Sample records for spontaneous chronic gvhd

  1. Corruption of dendritic cell antigen presentation during acute GVHD leads to regulatory T-cell failure and chronic GVHD. (United States)

    Leveque-El Mouttie, Lucie; Koyama, Motoko; Le Texier, Laetitia; Markey, Kate A; Cheong, Melody; Kuns, Rachel D; Lineburg, Katie E; Teal, Bianca E; Alexander, Kylie A; Clouston, Andrew D; Blazar, Bruce R; Hill, Geoffrey R; MacDonald, Kelli P A


    Chronic graft-versus-host disease (cGVHD) is a major cause of late mortality following allogeneic bone marrow transplantation (BMT) and is characterized by tissue fibrosis manifesting as scleroderma and bronchiolitis obliterans. The development of acute GVHD (aGVHD) is a powerful clinical predictor of subsequent cGVHD, suggesting that aGVHD may invoke the immunologic pathways responsible for cGVHD. In preclinical models in which sclerodermatous cGVHD develops after a preceding period of mild aGVHD, we show that antigen presentation within major histocompatibility complex (MHC) class II of donor dendritic cells (DCs) is markedly impaired early after BMT. This is associated with a failure of regulatory T-cell (Treg) homeostasis and cGVHD. Donor DC-restricted deletion of MHC class II phenocopied this Treg deficiency and cGVHD. Moreover, specific depletion of donor Tregs after BMT also induced cGVHD, whereas adoptive transfer of Tregs ameliorated it. These data demonstrate that the defect in Treg homeostasis seen in cGVHD is a causative lesion and is downstream of defective antigen presentation within MHC class II that is induced by aGVHD. © 2016 by The American Society of Hematology.

  2. Mycophenolate mofetil (MMF) as therapy for refractory chronic GVHD (cGVHD) in children receiving bone marrow transplantation. (United States)

    Busca, A; Saroglia, E M; Lanino, E; Manfredini, L; Uderzo, C; Nicolini, B; Messina, C; Rabusin, M; Miniero, R


    Mycophenolate mofetil (MMF) is an alternative immunosuppressant which inhibits the proliferation of T and B lymphocytes. The purpose of the present study was to evaluate the safety and efficacy of MMF as salvage therapy for chronic GVHD (cGVHD) in children receiving allogeneic bone marrow transplantation. Fifteen children, 3-16 years of age, who had received grafts from HLA-compatible siblings (n = 8), partially matched related donors (n= 2) or matched unrelated donors (n = 5), developed extensive cGVHD which had proved unresponsive to standard immunosuppressive therapy. Patients were treated with MMF at the dose of 15-40 mg/kg/day in combination with other immunosuppressive therapy for a median of 4 months (range 1-15 months). The overall response rate (complete or partial response) was 60%. Thirteen percent had only minor responses, whereas 27% of patients had progressive disease. Best responses were seen in patients with GI tract (60% of complete responses) or mouth (33% of complete responses) cGVHD and skin involvement (43% of complete responses) that did not include sclerodermatous manifestations. Once MMF was started, improvements in the clinical manifestations of cGVHD allowed a significant reduction of steroids in 45% of patients and discontinuation in 27% of cases. Six patients (40%) experienced adverse events, with gastrointestinal symptoms predominating. Five patients experienced opportunistic infections. MMF was discontinued after 35-180 days in six patients for the following reasons: parents choice (n = 2), liver toxicity (n = 1), poor compliance (n = 2), and no response (n = 1). In conclusion, these preliminary results suggest that MMF in combination with other immunosuppressive agents may have a role to play in patients with cGVHD. Prospective clinical trials are needed to establish exact indications for therapy and dosage scheduling. Bone Marrow Transplantation (2000).


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    O. T. Kudaeva


    Full Text Available Abstract. Induction of chronic GVHD in the DBA/2→(C57Bl/6xDBA/2 F1 semi-allogeneic murine model results into development of Th1- and Th2-dependent immunopathological conditions that are characterized by different cytokine profiles. Chronic GVHD is accompanied by a sharp increase in IgE levels, thus presuming considerable IL-4 production. In recipients with Th2-dependent GvHD variant, elevated contents of serum IL-6, IL-7 and TNFα were also observed, which, along with other effects, may support polyclonal activation of B cells, thus leading to development of autoimmune pathology.

  4. Therapeutic regulatory T-cell adoptive transfer ameliorates established murine chronic GVHD in a CXCR5-dependent manner (United States)

    McDonald-Hyman, Cameron; Flynn, Ryan; Panoskaltsis-Mortari, Angela; Peterson, Nicholas; MacDonald, Kelli P. A.; Hill, Geoffrey R.; Luznik, Leo; Serody, Jonathan S.; Murphy, William J.; Maillard, Ivan; Munn, David H.; Turka, Laurence A.; Koreth, John; Cutler, Corey S.; Soiffer, Robert J.; Antin, Joseph H.; Ritz, Jerome


    Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation. In cGVHD, alloreactive T cells and germinal center (GC) B cells often participate in GC reactions to produce pathogenic antibodies. Although regulatory T cells (Tregs) can inhibit GC reactions, Treg numbers are reduced in cGVHD, contributing to cGVHD pathogenesis. Here, we explored 2 means to increase Tregs in cGVHD: interleukin-2/monoclonal antibody (IL-2/mAb) complexes and donor Treg infusions. IL-2/mAb complexes given over 1 month were efficacious in expanding Tregs and treating established cGVHD in a multi-organ-system disease mouse model characterized by GC reactions, antibody deposition, and lung dysfunction. In an acute GVHD (aGVHD) model, IL-2/mAb complexes given for only 4 days resulted in rapid mortality, indicating IL-2/mAb complexes can drive conventional T-cell (Tcon)-mediated injury. In contrast, Treg infusions, which uniformly suppress aGVHD, increased Treg frequency and were effective in preventing the onset of, and treating, established cGVHD. Efficacy was dependent upon CXCR5-sufficient Tregs homing to, and inhibiting, GC reactions. These studies indicate that the infusion of Tregs, especially ones enriched for GC homing, may be desirable for cGVHD therapy. Although IL-2/mAb complexes can be efficacious in cGVHD, a cautious approach needs to be taken in settings in which aGVHD elements, and associated Tcon, are present. PMID:27385791

  5. Topical Tacrolimus and Periodontal Therapy in the Management of a Case of Oral Chronic GVHD Characterized by Specific Gingival Localization

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    Davide Conrotto


    Full Text Available Background. Chronic graft versus host disease (cGVHD is a complication following bone marrow transplantation. The oral lesions are difficult to control with a systemic pharmacological therapy. Case Description. A 63-year-old female patient, who underwent an allogeniec transplantation for acute myeloid leukemia, developed a chronic oral and cutaneous GVHD. The patient was treated with topical tacrolimus 0.1%, twice daily for two months, and underwent a protocol of oral hygiene characterized by 3 appointments of scaling, root planning, and daily oral hygiene instructions. The patient showed marked resolution of gingival lesions and a significant improvement of related pain and gingival inflammatory indexes. Clinical Implications. This case report suggests that treatment with topical tacrolimus and professional oral hygiene may be helpful in the management of chronic oral GVHD with severe gingival involvement.

  6. Topical tacrolimus and periodontal therapy in the management of a case of oral chronic GVHD characterized by specific gingival localization. (United States)

    Conrotto, Davide; Broccoletti, Roberto; Carcieri, Paola; Giaccone, Luisa; Arduino, Paolo G


    Background. Chronic graft versus host disease (cGVHD) is a complication following bone marrow transplantation. The oral lesions are difficult to control with a systemic pharmacological therapy. Case Description. A 63-year-old female patient, who underwent an allogeniec transplantation for acute myeloid leukemia, developed a chronic oral and cutaneous GVHD. The patient was treated with topical tacrolimus 0.1%, twice daily for two months, and underwent a protocol of oral hygiene characterized by 3 appointments of scaling, root planning, and daily oral hygiene instructions. The patient showed marked resolution of gingival lesions and a significant improvement of related pain and gingival inflammatory indexes. Clinical Implications. This case report suggests that treatment with topical tacrolimus and professional oral hygiene may be helpful in the management of chronic oral GVHD with severe gingival involvement.

  7. Isolated Testicular Recurrence of AML in Patients With Chronic GVHD >1 Year Following Allogeneic Stem Cell Transplant. (United States)

    Dang, Brian N; De Oliveira, Satiro; Bowles, LaVette; Moore, Theodore B


    Patients with chronic graft-versus-host disease (cGVHD) following allogeneic transplant for myeloid leukemias seem to experience a reduced risk of relapse than comparable patients without cGVHD. It is unclear to what extent extramedullary sites are impacted by a graft-versus-leukemia effect. Case Series and review of the literature. We present 2 cases of pediatric patients with Acute Myelogenous Leukemia who developed isolated testicular relapse more than a year following hematopoietic stem cell transplantation despite having had extensive cGVHD. Both patients were off immunosuppression and cGVHD medications when testicular relapse occurred. At time of relapse, these patients were negative for minimal residual disease in the marrow and the marrow contained all donor cells by engraftment studies. No evidence was found for lymphocyte infiltration into the affected testicle in either patient. Although a reduction of marrow relapse can be appreciated in patients with myeloid leukemias and chronic GVHD, this graft-versus-leukemia process may be less robust in extramedullary sites and careful surveillance should be maintained to allow early intervention before overt marrow involvement.

  8. Clinical approach in the management of oral chronic graft-versus-host disease (cGVHD) in a series of specialized medical centers

    NARCIS (Netherlands)

    Elad, Sharon; Jensen, Siri Beier; Raber-Durlacher, Judith E.; Mouradian, Nancy; Correa, Elvira M. P.; Schubert, Mark M.; Blijlevens, Nicole M. A.; Epstein, Joel B.; Saunders, Deborah P.; Waltimo, Tuomas; Yarom, Noam; Zadik, Yehuda; Brennan, Michael T.


