliximab can experience side effects, inducing an autoimmune reaction. Treatment is unclear for sarcoidosis patients who develop autoimmune reactions to infliximab. We report a case of a patient with advanced sarcoidosis who developed a myositis type reaction to infliximab characterized by diffuse muscle achiness and weakness and marked elevations in serum creatinine phosphokinase (CPK) and aldolase. Manifestations of sarcoidosis and myositis improved after Acthar treatment. This is the first report of successful treatment with Acthar in a patient with advanced sarcoidosis with an autoimmune reaction to infliximab.

  15. Carbon Nanotube-Induced Pulmonary Granulomatous Disease: Twist1 and Alveolar Macrophage M1 Activation

    PubMed Central

    Barna, Barbara P.; Huizar, Isham; Malur, Anagha; McPeek, Matthew; Marshall, Irene; Jacob, Mark; Dobbs, Larry; Kavuru, Mani S.; Thomassen, Mary Jane

    2013-01-01

    Sarcoidosis, a chronic granulomatous disease of unknown cause, has been linked to several environmental risk factors, among which are some that may favor carbon nanotube formation. Using gene array data, we initially observed that bronchoalveolar lavage (BAL) cells from sarcoidosis patients displayed elevated mRNA of the transcription factor, Twist1, among many M1-associated genes compared to healthy controls. Based on this observation we hypothesized that Twist1 mRNA and protein expression might become elevated in alveolar macrophages from animals bearing granulomas induced by carbon nanotube instillation. To address this hypothesis, wild-type and macrophage-specific peroxisome proliferator-activated receptor gamma (PPARγ) knock out mice were given oropharyngeal instillation of multiwall carbon nanotubes (MWCNT). BAL cells obtained 60 days later exhibited significantly elevated Twist1 mRNA expression in granuloma-bearing wild-type or PPARγ knock out alveolar macrophages compared to sham controls. Overall, Twist1 expression levels in PPARγ knock out mice were higher than those of wild-type. Concurrently, BAL cells obtained from sarcoidosis patients and healthy controls validated gene array data: qPCR and protein analysis showed significantly elevated Twist1 in sarcoidosis compared to healthy controls. In vitro studies of alveolar macrophages from healthy controls indicated that Twist1 was inducible by classical (M1) macrophage activation stimuli (LPS, TNFα) but not by IL-4, an inducer of alternative (M2) macrophage activation. Findings suggest that Twist1 represents a PPARγ-sensitive alveolar macrophage M1 biomarker which is induced by inflammatory granulomatous disease in the MWCNT model and in human sarcoidosis. PMID:24322444

  16. Barcoding Human Physical Activity to Assess Chronic Pain Conditions

    PubMed Central

    Paraschiv-Ionescu, Anisoara; Perruchoud, Christophe; Buchser, Eric; Aminian, Kamiar

    2012-01-01

    Background Modern theories define chronic pain as a multidimensional experience – the result of complex interplay between physiological and psychological factors with significant impact on patients' physical, emotional and social functioning. The development of reliable assessment tools capable of capturing the multidimensional impact of chronic pain has challenged the medical community for decades. A number of validated tools are currently used in clinical practice however they all rely on self-reporting and are therefore inherently subjective. In this study we show that a comprehensive analysis of physical activity (PA) under real life conditions may capture behavioral aspects that may reflect physical and emotional functioning. Methodology PA was monitored during five consecutive days in 60 chronic pain patients and 15 pain-free healthy subjects. To analyze the various aspects of pain-related activity behaviors we defined the concept of PA ‘barcoding’. The main idea was to combine different features of PA (type, intensity, duration) to define various PA states. The temporal sequence of different states was visualized as a ‘barcode’ which indicated that significant information about daily activity can be contained in the amount and variety of PA states, and in the temporal structure of sequence. This information was quantified using complementary measures such as structural complexity metrics (information and sample entropy, Lempel-Ziv complexity), time spent in PA states, and two composite scores, which integrate all measures. The reliability of these measures to characterize chronic pain conditions was assessed by comparing groups of subjects with clinically different pain intensity. Conclusion The defined measures of PA showed good discriminative features. The results suggest that significant information about pain-related functional limitations is captured by the structural complexity of PA barcodes, which decreases when the intensity of pain

  17. Validity of mini-dose gallium for objective quantification of alveolitis in pulmonary sarcoidosis

    SciTech Connect

    Vitti, R.; Maurer, A.H.; Siegel, J.A.; Fewell, J.W.; Malmud, L.S.

    1985-05-01

    Patents (pts) with pulmonary sarcoidosis will often have frequent gallium (Ga) studies to assess the response of alveolitis to corticosteroid therapy. Since many pts are young and the cumulative radiation burden significant the authors have evaluated the ability of computer based Ga lung imaging to reliably quantify Ga activity using a 0.5 mCi dose of Ga. Twelve pts with biopsy proven pulmonary sarcoidosis received 0.5 mCi of Ga-67 citrate intravenously and had a posterior view of the chest including a portion of the liver obtained at 24 hrs post injection. At 24 hrs the pts received an additional 2.5 mCi and were then imaged at 48 and 72 hrs. A gallium score (GS) was computer generated as follows: regions of interest (ROI's) were manually created for the lungs, liver and background. Following a 9 point spatial smooth and background subtraction, the images were scaled so that the liver activity was assigned an arbitrary value of 400 counts per pixel. The resulting average counts per pixel for the lungs were then summed for the GS. Using a paired T-test there was only a borderline significant difference (0.05activity can reliably be performed with significantly lower doses of Ga than are currently being used and that this can lower the cumulative radiation exposure to pts with sarcoidosis who commonly have serial studies.

  18. Chronic hyperammonemia induces tonic activation of NMDA receptors in cerebellum.

    PubMed

    ElMlili, Nisrin; Boix, Jordi; Ahabrach, Hanan; Rodrigo, Regina; Errami, Mohammed; Felipo, Vicente

    2010-02-01

    Reduced function of the glutamate--nitric oxide (NO)--cGMP pathway is responsible for some cognitive alterations in rats with hyperammonemia and hepatic encephalopathy. Hyperammonemia impairs the pathway in cerebellum by increasing neuronal nitric oxide synthase (nNOS) phosphorylation in Ser847 by calcium-calmodulin-dependent protein kinase II (CaMKII), reducing nNOS activity, and by reducing nNOS amount in synaptic membranes, which reduces its activation following NMDA receptors activation. The reason for increased CaMKII activity in hyperammonemia remains unknown. We hypothesized that it would be as a result of increased tonic activation of NMDA receptors. The aims of this work were to assess: (i) whether tonic NMDA activation receptors is increased in cerebellum in chronic hyperammonemia in vivo; and (ii) whether this tonic activation is responsible for increased CaMKII activity and reduced activity of nNOS and of the glutamate--NO--cGMP pathway. Blocking NMDA receptors with MK-801 increases cGMP and NO metabolites in cerebellum in vivo and in slices from hyperammonemic rats. This is because of reduced phosphorylation and activity of CaMKII, leading to normalization of nNOS phosphorylation and activity. MK-801 also increases nNOS in synaptic membranes and reduces it in cytosol. This indicates that hyperammonemia increases tonic activation of NMDA receptors leading to reduced activity of nNOS and of the glutamate--NO--cGMP pathway. PMID:20002515

  19. Sarcoidosis detected due to tattoo swellings in an Indian female.

    PubMed

    Ghorpade, Ashok

    2015-01-01

    A female patient presented with asymptomatic swellings in old blue-black tattoo marks of her forearms. On careful skin examination, few raised erythematous, circular plaques were also found on the non-tattooed skin on her back, about which she was unaware. The diagnosis of cutaneous and systemic sarcoidosis was confirmed after classical histopathological findings from skin lesions from her non tattooed back and from papulonodular tattooed lesions, ruling out other causes of granulomas and supported by a negative Mantoux test, raised serum angiotensin converting enzyme level, high resolution computed tomography thorax, etc. She responded well to oral steroid therapy. The importance of a careful skin examination, easy access provided by skin lesions in suspected cases of cutaneous/systemic sarcoidosis, the value of sudden tattoo changes in the diagnosis here and the possible contribution of tattoos toward the causation of cutaneous and/or systemic sarcoidosis are highlighted. PMID:26275266

  20. Electrophysiological correlates of cardiac sarcoidosis: an appraisal of current evidence.

    PubMed

    Yadava, Mrinal; Bala, Rupa

    2015-06-01

    Cardiac sarcoidosis is an underdiagnosed condition that may be present in as many as 25% of patients with systemic sarcoidosis. It is associated with significant morbidity and mortality in affected individuals. The presentation of cardiac involvement in sarcoidosis includes sudden death in the absence of preceding symptoms, conduction disturbances, ventricular arrhythmias, and heart failure. A scarcity of randomized data and a lack of prospective trials underlies the contention between experts on the most appropriate strategies for diagnosis and therapy. This review focuses on the electrophysiological sequelae of the disease, with an emphasis on current diagnostic guidelines, multimodality imaging for early detection, and the role of various therapeutic interventions. Multicentre collaboration is necessary to address the numerous unanswered questions pertaining to management of this disease. PMID:26142797

  1. /sup 67/Ga citrate scanning and serum angiotensin converting enzyme levels in sarcoidosis

    SciTech Connect

    Gupta, R.G.; Bekerman, C.; Sicilian, L.; Oparil, S.; Pinsky, S.M.; Szidon, J.P.

    1982-09-01

    /sup 67/Ga citrate scans and serum angiotensin converting enzyme (ACE) levels were obtained in 54 patients with sarcoidosis and analyzed in relation to clinical manifestations. /sup 67/Ga scans were abnormal in 97% of patients with clinically active disease (n . 30) and in 71% of patients with inactive disease (n . 24). Serum ACE levels were abnormally high (2 standard deviations above the control mean) in 73% of patients with clinically active disease and in 54% of patients with inactive disease. Serum ACE levels correlated significantly with /sup 67/Ga uptake score (r..436; p less than .005). The frequency of abnormal /sup 67/Ga scans and elevated serum ACE levels suggests that inflammatory activity with little or no clinical expression is common in sarcoidosis. Abnormal /sup 67/Ga scans were highly sensitive (97%) but had poor specificity (29%) to clinical disease activity. The accuracy of negative prediction of clinical activity by normal scans (87%) was better than the accuracy of positive prediction of clinical activity by abnormal scans (63%). /sup 67/Ga scans can be used to support the clinical indentification of inactive sacoidosis.

  2. Sarcoidosis in Black Women in the United States

    PubMed Central

    Berman, Jeffrey S.; Palmer, Julie R.; Boggs, Deborah A.; Serlin, David M.; Rosenberg, Lynn

    2011-01-01

    Background: Sarcoidosis is a systemic granulomatous disorder of unknown cause that occurs among men and women of all races. In the United States, black women are most frequently and most severely affected. There have been few epidemiologic studies of sarcoidosis focusing on black women. Methods: In this article, we present data on incidence, prevalence, and clinical characteristics of sarcoidosis among participants in the Black Women’s Health Study, a cohort study of 59,000 black women from across the United States. Data on incident disease and potential risk factors are obtained through biennial questionnaires. Follow-up has been > 80% through six completed cycles. Results: There were 685 prevalent cases of sarcoidosis at baseline in 1995 and 435 incident cases reported during 611,585 person-years of follow-up through 2007, for an average annual incidence rate of 71/100,000 and a current prevalence of 2.0%. The sarcoid diagnosis was confirmed in 96% of self-reported cases for whom medical records or physician checklists were obtained. The most frequently affected site was the lung. Most patients also had extrapulmonary involvement, with the most common sites being lymph nodes, skin, and eyes. Prednisone had the highest prevalence of use, followed by inhaled corticosteroids. Conclusions: This study confirms previous reports of high incidence and prevalence of sarcoidosis among black women, as well as the extent of extrapulmonary disease, frequent need for steroid therapy, and comorbid conditions in this population. The prospective identification of sarcoidosis cases from a defined population will enable a valid assessment of risk factors for incident disease as follow-up continues. PMID:20595459

  3. Studies of T-cell activation in chronic inflammation

    PubMed Central

    2002-01-01

    Chapter summary The strong association between specific alleles encoded within the MHC class II region and the development of rheumatoid arthritis (RA) has provided the best evidence to date that CD4+ T cells play a role in the pathogenesis of this chronic inflammatory disease. However, the unusual phenotype of synovial T cells, including their profound proliferative hyporesponsiveness to TCR ligation, has challenged the notion that T-cell effector responses are driven by cognate cartilage antigens in inflamed synovial joints. The hierarchy of T-cell dysfunction from peripheral blood to inflamed joint suggests that these defects are acquired through prolonged exposure to proinflammatory cytokines such as tumour necrosis factor (TNF)-α. Indeed, there are now compelling data to suggest that chronic cytokine activation may contribute substantially to the phenotype and effector function of synovial T cells. Studies reveal that chronic exposure of T cells to TNF uncouples TCR signal transduction pathways by impairing the assembly and stability of the TCR/CD3 complex at the cell surface. Despite this membrane-proximal effect, TNF selectively uncouples downstream signalling pathways, as is shown by the dramatic suppression of calcium signalling responses, while Ras/ERK activation is spared. On the basis of these data, it is proposed that T-cell survival and effector responses are driven by antigen-independent, cytokine-dependent mechanisms, and that therapeutic strategies that seek to restore T-cell homeostasis rather than further depress T-cell function should be explored in the future. PMID:12110140

  4. Chronic Assessment of Diaphragm Muscle EMG Activity across Motor Behaviors

    PubMed Central

    Mantilla, Carlos B.; Seven, Yasin B.; Hurtado-Palomino, Juan N.; Zhan, Wen-Zhi; Sieck, Gary C.

    2011-01-01

    The diaphragm muscle is main inspiratory muscle in mammals. Quantitative analyses documenting the reliability of chronic diaphragm EMG recordings are lacking. Assessment of ventilatory and non-ventilatory motor behaviors may facilitate evaluating diaphragm EMG activity over time. We hypothesized that normalization of diaphragm EMG amplitude across behaviors provides stable and reliable parameters for longitudinal assessments of diaphragm activity. We found that diaphragm EMG activity shows substantial intra-animal variability over 6 weeks, with coefficient of variation (CV) for different behaviors ~29–42%. Normalization of diaphragm EMG activity to near maximal behaviors (e.g., deep breathing) reduced intra-animal variability over time (CV ~22–29%). Plethysmographic measurements of eupneic ventilation were also stable over 6 weeks (CV ~13% for minute ventilation). Thus, stable and reliable measurements of diaphragm EMG activity can be obtained longitudinally using chronically implanted electrodes by examining multiple motor behaviors. By quantitatively determining the reliability of longitudinal diaphragm EMG analyses, we provide an important tool for evaluating the progression of diseases or injuries that impair ventilation. PMID:21414423

  5. Radioisotope bone scanning in a case of sarcoidosis

    SciTech Connect

    Cinti, D.C.; Hawkins, H.B.; Slavin, J.D. Jr.

    1985-03-01

    The application of radioisotope scanning to osseous involvement from systemic sarcoidosis has been infrequently described in the scientific literature. Most commonly, the small bones of the hands and feet are affected if sarcoidosis involves the skeleton. Nonetheless, there are also occasional manifestations of sarcoid in the skull, long bones, and vertebral bodies. This paper describes a case of sarcoid involving the lung parenchyma with multiple lesions in the skull and ribs demonstrated by bone scanning with Tc-99m MDP. Following treatment with steroids, the bone scan showed complete resolution of the rib lesions and almost complete resolution of the lesions in the calvarium.

  6. Diagnosis and treatment of azoospermia resulting from testicular sarcoidosis.

    PubMed

    Kovac, Jason R; Flood, Diane; Mullen, J Brendan; Fischer, Marc Anthony

    2012-01-01

    Genitourinary sarcoidosis is uncommon, with only rare documented cases of testicular involvement reported. We detail the case of a 37-year-old male who initially presented for azoospermia and secondary infertility. A testicular biopsy revealed nonnecrotizing granulomas and a chest x-ray identified perihilar lymphadenopathy and granulomatous lung nodules. A corticosteroid regimen was administered, and routine semen analyses were conducted. Significant improvements were noted after prednisone treatments. A successful in vivo fertilization was obtained. This is the first known case of testicular sarcoidosis diagnosed during investigations into azoospermia and secondary infertility which, after treatment with corticosteroids, resulted in natural fertilization. PMID:21546613

  7. Cutaneous Sarcoidosis: Preamble of a Paucisymptomatic Systemic Disease.

    PubMed

    Ramírez Huaranga, Marco Aurelio; Ramos Rodríguez, Claudia Carolina; de la Rocha Vedia, Iris Violeta; García Arpa, Mónica; Murillo Lázaro, Cristina; Bellón Guardia, María

    2015-01-01

    Sarcoidosis is a systemic granulomatous disease with a wide range of clinical manifestations. Skin involvement is an early, frequent and accessible location for a histopathological study. Several risk factors have been described to determine the likelihood of systemic involvement of an apparent cutaneous condition. Early diagnosis and systemic treatment could prevent future complications. A series of three cases is presented in which the initial diagnosis was cutaneous sarcoidosis, but it was actually the first manifestation of a systemic disease. A review of this topic is also presented. PMID:25823568

  8. Sarcoidosis presenting with an unusual erythematous rash and persistent hypercalcemia.

    PubMed Central

    Barney, B. L.

    1992-01-01

    Sarcoidosis is a multisystem disease that often presents with constitutional symptoms and ocular and skin manifestations. The chest roentgenogram may show no abnormalities or only diffuse interstitial disease. The serum calcium level is uncommonly persistently elevated and responds rapidly to low-dose corticosteroid therapy. The level of 1,25-dihydroxyvitamin D is often elevated, and the level of parathyroid hormone is almost always suppressed. Skin manifestations vary considerably and may appear in an unusual fashion. A skin biopsy may often be essential in the diagnosis of sarcoidosis. Images PMID:1595285

  9. No impact of tumor necrosis-factor antagonists on the joint manifestations of sarcoidosis

    PubMed Central

    Banse, Christopher; Bisson-Vaivre, Aurélia; Kozyreff-Meurice, Marie; Vittecoq, Olivier; Goëb, Vincent

    2013-01-01

    Objective The use of anti-tumor necrosis factor (TNF) agents to treat joint manifestations of sarcoidosis has not been described. We evaluated the efficacy and safety of three such biologics in patients with these symptoms refractory to conventional therapy (nonsteroidal anti-inflammatory drugs, corticosteroids, and/or disease-modifying antirheumatic drugs). Methods This retrospective study, covering January 2001 to September 2011, examined clinical–biological parameters collected before anti-TNF treatment (age, sex, duration of disease evolution, drugs taken), and at introduction and under anti-TNF therapy (number of painful and swollen joints, visual analog scale score of global disease activity, disease-activity score of 28 joints with erythrocyte sedimentation rate or C-reactive protein, TNF-antagonist duration). At 3, 6, and 12 months, anti-TNF impact on joints and the therapeutic response according to European League Against Rheumatism criteria used for rheumatoid arthritis were assessed. Results Ten patients’ data were evaluated; some of them had received several anti-TNF agents (median [range] duration on each biotherapy was 10 [4–30] months), which enabled analysis of 19 prescriptions. The total duration of anti-TNF exposure was 17.6 patient-years, which was started a median of 3 (0.33–17) years after sarcoidosis diagnosis. The median numbers of painful and swollen joints were 1 (0–28) and 0 (0–9), respectively. Despite rapid efficacy, after 1 year of treatment, clinical (especially joint) and biological parameters were comparable to pretreatment, and only the corticosteroid dose was significantly lower (P=0.03). One case of mild skin toxicity was noted. Conclusion TNF antagonists allowed significant steroid sparing and were well tolerated, but do not seem to be effective against sarcoidosis joint involvement. PMID:23901289

  10. Chronic lymphocytic leukemia: a disease of activated monoclonal B cells

    PubMed Central

    Damle, Rajendra N.; Calissano, Carlo; Chiorazzi, Nicholas

    2010-01-01

    B-cell type chronic lymphocytic leukemia (CLL) has long been considered a disease of resting lymphocytes. However cell surface and intracellular phenotypes suggest that most CLL cells are activated cells, although only a small subset progresses beyond the G1 stage of the cell cycle. In addition, traditional teaching says that CLL cells divide rarely, and therefore the buildup of leukemic cells is due to an inherent defect in cell death. However, in vivo labeling of CLL cells indicates a much more active rate of cell birth than originally estimated, suggesting that CLL is a dynamic disease. Here we review the observations that have led to these altered views of the activation state and proliferative capacities of CLL cells and also provide our interpretation of these observations in light of their potential impact on patients. PMID:20620969

  11. Coupled Activation of Primary Sensory Neurons Contributes to Chronic Pain.

    PubMed

    Kim, Yu Shin; Anderson, Michael; Park, Kyoungsook; Zheng, Qin; Agarwal, Amit; Gong, Catherine; Saijilafu; Young, LeAnne; He, Shaoqiu; LaVinka, Pamela Colleen; Zhou, Fengquan; Bergles, Dwight; Hanani, Menachem; Guan, Yun; Spray, David C; Dong, Xinzhong

    2016-09-01

    Primary sensory neurons in the DRG play an essential role in initiating pain by detecting painful stimuli in the periphery. Tissue injury can sensitize DRG neurons, causing heightened pain sensitivity, often leading to chronic pain. Despite the functional importance, how DRG neurons function at a population level is unclear due to the lack of suitable tools. Here we developed an imaging technique that allowed us to simultaneously monitor the activities of >1,600 neurons/DRG in live mice and discovered a striking neuronal coupling phenomenon that adjacent neurons tend to activate together following tissue injury. This coupled activation occurs among various neurons and is mediated by an injury-induced upregulation of gap junctions in glial cells surrounding DRG neurons. Blocking gap junctions attenuated neuronal coupling and mechanical hyperalgesia. Therefore, neuronal coupling represents a new form of neuronal plasticity in the DRG and contributes to pain hypersensitivity by "hijacking" neighboring neurons through gap junctions. PMID:27568517

  12. Redistribution on the thallium scan in myocardial sarcoidosis: concise communication

    SciTech Connect

    Makler, P.T.; Lavine, S.J.; Denenberg, B.S.; Bove, A.A.; Idell, S.

    1981-05-01

    Resting and redistribution thallium studies were performed in four young patients with sarcoidosis to evaluate the possibility of myocardial involvement. In each case the resting scan showed marked defects that resolved on the redistribution studies. In a different patient population, these results would have implied significant coronary artery disease.

  13. Multicentric Castleman's disease developing during follow-up of sarcoidosis.

    PubMed

    Sawata, Tetsuro; Bando, Masashi; Nakayama, Masayuki; Mato, Naoko; Takemura, Tamiko; Sugiyama, Yukihiko

    2016-07-01

    Pulmonary sarcoidosis is reported to have complication of lymphoproliferative disease such as malignant lymphoma, but the complication of multicentric Castleman's disease (MCD) is rarely reported. In our case of a 60-year-old woman, bilateral hilar lymphadenopathy was noted in her chest X-ray. We performed a transbronchial lung biopsy. She was diagnosed as having pulmonary sarcoidosis (Stage II). The shadow on chest X-ray disappeared without treatment. However, after 8 years, swelling of the mediastinal and abdominal lymph node, thickened bronchovascular bundle, and multiple nodular shadows were identified, and a thoracoscopic lung biopsy was performed. Based on the histopathological findings and elevated serum interleukin-6 level (75.7 pg/mL), she was diagnosed with pulmonary sarcoidosis complicated by MCD. When a change in chest X-ray findings are found during monitoring of pulmonary sarcoidosis, it is important to proceed with a thoracoscopic lung biopsy, because of the possibility of the rare complication of MCD. PMID:27512568

  14. Renal confined sarcoidosis: Natural history and diagnostic challenge

    PubMed Central

    Ghafoor, Azam; Almakki, Akram

    2014-01-01

    A 69 year old male referred to nephrology clinic for uncontrolled hypertension. During his follow up over two years, he developed renal disease and hypercalcemia. He was found to have monoclonal gammopathy (MGUS). Urinalysis was negative except for Monoclonal IgG on immunoelectrophoresis. Workup for malignancy was negative including chest X-ray and bone marrow biopsy. He progressed into renal failure and ended up on dialysis. Interestingly, the renal biopsy showed non-caseating granulomas, and the patient was diagnosed with renal confined sarcoidosis which is extremely rare. PPD was negative. He was treated with Prednisone 60 mg daily. Surprisingly, his kidney disease was not responsive to steroids. Despite improvement in his calcium with treatment, his kidney function did not improve and he remained on hemodialysis but needed to stay on small dose of Prednisone to keep his calcium under control. Our case is the first in the literature that demonstrates the natural history of renal-confined sarcoidosis. In addition, the presence of MGUS created a diagnostic challenge and delayed diagnosis of sarcoidosis. Although the renal biopsy did not show direct damage from MGUS, a potential relation between renal sarcoidosis and MGUS is worth studied. PMID:24761384

  15. Systemic Sarcoidosis Mimicking a Behavioural Variant of Frontotemporal Dementia

    PubMed Central

    De Maindreville, Anne; Bedos, Line; Bakchine, Serge

    2015-01-01

    Among rare neurological manifestations, a progressive dementia may exceptionally be the revealing clinical feature of a sarcoidosis. Diagnosis may then be difficult, especially when systemic signs are missing or latent, with a risk of therapeutic delay. We report the first case of sarcoidosis mimicking a frontotemporal dementia. A 53-year-old man presented with a dementia clinically suggestive of frontotemporal dementia, progressing slowly for about 2 years. However, MRI revealed unusual aspects, mainly large areas of T2/FLAIR hypersignal within temporal regions and cerebellum, with nodular leptomeningeal and juxtacortical Gadolinium enhancement. The patient was finally diagnosed with a systemic sarcoidosis. We discuss the differential diagnosis based on MRI aspects and review the literature on the clinical, biological, and imaging features of sarcoidosis presenting with dementia. This case demonstrates that brain imaging remains mandatory in the exploration process of a patient with dementia. Although the patient presented with rather typical features of a behavioural variant of frontotemporal dementia, the MRI aspect was the key exploration that leaded to the diagnosis. PMID:26442161

  16. Early microglia activation in a mouse model of chronic glaucoma

    PubMed Central

    Bosco, Alejandra; Steele, Michael R.; Vetter, Monica L.

    2014-01-01

    Changes in microglial cell activation and distribution are associated with neuronal decline in the CNS, particularly under pathological conditions. Activated microglia converge on the initial site of axonal degeneration in human glaucoma, yet, their part in its pathophysiology remains unresolved. To begin with, it is unknown whether microglia activation precedes or is a late consequence of retinal ganglion cell (RGC) neurodegeneration. Here, we address this critical element in DBA/2J (D2) mice, an established model of chronic inherited glaucoma, using as a control the congenic substrain DBA/2J Gpnmb+/SjJ (D2G), which is not affected by glaucoma. We analyzed the spatial distribution and timecourse of microglial changes in the retina, as well as within the proximal optic nerve prior to and throughout ages when neurodegeneration has been reported. Exclusively in D2 mice, we detected early microglia clustering in the inner central retina and unmyelinated optic nerve regions, with microglia activation peaking by 3 months of age. Between 5 and 8 months of age, activated microglia persisted and concentrated in the optic disc, but also localized to the retinal periphery. Collectively, our findings suggest microglia activation is an early alteration in the retina and optic nerve in D2 glaucoma, potentially contributing to disease onset or progression. Ultimately, detection of microglial activation may have value in early disease diagnosis, while modulation of microglial responses may alter disease progression. PMID:21246546

  17. Cardiac sarcoidosis-state of the art review.

    PubMed

    Hulten, Edward; Aslam, Saira; Osborne, Michael; Abbasi, Siddique; Bittencourt, Marcio Sommer; Blankstein, Ron

    2016-02-01

    Sarcoidosis is a multi-system inflammatory disorder of unknown etiology resulting in formation of non-caseating granulomas. Cardiac involvement-which is associated with worse prognosis-has been detected in approximately 25% of individuals based on autopsy or cardiac imaging studies. Nevertheless, the diagnosis of cardiac sarcoidosis is challenging due to the low yield of endomyocardial biopsy, and the limited accuracy of various clinical criteria. Thus, no gold standard diagnostic criterion exists. This review will summarize the pathophysiology, diagnosis, and treatment of cardiac sarcoidosis with a focus on advanced cardiovascular imaging, We review the evidence to support a role for cardiac magnetic resonance (CMR) imaging in the initial evaluation of selected patients with suspected cardiac sarcoidosis, with cardiac positron emission tomography (PET) as an alternative or complementary initial diagnostic test in a subgroup of patients in whom CMR may be contra-indicated or when CMR is negative with continued clinical concern for myocardial inflammation. In addition to the diagnostic value of these tests, CMR and PET are also useful in identifying patients who have higher risk of adverse events such as ventricular tachycardia or death, in whom preventive therapies such as defibrillators should be more strongly considered. Although no randomized controlled trials for treatment of cardiac sarcoidosis exist, immunosuppressive therapy is often used. We review emerging evidence regarding the use of cardiac PET to identify and quantity the amount of myocardial inflammation as well as to guide the use of immunotherapy. Future studies are needed to determine the benefit of imaging guided therapies aimed at improving patient outcomes. PMID:26885492

  18. Tuberculosis lymphadenitis in a well managed case of sarcoidosis.

    PubMed

    Mohapatra, P R; Garg, Kranti; Singhal, Niti; Aggarwal, D; Gupta, R; Khurana, A; Janmeja, A K

    2013-01-01

    Differentiation between tuberculosis (TB) and sarcoidoisis is sometimes extremely difficult. Sequential occurrence of sarcoidosis and TB in the same patient is uncommon. We present the case of a young man, with a proven diagnosis of sarcoidosis who later developed TB after completion of treatment for sarcoidosis. A 32-year-old male patient presented with low-grade fever since two months. Physical examination revealed cervical lymphadenopathy. Initial fine needle aspiration cytology (FNAC) of the cervical lymph node was suggestive of granulomatous inflammation; the chest radiograph was normal. Repeat FNAC from the same lymph node was suggestive of reactive lymphoid hyperplasia. The patient was treated with antibiotics and followed-up. He again presented with persistence of fever and lymphadenopathy and blurring of vision. Ophthalmological examination revealed uveitis, possibly due to a granulomatous cause. His repeat Mantoux test again was non-reactive; serum angiotensin converting enzyme (ACE) levels were raised. This time an excision biopsy of the lymph node was done which revealed discrete, non-caseating, reticulin rich granulomatous inflammation suggestive of sarcoidosis. The patient was treated with oral prednisolone and imporved symptomatically. Subsequently, nearly nine months after completion of corticosteroid treatment, he presented with low-grade, intermittent fever and a lymph node enlargement in the right parotid region. FNAC from this lymph node showed caseating granulomatous inflammation and the stain for acid-fast bacilli was positive. He was treated with Category I DOTS under the Revised National Tuberculosis Control Programme and improved significantly. The present case highlights the need for further research into the aetiology of TB and sarcoidosis. PMID:24660565

  19. Reduced Oxygen Uptake Efficiency Slope in Patients with Cardiac Sarcoidosis

    PubMed Central

    Ammenwerth, Wilhelm; Wurps, Henrik; Klemens, Mark A.; Crolow, Catharina; Schulz-Menger, Jeanette; Schönfeld, Nicolas; Bittner, Roland C.; Bauer, Torsten T.

    2014-01-01

    Background The non-invasive diagnosis of cardiac sarcoidosis (CS) is difficult. Cardiovascular magnetic resonance (CMR) has become a very valuable diagnostic tool in patients with suspected CS, but usually a combination of different tests is used. Oxygen uptake efficiency slope (OUES) is a parameter of cardiopulmonary exercise testing (CPET), which is used as an indicator for cardiovascular impairment. We investigated the predictive value of OUES for the diagnosis of myocardial involvement in sarcoid patients. Methods Retrospectively 37 consecutive patients (44.9±13.8 years) with histologically confirmed sarcoidosis and clinical suspicion of heart involvement underwent noninvasive diagnostic testing including CMR. CS was diagnosed according to the guidelines from the Japanese Society of Sarcoidosis and other Granulomatous Disorders with additional consideration of CMR findings. Furthermore, CPET with calculation of predicted OUES according to equations by Hollenberg et al. was carried out. Results Patients with CS (11/37; 30%) had a worse cardiovascular response to exercise. OUES was significantly lower in CS-group compared to non-CS-group (59.3±19.1 vs 88.0±15.4%pred., p<0.0001). ROC curve method identified 70%pred. as the OUES cut-off point, which maximized sensitivity and specificity for detection of CS (96% sensitivity, 82% specificity, 89% overall accuracy). OUES <70%pred. was the single best predictor of CS (Odds ratio: 100.43, 95% CI: 1.99 to 5064, p<0.001) even in multivariate analyses. Conclusion OUES assessed in CPET may be helpful in identifying patient with cardiac involvement of sarcoidosis. Patient selection for CMR may be assisted by CPET findings in patients with sarcoidosis. PMID:25029031

  20. In vitro gallium-67 lung index for the evaluation of sarcoidosis

    SciTech Connect

    Braude, A.C.; Cohen, R.; Rahmani, R.; Hornstein, A.; Klein, M.; Meindok, H.O.; Chamberlain, D.W.; Rebuck, A.S.

    1984-11-01

    In the evaluation of the active alveolitis of pulmonary sarcoidosis, both the proportional lymphocyte count obtained by bronchoalveolar lavage and state of activation of the alveolar macrophage by gallium scanning are required. We injected 6 mCi (200 MBq) of /sup 67/Ga intravenously on 24 occasions in 13 patients with biopsy-proved sarcoidosis. Forty-eight hours later, patients were scanned with a rectilinear scanner and the generated scintigrams were evaluated using the NIH index. Seventy-two hours after injection, bronchoalveolar lavage was performed, and venous blood was sampled. The harvested lavage fluid was analyzed for absolute and proportional cell counts, and radioactivity was measured in blood and BAL fluid. An in vitro /sup 67/Ga index was generated and expressed as counts/100,000 alveolar macrophages/ml blood (mean, 0.0146 +/- 0.0087 SD). There was a significant relationship between the in vitro index and proportional lymphocyte BAL counts (r . 0.79; p less than 0.002) that was comparable to that obtained using the NIH index (r . 0.74; p less than 0.005). These data suggest that the in vitro index might offer a more objective assessment of /sup 67/Ga uptake by the lung, but this would require validation against clinical parameters in a prospective study.

  1. Thomé Villar memorial lecture--the many faces of sarcoidosis.

    PubMed

    James, D G

    1989-10-01

    The late and great Thomé Villar established a basic understanding of sarcoidosis in Lisbon, and his successors have added scholarly contributions to this firm foundation. He recognised its worldwide distribution and prevalence, the several interwoven patterns of presentation, the importance of histological confirmation, and the value of corticosteroid therapy. His successors have clarified our understanding of extrinsic allergic alveolitis (hypersensitivity pneumonitis), shown us how to differentiate the two disorders and expanded our knowledge of immunology and markers of activity of both disorders. Although we do not know the cause, we can recognise the terrain or soil in which it flourishes; factors which includes age, sex, race, HLA affinity and hormonal status. The road which will lead us to the cause(s) is in immunology, particularly macrophages and lymphocytes and the chemical mediators which influence the development of granuloma formation and ultimate fibrosis. Professor Thomé George Villar was a Man of Lisbon in every sense of the word - by birth, education, and academic achievement. He would have rejoiced that Lisbon was chosen for an International Conference on Sarcoidosis and he would have approved of his successor's choice of four topics--granuloma formation, granuloma vasculitis, markers of activity and occupational granulomatous lung disease. These are all important growing points in our advances in knowledge. PMID:2623377

  2. Systemic sarcoidosis with hypercalcaemia, hypothalamic-pituitary dysfunction and thyroid involvement.

    PubMed

    Alsahwi, Nassib; Blavo, Delali; Karanchi, Harsha

    2016-01-01

    Sarcoidosis is a multisystem granulomatous disorder. The lungs are the principal organs affected, however, extrapulmonary involvement including disorders of the pituitary and thyroid glands has been reported but presentation with multiple endocrine manifestations is rare. We report the case of a 36-year-old African-American woman who presented with hypercalcaemia, abnormal thyroid function studies and secondary amenorrhoea. On workup including laboratory, radiological testing and biopsy she was diagnosed with sarcoidosis with multi-organ involvement. Endocrine manifestations included non-parathyroid hormone mediated hypercalcaemia related to sarcoidosis, thyroid involvement with sarcoidosis and hypothalamic-pituitary involvement with a sellar and suprasellar mass associated with secondary adrenal insufficiency, secondary hypogonadism, growth hormone deficiency and secondary hypothyroidism. We report to the best of our knowledge the first case of simultaneous multiple endocrine manifestations of sarcoidosis that included hypercalcaemia, hypopituitarism and sarcoidosis of the thyroid gland. PMID:27495178

  3. Key messages from a rare case of annular sarcoidosis of scalp

    PubMed Central

    Bhushan, Premanshu; Thatte, Sarvesh S.; Singh, Avninder

    2016-01-01

    Sarcoidosis, a multisystem disease of obscure etiology, is characterized by the formation of noncaseating epithelioid cell granulomas in several organs or tissues. The diagnosis of sarcoidosis requires a compatible clinical picture, histologic demonstration of noncaseating granulomas, and exclusion of other diseases capable of producing similar histology or clinical features. The lung is the most commonly affected organ, but the skin is frequently involved. Sarcoidosis occurs worldwide and affects all ages and races with female predominance. Scalp involvement is decidedly rare among the myriad cutaneous manifestations of sarcoidosis. Alopecia is common in sarcoidosis and is generally scarring in nature. Annular sarcoidosis is a rare morphology and annular sarcoid of scalp is seldom reported. Herein we present a case of annular scalp sarcoid with systemic involvement and without alopecia. PMID:27294057

  4. Key messages from a rare case of annular sarcoidosis of scalp.

    PubMed

    Bhushan, Premanshu; Thatte, Sarvesh S; Singh, Avninder

    2016-01-01

    Sarcoidosis, a multisystem disease of obscure etiology, is characterized by the formation of noncaseating epithelioid cell granulomas in several organs or tissues. The diagnosis of sarcoidosis requires a compatible clinical picture, histologic demonstration of noncaseating granulomas, and exclusion of other diseases capable of producing similar histology or clinical features. The lung is the most commonly affected organ, but the skin is frequently involved. Sarcoidosis occurs worldwide and affects all ages and races with female predominance. Scalp involvement is decidedly rare among the myriad cutaneous manifestations of sarcoidosis. Alopecia is common in sarcoidosis and is generally scarring in nature. Annular sarcoidosis is a rare morphology and annular sarcoid of scalp is seldom reported. Herein we present a case of annular scalp sarcoid with systemic involvement and without alopecia. PMID:27294057

  5. Sarcoidosis during etanercept treatment for rheumatoid arthritis in women with a history of bilateral oophorectomy.

    PubMed

    Sawahata, Michiru; Sigiyama, Yukihiko; Yamasawa, Hideaki; Miki, Atsushi; Yamamoto, Hisashi; Muto, Shigeaki; Yamamoto, Hironori; Bando, Masashi

    2016-01-01

    nd in immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA). Paradoxically, this treatment induces sarcoidosis in a small population of RA patients as a class effect. A safer anti-TNF therapeutic strategy requires understanding of the risk factors for sarcoidosis. In Japan, TNF inhibitor was introduced in 2003. We reviewed 226 consecutive patients (65 men and 161 women) who were newly diagnosed with sarcoidosis between 2003 and 2012 at Jichi Medical University Hospital, Japan. We detected 3 cases in which sarcoidosis developed during etanercept treatment for RA. All 3 cases were women who had undergone bilateral oophorectomy more than 20 years earlier. Taken together with our previous epidemiologic findings of a consistently maintained second peak after menopause in the age-specific distribution of sarcoidosis in women over four decades, long-term insidious ovarian dysfunction was a possible risk factor for sarcoidosis under certain conditions, especially during etanercept treatment. PMID:27537723

  6. Return to activity following fasciotomy for chronic exertional compartment syndrome.

    PubMed

    Irion, Val; Magnussen, Robert A; Miller, Timothy L; Kaeding, Christopher C

    2014-10-01

    Diagnosis of chronic exertional compartment syndrome (CECS) is relatively rare but has been well documented in athletes. There are, however, few reports regarding return to athletic activity after surgery among elite-level athletes. We hypothesized that a majority of elite-level athletes would successfully return to their previous level of competition following fasciotomy for CECS. A retrospective chart review was performed to identify elite-level athletes (collegiate or professional sport participation) who underwent fasciotomy for CECS over a 3-year period. Data collected included sport or activity, treatment and surgical details, time away from sport/activity after surgery, and ability to return to prior level of activity. Six males and seven females were included in the analysis. Patient age ranged from 17 to 24 years with a mean of 19.7 years. Six patients underwent unilateral lower extremity compartment release, and seven underwent bilateral lower extremity compartment release. The anterior and lateral compartments alone were released in 11 patients (84.6%). Two patients (15.4%) underwent four-compartment releases. Eleven patients (84.6%) were able to return to their previous elite level of sport participation at a mean of 10.6 weeks following surgical fasciotomy. Patients who had four-compartment release had a more than 3.5 week average longer return to full sporting activities (p = 0.011). Fasciotomy is effective in allowing elite athletes with CECS to return to sport. PMID:24664450

  7. Overcoming the Influence of Chronic Pain on Older Patients' Difficulty with Recommended Self-Management Activities

    ERIC Educational Resources Information Center

    Krein, Sarah L.; Heisler, Michele; Piette, John D.; Butchart, Amy; Kerr, Eve A.

    2007-01-01

    Purpose: Many older patients with common chronic conditions also experience chronic pain. We examined how chronic pain affects patients' difficulty with recommended self-management activities and the potential intervening role of self-efficacy (the level of confidence in one's own ability to perform a specific task). Design and Methods: We…

  8. Reduced Variability of Auditory Alpha Activity in Chronic Tinnitus

    PubMed Central

    Schecklmann, Martin; Kreuzer, Peter M.; Vielsmeier, Veronika; Poeppl, Timm B.; Langguth, Berthold

    2014-01-01

    Subjective tinnitus is characterized by the conscious perception of a phantom sound which is usually more prominent under silence. Resting state recordings without any auditory stimulation demonstrated a decrease of cortical alpha activity in temporal areas of subjects with an ongoing tinnitus perception. This is often interpreted as an indicator for enhanced excitability of the auditory cortex in tinnitus. In this study we want to further investigate this effect by analysing the moment-to-moment variability of the alpha activity in temporal areas. Magnetoencephalographic resting state recordings of 21 tinnitus subjects and 21 healthy controls were analysed with respect to the mean and the variability of spectral power in the alpha frequency band over temporal areas. A significant decrease of auditory alpha activity was detected for the low alpha frequency band (8–10 Hz) but not for the upper alpha band (10–12 Hz). Furthermore, we found a significant decrease of alpha variability for the tinnitus group. This result was significant for the lower alpha frequency range and not significant for the upper alpha frequencies. Tinnitus subjects with a longer history of tinnitus showed less variability of their auditory alpha activity which might be an indicator for reduced adaptability of the auditory cortex in chronic tinnitus. PMID:24967106

  9. Sympatho-adrenal activation by chronic intermittent hypoxia

    PubMed Central

    Kumar, Ganesh K.; Peng, Ying-Jie

    2012-01-01

    Recurrent apnea with chronic intermittent hypoxia (CIH) is a major clinical problem in adult humans and infants born preterm. Patients with recurrent apnea exhibit heightened sympathetic activity as well as elevated plasma catecholamine levels, and these phenotypes are effectively recapitulated in rodent models of CIH. This article summarizes findings from studies addressing sympathetic activation in recurrent apnea patients and rodent models of CIH and the underlying cellular and molecular mechanisms. Available evidence suggests that augmented chemoreflex and attenuated baroreflex contribute to sympathetic activation by CIH. Studies on rodents showed that CIH augments the carotid body response to hypoxia and attenuates the carotid baroreceptor response to increased sinus pressures. Processing of afferent information from chemoreceptors at the central nervous system is also facilitated by CIH. Adult and neonatal rats exposed to CIH exhibit augmented catecholamine secretion from the adrenal medulla. Adrenal demedullation prevents the elevation of circulating catecholamines in CIH-exposed rodents. Reactive oxygen species (ROS)-mediated signaling is emerging as the major cellular mechanism triggering sympatho-adrenal activation by CIH. Molecular mechanisms underlying increased ROS generation by CIH seem to involve transcriptional dysregulation of genes encoding pro-and antioxidant enzymes by hypoxia-inducible factor-1 and -2, respectively. PMID:22723632

  10. Decoding upper limb residual muscle activity in severe chronic stroke

    PubMed Central

    Ramos-Murguialday, Ander; García-Cossio, Eliana; Walter, Armin; Cho, Woosang; Broetz, Doris; Bogdan, Martin; Cohen, Leonardo G; Birbaumer, Niels

    2015-01-01

    Objective Stroke is a leading cause of long-term motor disability. Stroke patients with severe hand weakness do not profit from rehabilitative treatments. Recently, brain-controlled robotics and sequential functional electrical stimulation allowed some improvement. However, for such therapies to succeed, it is required to decode patients' intentions for different arm movements. Here, we evaluated whether residual muscle activity could be used to predict movements from paralyzed joints in severely impaired chronic stroke patients. Methods Muscle activity was recorded with surface-electromyography (EMG) in 41 patients, with severe hand weakness (Fugl-Meyer Assessment [FMA] hand subscores of 2.93 ± 2.7), in order to decode their intention to perform six different motions of the affected arm, required for voluntary muscle activity and to control neuroprostheses. Decoding of paretic and nonparetic muscle activity was performed using a feed-forward neural network classifier. The contribution of each muscle to the intended movement was determined. Results Decoding of up to six arm movements was accurate (>65%) in more than 97% of nonparetic and 46% of paretic muscles. Interpretation These results demonstrate that some level of neuronal innervation to the paretic muscle remains preserved and can be used to implement neurorehabilitative treatments in 46% of patients with severe paralysis and extensive cortical and/or subcortical lesions. Such decoding may allow these patients for the first time after stroke to control different motions of arm prostheses through muscle-triggered rehabilitative treatments. PMID:25642429

  11. Chronic active thrombotic microangiopathy in native and transplanted kidneys.

    PubMed

    Zhang, Ping L; Prichard, Jeffery W; Lin, Fan; Shultz, Michael F; Malek, Sayeed K; Shaw, John H; Hartle, James E

    2006-01-01

    We report 2 complicated cases of thrombotic microangiopathy with chronic features and active components. The first case was a 36-yr-old woman with positive anti-DNA antibody and possible lupus cerebritis, who developed thrombotic microangiopathy secondary to a series of syndromes, including preeclampsia and anti-phospholipid antibody syndrome. Renal biopsy revealed no evidence of lupus nephritis and her renal function returned to normal 1 week after the biopsy. The second case was a 46-yr-old man who developed thrombotic microangiopathy of unknown etiology, which led to end-stage renal disease within 6 mo. The patient received a living related-donor transplant, but thrombotic microangiopathy recurred in the donor kidney only 40 days after the renal transplantation. PMID:16951274

  12. Hypercalcemia and renal failure in the course of sarcoidosis--case report.

    PubMed

    Kempisty, Anna; Kuś, Jan

    2012-01-01

    Disturbances of calcium metabolism such as hypercalcemia or/and hypercalciuria in the course of sarcoidosis can be a cause of renal failure in some patients. Life threatening hypercalcemia in sarcoidosis patients is not very frequent. Severe hypercalcemia leading to renal insufficiency is a very rare condition. We present a case of 53-year old man who was admitted to Department of Lung Diseases because of hypercalcemic syndrome and renal failure, and in whom diagnosis of sarcoidosis was made. He was successfully treated with systemic corticosteroids. In this article we present physiological mechanism of hypercalcemia in sarcoidosis patients, mechanism of renal damage and management of these difficult problems. PMID:23109211

  13. Sarcoid Myositis with Anti-Ku Antibody Consistent with both Sarcoidosis and Polymyositis.

    PubMed

    Awano, Nobuyasu; Fukuda, Kensuke; Sakayori, Masashi; Kondoh, Keisuke; Ono, Ryu; Moriya, Atsuko; Ando, Tsunehiro; Kumasaka, Toshio; Takemura, Tamiko; Ikushima, Soichiro

    2016-01-01

    We herein describe a case of sarcoid myositis with anti-Ku antibody positivity. Pathological findings of the muscle were compatible with sarcoidosis, but could not be completely distinguished from myositis diseases that arise from other causes. According to a physical examination, pathological findings, the detection of anti-Ku antibody and the human leukocyte antigen (HLA)-DPB1 allele, we strongly suspected that the patient developed both sarcoidosis and polymyositis. Sarcoidosis is often complicated by autoimmune diseases. This case suggests the possibility that sarcoidosis and other autoimmune diseases may have common causal genetic factors. PMID:27477413

  14. Influenza vaccination in patients with pulmonary sarcoidosis: efficacy and safety

    PubMed Central

    Tavana, Sasan; Argani, Hassan; Gholamin, Sharareh; Razavi, Seyed‐Mostafa; Keshtkar‐Jahromi, Marzieh; Talebian, Amir S.; Moghaddam, Keivan G.; Sepehri, Zahra; Azad, Talat M.; Keshtkar‐Jahromi, Maryam

    2011-01-01

    Please cite this paper as: Tavana et al. (2011) Influenza vaccination in patients with pulmonary sarcoidosis: efficacy and safety. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2011.00290.x. Background  Sarcoidosis is an inflammatory, granulomatous disorder of unknown etiology. The role of cellular and humoral immune systems in this disease is unclear, whereas dysregulation of the immune system is suggested. Patients with sarcoidosis show diverse responses while exposed to various antigens. Although influenza vaccination is recommended in pulmonary sarcoidosis, its efficacy and safety has not been investigated. Objectives  To evaluate safety and immunogenicity of influenza vaccine in patients with sarcoidosis. Patients/Methods  Influenza vaccination was performed in 23 eligible patients with sarcoidosis (SP) and 26 healthy controls (HC). Antibody titers against H1N1, H3N2, and B influenza virus antigens were evaluated just before and 1 month after vaccination. Patients were followed for 6 months to assess vaccine safety. Results  Serological response and magnitude of changes in antibody titers against influenza vaccine antigens were comparable between SPs and HCs. Women showed a better serological response against B antigen (P = 0·034) than men. Twenty‐four‐hour urine calcium was associated with antibody response against H1N1 [correlation coefficient (CC) = 0·477, P = 0·003] and H3N2 (CC = 0·352, P = 0·028) antigens. Serum angiotensin‐converting enzyme correlated negatively with antibody response against B antigen (CC = −0·331, P = 0·040). Higher residual volume was associated with fewer rises in antibody titer against H3N2 antigen (CC = −0·377, P = 0·035). No major adverse events or disease flare‐up was observed during follow‐up. Conclusions  In this study, influenza vaccination did not cause any major adverse event in SPs, and their serological response was equal to HCs

  15. Trends in activity-limiting chronic conditions among children.

    PubMed Central

    Newacheck, P W; Budetti, P P; Halfon, N

    1986-01-01

    Data from the National Health Interview Survey indicate that the prevalence of activity-limiting chronic conditions among children under age 17 years doubled between 1960 and 1981, from 1.8 to 3.8 per cent. Approximately 40 per cent of the overall rise in prevalence occurred before 1970. Most of the increase in prevalence during this early period can be attributed to changes in questionnaire design and aging of the child population following the "baby boom" years. The factors responsible for increases in reported cases of activity limitation following 1970 are more difficult to specify and evaluate. During this later period, the increase in prevalence was restricted to less severe levels of limitations. While prevalence levels rose for a variety of conditions during this period, respiratory conditions and mental and nervous system disorders demonstrated the largest changes. It appears that much of the increase in reported cases of activity limitations during the 1970s can be attributed to shifting perceptions on the part of parents, educators, and physicians. PMID:2936257

  16. Physical Activity and Hemodynamic Reactivity in Chronic Kidney Disease

    PubMed Central

    Agarwal, Rajiv; Light, Robert P.

    2008-01-01

    Background and objectives: Patients with chronic kidney disease (CKD) have an elevated cardiovascular risk. This study was designed to understand better the presence and strength of the relationship between physical activity and BP and to explore determinants of hemodynamic reactivity. Design, setting, participants, & measurements: Twenty-four patients with CKD (mean age 69.5 yr; 3.1 antihypertensive drugs; estimated GFR 47 ml/min per 1.73 m2, albumin/creatinine ratio 403 mg/g) were studied on three occasions during a 6-wk period with 24-h ambulatory BP monitoring and simultaneous activity monitoring with wrist actigraphy. Results: Nondippers were found have a greater level of sleep activity compared with dippers, although the awake activity level was similar (7.06 versus 6.73) between groups (P = 0.042 for interaction). In 3587 BP activity pairs, hemodynamic reactivity was variable between individuals (systolic BP reactivity 1.06 [SD 10.50]; diastolic BP reactivity 0.89 [SD 7.80] heart rate reactivity 1.18 [SD 11.00]); those who were more sedentary had a greater increment in systolic BP compared with those who were less sedentary. Antihypertensive drugs blunted hemodynamic reactivity. Hemodynamic reactivity was greatest between 12 a.m. and 8 a.m., making this a vulnerable period for cardiovascular events. Conclusions: Greater hemodynamic reactivity in sedentary people with CKD offers a possible and thus far unrecognized mechanism of cardiovascular damage. Besides reducing BP, antihypertensive drugs reduce hemodynamic reactivity, which offers another plausible mechanism of cardiovascular protection with their use. PMID:18922983

  17. Recording sympathetic nerve activity chronically in rats: surgery techniques, assessment of nerve activity, and quantification

    PubMed Central

    Muntzel, Martin S.

    2013-01-01

    The sympathetic nervous system plays a pivotal role in homeostasis through its direct innervation and functional impact on a variety of end organs. In rats, a number of methods are available to assess sympathetic nervous system function. Traditionally, direct recording of sympathetic nerve activity (SNA) has been restricted to acute, anesthetized preparations or conscious animals within a few days after electrode implantation. However, these approaches provide short-term data in studies designed to investigate changes in SNA during chronic disease states. Over the last several years, chronic SNA recording has been pioneered in rabbits and more recently in rats. The purpose of this article is to provide insights and a “how to” guide for chronic SNA recordings in rats based on experiences from two independent laboratories. We will present common methodologies used to chronically record SNA, characteristics and methods to distinguish sympathetic bursts versus electrical artifacts (and provide corresponding audio clips when available), and provide suggestions for analysis and presentation of data. In many instances, these same guidelines are applicable to acute SNA recordings. Using the surgical approaches described herein, both laboratories have been able to chronically record SNA in >50% of rats for a duration >3 wk. The ability to record SNA over the time course of several weeks will, undoubtedly, greatly impact the field of autonomic and cardiovascular physiology. PMID:24014674

  18. Sarcoidosis following successful treatment of pemphigus vulgaris with rituximab: a rituximab-induced reaction further supporting B-cell contribution to sarcoidosis pathogenesis?

    PubMed

    Galimberti, F; Fernandez, A P

    2016-06-01

    The anti-CD20 peripheral B-cell depleting monoclonal antibody, rituximab, has been shown to be a safe and effective treatment for refractory pemphigus vulgaris (PV), a potentially fatal autoimmune blistering disease. We report a patient who developed skin nodules and arthralgias following successful treatment of refractory PV with rituximab. Clinical, serological and histological findings were consistent with a diagnosis of sarcoidosis. The nodules promptly responded to treatment with corticosteroids, and resolved without recurrence when the medication was tapered several months later. The temporal onset of sarcoidosis following treatment with rituximab and the eventual resolution, coupled with the remarkable similarities between the B-cell immunological environment expected in our patient during the post-rituximab period and the immunological environment described in patients with idiopathic sarcoidosis, strongly implicates exposure to rituximab as the trigger for sarcoidosis development in our patient. We propose that rituximab-induced sarcoidal granulomas may be a rare adverse effect of treatment with this medication, providing further support for an important role of B cells in the pathogenesis of sarcoidosis. With better understanding of the circumstances surrounding sarcoidosis development following rituximab administration, this medication could potentially be used to induce sarcoidosis in animal research models to study the immunopathogenesis of this disease. PMID:26800651

  19. Spontaneous improvement of laryngeal sarcoidosis resistant to systemic corticosteroid administration

    PubMed Central

    Tsubouchi, Kazuya; Hamada, Naoki; Ijichi, Kayo; Umezaki, Toshiro; Takayama, Koichi; Nakanishi, Yoichi

    2015-01-01

    We report herein a case of laryngeal sarcoidosis that was refractory to systemic corticosteroids, but that improved spontaneously. A 49-year-old woman complained of dysphagia and hoarseness with accompanying edematous swellings of both arytenoid regions. She was referred to our hospital after systemic corticosteroid therapy failed to achieve any improvement. Laryngoscopy showed marked edema of the epiglottis and both arytenoid regions. The flow–volume curve on spirometry showed flattening of the expiratory flows. Histopathological examination of the arytenoid region showed non-caseating epithelioid granulomas, and laryngeal sarcoidosis was diagnosed with the result of BAL study. She was observed without treatment as symptoms were mild. Although edema of the left arytenoid region seemed to be somewhat worsened after 6 months, she continued to be followed closely because of improvements in the flow–volume curve and increasing peak expiratory flow. By 1 year after onset, symptoms and epiglottal swelling had spontaneously improved. PMID:26392860

  20. Chronic pain management in the active-duty military

    NASA Astrophysics Data System (ADS)

    Jamison, David; Cohen, Steven P.

    2012-06-01

    As in the general population, chronic pain is a prevalent and burdensome affliction in active-duty military personnel. Painful conditions in military members can be categorized broadly in terms of whether they arise directly from combat injuries (gunshot, fragmentation wound, blast impact) or whether they result from non-combat injuries (sprains, herniated discs, motor vehicle accidents). Both combat-related and non-combat-related causes of pain can further be classified as either acute or chronic. Here we discuss the state of pain management as it relates to the military population in both deployed and non-deployed settings. The term non-battle injury (NBI) is commonly used to refer to those conditions not directly associated with the combat actions of war. In the history of warfare, NBI have far outstripped battle-related injuries in terms not only of morbidity, but also mortality. It was not until improvements in health care and field medicine were applied in World War I that battle-related deaths finally outnumbered those attributed to disease and pestilence. However, NBI have been the leading cause of morbidity and hospital admission in every major conflict since the Korean War. Pain remains a leading cause of presentation to military medical facilities, both in and out of theater. The absence of pain services is associated with a low return-to-duty rate among the deployed population. The most common pain complaints involve the low-back and neck, and studies have suggested that earlier treatment is associated with more significant improvement and a higher return to duty rate. It is recognized that military medicine is often at the forefront of medical innovation, and that many fields of medicine have reaped benefit from the conduct of war.

  1. T-cell activation profiles in different granulomatous interstitial lung diseases--a role for CD8+CD28(null) cells?

    PubMed

    Heron, M; Claessen, A M E; Grutters, J C; van den Bosch, J M M

    2010-05-01

    Lymphocytes play a crucial role in lung inflammation. Different interstitial lung diseases may show distinct lymphocyte activation profiles. The aim of this study was to examine the expression of a variety of activation markers on T lymphocyte subsets from blood and bronchoalveolar lavage fluid (BALF) of patients with different granulomatous interstitial lung diseases and healthy controls. Bronchoalveolar lavage cells and blood cells from 23 sarcoidosis patients, seven patients with hypersensitivity pneumonitis and 24 healthy controls were analysed. Lymphocyte activation status was determined by flow cytometry. Lymphocytes were stained with antibodies against CD3, CD4, CD8, CD25, CD28, CD69, very late antigen-1 (VLA)-1, VLA-4 and human leucocyte antigen D-related (HLA-DR). In general, CD28, CD69 and VLA-1 expression on BALF CD4+ lymphocytes and HLA-DR expression on BALF CD8+ lymphocytes was different in patients with hypersensitivity pneumonitis and sarcoidosis patients with parenchymal involvement. This BALF lymphocyte phenotype correlated with carbon monoxide diffusing lung capacity (Dlco) values across interstitial lung diseases (ILD) (r2 = 0.48, P = 0.0002). In sarcoidosis patients, CD8+CD28(null) blood lymphocytes correlated with lower Dlco values (r = -0.66, P = 0.004), chronic BALF lymphocyte activation phenotype (r2 = 0.65, P < 0.0001), radiographic staging (stage I versus stage II and higher, P = 0.006) and with the need for corticosteroid treatment (P = 0.001). Higher expression of CD69, VLA-1 and HLA-DR and lower expression of CD28 on BALF lymphocytes suggests prolonged stimulation and chronic lymphocyte activation in patients with ILD. In sarcoidosis, blood CD8+CD28(null) cells might be a new biomarker for disease severity but needs further investigation. PMID:20030671

  2. Steroid-Sparing effects of pentoxifylline in pulmonary sarcoidosis

    PubMed Central

    Park, M.K.; Fontana, J.R.; Babaali, H.; Gilbert-McClain, L.I.; Stylianou, M.; Joo, J.; Moss, J.; Manganiello, V.C.

    2010-01-01

    Background Agents that target pro-inflammatory cytokines may be useful in pulmonary sarcoidosis. Objective To determine effectiveness of a non-selective cyclic nucleotide phosphodiesterase (PDE) inhibitor, pentoxifylline (POF). Design Randomized, double-blind, placebo-controlled trial Setting Clinical Research Center, National Institutes of Health. Patients 27 patients with biopsy-confirmed pulmonary sarcoidosis receiving prednisone. Intervention Placebo or POF (1200-2000 mg/day) for 10 months, as prednisone was tapered. Measurements Primary endpoints: sustained improvement in two or more pulmonary function parameters, or a combination of one pulmonary function parameter and dyspnea. Results Except for one patient, primary endpoints were not reached in POF-treated patients. Therefore, a post hoc analysis was performed. The observed relative risk reduction for flares associated with POF treatment was 54.9% (95% CI 0.21, 0.89) and the absolute risk reduction was 50.6% (95% CI 0.22, 0.80). Compared to placebo treatment, in the POF group, the mean prednisone dose was lower at 8 and 10 months (p = 0.007 and 0.01 respectively), and there was a trend towards less prednisone usage over the entire study period (p = 0.053), as determined by cumulative change analysis. Conclusions Although our exploratory post hoc analysis suggested that POF reduced flares and had steroid-sparing effects, given the study limitations, definitive conclusions cannot be drawn regarding the efficacy of POF in pulmonary sarcoidosis. In addition, gastrointestinal side-effects, at the doses used, would seem to limit the use of POF in treating pulmonary sarcoidosis. Overall, however, this trial may provide a basis for using more specific, better-tolerated, PDE inhibitors in future clinical trials. PMID:20560292

  3. Treatment of laryngeal sarcoidosis with intralesional steroid injection.

    PubMed

    Krespi, Y P; Mitrani, M; Husain, S; Meltzer, C J

    1987-01-01

    Laryngeal sarcoidosis presents with hoarseness, cough, and dysphagia. Shortness of breath due to upper airway obstruction may occur. Indirect laryngoscopy reveals mucosal edema and erythema, granulomas, and nodules. The supraglottic larynx is the most frequently affected area. Systemic corticosteroids can be used initially; however, with persistent symptoms and/or severe airway problems, intralesional steroid injections may be more effective, as in the six patients presented. PMID:3688765

  4. Cardiac sarcoidosis &hypen; the value of magnetic resonance imaging.

    PubMed

    Smedema, J. P.; Doubell, A. F.

    2000-08-01

    This report describes the management of a 40-year-old woman presenting with recurrent monomorphic ventricular tachycardias secondary to cardiac sarcoidosis. She was managed with a combination of steroids, azathioprine and mexiletine. Magnetic resonance imaging proved to be of great help in diagnosing this condition as well as in following up the response to therapy. A brief review on the management of this condition is presented. PMID:11447482

  5. Activation of Corticostriatal Circuitry Relieves Chronic Neuropathic Pain

    PubMed Central

    Lee, Michelle; Manders, Toby R.; Eberle, Sarah E.; Su, Chen; D'amour, James; Yang, Runtao; Lin, Hau Yueh; Deisseroth, Karl; Froemke, Robert C.

    2015-01-01

    Neural circuits that determine the perception and modulation of pain remain poorly understood. The prefrontal cortex (PFC) provides top-down control of sensory and affective processes. While animal and human imaging studies have shown that the PFC is involved in pain regulation, its exact role in pain states remains incompletely understood. A key output target for the PFC is the nucleus accumbens (NAc), an important component of the reward circuitry. Interestingly, recent human imaging studies suggest that the projection from the PFC to the NAc is altered in chronic pain. The function of this corticostriatal projection in pain states, however, is not known. Here we show that optogenetic activation of the PFC produces strong antinociceptive effects in a rat model (spared nerve injury model) of persistent neuropathic pain. PFC activation also reduces the affective symptoms of pain. Furthermore, we show that this pain-relieving function of the PFC is likely mediated by projections to the NAc. Thus, our results support a novel role for corticostriatal circuitry in pain regulation. PMID:25834050

  6. Diaphragm activation during exercise in chronic obstructive pulmonary disease.

    PubMed

    Sinderby, C; Spahija, J; Beck, J; Kaminski, D; Yan, S; Comtois, N; Sliwinski, P

    2001-06-01

    Although it has been postulated that central inhibition of respiratory drive may prevent development of diaphragm fatigue in patients with chronic obstructive pulmonary disease (COPD) during exercise, this premise has not been validated. We evaluated diaphragm electrical activation (EAdi) relative to maximum in 10 patients with moderately severe COPD at rest and during incremental exhaustive bicycle exercise. Flow was measured with a pneumotachograph and volume by integration of flow. EAdi and transdiaphragmatic pressures (Pdi) were measured using an esophageal catheter. End-expiratory lung volume (EELV) was assessed by inspiratory capacity (IC) maneuvers, and maximal voluntary EAdi was obtained during these maneuvers. Minute ventilation (V E) was 12.2 +/- 1.9 L/min (mean +/- SD) at rest, and increased progressively (p < 0.001) to 31.0 +/- 7.8 L/min at end-exercise. EELV increased during exercise (p < 0.001) causing end-inspiratory lung volume to attain 97 +/- 3% of TLC at end-exercise. Pdi at rest was 9.4 +/- 3.2 cm H(2)O and increased during the first two thirds of exercise (p < 0.001) to plateau at about 13 cm H(2)O. EAdi was 24 +/- 6% of voluntary maximal at rest and increased progressively during exercise (p < 0.001) to reach 81 +/- 7% at end-exercise. In conclusion, dynamic hyperinflation during exhaustive exercise in patients with COPD reduces diaphragm pressure-generating capacity, promoting high levels of diaphragm activation. PMID:11401887

  7. Early Interfaced Neural Activity from Chronic Amputated Nerves

    PubMed Central

    Garde, Kshitija; Keefer, Edward; Botterman, Barry; Galvan, Pedro; Romero, Mario I.

    2009-01-01

    Direct interfacing of transected peripheral nerves with advanced robotic prosthetic devices has been proposed as a strategy for achieving natural motor control and sensory perception of such bionic substitutes, thus fully functionally replacing missing limbs in amputees. Multi-electrode arrays placed in the brain and peripheral nerves have been used successfully to convey neural control of prosthetic devices to the user. However, reactive gliosis, micro hemorrhages, axonopathy and excessive inflammation currently limit their long-term use. Here we demonstrate that enticement of peripheral nerve regeneration through a non-obstructive multi-electrode array, after either acute or chronic nerve amputation, offers a viable alternative to obtain early neural recordings and to enhance long-term interfacing of nerve activity. Non-restrictive electrode arrays placed in the path of regenerating nerve fibers allowed the recording of action potentials as early as 8 days post-implantation with high signal-to-noise ratio, as long as 3 months in some animals, and with minimal inflammation at the nerve tissue-metal electrode interface. Our findings suggest that regenerative multi-electrode arrays of open design allow early and stable interfacing of neural activity from amputated peripheral nerves and might contribute towards conveying full neural control and sensory feedback to users of robotic prosthetic devices. PMID:19506704

  8. Retarded release phosphatidylcholine benefits patients with chronic active ulcerative colitis

    PubMed Central

    Stremmel, W; Merle, U; Zahn, A; Autschbach, F; Hinz, U; Ehehalt, R

    2005-01-01

    Background and aims: We examined the hypothesis of an anti-inflammatory effect of phosphatidylcholine in ulcerative colitis. Methods: A phase IIA, double blind, randomised, placebo controlled study was performed in 60 patients with chronic active, non steroid dependent, ulcerative colitis, with a clinical activity index (CAI) of ⩾4. Retarded release phosphatidylcholine rich phospholipids and placebo were administered at a dose of 6 g daily over three months. The primary end point was a change in CAI towards clinical remission (CAI ⩽3) or CAI improvement by ⩾50%. Secondary end points included ⩾50% changes in endoscopic activity index (EAI), histology, and quality of life scores. Results: Induction of clinical remission (CAI ⩽3) as the primary outcome variable was attained by 16 (53%) patients in the phosphatidylcholine treated group compared with three (10%) in the placebo group (p<0.00001). The rate of clinical remission and CAI improvement was 90% in the phosphatidylcholine group and only 10% in the placebo group. A median drop of seven points in the CAI score (70% improvement) was recorded in the phosphatidylcholine group compared with no change in the placebo group. Secondary end point analysis revealed concomitant drops in EAI and histology scores (p = 0.00016 and p = 0.0067 compared with placebo, respectively). Improvement in quality of life was reported by 16 of 29 evaluated patients in the phosphatidylcholine group compared with two of 30 in the placebo group (p = 0.00005). Conclusion: Retarded release oral phosphatidylcholine is effective in alleviating inflammatory activity caused by ulcerative colitis. PMID:15951544

  9. Sudden unexpected death due to severe pulmonary and cardiac sarcoidosis.

    PubMed

    Ginelliová, Alžbeta; Farkaš, Daniel; Farkašová Iannaccone, Silvia; Vyhnálková, Vlasta

    2016-09-01

    In this paper we report the autopsy findings of a 57 year old woman who died unexpectedly at home. She had been complaining of shortness of breath, episodes of dry coughing, and nausea. Her past medical and social history was unremarkable. She had no previous history of any viral or bacterial disease and no history of oncological disorders. Autopsy revealed multiple grayish-white nodular lesions in the pleura and epicardial fat and areas resembling fibrosis on the cut surface of the anterior and posterior wall of the left ventricle and interventricular septum. Histological examination of the lungs and heart revealed multiple well-formed noncaseating epithelioid cell granulomas with multinucleated giant cells. Death was attributed to myocardial ischemia due to vasculitis of intramural coronary artery branches associated with sarcoidosis. Sarcoidosis is a multisystemic disease of unknown etiology characterized by the formation of noncaseating epithelioid cell granulomas in the affected organs and tissues. The diagnosis of sarcoidosis in this case was established when other causes of granulomatous disease such as tuberculosis, berylliosis, hypersensitivity pneumonitis, and giant cell myocarditis had been reasonably excluded. PMID:27379608

  10. Two Cases of Heerfordt's Syndrome: A Rare Manifestation of Sarcoidosis

    PubMed Central

    Furuta, Yasushi; Fukuda, Satoshi

    2016-01-01

    Heerfordt's syndrome is a rare manifestation of sarcoidosis characterized by the presence of facial nerve palsy, parotid gland enlargement, anterior uveitis, and low grade fever. Two cases of Heerfordt's syndrome and a literature review are presented. Case  1. A 53-year-old man presented with swelling of his right eyelid, right facial nerve palsy, and swelling of his right parotid gland. A biopsy specimen from the swollen eyelid indicated sarcoidosis and he was diagnosed with incomplete Heerfordt's syndrome based on the absence of uveitis. His symptoms were improved by corticosteroid therapy. Case  2. A 55-year-old woman presented with left facial nerve palsy, bilateral hearing loss, and swelling of her bilateral parotid glands. She had been previously diagnosed with uveitis and bilateral hilar lymphadenopathy. Although no histological confirmation was performed, she was diagnosed with complete Heerfordt's syndrome on the basis of her clinical symptoms. Swelling of the bilateral parotid glands and left facial nerve palsy were improved immediately by corticosteroid therapy. Sarcoidosis is a relatively uncommon disease for the otolaryngologist. However, the otolaryngologist may encounter Heerfordt's syndrome as this syndrome presents with facial nerve palsy and swelling of the parotid gland. Therefore, we otolaryngologists should diagnose and treat Heerfordt's syndrome appropriately in cooperation with pneumologists and ophthalmologists. PMID:26885424

  11. Histopathologic aid to diagnosis of sarcoidosis: report of 8 cases.

    PubMed

    Manonukul, Jane; Wanitphakdeedecha, Rungsima; Wisuthsarewong, Wanee; Thirapote, Panitta

    2006-06-01

    Sarcoidosis is a multisystemic disease of unknown etiology. The disease is common in blacks and is very rare in Thailand. It presents as one of the most variable manifestations usually affecting the lungs and intrathoracic lymph nodes. Other organs such as liver, spleen, joints and eyes including skin are also involved The common cutaneous lesions are maculopapular, erythematous plaque, subcutaneous nodule, scar and lupus pernio. No reliable indicator is useful for diagnosis except the histopathologic change which is the only way for approaching this disease. Sarcoidosis is the disease of exclusion. Various infections producing granulomas should be excluded histologically. The ultimate diagnosis requires clinical correlation, laboratory investigations, chest X-ray as well as available tissue culture. Herein, the authors reported eight cases of sarcoidosis by retrospective study primarily diagnosed by histopathological findings at Siriraj Hospital from January, 1997 to December, 2004 with many different clinical presentations. Despite the diverse clinical pictures, interestingly, the presented patients almost had the same histopathologic findings as small, uniform, discrete naked granulomas usually without necrosis. These findings act as a hallmark for diagnosis of this disease. PMID:16850689

  12. Pulmonary metastases from low grade sarcoma in a patient with pulmonary sarcoidosis. Sarcoidosis or sarcoid-like reaction?

    PubMed

    Majori, Maria; Anghinolfi, Miriam; Gnetti, Letizia; Casalini, Angelo Gianni

    2016-01-01

    An asymptomatic man with previous histopatological diagnosis of pulmonary sarcoidosis in radiological follow-up (stable for about 4 years) presented massive right pleural effusion. After drainage, CT of the chest showed an increase in number and size of pulmonary nodules compared to the last check (8 months before). Surgical pulmonary biopsies were performed with the diagnosis of metastases from low grade sarcoma. The primary tumor was localized to the right buttock. Given the absence of symptoms, the extent of disease and many comorbidities the patient underwent only treatment with gemcitabine that was not tolerated and discontinued after the first few cycles 1 year ago. At the present the patientis still asymptomatic even if the CT of the chest shows a slow but continuous progression of the disease. The question is: is this an association between sarcoidosis and malignancy? or was this a sarcoid-like reaction during malignancy? PMID:27537721

  13. Toxoplasma gondii Actively Inhibits Neuronal Function in Chronically Infected Mice

    PubMed Central

    Haroon, Fahad; Händel, Ulrike; Angenstein, Frank; Goldschmidt, Jürgen; Kreutzmann, Peter; Lison, Holger; Fischer, Klaus-Dieter; Scheich, Henning; Wetzel, Wolfram; Schlüter, Dirk; Budinger, Eike

    2012-01-01

    Upon infection with the obligate intracellular parasite Toxoplasma gondii, fast replicating tachyzoites infect a broad spectrum of host cells including neurons. Under the pressure of the immune response, tachyzoites convert into slow-replicating bradyzoites, which persist as cysts in neurons. Currently, it is unclear whether T. gondii alters the functional activity of neurons, which may contribute to altered behaviour of T. gondii–infected mice and men. In the present study we demonstrate that upon oral infection with T. gondii cysts, chronically infected BALB/c mice lost over time their natural fear against cat urine which was paralleled by the persistence of the parasite in brain regions affecting behaviour and odor perception. Detailed immunohistochemistry showed that in infected neurons not only parasitic cysts but also the host cell cytoplasm and some axons stained positive for Toxoplasma antigen suggesting that parasitic proteins might directly interfere with neuronal function. In fact, in vitro live cell calcium (Ca2+) imaging studies revealed that tachyzoites actively manipulated Ca2+ signalling upon glutamate stimulation leading either to hyper- or hypo-responsive neurons. Experiments with the endoplasmatic reticulum Ca2+ uptake inhibitor thapsigargin indicate that tachyzoites deplete Ca2+ stores in the endoplasmatic reticulum. Furthermore in vivo studies revealed that the activity-dependent uptake of the potassium analogue thallium was reduced in cyst harbouring neurons indicating their functional impairment. The percentage of non-functional neurons increased over time In conclusion, both bradyzoites and tachyzoites functionally silence infected neurons, which may significantly contribute to the altered behaviour of the host. PMID:22530040

  14. Toxoplasma gondii actively inhibits neuronal function in chronically infected mice.

    PubMed

    Haroon, Fahad; Händel, Ulrike; Angenstein, Frank; Goldschmidt, Jürgen; Kreutzmann, Peter; Lison, Holger; Fischer, Klaus-Dieter; Scheich, Henning; Wetzel, Wolfram; Schlüter, Dirk; Budinger, Eike

    2012-01-01

    Upon infection with the obligate intracellular parasite Toxoplasma gondii, fast replicating tachyzoites infect a broad spectrum of host cells including neurons. Under the pressure of the immune response, tachyzoites convert into slow-replicating bradyzoites, which persist as cysts in neurons. Currently, it is unclear whether T. gondii alters the functional activity of neurons, which may contribute to altered behaviour of T. gondii-infected mice and men. In the present study we demonstrate that upon oral infection with T. gondii cysts, chronically infected BALB/c mice lost over time their natural fear against cat urine which was paralleled by the persistence of the parasite in brain regions affecting behaviour and odor perception. Detailed immunohistochemistry showed that in infected neurons not only parasitic cysts but also the host cell cytoplasm and some axons stained positive for Toxoplasma antigen suggesting that parasitic proteins might directly interfere with neuronal function. In fact, in vitro live cell calcium (Ca(2+)) imaging studies revealed that tachyzoites actively manipulated Ca(2+) signalling upon glutamate stimulation leading either to hyper- or hypo-responsive neurons. Experiments with the endoplasmatic reticulum Ca(2+) uptake inhibitor thapsigargin indicate that tachyzoites deplete Ca(2+) stores in the endoplasmatic reticulum. Furthermore in vivo studies revealed that the activity-dependent uptake of the potassium analogue thallium was reduced in cyst harbouring neurons indicating their functional impairment. The percentage of non-functional neurons increased over time In conclusion, both bradyzoites and tachyzoites functionally silence infected neurons, which may significantly contribute to the altered behaviour of the host. PMID:22530040

  15. Severe hypercalcemia unmasked by Vitamin D in a patient with sarcoidosis

    PubMed Central

    Nayak-Rao, S

    2013-01-01

    Severe hypercalcemia is uncommon in clinical practice and is usually due to primary hperparathyroidism or malignancy. We present a patient who presented with severe hypercalcemia with renal failure; further evaluation of which revealed the diagnosis of sarcoidosis. This case is presented in view of the rarity of presentation of sarcoidosis with hypercalcemic crisis. PMID:24049278

  16. Increased serum cortisol binding in chronic active hepatitis

    SciTech Connect

    Orbach, O.; Schussler, G.C.

    1989-01-01

    A high serum cortisol concentration, apparently due to increased cortisol-binding globulin (CBG), was found in a patient (index case) with chronic active hepatitis (CAH). We therefore performed further studies to determine whether increased cortisol binding is generally associated with CAH. Serum samples were obtained from 15 hospitalized patients with long-term liver function test elevations but no evidence of cirrhosis, 15 normal subjects without a history of hepatitis, four healthy pregnant women, and 10 alcoholic patients with stigmata of cirrhosis. Serum cortisol binding was measured by an adaptation of a previously described charcoal uptake method. Thyroxine-binding globulin (TBG) and sex hormone-binding globulin were determined by radioimmunoassays. Charcoal uptake of 125I cortisol from sera of normal subjects and additional patients with CAH revealed that increased serum cortisol binding by a saturable site, presumably CBG, was associated with CAH. Cortisol binding was significantly correlated with immunoassayable TBG, suggesting that in CAH, similar mechanisms may be responsible for increasing the serum concentrations of CBG and TBG.

  17. Comparative activities of milk components in reversing chronic colitis.

    PubMed

    Kanwar, J R; Kanwar, R K; Stathopoulos, S; Haggarty, N W; MacGibbon, A K H; Palmano, K P; Roy, K; Rowan, A; Krissansen, G W

    2016-04-01

    Inflammatory bowel disease (IBD) is a poorly understood chronic immune disorder for which there is no medical cure. Milk and colostrum are rich sources of bioactives with immunomodulatory properties. Here we compared the therapeutic effects of oral delivery of bovine milk-derived iron-saturated lactoferrin (Fe-bLF), angiogenin, osteopontin (OPN), colostrum whey protein, Modulen IBD (Nestle Healthsciences, Rhodes, Australia), and cis-9,trans-11 conjugated linoleic acid (CLA)-enriched milk fat in a mouse model of dextran sulfate-induced colitis. The CLA-enriched milk fat significantly increased mouse body weights after 24d of treatment, reduced epithelium damage, and downregulated the expression of proinflammatory cytokines and nitrous oxide. Modulen IBD most effectively decreased the clinical score at d 12, and Modulen IBD and OPN most effectively lowered the inflammatory score. Myeloperoxidase activity that denotes neutrophil infiltration was significantly lower in mice fed Modulen IBD, OPN, angiogenin, and Fe-bLF. A significant decrease in the numbers of T cells, natural killer cells, dendritic cells, and a significant decrease in cytokine expression were observed in mice fed the treatment diets compared with dextran sulfate administered mice. The Fe-bLF, CLA-enriched milk fat, and Modulen IBD inhibited intestinal angiogenesis. In summary, each of the milk components attenuated IBD in mice, but with differing effectiveness against specific disease parameters. PMID:26805965

  18. Basophil Activation Test with Food Additives in Chronic Urticaria Patients

    PubMed Central

    Kang, Min-Gyu; Song, Woo-Jung; Park, Han-Ki; Lim, Kyung-Hwan; Kim, Su-Jung; Lee, Suh-Young; Kim, Sae-Hoon; Cho, Sang-Heon; Min, Kyung-Up

    2014-01-01

    The role of food additives in chronic urticaria (CU) is still under investigation. In this study, we aimed to explore the association between food additives and CU by using the basophil activation test (BAT). The BAT using 15 common food additives was performed for 15 patients with CU who had a history of recurrent urticarial aggravation following intake of various foods without a definite food-specific IgE. Of the 15 patients studied, two (13.3%) showed positive BAT results for one of the tested food additives. One patient responded to monosodium glutamate, showing 18.7% of CD203c-positive basophils. Another patient showed a positive BAT result to sodium benzoate. Both patients had clinical correlations with the agents, which were partly determined by elimination diets. The present study suggested that at least a small proportion of patients with CU had symptoms associated with food additives. The results may suggest the potential utility of the BAT to identity the role of food additives in CU. PMID:24527415

  19. Physical Activity Levels in College Students With Chronic Ankle Instability

    PubMed Central

    Hubbard-Turner, Tricia; Turner, Michael J.

    2015-01-01

    Context Ankle sprains are the most common orthopaedic pathologic condition, and more concerning is the high percentage of persons who develop chronic ankle instability (CAI). Researchers have reported that patients with CAI are restricted occupationally, have more functional limitations, and have a poorer health-related quality of life. We do not know if these limitations decrease physical activity levels. Objective To assess total weekly steps taken between persons with CAI and persons with healthy ankles. Design Case-control study. Setting University research laboratory. Patients or Other Participants A total of 20 participants with unilateral CAI (9 men, 11 women; age = 21.2 ± 1.9 years, height = 174.3 ± 6.9 cm, mass = 71.9 ± 11.7 kg) and 20 healthy participants (9 men, 11 women; age = 20.4 ± 2.1 years, height = 172.1 ± 5.5 cm, mass = 73.1 ± 13.4 kg) volunteered. Main Outcome Measure(s) We provided all participants with a pedometer and instructed them to wear it every day for 7 days and to complete a daily step log. They also completed the Foot and Ankle Ability Measure (FAAM), the FAAM Sport version, and the International Physical Activity Questionnaire. A 2-way analysis of variance (group × sex) was used to determine if differences existed in the total number of weekly steps, ankle laxity, and answers on the International Physical Activity Questionnaire between groups and between sexes. Results We found no group × sex interaction for step count (F range = 0.439–2.108, P = .08). A main effect for group was observed (F1,38 = 10.45, P = .04). The CAI group took fewer steps than the healthy group (P = .04). The average daily step count was 6694.47 ± 1603.35 for the CAI group and 8831.01 ± 1290.01 for the healthy group. The CAI group also scored lower on the FAAM (P = .01) and the FAAM Sport version (P = .01). Conclusions The decreased step count that the participants with CAI demonstrated is concerning. This decreased physical activity may be secondary

  20. Parallel Gene Expression Changes in Sarcoidosis Involving the Lacrimal Gland, Orbital Tissue, or Blood

    PubMed Central

    Rosenbaum, James T.; Choi, Dongseok; Wilson, David J.; Grossniklaus, Hans E.; Harrington, Christina A.; Sibley, Cailin H.; Dailey, Roger A.; Ng, John D.; Steele, Eric A.; Czyz, Craig N.; Foster, Jill A.; Tse, David; Alabiad, Chris; Dubovy, Sander; Parekh, Prashant; Harris, Gerald J.; Kazim, Michael; Patel, Payal; White, Valerie; Dolman, Peter; Korn, Bobby S.; Kikkawa, Don; Edward, Deepak P.; Alkatan, Hind; al-Hussain, Hailah; Yeatts, R. Patrick; Selva, Dinesh; Stauffer, Patrick; Planck, Stephen R.

    2016-01-01

    IMPORTANCE Sarcoidosis is a major cause of ocular or periocular inflammation. The pathogenesis of sarcoidosis is incompletely understood and diagnosis often requires a biopsy. OBJECTIVE To determine how gene expression in either orbital adipose tissue or the lacrimal gland affected by sarcoidosis compares with gene expression in other causes of orbital disease and how gene expression in tissue affected by sarcoidosis compares with gene expression in peripheral blood samples obtained from patients with sarcoidosis. DESIGN, SETTING, AND PARTICIPANTS In a multicenter, international, observational study, gene expression profiling of formalin-fixed biopsy specimens, using GeneChipp U133 Plus 2 microarrays (Affymetrix), was conducted between October 2012 and January 2014 on tissues biopsied from January 2000 through June 2013. Participants included 12 patients with orbital sarcoidosis (7 in adipose tissue; 5 affecting the lacrimal gland) as well as comparable tissue from 6 healthy individuals serving as controls or patients with thyroid eye disease, nonspecific orbital inflammation, or granulomatosis with polyangiitis. In addition, results were compared with gene expression in peripheral blood samples obtained from 12 historical individuals with sarcoidosis. MAIN OUTCOMES AND MEASURES Significantly differentially expressed transcripts defined as a minimum of a 1.5-fold increase or a comparable decrease and a false discovery rate of P < .05. RESULTS Signals from 2449 probe sets (transcripts from approximately 1522 genes) were significantly increased in the orbital adipose tissue from patients with sarcoidosis. Signals from 4050 probe sets (approximately 2619 genes) were significantly decreased. Signals from 3069 probe sets (approximately 2001 genes) were significantly higher and 3320 (approximately 2283 genes) were significantly lower in the lacrimal gland for patients with sarcoidosis. Ninety-two probe sets (approximately 69 genes) had significantly elevated signals and

  1. Evidence for brain glial activation in chronic pain patients

    PubMed Central

    Loggia, Marco L.; Chonde, Daniel B.; Akeju, Oluwaseun; Arabasz, Grae; Catana, Ciprian; Edwards, Robert R.; Hill, Elena; Hsu, Shirley; Izquierdo-Garcia, David; Ji, Ru-Rong; Riley, Misha; Wasan, Ajay D.; Zürcher, Nicole R.; Albrecht, Daniel S.; Vangel, Mark G.; Rosen, Bruce R.; Napadow, Vitaly; Hooker, Jacob M.