    The oral cavity is frequently affected in chronic graft-versus-host disease (cGVHD), with variable clinical presentations. The literature on the effective management of patients suffering from oral cGVHD is limited. The objective of this study was to assess the clinical approaches used in the

  9. Unbalanced recovery of regulatory and effector T cells after allogeneic stem cell transplantation contributes to chronic GVHD. (United States)

    Alho, Ana C; Kim, Haesook T; Chammas, Marie J; Reynolds, Carol G; Matos, Tiago R; Forcade, Edouard; Whangbo, Jennifer; Nikiforow, Sarah; Cutler, Corey S; Koreth, John; Ho, Vincent T; Armand, Philippe; Antin, Joseph H; Alyea, Edwin P; Lacerda, Joao F; Soiffer, Robert J; Ritz, Jerome


    The development and maintenance of immune tolerance after allogeneic hematopoietic stem cell transplantation (HSCT) requires the balanced reconstitution of donor-derived CD4 regulatory T cells (CD4Tregs) as well as effector CD4 (conventional CD4 T cells [CD4Tcons]) and CD8 T cells. To characterize the complex mechanisms that lead to unbalanced recovery of these distinct T-cell populations, we studied 107 adult patients who received T-replete stem cell grafts after reduced-intensity conditioning. Immune reconstitution of CD4Treg, CD4Tcon, and CD8 T cells was monitored for a 2-year period. CD3 T-cell counts gradually recovered to normal levels during this period but CD8 T cells recovered more rapidly than either CD4Tregs or CD4Tcons. Reconstituting CD4Tregs and CD4Tcons were predominantly central memory (CM) and effector memory (EM) cells and CD8 T cells were predominantly terminal EM cells. Thymic generation of naive CD4Tcon and CD8 T cells was maintained but thymic production of CD4Tregs was markedly decreased with little recovery during the 2-year study. T-cell proliferation was skewed in favor of CM and EM CD4Tcon and CD8 T cells, especially 6 to 12 months after HSCT. Intracellular expression of BCL2 was increased in CD4Tcon and CD8 T cells in the first 3 to 6 months after HSCT. Early recovery of naive and CM fractions within each T-cell population 3 months after transplant was also strongly correlated with the subsequent development of chronic graft-versus-host disease (GVHD). These dynamic imbalances favor the production, expansion, and persistence of effector T cells over CD4Tregs and were associated with the development of chronic GVHD. © 2016 by The American Society of Hematology.

  10. Donor-Recipient Matching for KIR Genotypes Reduces Chronic GVHD and Missing Inhibitory KIR Ligands Protect against Relapse after Myeloablative, HLA Matched Hematopoietic Cell Transplantation.

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    Rehan Mujeeb Faridi

    Full Text Available Allogeneic hematopoietic cell transplantation (HCT can be curative for many hematologic diseases. However, complications such as graft-versus-host disease (GVHD and relapse of primary malignancy remain significant and are the leading causes of morbidity and mortality. Effects of killer Ig-like receptors (KIR-influenced NK cells on HCT outcomes have been extensively pursued over the last decade. However, the relevance of the reported algorithms on HLA matched myeloablative HCT with rabbit antithymocyte globulin (ATG is used for GVHD prophylaxis remains elusive. Here we examined the role of KIR and KIR-ligands of donor-recipient pairs in modifying the outcomes of ATG conditioned HLA matched sibling and unrelated donor HCT.The study cohort consisted of 281 HLA matched sibling and unrelated donor-recipient pairs of first allogeneic marrow or blood stem cell transplantation allocated into 'discovery' (135 pairs and 'validation' (146 pairs cohorts. High resolution HLA typing was obtained from the medical charts and KIR gene repertoires were obtained by a Luminex® based SSO method. All surviving patients were followed-up for a minimum of two years. KIR and HLA class I distributions of HCT pairs were stratified as per applicable definitions and were tested for their association with cause specific outcomes [acute GVHD grade II-IV (aGVHD, chronic GVHD needing systemic therapy (cGVHD and relapse] using a multivariate competing risks regression model as well as with survival outcomes [relapse-free survival (RFS, cGVHD & relapse free survival (cGRFS and overall survival (OS] by multivariate Cox proportional hazards regression model. A significant association between KIR genotype mismatching (KIR-B/x donor into KIR-AA recipient or vice versa and cGVHD was found in both discovery (p = 0.001; SHR = 2.78; 95%CI: 1.50-5.17 and validation cohorts (p = 0.005; SHR = 2.61; 95%CI: 1.33-5.11. High incidence of cGVHD associated with KIR genotype mismatching was

  11. Donor-Recipient Matching for KIR Genotypes Reduces Chronic GVHD and Missing Inhibitory KIR Ligands Protect against Relapse after Myeloablative, HLA Matched Hematopoietic Cell Transplantation. (United States)

    Faridi, Rehan Mujeeb; Kemp, Taylor J; Dharmani-Khan, Poonam; Lewis, Victor; Tripathi, Gaurav; Rajalingam, Raja; Daly, Andrew; Berka, Noureddine; Storek, Jan; Masood Khan, Faisal


    Allogeneic hematopoietic cell transplantation (HCT) can be curative for many hematologic diseases. However, complications such as graft-versus-host disease (GVHD) and relapse of primary malignancy remain significant and are the leading causes of morbidity and mortality. Effects of killer Ig-like receptors (KIR)-influenced NK cells on HCT outcomes have been extensively pursued over the last decade. However, the relevance of the reported algorithms on HLA matched myeloablative HCT with rabbit antithymocyte globulin (ATG) is used for GVHD prophylaxis remains elusive. Here we examined the role of KIR and KIR-ligands of donor-recipient pairs in modifying the outcomes of ATG conditioned HLA matched sibling and unrelated donor HCT. The study cohort consisted of 281 HLA matched sibling and unrelated donor-recipient pairs of first allogeneic marrow or blood stem cell transplantation allocated into 'discovery' (135 pairs) and 'validation' (146 pairs) cohorts. High resolution HLA typing was obtained from the medical charts and KIR gene repertoires were obtained by a Luminex® based SSO method. All surviving patients were followed-up for a minimum of two years. KIR and HLA class I distributions of HCT pairs were stratified as per applicable definitions and were tested for their association with cause specific outcomes [acute GVHD grade II-IV (aGVHD), chronic GVHD needing systemic therapy (cGVHD) and relapse] using a multivariate competing risks regression model as well as with survival outcomes [relapse-free survival (RFS), cGVHD & relapse free survival (cGRFS) and overall survival (OS)] by multivariate Cox proportional hazards regression model. A significant association between KIR genotype mismatching (KIR-B/x donor into KIR-AA recipient or vice versa) and cGVHD was found in both discovery (p = 0.001; SHR = 2.78; 95%CI: 1.50-5.17) and validation cohorts (p = 0.005; SHR = 2.61; 95%CI: 1.33-5.11). High incidence of cGVHD associated with KIR genotype mismatching was applicable