    2015-01-01

    Although substantial evidence has established that microglia and astrocytes play a key role in the establishment and maintenance of persistent pain in animal models, the role of glial cells in human pain disorders remains unknown. Here, using the novel technology of integrated positron emission tomography-magnetic resonance imaging and the recently developed radioligand 11C-PBR28, we show increased brain levels of the translocator protein (TSPO), a marker of glial activation, in patients with chronic low back pain. As the Ala147Thr polymorphism in the TSPO gene affects binding affinity for 11C-PBR28, nine patient–control pairs were identified from a larger sample of subjects screened and genotyped, and compared in a matched-pairs design, in which each patient was matched to a TSPO polymorphism-, age- and sex-matched control subject (seven Ala/Ala and two Ala/Thr, five males and four females in each group; median age difference: 1 year; age range: 29–63 for patients and 28–65 for controls). Standardized uptake values normalized to whole brain were significantly higher in patients than controls in multiple brain regions, including thalamus and the putative somatosensory representations of the lumbar spine and leg. The thalamic levels of TSPO were negatively correlated with clinical pain and circulating levels of the proinflammatory citokine interleukin-6, suggesting that TSPO expression exerts pain-protective/anti-inflammatory effects in humans, as predicted by animal studies. Given the putative role of activated glia in the establishment and or maintenance of persistent pain, the present findings offer clinical implications that may serve to guide future studies of the pathophysiology and management of a variety of persistent pain conditions. PMID:25582579

  2. Evidence for brain glial activation in chronic pain patients.

    PubMed

    Loggia, Marco L; Chonde, Daniel B; Akeju, Oluwaseun; Arabasz, Grae; Catana, Ciprian; Edwards, Robert R; Hill, Elena; Hsu, Shirley; Izquierdo-Garcia, David; Ji, Ru-Rong; Riley, Misha; Wasan, Ajay D; Zürcher, Nicole R; Albrecht, Daniel S; Vangel, Mark G; Rosen, Bruce R; Napadow, Vitaly; Hooker, Jacob M

    2015-03-01

    Although substantial evidence has established that microglia and astrocytes play a key role in the establishment and maintenance of persistent pain in animal models, the role of glial cells in human pain disorders remains unknown. Here, using the novel technology of integrated positron emission tomography-magnetic resonance imaging and the recently developed radioligand (11)C-PBR28, we show increased brain levels of the translocator protein (TSPO), a marker of glial activation, in patients with chronic low back pain. As the Ala147Thr polymorphism in the TSPO gene affects binding affinity for (11)C-PBR28, nine patient-control pairs were identified from a larger sample of subjects screened and genotyped, and compared in a matched-pairs design, in which each patient was matched to a TSPO polymorphism-, age- and sex-matched control subject (seven Ala/Ala and two Ala/Thr, five males and four females in each group; median age difference: 1 year; age range: 29-63 for patients and 28-65 for controls). Standardized uptake values normalized to whole brain were significantly higher in patients than controls in multiple brain regions, including thalamus and the putative somatosensory representations of the lumbar spine and leg. The thalamic levels of TSPO were negatively correlated with clinical pain and circulating levels of the proinflammatory citokine interleukin-6, suggesting that TSPO expression exerts pain-protective/anti-inflammatory effects in humans, as predicted by animal studies. Given the putative role of activated glia in the establishment and or maintenance of persistent pain, the present findings offer clinical implications that may serve to guide future studies of the pathophysiology and management of a variety of persistent pain conditions. PMID:25582579

  3. Chronic neck pain alters muscle activation patterns to sudden movements.

    PubMed

    Boudreau, Shellie A; Falla, Deborah

    2014-06-01

    The aim of this study was to assess the activation of the sternocleidomastoid (SCM) and splenius capitis (SC) muscles in response to unanticipated, full body perturbations in individuals with chronic neck pain (NP) and age-matched healthy controls (HC). Individuals with NP had a history of NP for 8.9 ± 7.8 years, rated the intensity of NP as 4.2 ± 2.0 (score out of 10), and scored 15.3 ± 6.5 on the Neck Disability Index. Participants stood on a moveable platform during which 32 randomized postural perturbations (eight repetitions of four perturbation types: 8 cm forward slide (FS), 8 cm backward slides, 10° forward tilt, and 10° backward tilt) with varying inter-perturbation time intervals were performed over a period of 5 min. Bilateral surface electromyography (EMG) from the SCM and SC was recorded, and the onset time and the average rectified value of the EMG signal was determined for epochs of 100 ms; starting 100 ms prior to and 500 ms after the perturbation onset. Individuals with NP, as compared to HC, demonstrated delayed onset times and reduced EMG amplitude of the SCM and SC muscles in response to all postural perturbations. Such findings were most pronounced following the FS postural perturbation (healthy vs. NP for SCM 83.3 ± 8.0 vs. 86.3 ± 4.4 and SC 75.6 ± 3.5 vs. 89.3 ± 4.2), which was also associated with the greatest change (expressed in % relative to baseline) in EMG amplitude (healthy vs. NP for SCM 206.6 ± 50.4 vs. 115.9 ± 15.7 and SC 83.4 ± 19.2 vs. 69.2 ± 10.9) across all postural perturbations types. Individuals with NP display altered neural control of the neck musculature in response to rapid, unanticipated full body postural perturbations. Although the relative timing of neck musculature activity in individuals with NP appears to be intact, simultaneous co-activation of the neck musculature emerges for unanticipated anterior-posterior postural perturbations. PMID:24632836

  4. FCGR3A and FCGR3B copy number variations are risk factors for sarcoidosis.

    PubMed

    Wu, Jianming; Li, Yunfang; Guan, Weihua; Viken, Kevin; Perlman, David M; Bhargava, Maneesh

    2016-07-01

    Sarcoidosis is a multisystem granulomatous disorder that causes significant morbidity. Genetic factors contribute to sarcoidosis risks. In this study, we investigated whether copy number variations (CNVs) of FCGR3A (coding for FcγRIIIA) and FCGR3B (coding for FcγRIIIB) genes are associated with sarcoidosis susceptibility and whether the expressions of FcγRIIIA on NK cells and FcγRIIIB on neutrophils are altered in sarcoidosis patients. TaqMan real-time PCR assays were used to analyze the CNV of FCGR3A and FCGR3B genes. FCGR3A and FCGR3B CNV genotypes were compared between 671 biopsy-proven sarcoidosis patients and the same number of healthy controls matched with age, sex, race, and geographic area from the ACCESS (A Case Control Etiologic Study of Sarcoidosis) cohort. Flow cytometry analyses were used to determine expressions of FcγRIIIA on NK cells and FcγRIIIB on neutrophils in phenotype analyses. We found that FCGR3A CNVs were significantly associated with sarcoidosis in females (CN = 1 vs. CN = 2 logistic regression adjusted for sex and race, OR 4.0156, SE = 2.2784, P = 0.0143; CN = 3 vs. CN = 2 logistic regression adjusted for sex and race, OR 2.8044, SE = 1.1065, P = 0.0090), suggesting that FCGR3A gene abnormality influences sarcoidosis development in a gender-specific manner. Furthermore, FcγRIIIA expressions were significantly decreased on NK cells from sarcoidosis patients compared to those from healthy controls (P = 0.0007). Additionally, low FCGR3B CN was associated with sarcoidosis (CN <2 vs. CN = 2 logistic regression adjusted for sex and race, OR 1.5025, SE = 0.2682, P = 0.0226), indicating that the functions of FCGR3B gene may also contribute to the pathogenesis of sarcoidosis. We conclude that FCGR3A CNVs are a major risk factor for female sarcoidosis and FCGR3B CNVs may also affect the development of sarcoidosis. PMID:27059607

  5. Randomised controlled trial of vitamin D supplementation in sarcoidosis

    PubMed Central

    Bolland, Mark J; Wilsher, Margaret L; Grey, Andrew; Horne, Anne M; Fenwick, Sheryl; Gamble, Greg D; Reid, Ian R

    2013-01-01

    Objectives The role vitamin D intake/production plays in sarcoidosis-associated hypercalcaemia is uncertain. However, authoritative reviews have recommended avoiding sunlight exposure and vitamin D supplements, which might lead to adverse skeletal outcomes from vitamin D insufficiency. We investigated the effects of vitamin D supplementation on surrogate measures of skeletal health in patients with sarcoidosis and vitamin D insufficiency. Design Randomised, placebo-controlled trial. Setting Clinical research centre. Participants 27 normocalcaemic patients with sarcoidosis and 25-hydroxyvitamin D (25OHD) <50 nmol/L. Intervention 50 000 IU weekly cholecalciferol for 4 weeks, then 50 000 IU monthly for 11 months or placebo. Primary and secondary outcome measures The primary endpoint was the change in serum calcium over 12 months, and secondary endpoints included measurements of calcitropic hormones, bone turnover markers and bone mineral density (BMD). Results The mean age of participants was 57 years and 70% were women. The mean (SD) screening 25OHD was 35 (12) and 38 (9) nmol/L in the treatment and control groups, respectively. Vitamin D supplementation increased 25OHD to 94 nmol/L after 4 weeks, 84 nmol/L at 6 months and 78 nmol/L at 12 months, while levels remained stable in the control group. 1,25-Dihydroxy vitamin D levels were significantly different between the groups at 4 weeks, but not at 6 or 12 months. There were no between-groups differences in albumin-adjusted serum calcium, 24 h urine calcium, markers of bone turnover, parathyroid hormone or BMD over the trial. One participant developed significant hypercalcaemia after 6 weeks (total cholecalciferol dose 250 000 IU). Conclusions In patients with sarcoidosis and 25OHD <50 nmol/L, vitamin D supplements did not alter average serum calcium or urine calcium, but had no benefit on surrogate markers of skeletal health and caused one case of significant hypercalcaemia

  6. Influence of mental practice on upper limb muscle activity and activities of daily living in chronic stroke patients

    PubMed Central

    Park, JuHyung

    2016-01-01

    [Purpose] The aim of this study was to determine the effects of mental practice on muscle activity of the upper extremity and performance of daily activities in chronic stroke patients. [Subjects and Methods] In this research, mental practice was conducted by 2 chronic hemiplegic stroke patients. Mental practice was conducted 30 minutes a day, 5 times a week, for 2 weeks. Evaluation was conducted 4 times before and after intervention. Muscle activity was measured using a surface electromyogram test, and the Modified Barthel Index was used to measure changes in the ability to carry out daily activities. [Results] Both the muscle activity of the upper extremity and capability to perform daily activities showed improved outcomes after mental practice was conducted. [Conclusion] Through this research, mental practice was proven to be effective in improving the muscle activity of upper extremity and capability to perform daily activities in chronic hemiplegic stroke patients. PMID:27134412

  7. Expanded lung T-bet+RORγT+ CD4+ T-cells in sarcoidosis patients with a favourable disease phenotype.

    PubMed

    Kaiser, Ylva; Lepzien, Rico; Kullberg, Susanna; Eklund, Anders; Smed-Sörensen, Anna; Grunewald, Johan

    2016-08-01

    Disease phenotypes of pulmonary sarcoidosis are distinguished by clinical rather than immunological criteria. We aimed to characterise patterns of CD4(+) T-cell lineage plasticity underlying the differences in clinical presentation and disease course between the acute form, Löfgren's syndrome, and the heterogeneous, potentially progressive "non-Löfgren" form.33 pulmonary sarcoidosis patients and nine controls underwent bronchoscopy with bronchoalveolar lavage. CD4(+) T-cell transcription factor, chemokine receptor and T-cell receptor expression, proliferation and cytokine production were assessed in the lavage fluid and peripheral blood using flow cytometry and multicolour FluoroSpot.CD4(+) T-cells simultaneously expressing the T-helper cell (Th)1 and Th17 transcriptional regulators T-bet and RORγT (T-bet(+)RORγT(+)) were identified in the lavage, but not blood, of all subjects, and to a significantly higher degree in Löfgren's patients. T-bet(+)RORγT(+) cells proliferated actively, produced interferon (IFN)γ and interleukin (IL)-17A, co-expressed the chemokine receptors CXCR3 and CCR6, and correlated with nonchronic disease. T-cell receptor-restricted Vα2.3(+)Vβ22(+) T-cells strongly co-expressed T-bet/RORγT and CXCR3/CCR6. Cytokine production was more heterogeneous in Löfgren's patients, with significantly higher IL-17A, IL-10, IL-22 and IL-2, but lower IFNγ.Here we demonstrate the presence of lung T-bet(+)RORγT(+)CXCR3(+)CCR6(+) CD4(+) T-cells and Th17-associated cytokines especially in sarcoidosis patients with a favourable prognosis, suggesting a Th1/Th17-permissive environment in the lung with implications for disease resolution. PMID:27230441

  8. PPARγ-mediated increase in glucose availability sustains chronic Brucella abortus infection in alternatively activated macrophages

    PubMed Central

    Xavier, Mariana N.; Winter, Maria G.; Spees, Alanna M.; den Hartigh, Andreas B.; Nguyen, Kim; Roux, Christelle M.; Silva, Teane M. A.; Atluri, Vidya L.; Kerrinnes, Tobias; Keestra, A. Marijke; Monack, Denise M.; Luciw, Paul A.; Eigenheer, Richard A.; Bäumler, Andreas J.; Santos, Renato L.; Tsolis, Renée M.

    2013-01-01

    SUMMARY Eradication of persistent intracellular bacterial pathogens with antibiotic therapy is often slow or incomplete. However, strategies to augment antibiotics are hampered by our poor understanding of the nutritional environment that sustains chronic infection. Here we show that the intracellular pathogen Brucella abortus survives and replicates preferentially in alternatively activated macrophages (AAM), which are more abundant during chronic infection. A metabolic shift induced by peroxisome proliferator activated receptor γ (PPARγ), which increases intracellular glucose availability, is identified as a causal mechanism promoting enhanced bacterial survival in AAM. Glucose uptake was crucial for increased replication of B. abortus in AAM, and chronic infection, as inactivation of the bacterial glucose transporter gluP reduced both intracellular survival in AAM and persistence in mice. Thus, a shift in intracellular nutrient availability induced by PPARγ promotes chronic persistence of B. abortus within AAM and targeting this pathway may aid in eradicating chronic infection. PMID:23954155

  9. PPARγ-mediated increase in glucose availability sustains chronic Brucella abortus infection in alternatively activated macrophages.

    PubMed

    Xavier, Mariana N; Winter, Maria G; Spees, Alanna M; den Hartigh, Andreas B; Nguyen, Kim; Roux, Christelle M; Silva, Teane M A; Atluri, Vidya L; Kerrinnes, Tobias; Keestra, A Marijke; Monack, Denise M; Luciw, Paul A; Eigenheer, Richard A; Bäumler, Andreas J; Santos, Renato L; Tsolis, Renée M

    2013-08-14

    Eradication of persistent intracellular bacterial pathogens with antibiotic therapy is often slow or incomplete. However, strategies to augment antibiotics are hampered by our poor understanding of the nutritional environment that sustains chronic infection. Here we show that the intracellular pathogen Brucella abortus survives and replicates preferentially in alternatively activated macrophages (AAMs), which are more abundant during chronic infection. A metabolic shift induced by peroxisome proliferator-activated receptor γ (PPARγ), which increases intracellular glucose availability, is identified as a causal mechanism promoting enhanced bacterial survival in AAMs. Glucose uptake was crucial for increased replication of B. abortus in AAMs, and for chronic infection, as inactivation of the bacterial glucose transporter gluP reduced both intracellular survival in AAMs and persistence in mice. Thus, a shift in intracellular nutrient availability induced by PPARγ promotes chronic persistence of B. abortus within AAMs, and targeting this pathway may aid in eradicating chronic infection. PMID:23954155

  10. Foreign body granulomatous reaction to silica, silicone, and hyaluronic acid in a patient with interferon-induced sarcoidosis.

    PubMed

    Novoa, R; Barnadas, M A; Torras, X; Curell, R; Alomar, A

    2013-12-01

    We report the case of a patient who developed sarcoid granulomas 11 months after starting treatment with pegylated interferon alfa and ribavirin for chronic hepatitis C. The sites of the lesions were related to 3 different foreign bodies: silica in old scars on the skin, hyaluronic acid that had been injected into facial tissues, and silicone in an axillary lymph node draining the area of a breast implant. Systemic sarcoidosis was diagnosed on the basis of a history of dry cough and fever and blood tests that revealed elevated angiotensin converting enzyme and liver enzymes. Interruption of the antiviral therapy led to normalization of liver function tests and disappearance of the skin lesions and lymphadenopathies. Dermatologists and cosmetic surgeons should be aware of the risk of sarcoid lesions related to cosmetic implants in patients who may require treatment with interferon in the future. PMID:22995946

  11. Aetiology of chronic constrictive pericarditis.

    PubMed Central

    Blake, S; Bonar, S; O'Neill, H; Hanly, P; Drury, I; Flanagan, M; Garrett, J

    1983-01-01

    In a consecutive series of 32 cases of chronic constrictive pericarditis treated by pericardiectomy during the past 25 years, four were attributable to rheumatoid disease, two to trauma, one to sarcoidosis, and four, at a maximum, to tuberculosis. In the remaining 21 cases of undetermined aetiology there was no evidence of tuberculosis. It appears, therefore, that tuberculosis was not a common cause of chronic constrictive pericarditis during the period under review, which included the 1950s and early 1960s when tuberculosis was widespread. PMID:6615663

  12. Sarcoidosis Presenting as Bilateral Vocal Cord Paralysis due to Bilateral Vagal Nerve Involvement.

    PubMed

    Yamasue, Mari; Nureki, Shin-Ichi; Ushijima, Ryoichi; Mukai, Yutaka; Goto, Akihiko; Kadota, Jun-Ichi

    2016-01-01

    We herein report a rare case of sarcoidosis presenting as bilateral vocal cord paralysis due to bilateral vagal nerve involvement. A 72-year-old woman with uveitis of the left eye complained of hoarseness and aspiration due to bilateral vocal cord paralysis. An endobronchial needle aspiration biopsy specimen of the mediastinal lymph nodes showed non-caseating epithelioid cell granuloma. Total protein and cell concentrations in the cerebrospinal fluid were increased. We diagnosed her to have sarcoidosis with bilateral vagal nerve involvement. Corticosteroid therapy improved her symptoms of hoarseness and aspiration. Sarcoidosis should therefore be taken into consideration as a potential cause of bilateral vocal cord paralysis. PMID:27150886

  13. Interesting case of ovarian sarcoidosis: The value of multi disciplinary team working

    PubMed Central

    Wuntakal, Rekha; Bharathan, Rasiah; Rockall, Andrea; Jeyarajah, Arjun

    2007-01-01

    Background Sarcoidosis of the genital tract is a rare condition. Ovarian manifestation of this disease is rarer still. Case presentation The case presented here represents ovarian manifestation of sarcoidosis. At the point of referral to our hospital, based on computerised tomography (CT) ovarian carcinoma was a differential diagnosis. Further magnetic resonance imaging along with CT guided biopsy aided by laboratory study supported a diagnosis of sarcoidosis. Patient responded to medical management by a multidisciplinary team. Conclusion The case shows the importance of FNAC and biopsy in case or ovarian masses and multi disciplinary team approach to management. PMID:17391534

  14. Isolated Bilateral Trigeminal Neuropathy in Sarcoidosis Presenting with Neurotrophic Corneal Ulcers

    PubMed Central

    Gupta, M.; Lascaratos, G.; Syrogiannis, A.; Esakowitz, L.

    2010-01-01

    Sarcoidosis is a multisystem granulomatous disease that may affect various organs. Nevertheless, involvement of the trigeminal nerve is exceedingly uncommon. This report presents a rare case of isolated bilateral trigeminal neuropathy presenting with neurotrophic corneal ulcers. The patient was treated with topical chloramphenicol and lubricants, as well as botulinum toxin injection to the upper eyelid to induce ptosis. Our case illustrates the importance of recognizing that bilateral corneal ulceration might be a manifestation of sarcoidosis. Physicians should be aware of this rare association, when treating sarcoidosis patients with eye related symptoms. PMID:23861615

  15. Sarcoidosis mimicking metastatic breast cancer in a patient with early-stage breast cancer

    PubMed Central

    Altınkaya, Metin; Altınkaya, Naime; Hazar, Burhan

    2016-01-01

    Sarcoidosis is a systemic granulomatous disorder of unknown origin that affects the lungs and mediastinal lymph nodes in most patients. The coexistence of sarcoidosis and breast cancer has been reported. An unfortunate consequence of the presence of both entities in the same patient is the risk of misdiagnosis. We report the case of a 70-year-old female with T1N0 cancer of the right breast that was initially diagnosed as stage IV because of mediastinal positron-emission tomography -positive lymphadenopathy. Biopsy of a mediastinal lymph node allowed us to diagnose sarcoidosis and correctly stage her disease as stage I breast cancer. PMID:26985162

  16. [Uncommon cutaneous ulcerative and systemic sarcoidosis. Successful treatment with hydroxychloroquine and compression therapy].

    PubMed

    Meyersburg, D; Schön, M P; Bertsch, H P; Seitz, C S

    2011-09-01

    Sarcoidosis is a granulomatous multisystemic disease of unclear etiology, which can affect any organ. The cutaneous manifestations are variable, but ulcerative cutaneous sarcoidosis is very rare. One must rule out other granulomatous skin diseases, especially necrobiosis lipoidica. There is no standarized therapy; usually an interdisciplinary approach over years taking multiple side effects into consideration is needed. A 58-year-old woman with a long history of cutaneous, nodal and pulmonary sarcoidosis suddenly developed ulcerations within the disseminated skin lesions on her legs. The combination of systemic hydroxychloroquine and modern wound management lead to complete healing of the ulcers and a significant improvement in the remaining skin lesions. PMID:21656110

  17. Annexins family: insights into their functions and potential role in pathogenesis of sarcoidosis.

    PubMed

    Mirsaeidi, Mehdi; Gidfar, Sanaz; Vu, Ann; Schraufnagel, Dean

    2016-01-01

    Annexins are Ca(2+)-regulated phospholipid-binding proteins that play an important role in the cell life cycle, exocytosis, and apoptosis. Annexin A11 is one of the oldest vertebrate annexins that has a crucial role in sarcoidosis pathogenesis. The mechanism of effect in sarcoidosis granuloma cells may be due to alterations in apoptosis. Immune cells with a specific mutation at protein location 230 are resistant to apoptosis and consequently have continued effects on inflammation and progression of sarcoidosis. The mechanism of action of annexin A11 may be based upon alterations in delivering calcium to two different apoptosis pathways (caspase and P53). PMID:27071553

  18. Cigarette smoking and male sex are independent and age concomitant risk factors for the development of ocular sarcoidosis in a new orleans sarcoidosis population

    PubMed Central

    Janot, Adam C.; Huscher, Dörte; Walker, McCall; Grewal, Harmanjot K.; Yu, Mary; Lammi, Matthew R.; Saketkoo, Lesley Ann

    2016-01-01

    Introduction Sarcoidosis is a multi-organ system granulomatous disease of unknown origin with an incidence of 1–40/100,000. Though pulmonary manifestations are predominant, ocular sarcoidosis (OS) affects 25–50% of patients with sarcoidosis and can lead to blindness. Methods A retrospective, single-center chart review of sarcoidosis cases investigated variables associated with the development of OS. Inclusion criteria were biopsy-proven sarcoidosis, disease duration greater than 1 year, documented smoking status on chart review and documentation of sarcoid-related eye disease. Multivariate analysis identified independent risk factors for OS. Results Of 269 charts reviewed, 109 patients met inclusion criteria. The OS group had a significantly higher proportion of smokers (71.4%) than without OS (42.0%, p=0.027) with no difference (p=0.61) in median number of pack years. Male sex was significantly higher in the OS group (57.1% versus 26.1%, p=0.009). Median duration of sarcoidosis was higher in the OS group (10 versus 4 years, p=0.031). Multivariate regression identified tobacco exposure (OR=5.25, p=0.007, 95% CI 1.58–17.41), male sex (OR=7.48, p=0.002, 95% CI 2.15–26.01), and age (OR=1.114, p=0.002, 95% CI 1.04–1.19) as concomitant risk factors for the development of OS. Conclusion To date, there are few dedicated investigations of risk factors for OS, especially smoking. This investigation identified male sex, age, and tobacco exposure as independent risk factors for OS. Though disease duration did not withstand regression analysis in this moderately sized group, age at chart review suggests screening for OS should not remit but rather intensify in aging patients with sarcoidosis. PMID:26278693

  19. Xanthogranuloma of the sellar region in a patient with sarcoidosis.

    PubMed

    Sulentić, Petra; Cupić, Hrvoje; Cerina, Vatroslav; Vrkljan, Milan

    2010-03-01

    Xanthogranuloma of the sellar region is a very rare brain tumor with favorable prognosis and without reported relapses of purely xanthogranulomatous lesion after complete resection. A case is presented of a 40-year-old male diagnosed with and treated for sarcoidosis, complaining of headache, photophobia and loss of libido. Physical examination revealed generally scarce hairiness, while laboratory investigations showed panhypopituitarism. Expansive sellar and suprasellar mass compressing the floor of the third ventricle and optical chiasm was confirmed by cranial multi-slice computerized tomography (MSCT). Complete resection of the tumor mass using trans-sphenoidal approach was performed. Histopathologic analysis revealed cholesterol clefts, sparse lymphoplasmacellular infiltrates, macrophages, siderophages and foreign body giant cells around cholesterol clefts confirming the diagnosis of xanthogranuloma of the sellar region. Since preoperative diagnosis of xanthogranuloma is very difficult, therapeutic algorithm does not differ from other expansive lesions of the sellar region, but pituitary involvement should always be considered in patient with sarcoidosis since therapeutic management is non-surgical. Follow up MSCT imaging after 6 months revealed a solid, contrast-enhanced mass at the posterior base of the sella. PMID:20635586

  20. Differential Neural Processing during Motor Imagery of Daily Activities in Chronic Low Back Pain Patients

    PubMed Central

    Vrana, Andrea; Hotz-Boendermaker, Sabina; Stämpfli, Philipp; Hänggi, Jürgen; Seifritz, Erich; Humphreys, B. Kim; Meier, Michael L.

    2015-01-01

    Chronic low back pain (chronic LBP) is both debilitating for patients but also a major burden on the health care system. Previous studies reported various maladaptive structural and functional changes among chronic LBP patients on spine- and supraspinal levels including behavioral alterations. However, evidence for cortical reorganization in the sensorimotor system of chronic LBP patients is scarce. Motor Imagery (MI) is suitable for investigating the cortical sensorimotor network as it serves as a proxy for motor execution. Our aim was to investigate differential MI-driven cortical processing in chronic LBP compared to healthy controls (HC) by means of functional magnetic resonance imaging (fMRI). Twenty-nine subjects (15 chronic LBP patients, 14 HC) were included in the current study. MI stimuli consisted of randomly presented video clips showing every-day activities involving different whole-body movements as well as walking on even ground and walking downstairs and upstairs. Guided by the video clips, subjects had to perform MI of these activities, subsequently rating the vividness of their MI performance. Brain activity analysis revealed that chronic LBP patients exhibited significantly reduced activity compared to HC subjects in MI-related brain regions, namely the left supplementary motor area and right superior temporal sulcus. Furthermore, psycho-physiological-interaction analysis yielded significantly enhanced functional connectivity (FC) between various MI-associated brain regions in chronic LBP patients indicating diffuse and non-specific changes in FC. Current results demonstrate initial findings about differences in MI-driven cortical processing in chronic LBP pointing towards reorganization processes in the sensorimotor network. PMID:26569602

  1. Differential Neural Processing during Motor Imagery of Daily Activities in Chronic Low Back Pain Patients.

    PubMed

    Vrana, Andrea; Hotz-Boendermaker, Sabina; Stämpfli, Philipp; Hänggi, Jürgen; Seifritz, Erich; Humphreys, B Kim; Meier, Michael L

    2015-01-01

    Chronic low back pain (chronic LBP) is both debilitating for patients but also a major burden on the health care system. Previous studies reported various maladaptive structural and functional changes among chronic LBP patients on spine- and supraspinal levels including behavioral alterations. However, evidence for cortical reorganization in the sensorimotor system of chronic LBP patients is scarce. Motor Imagery (MI) is suitable for investigating the cortical sensorimotor network as it serves as a proxy for motor execution. Our aim was to investigate differential MI-driven cortical processing in chronic LBP compared to healthy controls (HC) by means of functional magnetic resonance imaging (fMRI). Twenty-nine subjects (15 chronic LBP patients, 14 HC) were included in the current study. MI stimuli consisted of randomly presented video clips showing every-day activities involving different whole-body movements as well as walking on even ground and walking downstairs and upstairs. Guided by the video clips, subjects had to perform MI of these activities, subsequently rating the vividness of their MI performance. Brain activity analysis revealed that chronic LBP patients exhibited significantly reduced activity compared to HC subjects in MI-related brain regions, namely the left supplementary motor area and right superior temporal sulcus. Furthermore, psycho-physiological-interaction analysis yielded significantly enhanced functional connectivity (FC) between various MI-associated brain regions in chronic LBP patients indicating diffuse and non-specific changes in FC. Current results demonstrate initial findings about differences in MI-driven cortical processing in chronic LBP pointing towards reorganization processes in the sensorimotor network. PMID:26569602

  2. A rare case of eyelid sarcoidosis presenting as an orbital mass.

    PubMed

    Gaspar, Balan Louis; Gupta, Kirti; Singh, Usha

    2016-03-01

    Intraorbital sarcoidosis presenting externally as a solitary eyelid mass has been described in the literature as isolated case reports. We describe a rare case of asymptomatic sarcoidosis with orbital mass as the presenting feature in a young woman. The lesion was excised with the clinical possibility of a thrombosed varix. On histology, the lesion was characterized by numerous nonnecrotizing epithelioid cell granulomas with several multinucleated giant cells containing abundant asteroid bodies and oxalate crystals. No tubercular bacilli were detected. A diagnosis of sarcoidosis was rendered and on further clinical work-up, she was detected to have hilar lymphadenopathy. Sarcoidosis should be considered in the differential diagnosis of orbital mass as it could be the initial manifestation of the disease process. PMID:27146941

  3. A rare case of eyelid sarcoidosis presenting as an orbital mass

    PubMed Central

    Gaspar, Balan Louis; Gupta, Kirti; Singh, Usha

    2016-01-01

    Intraorbital sarcoidosis presenting externally as a solitary eyelid mass has been described in the literature as isolated case reports. We describe a rare case of asymptomatic sarcoidosis with orbital mass as the presenting feature in a young woman. The lesion was excised with the clinical possibility of a thrombosed varix. On histology, the lesion was characterized by numerous nonnecrotizing epithelioid cell granulomas with several multinucleated giant cells containing abundant asteroid bodies and oxalate crystals. No tubercular bacilli were detected. A diagnosis of sarcoidosis was rendered and on further clinical work-up, she was detected to have hilar lymphadenopathy. Sarcoidosis should be considered in the differential diagnosis of orbital mass as it could be the initial manifestation of the disease process. PMID:27146941

  4. Interstitial granulomatous lesions as part of the spectrum of presenting cutaneous signs in pediatric sarcoidosis.

    PubMed

    Kwon, Eun J; Hivnor, Chad M; Yan, Albert C; Forbes, Brian; Elenitsas, Rosalie; Albert, Dan; Pawel, Bruce; Honig, Paul; Pessler, Frank

    2007-01-01

    Skin findings in childhood sarcoidosis vary greatly, but only a few occurrences have been published in which the histopathology has been characterized well. We describe a child with sarcoidosis in whom the cutaneous findings were atypical, resembling granuloma annulare. Histologic examination of these cutaneous lesions, however, revealed areas of sarcoid-like epithelioid cell granulomas, a palisading granulomatous process with features of granuloma annulare, as well as palisading neutrophilic and granulomatous dermatitis and interstitial granulomatous dermatitis. This underscores the variability of skin findings in childhood sarcoidosis--even within the same patient--and suggests that sarcoidosis should be considered in the differential diagnosis of children initially diagnosed with granulomatous skin lesions, such as granuloma annulare, palisading neutrophilic, and granulomatous dermatitis or interstitial granulomatous dermatitis, who demonstrate associated signs of systemic disease. PMID:17958801

  5. Hepatosplenic sarcoidosis: contrast-enhanced ultrasound findings and implications for clinical practice.

    PubMed

    Tana, Claudio; Dietrich, Christoph F; Schiavone, Cosima

    2014-01-01

    Sarcoidosis is a complex granulomatous disease that affects virtually every organ and tissue, with a prevalence that varies significantly among the sites involved. The role of conventional imaging, such as computed tomography and magnetic resonance imaging, in the assessment of hepatosplenic sarcoidosis is well established by revealing organ enlargement, multiple discrete nodules, and lymphadenopathy. In this review, we aim to describe contrast-enhanced ultrasound (CEUS) findings in liver and spleen involvement by sarcoidosis, reporting evidence from the literature and cases from our experience, after a brief update on safety profile, cost-effectiveness, and clinical indications of this novel technique. Furthermore, we highlight potential advantages of CEUS in assessing hepatosplenic sarcoidosis that may be useful in the clinical practice. PMID:25215299

  6. Gallium-67 imaging in muscular sarcoidosis

    SciTech Connect

    Edan, G.; Bourguet, P.; Delaval, P.; Herry, J.Y.

    1984-07-01

    A case is presented of sarcoid myopathy in which radiogallium was seen to accumulate in the sites of muscle involvement. Uptake of the radiotracer disappeared following institution of corticosteroid therapy. The exceptional nature of this case contrasts with the high frequency of biopsy evidence of sarcoid granulomas in muscle. Gallium-67 imaging can be used to determine the extent of muscle involvement and, through evaluation of uptake intensity, the degree of disease activity before and after treatment.

  7. Chronic Fatigue Syndrome (CFS): Managing Activities and Exercise

    MedlinePlus

    ... Fatigue Syndrome (CFS) Share Compartir Managing Activities and Exercise On this Page Avoiding Extremes Developing an Activity ... recent manageable level of activity. Strength and Conditioning Exercises Strength and conditioning exercises are an important component ...

  8. Predominant diffuse ground glass opacity in both lung fields: A case of sarcoidosis with atypical CT findings

    PubMed Central

    Ma, Chunmei; Zhao, Yadong; Wu, Taihua

    2016-01-01

    Sarcoidosis can cause fatal diffuse lung fibrosis in the end stage, so its early diagnosis and treatment can prevent the progression of fibrosis. Predominant ground glass opacity on high-resolution CT (HRCT) scans is a rare presentation of sarcoidosis. We report the case of a patient who presented with very few symptoms and signs of sarcoidosis; HRCT revealed large-scale ground glass opacity and minor lymphadenopathy. Bronchoalveolar lavage fluid contained turbid liquid. Sarcoidosis could be confirmed only based on pathological examination of the resected tissue. The patient was administrated prednisone at 40 mg/d orally with tapering of the dose. Lung HRCT scans taken 6 months after the prednisone treatment showed ablation of the ground glass opacity. This case report sheds light on an atypical HRCT presentation of sarcoidosis; the findings here will be useful for the early diagnosis of sarcoidosis and prevention of fatal complications.

  9. [Clinical diagnostic and organizational aspects of providing care to patients with pulmonary sarcoidosis in the Armed Forces].

    PubMed

    Ovchinnikov, Iu V; Kriukov, E V; Zaĭtsev, A A; Antipushina, D N

    2014-11-01

    The data on the epidemiology and aetiology of sarcoidosis, the current classifications are presented. The basic provisions of the legal framework of medical management of patients suffering from sarcoidosis are given. The authors provided an analysis of the characteristics of diagnosis and treatment of sarcoidosis in the military, based on which we propose an algorithm of examination of patients with respiratory sarcoidosis in military health care facilities the Russian Defence Ministry, the recommended treatment regimens and order dynamic observation of patients. Invited to provide skilled care to patients with respiratory sarcoidosis selection based on the Main Military Clinical Burdenko Hospital specialized centre (department with bunks for the treatment of patients with sarcoidosis). PMID:25816680

  10. Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice

    PubMed Central

    Azuma, Kagaku; Furuzawa, Manabu; Fujiwara, Shu; Yamada, Kumiko; Kubo, Kin-ya

    2015-01-01

    Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a wooden stick to chew during the experimental period. Quantitative micro-computed tomography, histologic analysis, and biochemical markers were used to evaluate the bone response. The stress/chewing group exhibited significantly attenuated stress-induced increases in serum corticosterone levels, suppressed bone formation, enhanced bone resorption, and decreased trabecular bone mass in the vertebrae and distal femurs, compared with mice in the stress group. Active mastication during exposure to chronic stress alleviated chronic stress-induced bone density loss in B6 mice. Active mastication during chronic psychologic stress may thus be an effective strategy to prevent and/or treat chronic stress-related osteopenia. PMID:26664256

  11. Physical Activity Protects the Human Brain against Metabolic Stress Induced by a Postprandial and Chronic Inflammation

    PubMed Central

    Pruimboom, Leo; Raison, Charles L.; Muskiet, Frits A. J.

    2015-01-01

    In recent years, it has become clear that chronic systemic low-grade inflammation is at the root of many, if not all, typically Western diseases associated with the metabolic syndrome. While much focus has been given to sedentary lifestyle as a cause of chronic inflammation, it is less often appreciated that chronic inflammation may also promote a sedentary lifestyle, which in turn causes chronic inflammation. Given that even minor increases in chronic inflammation reduce brain volume in otherwise healthy individuals, the bidirectional relationship between inflammation and sedentary behaviour may explain why humans have lost brain volume in the last 30,000 years and also intelligence in the last 30 years. We review evidence that lack of physical activity induces chronic low-grade inflammation and, consequently, an energy conflict between the selfish immune system and the selfish brain. Although the notion that increased physical activity would improve health in the modern world is widespread, here we provide a novel perspective on this truism by providing evidence that recovery of normal human behaviour, such as spontaneous physical activity, would calm proinflammatory activity, thereby allocating more energy to the brain and other organs, and by doing so would improve human health. PMID:26074674

  12. Isolated oculocutaneous sarcoidosis in a teenage male: a rare case report.

    PubMed

    Aggarwal, H K; Jain, D; Mittal, A; Dabas, G

    2016-01-01

    Sarcoidosis is an inflammatory disease with multisystem involvement characterized by the presence of noncaseating granulomas. It can affect virtually every organ of the body, with lung involvement being most common occurring in >90% of patients. Other organs affected are skin, eye and liver. Skin involvement is common, affecting 25-35%. Here we present a rare case of a 15 year-old male with isolated oculocutaneous sarcoidosis without systemic involvement. PMID:27608799

  13. Cardiac sarcoidosis demonstrated by Tl-201 and Ga-67 SPECT imaging

    SciTech Connect

    Taki, J.; Nakajima, K.; Bunko, H.; Ohguchi, M.; Tonami, N.; Hisada, K. )

    1990-09-01

    Ga-67 and Tl-201 SPECT was performed to evaluate cardiac sarcoidosis in a 15-year-old boy. Tl-201 SPECT imaging showed decreased uptake in the inferior to lateral wall and Ga-67 accumulation in the area of decreased Tl-201 uptake. These findings suggested cardiac sarcoidosis, and cardiac biopsy confirmed this diagnosis. After corticosteroid therapy, myocardial uptake of Ga-67 disappeared and myocardial TI-201 uptake became more homogeneous.

  14. Tumoral calcinosis associated with sarcoidosis and positive bone and gallium imaging

    SciTech Connect

    Wolpe, F.M.; Khedkar, N.Y.; Gordon, D.; Werner, P.; Shirazi, P.; Al-Sabban, M.H.

    1987-07-01

    A 63-year-old female with biopsy proven tumoral calcinosis presented with progressive and recurrent swelling and tenderness of the right hip, thigh, elbow, and wrist. Both gallium and bone imaging demonstrated intense, congruent uptake in these areas. This is the third case of tumoral calcinosis with sarcoidosis documented in the literature. However, these are the first published bone and gallium scans in a patient with a history of sarcoidosis and tumoral calcinosis.

  15. SPECT imaging with Tl-201 and Ga-67 in myocardial sarcoidosis

    SciTech Connect

    Kurata, C.; Sakata, K.; Taguchi, T.; Fukumoto, Y.; Miyata, H.; Aoshima, S.; Yamazaki, N. )

    1990-06-01

    Two patients with myocardial sarcoidosis are presented, both of whom underwent SPECT imaging with Tl-201 and Ga-67. The first had Ga-67 myocardial uptake with a Tl-201 defect, which disappeared with corticosteroid therapy. The second had multiple Tl-201 defects without Ga-67 uptake, which persisted despite corticosteroid therapy. Therefore, the combination of Tl-201 and Ga-67 imaging may be useful for recognizing myocardial sarcoidosis and for predicting the response to corticosteroid therapy.

  16. Isolated sarcoidosis of accessory spleen in the greater omentum: A case report

    PubMed Central

    TU, CHAOYONG; LIN, QIAOMEI; ZHU, JINGDE; SHAO, CHUXIAO; ZHANG, KUN; JIANG, CHUAN; DING, ZHIYONG; ZHOU, XINGMU; TU, JIEFEI; ZHU, WANLIN; CHEN, WEI

    2016-01-01

    Sarcoidosis is a multisystemic disease of unknown origin characterized by the formation of non-caseating granulomas. Thoracic involvement is the most common presentation; however, sarcoidosis can involve almost any other organ. To the best of our knowledge there have been only 10 cases of splenic sarcoidosis reported in the English literature, with no reports of sarcoidosis of an accessory spleen. The present study reports a case of isolated sarcoidosis of an accessory spleen in the greater omentum, which was identified postoperatively in a 44-year-old female. Chest X-ray results were normal. Gastric endoscopy demonstrated an ulcer in the antrum, which was confirmed to be a signet-ring cell carcinoma via biopsy. Computed tomography of the abdomen revealed mild thickening of the posterior antrum, and a mass in the inferior pole of the left kidney. Intraoperatively, no masses were detected in the liver and spleen. Moreover, no enlarged lymph nodes were detected in the abdominal cavity, pelvic cavity, mesenteric and para-aorta. Following a radical distal gastrectomy and left radical nephrectomy, postoperative pathology demonstrated signet-ring cell carcinoma in the antrum, left renal clear cell cancer and a red lesion measuring 0.5×0.5 cm in the greater omentum, which was similar to the spleen in the splenic cavity and was regarded as an accessory spleen. Following exclusion of fungi and acid-fast bacilli as causative agents, sarcoidosis of the accessory spleen in the greater omentum was confirmed. The patient recovered uneventfully and was discharged on day 8 postoperation. The patient remained alive after two-year follow-up without sarcoidosis and malignant tumor recurrence. The present case demonstrated that, intraoperatively, comprehensive exploration should be conducted to exclude the accessory spleen, which may also suffer from sarcoidosis. PMID:27284324

  17. Development of a sarcoidosis murine lung granuloma model using Mycobacterium superoxide dismutase A peptide.

    PubMed

    Swaisgood, Carmen M; Oswald-Richter, Kyra; Moeller, Stephen D; Klemenc, Jennifer M; Ruple, Lisa M; Farver, Carol F; Drake, John M; Culver, Daniel A; Drake, Wonder P

    2011-02-01

    Sarcoidosis is characterized by noncaseating granulomas containing CD4(+) T cells with a Th1 immunophenotype. Although the causative antigens remain unknown, independent studies noted molecular and immunologic evidence of mycobacterial virulence factors in sarcoidosis specimens. A major limiting factor in discovering new insights into the pathogenesis of sarcoidosis is the lack of an animal model. Using a distinct superoxide dismutase A peptide (sodA) associated with sarcoidosis granulomas, we developed a pulmonary model of sarcoidosis granulomatous inflammation. Mice were sensitized by a subcutaneous injection of sodA, incorporated in incomplete Freund's adjuvant (IFA). Control subjects consisted of mice with no sensitization (ConNS), sensitized with IFA only (ConIFA), or with Schistosoma mansoni eggs. Fourteen days later, sensitized mice were challenged by tail-vein injection of naked beads, covalently coupled to sodA peptides or to schistosome egg antigens (SEA). Histologic analysis revealed hilar lymphadenopathy and noncaseating granulomas in the lungs of sodA-treated or SEA-treated mice. Flow cytometry of bronchoalveolar lavage (BAL) demonstrated CD4(+) T-cell responses against sodA peptide in the sodA-sensitized mice only. Cytometric bead analysis revealed significant differences in IL-2 and IFN-γ secretion in the BAL fluid of sodA-treated mice, compared with mice that received SEA or naked beads (P = 0.008, Wilcoxon rank sum test). ConNS and ConIFA mice demonstrated no significant formation of granuloma, and no Th1 immunophenotype. The use of microbial peptides distinct for sarcoidosis reveals a histologic and immunologic profile in the murine model that correlates well with those profiles noted in human sarcoidosis, providing the framework to investigate the molecular basis for the progression or resolution of sarcoidosis. PMID:20348207

  18. In vitro and in vivo reactivity to fungal cell wall agents in sarcoidosis

    PubMed Central

    Terčelj, M; Stopinšek, S; Ihan, A; Salobir, B; Simčič, S; Wraber, B; Rylander, R

    2011-01-01

    Sarcoidosis is an inflammatory disease. Epidemiological and treatment studies suggest that fungi play a part in the pathogenesis. The aim of this work was to study the effect of fungal cell wall agents (FCWA) on the in vitro secretion of cytokines from peripheral blood monocytes from subjects with sarcoidosis and relate the results to fungal exposure at home and clinical findings. Subjects with sarcoidosis (n = 22) and controls (n = 20) participated. Peripheral blood mononuclear cells were stimulated with soluble or particulate β-glucan (S-glucan, P-glucan), chitin or lipopolysaccharide (LPS), whereafter tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and IL-12 were measured. The severity of sarcoidosis was determined using a chest X-ray-based score. Serum cytokines (IL-2R, IL-6, IL-10 and IL-12) were determined. To measure domestic fungal exposure, air in the bedrooms was sampled on filters. N-acetylhexosaminidase (NAHA) on the filters was measured as a marker of fungal cell biomass. The induced secretion of cytokines was higher from peripheral blood mononuclear cells (PBMC) from subjects with sarcoidosis. P-glucan was more potent than S-glucan inducing a secretion. Chitin had a small effect. Among subjects with sarcoidosis there was a significant relation between the spontaneous PBMC production of IL-6, IL-10 and IL-12 and the NAHA levels at home. The P-glucan induced secretion of IL-12 was related to the duration of symptoms at the time of diagnosis. Their X-ray scores were related to an increased secretion of cytokines after stimulation with LPS or P-glucan. Subjects with sarcoidosis have a higher reactivity to FCWA in vitro and to home exposure. The influence of FCWA on inflammatory cells and their interference with the inflammatory defense mechanisms in terms of cytokine secretion could be important factors for the development of sarcoidosis. PMID:21910725

  19. Gallium-67 imaging in muscular sarcoidosis

    SciTech Connect

    Edan, G.; Bourguet, P.; Delaval, P.; Herry, J.Y.