  12. Increased incidence of chronic GvHD and CMV disease in patients with vitamin D deficiency before allogeneic stem cell transplantation. (United States)

    von Bahr, L; Blennow, O; Alm, J; Björklund, A; Malmberg, K-J; Mougiakakos, D; Le Blanc, A; Oefner, P J; Labopin, M; Ljungman, P; Le Blanc, K


    Vitamin D has emerged as a central player in the immune system, with its deficiency being implicated in the pathogenesis of several autoimmune diseases, including chronic GvHD. This is a retrospective cohort analysis of 166 patients, who underwent allogeneic hematopoietic stem cell transplantation (HSCT) at the Karolinska University Hospital, evaluating GvHD, graft failure, infectious complications and survival after HSCT in relation to pre-transplantation vitamin D levels. Most of the patients were deficient in vitamin D before HSCT (median 42 nmol/L). In multivariate analysis, vitamin D level before HSCT was identified as a significant independent risk factor for development of cGvHD. The increased incidence of cGvHD was not coupled to better disease-free survival; instead there was a trend towards lower overall survival in the vitamin D-deficient patients. In addition, we found a significant correlation between vitamin D deficiency and incidence of CMV disease, with no case of CMV disease occurring in patients with sufficient levels of vitamin D before HSCT. Our results support a role of vitamin D in immune tolerance following HSCT. These findings could be highly relevant for the care of HSCT patients, and prospective, randomized studies on the effect of vitamin D supplementation are therefore needed.

  13. Spontaneous resolution of post-traumatic chronic subdural hematoma

    African Journals Online (AJOL)

    Here, we present a case of spontaneously resolved post-traumatic bilateral chronic subdural hematoma within a period of one month in a 55-year-old male and we discuss the probable mechanisms of pathophysiology in the spontaneous resolution of chronic subdural hematoma. Keywords: Antiaggregation therapy, chronic ...

  14. The impact of chronic GVHD on survival of Patients with acute myeloid leukemia after non-T-cell depleted HLA-identical sibling peripheral blood stem cells transplantation

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    farhad Shahsavar


    Conclusion: These data indicate that the occurrence of cGVHD is an important predictor of outcome of non-T-cell depleted HLA-identical sibling allogeneic PBSCT, in those AML patients who develope cGVHD have a high chance of survival.

  15. B-cell activating factor (BAFF) plasma level at the time of chronic GvHD diagnosis is a potential predictor of non-relapse mortality. (United States)

    Saliba, R M; Sarantopoulos, S; Kitko, C L; Pawarode, A; Goldstein, S C; Magenau, J; Alousi, A M; Churay, T; Justman, H; Paczesny, S; Reddy, P; Couriel, D R


    Biological markers for risk stratification of chronic GvHD (cGvHD) could improve the care of patients undergoing allogeneic hematopoietic stem cell transplantation. Increased plasma levels of B-cell activating factor (BAFF), chemokine (C-X-C motif) ligand 9 (CXCL9) and elafin have been associated with the diagnosis, but not with outcome in patients with cGvHD. We evaluated the association between levels of these soluble proteins, measured by ELISA at the time of cGvHD diagnosis and before the initiation of therapy, with non-relapse-mortality (NRM). Based on the log-transformed values, factor levels were divided into tertiles defined respectively as low, intermediate, and high levels. On univariable analysis, BAFF levels were significantly associated with NRM, whereas CXCL9 and elafin levels were not. Both low (⩽2.3 ng/mL, hazard ratio (HR)=5.8, P=0.03) and high (>5.7 ng/mL, HR=5.4, P=0.03) BAFF levels were associated with a significantly higher NRM compared with intermediate BAFF level. The significant effect of high or low BAFF levels persisted in multivariable analysis. A subset of cGvHD patients had persistently low BAFF levels. In conclusion, our data show that BAFF levels at the time of cGvHD diagnosis are associated with NRM, and also are potentially useful for risk stratification. These results warrant confirmation in larger studies.

  16. Spontaneous globe luxation associated with chronic obstructive pulmonary disease

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    M Ashok Kumar


    Full Text Available Spontaneous globe luxation is a rarely reported condition which can lead to complications like optic neuropathy. Common causes are thyroid eye disease, shallow orbit and floppy eyelid syndrome. We report a case of spontaneous globe luxation with the onset and severity associated with chronic obstructive pulmonary disease (COPD. To our knowledge, this is the first case of spontaneous globe luxation associated with COPD.

  17. Probiotics and refractory chronic spontaneous urticaria. (United States)

    Nettis, E; Di Leo, E; Pastore, A; Distaso, M; Zaza, I; Vacca, M; Macchia, L; Vacca, A


    Background. In chronic spontaneous urticaria (CSU) first-line therapy with an antihistamine-based regimen may not achieve satisfactory control in patients. Thus, a continuing need exists for effective and safe treatments for refractory CSU. Aim. To evaluate the clinical efficacy and safety of an intake of a combination of 2 probiotics (Lactobacillus salivarius LS01 and Bifidobacterium breve BR03) in patients with CSU who remain symptomatic despite concomitant H1-antihistamine therapy. Methods. This report analyzes the effects of therapy with two probiotic strains on the clinical progress of 52 unselected patients with difficulty to treat CSU underwent to medical examination in two Italian specialist urticaria Clinics between September 2013 and September 2014. A mixture of Lactobacillus LS01 and Bifidobacterium BR03 were administered in each patient twice daily for 8 weeks. To evaluate patients' improvement with probiotics, urticaria activity score over 7 days (UAS7) was used at baseline and at week 8 in addition to a 5-question urticaria quality of life questionnaire. Results. Fifty-two patients with CSU were included in this study (10 male and 42 female, age range 19-72 years). Mean disease duration was 1.5 years. Fourteen patients discontinued treatment, so evaluable population consisted of 38 patients. Nine of the 38 patients experienced mild clinical improvement during probiotic treatment (23.7%); one patient reported significant clinical improvement (2.6%) and one patient had complete remission of urticaria (2.6%). Twenty-seven patients did not have improvement in symptoms (71.1%). No side effects during the course of therapy were reported. Conclusions. A combination of Lactobacillus salivarius LS01 and Bifidobacterium breve BR03 administered twice daily for 8 weeks might reduce the symptoms scores and improve quality of life scores in a part of patients with CSU who remained symptomatic despite treatment with H1 antihistamine mostly in subjects with allergic

  18. Spontaneous choledochal cyst rupture in pregnancy with concomitant chronic pancreatitis. (United States)

    Pal, Sandip; Simon, Ebby George; Koshy, Anoop K; Ramakrishna, B S; Raju, Ravish S; Vyas, Fredrick L; Joseph, Philip; Sitaram, V; Eapen, Anu


    Choledochal cysts are rare cystic transformations of the biliary tree that are increasingly diagnosed in adult patients. We report here a case of spontaneous rupture of a choledochal cyst in a pregnant young lady with chronic pancreatitis.

  19. Clinical approach in the management of oral chronic graft-versus-host disease (cGVHD) in a series of specialized medical centers

    DEFF Research Database (Denmark)

    Elad, Sharon; Jensen, Siri Beier; Raber-Durlacher, Judith E


    GVHD patients, diagnostic and evaluation methods in their practice, preferred treatment strategies for mucosal and salivary gland involvement, and preventive measures. RESULTS: Twelve responders, representing 12 sites, stated that they treat oral cGVHD patients on a regular basis. This fraction of responders...... twenty questionnaires were sent to the members of the Oral Care Study Group (OCSG) of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). The questionnaire included 50 questions about the responder's demographics, level of exposure to c......GVHD was predominantly steroids (91.7 %), and the second preferred treatment was tacrolimus (41.7 %). The preferred treatment for hyposalivation was pilocarpine (41.7 %). The recommended frequency of oral cancer screening varied; half of the providers suggest a follow-up every 6 months. CONCLUSIONS: The responses...

  20. Chronic Allium sativum administration alters spontaneous ...

    African Journals Online (AJOL)

    This study was conducted to investigate the effects of Allium sativum extract on the medial prefrontal cortex and neurobehaviour of adult Wistar rats. ... altered spontaneous alternation, while cellular pathologic changes were observed in the medial prefrontal cortex of these test groups in a dose dependent sequence.

  1. Aspirin attenuates spontaneous recurrent seizures in the chronically epileptic mice. (United States)

    Zhu, Kun; Hu, Ming; Yuan, Bo; Liu, Jian-Xin; Liu, Yong


    Neuroinflammatory processes are pathologic hallmarks of both experimental and human epilepsy, and could be implicated in the neuronal hyperexcitability. Aspirin represents one of the non-selective nonsteroidal anti-inflammatory drugs with fewer side effects in long-term application. This study was carried out to assess the anti-epileptic effects of aspirin when administered during the chronic stage of temporal lobe epilepsy [TLE] in mice. The alteration of hippocampal neurogenesis was also examined for raising a possible mechanism underlying the protective effect of anti-inflammatory treatment in the TLE. Two months after pilocarpine-induced status epilepticus, the chronically epileptic mice were treated with aspirin (20 mg, 60 mg or 80 mg/kg) once a day for 10 weeks. Spontaneous recurrent seizures were monitored by video camera for 2 weeks. To evaluate the profile of hippocampal neurogenesis, the newly generated cells in the dentate gyrus were labeled by the proliferation marker BrdU. The newborn neurons that extended axons to CA3 area were visualized by cholera toxin B subunit retrograde tracing. Administration of aspirin with a dosage of 60 mg or 80 mg/kg initiated at 2 months after pilocarpine-induced status epilepticus significantly reduced the frequency and duration of spontaneous recurrent seizures. Aspirin treatment also increased the number of newborn neurons with anatomic integration through improving the survival of the newly generated cells. Aspirin treatment during the chronic stage of TLE could attenuate the spontaneous recurrent seizures in mice. Promotion of hippocampal neurogenesis and inhibition of COX-PGE2 pathway might partly contribute to this anti-epileptic effect. Highlights • Aspirin attenuates spontaneous recurrent seizures of chronically epileptic mice • Aspirin increases neurogenesis of chronically epileptic hippocampus by improving the survival of newly generated cells • Promotion of hippocampal neurogenesis and inhibition