    1984-07-01

    A case is presented of sarcoid myopathy in which radiogallium was seen to accumulate in the sites of muscle involvement. Uptake of the radiotracer disappeared following institution of corticosteroid therapy. The exceptional nature of this case contrasts with the high frequency of biopsy evidence of sarcoid muscle disease but is consistent with the rarity of clinical evidence of sarcoid granulomas in muscle. Gallium-67 imaging can be used to determine the extent of muscle involvement and, through evaluation of uptake intensity, the degree of disease activity before and after treatment.

  20. Chronic beryllium disease: Diagnosis and management

    SciTech Connect

    Rossman, M.D.

    1996-10-01

    Chronic beryllium disease is predominantly a pulmonary granulomatosis that was originally described in 1946. Symptoms usually include dyspnea and cough. Fever, anorexia, and weight loss are common. Skin lesions are the most common extrathoracic manifestation. Granulomatous hepatitis, hypercalcemia, and kidney stones can also occur. Radiographic and physiologic abnormalities are similar to those in sarcoidosis. While traditionally the pathologic changes included granulomas and cellular interstitial changes, the hallmark of the disease today is the well-formed granuloma. Immunologic studies have demonstrated a cell-mediated response to beryllium that is due to an accumulation of CD4{sup +} T cells at the site of disease activity. Diagnosis depends on the demonstration of pathologic changes (i.e., granuloma) and evidence that the granuloma was caused by a hypersensitivity to beryllium (i.e., positive lung proliferative response to beryllium). Using these criteria, the diagnosis of chronic beryllium disease can now be made before the onset of clinical symptoms. Whether, with early diagnosis, the natural course of this condition will be the same as when it was traditionally diagnosed is not known. Currently, corticosteroids are used to treat patients with significant symptoms or evidence of progressive disease. 21 refs.

  1. [Cryptococcal meningitis in a patient with a ventriculoperitoneal shunt and monitoring for pulmonary sarcoidosis].

    PubMed

    Baallal, H; El Asri, A C; Eljebbouri, B; Akhaddar, A; Gazzaz, M; El Mostarchid, B; Boucetta, M

    2013-02-01

    The fungus Cryptococcus neoformans can cause common opportunistic infection in acquired immune deficiency syndrome (AIDS) patients. But other conditions can be associated with sarcoidosis. Meningoencephalitis is the most common manifestation of this disease. One of the most important neurological complications is the development of intracranial hypertension (ICH), which may result in high morbidity and mortality. We report the case of a patient harboring a ventriculoperitoneal shunt, and having contracted a cryptococcal meningitis as a risk factor for pulmonary sarcoidosis. Brain MRI showed arachnoiditis, with a mass in contact with the right frontal horn. Indian ink staining of the cerebrospinal fluid (CSF) showed positivity that was confirmed by the identification of Cryptococcus neoformans after culture. The evolution was favorable under medical treatment with removal of material. The relationship between sarcoidosis and cryptococcosis, described in the literature is not coincidental but is a rare complication of sarcoidosis of potential severity (40% of mortality). Sarcoidosis is a common systemic disease that may increase host susceptibility to CNS cryptococcal infection without any other signs or symptoms of host immunosuppression. The diagnosis of cryptococcosis should be evoked as a differential diagnosis of neuro-sarcoidosis. PMID:23395187

  2. Chronology of UPR activation in skeletal muscle adaptations to chronic contractile activity.

    PubMed

    Memme, Jonathan M; Oliveira, Ashley N; Hood, David A

    2016-06-01

    The mitochondrial and endoplasmic reticulum unfolded protein responses (UPR(mt) and UPR(ER)) are important for cellular homeostasis during stimulus-induced increases in protein synthesis. Exercise triggers the synthesis of mitochondrial proteins, regulated in part by peroxisome proliferator activator receptor-γ coactivator 1α (PGC-1α). To investigate the role of the UPR in exercise-induced adaptations, we subjected rats to 3 h of chronic contractile activity (CCA) for 1, 2, 3, 5, or 7 days followed by 3 h of recovery. Mitochondrial biogenesis signaling, through PGC-1α mRNA, increased 14-fold after 1 day of CCA. This resulted in 10-32% increases in cytochrome c oxidase activity, indicative of mitochondrial content, between days 3 and 7, as well as increases in the autophagic degradation of p62 and microtubule-associated proteins 1A/1B light chain 3A (LC3)-II protein. Before these adaptations, the UPR(ER) transcripts activating transcription factor-4, spliced X-box-binding protein 1, and binding immunoglobulin protein were elevated (1.3- to 3.8-fold) at days 1-3, while CCAAT/enhancer-binding protein homologous protein (CHOP) and chaperones binding immunoglobulin protein and heat shock protein (HSP) 70 were elevated at mRNA and protein levels (1.5- to 3.9-fold) at days 1-7 of CCA. The mitochondrial chaperones 10-kDa chaperonin, HSP60, and 75-kDa mitochondrial HSP, the protease ATP-dependent Clp protease proteolytic subunit, and the regulatory protein sirtuin-3 of the UPR(mt) were concurrently induced 10-80% between days 1 and 7 To test the role of the UPR in CCA-induced remodeling, we treated animals with the endoplasmic reticulum stress suppressor tauroursodeoxycholic acid and subjected them to 2 or 7 days of CCA. Tauroursodeoxycholic acid attenuated CHOP and HSP70 protein induction; however, this failed to impact mitochondrial remodeling. Our data indicate that signaling to the UPR is rapidly activated following acute contractile activity, that this is

  3. Mapping ongoing European research activities examining the infectious aetiology of chronic conditions.

    PubMed

    Semenza, J C; Svederud, I; Medin, E; Orrskog, S; Tsolova, S

    2013-09-01

    Chronic conditions contribute to the majority of the mortality and morbidity burden in Europe. The extent to which infectious agents are responsible for the chronic disease burden remains elusive. The complex nature of the natural history of chronic conditions calls for an overview of ongoing research activities linking infectious agents with these conditions in order to guide research endeavours, direct research funding, steer prevention efforts, and point health policy towards promising interventions. A selection of websites hosted by institutions either financing or conducting research within the European Union was screened for ongoing research activities examining infectious aetiology of chronic conditions. The searches were conducted until September 2011, applying search strategies and inclusion criteria predefined in a study protocol. In total, 25 research activities met the inclusion criteria. Of those, ten activities were focused to investigate infectious aetiology of cancer, four focused on type 2 diabetes mellitus, and 11 focused on a wide spectrum of other chronic conditions. The identified research projects did not cover areas such as mental and behavioural disorders. Infectious agents analysed included enteroviruses, Epstein-Barr virus, human rhinoviruses, P. gingivalis, human papillomaviruses, cytomegalovirus, Helicobacter spp. and human parvovirus. Only three projects specifically addressed therapeutic interventions. Ultimately, linking infectious agents with chronic conditions may translate into prevention efforts with vaccinations or treatment strategies with antimicrobial agents, and could, thus, eventually reduce the heavy disease burden from chronic conditions. However, little translational research on therapeutic interventions was found in our search and should be fostered, particularly for more established infectious-chronic disease associations. PMID:23046318

  4. Effects of chronic stress and corticosterone on sialidase activity in the rat hippocampus.

    PubMed

    Wielgat, Przemyslaw; Walesiuk, Anna; Braszko, Jan J

    2011-09-23

    Sialidases are acid exoglycosidases that catalyse the removal of sialic acid from non-reducing end of sialoglucoconjugated substrates. Synaptic plasticity depends on sialylation state of proteins and lipids mediated by sialic acid-metabolizing enzymes. Since chronic stress causes both, hippocampal atrophy and impairment of learning, it is reasonable to investigate whether sialidase is implicated in these processes. In this study, we tested effects of chronic stress (immobilization, 2h daily, 21 days) or chronic corticosterone administration (5 mg/kg, sc, daily) on sialidase activity and sialylated NCAMs expression in rat hippocampus. The results showed that chronic stress affects hippocampus-depended spatial learning in the Barnes maze. Both, stress (p > 0.05) and corticosterone (p < 0.001), increased latencies to enter the escape tunnel of the maze in comparison to control animals. Similar but not significant differences between control and other experimental groups were observed in the numbers of errors. Chronic stress (p > 0.05) and corticosterone (p < 0.05) decreased sialidase activity in the brain homogenates and synaptosomes (p < 0.05, both). In the stressed animals, these changes were related to significantly higher expression of polysialic acid. These results indicate that changes in sialidase activity caused by stress and chronic corticosterone administration reflect disturbances of polysialylated glycoconjugates known to be related to synaptic plasticity in hippocampus. PMID:21501633

  5. Sarcoidosis and Histoplasmosis: Is One a Consequence of the Other? A Case Report and Review of the Literature

    PubMed Central

    Bansal, Anupam; Drewek, Rupali

    2015-01-01

    Sarcoidosis involves abnormal collections of inflammatory cells (granulomas) which may form as nodules in multiple organs. 90% of affected patients have respiratory tract abnormalities. We present a 61-year-old male with sarcoidosis who was admitted for respiratory distress. Fibrosing mediastinitis was seen in the chest computograph. Management was conservative and included steroids, antibiotics, and oxygen therapy. Sarcoidosis and fibrosing mediastinitis are rare. Fibrosing mediastinitis is more commonly seen with histoplasmosis. We explore the clinical similarities between histoplasmosis and sarcoidosis. We also explore the potential cause and effect relationship and workup for each disease entity. PMID:26345350

  6. Variation in the Lymphotoxin-α/Tumor Necrosis Factor Locus Modifies Risk of Erythema Nodosum in Sarcoidosis

    PubMed Central

    McDougal, Kathryn E.; Fallin, M. Daniele; Moller, David R.; Song, Zhimin; Cutler, David J.; Steiner, Lori L.; Cutting, Garry R.

    2010-01-01

    Sarcoidosis is a multi-system inflammatory disease with organ involvement that varies by race and sex. Family studies indicate that genes play a role in the etiology and extent of organ involvement in sarcoidosis. In this study, we evaluated whether 25 variants distributed in 19 genes with a known role in inflammation were associated with erythema nodosum status in 659 sarcoidosis patients and 658 controls from A Case–Control Etiologic Study of Sarcoidosis (ACCESS). We found no association with affectation status; however, a variant in the promoter of tumor necrosis factor (TNF) at position −308 was found to be associated with erythema nodosum in Caucasian sarcoidosis patients (study-wide P = 0.027). When separated by sex, a variant in intron 1 of lymphotoxin-α (LTA), a gene adjacent to TNF, was associated with erythema nodosum in female Caucasian sarcoidosis patients (study-wide P = 0.027). These DNA variants frequently occur together in Caucasians, and each variant has individually been associated with erythema nodosum in sarcoidosis patients. These results confirm that variation in the LTA/TNF gene cluster modifies a major skin manifestation of sarcoidosis and may explain the higher rate of erythema nodosum in females with sarcoidosis. PMID:19225544

  7. Plasticity of TOM complex assembly in skeletal muscle mitochondria in response to chronic contractile activity.

    PubMed

    Joseph, Anna-Maria; Hood, David A

    2012-03-01

    We investigated the assembly of the TOM complex within skeletal muscle under conditions of chronic contractile activity-induced mitochondrial biogenesis. Tom40 import into mitochondria was increased by chronic contractile activity, as was its time-dependent assembly into the TOM complex. These changes coincided with contractile activity-induced augmentations in the expression of key protein import machinery components Tim17, Tim23, and Tom22, as well as the cytosolic chaperone Hsp90. These data indicate the adaptability of the TOM protein import complex and suggest a regulatory role for the assembly of this complex in exercise-induced mitochondrial biogenesis. PMID:22142511

  8. Peroxisome Proliferator-Activated Receptor Ligands and Their Role in Chronic Myeloid Leukemia: Therapeutic Strategies.

    PubMed

    Yousefi, Bahman; Samadi, Nasser; Baradaran, Behzad; Shafiei-Irannejad, Vahid; Zarghami, Nosratollah

    2016-07-01

    Imatinib therapy remains the gold standard for treatment of chronic myeloid leukemia; however, the acquired resistance to this therapeutic agent in patients has urged the scientists to devise modalities for overcoming this chemoresistance. For this purpose, initially therapeutic agents with higher tyrosine kinase activity were introduced, which had the potential for inhibiting even mutant forms of Bcr-Abl. Furthermore, coupling imatinib with peroxisome proliferator-activated receptor ligands also showed beneficial effects in chronic myeloid leukemia cell proliferation. These combination protocols inhibited cell growth and induced apoptosis as well as differentiation in chronic myeloid leukemia cell lines. In addition, peroxisome proliferator-activated receptors ligands increased imatinib uptake by upregulating the expression of human organic cation transporter 1. Taken together, peroxisome proliferator-activated receptors ligands are currently being considered as novel promising therapeutic candidates for chronic myeloid leukemia treatment, because they can synergistically enhance the efficacy of imatinib. In this article, we reviewed the potential of peroxisome proliferator-activated receptors ligands for use in chronic myeloid leukemia treatment. The mechanism of action of these therapeutics modalities are also presented in detail. PMID:26841308

  9. Leisure Time Physical Activity and Mortality in Chronic Kidney Disease: Preliminary findings from the MDRD study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic kidney disease (CKD) is an important risk factor for cardiovascular disease and all-cause mortality. In the general population, physical activity is associated with reduced mortality. We examined physical activity status in CKD patients and its relation to all-cause mortality. The Modified...

  10. Microglia activation regulates GluR1 phosphorylation in chronic unpredictable stress-induced cognitive dysfunction.

    PubMed

    Liu, Mingchao; Li, Juan; Dai, Peng; Zhao, Fang; Zheng, Gang; Jing, Jinfei; Wang, Jiye; Luo, Wenjing; Chen, Jingyuan

    2015-01-01

    Chronic stress is considered to be a major risk factor in the development of psychopathological syndromes in humans. Cognitive impairments and long-term potentiation (LTP) impairments are increasingly recognized as major components of depression, anxiety disorders and other stress-related chronic psychological illnesses. It seems timely to systematically study the potentially underlying neurobiological mechanisms of altered cognitive and synaptic plasticity in the course of chronic stress. In the present study, a rat model of chronic unpredictable stress (CUS) induced a cognitive impairment in spatial memory in the Morris water maze (MWM) test and a hippocampal LTP impairment. CUS also induced hippocampal microglial activation and attenuated phosphorylation of glutamate receptor 1 (GluR1 or GluA1). Moreover, chronic treatment with the selective microglial activation blocker, minocycline (120 mg/kg per day), beginning 3 d before CUS treatment and continuing through the behavioral testing period, prevented the CUS-induced impairments of spatial memory and LTP induction. Additional studies showed that minocycline-induced inhibition of microglia activation was associated with increased phosphorylation of GluR1. These results suggest that hippocampal microglial activation modulates the level of GluR1 phosphorylation and might play a causal role in CUS-induced cognitive and LTP disturbances. PMID:25472821

  11. [Subpopulations and phagocytic activity of monocytes in chronic gastroduodenitis in children].

    PubMed

    Agafonova, E V; Malanicheva, T G; Denisova, S N

    2013-01-01

    There was conducted a study of the phagocytic activity, immunophenotype and peripheral blood monocytes by flow cytometry in children with chronic gastroduodenitis associated with Helicobacter pylori, as well as the association of Helicobacter pylori with fungi of the genus Candida and markers of secondary immune deficiency. The differential changes in the structure of circulating profile of monocytes were revealed, that indicate the pathogenetic significance of these disorders in chronic gastroduodenitis with H. pylori etiology, as well as at association of Helicobacter pylori with fungi of the genus Candida. Violations of the phagocytic activity of monocytes in chronic gastroduodenitis in children are associated with depression of different stages of phagocytosis--capture functions, mobilization, killing, intracellular biocidity. A severe depression in phagocytic activity of monocytes occurs in CGD associated with Hp and fungi of the genus Candida. PMID:24501955

  12. Nitric oxide-induced cellular stress and p53 activation in chronic inflammation

    PubMed Central

    Hofseth, Lorne J.; Saito, Shin'ichi; Hussain, S. Perwez; Espey, Michael G.; Miranda, Katrina M.; Araki, Yuzuru; Jhappan, Chamelli; Higashimoto, Yuichiro; He, Peijun; Linke, Steven P.; Quezado, Martha M.; Zurer, Irit; Rotter, Varda; Wink, David A.; Appella, Ettore; Harris, Curtis C.

    2003-01-01

    Free radical-induced cellular stress contributes to cancer during chronic inflammation. Here, we investigated mechanisms of p53 activation by the free radical, NO. NO from donor drugs induced both ataxia-telangiectasia mutated (ATM)- and ataxia-telangiectasia mutated and Rad3-related-dependent p53 posttranslational modifications, leading to an increase in p53 transcriptional targets and a G2/M cell cycle checkpoint. Such modifications were also identified in cells cocultured with NO-releasing macrophages. In noncancerous colon tissues from patients with ulcerative colitis (a cancer-prone chronic inflammatory disease), inducible NO synthase protein levels were positively correlated with p53 serine 15 phosphorylation levels. Immunostaining of HDM-2 and p21WAF1 was consistent with transcriptionally active p53. Our study highlights a pivotal role of NO in the induction of cellular stress and the activation of a p53 response pathway during chronic inflammation. PMID:12518062

  13. Activation of nuclear factor-kappaB in dogs with chronic enteropathies.

    PubMed

    Luckschander, Nicole; Hall, Jean A; Gaschen, Frédéric; Forster, Ursula; Wenzlow, Nanny; Hermann, Pascal; Allenspach, Karin; Dobbelaere, Dirk; Burgener, Iwan A; Welle, Monika

    2010-02-15

    Homeostasis in the intestinal microenvironment between the immune system and luminal antigens appears disturbed in chronic enteropathies. Pro-inflammatory cytokines likely play a role in the pathogenesis of intestinal inflammation. Several inflammatory and immunoregulatory genes have associated nuclear factor-kappaB (NF-kappaB) binding sites, which allow NF-kappaB to regulate gene transcription. The purpose of this study was to investigate (1) the occurrence of NF-kappaB activation during mucosal inflammation in situ, (2) the mucosal distribution pattern of cells expressing activated NF-kappaB within treatment groups, and (3) the effect of specific therapy on NF-kappaB activation. Dogs with chronic enteropathy were studied (n=26) and compared with 13 healthy dogs. Ten dogs had food responsive disease (FRD) and 16 had inflammatory bowel disease (IBD). NF-kappaB activation was detected in duodenal mucosal biopsies using a mouse monoclonal antibody (MAB 3026) that selectively binds the nuclear localization sequence of activated NF-kappaB. To identify macrophages, biopsies were stained using the MAC 387 antibody. Macrophages in the lamina propria double-stained for MAC 387 and NF-kappaB were quantitated; epithelial cell expression of activated NF-kappaB was determined semi-quantitatively. Results showed that more macrophages positive for activated NF-kappaB were present in lamina propria of dogs with chronic enteropathy compared to control dogs (p<0.01). More NF-kappaB positive epithelial cells were observed in FRD dogs compared to IBD dogs (p<0.05). After therapy, the number of macrophages and epithelial cells staining positive for activated NF-kappaB decreased (p<0.01) in chronic enteropathy dogs. In conclusion, activation of NF-kappaB is closely associated with the pathophysiology of canine chronic enteropathy. Down-regulation follows successful therapy. PMID:19740552

  14. Screening for Differentially Expressed Proteins Relevant to the Differential Diagnosis of Sarcoidosis and Tuberculosis

    PubMed Central

    Hu, Yang; Wang, Liu-Sheng; Zhou, Ying; Li, Qiu-Hong; Li, Yan; Du, Yu-Kui; He, Xian; Li, Nan; Yin, Zhao-Fang; Wei, Ya-Ru; Weng, Dong; Li, Hui-Ping

    2015-01-01

    Background In this study, we sought to identify differentially expressed proteins in the serum of patients with sarcoidosis or tuberculosis and to evaluate these proteins as markers for the differential diagnosis of sarcoidosis and sputum-negative tuberculosis. Methods Using protein microarrays, we identified 3 proteins exhibiting differential expression between patients with sarcoidosis and tuberculosis. Elevated expression of these proteins was verified using the enzyme-linked immunosorbent assay (ELISA) and was further confirmed by immunohistochemistry. Receiver operating characteristic (ROC) curve, logistic regression analysis, parallel, and serial tests were used to evaluate the diagnostic efficacy of the proteins. Results Intercellular Adhesion Molecule 1(ICAM-1) and leptin were screened for differentially expressed proteins relevant to sarcoidosis and tuberculosis. Using ROC curves, we found that ICAM-1 (cutoff value: 57740 pg/mL) had an area under the curve (AUC), sensitivity, and specificity of 0.718, 62.3%, and 79.5% respectively, while leptin (cutoff value: 1193.186 pg/mL) had an AUC, sensitivity, and specificity of 0.763, 88.3%, and 65.8%, respectively. Logistic regression analysis revealed that the AUC, sensitivity, and specificity of combined leptin and ICAM-1 were 0.787, 89.6%, and 65.8%, respectively, while those of combined leptin, ICAM-1, and body mass index (BMI) were 0.837, 90.9%, and 64.4%, respectively, which had the greatest diagnostic value. Parallel and serial tests indicated that the BMI-leptin parallel with the ICAM-1 serial was the best diagnostic method, achieving a sensitivity and specificity of 86.5% and 73.1%, respectively. Thus, our results identified elevated expression of ICAM-1 and leptin in serum and granulomas of sarcoidosis patients. Conclusions ICAM-1 and leptin were found to be potential markers for the diagnosis of sarcoidosis and differential diagnosis of sarcoidosis and sputum-negative tuberculosis. PMID:26368286

  15. Wearable Systems for Monitoring Mobility-Related Activities in Chronic Disease: A Systematic Review

    PubMed Central

    Allet, Lara; Knols, Ruud H.; Shirato, Kei; de Bruin, Eling D.

    2010-01-01

    The use of wearable motion sensing technology offers important advantages over conventional methods for obtaining measures of physical activity and/or physical functioning in individuals with chronic diseases. This review aims to identify the actual state of applying wearable systems for monitoring mobility-related activity in individuals with chronic disease conditions. In this review we focus on technologies and applications, feasibility and adherence aspects, and clinical relevance of wearable motion sensing technology. PubMed (Medline since 1990), PEdro, and reference lists of all relevant articles were searched. Two authors independently reviewed randomised trials systematically. The quality of selected articles was scored and study results were summarised and discussed. 163 abstracts were considered. After application of inclusion criteria and full text reading, 25 articles were taken into account in a full text review. Twelve of these papers evaluated walking with pedometers, seven used uniaxial accelerometers to assess physical activity, six used multiaxial accelerometers, and two papers used a combination approach of a pedometer and a multiaxial accelerometer for obtaining overall activity and energy expenditure measures. Seven studies mentioned feasibility and/or adherence aspects. The number of studies that use movement sensors for monitoring of activity patterns in chronic disease (postural transitions, time spent in certain positions or activities) is nonexistent on the RCT level of study design. Although feasible methods for monitoring human mobility are available, evidence-based clinical applications of these methods in individuals with chronic diseases are in need of further development. PMID:22163393

  16. Chronic Activation of γ2 AMPK Induces Obesity and Reduces β Cell Function.

    PubMed

    Yavari, Arash; Stocker, Claire J; Ghaffari, Sahar; Wargent, Edward T; Steeples, Violetta; Czibik, Gabor; Pinter, Katalin; Bellahcene, Mohamed; Woods, Angela; Martínez de Morentin, Pablo B; Cansell, Céline; Lam, Brian Y H; Chuster, André; Petkevicius, Kasparas; Nguyen-Tu, Marie-Sophie; Martinez-Sanchez, Aida; Pullen, Timothy J; Oliver, Peter L; Stockenhuber, Alexander; Nguyen, Chinh; Lazdam, Merzaka; O'Dowd, Jacqueline F; Harikumar, Parvathy; Tóth, Mónika; Beall, Craig; Kyriakou, Theodosios; Parnis, Julia; Sarma, Dhruv; Katritsis, George; Wortmann, Diana D J; Harper, Andrew R; Brown, Laurence A; Willows, Robin; Gandra, Silvia; Poncio, Victor; de Oliveira Figueiredo, Márcio J; Qi, Nathan R; Peirson, Stuart N; McCrimmon, Rory J; Gereben, Balázs; Tretter, László; Fekete, Csaba; Redwood, Charles; Yeo, Giles S H; Heisler, Lora K; Rutter, Guy A; Smith, Mark A; Withers, Dominic J; Carling, David; Sternick, Eduardo B; Arch, Jonathan R S; Cawthorne, Michael A; Watkins, Hugh; Ashrafian, Houman

    2016-05-10

    Despite significant advances in our understanding of the biology determining systemic energy homeostasis, the treatment of obesity remains a medical challenge. Activation of AMP-activated protein kinase (AMPK) has been proposed as an attractive strategy for the treatment of obesity and its complications. AMPK is a conserved, ubiquitously expressed, heterotrimeric serine/threonine kinase whose short-term activation has multiple beneficial metabolic effects. Whether these translate into long-term benefits for obesity and its complications is unknown. Here, we observe that mice with chronic AMPK activation, resulting from mutation of the AMPK γ2 subunit, exhibit ghrelin signaling-dependent hyperphagia, obesity, and impaired pancreatic islet insulin secretion. Humans bearing the homologous mutation manifest a congruent phenotype. Our studies highlight that long-term AMPK activation throughout all tissues can have adverse metabolic consequences, with implications for pharmacological strategies seeking to chronically activate AMPK systemically to treat metabolic disease. PMID:27133129

  17. The neurological significance of abnormal natural killer cell activity in chronic toxigenic mold exposures.

    PubMed

    Anyanwu, Ebere; Campbell, Andrew W; Jones, Joseph; Ehiri, John E; Akpan, Akpan I

    2003-11-13

    Toxigenic mold activities produce metabolites that are either broad-spectrum antibiotics or mycotoxins that are cytotoxic. Indoor environmental exposure to these toxigenic molds leads to adverse health conditions with the main outcome measure of frequent neuroimmunologic and behavioral consequences. One of the immune system disorders found in patients presenting with toxigenic mold exposure is an abnormal natural killer cell activity. This paper presents an overview of the neurological significance of abnormal natural killer cell (NKC) activity in chronic toxigenic mold exposure. A comprehensive review of the literature was carried out to evaluate and assess the conditions under which the immune system could be dysfunctionally interfered with leading to abnormal NKC activity and the involvement of mycotoxins in these processes. The functions, mechanism, the factors that influence NKC activities, and the roles of mycotoxins in NKCs were cited wherever necessary. The major presentations are headache, general debilitating pains, nose bleeding, fevers with body temperatures up to 40 degrees C (104 degrees F), cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, vertigo/dizziness, and in some cases, seizures. Although sleep is commonly considered a restorative process that is important for the proper functioning of the immune system, it could be disturbed by mycotoxins. Most likely, mycotoxins exert some rigorous effects on the circadian rhythmic processes resulting in sleep deprivation to which an acute and transient increase in NKC activity is observed. Depression, psychological stress, tissue injuries, malignancies, carcinogenesis, chronic fatigue syndrome, and experimental allergic encephalomyelitis could be induced at very low physiological concentrations by mycotoxin-induced NKC activity. In the light of this review, it is concluded that chronic exposures to toxigenic mold could lead to abnormal NKC activity with a wide range

  18. Oligoclonal banding of IgG in CSF, blood-brain barrier function, and MRI findings in patients with sarcoidosis, systemic lupus erythematosus, and Behçet's disease involving the nervous system.

    PubMed Central

    McLean, B N; Miller, D; Thompson, E J

    1995-01-01

    A retrospective study of CSF and serum analysis from a total of 43 patients with sarcoidosis, 20 with systemic lupus erythematosus, and 12 with Behçet's disease with neurological involvement found local synthesis of oligoclonal IgG using isoelectric focusing and immunoblotting in 51%, 25%, and 8% respectively at some stage in their disease. Blood-brain barrier breakdown, when assessed with an albumin ratio found 47% of patients with sarcoidosis, 30% of those with systemic lupus erythematosus, and 42% of patients with Behçet's disease exhibiting abnormal barrier function at some time. Serial CSF analysis showed that clinical relapses were associated with worsening barrier function and in some patients the development of local oligoclonal IgG synthesis; conversely steroid treatment led to a statistically significant improvement in barrier function, and in two patients a loss of oligoclonal IgG bands. A higher proportion of patients had MRI abnormalities than oligoclonal IgG or blood-brain barrier breakdown, MRI being abnormal in 16 of 19 patients with sarcoidosis, three of four patients with systemic lupus erythematosus, and seven of nine patients with Behçet's disease, although this may have been due to temporal factors. In the differential diagnosis of chronic neurological disorders, locally synthesised oligoclonal IgG cannot distinguish between diseases, but the loss of bands seen in two patients contrasts with what is seen in multiple sclerosis, and thus may be a useful diagnostic clue. PMID:7745401

  19. Defective insulin secretion by chronic glucagon receptor activation in glucose intolerant mice.

    PubMed

    Ahlkvist, Linda; Omar, Bilal; Valeur, Anders; Fosgerau, Keld; Ahrén, Bo

    2016-03-01

    Stimulation of insulin secretion by short-term glucagon receptor (GCGR) activation is well characterized; however, the effect of long-term GCGR activation on β-cell function is not known, but of interest, since hyperglucagonemia occurs early during development of type 2 diabetes. Therefore, we examined whether chronic GCGR activation affects insulin secretion in glucose intolerant mice. To induce chronic GCGR activation, high-fat diet fed mice were continuously (2 weeks) infused with the stable glucagon analog ZP-GA-1 and challenged with oral glucose and intravenous glucose±glucagon-like peptide 1 (GLP1). Islets were isolated to evaluate the insulin secretory response to glucose±GLP1 and their pancreas were collected for immunohistochemical analysis. Two weeks of ZP-GA-1 infusion reduced insulin secretion both after oral and intravenous glucose challenges in vivo and in isolated islets. These inhibitory effects were corrected for by GLP1. Also, we observed increased β-cell area and islet size. We conclude that induction of chronic ZP-GA-1 levels in glucose intolerant mice markedly reduces insulin secretion, and thus, we suggest that chronic activation of the GCGR may contribute to the failure of β-cell function during development of type 2 diabetes. PMID:26698567

  20. Unraveling dynamics of human physical activity patterns in chronic pain conditions

    NASA Astrophysics Data System (ADS)

    Paraschiv-Ionescu, Anisoara; Buchser, Eric; Aminian, Kamiar

    2013-06-01

    Chronic pain is a complex disabling experience that negatively affects the cognitive, affective and physical functions as well as behavior. Although the interaction between chronic pain and physical functioning is a well-accepted paradigm in clinical research, the understanding of how pain affects individuals' daily life behavior remains a challenging task. Here we develop a methodological framework allowing to objectively document disruptive pain related interferences on real-life physical activity. The results reveal that meaningful information is contained in the temporal dynamics of activity patterns and an analytical model based on the theory of bivariate point processes can be used to describe physical activity behavior. The model parameters capture the dynamic interdependence between periods and events and determine a `signature' of activity pattern. The study is likely to contribute to the clinical understanding of complex pain/disease-related behaviors and establish a unified mathematical framework to quantify the complex dynamics of various human activities.

  1. Immunological Evidence for the Role of Mycobacteria in Sarcoidosis: A Meta-Analysis

    PubMed Central

    Fang, Chuling; Huang, Hui; Xu, Zuojun

    2016-01-01

    Background Sarcoidosis is a granulomatous disease, the etiology of which is currently unknown. The role of mycobacteria in the etiology of sarcoidosis has been extensively investigated. In this meta-analysis, we assessed the immunological evidence of the possible role of mycobacteria in the pathogenesis and development of sarcoidosis. Methods We performed a systematic search of relevant articles from PubMed, Embase and Cochrane Library databases published between January 1990 and October 2015. Data extracted from the articles were analyzed with Review Manager 5.3 (Cochrane Collaboration, Oxford, UK). Results In this meta-analysis, 13 case-control studies (733 participants) were considered eligible according to our criteria. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). The positivity incidence of the immune response (either the cell-mediated response or humoral response) in sarcoidosis patients was significantly higher than that in controls, as determined using fixed-effects model. The odds ratio (OR) of the positivity incidence of T-cell response in the patients with sarcoidosis versus the controls with PPD- or unknown PPD status was 5.54 (95% CI 3.56–8.61); the ORs were 16.70 (95% CI 8.19–34.08) and 1.48 (95% CI 0.74–2.96) for the two subgroups with PPD- controls and unknown PPD status respectively. However, the OR of the positivity incidence in patients with sarcoidosis versus PPD+ controls (latent tuberculosis infection; LTBI) was 0.26 (95% 0.10–0.66). Regarding the humoral response, pooled analysis of the positivity incidence revealed an OR (95%CI) of 20.43 (5.53–75.53) for the patients with sarcoidosis versus controls; the ORs were 11.93 (95% CI 2.15–66.27) and 41.97 (95% CI 5.24–336.15) in two subgroups of controls with PPD- and unknown PPD statuses respectively. Data on heterogeneity and evidence of publication bias were examined. Conclusions This meta-analysis confirmed the existence of an association between

  2. Chronic hyperammonemia alters the circadian rhythms of corticosteroid hormone levels and of motor activity in rats.

    PubMed

    Ahabrach, Hanan; Piedrafita, Blanca; Ayad, Abdelmalik; El Mlili, Nisrin; Errami, Mohammed; Felipo, Vicente; Llansola, Marta

    2010-05-15

    Patients with liver cirrhosis may present hepatic encephalopathy with a wide range of neurological disturbances and alterations in sleep quality and in the sleep-wake circadian rhythm. Hyperammonemia is a main contributor to the neurological alterations in hepatic encephalopathy. We have assessed, in an animal model of chronic hyperammonemia without liver failure, the effects of hyperammonemia per se on the circadian rhythms of motor activity, temperature, and plasma levels of adrenal corticosteroid hormones. Chronic hyperammonemia alters the circadian rhythms of locomotor activity and of cortisol and corticosterone levels in blood. Different types of motor activity are affected differentially. Hyperammonemia significantly alters the rhythm of spontaneous ambulatory activity, reducing strongly ambulatory counts and slightly average velocity during the night (the active phase) but not during the day, resulting in altered circadian rhythms. In contrast, hyperammonemia did not affect wheel running at all, indicating that it affects spontaneous but not voluntary activity. Vertical activity was affected only very slightly, indicating that hyperammonemia does not induce anxiety. Hyperammonemia abolished completely the circadian rhythm of corticosteroid hormones in plasma, completely eliminating the peaks of cortisol and corticosterone present in control rats at the start of the dark period. The data reported show that chronic hyperammonemia, similar to that present in patients with liver cirrhosis, alters the circadian rhythms of corticosteroid hormones and of motor activity. This suggests that hyperammonemia would be a relevant contributor to the alterations in corticosteroid hormones and in circadian rhythms in patients with liver cirrhosis. PMID:19998493

  3. Exhaled 8-isoprostane in sarcoidosis: relation to superoxide anion production by bronchoalveolar lavage cells

    PubMed Central

    Kurmanowska, Zofia; Antczak, Adam; Marczak, Jerzy; Ciebiada, Maciej; Górski, Paweł

    2010-01-01

    Objective This study was designed to examine the mutual relationship between 8-isoprostane in exhaled breath condensate (EBC) and superoxide anion generation by bronchoalveolar lavage fluid (BALF) cells in patients with sarcoidosis. Design About 29 patients with sarcoidosis, 34 healthy never smokers (control group for EBC) and 15 healthy never smokers (control group for BAL) were examined. EBC was collected directly before bronchoscopy. 8-Isoprostane was measured by ELISA, and superoxide anion by colorimetry. Results Exhaled breath condensate 8-isoprostane is increased in sarcoidosis (median, 25–75 percentile): 2.50; 2.50–3.90 versus 6.20; 2.50–16.95 pg/ml, p ≤ 0.05). Spontaneous superoxide anion release from BALF cells was significantly elevated only in patients with a high percentage of lymphocytes in BALF (6.42 ± 1.24 vs. 23.52 ± 4.30 nmol/106 cells, p ≤ 0.01). There were no correlations between 8-isoprostane and spontaneous or stimulated superoxide anion release. Conclusions We confirmed higher concentrations of EBC 8-isoprostane in sarcoidosis and higher spontaneous release of superoxide anion from BALF cells in patients with sarcoidosis. The increase of EBC 8-isoprostane is not directly related to superoxide anion released from BALF cells. PMID:20521080

  4. Resolution of abnormal cardiac MRI T2 signal following immune suppression for cardiac sarcoidosis.

    PubMed

    Crouser, Elliott D; Ruden, Emily; Julian, Mark W; Raman, Subha V

    2016-08-01

    Cardiac MR (CMR) with late gadolinium enhancement is commonly used to detect cardiac damage in the setting of cardiac sarcoidosis. The addition of T2 mapping to CMR was recently shown to enhance cardiac sarcoidosis detection and correlates with increased cardiac arrhythmia risk. This study was conducted to determine if CMR T2 abnormalities and related arrhythmias are reversible following immune suppression therapy. A retrospective study of subjects with cardiac sarcoidosis with abnormal T2 signal on baseline CMR and a follow-up CMR study at least 4 months later was conducted at The Ohio State University from 2011 to 2015. Immune suppression treated participants had a significant reduction in peak myocardial T2 value (70.0±5.5 vs 59.2±6.1 ms, pretreatment vs post-treatment; p=0.017), and 83% of immune suppression treated subjects had objective improvement in cardiac arrhythmias. Two subjects who had received inadequate immune suppression treatment experienced progression of cardiac sarcoidosis. This report indicates that abnormal CMR T2 signal represents an acute inflammatory manifestation of cardiac sarcoidosis that is potentially reversible with adequate immune suppression therapy. PMID:27354042

  5. Granulomatous dysimmune reactions (sarcoidosis, granuloma annulare, and others) on differently injured skin areas.

    PubMed

    Lo Schiavo, Ada; Ruocco, Eleonora; Gambardella, Alessio; O'Leary, Ryan E; Gee, Sarah

    2014-01-01

    Granulomatous disorders are chronic cell-mediated immune responses histologically characterized by collections of macrophages, epithelioid cells, and multinucleated giant cells. This disease spectrum often has an infectious origin, but sometimes neither an infective agent nor an inciting antigenic stimulus can be identified. The skin may be a preferential target for these disorders, especially in the areas that have been damaged by various forms of skin injury (eg, herpetic infections, trauma, thermal or solar burns, vaccinations, tattoos). These damaged skin sites frame the new concept of an immunocompromised cutaneous district (ICD), which defines a skin area with acquired immune dysregulation that can pave the way for the local onset of opportunistic disorders, such as infections, tumors, and granulomatous disorders. Sarcoidosis, granuloma annulare (GA), and forms of granulomatous vasculitis, such as Churg-Strauss syndrome (CSS) and Wegener's granulomatosis (WG), are the most common granulomatous disorders that occur in an ICD and may share common pathogenic mechanisms. Recent studies have found clinical and pathologic overlapping features across noninfectious granulomas. Although no unifying etiology exists, the development of granulomatous processes in the ICD has often been reported and the literature contains various hypotheses to explain it: (1) overactive immune response in a previously injured region with or without loss of immune tolerance; (2) overall reduced immune response; (3) retention of an exogeneous antigen or foreign body; (4) altered neural signaling; and (5) a combination of all the aforementioned processes. T helper cells, T regulatory cells, and macrophages, as well as a number of antigenic proteins, have been identified as potential contributing factors. In addition, a genetic predisposition and an intact systemic immune system are both instrumental for the persistence of local granuloma formation in the ICD. PMID:25160106

  6. Functional activity of sphingomyelin cycle in rat liver in chronic toxic hepatitis.

    PubMed

    Serebrov, V Yu; Kuzmenko, D I; Burov, P G; Novitsky, S V

    2008-12-01

    Activities of sphingomyelinase and ceramidase decreased in the liver in chronic toxic hepatitis and the balance between the levels of proapoptotic ceramide and antiapoptotic sphyngosine-1-phosphate shifts towards the latter substance. Pronounced changes in the qualitative and quantitative composition of fatty acids in the sphingomyelin cycle effector molecules were revealed. PMID:19513367

  7. Activated ClpP kills persisters and eradicates a chronic biofilm infection.

    PubMed

    Conlon, B P; Nakayasu, E S; Fleck, L E; LaFleur, M D; Isabella, V M; Coleman, K; Leonard, S N; Smith, R D; Adkins, J N; Lewis, K

    2013-11-21

    Chronic infections are difficult to treat with antibiotics but are caused primarily by drug-sensitive pathogens. Dormant persister cells that are tolerant to killing by antibiotics are responsible for this apparent paradox. Persisters are phenotypic variants of normal cells and pathways leading to dormancy are redundant, making it challenging to develop anti-persister compounds. Biofilms shield persisters from the immune system, suggesting that an antibiotic for treating a chronic infection should be able to eradicate the infection on its own. We reasoned that a compound capable of corrupting a target in dormant cells will kill persisters. The acyldepsipeptide antibiotic (ADEP4) has been shown to activate the ClpP protease, resulting in death of growing cells. Here we show that ADEP4-activated ClpP becomes a fairly nonspecific protease and kills persisters by degrading over 400 proteins, forcing cells to self-digest. Null mutants of clpP arise with high probability, but combining ADEP4 with rifampicin produced complete eradication of Staphylococcus aureus biofilms in vitro and in a mouse model of a chronic infection. Our findings indicate a general principle for killing dormant cells-activation and corruption of a target, rather than conventional inhibition. Eradication of a biofilm in an animal model by activating a protease suggests a realistic path towards developing therapies to treat chronic infections. PMID:24226776

  8. Chronic Enhancement of CREB Activity in the Hippocampus Interferes with the Retrieval of Spatial Information

    ERIC Educational Resources Information Center

    Viosca, Jose; Malleret, Gael; Bourtchouladze, Rusiko; Benito, Eva; Vronskava, Svetlana; Kandel, Eric R.; Barco, Angel

    2009-01-01

    The activation of cAMP-responsive element-binding protein (CREB)-dependent gene expression is thought to be critical for the formation of different types of long-term memory. To explore the consequences of chronic enhancement of CREB function on spatial memory in mammals, we examined spatial navigation in bitransgenic mice that express in a…

  9. Chronic active interstitial pancreatitis as a cause of transverse colonic obstruction and colic in a horse

    PubMed Central

    Lohmann, Katharina L.; Allen, Andrew L.

    2015-01-01

    A mature Quarter horse was euthanized following colic of 3 days duration. Postmortem, the large intestine, except the descending colon, was diffusely distended and associated with adhesion of the transverse colon to the pancreas, which had changes consistent with chronic active interstitial pancreatitis. Other lesions included hepatic fibrosis, erosive gastritis, and bilateral adrenal cortical hyperplasia. PMID:26538675

  10. Web-Based Self-Management in Chronic Care: A Study of Change in Patient Activation

    ERIC Educational Resources Information Center

    Solomon, Michael R.

    2010-01-01

    Web-based self-management interventions (W-SMIs) are designed to help a large number of chronically ill people become more actively engaged in their health care. Despite the potential to engage more patients in self-managing their health, the use of W-SMIs by patients and their clinicians is low. Using a self-management conceptual model based on…

  11. Association between Therapy Outcome and Right-Hemispheric Activation in Chronic Aphasia

    ERIC Educational Resources Information Center

    Richter, Maria; Miltner, Wolfgang H. R.; Straube, Thomas

    2008-01-01

    The role of the right hemisphere for language processing and successful therapeutic interventions in aphasic patients is a matter of debate. This study explored brain activation in right-hemispheric areas and left-hemispheric perilesional areas in response to language tasks in chronic non-fluent aphasic patients before and after constraint-induced…

  12. Changes in Muscle Activation after Reach Training with Gravity Compensation in Chronic Stroke Patients

    ERIC Educational Resources Information Center

    Prange, Gerdienke B.; Krabben, Thijs; Renzenbrink, Gerbert J.; Ijzerman, Maarten J.; Hermens, Hermie J.; Jannink, Michiel J. A.

    2012-01-01

    The objective of this study is to examine the effect of gravity compensation training on reaching and underlying changes in muscle activation. In this clinical trial, eight chronic stroke patients with limited arm function received 18 sessions (30 min) of gravity-compensated reach training (during 6 weeks) in combination with a rehabilitation…

  13. Primary Cardiac Sarcoidosis with Syncope and Refractory Atrial Arrhythmia: A Case Report and Review of the Literature.

    PubMed

    Thangam, Manoj; Nathan, Sriram; Kar, Biswajit; Petrovic, Marija; Patel, Manish; Loyalka, Pranav; Buja, L Maximilian; Gregoric, Igor D

    2016-06-01

    We discuss the case of a 38-year-old black man who presented at our hospital with his first episode of syncope, recently developed atrial arrhythmias refractory to pharmacologic therapy, and a left atrial thrombus. He was diagnosed with primary cardiac sarcoidosis characterized by predominant involvement of the epicardium that caused atrial fibrillation and atrial flutter. Histologic analysis of his epicardial lesions yielded a diagnosis of sarcoidosis. This patient's atrial arrhythmia was successfully treated with a hybrid operation that involved resection of his atrial appendage, an Epicor maze procedure, and radiofrequency ablation during a catheter-based electrophysiologic study. The cardiac sarcoidosis was successfully managed with corticosteroid therapy. Our case report shows that sarcoidosis can initially manifest itself as syncope with new-onset atrial arrhythmia. Sarcoidosis is important in the differential diagnosis because of its progressive nature and its potential for treatment with pharmacologic, surgical, and catheter-based interventions. PMID:27303240

  14. Primary Cardiac Sarcoidosis with Syncope and Refractory Atrial Arrhythmia: A Case Report and Review of the Literature

    PubMed Central

    Thangam, Manoj; Nathan, Sriram; Kar, Biswajit; Petrovic, Marija; Patel, Manish; Loyalka, Pranav; Buja, L. Maximilian

    2016-01-01

    We discuss the case of a 38-year-old black man who presented at our hospital with his first episode of syncope, recently developed atrial arrhythmias refractory to pharmacologic therapy, and a left atrial thrombus. He was diagnosed with primary cardiac sarcoidosis characterized by predominant involvement of the epicardium that caused atrial fibrillation and atrial flutter. Histologic analysis of his epicardial lesions yielded a diagnosis of sarcoidosis. This patient's atrial arrhythmia was successfully treated with a hybrid operation that involved resection of his atrial appendage, an Epicor maze procedure, and radiofrequency ablation during a catheter-based electrophysiologic study. The cardiac sarcoidosis was successfully managed with corticosteroid therapy. Our case report shows that sarcoidosis can initially manifest itself as syncope with new-onset atrial arrhythmia. Sarcoidosis is important in the differential diagnosis because of its progressive nature and its potential for treatment with pharmacologic, surgical, and catheter-based interventions. PMID:27303240

  15. Effects of Chronic Marijuana Use on Brain Activity During Monetary Decision-Making

    PubMed Central

    Vaidya, Jatin G; Block, Robert I; O'Leary, Daniel S; Ponto, Laura B; Ghoneim, Mohamed M; Bechara, Antoine

    2012-01-01

    Marijuana (MJ) acutely acts on cannabinoid receptors that are found in numerous brain regions, including those involved in reward processing and decision-making. However, it remains unclear how long-term, chronic MJ use alters reward-based decision-making. In the present study, using [15O]water PET imaging, we measured brain activity in chronic MJ users, who underwent monitored abstinence from MJ for approximately 24 h before imaging, and control participants, while they took part in the Iowa Gambling Task (IGT), a monetary decision making task that strongly relies on the ventromedial prefrontal cortex (vmPFC). During PET imaging, participants took part in the standard and a variant version of the IGT as well as a control task. Chronic MJ users performed equally well on the standard IGT, but significantly worse than controls on the variant IGT. Chronic MJ users and control subjects showed increased regional cerebral blood flow (rCBF) in the vmPFC on both versions of the IGT compared to the control task. In the two-group comparison, chronic MJ users showed significantly greater rCBF than controls in the vmPFC on the standard IGT and greater activity in the cerebellum on both versions of the IGT. Furthermore, duration of use, but not age of first use, was associated with greater activity in the vmPFC. Thus, chronic MJ users tend to strongly recruit neural circuitry involved in decision-making and reward processing (vmPFC), and probabilistic learning (cerebellum) when performing the IGT. PMID:21956445

  16. Effects of acute and chronic uremia on active cation transport in rat myocardium

    SciTech Connect

    Druml, W.; Kelly, R.A.; England, B.K.; O'Hara, D.S.; Mitch, W.E. )

    1990-12-01

    As abnormalities of active cation transport could contribute to the genesis of uremic cardiomyopathy, we investigated myocardial sodium pump function in rats with acute renal failure (ARF) and with a model of experimental chronic renal failure (CRF) that has metabolic similarities to advanced chronic uremia in humans. CRF rats were hypertensive and had left ventricular hypertrophy (33% higher heart:body weight ratio; P less than 0.01) at four weeks compared to pair-fed sham-operated rats. Importantly, both ouabain- and furosemide-sensitive 86Rb uptake rates were unchanged in left ventricular myocardial slices from CRF, and the intracellular sodium concentration was not different from that of control rats even though skeletal muscle sodium was increased, as we found previously. Insulin-stimulated, ouabain-sensitive 86Rb influx was also preserved. There also were no abnormalities in myocardium cation transport in rats with ARF. However, (3H)ouabain binding was decreased 45% in CRF rats (P less than 0.01); it was unchanged in acute uremia. Decreased ouabain binding in chronic uremia was due entirely to fewer low affinity (3H)ouabain binding sites (the binding affinity for ouabain was unaffected). We conclude that in chronic, (but not acute) renal failure, sodium pump number is reduced in myocardium but intracellular sodium is unchanged and active cation flux rates are maintained. These results emphasize that in rats with chronic uremia, intracellular sodium homeostasis is preserved in myocardium, despite the presence of marked abnormalities of active cation transport in skeletal muscle that are characteristic of chronic uremia.

  17. Electrical neurostimulation for chronic pain: On selective relay of sensory neural activities in myelinated nerve fibers.

    PubMed

    Sacré, Pierre; Sarma, Sridevi V; Guan, Yun; Anderson, William S

    2015-08-01

    Chronic pain affects about 100 million adults in the US. Despite their great need, neuropharmacology and neurostimulation therapies for chronic pain have been associated with suboptimal efficacy and limited long-term success, as their mechanisms of action are unclear. Yet current computational models of pain transmission suffer from several limitations. In particular, dorsal column models do not include the fundamental underlying sensory activity traveling in these nerve fibers. We developed a (simple) simulation test bed of electrical neurostimulation of myelinated nerve fibers with underlying sensory activity. This paper reports our findings so far. Interactions between stimulation-evoked and underlying activities are mainly due to collisions of action potentials and losses of excitability due to the refractory period following an action potential. In addition, intuitively, the reliability of sensory activity decreases as the stimulation frequency increases. This first step opens the door to a better understanding of pain transmission and its modulation by neurostimulation therapies. PMID:26737344

  18. Chronic alcohol consumption enhances iNKT cell maturation and activation

    SciTech Connect

    Zhang, Hui Zhang, Faya; Zhu, Zhaohui; Luong, Dung; Meadows, Gary G.

    2015-01-15

    Alcohol consumption exhibits diverse effects on different types of immune cells. NKT cells are a unique T cell population and play important immunoregulatory roles in different types of immune responses. The effects of chronic alcohol consumption on NKT cells remain to be elucidated. Using a mouse model of chronic alcohol consumption, we found that alcohol increases the percentage of NKT cells, especially iNKT cells in the thymus and liver, but not in the spleen or blood. Alcohol consumption decreases the percentage of NK1.1{sup −} iNKT cells in the total iNKT cell population in all of the tissues and organs examined. In the thymus, alcohol consumption increases the number of NK1.1{sup +}CD44{sup hi} mature iNKT cells but does not alter the number of NK1.1{sup −} immature iNKT cells. A BrdU incorporation assay shows that alcohol consumption increases the proliferation of thymic NK1.1{sup −} iNKT cells, especially the NK1.1{sup −}CD44{sup lo} Stage I iNKT cells. The percentage of NKG2A{sup +} iNKT cells increases in all of the tissues and organs examined; whereas CXCR3{sup +} iNKT cells only increases in the thymus of alcohol-consuming mice. Chronic alcohol consumption increases the percentage of IFN-γ-producing iNKT cells and increases the blood concentration of IFN-γ and IL-12 after in vivo α-galactosylceramide (αGalCer) stimulation. Consistent with the increased cytokine production, the in vivo activation of iNKT cells also enhances the activation of dendritic cells (DC) and NK, B, and T cells in the alcohol-consuming mice. Taken together the data indicate that chronic alcohol consumption enhances iNKT cell maturation and activation, which favors the Th1 immune response. - Highlights: • Chronic alcohol consumption increases iNKT cells in the thymus and liver • Chronic alcohol consumption enhances thymic Stage I iNKT cell proliferation • Chronic alcohol consumption enhances iNKT cell maturation in thymus and periphery • Chronic alcohol

  19. Identification of Chronic Stress Activated Regions Reveals a Potential Recruited Circuit in Rat Brain

    PubMed Central

    Flak, Jonathan N.; Solomon, Matia B.; Jankord, Ryan; Krause, Eric G.; Herman, James P.

    2015-01-01

    Chronic stress induces pre-synaptic and post-synaptic modifications in the paraventricular nucleus of the hypothalamus (PVN) that are consistent with enhanced excitatory hypothalamo-pituitary-adrenocortical (HPA) axis drive. The brain regions mediating these molecular modifications are not known. We hypothesized that chronic variable stress (CVS) tonically activates stress-excitatory regions that interact with the PVN, culminating in stress facilitation. In order to identify chronically activated brain regions, ΔFosB, a documented marker of tonic neuronal activation, was assessed in known stress regulatory limbic and brainstem sites. Four experimental groups were included: CVS, repeated restraint (RR) (control for HPA habituation), animals weight-matched (WM) to CVS animals (control for changes in circulating metabolic factors due to reduced weight gain), and non-handled controls. CVS, but not RR or WM, induced adrenal hypertrophy, indicating that sustained HPA axis drive only occurred in the CVS group. CVS (but not RR or WM) selectively increased the number of FosB/ΔFosB nuclei in the nucleus of the solitary tract, posterior hypothalamic nucleus, and both the infralimbic and prelimbic divisions of the medial prefrontal cortex, indicating an involvement of these regions in chronic drive of the HPA axis. Increases in FosB/ΔFosB-immunoreactive cells were observed following both RR and CVS in the other regions (e.g., the dorsomedial hypothalamus), suggesting activation by both habituating and non-habituating stress conditions. The data suggest that unpredictable stress uniquely activates interconnected cortical, hypothalamic, and brainstem nuclei, potentially revealing the existence of a recruited circuitry mediating chronic drive of brain stress effector systems. PMID:22789020

  20. Phenotype Specific Analyses Reveal Distinct Regulatory Mechanism for Chronically Activated p53

    PubMed Central

    Cairns, Jonathan M.; Menon, Suraj; Pérez-Mancera, Pedro A.; Tomimatsu, Kosuke; Bermejo-Rodriguez, Camino; Ito, Yoko; Chandra, Tamir; Narita, Masako; Lyons, Scott K.; Lynch, Andy G.; Kimura, Hiroshi; Ohbayashi, Tetsuya; Tavaré, Simon; Narita, Masashi

    2015-01-01

    The downstream functions of the DNA binding tumor suppressor p53 vary depending on the cellular context, and persistent p53 activation has recently been implicated in tumor suppression and senescence. However, genome-wide information about p53-target gene regulation has been derived mostly from acute genotoxic conditions. Using ChIP-seq and expression data, we have found distinct p53 binding profiles between acutely activated (through DNA damage) and chronically activated (in senescent or pro-apoptotic conditions) p53. Compared to the classical ‘acute’ p53 binding profile, ‘chronic’ p53 peaks were closely associated with CpG-islands. Furthermore, the chronic CpG-island binding of p53 conferred distinct expression patterns between senescent and pro-apoptotic conditions. Using the p53 targets seen in the chronic conditions together with external high-throughput datasets, we have built p53 networks that revealed extensive self-regulatory ‘p53 hubs’ where p53 and many p53 targets can physically interact with each other. Integrating these results with public clinical datasets identified the cancer-associated lipogenic enzyme, SCD, which we found to be directly repressed by p53 through the CpG-island promoter, providing a mechanistic link between p53 and the ‘lipogenic phenotype’, a hallmark of cancer. Our data reveal distinct phenotype associations of chronic p53 targets that underlie specific gene regulatory mechanisms. PMID:25790137

  1. Chronic active destructive herpes simplex encephalitis with recovery of viral DNA 12 years after disease onset.

    PubMed

    Asenbauer, B; McEntagart, M; King, M D; Gallagher, P; Burke, M; Farrell, M A

    1998-06-01

    Acute herpes simplex encephalitis (HSE) carries significant morbidity and mortality even after early treatment with antiviral agents (7). As well as causing acute neurological disease, Herpes viruses are associated with relapsing--remitting (Varicella--Zoster, Epstein-Barr) and chronic (Rasmussen encephalitis) disease processes (1). A two-year-old girl developed acute HSE which was followed by a 10-year neurologic illness characterised by asymmetric spastic tetraparesis, pseudobulbar palsy, the opercular syndrome of Foix-Chavany-Marie (4) and seizures. The neurological signs remained static until the child died suddenly 12 years after disease onset. Neuropathologic examination demonstrated active chronic encephalitis. Herpes simplex virus (HSV) DNA was recovered from formalin-fixed paraffin-embedded brain tissue. This case provides additional evidence for the development of chronic neurological disease attributable to persistence of herpes simplex virus type 1. PMID:9706620

  2. Immune function in sarcoidosis. Studies on delayed hypersensitivity, B and T lymphocytes, serum immunoglobulins and serum complement components.

    PubMed Central

    Tannenbaum, H; Rocklin, R E; Schur, P H; Sheffer, A L

    1976-01-01

    An assessment of immune function was performed in twenty-four patients with recently diagnosed active sarcoidosis. Four patients manifested skin anergy to four antigens. All subjects except one were capable of generating a positive skin response to a croton oil patch test. The incorporation of [3H]thymidine by lymphocytes in vitro in response to the nonspecific mitogens--phytohaemagglutinin, pokeweed mitogen and Con A did not differ between anergic and non-anergic thymidine incorporation in vitro when stimulated by the specific antigens, streptokinase/streptodornase or Candida albicans. Lymphocytes obtained from nine of eleven patients having positive delayed hypersensitivity skin reactions demonstrated MIF production in vitro upon specific antigen challenge. Quantities of circulating B and T lymphocytes did not differ between anergic and absolute numbers of circulating B and T lymphocytes, as well as hypercomplementaemia and hypergammaglobulinaemia when compared to the control group. PMID:795577

  3. Left Ventricular Aneurysm and Ventricular Tachycardia as Initial Presentation of Cardiac Sarcoidosis

    PubMed Central

    Jmeian, Ashraf; Thawabi, Mohammad; Goldfarb, Irvin; Shamoon, Fayez

    2015-01-01

    Context: Cardiac sarcoidosis (CS) is a rare, potentially fatal disease. It has a wide range of clinical presentations that range from asymptomatic electrocardiogram changes to sudden cardiac death. Ventricular aneurysms and ventricular tachycardia are seen late in the disease, and are rarely the presenting manifestation of the disease. Diagnosis of CS is challenging and often missed or delayed. Case Report: We report a 35-year-old patient who presented with sustained ventricular tachycardia and ST-elevation on electrocardiogram. Cardiac catheterization showed normal coronaries and left ventricular aneurysm. Subsequent 2D-echocardiography showed an infiltrative disease pattern. Cardiac MRI was done and showed late gadolinium enhancement in the septum, apex and lateral wall. The patient was diagnosed with cardiac sarcoidosis and treated with immune suppression and antiarrhythmic agent. In addition underwent AICD implantation. Conclusion: Our case highlights the importance of suspecting cardiac sarcoidosis in young patients presenting with electrocardiogram changes, and present an atypical presentation of this disease. PMID:25839003

  4. A case of sarcoidosis diagnosed by positron emission tomography/computed tomography.

    PubMed

    Aksoy, Sabire Yilmaz; Özdemir, Elif; Sentürk, Aysegül; Türkölmez, Seyda

    2016-01-01

    Sarcoidosis is a multisystem granulomatous disorder of unknown cause which may affect any organ or system but primarily involve the lungs and the lymphatic system. Extrapulmonary sarcoidosis represents approximately 30-50% of patients. We report the case of a 51-year-old female who presented with increasing complaints of a cough, weakness, weight loss, and chest pain and who was found to have a suspicious lesion on thorax computed tomography(CT). Fluorodeoxyglucose (FDG) positron emission tomography/CT performed for diagnostic purposes demonstrated increased FDG accumulation at the bilateral enlarged parotid and lacrimal gland and in the reticulonodular infiltration area located in the left lung as well as multiple lymphadenopathies with increased FDG accumulation. There were also hepatosplenomegaly and splenic uptake. Skin biopsy showed noncaseating granulomas, and the patient was diagnosed as stage 2 sarcoidosis. PMID:27385890

  5. Calcium and Vitamin D in Sarcoidosis: How to Assess and Manage

    PubMed Central

    Burke, Robert R.; Rybicki, Benjamin A.; Rao, D. Sudhaker

    2016-01-01

    The synthesis of vitamin D is altered by the granulomatous inflammation of sarcoidosis leading to increased production of 1, 25-dihydroxyvitamin D. Mounting evidence suggests that vitamin D is an immunomodulating hormone that inhibits both antigen presentation by cells of the innate immune system, and the cytokine release and proliferation of Th1 cells. These and other extraskeletal health benefits have led to an increase in vitamin D assessment and pharmacological supplementation in the general population. This review highlights the altered synthesis and general immunomodulating properties of vitamin D with a special emphasis on known interactions with sarcoidosis. In addition, the assessment of vitamin D nutritional status, its pharmacological supplementation, and the management of bone health in patients with sarcoidosis are reviewed. PMID:20665397

  6. A case of sarcoidosis diagnosed by positron emission tomography/computed tomography

    PubMed Central

    Aksoy, Sabire Yilmaz; Özdemir, Elif; Sentürk, Aysegül; Türkölmez, Seyda

    2016-01-01

    Sarcoidosis is a multisystem granulomatous disorder of unknown cause which may affect any organ or system but primarily involve the lungs and the lymphatic system. Extrapulmonary sarcoidosis represents approximately 30-50% of patients. We report the case of a 51-year-old female who presented with increasing complaints of a cough, weakness, weight loss, and chest pain and who was found to have a suspicious lesion on thorax computed tomography(CT). Fluorodeoxyglucose (FDG) positron emission tomography/CT performed for diagnostic purposes demonstrated increased FDG accumulation at the bilateral enlarged parotid and lacrimal gland and in the reticulonodular infiltration area located in the left lung as well as multiple lymphadenopathies with increased FDG accumulation. There were also hepatosplenomegaly and splenic uptake. Skin biopsy showed noncaseating granulomas, and the patient was diagnosed as stage 2 sarcoidosis. PMID:27385890

  7. [A case of pulmonary sarcoidosis complicated with bronchial asthma that proved eosinophilic invasion].

    PubMed

    Harada, Tomoya; Kawasaki, Yuji; Touge, Hirokazu; Tokuyasu, Hirokazu; Yamasaki, Akira; Shimizu, Eiji

    2012-12-01

    A 33-year-old man complaining of cough admitted our hospital for examination of bilateral hilar and mediastinal lymphadenopathy. He diagnosed pulmonary sarcoidosis, because of elevation of serum angiotensin converting enzyme (ACE), epitheloid granuloma with noncaseating necrosis from transbronchial lung biopsy (TBLB) specimen, increasing of lymphocyte and elevation of the CD4/CD8 ratio in bronchoalveolar lavage fluid (BALF). Furthermore, eosinophil ratio in BALF was 3%, hyperplasia of goblet cell, eosinophilic invasion to bronchial epithelium, and thickened basal membrane were found in same biopsy specimen. He had mild reversible airway obstruction. He was diagnosed pulmonary sarcoidosis complicated with bronchial asthma. Sarcoidosis is characteristic of the T helper type 1 (Th1) mediated immune response, and bronchial asthma is characteristic of the Th2. This case histopathologically revealed that both Th1 mediated immune response and Th2 could be coexisted. PMID:23466616

  8. Intrahepatic Toll-Like Receptor 3 in Chronic HBV Infection Subjects: Asymptomatic Carriers, Active Chronic Hepatitis, Cirrhosis, and Hepatocellular Carcinoma

    PubMed Central

    Yin, Jia Wen; Ping Huang, Mao; Zhong, Bei

    2016-01-01

    Background The entire disease spectrum of chronic HBV infection (CHB) includes asymptomatic carriers (AC), active chronic hepatitis (ACH), cirrhosis (Cir), and hepatocellular carcinoma (HCC). Previous study have demonstrated that the costimulation profiles from the livers of patients influenced immune responses and played various immunological roles in AC, ACH, Cir, and HCC. In addition, activation of TLR3 signaling in the liver may contribute to HBV clearance, although some HBV components are able to block TLR3 signaling and counteract HBV clearance through positive or negative feedback loops. Previous clinical studies have demonstrated that different TLR3 expressions are present in ACH patients, but no studies investigated the expression of TLR3 proteins in the livers of patients with AC, Cir, or HCC. Objectives This study investigated intrahepatic TLR3 expression throughout the entire disease spectrum of CHB patients and assessed the interrelations between TLR3 and costimulation proteins. Patients and Methods Patients with ACH, Cir, HCC, and AC and healthy donors (HD) were recruited. TLR3 expression in the livers of patients were investigated using western blot analysis and immunohistochemistry. Correlations between TLR3 and costimulation proteins, including CD80, CD86, CD83, CD28, CTLA-4, CD40, and ICAM-1, were assessed. Results The TLR3 protein in the ACH group tended toward reduction although the P Value of the comparison between the ACH group and HD group was not statistically significant. The TLR3 levels in the HCC, AC, and Cir groups were higher than those in the HD and ACH groups. TLR3 was not interrelated with all costimulation proteins in the DCs and T cells in all five groups. No group presented any interrelation between TLR3 and CD40, except the AC group. Conclusions The AC, HCC, and Cir patients displayed increased levels of the intrahepatic TLR3 protein compared to the HD and AC patients. Both activation of TLR3/INF-β signaling and inhibition of

  9. Time spent on health related activities associated with chronic illness: a scoping literature review

    PubMed Central

    2012-01-01

    Background The management of health care, particularly for people with chronic conditions, combines the activities of health professionals, patients, informal carers and social networks that support them. Understanding the non-professional roles in health management requires information about the health related activities (HRA) that are undertaken by patients and informal carers. This understanding allows management planning that incorporates the capacity of patients and informal carers, as well as identifying the particular skills, knowledge and technical support that are necessary. This review was undertaken to identify how much time people with chronic illness and their informal carers spend on HRA. Methods Literature searches of three electronic databases (CINAHL, Medline, and PubMed) and two journals (Time and Society, Sociology of Health and Illness) were carried out in 2011 using the following search terms (and derivatives): chronic illness AND time AND consumer OR carer. The search was aimed at finding studies of time spent on HRA. A scoping literature review method was utilised. Results Twenty-two peer reviewed articles published between 1990 and 2010 were included for review. The review identified limited but specific studies about time use by people with a chronic illness and/or their carers. While illness work was seen as demanding, few studies combined inquiry about both defined tasks and defined time use. It also identified methodological issues such as consistency of definition and data collection methods, which remain unresolved. Conclusions While HRA are seen as demanding by people doing them, few studies have measured actual time taken to carry out a comprehensive range of HRA. The results of this review suggest that both patients with chronic illness and informal carers may be spending 2 hours a day or more on HRA. Illnesses such as diabetes may be associated with higher time use. More empirical research is needed to understand the time demands

  10. Hepatocellular expression of a novel glycoprotein with sialylated difucosyl Lex activity in the active inflammatory lesions of chronic liver disease.

    PubMed Central

    Okada, Y.; Shimoe, T.; Muguruma, M.; Usumoto, R.; Tsuji, T.; Jinno, K.; Moriwaki, S.; Shin, S.; Hakomori, S.

    1988-01-01

    Hepatic expression of sialylated difucosyl Lex antigen (SDLex, NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-) was studied with monoclonal antibody FH6, which defines this structure. Hepatocytes in the severe form of chronic active hepatitis and liver cirrhosis strongly expressed SDLex. The antigen was only weakly and focally detected in chronic persistent hepatitis. The mild form of chronic active hepatitis showed intermediate expression. SDLex expressed along the liver cell membranes displayed a honeycomb pattern when extensively expressed in the severe form of chronic active hepatitis or in liver cirrhosis. Cytoplasmic expression was faint and focal. Preferential tissue distribution was at the periphery of the hepatic lobules where the distruction of the limiting plate was present. The antigen was also expressed in sinusoidal lining cells and polymorphonuclear cells but not in the biliary epithelia. Hepatocytes expressing SDLex did not express related carbohydrate antigens, ie, Type 2 chain N-acetyllactosamine, Lex, and sialylated Lea. On subcellular fractionation, the microsome fraction contained the majority of the antigen activity. SDS-PAGE and Western blot analysis revealed one major SDLex-active glycoprotein with an apparent molecular weight of 110 kilodaltons. This glycoprotein was different from SDLex-active glycoproteins found in the sera of cancer patients. No ganglioside showed FH6 reactivity. These results indicate that liver cells in active inflammatory lesion expressed a novel glycoprotein carrying SDLex antigen in honeycomblike membrane-associated pattern. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:3341453

  11. Yield of EBUS-TBNA for the diagnosis of sarcoidosis: impact of operator and cytopathologist experience

    PubMed Central

    Navasakulpong, Asma; Auger, Manon; Gonzalez, Anne V

    2016-01-01

    Background Studies have reported a high diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the diagnosis of sarcoidosis. We sought to review the yield of EBUS-TBNA for the diagnosis of sarcoidosis at our institution over time, and examine factors that may influence this yield. Methods Patients who underwent EBUS-TBNA for suspected sarcoidosis between December 2008 and November 2011 were identified. EBUS was performed without rapid on-site evaluation (ROSE) of samples. The final diagnosis was based on the results of all invasive diagnostic procedures and/or clinical follow-up. Logistic regression analysis was used to examine the effect of various factors on yield. Results 43 patients underwent 45 EBUS-TBNA procedures for suspected sarcoidosis. A total of 115 lymph nodes were sampled. The 21 G needle was used in 51% of procedures. The mean number of lymph node stations sampled was 2.6 (SD 0.7) and the mean number of needle passes per procedure was 7.8 (SD 2.0). Non-necrotising granulomatous inflammation was detected in EBUS-TBNA samples from 34/45 (76%) procedures. The overall diagnostic yield increased to 36/45 (80%) following a cytopathology review for this study. Needle gauge, number of lymph node stations sampled and number of needle passes were not associated with diagnostic yield. The yield of EBUS-TBNA increased significantly after the first 15 procedures performed for suspected sarcoidosis; the 2 additional cases diagnosed after the cytopathology review were part of this early experience. Conclusions EBUS-TBNA is a valuable technique for the diagnosis of sarcoidosis when performed without ROSE. The yield of the procedure improved significantly over time, based on operator and cytopathologist experience. PMID:27547408

  12. Clinical approach to chronic beryllium disease and other nonpneumoconiotic interstitial lung diseases.

    PubMed

    Maier, Lisa A

    2002-10-01

    Exposures in the workplace result in a diverse set of diseases ranging from the pneumoconiosis to other interstitial lung diseases to acute lung injury. Physician awareness of the potential disease manifestations associated with specific exposures is important in defining these diseases and in preventing additional disease. Most occupational diseases mimic other forms of lung disease, including pulmonary fibrosis, sarcoidosis, adult respiratory distress syndrome (ARDS), and bronchiolitis. A "sarcoidosis"-like syndrome, usually limited to the lungs, may result from exposure to bioaerosols and a number of metals. Exposure to beryllium in the workplace produces a granulomatous lung disease clinically indistinguishable from sarcoidosis, chronic beryllium disease (CBD). Beryllium's ability to produce a beryllium-specific immune response is used in the beryllium lymphocyte proliferation tests to confirm a diagnosis of CBD and exclude sarcoidosis. Exposure to other metals must also be considered in the differential diagnosis of sarcoidosis. When an individual presents acutely with ARDS or acute lung injury, an acute inhalational exposure must be considered. Exposure to a number of irritant substances at high levels may cause a "chemical pneumonitis" or acute lung injury, depending on the solubility and physicochemical properties of the substance. Some of the most notable agents include nitrogen and sulfur oxides, phosgene, and smoke breakdown products. Ingestion of paraquat may also result in an ARDS syndrome, with pulmonary fibrosis eventually resulting. Bronchiolitis is a rare manifestation of inhalational exposures but must also be considered in the clinical evaluation of inhalational exposure. PMID:12362066

  13. Sarcoid-like lymphocytosis of the lower respiratory tract in patients with active Crohn's disease.

    PubMed

    Smiéjan, J M; Cosnes, J; Chollet-Martin, S; Soler, P; Basset, F M; Le Quintrec, Y; Hance, A J

    1986-01-01

    To re-evaluate the relationship between Crohn's disease and sarcoidosis, we compared the numbers and types of cells recovered by bronchoalveolar lavage from normal volunteers and patients with Crohn's disease, with other forms of inflammatory bowel disease, and with sarcoidosis. Patients with Crohn's disease, but not patients with other inflammatory bowel disorders, had an increase in the number of T lymphocytes on the surface of the lower respiratory tract similar to that seen in patients with sarcoidosis. As in sarcoidosis, this lymphocytosis results from an expansion of the T4+ T-lymphocyte subset, is characteristic of patients with active disease only, and is not associated with similar abnormalities in the peripheral blood. Thus, patients with apparently localized Crohn's disease have sarcoid-like lymphocytosis of the lower respiratory tract, a finding that emphasizes the systemic nature of Crohn's disease and the disorder's close relationship to sarcoidosis. PMID:3940500

  14. Activation of autophagy induces retinal ganglion cell death in a chronic hypertensive glaucoma model

    PubMed Central

    Park, H-Y Lopilly; Kim, J H; Park, C K

    2012-01-01

    Autophagy is reported to have important roles in relation to regulated cell death pathways and neurodegeneration. This study used chronic hypertensive glaucoma rat model to investigate whether the autophagy pathway has a role in the apoptosis of retinal ganglion cells (RGCs) after chronic intraocular pressure (IOP) elevation. Under electron microscopy, autophagosomes were markedly accumulated in the dendrites and cytoplasm of RGCs after IOP elevation. Western blot analysis showed that LC3-II/LC3-I and beclin-1 were upregulated throughout the 8-weeks period after IOP elevation. The pattern of LC3 immunostaining showed autophagy activation in the cytoplasm of RGCs to increase and peak at 4 weeks after IOP elevation. Most of these LC3B-positive RGCs underwent apoptosis by terminal deoxynucleotidyltransferase-mediated biotinylated UTP nick end labeling, and inhibition of autophagy with 3-methyladenine decreased RGC apoptosis. The activated pattern shows that autophagy is initially activated in the dendrites of the RGCs, but, thereafter autophagy is mainly activated in the cytoplasm of RGCs. This may show that autophagy is differently regulated in different compartments of the neuron. This present study showed that autophgy is activated in RGCs and has a role in autophagic cell death after chronic IOP elevation. PMID:22476098

  15. [Multicenter retrospective analysis of the patients with sarcoidosis with a 10 year interval in observations].

    PubMed

    Vizel', I Iu; Shmelev, E I; Baranova, O P; Barlamov, P N; Borodina, G L; Denisova, O A; Dobin, V L; Kulbaisov, A M; Kupaev, V I; Listopadova, M V; Ovsiannikov, N V; Os'kin, D N; Petrov, D V; Solov'ev, K I; Shul'zhenko, L V; Vizel', A A

    2014-01-01

    Comparison of the state of 83 patients with histologically confirmed sarcoidosis observed with a 10 year interval revealed remission in 47% of the cases. The main factors having negative effect on prognosis of the disease included extrapulmonary symptoms, the use ofcorticosteroids (at all stages, especially at stage I and in Lofgren syndrome) and antituberculosis drugs, positive TB test. Risk factors of relapses were stage II sarcoidosis, the use of systemic corticosteroids in patients with Lofgren syndrome and antituberculosis drugs, initially low FEV1/FVLC ratio and the number of lymphocytes in peripheral blood. PMID:25799827

  16. Mediastinal sarcoidosis mimicking lymph malignancy recurrence after anti-neoplastic therapy.

    PubMed

    El Hammoumi, Massine; El Marjany, Mohamed; Moussaoui, Driss; Doudouh, Aberahim; Mansouri, Hamid; Kabiri, El Hassane

    2015-07-01

    The aim of our work is to promote the awareness about the development of sarcoidosis after antineoplastic therapy in order to avoid diagnostic errors with FDG-PET/CT findings. We report the observation of three women with breast, cervix and stomach treated cancers who developed a sarcoidosis after the end of anti-neoplastic therapy. The utility of FDG-PET/CT is in pinpointing the organs candidates for diagnostic biopsy and not distinguishing between the malignancy and granulomatous or inflammatory diseases. PMID:25294405

  17. Bronchoalveolar lavage, serum angiotensin-converting enzyme, and /sup 67/Ga scanning in extrathoracic sarcoidosis

    SciTech Connect

    Wallaert, B.; Ramon, P.; Fournier, E.; Tonnel, A.B.; Voisin, C.

    1982-11-01

    Results of bronchoalveolar lavage (BAL), 67Ga scanning, and serum angiotensin-converting enzyme (SACE) assay are compared in the assessment of pulmonary involvement in ten cases of extrathoracic sarcoidosis. Standard clinical, radiologic, and pulmonary function tests detected no pulmonary changes in these patients, but BAL demonstrated an increased alveolar lymphocytosis in eight of ten cases. SACE levels were increased in two cases, and the thoracic gallium uptake was normal in all cases. BAL appears to be the best technique for diagnosing latent pulmonary involvement in extrathoracic sarcoidosis.

  18. Thallium-201 scintigraphy in the diagnosis and management of myocardial sarcoidosis

    SciTech Connect

    Fields, C.L.; Ossorio, M.A.; Roy, T.M.; Denny, D.M.; Varga, D.W. )

    1990-03-01

    We have described three patients with clinical evidence of myocardial sarcoidosis to illustrate the utility of thallium-201 scintigraphy in demonstrating the myocardial lesions. Both the symptomatic and asymptomatic individuals studied showed the characteristic reverse redistribution phenomenon. No abnormalities were seen during the exercise phase of the thallium study, but myocardial defects were detected in each patient when repeat studies were obtained at rest six hours later. Steroid therapy resolved the defects in each case. We propose thallium-201 scintigraphy of the heart as a safe and useful tool for documenting myocardial involvement in sarcoidosis and following the effects of therapy.

  19. Tl-201 uptake in bone and soft tissue involvement of sarcoidosis.

    PubMed

    Degirmenci, B; Mavi, A; Ozkal, S; Itil, O; Havitcioglu, H; Ozaksoy, D; Yilmaz, M; Kaya, G C

    2001-06-01

    The authors describe a 38-year-old man who was referred to the nuclear medicine department because of pain and swelling of his fingers in both hands. Tc-99m MDP and Tl-201 scans were performed to evaluate the lesions. A Tc-99m MDP bone scan showed hyperemia and increased uptake in the lesions. A Tl-201 scan showed marked uptake in both early and delayed images in the lesions of his fingers. Bone biopsy and histologic examination confirmed sarcoidosis. This case indicates that Tl-201 uptake can be seen in bone lesions resulting from sarcoidosis. PMID:11353294

  20. Cystic Fibrosis Transmembrane Conductance Regulator Activation by Roflumilast Contributes to Therapeutic Benefit in Chronic Bronchitis

    PubMed Central

    Lambert, James A.; Raju, S. Vamsee; Tang, Li Ping; McNicholas, Carmel M.; Li, Yao; Courville, Clifford A.; Farris, Roopan F.; Coricor, George E.; Smoot, Lisa H.; Mazur, Marina M.; Dransfield, Mark T.; Bolger, Graeme B.

    2014-01-01

    Cigarette smoking causes acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction and is associated with delayed mucociliary clearance and chronic bronchitis. Roflumilast is a clinically approved phosphodiesterase 4 inhibitor that improves lung function in patients with chronic bronchitis. We hypothesized that its therapeutic benefit was related in part to activation of CFTR. Primary human bronchial epithelial (HBE) cells, Calu-3, and T84 monolayers were exposed to whole cigarette smoke (WCS) or air with or without roflumilast treatment. CFTR-dependent ion transport was measured in modified Ussing chambers. Airway surface liquid (ASL) was determined by confocal microscopy. Intestinal fluid secretion of ligated murine intestine was monitored ex vivo. Roflumilast activated CFTR-dependent anion transport in normal HBE cells with a half maximal effective concentration of 2.9 nM. Roflumilast partially restored CFTR activity in WCS-exposed HBE cells (5.3 ± 1.1 μA/cm2 vs. 1.2 ± 0.2 μA/cm2 [control]; P < 0.05) and was additive with ivacaftor, a specific CFTR potentiator approved for the treatment of CF. Roflumilast improved the depleted ASL depth of HBE monolayers exposed to WCS (9.0 ± 3.1 μm vs. 5.6 ± 2.0 μm [control]; P < 0.05), achieving 79% of that observed in air controls. CFTR activation by roflumilast also induced CFTR-dependent fluid secretion in murine intestine, increasing the wet:dry ratio and the diameter of ligated murine segments. Roflumilast activates CFTR-mediated anion transport in airway and intestinal epithelia via a cyclic adenosine monophosphate–dependent pathway and partially reverses the deleterious effects of WCS, resulting in augmented ASL depth. Roflumilast may benefit patients with chronic obstructive pulmonary disease with chronic bronchitis by activating CFTR, which may also underlie noninfectious diarrhea caused by roflumilast. PMID:24106801

  1. Oxytocin neuron activation prevents hypertension that occurs with chronic intermittent hypoxia/hypercapnia in rats.

    PubMed

    Jameson, Heather; Bateman, Ryan; Byrne, Peter; Dyavanapalli, Jhansi; Wang, Xin; Jain, Vivek; Mendelowitz, David

    2016-06-01

    Hypertension is a common outcome associated with obstructive sleep apnea (OSA), a prevalent yet poorly treated cardiovascular disease. Recent studies showed oxytocin (OXT), released from hypothalamic paraventricular nucleus (PVN) neurons, activates cardiac vagal neurons in the dorsal motor nucleus of the vagus (DMNX) and may blunt cardiovascular responses to stress. This study tests whether the release of OXT from PVN fibers in the DMNX is diminished with chronic intermittent hypoxia-hypercapnia (CIH/H) exposure, an animal model of OSA, and whether activation of PVN OXT neurons restores OXT release in the DMNX and prevents the hypertension resulting from CIH/H. To assess OXT release from PVN fibers, Chinese hamster ovarian (CHO) cells were engineered to be highly sensitive to OXT by stable expression of the human recombinant OXT receptor and the calcium indicator R-GECO1. PVN fibers in the DMNX were selectively photoactivated in vitro by expression of channelrhodopsin. The release of OXT onto CHO cells in the DMNX was blunted in rats exposed to 21 days of CIH/H. Chronic activation of PVN OXT neurons in vivo, using designer receptors exclusively activated by designer drugs, restored the release of OXT onto CHO cells in the DMNX. Chronic PVN OXT neuron activation in vivo also prevented the hypertension that occurred in conscious unrestrained telemetry-equipped sham rats exposed to 3 wk of CIH/H. These results demonstrate that chronic activation of OXT neurons restores the release of OXT from PVN fibers in the DMNX and prevents the hypertension that occurs with 3 wk of CIH/H exposure. PMID:27016581

  2. Local NMDA Receptor Blockade Attenuates Chronic Tinnitus and Associated Brain Activity in an Animal Model

    PubMed Central

    Brozoski, Thomas J.; Wisner, Kurt W.; Odintsov, Boris; Bauer, Carol A.

    2013-01-01

    Chronic tinnitus has no broadly effective treatment. Identification of specific markers for tinnitus should facilitate the development of effective therapeutics. Recently it was shown that glutamatergic blockade in the cerebellar paraflocculus, using an antagonist cocktail was successful in reducing chronic tinnitus. The present experiment examined the effect of selective N-methyl d-aspartate (NMDA) receptor blockade on tinnitus and associated spontaneous brain activity in a rat model. The NMDA antagonist, D(−)-2-amino-5-phosphonopentanoic acid (D-AP5) (0.5 mM), was continuously infused for 2 weeks directly to the ipsilateral paraflocculus of rats with tinnitus induced months prior by unilateral noise exposure. Treated rats were compared to untreated normal controls without tinnitus, and to untreated positive controls with tinnitus. D-AP5 significantly decreased tinnitus within three days of beginning treatment, and continued to significantly reduce tinnitus throughout the course of treatment and for 23 days thereafter, at which time testing was halted. At the conclusion of psychophysical testing, neural activity was assessed using manganese enhanced magnetic resonance imaging (MEMRI). In agreement with previous research, untreated animals with chronic tinnitus showed significantly elevated bilateral activity in their paraflocculus and brainstem cochlear nuclei, but not in mid or forebrain structures. In contrast, D-AP5-treated-tinnitus animals showed significantly less bilateral parafloccular and dorsal cochlear nucleus activity, as well as significantly less contralateral ventral cochlear nucleus activity. It was concluded that NMDA-mediated glutamatergic transmission in the paraflocculus appears to be a necessary component of chronic noise-induced tinnitus in a rat model. Additionally, it was confirmed that in this model, elevated spontaneous activity in the cerebellar paraflocculus and auditory brainstem is associated with tinnitus. PMID:24282480

  3. Cortical activation following chronic passive implantation of a wide-field suprachoroidal retinal prosthesis

    NASA Astrophysics Data System (ADS)

    Villalobos, Joel; Fallon, James B.; Nayagam, David A. X.; Shivdasani, Mohit N.; Luu, Chi D.; Allen, Penelope J.; Shepherd, Robert K.; Williams, Chris E.

    2014-08-01

    Objective. The research goal is to develop a wide-field retinal stimulating array for prosthetic vision. This study aimed at evaluating the efficacy of a suprachoroidal electrode array in evoking visual cortex activity after long term implantation. Approach. A planar silicone based electrode array (8 mm × 19 mm) was implanted into the suprachoroidal space in cats (ntotal = 10). It consisted of 20 platinum stimulating electrodes (600 μm diameter) and a trans-scleral cable terminated in a subcutaneous connector. Three months after implantation (nchronic = 6), or immediately after implantation (nacute = 4), an electrophysiological study was performed. Electrode total impedance was measured from voltage transients using 500 μs, 1 mA pulses. Electrically evoked potentials (EEPs) and multi-unit activity were recorded from the visual cortex in response to monopolar retinal stimulation. Dynamic range and cortical activation spread were calculated from the multi-unit recordings. Main results. The mean electrode total impedance in vivo following 3 months was 12.5 ± 0.3 kΩ. EEPs were recorded for 98% of the electrodes. The median evoked potential threshold was 150 nC (charge density 53 μC cm-2). The lowest stimulation thresholds were found proximal to the area centralis. Mean thresholds from multiunit activity were lower for chronic (181 ± 14 nC) compared to acute (322 ± 20 nC) electrodes (P < 0.001), but there was no difference in dynamic range or cortical activation spread. Significance. Suprachoroidal stimulation threshold was lower in chronic than acute implantation and was within safe charge limits for platinum. Electrode-tissue impedance following chronic implantation was higher, indicating the need for sufficient compliance voltage (e.g. 12.8 V for mean impedance, threshold and dynamic range). The wide-field suprachoroidal array reliably activated the retina after chronic implantation.

  4. Combined administration of secretin and oxytocin inhibits chronic colitis and associated activation of forebrain neurons

    PubMed Central

    Welch, Martha G.; Anwar, Muhammad; Chang, Christine Y.; Gross, Kara J.; Ruggiero, David A.; Gershon, Michael D.