  2. Spontaneous intracranial haemorrhage in children with chronic immune thrombocytopenic purpura. (United States)

    Muda, Z; Ibrahim, H; Abdulrahman, E J; Mahfuzah, M; Othman, I S; Asohan, T; Menon, B S


    Spontaneous intracranial haemorrhage (ICH) is a rare complication of chronic immune thrombocytopenic purpura (ITP) in children. We report four patients with cITP who developed ICH. The latency between onset of ITP and ICH varied from 1-8 years. All our patients were profoundly thrombocytopenic (platelet count of <10 x 109/l) at the time of their intracranial bleed. The presenting features and management are discussed. All patients survived, three had complete neurological recovery while one had a minimal residual neurological deficit.

  3. Bilateral Spontaneous Pneumothorax in Chronic Silicosis: A Case Report

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    Pritinanda Mishra


    Full Text Available Silicosis is an occupational lung disease caused by inhalation of crystalline silica. People working in occupations like sandblasting, surface drilling, tunneling, silica flour milling, ceramic making, and so forth are predisposed to develop silicosis. Crystalline forms of silica are more fibrogenic than the amorphous forms, highlighting the importance of the physical form in pathogenesis. Lung biopsy is rarely performed for the diagnosis of silicosis as it can easily be detected by occupational history and radiological features. Patients with silicosis can develop complications like tuberculosis, lung cancer, progressive massive fibrosis, cor pulmonale, broncholithiasis, or tracheobronchial compression by lymph nodes. Pleural involvement in silicosis is rare. Spontaneous pneumothorax is a pleural complication that can develop in such patients. Usually in silicosis pneumothorax is unilateral. We hereby report the lung biopsy findings and discuss the mechanism of pneumothorax development in a case of chronic silicosis who, later on died during the course of the disease.

  4. [Detection of NK and NKT cells in peripheral blood of patients with cGVHD and its significance]. (United States)

    Zhou, Mao-Hua; Wang, Chun-Miao; Gong, Cai-Ping; Luo, Yin; Zhang, Min


    The aim of this study was to investigate the correlation of NK and NKT cells in peripheral blood of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) with chronic graft-versus-host disease (cGVHD). 64 patients undergoing allo-HSCT in Guangdong Provincial People Hospital were studied retrospectively. Among 64 cases, 21 cases were did not develop with cGVHD, 43 cases (mild 15, moderate 18, severe 10) were recorded with cGVHD. The frequency of NK and NKT cells in peripheral blood of patients were measured by flow cytometry. The counts of NK and NKT cells were measured by automatic five sort hematology cyto-analyser (LH-750). The frequency and counts of NK and NKT cells between patients with non-cGVHD and patients with different status of cGVHD were analysed. The results indicated that as compared with the non-cGVHD patients, the frequency and counts of NK cells in patients with cGVHD obviously reduced (P NKT cells were did not changed significantly. The frequency and counts of NK cells gradually decreased within the different status of cGVHD, the frequency and counts of NK cells in severe-cGVHD were significantly lower than that in mild-cGVHD. It is concluded that NK cells may play an important role in the incidence and development of cGVHD. The detection of frequency and counts of NK cells should be helpful to early diagnose cGVHD and provide valuable clues for assessing the severity of illnesses. NKT cells may have little effect on the incidence and development of cGVHD.

  5. Profile of omalizumab in the treatment of chronic spontaneous urticaria

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    Labrador-Horrillo M


    Full Text Available Moises Labrador-Horrillo,1 Marta Ferrer2 1Allergy Section, Internal Medicine Department, Vall d’Hebron Hospital, Universitat Autònoma de Barcelona, Barcelona, 2Department of Allergy and Clinical Immunology, Clínica Universidad de Navarra, IDISNA, Instituto de Investigación de Navarra, Pamplona, Spain Abstract: Chronic spontaneous urticaria (CSU is a disease with significant morbidity and relative prevalence that has important effects on the quality of life (QoL of those who suffer from it. Omalizumab is a recombinant humanized anti-immunoglobulin E (IgE antibody that binds to the Cε3 domain of the IgE heavy chain and prevents it from binding to its high-affinity receptor FcεRI. It has been largely studied in the field of asthma and is currently approved for the treatment of both adult and pediatric (children; >6-year-old patients. In addition, in recent, well-controlled clinical trials in patients with CSU resistant to antihistamines, add-on therapy with subcutaneous omalizumab significantly reduced the severity of itching, and the number and size of hives, and increased patients’ health-related QoL and the proportion of days free from angioedema compared with placebo, with an excellent tolerance. Thus, omalizumab is an effective and well-tolerated add-on therapy for patients with CSU who are symptomatic despite background therapy with H1 antihistamines. In this review, we cover the following points: epidemiology, pathogenesis, assessment of activity, impact on QoL, and treatment of CSU, and finally, we focus on omalizumab in the treatment of CSU including the pharmacokinetic properties and mechanism of action, and use in pregnant women, nursing infants, and children. Keywords: omalizumab, chronic spontaneous urticaria, antihistamines, subcutaneous administration, add-on therapy

  6. Chronic Hepatitis B with Spontaneous Severe Acute Exacerbation

    Directory of Open Access Journals (Sweden)