    2011-01-01

    Background The pathogenesis of inflammatory bowel disease is unknown; however, the disorder is aggravated by psychological stress and is itself psychologically stressful. Chronic intestinal inflammation, moreover, has been reported to activate forebrain neurons. We tested the hypotheses that the chronically inflamed bowel signals to the brain through the vagi and that administration of a combination of secretin (S) and oxytocin (OT) inhibits this signaling. Methods Three daily enemas containing 2,4,6-trinitrobenzene sulfonic acid (TNBS), which were given to rats produced chronic colitis and ongoing activation of Fos in brain neurons. Key Results Fos was induced in neurons in the paraventricular nucleus of the hypothalamus, basolateral amygdala, central amygdala, and piriform cortex. Subdiaphragmatic vagotomy failed to inhibit this activation of Fos, suggesting that colitis activates forebrain neurons independently of the vagi. When administered intravenously, but not when given intracerebroventricularly, in doses that were individually ineffective, combined S/OT prevented colitis-associated activation of central neurons. Strikingly, S/OT decreased inflammatory infiltrates into the colon and colonic expression of tumor necrosis factor-α and interferon-γ. Conclusions & Inferences These observations suggest that chronic colonic inflammation is ameliorated by the systemic administration of S/OT, which probably explains the parallel ability of systemic S/OT to inhibit the colitis-associated activation of forebrain neurons. It is possible that S and OT, which are endogenous to the colon, might normally combine to restrict the severity of colonic inflammatory responses and that advantage might be taken of this system to develop novel means of treating inflammation-associated intestinal disorders. PMID:20210978

  5. Local NMDA receptor blockade attenuates chronic tinnitus and associated brain activity in an animal model.

    PubMed

    Brozoski, Thomas J; Wisner, Kurt W; Odintsov, Boris; Bauer, Carol A

    2013-01-01

    Chronic tinnitus has no broadly effective treatment. Identification of specific markers for tinnitus should facilitate the development of effective therapeutics. Recently it was shown that glutamatergic blockade in the cerebellar paraflocculus, using an antagonist cocktail was successful in reducing chronic tinnitus. The present experiment examined the effect of selective N-methyl d-aspartate (NMDA) receptor blockade on tinnitus and associated spontaneous brain activity in a rat model. The NMDA antagonist, D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) (0.5 mM), was continuously infused for 2 weeks directly to the ipsilateral paraflocculus of rats with tinnitus induced months prior by unilateral noise exposure. Treated rats were compared to untreated normal controls without tinnitus, and to untreated positive controls with tinnitus. D-AP5 significantly decreased tinnitus within three days of beginning treatment, and continued to significantly reduce tinnitus throughout the course of treatment and for 23 days thereafter, at which time testing was halted. At the conclusion of psychophysical testing, neural activity was assessed using manganese enhanced magnetic resonance imaging (MEMRI). In agreement with previous research, untreated animals with chronic tinnitus showed significantly elevated bilateral activity in their paraflocculus and brainstem cochlear nuclei, but not in mid or forebrain structures. In contrast, D-AP5-treated-tinnitus animals showed significantly less bilateral parafloccular and dorsal cochlear nucleus activity, as well as significantly less contralateral ventral cochlear nucleus activity. It was concluded that NMDA-mediated glutamatergic transmission in the paraflocculus appears to be a necessary component of chronic noise-induced tinnitus in a rat model. Additionally, it was confirmed that in this model, elevated spontaneous activity in the cerebellar paraflocculus and auditory brainstem is associated with tinnitus. PMID:24282480

  6. Aberrant spontaneous brain activity in chronic tinnitus patients revealed by resting-state functional MRI

    PubMed Central

    Chen, Yu-Chen; Zhang, Jian; Li, Xiao-Wei; Xia, Wenqing; Feng, Xu; Gao, Bo; Ju, Sheng-Hong; Wang, Jian; Salvi, Richard; Teng, Gao-Jun

    2014-01-01

    Objective The neural mechanisms that give rise to the phantom sound of tinnitus are poorly understood. This study aims to investigate whether aberrant spontaneous brain activity exists in chronic tinnitus patients using resting-state functional magnetic resonance imaging (fMRI) technique. Materials and methods A total of 31 patients with chronic tinnitus patients and 32 healthy age-, sex-, and education-matched healthy controls were prospectively examined. Both groups had normal hearing thresholds. We calculated the amplitude of low-frequency fluctuations (ALFFs) of fMRI signals to measure spontaneous neuronal activity and detect the relationship between fMRI information and clinical data of tinnitus. Results Compared with healthy controls, we observed significant increased ALFF within several selected regions including the right middle temporal gyrus (MTG), right superior frontal gyrus (SFG), and right angular gyrus; decreased ALFF was detected in the left cuneus, right middle occipital gyrus and bilateral thalamus. Moreover, tinnitus distress correlated positively with increased ALFF in right MTG and right SFG; tinnitus duration correlated positively with higher ALFF values in right SFG. Conclusions The present study confirms that chronic tinnitus patients have aberrant ALFF in many brain regions, which is associated with specific clinical tinnitus characteristics. ALFF disturbance in specific brain regions might be used to identify the neuro-pathophysiological mechanisms in chronic tinnitus patients. PMID:25379434

  7. Interleukin-1β biosynthesis inhibition reduces acute seizures and drug resistant chronic epileptic activity in mice.

    PubMed

    Maroso, Mattia; Balosso, Silvia; Ravizza, Teresa; Iori, Valentina; Wright, Christopher Ian; French, Jacqueline; Vezzani, Annamaria

    2011-04-01

    Experimental evidence and clinical observations indicate that brain inflammation is an important factor in epilepsy. In particular, induction of interleukin-converting enzyme (ICE)/caspase-1 and activation of interleukin (IL)-1β/IL-1 receptor type 1 axis both occur in human epilepsy, and contribute to experimentally induced acute seizures. In this study, the anticonvulsant activity of VX-765 (a selective ICE/caspase-1 inhibitor) was examined in a mouse model of chronic epilepsy with spontaneous recurrent epileptic activity refractory to some common anticonvulsant drugs. Moreover, the effects of this drug were studied in one acute model of seizures in mice, previously shown to involve activation of ICE/caspase-1. Quantitative analysis of electroencephalogram activity was done in mice exposed to acute seizures or those developing chronic epileptic activity after status epilepticus to assess the anticonvulsant effects of systemic administration of VX-765. Histological and immunohistochemical analysis of brain tissue was carried out at the end of pharmacological experiments in epileptic mice to evaluate neuropathology, glia activation and IL-1β expression, and the effect of treatment. Repeated systemic administration of VX-765 significantly reduced chronic epileptic activity in mice in a dose-dependent fashion (12.5-200 mg/kg). This effect was observed at doses ≥ 50 mg/kg, and was reversible with discontinuation of the drug. Maximal drug effect was associated with inhibition of IL-1β synthesis in activated astrocytes. The same dose regimen of VX-765 also reduced acute seizures in mice and delayed their onset time. These results support a new target system for anticonvulsant pharmacological intervention to control epileptic activity that does not respond to some common anticonvulsant drugs. PMID:21431948

  8. Increased serum mitochondrial creatine kinase activity as a risk for hepatocarcinogenesis in chronic hepatitis C patients.

    PubMed

    Enooku, Kenichiro; Nakagawa, Hayato; Soroida, Yoko; Ohkawa, Ryunosuke; Kageyama, Yuko; Uranbileg, Baasanjav; Watanabe, Naoko; Tateishi, Ryosuke; Yoshida, Haruhiko; Koike, Kazuhiko; Yatomi, Yutaka; Ikeda, Hitoshi

    2014-08-15

    Serum mitochondrial creatine kinase (MtCK) activity was reportedly increased in cirrhotic patients although less prominent than that in hepatocellular carcinoma (HCC) patients. To elucidate the clinical significance of serum MtCK activity in chronic liver disease, 171 chronic hepatitis C patients were enrolled. Serum MtCK activity in study subjects was correlated with serum albumin, platelet counts, liver stiffness values and serum aspartate and alanine aminotransferase. In mouse fibrotic liver induced by bile duct ligation, ubiquitous MtCK mRNA and protein expressions were significantly enhanced and its immunoreactivity was increased, predominantly in hepatocytes. During the mean follow-up period of 2.7 years, HCC developed in 21 patients, in whom serum MtCK activity was significantly higher than that in patients without HCC development. Multivariate Cox regression analysis revealed that higher serum MtCK activity was a risk for HCC development. A cutoff value of MtCK for the prediction of HCC development was determined as 9.0 U/L on receiver operating characteristics analysis, where area under receiver operating characteristics curve was 0.754, with a sensitivity of 61.9%, a specificity of 92.8% and a high negative predictive value of 94.2%. Cumulative incidence of HCC was significantly higher in patients with serum MtCK activity of >9.0 U/L compared to those with serum MtCK activity of ≤ 9.0 U/L even in patients with elevated liver stiffness value, >15 kPa. In conclusion, serum MtCK activity may be increased correlatively with the stage of liver fibrosis and hepatocellular damage. Increased serum MtCK activity is an independent risk for hepatocarcinogenesis in chronic hepatitis C patients. PMID:24420733

  9. Chronic methylphenidate alters locomotor activity and dopamine transporters differently from cocaine.

    PubMed

    Izenwasser, S; Coy, A E; Ladenheim, B; Loeloff, R J; Cadet, J L; French, D

    1999-06-01

    Continuous infusion of cocaine produces partial behavioral tolerance to its locomotor activating effects, while daily injections produce sensitization. Methylphenidate binds with a similar affinity to cocaine at the dopamine transporter, but has a much lower affinity for the serotonin transporter than does cocaine. This study was done to compare the effects of chronic methylphenidate with chronic cocaine. The pattern of locomotor activity over a 7 day treatment period was significantly different from cocaine. Methylphenidate elevated activity on each day, compared to saline, yet neither tolerance to a continuous infusion of the drug, nor sensitization to repeated daily injections was produced. We have previously shown that neither of these treatments with cocaine produces significant alterations in dopamine transporter density 1 day after the end of treatment. In contrast, methylphenidate injections significantly decreased dopamine transporters in rostral caudate putamen, with no change in nucleus accumbens. Continuous infusion of methylphenidate had no effect on dopamine transporters in either brain region. These findings provide further evidence that different classes of dopamine uptake inhibitors may interact with the dopamine transporter in qualitatively different manners. Furthermore, it is possible that the inhibition of serotonin uptake by cocaine may contribute to the adaptations in behavioral activity that are seen during chronic treatment. PMID:10414438

  10. [Adapted Physical Activity for patients with chronic diseases in a therapeutic community].

    PubMed

    Bouricha, Rémy; Thöni, Gilles; Raffard, Laurence; Cochet, Laurence; Saucourt, Vincent; Tirode, Véronique

    2015-01-01

    The French therapeutic communities ("Appartements de Coordination Therapeutique (ACT)") are mostly members of the "National Federation of Accommodation for HIV+ and other chronic diseases. They provide accommodation for people living with chronic conditions (HIV hepatitis, cancers...) and in a situation of high psychosocial frailty. As a result of their coordinated multidisciplinary intervention, these structures provide the required support to access health care and facilitate social inclusion. They are designed to provide an appropriate response to people with cumulative medical and social conditions (chronic diseases, precariousness, addictions and other comorbidities). Our innovative local experiment integrates Adapted Physical Activities (APA) into the global medical and social follow-up, in line with the patient's individual health care project. The characteristics of each APA project (nature of the activities proposed, intensity, duration, frequency, individual vs. team activity and accompanying methods) are defined on an individual basis, according to the user's motivations and inputs from the support team (medical, psychological and social coordination). The follow-up ensured by our APA professionals allows the residents to participate in a regular and attractive physical activity and could contribute to their social inclusion. The multidisciplinary approach proposed by ACTs determines the beneficial effects observed in such vulnerable patients. PMID:26168635

  11. [Measurement of physical activity in patients with chronic obstructive pulmonary disease].

    PubMed

    Magnussen, Helgo; Waschki, Benjamin; Watz, Henrik

    2009-04-15

    Physical activity is an important parameter related to morbidity and mortality in cardiovascular disease, metabolic syndrome/diabetes, mental disorders, cancer, and chronic obstructive pulmonary disease (COPD). In COPD, lower levels of physical activity as reported by the patients are associated with a faster annual lung function decline, increased number of hospitalizations, and higher risk of mortality. Self-reported physical activity, however, correlates only poorly with objectively quantified physical activity in patients with COPD. Recent data show that physical activity can reliably be measured in a substantial number of patients with COPD. Extrapulmonary effects of COPD are associated with reduced physical activity. Clinical characteristics commonly used to assess disease severity like the forced expiratory volume in 1 s or the 6-min walk distance only incompletely reflect the physical activity of patients with COPD. PMID:19399389

  12. Acetylcholinesterase activity in regions of mouse brain following acute and chronic treatment with a benzodiazepine inverse agonist.

    PubMed Central

    Appleyard, M. E.; Taylor, S. C.; Little, H. J.

    1990-01-01

    1. Chronic administration of the benzodiazepine inverse agonist FG 7142 has previously been shown to induce seizure activity in mice. In the present study we have investigated the effects of acute and chronic treatment with FG 7142 in mice on the levels of acetylcholinesterase activity in cortex, hippocampus, midbrain and striatum. We have also investigated the effects of acute and chronic stress in the form of handling (vehicle-injection) on acetylcholinesterase levels. 2. A single dose of FG 7142 produced a marked elevation of total acetylcholinesterase activities in the hippocampus and midbrain when compared with vehicle-injected control levels, but the levels were not different from those in unhandled animals. 3. Acute stress, in the form of vehicle-injection produced decreases in cortical and hippocampal soluble acetylcholinesterase activity but FG 7142 had no effect upon these stress-induced changes. 4. Total cortical and hippocampal acetylcholinesterase activities were increased by 56% and 16% respectively in the chronic FG 7142-treated mice that exhibited seizure activity (compared with vehicle-injected controls). 5. Soluble acetylcholinesterase activity in the midbrain was decreased to 82% of control levels only in animals that had undergone FG 7142-induced kindling. Smaller or no changes in acetylcholinesterase activity in the midbrain were observed in chronically FG 7142-treated animals that exhibited no seizure activity. 6. Mice that did not demonstrate seizure activity in response to chronic FG 7142 treatment showed alterations in the soluble acetylcholinesterase activities of the hippocampus and midbrain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1963800

  13. Macrophage activation associated with chronic murine cytomegalovirus infection results in more severe experimental choroidal neovascularization.

    PubMed

    Cousins, Scott W; Espinosa-Heidmann, Diego G; Miller, Daniel M; Pereira-Simon, Simone; Hernandez, Eleut P; Chien, Hsin; Meier-Jewett, Courtney; Dix, Richard D

    2012-01-01

    The neovascular (wet) form of age-related macular degeneration (AMD) leads to vision loss due to choroidal neovascularization (CNV). Since macrophages are important in CNV development, and cytomegalovirus (CMV)-specific IgG serum titers in patients with wet AMD are elevated, we hypothesized that chronic CMV infection contributes to wet AMD, possibly by pro-angiogenic macrophage activation. This hypothesis was tested using an established mouse model of experimental CNV. At 6 days, 6 weeks, or 12 weeks after infection with murine CMV (MCMV), laser-induced CNV was performed, and CNV severity was determined 4 weeks later by analysis of choroidal flatmounts. Although all MCMV-infected mice exhibited more severe CNV when compared with control mice, the most severe CNV developed in mice with chronic infection, a time when MCMV-specific gene sequences could not be detected within choroidal tissues. Splenic macrophages collected from mice with chronic MCMV infection, however, expressed significantly greater levels of TNF-α, COX-2, MMP-9, and, most significantly, VEGF transcripts by quantitative RT-PCR assay when compared to splenic macrophages from control mice. Direct MCMV infection of monolayers of IC-21 mouse macrophages confirmed significant stimulation of VEGF mRNA and VEGF protein as determined by quantitative RT-PCR assay, ELISA, and immunostaining. Stimulation of VEGF production in vivo and in vitro was sensitive to the antiviral ganciclovir. These studies suggest that chronic CMV infection may serve as a heretofore unrecognized risk factor in the pathogenesis of wet AMD. One mechanism by which chronic CMV infection might promote increased CNV severity is via stimulation of macrophages to make pro-angiogenic factors (VEGF), an outcome that requires active virus replication. PMID:22570607

  14. Chronic Low Dose Chlorine Exposure Aggravates Allergic Inflammation and Airway Hyperresponsiveness and Activates Inflammasome Pathway

    PubMed Central

    Kim, Sae-Hoon; Park, Da-Eun; Lee, Hyun-Seung; Kang, Hye-Ryun; Cho, Sang-Heon

    2014-01-01

    Background Epidemiologic clinical studies suggested that chronic exposure to chlorine products is associated with development of asthma and aggravation of asthmatic symptoms. However, its underlying mechanism was not clearly understood. Studies were undertaken to define the effects and mechanisms of chronic low-dose chlorine exposure in the pathogenesis of airway inflammation and airway hyperresponsiveness (AHR). Methods Six week-old female BALB/c mice were sensitized and challenged with OVA in the presence and absence of chronic low dose chlorine exposure of naturally vaporized gas of 5% sodium hypochlorite solution. Airway inflammation and AHR were evaluated by bronchoalveolar lavage (BAL) cell recovery and non-invasive phlethysmography, respectively. Real-time qPCR, Western blot assay, and ELISA were used to evaluate the mRNA and protein expressions of cytokines and other inflammatory mediators. Human A549 and murine epithelial (A549 and MLE12) and macrophage (AMJ2-C11) cells were used to define the responses to low dose chlorine exposure in vitro. Results Chronic low dose chlorine exposure significantly augmented airway inflammation and AHR in OVA-sensitized and challenged mice. The expression of Th2 cytokines IL-4 and IL-5 and proinflammatory cytokine IL-1β and IL-33 were significantly increased in OVA/Cl group compared with OVA group. The chlorine exposure also activates the major molecules associated with inflammasome pathway in the macrophages with increased expression of epithelial alarmins IL-33 and TSLP in vitro. Conclusion Chronic low dose exposure of chlorine aggravates allergic Th2 inflammation and AHR potentially through activation of inflammasome danger signaling pathways. PMID:25202911

  15. Macrophage Activation Associated with Chronic Murine Cytomegalovirus Infection Results in More Severe Experimental Choroidal Neovascularization

    PubMed Central

    Cousins, Scott W.; Espinosa-Heidmann, Diego G.; Miller, Daniel M.; Pereira-Simon, Simone; Hernandez, Eleut P.; Chien, Hsin; Meier-Jewett, Courtney; Dix, Richard D.

    2012-01-01

    The neovascular (wet) form of age-related macular degeneration (AMD) leads to vision loss due to choroidal neovascularization (CNV). Since macrophages are important in CNV development, and cytomegalovirus (CMV)-specific IgG serum titers in patients with wet AMD are elevated, we hypothesized that chronic CMV infection contributes to wet AMD, possibly by pro-angiogenic macrophage activation. This hypothesis was tested using an established mouse model of experimental CNV. At 6 days, 6 weeks, or 12 weeks after infection with murine CMV (MCMV), laser-induced CNV was performed, and CNV severity was determined 4 weeks later by analysis of choroidal flatmounts. Although all MCMV-infected mice exhibited more severe CNV when compared with control mice, the most severe CNV developed in mice with chronic infection, a time when MCMV-specific gene sequences could not be detected within choroidal tissues. Splenic macrophages collected from mice with chronic MCMV infection, however, expressed significantly greater levels of TNF-α, COX-2, MMP-9, and, most significantly, VEGF transcripts by quantitative RT-PCR assay when compared to splenic macrophages from control mice. Direct MCMV infection of monolayers of IC-21 mouse macrophages confirmed significant stimulation of VEGF mRNA and VEGF protein as determined by quantitative RT-PCR assay, ELISA, and immunostaining. Stimulation of VEGF production in vivo and in vitro was sensitive to the antiviral ganciclovir. These studies suggest that chronic CMV infection may serve as a heretofore unrecognized risk factor in the pathogenesis of wet AMD. One mechanism by which chronic CMV infection might promote increased CNV severity is via stimulation of macrophages to make pro-angiogenic factors (VEGF), an outcome that requires active virus replication. PMID:22570607

  16. Correlation of Tc-99m GSA hepatic studies with biopsies in patients with chronic active hepatitis.

    PubMed

    Tomiguchi, S; Kira, T; Oyama, Y; Nabeshima, M; Nakashima, R; Tsuji, A; Kojima, A; Takahashi, M; Yoshimatsu, S; Sagara, K

    1995-08-01

    To determine whether scintigraphic findings of Tc-99m DTPA-galactosyl-HSA (GSA) correspond to histopathologic findings, Tc-99m GSA hepatic scintigraphy and biopsy were compared in 65 patients with chronic active hepatitis. After injecting 185 MBq of Tc-99m GSA, anterior images were obtained at 5 minutes and 15 minutes. Scintigrams were classified into three grades according to the extent of visualization of the cardiac blood pool on 5 minute and 15 minute images. Biopsies were subjectively graded for findings of necrosis and fibrosis. Scintigraphic grades on 5 minute images were correlated with hepatic necrosis and fibrosis and those on 15-minute images with hepatic fibrosis. Scintigraphic abnormalities of Tc-99m GSA correlated well with histopathologic abnormalities, especially with hepatic fibrosis and necrosis in patients with chronic active hepatitis. PMID:7586877

  17. How do people with chronically painful joint hypermobility syndrome make decisions about activity?

    PubMed Central

    Schmidt, Anne; Corcoran, Kelley; Grahame, Rodney

    2015-01-01

    Background: The model of activity avoidance prompted by fear of increased pain and/or harm dominates understanding and research into activity limitation in chronic pain. Yet, the accounts of people with chronic pain on decisions about activity limitation are rarely heard beyond the confines of fear and avoidance questionnaires. Methods: We used semi-structured interviews to explore the decisions of 11 women attending a pain management clinic with chronically painful Joint Hypermobility Syndrome (JHS). Results: Six themes emerged from Interpretative Phenomenological Analysis: the overall aim of keeping pain to a manageable level, considering whether the planned activity was worth it and, running through all judgements, the influence of pain intensity. The decision was tipped towards avoidance by unpredictability of pain and by high emotional cost and towards going ahead with the activity by the wish to exert control and by low emotional cost. Many accounts described a specifiable cost–benefit analysis of individual decisions, weighing the importance of each activity against its potential aversive consequences, which only in a minority of cases was dominated by fear of pain or injury. Conclusion: Assumptions of fear as the basis of activity avoidance should not be used uncritically in clinical settings. Decisions about activity should explore beyond pain expectancy, incorporating goals, values, and decision processes. Summary points The model of fear of pain or re/injury and associated avoidance, an important insight that has generated effective therapeutic interventions, risks being over-applied and assumed rather than demonstrated. Patients’ own accounts, using qualitative analysis of interview in 11 women with long term chronic pain associated with joint hypermobility, give a more nuanced description of complex decision-making around activity. While a few activities were unquestionably avoided because of such fears, others were undertaken when benefits

  18. Neutrophil proteolytic activation cascades: a possible mechanistic link between chronic periodontitis and coronary heart disease.

    PubMed

    Alfakry, Hatem; Malle, Ernst; Koyani, Chintan N; Pussinen, Pirkko J; Sorsa, Timo

    2016-01-01

    Cardiovascular diseases are chronic inflammatory diseases that affect a large segment of society. Coronary heart disease (CHD), the most common cardiovascular disease, progresses over several years and affects millions of people worldwide. Chronic infections may contribute to the systemic inflammation and enhance the risk for CHD. Periodontitis is one of the most common chronic infections that affects up to 50% of the adult population. Under inflammatory conditions the activation of endogenous degradation pathways mediated by immune responses leads to the release of destructive cellular molecules from both resident and immigrant cells. Matrix metalloproteinases (MMPs) and their regulators can activate each other and play an important role in immune response via degrading extracellular matrix components and modulating cytokines and chemokines. The action of MMPs is required for immigrant cell recruitment at the site of inflammation. Stimulated neutrophils represent the major pathogen-fighting immune cells that upregulate expression of several proteinases and oxidative enzymes, which can degrade extracellular matrix components (e.g. MMP-8, MMP-9 and neutrophil elastase). The activity of MMPs is regulated by endogenous inhibitors and/or candidate MMPs (e.g. MMP-7). The balance between MMPs and their inhibitors is thought to mirror the proteolytic burden. Thus, neutrophil-derived biomarkers, including myeloperoxidase, may activate proteolytic destructive cascades that are involved in subsequent immune-pathological events associated with both periodontitis and CHD. Here, we review the existing studies on the contribution of MMPs and their regulators to the infection-related pathology. Also, we discuss the possible proteolytic involvement and role of neutrophil-derived enzymes as an etiological link between chronic periodontitis and CHD. PMID:26608308

  19. Effect of Citrocard on functional activity of cardiomyocyte mitochondria during chronic alcohol intoxication.

    PubMed

    Perfilova, V N; Ostrovskii, O V; Verovskii, V E; Popova, T A; Lebedeva, S A; Dib, H

    2007-03-01

    Chronic administration of 50% ethanol in a dose of 8 g/kg produces a toxic effect on functional activity of cardiomyocyte mitochondria, which manifested in decreased rates of respiration and oxidative phosphorylation. Structural GABA analogue Citrocard (phenibut citrate) and reference preparation piracetam in doses of 50 and 200 mg/kg, respectively, prevented the damaging effect of alcohol, which was seen from increased indexes of oxidative phosphorylation in treated animals compared to the control group. PMID:18225758

  20. The hypotensive effect of acute and chronic AMP-activated protein kinase activation in normal and hyperlipidemic mice

    PubMed Central

    Greig, Fiona H.; Ewart, Marie-Ann; McNaughton, Eilidh; Cooney, Josephine; Spickett, Corinne M.; Kennedy, Simon

    2015-01-01

    AMP-activated protein kinase (AMPK) is present in the arterial wall and is activated in response to cellular stressors that raise AMP relative to ADP/ATP. Activation of AMPK in vivo lowers blood pressure but the influence of hyperlipidemia on this response has not been studied. ApoE−/− mice on high fat diet for 6 weeks and age-matched controls were treated with the AMPK activator, AICAR daily for two weeks. Under anesthesia, the carotid artery was cannulated for blood pressure measurements. Aortic tissue was removed for in vitro functional experiments and AMPK activity was measured in artery homogenates by Western blotting. ApoE−/− mice had significantly raised mean arterial pressure; chronic AICAR treatment normalized this but had no effect in normolipidemic mice, whereas acute administration of AICAR lowered mean arterial pressure in both groups. Chronic AICAR treatment increased phosphorylation of AMPK and its downstream target acetyl-CoA carboxylase in normolipidemic but not ApoE−/− mice. In aortic rings, AMPK activation induced vasodilation and an anticontractile effect, which was attenuated in ApoE−/− mice. This study demonstrates that hyperlipidemia dysregulates the AMPK pathway in the arterial wall but this effect can be reversed by AMPK activation, possibly through improving vessel compliance. PMID:26196300

  1. Physical activity and sedentary behaviour: applying lessons to chronic obstructive pulmonary disease.

    PubMed

    Hill, K; Gardiner, P A; Cavalheri, V; Jenkins, S C; Healy, G N

    2015-05-01

    In health and disease, the benefits of regular participation in moderate to vigorous intensity physical activity are well documented. However, individuals with chronic conditions, such as those with chronic obstructive pulmonary disease (COPD), typically do very little activity at a moderate or vigorous intensity. Much of their day is instead spent in sedentary behaviour, such as sitting or reclining, which requires very little energy expenditure. This high level of time spent in sedentary behaviour can have serious health consequences, including increased risk of diabetes, cardiovascular disease and premature mortality. There is emerging evidence to suggest that participation in light intensity physical activities (e.g. standing or slow walking) may have benefits for cardio-metabolic health. Given the low aerobic capacity of individuals with moderate to severe COPD, increasing light intensity activity (through reducing sedentary time) may be a feasible additional strategy to improve health in this population, alongside traditional recommendations to increase the time spent in moderate to vigorous intensity physical activity. This review provides an overview of physical activity and sedentary behaviour, with a particular emphasis on these behaviours for people with COPD. It provides suggestions for the measurement of these behaviours within the clinical setting, as well as for interventions that may be effective at increasing physical activity and reducing sedentary behaviour in this population. PMID:25164319

  2. Correlation of alkaline phosphatase activity to clinical parameters of inflammation in smokers suffering from chronic periodontitis

    PubMed Central

    Grover, Vishakha; Malhotra, Ranjan; Kapoor, Anoop; Bither, Rupika; Sachdeva, Sonia

    2016-01-01

    Context: Current clinical periodontal diagnostic techniques emphasize the assessment of clinical and radiographic signs of periodontal diseases which can provide a measure of history of disease. Hence, new methodologies for early identification and determination of periodontal disease activity need to be explored which will eventually result in expedited treatment. Aim: To evaluate the correlation of alkaline phosphatase (ALP) activity in gingival crevicular fluid (GCF) to clinical parameters of periodontal inflammation in smokers with chronic periodontitis. Materials and Methods: Study population included 15 smoker male patients in the age group of 35–55 years suffering from moderate generalized chronic periodontitis with history of smoking present. Following parameters were evaluated at baseline, 1 month and 3 months after scaling and root planing: plaque index, bleeding index, probing pocket depth (PD), relative attachment level (RAL), and GCF ALP activity. Statistical Analysis Used: Independent variables for measurements over time were analyzed by using Wilcoxon signed rank test. Results: A statistically significant reduction in all the clinical parameters and GCF ALP activity was observed from baseline to 1 month and 3 months. A correlation was observed between change in GCF ALP activity and PD reduction as well as gain in RAL at 3 months. Conclusion: The present study emphasizes that total ALP activity could be used as a marker for periodontal disease activity in smokers. Estimation of changes in the levels of this enzyme has a potential to aid in the detection of progression of periodontal disease and monitoring the response to periodontal therapy. PMID:27563197

  3. Sleep is associated with task-negative brain activity in fibromyalgia participants with comorbid chronic insomnia

    PubMed Central

    Vatthauer, Karlyn E; Craggs, Jason G; Robinson, Michael E; Staud, Roland; Berry, Richard B; Perlstein, William M; McCrae, Christina S

    2015-01-01

    Patients with chronic pain exhibit altered default mode network (DMN) activity. This preliminary project questioned whether comorbid disease states are associated with further brain alterations. Thirteen women with fibromyalgia (FM) only and 26 women with fibromyalgia with comorbid chronic insomnia (FMI) underwent a single night of ambulatory polysomnography and completed a sleep diary each morning for 14 days prior to performing a neuroimaging protocol. Novel imaging analyses were utilized to identify regions associated with significantly disordered sleep that were more active in task-negative periods than task-oriented periods in participants with FMI, when compared to participants with FM. It was hypothesized that core DMN areas (ie, cingulate cortex, inferior parietal lobule, medial prefrontal cortex, medial temporal cortex, precuneus) would exhibit increased activity during task-negative periods. Analyses revealed that significantly disordered sleep significantly contributed to group differences in the right cingulate gyrus, left lentiform nucleus, left anterior cingulate, left superior gyrus, medial frontal gyrus, right caudate, and the left inferior parietal lobules. Results suggest that FMI may alter some brain areas of the DMN, above and beyond FM. However, future work will need to investigate these results further by controlling for chronic insomnia only before conclusions can be made regarding the effect of FMI comorbidity on the DMN. PMID:26648751

  4. Subconjunctival Sirolimus for the Treatment of Chronic Active Anterior Uveitis: Results of a Pilot Trial

    PubMed Central

    Sen, H. Nida; Larson, Theresa A.; Meleth, Annal D.; Smith, Wendy M.; Nussenblatt, Robert B.

    2012-01-01

    Purpose To evaluate the safety and possible efficacy of subconjunctival sirolimus for the treatment of chronic active anterior uveitis Design Prospective, non-randomized, open-label clinical trial. Methods This single-center pilot trial enrolled 5 patients with chronic active anterior uveitis. The study drug was administered as single subconjunctival injection of 30μL (1,320μg) sirolimus in the study eye at the baseline visit. Study visits were performed at baseline, 2 weeks, 4 weeks and monthly until 4 months, and included a complete ophthalmic exam, review of systems, adverse event assessment at each visit, physical exam and ancillary ophthalmic testing at some visits. The primary outcome measure was a 2-step reduction in the anterior chamber inflammation within 4 weeks of injection of the study drug. Results There were 3 females and 2 males; 4 patients had idiopathic anterior uveitis and one had psoriatic arthritis-associated anterior uveitis. Three of the five patients met the primary outcome criteria by showing at least a 2-step decrease in inflammation within 4 weeks, 2 patients showed a 1-step decrease in inflammation within the same time frame. No recurrence was encountered during a 4 month follow-up. There were no serious adverse events. Conclusions Subconjunctival sirolimus appears to be well tolerated in this pilot trial and shows promise as a treatment for active inflammation in patients with chronic anterior uveitis. Larger studies are needed to assess its usefulness in uveitis. PMID:22465364

  5. Autoantibodies to thyroid peroxidase in patients with chronic thyroiditis: effect of antibody binding on enzyme activities.

    PubMed Central

    Kohno, Y; Hiyama, Y; Shimojo, N; Niimi, H; Nakajima, H; Hosoya, T

    1986-01-01

    Using thyroid peroxidase (TPO), which was purified from the thyroid of patients with Graves' disease, we attempted to determine whether sera from patients with chronic thyroiditis contained antibodies to the enzyme. When the binding was tested by ELISA, sera from patients with chronic thyroiditis revealed high binding activities to TPO. When TPO was incubated with IgG from sera followed by treatment with protein A-Sepharose and centrifugation, the remaining TPO activities in the supernatant fraction were lower in most of the patients, as compared to normal controls. Moreover, IgG purified by DEAE-cellulose chromatography from sera in patients interfered with the TPO activities. Titres of anti-TPO antibodies correlated well with those of anti-microsome antibodies. These results indicate the presence of autoantibodies to TPO in sera of most patients with chronic thyroiditis and that TPO may be one component of microsome antigen complexes recognized by the autoantibodies. Studies on the inhibition of TPO by IgG isolated from sera of patients using guaiacol and iodide assays revealed that at least three epitopes of TPO molecule were recognized by autoantibodies and that the antigenic determinants on TPO molecule recognized by autoantibodies could be heterogeneous in patients. PMID:2430744

  6. Sleep is associated with task-negative brain activity in fibromyalgia participants with comorbid chronic insomnia.

    PubMed

    Vatthauer, Karlyn E; Craggs, Jason G; Robinson, Michael E; Staud, Roland; Berry, Richard B; Perlstein, William M; McCrae, Christina S

    2015-01-01

    Patients with chronic pain exhibit altered default mode network (DMN) activity. This preliminary project questioned whether comorbid disease states are associated with further brain alterations. Thirteen women with fibromyalgia (FM) only and 26 women with fibromyalgia with comorbid chronic insomnia (FMI) underwent a single night of ambulatory polysomnography and completed a sleep diary each morning for 14 days prior to performing a neuroimaging protocol. Novel imaging analyses were utilized to identify regions associated with significantly disordered sleep that were more active in task-negative periods than task-oriented periods in participants with FMI, when compared to participants with FM. It was hypothesized that core DMN areas (ie, cingulate cortex, inferior parietal lobule, medial prefrontal cortex, medial temporal cortex, precuneus) would exhibit increased activity during task-negative periods. Analyses revealed that significantly disordered sleep significantly contributed to group differences in the right cingulate gyrus, left lentiform nucleus, left anterior cingulate, left superior gyrus, medial frontal gyrus, right caudate, and the left inferior parietal lobules. Results suggest that FMI may alter some brain areas of the DMN, above and beyond FM. However, future work will need to investigate these results further by controlling for chronic insomnia only before conclusions can be made regarding the effect of FMI comorbidity on the DMN. PMID:26648751

  7. Brain activity for chronic knee osteoarthritis: dissociating evoked pain from spontaneous pain

    PubMed Central

    Parks, Elle L.; Geha, Paul Y.; Baliki, Marwan N.; Katz, Jeffrey; Schnitzer, Thomas J.; Apkarian, A. Vania

    2011-01-01

    Chronic pain is a hallmark of osteoarthritis (OA), yet little is known about its properties and representation in the brain. Here we use fMRI combined with psychophysics to study knee pain in 14 OA patients and 9 healthy controls. Mechanical painful pressure stimuli were applied to the knee in both groups and ratings of evoked pain and related brain activity examined. We observe that psychophysical properties and brain activation patterns of evoked pain are essentially the same between OA patients and healthy subjects, and between worse and better OA knees. In OA patients, stimulus-related brain activity could be distinguished from brain activity associated with spontaneous pain. The former activated brain regions commonly observed for acute painful stimuli in healthy subjects, while the spontaneous pain of OA engaged prefrontal-limbic regions closely corresponding to areas observed for spontaneous pain in other chronic pain conditions, such as chronic back pain and post-herpetic neuralgia. Arthritis-related clinical characteristics of knee OA also mapped to prefrontal-limbic regions. In a subgroup of patients (n = 6) we examined brain activity changes for a 2-week, repeat measure, cyclooxygenase-2 inhibitor (valdecoxib) therapy. Treatment decreased spontaneous pain for the worse knee and clinical characteristics of OA, and increased blood and csf levels of the drug which correlated positively with prefrontal-limbic brain activity. These findings indicate dissociation between mechanically induced and spontaneous OA knee pain, the latter engaging brain regions involved in emotional assessment of the self, and challenge the standard clinical view regarding the nature of OA pain. PMID:21315627

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

    SciTech Connect

    Moreno, A.J.; Brown, J.M.; Salinas, J.A.; Feaster, B.L.; Brown, T.J.

    1984-03-01

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

  9. Topical pimecrolimus as a new optional treatment in cutaneous sarcoidosis of lichenoid type.

    PubMed

    Tammaro, Antonella; Abruzzese, Claudia; Narcisi, Alessandra; Cortesi, Giorgia; Parisella, Francesca Romana; Di Russo, Pier Paolo; De Marco, Gabriella; Persechino, Severino

    2014-01-01

    We report the case of cutaneous sarcoidosis of lichenoid type successfully treated with pimecrolimus. For the first time in the literature, we propose the use of this topical calcineurin inhibitor for the treatment of the cases refractory to common therapy regimens. PMID:24826355

  10. Association of Neutrophil to Lymphocyte Ratio and Pulmonary Hypertension in Sarcoidosis Patients

    PubMed Central

    Mortaz, Esmaeil; Omar, Hesham R.; Camporesi, Enrico M.; Sweiss, Nadera

    2016-01-01

    Background: The neutrophil-to-lymphocyte ratio (NLR) has emerged as a new marker of inflammation associated with the severity of several respiratory and cardiac diseases. Materials and Methods: We investigated whether the degree of systemic inflammation in sarcoidosis patients as measured by the NLR is associated with pulmonary hypertension (PH). Results: A NLR > 3.5 occurred with a significantly higher frequency in sarcoidosis patients with PH (50% vs. 24%, P=0.016) yielding a sensitivity of 50%, specificity of 78%, positive predictive value (PPV) of 41.9% and negative predictive value (NPV) of 81.4% and remained independently associated with PH in multivariate analysis (OR: 3.254, 95% CI: 1.094–9.678, P=0.034). Conclusion: We conclude that level of inflammation in sarcoidosis patients may be associated with the development of PH. Owing to the relatively good specificity and NPV, NLR may be a good negative test, which is a simple, inexpensive and widely available in office-based setting to predict the risk of PH in sarcoidosis patients. PMID:27403178

  11. Cardiac sarcoidosis mimicking hypertrophic cardiomyopathy: clinical utility of radionuclide imaging for differential diagnosis.

    PubMed

    Yazaki, Y; Isobe, M; Hayasaka, M; Tanaka, M; Fujii, T; Sekiguchi, M

    1998-06-01

    A 62-year-old woman with skin sarcoidosis was admitted to our hospital to ascertain whether she had cardiac involvement. Although she displayed no cardiac signs or symptoms, the electrocardiogram showed first-degree atrioventricular block, right bundle branch block with left anterior fascicular block, and giant negative T waves in the V3 lead. Echocardiography revealed marked hypertrophy localized in the basal portion of the interventricular septum (IVS) without systolic dysfunction, mimicking hypertrophic cardiomyopathy (HCM). Exercise thallium-201 myocardial imaging revealed redistribution in the anteroseptal region. Both gallium-67 (67Ga) and technetium-99m pyrophosphate (99mTc-PYP) scintigraphy revealed abnormal uptake in the myocardium. These findings disappeared after 2 months of steroid treatment. Reports of cardiac sarcoidosis mimicking HCM are rare. However, hypertrophy in the basal portion of the IVS is an important sign of early cardiac involvement in sarcoidosis. 67Ga and 99mTc-PYP scintigraphy were useful and necessary to differentiate this type of cardiac sarcoidosis from HCM. PMID:9652326

  12. Sarcoidosis in children. Epidemiology in Danes, clinical features, diagnosis, treatment and prognosis.

    PubMed

    Milman, N; Hoffmann, A L; Byg, K E

    1998-08-01

    This paper reviews current knowledge of childhood sarcoidosis with regard to the epidemiology in Danes, clinical presentation, diagnostic procedures, treatment and prognosis. Sarcoidosis is a granulomatous disease of unknown aetiology, with multiorgan involvement. The diagnosis is confirmed by the demonstration of epitheloid cell granulomas in tissue biopsy specimens. During the period 1980-92, three cases of childhood sarcoidosis were recorded in Copenhagen County, which has a total population of 610,000. The approximate incidence of clinically recognized sarcoidosis in Danish children younger than 15 y of age was 0.22-0.27/100,000 children per year, corresponding to approximately three new cases in Denmark each year. The true incidence is unknown, since the disease is often asymptomatic and resolves without a clinical diagnosis being made. In children younger than 5 y of age, the disease is characterized by involvement of skin, eyes and joints, whereas in older children involvement of lungs, lymph nodes and eyes predominate. The mainstay of treatment consists of oral corticosteroids. The risk/benefit ratio of using long-term corticosteroids needs to be evaluated in each individual patient. Some patients may benefit from additional therapy with methotrexate. The long-term prognosis is not well established, but it seems to be poorer in children younger than 5 y. Older children appear to have as favourable a prognosis as young adults. PMID:9736236

  13. Acute and chronic responses of activated sludge viability and performance to silica nanoparticles.

    PubMed

    Zheng, Xiong; Su, Yinglong; Chen, Yinguang

    2012-07-01

    Recently, the potential health and environmental risks of silica nanoparticles (SiO(2) NPs) are attracting great interest. However, little is known about their possible impacts on wastewater biological nitrogen and phosphorus removal. In this study, the acute and chronic effects of SiO(2) NPs on activated sludge viability and biological nutrient removal performance were investigated. It was found that the presence of environmentally relevant concentration (1 mg/L) of SiO(2) NPs caused no adverse acute and chronic effects on sludge viability and wastewater nitrogen and phosphorus removal. However, chronic exposure to 50 mg/L SiO(2) NPs induced the increase of effluent nitrate concentration, and thus depressed the total nitrogen (TN) removal efficiency from 79.6% to 51.6% after 70 days of exposure, which was due to the declined activities of denitrifying enzymes, nitrate reductase and nitrite reductase. Wastewater phosphorus removal was insensitive to 1 and 50 mg/L SiO(2) NPs after either the acute or chronic exposure, because the critical factors closely related to biological phosphorus removal were not significantly changed, such as the activities of exopolyphosphatase and polyphosphate kinase and the intracellular transformations of polyhydroxyalkanoates and glycogen. Denaturing gradient gel electrophoresis (DGGE) analysis revealed that the bacterial community structure was changed after long-term exposure to 50 mg/L SiO(2) NPs, and the quantitative PCR assays indicated that the abundance of denitrifying bacteria was decreased, which was consistent with the declined wastewater nitrogen removal. PMID:22697807

  14. Chronic alcohol consumption enhances iNKT cell maturation and activation.

    PubMed

    Zhang, Hui; Zhang, Faya; Zhu, Zhaohui; Luong, Dung; Meadows, Gary G

    2015-01-15

    Alcohol consumption exhibits diverse effects on different types of immune cells. NKT cells are a unique T cell population and play important immunoregulatory roles in different types of immune responses. The effects of chronic alcohol consumption on NKT cells remain to be elucidated. Using a mouse model of chronic alcohol consumption, we found that alcohol increases the percentage of NKT cells, especially iNKT cells in the thymus and liver, but not in the spleen or blood. Alcohol consumption decreases the percentage of NK1.1(-) iNKT cells in the total iNKT cell population in all of the tissues and organs examined. In the thymus, alcohol consumption increases the number of NK1.1(+)CD44(hi) mature iNKT cells but does not alter the number of NK1.1(-) immature iNKT cells. A BrdU incorporation assay shows that alcohol consumption increases the proliferation of thymic NK1.1(-) iNKT cells, especially the NK1.1(-)CD44(lo) Stage I iNKT cells. The percentage of NKG2A(+) iNKT cells increases in all of the tissues and organs examined; whereas CXCR3(+) iNKT cells only increases in the thymus of alcohol-consuming mice. Chronic alcohol consumption increases the percentage of IFN-γ-producing iNKT cells and increases the blood concentration of IFN-γ and IL-12 after in vivo α-galactosylceramide (αGalCer) stimulation. Consistent with the increased cytokine production, the in vivo activation of iNKT cells also enhances the activation of dendritic cells (DC) and NK, B, and T cells in the alcohol-consuming mice. Taken together the data indicate that chronic alcohol consumption enhances iNKT cell maturation and activation, which favors the Th1 immune response. PMID:25499027

  15. Urinary neutral endopeptidase 24.11 activity: modulation by chronic salt loading.

    PubMed

    Aviv, R; Gurbanov, K; Hoffman, A; Blumberg, S; Winaver, J

    1995-03-01

    Neutral endopeptidase (NEP) 24.11 is a zinc-metallopeptidase involved in the metabolism of several biologically active peptides including enkephalin, atrial natriuretic peptide, bradykinin, and endothelin. The enzyme is found in abundant amounts in the brush border of renal proximal epithelial cells. A soluble form of NEP was previously identified in human urine with characteristics similar to the renal enzyme. The present study further characterized the excreted form of NEP activity in urine of normal rats using a sensitive two-stage enzymatic assay. The response of urinary NEP to known inhibitors such as phosphoramidon and thiorphan, and its dependence on pH and salt concentration was studied. In addition, we evaluated the effects of acute and chronic changes in salt balance, induced by i.v. saline infusion and drinking of saline solution, on urinary NEP and on the activity of the enzyme in isolated proximal tubules. Our findings demonstrated that abundant NEP activity was detected in the urine of normal rats. Furthermore, chronic salt loading, but not acute salt infusion, was associated with increased activity of NEP in urine and in isolated proximal tubules, suggesting that the enzyme may be regulated by salt balance. Finally, the data suggest that urinary NEP may be used as an index of enzyme activity in the kidney. PMID:7752584

  16. Pulmonary Rehabilitation and Physical Activity in Patients with Chronic Obstructive Pulmonary Disease.

    PubMed

    Spruit, Martijn A; Pitta, Fabio; McAuley, Edward; ZuWallack, Richard L; Nici, Linda

    2015-10-15

    Physical inactivity is common in patients with chronic obstructive pulmonary disease (COPD) compared with age-matched healthy individuals or patients with other chronic diseases. Physical inactivity independently predicts poor outcomes across several aspects of this disease, but it is (at least in principle) treatable in patients with COPD. Pulmonary rehabilitation has arguably the greatest positive effect of any current therapy on exercise capacity in COPD; as such, gains in this area should facilitate increases in physical activity. Furthermore, because pulmonary rehabilitation also emphasizes behavior change through collaborative self-management, it may aid in the translation of increased exercise capacity to greater participation in activities involving physical activity. Both increased exercise capacity and adaptive behavior change are necessary to achieve significant and lasting increases in physical activity in patients with COPD. Unfortunately, it is readily assumed that this translation occurs naturally. This concise clinical review will focus on the effects of a comprehensive pulmonary rehabilitation program on physical activity in patients with COPD. Changing physical activity behavior in patients with COPD needs an interdisciplinary approach, bringing together respiratory medicine, rehabilitation sciences, social sciences, and behavioral sciences. PMID:26161676

  17. Prevalence of cardiac sarcoidosis in white population: a case–control study

    PubMed Central

    Martusewicz-Boros, Magdalena M.; Boros, Piotr W.; Wiatr, Elżbieta; Zych, Jacek; Piotrowska-Kownacka, Dorota; Roszkowski-Śliż, Kazimierz

    2016-01-01

    Abstract Cardiac sarcoidosis (CS) is a life-threatening and underdiagnosed manifestation of the disease, which requires a complicated and expensive diagnostic pathway. There is a need for simple tool for practitioners to determine the risk of CS without access to specialized equipment. The aim of study was to determine the prevalence of CS in a group of patients diagnosed with or followed up because of sarcoidosis. A secondary objective was the search for factors associated with heart involvement. We performed a prospective case–control study (screening analysis) in consecutive sarcoidosis patients collected from October 2012 to September 2015. Cardiac magnetic resonance (CMR) imaging was performed to confirm or exclude cardiac involvement in all patients. The study was conducted in a hospital-based referral center for patients with sarcoidosis and other interstitial lung diseases. Analysis was performed in a group of 201 patients (all white) with biopsy-proven sarcoidosis, mean age 41.4 ± 10.2, 121 of them (60.2%) males. Four patients with previously recognized cardiac diseases, which make CMR imaging for CS inconclusive, were not included. Cardiac involvement was detected by CMR in 49 patients (24.4%). Factors associated with an increased risk of CS (univariate analyses) included male sex (odds ratio [OR]: 2.5; 1.21–5.16, P = 0.01), cardiac-related symptoms (OR: 3.53; 1.81–6.89, P = 0.0002), extrathoracic sarcoidosis (OR: 3.48; 1.77–6.84, P = 0.0003), elevated serum NT-proBNP (OR: 3.82; 1.55–9.42, P = 0.004), any electrocardiography abnormality (OR: 5.38; 2.48–11.67, P = 0.0001), and contemporary radiological progression sarcoidosis in the lungs (OR: 2.98; 1.52–5.84, P = 0.001). Abnormalities in echocardiography and Holter ECG were also risk factors, but not significant in multivariate analyses. A CS Risk Index was developed using a multivariate model to predict CS, achieving an accuracy of 82%, sensitivity of 50

  18. In-Hospital Disease Burden of Sarcoidosis in Switzerland from 2002 to 2012

    PubMed Central

    Pohle, Susanne; Baty, Florent; Brutsche, Martin

    2016-01-01

    Sarcoidosis is a multisystem disease with an unpredictable and sometimes fatal course while the underlying pathomechanism is still unclear. Reasons of the increasing hospitalization rate and mortality in the United States remain in dispute but incriminated are a number of distinct comorbidities and risk factors as well as the application of more aggressive therapeutic agents. Studies reflecting the recent development in central Europe are lacking. Our aim was to investigate the recent mortality and hospitalization rates as well as the underlying comorbidities of hospitalized sarcoidosis patients in Switzerland. In this longitudinal, nested case-control study, a nation-wide database provided by the Swiss Federal Office for Statistics enclosing every hospital entry covering the years 2002–2012 (n = 15,627,573) was analyzed. There were 8,385 cases with a diagnosis of sarcoidosis representing 0.054% (8,385 / 15,627,573) of all hospitalizations in Switzerland. These cases were compared with age- and sex-matched controls without the diagnosis of sarcoidosis. Hospitalization and mortality rates in Switzerland remained stable over the observed time period. Comorbidity analysis revealed that sarcoidosis patients had significantly higher medication-related comorbidities compared to matched controls, probably due to systemic corticosteroids and immunosuppressive therapy. Sarcoidosis patients were also more frequently re-hospitalized (median annual hospitalization rate 0.28 [IQR 0.15-0.65] vs. 0.19 [IQR 0.13-0.36] per year; p < 0.001), had a longer hospital stay (6 [IQR 2-13] vs. 4 [IQR 1-8] days; p < 0.001), had more comorbidities (4 [IQR 2-7] vs. 2 [IQR 1-5]; p < 0.001), and had a significantly higher in-hospital mortality (2.6% [95% CI 2.3%-2.9%] vs. 1.8% [95% CI 1.5%-2.1%] (p < 0.001). A worse outcome was observed among sarcoidosis patients having co-occurrence of associated respiratory diseases. Moreover, age was an important risk factor for re-hospitalization. PMID

  19. Differential effects of acute and chronic fructose administration on pyruvate dehydrogenase activity and lipogenesis

    SciTech Connect

    Wilson, L.

    1988-01-01

    These studies were undertaken to distinguish between the acute and chronic effects of fructose administration. In vivo, liver lipogenesis, as measured by {sup 3}H{sub 2}O incorporation, was greater in rats fed 60% fructose than in their glucose fed controls. Both fructose feeding, and fructose feeding plus intraperitoneal fructose injection increased the activities of 6-phosphogluconate dehydrogenase and malic enzyme. Liver PDH activity was increased by fructose feeding, and was increased even more by fructose feeding and injection of fructose, but this was not associated with any changes in hepatic ATP concentrations.

  20. Phenomenological correlates of metabolic activity in 18 patients with chronic schizophrenia

    SciTech Connect

    Volkow, N.D.; Wolf, A.P.; Van Gelder, P.; Brodie, J.D.; Overall, J.E.; Cancro, R.; Gomez-Mont, F.

    1987-02-01

    Using (11C)-deoxy-D-glucose and positron emission tomography (PET), the authors measured brain metabolism in 18 patients with chronic schizophrenia to assess which of the metabolic measures from two test conditions was more closely related to the patients' differing clinical characteristics. The two conditions were resting and activation, and an eye tracking task was used. Patients with more negative symptoms showed lower global metabolic rates and more severe hypofrontality than did the patients with fewer negative symptoms. Differences among the patients were distinguished by the task: sicker patients failed to show a metabolic activation response. These findings suggest that cerebral metabolic patterns reflect clinical characteristics of schizophrenic patients.

  1. Down-regulation of phospholipase C-beta1 following chronic muscarinic receptor activation.

    PubMed

    Sorensen, S D; Linseman, D A; Fisher, S K

    1998-04-01

    To determine whether prolonged activation of a phospholipase C-coupled receptor can lead to a down-regulation of its effector enzyme, SH-SY5Y neuroblastoma cells were incubated for 24 h with the muscarinic receptor agonist, oxotremorine-M. Under these conditions, significant reductions (46-53%) in muscarinic cholinergic receptor density, G(alphaq/11) and phospholipase C-beta1 (but not the beta3-or gamma1 isoforms) were observed. These results suggest that a selective down-regulation of phospholipase C-beta1 may play a role in adaptation to chronic muscarinic receptor activation. PMID:9617763

  2. Specific pollen allergen activates eosinophils of the patient with chronic allergic contact urticaria.

    PubMed

    Panaszek, B; Małolepszy, J; Kuryszko, J; Litwa, M

    1994-01-01

    The aim of the study was to evaluate the activation of eosinophils in an unique case of a young man with atopy manifested as chronic pollen contact urticaria. In order to reveal the role of eosinophils in that case, the study was performed by means of monoclonal antibodies EG2 and chemiluminescence. In addition, comparative electron microscopic study of peripheral blood and skin infiltrating eosinophils were performed for which the name ultrastructural morphometric analysis of intracytoplasmic eosinophil granules has been proposed. The results indicated, that 40% of peripheral blood eosinophils were activated spontaneously and they were more active than those in skin infiltrates. Specific pollen allergen caused activation of 100% of peripheral blood eosinophils. The study suggests presence of a systemic pattern of eosinophil activation in atopy. PMID:7487362

  3. Development of the chronic obstructive pulmonary disease activity rating scale: reliability, validity and factorial structure.

    PubMed

    Morimoto, Michiko; Takai, Kenichi; Nakajima, Kazuo; Kagawa, Koujiro

    2003-03-01

    The purpose of the present study was to develop the Chronic Obstructive Pulmonary Disease (COPD) Activity Rating Scale (CARS) to measure life-related activity in patients with COPD, and to confirm its reliability and constructive validity in a factorial structure model. The subjects consisted of 114 patients with COPD. An 88-item life-related activity list, generated previously from a literature review, was administered. The secondary structural model consisted of four factors with 12 items. The results of the confirmatory factor analysis by structural equation modeling showed the fit criteria to be statistically significant. The internal consistency of the 12 items was highly reliable (Cronbach's alpha = 0.924). The CARS score was correlated with pulmonary function tests, breathlessness, and the health-related quality of life (QOL) scales in Pearson correlation coefficient. The results suggest that the COPD Activity Rating Scale is a valid scale for the assessment of life-related activity in patients with COPD. PMID:12603718

  4. Heightened free radical activity in blacks with chronic pancreatitis at Johannesburg, South Africa.

    PubMed

    Gut, A; Shiel, N; Kay, P M; Segal, I; Braganza, J M

    1994-10-31

    Four indices of free radical activity were measured in fasting serum/plasma samples from 14 consecutive blacks with clinically quiescent chronic pancreatitis and 15 outwardly healthy hospital personnel at Soweto, the township near Johannesburg in South Africa. The patients had higher serum levels than did controls of lipid isomerisation (P < 0.002) and peroxidation (P < 0.05) markers, with lower plasma levels of glutathione (P < 0.0001) and bioactive fraction of vitamin C (P < 0.002). Lipid peroxide and non-bioavailable vitamin C concentrations in Sowetan patients were significantly higher than in their counterparts from Manchester, UK (P < 0.0001, P < 0.0005, respectively). These differences mirrored those in controls in that outwardly healthy Sowetans had much higher serum lipid peroxide levels than Manchester controls (P < 0.001) and much lower plasma concentration of vitamin C (P < 0.001) and hence of the bioavailable fraction ascorbate (P < 0.0002). Heightened free radical activity is thus a common denominator in chronic pancreatitis irrespective of geography, or putative aetiological factors whether alcoholism or idiopathic, since that ratio was approximately 95:5 at Johannesburg and 50:50 at Manchester. The further finding of subclinical oxidative stress in Sowetan controls and the endemic nature of chronic pancreatitis in that area supports the hypothesis that oxidative stress may be involved in its pathogenesis. PMID:7834869

  5. Efficacy of physical activity counseling plus sleep restriction therapy on the patients with chronic insomnia

    PubMed Central

    Wang, Jihui; Yin, Guangxia; Li, Guanying; Liang, Wenjing; Wei, Qinling

    2015-01-01

    Objective Lack of physical activity (PA) is common in patients with chronic insomnia. Studies to increase PA and decrease sedentary behavior in those patients are limited. Therefore, we investigated the efficacy of “PA counseling combined with sleep restriction (SR) therapy (PASR)” vs only SR in the patients with chronic insomnia. Methods Seventy-one outpatients were assigned to either PASR (n=35), consisting of four weekly PA counseling sessions based on 5A model (assess, advise, agree, assist, and arrange) + SR, or SR (n=36), consisting of four weekly SR. International Physical Activity Questionnaire (Chinese version) and pedometer-based daily steps were evaluated as the primary endpoints. Insomnia Severity Index, Epworth Sleepiness Scale, Fatigue Scale-14, and Sleep Diary were evaluated as the secondary endpoints. Results The results showed that the patients in the PASR group gained more benefits than the SR group in terms of PA level and pedometer-based daily steps (all P<0.05). Better improvements of the study group were also shown in Epworth Sleepiness Scale, Fatigue Scale-14, and Sleep efficiency (all P<0.05). Conclusion We conclude that PA counseling based on 5A model combined with SR cannot only effectively increase the PA levels but also improve the sleep quality for patients with chronic insomnia. PMID:26566369

  6. Dormancy of Cancer Cells with Suppression of AKT Activity Contributes to Survival in Chronic Hypoxia

    PubMed Central

    Endo, Hiroko; Okuyama, Hiroaki; Ohue, Masayuki; Inoue, Masahiro

    2014-01-01

    A hypoxic microenvironment in tumors has been recognized as a cause of malignancy or resistance to various cancer therapies. In contrast to recent progress in understanding the acute response of cancer cells to hypoxia, the characteristics of tumor cells in chronic hypoxia remain elusive. We have identified a pancreatic cancer cell line, AsPC-1, that is exceptionally able to survive for weeks under 1% oxygen conditions while most tested cancer cell lines die after only some days under these conditions. In chronic hypoxia, AsPC-1 cells entered a state of dormancy characterized by no proliferation, no death, and metabolic suppression. They reversibly switched to active status after being placed again in optimal culture conditions. ATP turnover, an indicator of energy demand, was markedly decreased and accompanied by reduced AKT phosphorylation. Forced activation of AKT resulted in increased ATP turnover and massive cell death in vitro and a decreased number of dormant cells in vivo. In contrast to most cancer cell lines, primary-cultured colorectal cancer cells easily entered the dormant status with AKT suppression under hypoxia combined with growth factor–depleted conditions. Primary colorectal cancer cells in dormancy were resistant to chemotherapy. Thus, the ability to survive in a deteriorated microenvironment by entering into dormancy under chronic hypoxia might be a common property among cancer cells. Targeting the regulatory mechanism inducing this dormant status could provide a new strategy for treating cancer. PMID:24905002

  7. Improved cognitive, affective and anxiety measures in patients with chronic systemic disorders following structured physical activity.

    PubMed

    Teixeira, Robson Bonoto; Marins, João Carlos Bouzas; de Sá Junior, Antonio Reis; de Carvalho, Cristiane Junqueira; da Silva Moura, Tiago Augusto; Lade, Carlos Gabriel; Rizvanov, Albert A; Kiyasov, Andrey P; Mukhamedyarov, Marat A; Zefirov, Andrey L; Palotás, András; Lima, Luciana Moreira

    2015-11-01

    Mental illnesses are frequent co-morbid conditions in chronic systemic diseases. High incidences of depression, anxiety and cognitive impairment complicate cardiovascular and metabolic disorders such as hypertension and diabetes mellitus. Lifestyle changes including regular exercise have been advocated to reduce blood pressure and improve glycaemic control. The purpose of this project was to evaluate the effect of physical training on the most prevalent corollary psychiatric problems in patients with chronic organic ailments. This longitudinal study assessed the mental health of hypertensive (age: 57 ± 8 years) and/or diabetic (age: 53 ± 8 years) patients using mini-mental state examination, Beck's depression inventory, Beck's anxiety inventory and self-reporting questionnaire-20 before and after a 3-month supervised resistance and aerobic exercise programme comprising structured physical activity three times a week. Clinically relevant improvement was observed in the Beck's depression inventory and Beck's anxiety inventory scores following the 12-week training (61%, p = 0.001, and 53%, p = 0.02, respectively). Even though statistically not significant (p = 0.398), the cognitive performance of this relatively young patient population also benefited from the programme. These results demonstrate positive effects of active lifestyle on non-psychotic mental disorders in patients with chronic systemic diseases, recommending exercise as an alternative treatment option. PMID:26410835

  8. Clinical effects of deep cervical flexor muscle activation in patients with chronic neck pain

    PubMed Central

    Kim, Jin Young; Kwag, Kwang Il

    2016-01-01

    [Purpose] The purpose of this study was to investigate clinical effects of deep cervical flexor (DCF) muscles exercise on pain, Neck Disability Index (NDI), and neck and shoulder postures in patients with chronic neck pain. [Subjects and Methods] Twenty-eight patients with chronic neck pain were randomly assigned into either the general strengthening exercise (GSE) group or the DCF activation group as control and experimental groups, respectively. All exercises were performed three times per week over 4 weeks. NDI and numeric rating scale (NRS) score for pain were determined and radiological assessment of neck-shoulder postures (head tilt angle [HTA], neck flexion angle [NFA], and forward shoulder angle [FSA]) was performed before (baseline), 4 weeks after, and 8 weeks after exercise in order to directly compare the exercise effects between the groups. [Results] In the DCF group, the NDI, NRS score, and neck-shoulder postures (analyzed by uisng HTA, NFA, and FSA) were significantly improved. [Conclusion] DCF activation exercise was effective to alleviate pain, recover functions, and correct forward head posture in the patients with neck pain. Hence, it might be recommended in the rehabilitation of patients with chronic neck pain. PMID:26957772

  9. Therapeutic activity of multiple common γ-chain cytokine inhibition in acute and chronic GVHD.

    PubMed

    Hechinger, Anne-Kathrin; Smith, Benjamin A H; Flynn, Ryan; Hanke, Kathrin; McDonald-Hyman, Cameron; Taylor, Patricia A; Pfeifer, Dietmar; Hackanson, Björn; Leonhardt, Franziska; Prinz, Gabriele; Dierbach, Heide; Schmitt-Graeff, Annette; Kovarik, Jiri; Blazar, Bruce R; Zeiser, Robert

    2015-01-15

    The common γ chain (CD132) is a subunit of the interleukin (IL) receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Because levels of several of these cytokines were shown to be increased in the serum of patients developing acute and chronic graft-versus-host disease (GVHD), we reasoned that inhibition of CD132 could have a profound effect on GVHD. We observed that anti-CD132 monoclonal antibody (mAb) reduced acute GVHD potently with respect to survival, production of tumor necrosis factor, interferon-γ, and IL-6, and GVHD histopathology. Anti-CD132 mAb afforded protection from GVHD partly via inhibition of granzyme B production in CD8 T cells, whereas exposure of CD8 T cells to IL-2, IL-7, IL-15, and IL-21 increased granzyme B production. Also, T cells exposed to anti-CD132 mAb displayed a more naive phenotype in microarray-based analyses and showed reduced Janus kinase 3 (JAK3) phosphorylation upon activation. Consistent with a role of JAK3 in GVHD, Jak3(-/-) T cells caused less severe GVHD. Additionally, anti-CD132 mAb treatment of established chronic GVHD reversed liver and lung fibrosis, and pulmonary dysfunction characteristic of bronchiolitis obliterans. We conclude that acute GVHD and chronic GVHD, caused by T cells activated by common γ-chain cytokines, each represent therapeutic targets for anti-CD132 mAb immunomodulation. PMID:25352130

  10. The Association between ESR and CRP and Systemic Hypertension in Sarcoidosis.

    PubMed

    Mirsaeidi, Mehdi; Omar, Hesham R; Ebrahimi, Golnaz; Campos, Micheal

    2016-01-01

    Introduction. The association between the level of systemic inflammation and systemic hypertension (sHTN) among subjects with sarcoidosis has not been previously explored. Methods. A retrospective study was conducted to investigate the relation between the level of systemic inflammation in sarcoidosis, measured by various serum inflammatory markers, and sHTN. Results. Among a total of 108 cases with sarcoidosis (mean age: 53.4 years, 76.9% females), 55 (50.9%) had sHTN and 53 (49.1%) were normotensive. ESR was highly associated with sHTN. The patients with sHTN had higher mean ESR levels compared with normotensives (48.8 ± 35 versus 23.2 ± 27 mm/hr, resp.; P = 0.001). ROC curve analysis for ESR revealed an AUC value of 0.795 (95% CI: 0.692-0.897; P = 0.0001). With regard to CRP, there was a trend towards higher mean values in sHTN group (3.4 versus 1.7 mg/L; P = 0.067) and significantly higher prevalence of sHTN in the highest CRP quartile compared to the lowest one (69.6% versus 30%; OR 4.95; P = 0.017). ROC curve analysis for CRP revealed an AUC value of 0.644 (95% CI: 0.518-0.769; P = 0.03). On multivariate analysis, ESR and the CRP remained independent predictors for sHTN among subjects with sarcoidosis. Conclusion. Systemic inflammation is associated with the presence of sHTN in sarcoidosis. PMID:27433355

  11. The Association between ESR and CRP and Systemic Hypertension in Sarcoidosis

    PubMed Central

    Mirsaeidi, Mehdi; Omar, Hesham R.; Ebrahimi, Golnaz; Campos, Micheal

    2016-01-01

    Introduction. The association between the level of systemic inflammation and systemic hypertension (sHTN) among subjects with sarcoidosis has not been previously explored. Methods. A retrospective study was conducted to investigate the relation between the level of systemic inflammation in sarcoidosis, measured by various serum inflammatory markers, and sHTN. Results. Among a total of 108 cases with sarcoidosis (mean age: 53.4 years, 76.9% females), 55 (50.9%) had sHTN and 53 (49.1%) were normotensive. ESR was highly associated with sHTN. The patients with sHTN had higher mean ESR levels compared with normotensives (48.8 ± 35 versus 23.2 ± 27 mm/hr, resp.; P = 0.001). ROC curve analysis for ESR revealed an AUC value of 0.795 (95% CI: 0.692–0.897; P = 0.0001). With regard to CRP, there was a trend towards higher mean values in sHTN group (3.4 versus 1.7 mg/L; P = 0.067) and significantly higher prevalence of sHTN in the highest CRP quartile compared to the lowest one (69.6% versus 30%; OR 4.95; P = 0.017). ROC curve analysis for CRP revealed an AUC value of 0.644 (95% CI: 0.518–0.769; P = 0.03). On multivariate analysis, ESR and the CRP remained independent predictors for sHTN among subjects with sarcoidosis. Conclusion. Systemic inflammation is associated with the presence of sHTN in sarcoidosis. PMID:27433355

  12. Effects of chronic administration and withdrawal of antidepressant agents on circadian activity rhythms in rats.

    PubMed

    Wollnik, F

    1992-10-01

    Experimental and clinical studies indicate that clinical depression may be associated with disturbances of circadian rhythms. To explore the interaction between circadian rhythmicity, behavioral state, and monoaminergic systems, the present study investigated the effects of chronic administration and withdrawal of the following antidepressant agents on circadian wheel-running rhythms of laboratory rats: a) moclobemide, a reversible and selective monoamine oxidase (MAO) type A inhibitor; b) Ro 19-6327, a selective MAO type B inhibitor; c) desipramine, a preferential norepinephrine reuptake inhibitor; d) clomipramine and e) fluoxetine, both serotonin reuptake inhibitors; and f) levoprotiline, an atypical antidepressant whose biochemical mechanism is still unknown. Wheel-running activity rhythms were studied in three inbred strains of laboratory rats (ACI, BH, LEW) under constant darkness (DD). Two of these inbred strains (BH and LEW) show profound abnormalities in their circadian activity rhythms, namely, a reduced overall level of activity and bimodal or multimodal activity patterns. Chronic treatment with moclobemide and desipramine consistently increased the overall level, as well as the circadian amplitude, of the activity rhythm. Furthermore, the abnormal activity pattern of the LEW strain was changed into a unimodal activity pattern like that of other laboratory rats. The free-running period tau was slightly shortened by moclobemide and dramatically shortened by desipramine. Effects of moclobemide and desipramine treatment on overall activity level and duration were reversed shortly after termination of treatment, whereas long aftereffects were observed for the free-running period. All other substances tested had no systematic effects on the activity rhythms of any of the strains. The fact that moclobemide and desipramine altered the period, amplitude, and pattern of circadian activity rhythms is consistent with the hypothesis that monoaminergic transmitters

  13. European survey on the usefulness of /sup 67/Ga lung scans in assessing sarcoidosis. Experience in 14 research centers in seven different countries

    SciTech Connect

    Rizzato, G.; Blasi, A.

    1986-01-01

    Fifty-eight contributors from 12 European and 2 American sarcoidosis centers have collaborated in a survey to define many questions concerning the use of /sup 67/Ga lung scan in sarcoidosis. The new quantitative scoring methods based on digital evaluation seem better in detecting lung activity. In 20.1% of untreated patients, the /sup 67/Ga lung scan appeared to be the only noninvasive method with which clinical activity could be detected. /sup 67/Ga scans may be useful in guiding lung biopsy and in choosing pulmonary segments for BAL. Of 382 patients studied during follow-up (154 patients with three to nine scans at intervals of 2 to 12 months), the /sup 67/Ga scan was far more sensitive than chest radiography, both in detecting improvement and in foreseeing relapses. Steroid therapy appears to suppress ACE levels more than /sup 67/Ga uptake, and /sup 67/Ga uptake more than the alveolitis detectable by BAL. Gallium-67 uptake rebounds to positivity occur in about 40% of patients after steroid discontinuation and in about 20% of patients after steroid reduction to daily doses of 10 mg or less of prednisone. The /sup 67/Ga dose of 1.5 mCi seems appropriate for clinical purposes and is recommended for the subjective scoring method in order to reduce the cost and the radiation burden.

  14. Physical activity: benefit or weakness in metabolic adaptations in a mouse model of chronic food restriction?

    PubMed

    Méquinion, Mathieu; Caron, Emilie; Zgheib, Sara; Stievenard, Aliçia; Zizzari, Philippe; Tolle, Virginie; Cortet, Bernard; Lucas, Stéphanie; Prévot, Vincent; Chauveau, Christophe; Viltart, Odile

    2015-02-01

    In restrictive-type anorexia nervosa (AN) patients, physical activity is usually associated with food restriction, but its physiological consequences remain poorly characterized. In female mice, we evaluated the impact of voluntary physical activity with/without chronic food restriction on metabolic and endocrine parameters that might contribute to AN. In this protocol, FRW mice (i.e., food restriction with running wheel) reached a crucial point of body weight loss (especially fat mass) faster than FR mice (i.e., food restriction only). However, in contrast to FR mice, their body weight stabilized, demonstrating a protective effect of a moderate, regular physical activity. Exercise delayed meal initiation and duration. FRW mice displayed food anticipatory activity compared with FR mice, which was strongly diminished with the prolongation of the protocol. The long-term nature of the protocol enabled assessment of bone parameters similar to those observed in AN patients. Both restricted groups adapted their energy metabolism differentially in the short and long term, with less fat oxidation in FRW mice and a preferential use of glucose to compensate for the chronic energy imbalance. Finally, like restrictive AN patients, FRW mice exhibited low leptin levels, high plasma concentrations of corticosterone and ghrelin, and a disruption of the estrous cycle. In conclusion, our model suggests that physical activity has beneficial effects on the adaptation to the severe condition of food restriction despite the absence of any protective effect on lean and bone mass. PMID:25465889

  15. Change in trunk muscle activities with prone bridge exercise in patients with chronic low back pain

    PubMed Central

    Kong, Yong-soo; Park, Seol; Kweon, Mi-Gyong; Park, Ji-won

    2016-01-01

    [Purpose] The aim of this study was to determine the effect of three different bridge exercises on internal oblique, external oblique, transverse abdominis, and erector spinae activities. [Subjects and Methods] Forty-five subjects with chronic low back pain participated in this study. The training outcome was evaluated with three different testing methods: supine bridge exercise, supine bridge on Swiss ball exercise, and prone bridge exercise. The activities of the transverse abdominis, internal oblique, external oblique, and erector spinae were measured using surface electromyography. [Results] There were significant differences in the internal oblique, external oblique, and erector spinae according to the three kinds of bridging exercises. The internal oblique, external oblique and transverse abdominis activities were highest in the prone bridge exercise, followed by those in the supine bridge on Swiss ball exercise, and supine bridge exercises. The activity of erector spine was highest in the supine bridge on Swiss ball exercise followed by the supine bridge exercise and prone bridge exercise. [Conclusion] These results suggest that prone bridge exercise is more effective than conventional supine bridge exercise and supine bridge on Swiss ball in increasing trunk muscle activity of chronic low back pain patients. PMID:26957771

  16. 77 FR 43092 - Agency Information Collection Activities; Proposed Collection; Comment Request; Chronic Disease...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-23

    ... Collection; Comment Request; Chronic Disease Self-Management Education Program Standardized Data Collection... collection requirements relating to the Chronic Disease Self-Management Education Program. DATES: Submit... Disabilities through Chronic Disease Self-Management Education (CDSME) Programs'' cooperative agreement...

  17. Deficient activity of von Willebrand factor-cleaving protease in chronic relapsing thrombotic thrombocytopenic purpura.

    PubMed

    Furlan, M; Robles, R; Solenthaler, M; Wassmer, M; Sandoz, P; Lämmle, B

    1997-05-01

    In patients with thrombotic thrombocytopenic purpura (TTP), excessive intravascular platelet aggregation has been associated with appearance in plasma of unusually large von Willebrand factor (vWF) multimers. These extremely adhesive vWF multimers may arise due to deficiency of a "depolymerase" cleaving vWF to smaller molecular forms, either by reducing the interdimeric disulfide bridges or by proteolytic degradation. We studied the activity of a recently described vWF-cleaving protease in four patients with chronic relapsing TTP. Diluted plasma samples of TTP patients were incubated with purified normal human vWF in the presence of a serine protease inhibitor, at low ionic strength, and in the presence of urea and barium ions. The extent of vWF degradation was assayed by electrophoresis in sodium dodecyl sulfate-agarose gels and immunoblotting. Four patients, that included two brothers, with chronic relapsing TTP displayed either substantially reduced levels or a complete absence of vWF-cleaving protease activity. In none of these patient plasmas was an inhibitor of or an antibody against the vWF-cleaving protease established. Our data suggest that the unusually large vWF multimers found in TTP patients may be caused by deficient vWF-cleaving protease activity. Deficiency of this protease may be inherited in an autosomal recessive manner and seems to predispose to chronic relapsing TTP. The assay of the vWF-cleaving protease activity may be used as a sensitive diagnostic tool for identification of subjects with a latent TTP tendency. PMID:9129011

  18. Chronic enhancement of CREB activity in the hippocampus interferes with the retrieval of spatial information

    PubMed Central

    Viosca, Jose; Malleret, Gaël; Bourtchouladze, Rusiko; Benito, Eva; Vronskava, Svetlana; Kandel, Eric R.; Barco, Angel

    2009-01-01

    The activation of cAMP-responsive element-binding protein (CREB)-dependent gene expression is thought to be critical for the formation of different types of long-term memory. To explore the consequences of chronic enhancement of CREB function on spatial memory in mammals, we examined spatial navigation in bitransgenic mice that express in a regulated and restricted manner a constitutively active form of CREB, VP16-CREB, in forebrain neurons. We found that chronic enhancement of CREB activity delayed the acquisition of an allocentric strategy to solve the hidden platform task. The ability to turn on and off transgene expression allowed us to dissect the role of CREB in dissociable memory processes. In mice in which transgene expression was turned on during memory acquisition, turning off the transgene re-established the access to the memory trace, whereas in mice in which transgene expression was turned off during acquisition, turning on the transgene impaired memory expression in a reversible manner, indicating that CREB enhancement specifically interfered with the retrieval of spatial information. The defects on spatial navigation in mice with chronic enhancement of CREB function were not corrected by conditions that increased further CREB-dependent activation of hippocampal memory systems, such as housing in an enriched environment. These results along with previous findings in CREB-deficient mutants indicate that the relationship of CREB-mediated plasticity to spatial memory is an inverted-U function, and that optimal learning in the water maze requires accurate regulation of this pathway. PMID:19237642

  19. [Activity of beta-N-acetylglucosaminidase in chronic alcoholic liver disease].

    PubMed

    Pinto, C; Galvão-Teles, A; Monteiro, E; Marques, C; Azevedo, M; Manso, C

    1990-01-01

    Serum N-acetyl-B-glucosaminidase (NAG) activity was determined in a control group of 76 normal people and in 23 patients with hepatic cirrhosis: 15 non-compensated patients and 8 with compensated chronic liver fibrosis. NAG is significantly increased in the non-compensated group--mean value of 931.67 units vs 637.71 units for the controls (p less than 0.001). There is no significant elevation regarding the compensated group. No significant correlations were observed between NAG activity and hepatic functional tests. In the follow-up of the non-compensated group, NAG activity returned to normal with the clinical improvement; in 7 cases where this goal was not achieved there was elevation of NAG activity, with higher values in photo-systemic encephalopathy. PMID:2349891

  20. Vitamin D Receptor Activators and Clinical Outcomes in Chronic Kidney Disease

    PubMed Central

    Gravellone, Luciana; Rizzo, Maria Antonietta; Martina, Valentina; Mezzina, Nicoletta; Regalia, Anna; Gallieni, Maurizio

    2011-01-01

    Vitamin D deficiency appears to be an underestimated risk factor for cardiovascular disease in patients with chronic kidney disease. Evidence from both basic science and clinical studies supports the possible protective role of vitamin D beyond its effect on mineral metabolism. Toxicity of pharmacologic doses of active vitamin D metabolites, in particular calcitriol, is mainly due to the possibility of positive calcium and phosphorus balance. Therefore, vitamin D analogs have been developed, which suppress PTH secretion and synthesis with reduced calcemic and phosphatemic effects. Observational studies suggest that in hemodialysis patients the use of a vitamin D receptor (VDR) activator, such as calcitriol, doxercalciferol, paricalcitol, or alfacalcidol, is associated with a reduced mortality when compared with nonusers of any VDR activator. In this article the existing literature on the topic is reviewed, although a more robust answer to the question of whether or not VDR activators have beneficial effects in hemodialysis patients will hopefully come from a randomized controlled trial. PMID:21647319

  1. Peroxisome Proliferator-Activated Receptor γ Regulates Chronic Alcohol-Induced Alveolar Macrophage Dysfunction.

    PubMed

    Yeligar, Samantha M; Mehta, Ashish J; Harris, Frank L; Brown, Lou Ann S; Hart, C Michael

    2016-07-01

    Peroxisome proliferator-activated receptor (PPAR) γ is critical for alveolar macrophage (AM) function. Chronic alcohol abuse causes AM phagocytic dysfunction and susceptibility to respiratory infections by stimulating nicotinamide adenine dinucleotide oxidases (Nox), transforming growth factor-β1, and oxidative stress in the AM. Because PPARγ inhibits Nox expression, we hypothesized that alcohol reduces PPARγ, stimulating AM dysfunction. AMs were examined from: (1) patients with alcoholism or control patients; (2) a mouse model of chronic ethanol consumption; (3) PPARγ knockout mice; or (4) MH-S cells exposed to ethanol in vitro. Alcohol reduced AM PPARγ levels and increased Nox1, -2, and -4, transforming growth factor-β1, oxidative stress, and phagocytic dysfunction. Genetic loss of PPARγ recapitulated, whereas stimulating PPARγ activity attenuated alcohol-mediated alterations in gene expression and phagocytic function, supporting the importance of PPARγ in alcohol-induced AM derangements. Similarly, PPARγ activation in vivo reduced alcohol-mediated impairments in lung bacterial clearance. Alcohol increased levels of microRNA-130a/-301a, which bind to the PPARγ 3' untranslated region to reduce PPARγ expression. MicroRNA-130a/-301a inhibition attenuated alcohol-mediated PPARγ reductions and derangements in AM gene expression and function. Alcohol-induced Toll-like receptor 4 endocytosis was reversed by PPARγ activation. These findings demonstrate that targeting PPARγ provides a novel therapeutic approach for mitigating alcohol-induced AM derangements and susceptibility to lung infection. PMID:26677910

  2. Effects of active chronic cocaine use on cardiac sympathetic neuronal function assessed by carbon-11-hydroxyephedrine

    SciTech Connect

    Melon, P.G.; Boyd, C.J.; McVey, S. |

    1997-03-01

    Cardiac toxicity of cocaine has been linked to its inhibitory effect on norepinephrine reuptake by sympathetic nerve terminals of the heart. Carbon-11-hydroxyephedrine is a positron-emitting tracer that has been validated as a highly specific marker for norepinephrine transporter activity of the sympathetic nerve terminals and thus makes possible in vivo assessment of the effect of cocaine on norepinephrine reuptake and storage in the cardiac sympathetic nerve terminals. The aim of the study was to use the catecholamine analog {sup 11}C-hydroxyephedrine with PET to determine whether active chronic use of cocaine in women modifies the function of sympathetic nerve terminals of the heart. Six normal female volunteers and nine female active chronic cocaine users were studied. Cardiac regional {sup 11}C-hydroxyephedrine uptake and blood flow, as assessed with {sup 13}N-ammonia, were determined using semi-quantitative polar map analysis of myocardial tracer distribution. Carbon-11-hydroxyephedrine cardiac retention was quantified using dynamic data acquisition and kinetic analysis of blood and tissue activity. 27 refs., 4 figs., 3 tabs.

  3. The Case for Increased Physical Activity in Chronic Inflammatory Bowel Disease: A Brief Review.

    PubMed

    Shephard, R J

    2016-06-01

    Regular physical activity reduces the risk of colon cancer, but there is little information on the merits of such activity in the prevention and management of chronic inflammatory bowel disease (CIBD). The present systematic review thus documents current levels of habitual physical activity and aerobic and muscular function in CIBD, and examines the safety, practicality and efficacy of exercise programmes in countering the disease process, correcting functional deficits and enhancing quality of life. A systematic search of the Ovid/Medline database from January 1996 to May 2015 linked the terms physical activity/motor activity/physical fitness/physical training/physical education/training/exercise/exercise therapy with Crohn's disease/colitis/ulcerative colitis/inflammatory bowel disease, supplementing this information by a scanning of reference lists and personal files.12 of 16 published studies show a low level of habitual physical activity in CIBD, with sub-normal values for aerobic power, lean tissue mass and muscular strength. 3 of 4 studies suggest physical activity may reduce the risk of developing IBD, and 11 interventions all note that exercise programmes are well tolerated with some decreases of disease activity, and functional gains leading to an increased health-related quality of life. Moreover, programme compliance rates compare favourably with those seen in the treatment of other chronic conditions. More information on mechanisms is needed, but regular moderate aerobic and/or resistance exercise improves the health status of patients with CIBD both by modulating immune function and by improving physical function. A regular exercise programme should thus become an important component in the management of CIBD. PMID:27116344

  4. Radionuclide imaging in myocardial sarcoidosis. Demonstration of myocardial uptake of /sup 99m/Tc pyrophosphate and gallium

    SciTech Connect

    Forman, M.B.; Sandler, M.P.; Sacks, G.A.; Kronenberg, M.W.; Powers, T.A.

    1983-03-01

    A patient had severe congestive cardiomyopathy secondary to myocardial sarcoidosis. The clinical diagnosis was confirmed by radionuclide ventriculography, /sup 201/Tl, /sup 67/Ga, and /sup 99m/Tc pyrophosphate (TcPYP) scintigraphy. Myocardial TcPYP uptake has not been reported previously in sarcoidosis. In this patient, TcPYP was as useful as gallium scanning and thallium imaging in documenting the myocardial process.

  5. Cardiac sarcoidosis evaluated with gadolinium-enhanced magnetic resonance and contrast-enhanced 64-slice computed tomography.

    PubMed

    Smedema, Jan-Peter; Truter, Rene; de Klerk, Petra A; Zaaiman, Leonie; White, Leonie; Doubell, Anton F

    2006-09-20

    Sarcoidosis is a multi-system granulomatous disorder of unknown etiology with symptomatic cardiac involvement in up to 7% of patients. The clinical features of sarcoid heart disease include congestive heart failure, arrhythmias, conduction disturbances, and sudden death. We evaluated the value of contrast-enhanced multi-detector computed tomography in delineating myocardial scar and granulomatous inflammation by comparing our findings with gadolinium magnetic resonance in a patient diagnosed with cardiac sarcoidosis. PMID:16257460

  6. Activation of retinal tyrosine hydroxylase: tolerance induced by chronic treatment with haloperidol does not modify response to light

    SciTech Connect

    Cohen, J.; Neff, N.H.

    1982-05-01

    A single dose of haloperidol administered to rats in the dark increases the activity of retinal tyrosine hydroxylase. The ability of haloperidol to activate the enzyme is diminished 24 hr after terminating 22 to 30 days of treatment with haloperidol. The retinal enzyme is also tolerant to activation by treatment with chlorpromazine. In contrast, exposure of the animals to light activates the enzyme to the same extent in chronic haloperidol-treated and control animals. Thus, chronic haloperidol treatment does not modify the ability of the retinal enzyme system to respond to the physiological stimulus, light. Apparently, activation of retinol tyrosine hydroxylase by haloperidol and light occurs by independent mechanisms.

  7. Chronic activation of NPFFR2 stimulates the stress-related depressive behaviors through HPA axis modulation.

    PubMed

    Lin, Ya-Tin; Liu, Tzu-Yu; Yang, Ching-Yao; Yu, Yu-Lian; Chen, Ting-Chun; Day, Yuan-Ji; Chang, Che-Chien; Huang, Guo-Jen; Chen, Jin-Chung

    2016-09-01

    Neuropeptide FF (NPFF) is a morphine-modulating peptide that regulates the analgesic effect of opioids, and also controls food consumption and cardiovascular function through its interaction with two cognate receptors, NPFFR1 and NPFFR2. In the present study, we explore a novel modulatory role for NPFF-NPFFR2 in stress-related depressive behaviors. In a mouse model of chronic mild stress (CMS)-induced depression, the expression of NPFF significantly increased in the hypothalamus, hippocampus, medial prefrontal cortex (mPFC) and amygdala. In addition, transgenic (Tg) mice over-expressing NPFFR2 displayed clear depression and anxiety-like behaviors with hyperactivity in the hypothalamic-pituitary-adrenal (HPA) axis, reduced expression of glucocorticoid receptor (GR) and neurogenesis in the hippocampus. Furthermore, acute treatment of NPFFR2 agonists in wild-type (WT) mice enhanced the activity of the HPA axis, and chronic administration resulted in depressive and anxiety-like behaviors. Chronic stimulation of NPFFR2 also decreased the expression of hippocampal GR and led to persistent activation of the HPA axis. Strikingly, bilateral intra-paraventricular nucleus (PVN) injection of NPFFR2 shRNA predominately inhibits the depressive-like behavior in CMS-exposed mice. Antidepressants, fluoxetine and ketamine, effectively relieved the depressive behaviors of NPFFR2-Tg mice. We speculate that persistent NPFFR2 activation, in particular in the hypothalamus, up-regulates the HPA axis and results in long-lasting increases in circulating corticosterone (CORT), consequently damaging hippocampal function. This novel role of NPFFR2 in regulating the HPA axis and hippocampal function provides a new avenue for combating depression and anxiety-like disorder. PMID:27243477

  8. Motor control or graded activity exercises for chronic low back pain? A randomised controlled trial

    PubMed Central

    Macedo, Luciana G; Latimer, Jane; Maher, Chris G; Hodges, Paul W; Nicholas, Michael; Tonkin, Lois; McAuley, James H; Stafford, Ryan

    2008-01-01

    Background Chronic low back pain remains a major health problem in Australia and around the world. Unfortunately the majority of treatments for this condition produce small effects because not all patients respond to each treatment. It appears that only 25–50% of patients respond to exercise. The two most popular types of exercise for low back pain are graded activity and motor control exercises. At present however, there are no guidelines to help clinicians select the best treatment for a patient. As a result, time and money are wasted on treatments which ultimately fail to help the patient. Methods This paper describes the protocol of a randomised clinical trial comparing the effects of motor control exercises with a graded activity program in the treatment of chronic non specific low back pain. Further analysis will identify clinical features that may predict a patient's response to each treatment. One hundred and seventy two participants will be randomly allocated to receive either a program of motor control exercises or graded activity. Measures of outcome will be obtained at 2, 6 and 12 months after randomisation. The primary outcomes are: pain (average pain intensity over the last week) and function (patient-specific functional scale) at 2 and 6 months. Potential treatment effect modifiers will be measured at baseline. Discussion This trial will not only evaluate which exercise approach is more effective in general for patients will chronic low back pain, but will also determine which exercise approach is best for an individual patient. Trial registration number ACTRN12607000432415 PMID:18454877

  9. Validity of activity monitors in health and chronic disease: a systematic review

    PubMed Central

    2012-01-01

    The assessment of physical activity in healthy populations and in those with chronic diseases is challenging. The aim of this systematic review was to identify whether available activity monitors (AM) have been appropriately validated for use in assessing physical activity in these groups. Following a systematic literature search we found 134 papers meeting the inclusion criteria; 40 conducted in a field setting (validation against doubly labelled water), 86 in a laboratory setting (validation against a metabolic cart, metabolic chamber) and 8 in a field and laboratory setting. Correlation coefficients between AM outcomes and energy expenditure (EE) by the criterion method (doubly labelled water and metabolic cart/chamber) and percentage mean differences between EE estimation from the monitor and EE measurement by the criterion method were extracted. Random-effects meta-analyses were performed to pool the results across studies where possible. Types of devices were compared using meta-regression analyses. Most validation studies had been performed in healthy adults (n = 118), with few carried out in patients with chronic diseases (n = 16). For total EE, correlation coefficients were statistically significantly lower in uniaxial compared to multisensor devices. For active EE, correlations were slightly but not significantly lower in uniaxial compared to triaxial and multisensor devices. Uniaxial devices tended to underestimate TEE (−12.07 (95%CI; -18.28 to −5.85) %) compared to triaxial (−6.85 (95%CI; -18.20 to 4.49) %, p = 0.37) and were statistically significantly less accurate than multisensor devices (−3.64 (95%CI; -8.97 to 1.70) %, p<0.001). TEE was underestimated during slow walking speeds in 69% of the lab validation studies compared to 37%, 30% and 37% of the studies during intermediate, fast walking speed and running, respectively. The high level of heterogeneity in the validation studies is only partly explained by the type of activity

  10. The effect of task-oriented training on the muscle activation of the upper extremity in chronic stroke patients.

    PubMed

    Park, JuHyung

    2016-04-01

    [Purpose] The aim of this study was to determine the effects of task-oriented training on upper extremity muscle activation in daily activities performed by chronic stoke patients. [Subjects and Methods] In this research, task-oriented training was conducted by 2 chronic hemiplegic stroke patients. Task-oriented training was conducted 5 times a week, 30 minutes per day, for 2 weeks. Evaluation was conducted 3 times before and after the intervention. The Change of muscle activation in the upper extremity was measured using a BTS FreeEMG 300. [Results] The subjects' root mean square values for agonistic muscles for the reaching activity increased after the intervention. All subjects' co-coordination ratios decreased after the intervention in all movements of reaching activity. [Conclusion] Through this research, task-oriented training was proven to be effective in improving the muscle activation of the upper extremity in chronic hemiplegic stroke patients. PMID:27190488

  11. The effect of task-oriented training on the muscle activation of the upper extremity in chronic stroke patients

    PubMed Central

    Park, JuHyung

    2016-01-01

    [Purpose] The aim of this study was to determine the effects of task-oriented training on upper extremity muscle activation in daily activities performed by chronic stoke patients. [Subjects and Methods] In this research, task-oriented training was conducted by 2 chronic hemiplegic stroke patients. Task-oriented training was conducted 5 times a week, 30 minutes per day, for 2 weeks. Evaluation was conducted 3 times before and after the intervention. The Change of muscle activation in the upper extremity was measured using a BTS FreeEMG 300. [Results] The subjects’ root mean square values for agonistic muscles for the reaching activity increased after the intervention. All subjects’ co-coordination ratios decreased after the intervention in all movements of reaching activity. [Conclusion] Through this research, task-oriented training was proven to be effective in improving the muscle activation of the upper extremity in chronic hemiplegic stroke patients. PMID:27190488

  12. Patient and disease characteristics associated with activation for self-management in patients with diabetes, chronic obstructive pulmonary disease, chronic heart failure and chronic renal disease: a cross-sectional survey study.