    Wei-Lun Tsai


    Full Text Available Chronic hepatitis B virus (HBV infection is a major global health problem with an estimated 400 million HBV carriers worldwide. In the natural history of chronic hepatitis B (CHB, spontaneous acute exacerbation (AE is not uncommon, with a cumulative incidence of 10%–30% every year. While exacerbations can be mild, some patients may develop hepatic decompensation and even die. The underlying pathogenesis is possibly related to the activation of cytotoxic T lymphocyte-mediated immune response against HBV. An upsurge of serum HBV DNA usually precedes the rise of alanine aminotransferase (ALT and bilirubin. Whether antiviral treatment can benefit CHB with severe AE remains controversial, but early nucleos(tide analogues treatment seemed to be associated with an improved outcome. There has been no randomized study that compared the effects of different nucleos(tide analogues (NA in the setting of CHB with severe AE. However, potent NAs with good resistance profiles are recommended. In this review, we summarized current knowledge regarding the natural history, pathogenetic mechanisms, and therapeutic options of CHB with severe AE.

  7. Involvement of new oxidative stress markers in chronic spontaneous urticaria

    Directory of Open Access Journals (Sweden)

    Eustachio Nettis


    Full Text Available Introduction : Oxidative stress is a result of an imbalance between endogenous production of free reactive oxygen species and reduced effectiveness of antioxidant defence mechanisms. Advanced glycation end products (AGEs and advanced oxidation protein products (AOPPs are compounds formed by transformation of macromolecules, including proteins which can serve as markers of oxidative stress and inflammation in several diseases. Aim : To investigate the role of AGEs and AOPPs as new markers of oxidative stress and inflammation in patients with chronic spontaneous urticaria (CSU. Material and methods : Advanced glycation end products and AOPP levels were determined in the sera of 85 patients with CSU and 64 healthy controls, using spectrofluorimetry and spectrophotometry, respectively. Results : Advanced oxidation protein products levels in patients were statistically higher than those in controls. These levels were not affected by the presence of positive autologous serum test results or autologous plasma test results. No statistically significant differences were found between AGE levels in patients and controls. Conclusions : Formation of AGEs and AOPPs may be accelerated in immunological and allergic disorders. Depending on the sites evaluated, the presence or absence of oxidative stress in chronic urticaria is controversial. To our knowledge, this is the first study showing the possible involvement of AOPPs in CSU. The different behaviour observed for these two biomarkers is very likely due to the activation of specific related biochemical pathways associated with the condition under study.

  8. The clinical and laboratory characteristics of acute spontaneous urticaria and its progression to chronic spontaneous urticaria. (United States)

    Magen, Eli; Zueva, Ekaterina; Mishal, Joseph; Schlesinger, Menachem


    The natural history of the progression from acute spontaneous urticaria (ASU) to chronic spontaneous urticaria (CSU), CSU remains poorly understood. To identify clinical and laboratory patient attributes that may be predictive of ASU progression to CSU. We prospectively studied consecutive adult patients (age ≥ 18 years) with a diagnosis of urticaria of urticaria activity score assessment were performed in all the patients at baseline and then at weeks 7, 12, 24, and 48. Of 114 patients with acute urticaria and without identifiable causes, 73 patients (64%) were included in the ASU group, 41 patients in the CSU group (36%), and 44 healthy subjects in the control group. At baseline, 26 patients in the CSU group (63.4%) had a positive ASST result, whereas only 17 patients with a positive ASST result (23.3%) were revealed in the ASU group (p < 0.001). Patients with baseline ASST positive results were characterized by more profound basopenia (mean [standard deviation], 0.05 ± 0.08 cell/mm(3)) and more anti-thyroid peroxidase antibodies (18 [41.8%]) than those with the negative baseline ASST result (mean [standard deviation], 0.13 ± 0.09 cell/mm(3), p < 0.001 more profound basopenia; and 13 (18.1%), p = 0.009 more thyroid peroxidase antibodies). We observed the disappearance of ASST positive result in some patients with CSU with baseline positive ASST results, whereas, in some subjects with CSU, baseline negative ASST results came to be positive results throughout the study period. A baseline positive ASST result of patients with ASU was a significant determinant (odds ratio 5.91 [95% confidence interval, 2.57-13.62]; p < 0.001) for a CSU diagnosis at week 7. The patients with ASU who progressed toward CSU were characterized by a positive ASST result, thyroid autoimmunity, and profound basopenia at baseline.

  9. Chronic spontaneous urticaria and internal parasites--a systematic review. (United States)

    Kolkhir, P; Balakirski, G; Merk, H F; Olisova, O; Maurer, M


    Chronic spontaneous urticaria (CSU) is defined as persistent wheals, angioedema, or both lasting for >6 weeks due to known or unknown causes. Some epidemiological studies and case reports suggest that internal parasite infections (PI) can cause CSU. Here, we provide a systematic overview of published findings on the prevalence and relevance of PI in CSU and we discuss possible pathomechanisms. The prevalence of PI in CSU was investigated by 39 independent studies and comorbidity reportedly ranged from 0 to 75.4% (two-thirds of these studies reported infection rates of 10% or less). The prevalence of PI in adult and pediatric CSU patients ranged from 0% to 75.4% and from 0% to 37.8%, respectively. CSU patients were more often diagnosed with protozoa and had a significantly higher risk of toxocariasis seropositivity and Anisakis simplex sensitization when compared to healthy controls. Patients with chronic urticaria more frequently had seropositivity of fasciolosis, Anisakis simplex sensitization, and the presence of Blastocystis hominis allele 34 (ST3) as compared with control subjects. In 21 studies, efficacy of treatment with antiparasitic drugs ranged from 0 to 100% (35.7% of 269 CSU patients benefitted). In 9 (42.8%) of 21 studies, more than 50% of efficacy was observed. The reported rate of urticaria comorbidity in PI patients in 18 independent studies is 1-66.7%. Urticaria including CSU might be a quite common symptom of strongyloidiasis and blastocystosis. Pathogenic mechanisms in CSU due to PI may include specific IgE, Th2 cytokine skewing, eosinophils, activation of the complement, and the coagulation systems. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Subcutaneous autologous serum therapy in chronic spontaneous urticaria