    PubMed

    Bos-Touwen, Irene; Schuurmans, Marieke; Monninkhof, Evelyn M; Korpershoek, Yvonne; Spruit-Bentvelzen, Lotte; Ertugrul-van der Graaf, Inge; de Wit, Niek; Trappenburg, Jaap

    2015-01-01

    A substantial proportion of chronic disease patients do not respond to self-management interventions, which suggests that one size interventions do not fit all, demanding more tailored interventions. To compose more individualized strategies, we aim to increase our understanding of characteristics associated with patient activation for self-management and to evaluate whether these are disease-transcending. A cross-sectional survey study was conducted in primary and secondary care in patients with type-2 Diabetes Mellitus (DM-II), Chronic Obstructive Pulmonary Disease (COPD), Chronic Heart Failure (CHF) and Chronic Renal Disease (CRD). Using multiple linear regression analysis, we analyzed associations between self-management activation (13-item Patient Activation Measure; PAM-13) and a wide range of socio-demographic, clinical, and psychosocial determinants. Furthermore, we assessed whether the associations between the determinants and the PAM were disease-transcending by testing whether disease was an effect modifier. In addition, we identified determinants associated with low activation for self-management using logistic regression analysis. We included 1154 patients (53% response rate); 422 DM-II patients, 290 COPD patients, 223 HF patients and 219 CRD patients. Mean age was 69.6±10.9. Multiple linear regression analysis revealed 9 explanatory determinants of activation for self-management: age, BMI, educational level, financial distress, physical health status, depression, illness perception, social support and underlying disease, explaining a variance of 16.3%. All associations, except for social support, were disease transcending. This study explored factors associated with varying levels of activation for self-management. These results are a first step in supporting clinicians and researchers to identify subpopulations of chronic disease patients less likely to be engaged in self-management. Increased scientific efforts are needed to explain the greater

  13. AMP-activated protein kinase is essential for survival in chronic hypoxia.

    PubMed

    Borger, Darrell R; Gavrilescu, L Cristina; Bucur, Maria C; Ivan, Mircea; Decaprio, James A

    2008-05-30

    This study was undertaken to interrogate cancer cell survival during long-term hypoxic stress. Two systems with relevance to carcinogenesis were employed: Fully transformed BJ cells and a renal carcinoma cell line (786-0). The dynamic of AMPK activity was consistent with a prosurvival role during chronic hypoxia. This was further supported by the effects of AMPK agonists and antagonists (AICAR and compound C). Expression of a dominant-negative AMPK alpha resulted in a decreased ATP level and significantly compromised survival in hypoxia. Dose-dependent prosurvival effects of rapamycin were consistent with mTOR inhibition being a critical downstream mediator of AMPK in persistent low oxygen. PMID:18359290

  14. Aggressive Peripheral CD70-positive T-cell Lymphoma Associated with Severe Chronic Active EBV Infection

    PubMed Central

    Shaffer, Donald R.; Sheehan, Andrea M.; Yi, Zhongzhen; Rodgers, Cheryl C; Bollard, Catherine M; Brenner, Malcolm K; Rooney, Cliona M; Heslop, Helen E; Gottschalk, Stephen

    2011-01-01

    Severe chronic active Epstein-Barr virus infection (CAEBV) in T or NK cells is a rare complication of latent EBV infection. CAEBV associated T-cell lymphoproliferative disease (LPD) consists of polyclonal lesions as well as aggressive lymphomas. Here we report such a patient. In addition, we show that this primary CAEBV associated T-cell lymphoma expresses CD70 and is sensitive to killing by CD70-specific T cells, identifying CD70 as a potential immunotherapeutic target for CAEBV-associated T-cell lymphoma. PMID:21994111

  15. Protective effect of carnosine after chronic cerebral hypoperfusion possibly through suppressing astrocyte activation

    PubMed Central

    Ma, Jing; Chen, Jihui; Bo, Shuhong; Lu, Xiaotong; Zhang, Jian

    2015-01-01

    Aim: Subcortical ischemic vascular dementia (SIVD) induced by chronic hypoperfusion is a common cause of vascular dementia. The aim of this study was to determine whether the protective effect of carnosine on white matter lesion after chronic cerebral hypoperfusion through suppressing astrocyte activation. Methods: Adult male mice (C57BL/6 strain) were subjected to permanent occlusion of the right unilateral common carotid arteries (rUCCAO) and treated with carnosine or histidine. Open field test, freezing test, Klüver-Barrera staining, immunohistochemical analyses and western blot were performed after rUCCAO. Results: We found that carnosine ameliorated white matter lesion and cognitive impairment after rUCCAO. Carnosine suppressed the activation of astrocyte in both wide type mice and histidine decarboxylase knockout mice. However, administration of histidine did not show the same effect. We found that there were no differences between rUCCAO group and sham group for the expression of glutamate transporter-1 (GLT-1) and glutamate/aspartate transporter (GLAST). Furthermore, carnosine significantly attenuated the increase of inflammatory cytokine interferon gama. Conclusion: These data suggest carnosine induced neuroprotection during SIVD in mice is not dependent on the histaminergic pathway or the regulation of the expression of GLT-1 and GLAST, but may be due to a suppression of astrocyte activation and inflammatory cytokine release. PMID:26885268

  16. The electricidal effect is active in an experimental model of Staphylococcus epidermidis chronic foreign body osteomyelitis.

    PubMed

    Del Pozo, Jose L; Rouse, Mark S; Euba, Gorane; Kang, Cheol-In; Mandrekar, Jayawant N; Steckelberg, James M; Patel, Robin

    2009-10-01

    Treatment with low-amperage (200 microA) electrical current was compared to intravenous doxycycline treatment or no treatment in a rabbit model of Staphylococcus epidermidis chronic foreign body osteomyelitis to determine if the electricidal effect is active in vivo. A stainless steel implant and 10(4) CFU of planktonic S. epidermidis were placed into the medullary cavity of the tibia. Four weeks later, rabbits were assigned to one of three groups with treatment administered for 21 days. The groups included those receiving no treatment (n = 10), intravenous doxycycline (n = 14; 8 mg/kg of body weight three times per day), and electrical current (n = 15; 200 microA continuous delivery). Following treatment, rabbits were sacrificed and the tibias quantitatively cultured. Bacterial load was significantly reduced in the doxycycline (median, 2.55 [range, 0.50 to 6.13] log10 CFU/g of bone) and electrical-current (median, 1.09 [range, 0.50 to 2.99] log10 CFU/g of bone) groups, compared to the level for the control group (median, 4.16 [range, 3.70 to 5.66] log10 CFU/g of bone) (P < 0.0001). Moreover, treatment with electrical current was statistically significantly more efficacious (P = 0.035) than doxycycline treatment. The electricidal effect (the bactericidal activity of low-amperage electrical current against bacterial biofilms) is active in vivo in the treatment of experimental S. epidermidis chronic foreign body osteomyelitis. PMID:19651912

  17. Effect of Chronic Athletic Activity on Brown Fat in Young Women

    PubMed Central

    Singhal, Vibha; Maffazioli, Giovana D.; Ackerman, Kate E.; Lee, Hang; Elia, Elisa F.; Woolley, Ryan; Kolodny, Gerald; Cypess, Aaron M.; Misra, Madhusmita

    2016-01-01

    Background The effect of chronic exercise activity on brown adipose tissue (BAT) is not clear, with some studies showing positive and others showing negative associations. Chronic exercise is associated with increased resting energy expenditure (REE) secondary to increased lean mass and a probable increase in BAT. Many athletes are in a state of relative energy deficit suggested by lower fat mass and hypothalamic amenorrhea. States of severe energy deficit such as anorexia nervosa are associated with reduced BAT. There are no data regarding the impact of chronic exercise activity on BAT volume or activity in young women and it is unclear whether relative energy deficiency modifies the effects of exercise on BAT. Purpose We assessed cold induced BAT volume and activity in young female athletes compared with non-athletes, and further evaluated associations of BAT with measures of REE, body composition and menstrual status. Methods The protocol was approved by our Institutional Review Board. Written informed consent was obtained from all participants prior to study initiation. This was a cross-sectional study of 24 women (16 athletes and8 non-athletes) between 18–25 years of age. Athletes were either oligo-amenorrheic (n = 8) or eumenorrheic (n = 8).We used PET/CT scans to determine cold induced BAT activity, VMAX Encore 29 metabolic cart to obtain measures of REE, and DXA for body composition. Results Athletes and non-athletes did not differ for age or BMI. Compared with non-athletes, athletes had lower percent body fat (p = 0.002), higher percent lean mass (p = 0.01) and trended higher in REE (p = 0.09). BAT volume and activity in athletes trended lower than in non-athletes (p = 0.06; p = 0.07, respectively). We found negative associations of BAT activity with duration of amenorrhea (r = -0.46, p = 0.02).BAT volume correlated inversely with lean mass (r = -0.46, p = 0.02), and positively with percent body fat, irisin and thyroid hormones. Conclusions Our study

  18. Anticancer activity of Pupalia lappacea on chronic myeloid leukemia K562 cells

    PubMed Central

    2012-01-01

    Background Cancer is one of the most prominent human diseases which has enthused scientific and commercial interest in the discovery of newer anticancer agents from natural sources. Here we demonstrated the anticancer activity of ethanolic extract of aerial parts of Pupalia lappacea (L) Juss (Amaranthaceae) (EAPL) on Chronic Myeloid Leukemia K562 cells. Methods Antiproliferative activity of EAPL was determined by MTT assay using carvacrol as a positive control. Induction of apoptosis was studied by annexin V, mitochondrial membrane potential, caspase activation and cell cycle analysis using flow cytometer and modulation in protein levels of p53, PCNA, Bax and Bcl2 ratio, cytochrome c and cleavage of PARP were studied by Western blot analysis. The standardization of the extract was performed through reverse phase-HPLC using Rutin as biomarker. Results The results showed dose dependent decrease in growth of K562 cells with an IC50 of 40 ± 0.01 μg/ml by EAPL. Induction of apoptosis by EAPL was dose dependent with the activation of p53, inhibition of PCNA, decrease in Bcl2/Bax ratio, decrease in the mitochondrial membrane potential resulting in release of cytochrome c, activation of multicaspase and cleavage of PARP. Further HPLC standardization of EAPL showed presence 0.024% of Rutin. Conclusion Present study significantly demonstrates anticancer activity of EAPL on Chronic Myeloid Leukemia (K562) cells which can lead to potential therapeutic agent in treating cancer. Rutin, a known anti cancer compound is being reported and quantified for the first time from EAPL. PMID:23351440

  19. Activation of pulmonary and lymph node dendritic cells during chronic Pseudomonas aeruginosa lung infection in mice.

    PubMed

    Damlund, Dina Silke Malling; Christophersen, Lars; Jensen, Peter Østrup; Alhede, Morten; Høiby, Niels; Moser, Claus

    2016-06-01

    The majority of cystic fibrosis (CF) patients acquire chronic Pseudomonas aeruginosa lung infection, resulting in increased mortality and morbidity. The chronic P. aeruginosa lung infection is characterized by bacteria growing in biofilm surrounded by polymorphonuclear neutrophils (PMNs). However, the infection is not eradicated and the inflammatory response leads to gradual degradation of the lung tissue. In CF patients, a Th2-dominated adaptive immune response with a pronounced antibody response is correlated with poorer outcome. Dendritic cells (DCs) are crucial in bridging the innate immune system with the adaptive immune response. Once activated, the DCs deliver a set of signals to uncommitted T cells that induce development, such as expansion of regulatory T cells and polarization of Th1, Th2 or Th17 subsets. In this study, we characterized DCs in lungs and regional lymph nodes in BALB/c mice infected using intratracheal installation of P. aeruginosa embedded in seaweed alginate in the lungs. A significantly elevated concentration of DCs was detected earlier in the lungs than in the regional lymph nodes. To evaluate whether the chronic P. aeruginosa lung infection leads to activation of DCs, costimulatory molecules CD80 and CD86 were analyzed. During infection, the DCs showed significant elevation of CD80 and CD86 expression in both the lungs and the regional lymph nodes. Interestingly, the percentage of CD86-positive cells was significantly higher than the percentage of CD80-positive cells in the lymph nodes. In addition, cytokine production from Lipopolysaccharides (LPS)-stimulated DCs was analyzed demonstrating elevated production of IL-6, IL-10 and IL-12. However, production of IL-12 was suppressed earlier than IL-6 and IL-10. These results support that DCs are involved in skewing of the Th1/Th2 balance in CF and may be a possible treatment target. PMID:27009697

  20. A Survey on the Willingness to Use Physical Activity Smartphone Applications (Apps) in Patients with Chronic Diseases.

    PubMed

    Sun, Liu; Jiao, Chen; Wang, Yanling; Xiao, Qian; Zhang, Yiling; Wu, Ying

    2016-01-01

    This study aimed to explore the willingness of using physical activity smartphone apps among patients with chronic diseases. 218 outpatients from a tertiary hospital in Beijing were involved using a questionnaire. Over half of the patients (53.7%) were willing to use smartphone apps to promote physical activities. The individuals more likely to use physical activity apps tended to be younger (≤44 years), be more educated, perceiving their disease need exercise instruction or professional support, current smartphone user, having previous experience of using physical activity apps, and accepting paid apps (P<0.05). The results could help health educator suggest chronic disease patients to use apps to do more exercises. Further research could be focus on evaluate the effects of using physical activity apps in chronic disease patients. PMID:27332468

  1. Stretch-activated channels in pulmonary arterial smooth muscle cells from normoxic and chronically hypoxic rats.

    PubMed

    Ducret, Thomas; El Arrouchi, Jalila; Courtois, Arnaud; Quignard, Jean-François; Marthan, Roger; Savineau, Jean-Pierre

    2010-11-01

    Stretch-activated channels (SACs) act as membrane mechanotransducers since they convert physical forces into biological signals and hence into a cell response. Pulmonary arterial smooth muscle cells (PASMCs) are continuously exposed to mechanical stimulations e.g., compression and stretch, that are enhanced under conditions of pulmonary arterial hypertension (PAH). Using the patch-clamp technique (cell-attached configuration) in PASMCs, we showed that applying graded negative pressures (from 0 to -60 mmHg) to the back end of the patch pipette increases occurrence and activity of SACs. The current-voltage relationship (from -80 to +40 mV) was almost linear with a reversal potential of 1 mV and a slope conductance of 34 pS. SACs were inhibited in the presence of GsMTx-4, a specific SACs blocker. Using microspectrofluorimetry (indo-1), we found that hypotonic-induced cell swelling increases intracellular Ca(2+) concentration ([Ca(2+)](i)). This [Ca(2+)](i) increase was markedly inhibited in the absence of external Ca(2+) or in the presence of the following blockers of SACs: gadolinium, streptomycin, and GsMTx-4. Interestingly, in chronically hypoxic rats, an animal model of PAH, SACs were more active and hypotonic-induced calcium response in PASMCs was significantly higher (nearly a two-fold increase). Moreover, unlike in normoxic rats, intrapulmonary artery rings from hypoxic rats mounted in a Mulvany myograph, exhibited a myogenic tone sensitive to SAC blockers. In conclusion, this work demonstrates that SACs in rat PASMCs can be activated by membrane stretch as well as hypotonic stimulation and are responsible for [Ca(2+)](i) increase. The link between SACs activation-induced calcium response and myogenic tone in chronically hypoxic rats suggests that SACs are an important element for the increased pulmonary vascular tone in PAH and that they may represent a molecular target for PAH treatment. PMID:21035852

  2. Acute and chronic caffeine administration increases physical activity in sedentary adults.

    PubMed

    Schrader, Patrick; Panek, Leah M; Temple, Jennifer L

    2013-06-01

    Caffeine is a commonly used stimulant thought to have ergogenic properties. Most studies on the ergogenic effects of caffeine have been conducted in athletes. The purpose of this study was to test the hypothesis that caffeine reduces ratings of perceived exertion and increases liking of physical activity in sedentary adults. Participants completed treadmill walking at 60% to 70% of their maximal heart rate at baseline and for 6 subsequent visits, during which half of the participants were given caffeine (3 mg/kg) and half given placebo in a sports drink vehicle. To investigate the potential synergistic effects of acute and chronic caffeine on self-determined exercise duration, participants were rerandomized to either the same or different condition for the last visit, creating 4 chronic/acute treatment groups (placebo/placebo, placebo/caffeine, caffeine/placebo, caffeine/caffeine). Participants rated how much they liked the activity and perceived exertion at each visit. There was a main effect of time on liking of physical activity, with liking increasing over time and an interaction of sex and caffeine treatment on liking, with liking of activity increasing in female participants treated with caffeine, but not with placebo. There was no effect of caffeine on ratings of perceived exertion. Individuals who received caffeine on the final test day exercised for significantly longer than those who received placebo. These data suggest that repeated exposure to physical activity significantly increases liking of exercise and reduces ratings of perceived exertion and that caffeine does little to further modify these effects. PMID:23746561

  3. Rifapentine Is Not More Active than Rifampin against Chronic Tuberculosis in Guinea Pigs

    PubMed Central

    Dutta, Noton K.; Illei, Peter B.; Peloquin, Charles A.; Pinn, Michael L.; Mdluli, Khisimuzi E.; Nuermberger, Eric L.; Grosset, Jacques H.

    2012-01-01

    Rifamycins are key sterilizing drugs in the current treatment of active tuberculosis (TB). Daily dosing of rifapentine (P), a potent rifamycin with high intracellular accumulation, in place of rifampin (R) in the standard antitubercular regimen significantly shortens the duration of treatment needed to prevent relapse in a murine model of active TB. We undertook the current study to compare directly the activities of human-equivalent doses of P and R in a guinea pig model of chronic TB, in which bacilli are predominantly extracellular within human-like necrotic granulomas. Hartley strain guinea pigs were aerosol infected with ∼200 bacilli of Mycobacterium tuberculosis H37Rv, and treatment given 5 days/week was initiated 6 weeks later. R at 100 mg/kg of body weight and P at 100 mg/kg were given orally alone or in combination with isoniazid (H) at 60 mg/kg and pyrazinamide (Z) at 300 mg/kg. Culture-positive relapse was assessed in subgroups of guinea pigs after completion of 1 and 2 months of treatment. Human-equivalent doses of R and P showed equivalent bactericidal activity when used alone and in combination therapy. In guinea pigs treated with rifampin, isoniazid, and pyrazinamide (RHZ) or PHZ, microbiological relapse occurred in the lungs of 8/10 animals treated for 1 month and in 0/10 animals treated for 2 months. Substitution of P for R in the standard antitubercular regimen did not shorten the time to cure in this guinea pig model of chronic TB. Data from ongoing clinical trials comparing the activity of these two drugs are awaited to determine the relevance of the guinea pig TB model in preclinical drug screening. PMID:22547623

  4. The Effects of Chronic Achievement Motivation and Achievement Primes on the Activation of Achievement and Fun Goals

    PubMed Central

    Hart, William; Albarracín, Dolores

    2013-01-01

    This research examined the hypothesis that situational achievement cues can elicit achievement or fun goals depending on chronic differences in achievement motivation. In 4 studies, chronic differences in achievement motivation were measured, and achievement-denoting words were used to influence behavior. The effects of these variables were assessed on self-report inventories, task performance, task resumption following an interruption, and the pursuit of means relevant to achieving or having fun. Findings indicated that achievement priming (vs. control priming) activated a goal to achieve and inhibited a goal to have fun in individuals with chronically high-achievement motivation but activated a goal to have fun and inhibited a goal to achieve in individuals with chronically low-achievement motivation. PMID:19968423

  5. Chronic ethanol consumption inhibits glucokinase transcriptional activity by Atf3 and triggers metabolic syndrome in vivo.

    PubMed

    Kim, Ji Yeon; Hwang, Joo-Yeon; Lee, Dae Yeon; Song, Eun Hyun; Park, Keon Jae; Kim, Gyu Hee; Jeong, Eun Ae; Lee, Yoo Jeong; Go, Min Jin; Kim, Dae Jin; Lee, Seong Su; Kim, Bong-Jo; Song, Jihyun; Roh, Gu Seob; Gao, Bin; Kim, Won-Ho

    2014-09-26

    Chronic ethanol consumption induces pancreatic β-cell dysfunction through glucokinase (Gck) nitration and down-regulation, leading to impaired glucose tolerance and insulin resistance, but the underlying mechanism remains largely unknown. Here, we demonstrate that Gck gene expression and promoter activity in pancreatic β-cells were suppressed by chronic ethanol exposure in vivo and in vitro, whereas expression of activating transcription factor 3 (Atf3) and its binding to the putative Atf/Creb site (from -287 to -158 bp) on the Gck promoter were up-regulated. Furthermore, in vitro ethanol-induced Atf3 inhibited the positive effect of Pdx-1 on Gck transcriptional regulation, enhanced recruitment of Hdac1/2 and histone H3 deacetylation, and subsequently augmented the interaction of Hdac1/Pdx-1 on the Gck promoter, which were diminished by Atf3 siRNA. In vivo Atf3-silencing reversed ethanol-mediated Gck down-regulation and β-cell dysfunction, followed by the amelioration of impaired glucose tolerance and insulin resistance. Together, we identified that ethanol-induced Atf3 fosters β-cell dysfunction via Gck down-regulation and that its loss ameliorates metabolic syndrome and could be a potential therapeutic target in treating type 2 diabetes. The Atf3 gene is associated with the induction of type 2 diabetes and alcohol consumption-induced metabolic impairment and thus may be the major negative regulator for glucose homeostasis. PMID:25074928

  6. Gallium-67 scintigraphy, bronchoalveolar lavage, and pathologic changes in patients with pulmonary sarcoidosis

    SciTech Connect

    Abe, S.; Munakata, M.; Nishimura, M.; Tsuneta, Y.; Terai, T.; Nakano, I.; Ohsaki, Y.; Kawakami, Y.

    1984-05-01

    The intensity of gallium-67 scintiscans, lymphocyte counts in bronchoalveolar lavage fluid, and pathologic changes were studied in 26 patients with untreated pulmonary sarcoidosis. Noncaseating granulomas were recognized with significantly greater frequency in stage 2 (80 percent; 8/10 cases) than in stage 1 (43 percent; 6/14 cases). Alveolitis showed little relation to the roentgenographic stage. There was a strong correlation between the intensity of gallium uptake in pulmonary parenchyma and the detection rate of granuloma; however, the detection rate of alveolitis was not statistically different from the intensity of gallium uptake. A highly significant correlation was revealed between the lymphocyte counts in bronchoalveolar lavage fluid and the intensity of alveolitis. These observations suggest that the gallium uptake reflects mainly the presence of granuloma, and the lymphocyte count in bronchoalveolar lavage fluid reflects the intensity of alveolitis in patients with pulmonary sarcoidosis.

  7. A rare manifestation of sarcoidosis with sensomotoric neuropathy of the ulnar nerve as the only symptom

    PubMed Central

    Mattiassich, Georg; Schubert, Heinrich; Hutarew, Georg; Wechselberger, Gottfried

    2012-01-01

    A 79-year-old woman was admitted complaining of progressive weakness and numbness of the right hand. The patient was otherwise healthy. The patient's history was unremarkable. Clinical and electrophysiological examination revealed a compression of the ulnar nerve in the ulnar sulcus and in Guyon's canal. Ultrasound evaluation showed a suspicious tumour proximal to the elbow close to the ulnar nerve. The ulnar sulcus was then released and an epineural and perineural lesion 3–4 cm proximal to the sulcus was excised under microscope. The histopathology confirmed the lesion as non-caseating sarcoid granulomas. The patient showed no other signs of systemic sarcoidosis, as neuropathy was the only symptom and the condition improved postoperatively. Sensory deficits and paraesthesia resolved fully. The extension of the minor finger remained slightly inferior compared with the not affected side. Sarcoid neuropathy is a rare neurological complication of sarcoidosis and has to be included in differential diagnosis of nerve conduction impairments. PMID:23192580

  8. Polarizable Material from a Conjunctival Biopsy in a Patient with Sarcoidosis

    PubMed Central

    Ali, Omair B.; Deroque, Ryan; Morshedi, R. Grant; Brown, Harry

    2016-01-01

    Purpose Conjunctival biopsies may contain polarizable material in patients with sarcoidosis despite no history of prior trauma or eye surgeries. Procedures A 39-year-old male with uveitic glaucoma presented with decreased vision and throbbing pain in his right eye. His intraocular pressure was elevated, and his vision was reduced to hand motion. Due to persistently elevated intraocular pressure refractory to medical treatment, the patient underwent a glaucoma drainage device procedure. During the procedure, a yellow, nodular conjunctival growth was noted and biopsied. Results Histopathological examination revealed multiple nonnecrotizing granulomata, some of which contained polarizable material. Conclusions Biopsies of patients with sarcoidosis may contain polarizable material without evidence of foreign body inoculation. PMID:27239467

  9. Gastric involvement of sarcoidosis in a patient with multiple lung nodules

    PubMed Central

    Ceylan, Emel; Şen, Serdar; Coşkun, Adil; Meteoğlu, İbrahim; Demirtaş, Nimet; Çildağ, Orhan

    2015-01-01

    Sarcoidosis is a granulomatous disorder mostly could involve intrathoracic structures. The gastric involvement is rare and the symptoms may be non-specific. We herein report a case of a 56-year-old female patient who was admitted due to chest tightness and discomfort. Computed tomography (CT) of the thorax revealed bilaterally nodular lesions in the lower lobes of the lung and pleural effusion on the left side. Positron emission tomography/CT showed lung nodules and gastric involvement with mesenteric lymphadenomegalies with pathological uptake of 18F-fluoro-2-deoxy-d-glucose. Pathological examination of the lung biopsy taken by thoracotomy demonstrated non-caseating granulomas. The gastric biopsies taken by endoscopy also showed non-caseating granulomas consistent with a diagnosis of sarcoidosis. PMID:26487882

  10. A rare manifestation of sarcoidosis with sensomotoric neuropathy of the ulnar nerve as the only symptom.

    PubMed

    Mattiassich, Georg; Schubert, Heinrich; Hutarew, Georg; Wechselberger, Gottfried

    2012-01-01

    A 79-year-old woman was admitted complaining of progressive weakness and numbness of the right hand. The patient was otherwise healthy. The patient's history was unremarkable. Clinical and electrophysiological examination revealed a compression of the ulnar nerve in the ulnar sulcus and in Guyon's canal. Ultrasound evaluation showed a suspicious tumour proximal to the elbow close to the ulnar nerve. The ulnar sulcus was then released and an epineural and perineural lesion 3-4 cm proximal to the sulcus was excised under microscope. The histopathology confirmed the lesion as non-caseating sarcoid granulomas. The patient showed no other signs of systemic sarcoidosis, as neuropathy was the only symptom and the condition improved postoperatively. Sensory deficits and paraesthesia resolved fully. The extension of the minor finger remained slightly inferior compared with the not affected side. Sarcoid neuropathy is a rare neurological complication of sarcoidosis and has to be included in differential diagnosis of nerve conduction impairments. PMID:23192580

  11. Concomitant Systemic Sclerosis and Sarcoidosis with Combined Pulmonary Fibrosis and Emphysema.

    PubMed

    Koguchi, Nobuo; Okada, Asuka; Choh, Sumito; Katayama, Kumiko; Takenaka, Hideaki; Tomoda, Koichi; Kimura, Hiroshi

    2016-01-01

    A 75-year-old woman was referred to our hospital with the chief symptom of dyspnea. Chest computed tomography revealed lymphadenopathy, emphysema, and honeycombing. Sarcoidosis was diagnosed due to an elevated serum ACE level and the findings of a lymph-node biopsy. Her smoking history, radiography findings, and impaired gas exchange indicated combined pulmonary fibrosis and emphysema (CPFE). Raynaud's phenomenon gradually appeared, and we also diagnosed her with systemic sclerosis (SSc). Right heart catheterization revealed pulmonary hypertension (PH). Smoking was assumed to be the chief cause, but SSc may also induce the development of CPFE. Severe PH induced by CPFE or SSc was present, but the influence of sarcoidosis also could not be ignored. PMID:27181542

  12. Expression of executioner procaspases and their activation by a procaspase-activating compound in chronic lymphocytic leukemia cells

    PubMed Central

    Patel, Viralkumar; Balakrishnan, Kumudha; Keating, Michael J.; Wierda, William G.

    2015-01-01

    Intrinsic and extrinsic apoptotic pathways converge to activate common downstream executioner caspases (caspase-3, -6, and -7), resulting in cell death. In chronic lymphocytic leukemia (CLL), neoplastic B cells evade apoptosis owing to the overexpression of survival proteins. We hypothesized that direct activation of procaspases could bypass the apoptosis resistance induced by the upstream prosurvival proteins. The procaspase-activating compounds (PAC-1), including B-PAC-1 (L14R8), convert inactive executioner procaspases to their active cleaved forms by chelation of labile zinc ions. Both at transcript and protein levels, primary CLL cells express high levels of latent procaspases (3, -7, and -9). B-PAC-1 treatment induced CLL lymphocyte death which was higher than that in normal peripheral blood mononuclear cells or B cells, and was independent of prognostic markers and microenvironmental factors. Mechanistically, B-PAC-1 treatment activated executioner procaspases and not other Zn-dependent enzymes. Exogenous zinc completely, and pancaspase inhibitors partially, reversed B-PAC-1–induced apoptosis, elucidating the zinc-mediated mechanism of action. The cell demise relied on the presence of caspase-3/7 but not caspase-8 or Bax/Bak proteins. B-PAC-1 in combination with an inhibitor of apoptosis protein antagonist (Smac066) synergistically induced apoptosis in CLL samples. Our investigations demonstrated that direct activation of executioner procaspases via B-PAC-1 treatment bypasses apoptosis resistance and is a novel approach for CLL therapeutics. PMID:25538042

  13. Reducing infection in chronic leg ulcers with an activated carbon cloth dressing.

    PubMed

    Murphy, Nina

    2016-06-23

    Zorflex is a new type of antimicrobial dressing composed of 100% activated carbon cloth. It attracts and binds bacteria to its surface, enabling them to be safely removed at dressing change. It has no reported toxic effects and can be used on either a short-or long-term basis. This article describes 4 case studies in which patients with recalcitrant chronic venous leg ulcers that were prone to recurrent infection were treated with the activated carbon cloth dressing. All of the wounds had failed to respond to antimicrobial dressings containing silver, iodine or polyhexamethylene biguanide (PHMB), and were heavily exuding and painful. In all cases, the signs of infection reduced significantly within 4 weeks, resulting in good patient outcomes. PMID:27345081

  14. Reversibility by dipyridamole of thallium-201 myocardial scan defects in patients with sarcoidosis

    SciTech Connect

    Tellier, P.; Paycha, F.; Antony, I.; Nitenberg, A.; Valeyre, D.; Foult, J.M.; Battesti, J.P.

    1988-08-01

    In order to clarify the significance of anginal pain and myocardial thallium-201 scan defects in cardiac sarcoidosis, the pharmacologic effect of dipyridamole on myocardial perfusion was assessed by planar thallium-201 myocardial scintigraphy in patients with sarcoidosis. Thallium-201 myocardial scintigraphy was performed at rest and after 0.56 mg/kg intravenous dipyridamole during four minutes in 16 patients with sarcoidosis. The myocardial scan (45-degree and 70-degree left anterior oblique, and anterior views) was divided into 15 segments. Results were evaluated by the number of segmental defects and with a global perfusion score (from 0 to 60) by a semi-quantitative index depending on the size and severity of myocardial thallium-201 defects. Thirteen of the 16 patients showed partial or total reversion of their thallium-201 defects on redistribution scanning either at rest or after dipyridamole. The mean (+/- SD) number of myocardial perfusion defects that were present in all the patients decreased from 5.31 +/- 1.78 at rest to 3.25 +/- 2.52 after redistribution (p less than 0.001) and to 2.19 +/- 2.10 after dipyridamole (p less than 0.001). The mean global perfusion score increased from 53.2 +/- 3.0 at rest to 56.2 +/- 2.9 after redistribution (p less than 0.001) and to 57.2 +/- 2.7 after dipyridamole (p less than 0.001). A significant correlation (r = 0.82, p less than 0.001) was found between the increase of global perfusion score on redistribution and after dipyridamole. The reversibility of myocardial scan defects is a common finding in sarcoidosis. It makes unlikely the role of scar fibrosis or extensive confluent granulomas as a mechanism for such defects. The effect of dipyridamole suggests the presence of reversible disorders lying at the coronary microvascular level.

  15. The Kmif (Kveim-induced macrophage migration inhibition factor) test in sarcoidosis

    PubMed Central

    Williams, W. Jones; Pioli, E.; Jones, D. J.; Dighero, M.

    1972-01-01

    Circulating lymphocytes from 30 patients with sarcoidosis when stimulated in vitro with Kveim-induced macrophage migration factor, the Kmif test, produced a guinea-pig macrophage migration inhibition factor in 21 of 30 cases (70%). In those patients not on steroids the results showed a good correlation with the cutaneous Kveim test. One positive test was found in 16 normal subjects. Our results suggest that the Kmif test may prove a useful rapid alternative to the Kveim test. PMID:4675181

  16. Increasing physical activity of high intensity to reduce the prevalence of chronic diseases and improve public health.

    PubMed

    Rehn, Tommy Aune; Winett, Richard A; Wisløff, Ulrik; Rognmo, Oivind

    2013-01-01

    High incidence and prevalence of chronic diseases, increasing obesity and inactivity as well as rising health expenditure represent a set of developments that cannot be considered sustainable, and will have dire long-term consequences given the increasing proportion of elderly people in our society. Based on a review of the experiences from previous large scale population-based prevention programs and the documented effects of increased physical activity and cardiorespiratory fitness on chronic diseases and its risk factors, we argue that increased physical activity, especially vigorous physical activity, is a major way to reduce the prevalence of chronic diseases and improve public health. We conclude that a coordinated population-based intervention program for improved health through increased physical activity in the entire population, with a special focus on high intensity exercise, urgently needs to be implemented nationally and internationally. PMID:23459225

  17. Chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: clinical implications.

    PubMed

    Vgontzas, A N; Bixler, E O; Lin, H M; Prolo, P; Mastorakos, G; Vela-Bueno, A; Kales, A; Chrousos, G P

    2001-08-01

    Although insomnia is, by far, the most commonly encountered sleep disorder in medical practice, our knowledge in regard to its neurobiology and medical significance is limited. Activation of the hypothalamic-pituitary-adrenal axis leads to arousal and sleeplessness in animals and humans; however, there is a paucity of data regarding the activity of the hypothalamic-pituitary-adrenal axis in insomniacs. We hypothesized that chronic insomnia is associated with increased plasma levels of ACTH and cortisol. Eleven young insomniacs (6 men and 5 women) and 13 healthy controls (9 men and 4 women) without sleep disturbances, matched for age and body mass index, were monitored in the sleep laboratory for 4 consecutive nights, whereas serial 24-h plasma measures of ACTH and cortisol were obtained during the fourth day. Insomniacs, compared with controls, slept poorly (significantly higher sleep latency and wake during baseline nights). The 24-h ACTH and cortisol secretions were significantly higher in insomniacs, compared with normal controls (4.2 +/- 0.3 vs. 3.3 +/- 0.3 pM, P = 0.04; and 218.0 +/- 11.0 vs. 190.4 +/- 8.3 nM, P = 0.07). Within the 24-h period, the greatest elevations were observed in the evening and first half of the night. Also, insomniacs with a high degree of objective sleep disturbance (% sleep time < 70), compared with those with a low degree of sleep disturbance, secreted a higher amount of cortisol. Pulsatile analysis revealed a significantly higher number of peaks per 24 h in insomniacs than in controls (P < 0.05), whereas cosinor analysis showed no differences in the temporal pattern of ACTH or cortisol secretion between insomniacs and controls. We conclude that insomnia is associated with an overall increase of ACTH and cortisol secretion, which, however, retains a normal circadian pattern. These findings are consistent with a disorder of central nervous system hyperarousal rather than one of sleep loss, which is usually associated with no change or

  18. Contrasting effects of Na+, K+-ATPase activation on seizure activity in acute versus chronic models.

    PubMed

    Funck, V R; Ribeiro, L R; Pereira, L M; de Oliveira, C V; Grigoletto, J; Della-Pace, I D; Fighera, M R; Royes, L F F; Furian, A F; Larrick, J W; Oliveira, M S

    2015-07-01

    Epilepsy is a life-shortening brain disorder affecting approximately 1% of the worldwide population. Most epilepsy patients are refractory to currently available antiepileptic drugs (AEDs). Knowledge about the mechanisms underlying seizure activity and probing for new AEDs is fundamental to the discovery of new therapeutic strategies. Brain Na(+), K(+)-ATPase activity contributes to the maintenance of the electrochemical gradients underlying neuronal resting and action potentials as well as the uptake and release of neurotransmitters. Accordingly, a decrease of Na(+), K(+)-ATPase increases neuronal excitability and may predispose to appearing of seizure activity. In the present study, we tested the hypothesis that activation of Na(+), K(+)-ATPase activity with a specific antibody (DRRSAb) raised against a regulatory site in the α subunit would decrease seizure susceptibility. We found that incubation of hippocampal homogenates with DRRSAb (1 μM) increased total and α1 Na(+), K(+)-ATPase activities. A higher concentration (3 μM) increased total, α1 and α2/α3 Na(+), K(+)-ATPase activities. Intrahippocampal injection of DRRSAb decreased the susceptibility of post status epilepticus animals to pentylenetetrazol (PTZ)-induced myoclonic seizures. In contrast, administration of DRRSAb into the hippocampus of naïve animals facilitated the appearance of PTZ-induced seizures. Quantitative analysis of hippocampal electroencephalography (EEG) recordings revealed that DRRSAb increased the percentage of total power contributed by the delta frequency band (0-3 Hz) to a large irregular amplitude pattern of hippocampal EEG. On the other hand, we found no DRRSAb-induced changes regarding the theta functional state. Further studies are necessary to define the potential of Na(+), K(+)-ATPase activation as a new therapeutic approach for seizure disorders. PMID:25907445

  19. Mutated KCNJ5 activates the acute and chronic regulatory steps in aldosterone production.

    PubMed

    Hattangady, Namita G; Karashima, Shigehiro; Yuan, Lucy; Ponce-Balbuena, Daniela; Jalife, José; Gomez-Sanchez, Celso E; Auchus, Richard J; Rainey, William E; Else, Tobias

    2016-07-01

    Somatic and germline mutations in the inward-rectifying K(+) channel (KCNJ5) are a common cause of primary aldosteronism (PA) in aldosterone-producing adenoma and familial hyperaldosteronism type III, respectively. Dysregulation of adrenal cell calcium signaling represents one mechanism for mutated KCNJ5 stimulation of aldosterone synthase (CYP11B2) expression and aldosterone production. However, the mechanisms stimulating acute and chronic production of aldosterone by mutant KCNJ5 have not been fully characterized. Herein, we defined the effects of the T158A KCNJ5 mutation (KCNJ5(T158A)) on acute and chronic regulation of aldosterone production using an adrenal cell line with a doxycycline-inducible KCNJ5(T158A) gene (HAC15-TRE-KCNJ5(T158A)). Doxycycline incubation caused a time-dependent increase in KCNJ5(T158A) and CYP11B2 mRNA and protein levels. Electrophysiological analyses confirm the loss of inward rectification and increased Na(+) permeability in KCNJ5(T158A)-expressing cells. KCNJ5(T158A) expression also led to the activation of CYP11B2 transcriptional regulators, NURR1 and ATF2. Acutely, KCNJ5(T158A) stimulated the expression of total and phosphorylated steroidogenic acute regulatory protein (StAR). KCNJ5(T158A) expression increased the synthesis of aldosterone and the hybrid steroids 18-hydroxycortisol and 18-oxocortisol, measured with liquid chromatography-tandem mass spectrometry (LC-MS/MS). All of these stimulatory effects of KCNJ5(T158A) were inhibited by the L-type Ca(2+) channel blocker, verapamil. Overall, KCNJ5(T158A)increases CYP11B2 expression and production of aldosterone, corticosterone and hybrid steroids by upregulating both acute and chronic regulatory events in aldosterone production, and verapamil blocks KCNJ5(T158A)-mediated pathways leading to aldosterone production. PMID:27099398

  20. Smoking and interstitial lung disease. The effect of cigarette smoking on the incidence of pulmonary histiocytosis X and sarcoidosis.

    PubMed

    Hance, A J; Basset, F; Saumon, G; Danel, C; Valeyre, D; Battesti, J P; Chrétien, J; Georges, R

    1986-01-01

    Cigarette smoking produces marked alterations in the lung parenchyma and in the population of immune and inflammatory cells present in the lower respiratory tract. These cigarette-induced changes appear to influence the incidence of two different interstitial lung diseases, histiocytosis X and sarcoidosis. Smoking is a strong risk factor for the development of pulmonary histiocytosis X, since the incidence of smoking is very high among patients with histiocytosis X: 90% of the patients with histiocytosis X were smokers; 46% of the controls were smokers (p less than .001). In contrast, smoking appears to reduce the incidence of sarcoidosis: 31% of the patients with sarcoidosis were smokers (p less than .05 compared to controls). In an effort to understand how cigarette smoking influences the incidence of these two disorders, we compared the numbers and types of immune and inflammatory cells recovered by bronchoalveolar lavage from nonsmoking and smoking controls and patients with histiocytosis X and sarcoidosis. Although nonsmoking patients with histiocytosis X did not have a significant increase in the number of alveolar macrophages recovered by lavage (p greater than .2 compared to normals), smoking patients had an increase in the number of alveolar macrophages similar to that observed in the control population. In contrast, the number of macrophages recovered from patients with sarcoidosis who smoked was considerably less than that observed in normal smokers (p less than .05 comparing patients with sarcoidosis and controls who smoked 1-20 cigarettes/day). This difference in the intensity of the cigarette-induced macrophage alveolitis observed in the two patient groups may be important in explaining the opposite effects of cigarette smoking on the incidence of histiocytosis X and sarcoidosis. PMID:3488004