    Directory of Open Access Journals (Sweden)

    Kiran Vasant Godse


    Full Text Available Background: There is a felt need for trying newer therapeutic modalities in patients with chronic spontaneous urticaria, especially in the subset of patients classified as non-responders to antihistamines. Autologous serum therapy is an upcoming modality of treatment, and we decided to study its efficacy by subcutaneous route. Aims: To evaluate the effectiveness of subcutaneous autologous serum therapy (AST in CSU. Methods: This was a single blind, placebo-controlled parallel group, randomized, controlled study. Twenty-four patients with CSU (11M: 13 F were given subcutaneous AST and seventeen patients (7 M: 10F patients were given subcutaneous injection normal saline (placebo, along with levocetirizine in an on-demand basis in both groups. Results: Urticaria activity score (UAS came down from 35.74 to 7 at the end of 9 weeks and the patients' requirement of antihistamines also reduced remarkably from 5.8 to 1.7 per week in the serum group. Sub-cutaneous saline group did not show statistically significant fall in UAS. Saline group showed UAS 32.8 at zero week to 22.1 at the end of 9 weeks. DLQI showed significant fall in serum group, from 14.26 to 4 at the end of 9 weeks. Conclusion: Subcutaneous autoserum therapy is effective in treatment of CSU.

  11. Profile of omalizumab in the treatment of chronic spontaneous urticaria. (United States)

    Labrador-Horrillo, Moises; Ferrer, Marta


    Chronic spontaneous urticaria (CSU) is a disease with significant morbidity and relative prevalence that has important effects on the quality of life (QoL) of those who suffer from it. Omalizumab is a recombinant humanized anti-immunoglobulin E (IgE) antibody that binds to the Cε3 domain of the IgE heavy chain and prevents it from binding to its high-affinity receptor FcεRI. It has been largely studied in the field of asthma and is currently approved for the treatment of both adult and pediatric (children; >6-year-old) patients. In addition, in recent, well-controlled clinical trials in patients with CSU resistant to antihistamines, add-on therapy with subcutaneous omalizumab significantly reduced the severity of itching, and the number and size of hives, and increased patients' health-related QoL and the proportion of days free from angioedema compared with placebo, with an excellent tolerance. Thus, omalizumab is an effective and well-tolerated add-on therapy for patients with CSU who are symptomatic despite background therapy with H1 antihistamines. In this review, we cover the following points: epidemiology, pathogenesis, assessment of activity, impact on QoL, and treatment of CSU, and finally, we focus on omalizumab in the treatment of CSU including the pharmacokinetic properties and mechanism of action, and use in pregnant women, nursing infants, and children.

  12. Vorinostat plus tacrolimus/methotrexate to prevent GVHD after myeloablative conditioning, unrelated donor HCT. (United States)

    Choi, Sung Won; Braun, Thomas; Henig, Israel; Gatza, Erin; Magenau, John; Parkin, Brian; Pawarode, Attaphol; Riwes, Mary; Yanik, Greg; Dinarello, Charles A; Reddy, Pavan


    The oral histone deacetylase (HDAC) inhibitor (vorinostat) is safe and results in low incidence of acute graft-versus-host disease (GVHD) after reduced-intensity conditioning, related donor hematopoietic cell transplantation (HCT). However, its safety and efficacy in preventing acute GVHD in settings of heightened clinical risk that use myeloablative conditioning, unrelated donor (URD), and methotrexate are not known. We conducted a prospective, phase 2 study in this higher-risk setting. We enrolled 37 patients to provide 80% power to detect a significant difference in grade 2 to 4 acute GVHD of 50% compared with a reduction in target to 28%. Eligibility included adults with a hematological malignancy to receive myeloablative HCT from an available 8/8-HLA matched URD. Patients received GVHD prophylaxis with tacrolimus and methotrexate. Vorinostat (100 mg twice daily) was started on day -10 and continued through day +100 post-HCT. Median age was 56 years (range, 18-69 years), and 95% had acute myelogenous leukemia or high-risk myelodysplastic syndrome. Vorinostat was safe and tolerable. The cumulative incidence of grade 2 to 4 acute GVHD at day 100 was 22%, and for grade 3 to 4 it was 8%. The cumulative incidence of chronic GVHD was 29%; relapse, nonrelapse mortality, GVHD-free relapse-free survival, and overall survival at 1 year were 19%, 16%, 47%, and 76%, respectively. Correlative analyses showed enhanced histone (H3) acetylation in peripheral blood mononuclear cells and reduced interleukin 6 ( P = .028) and GVHD biomarkers (Reg3, P = .041; ST2, P = .002) at day 30 post-HCT in vorinostat-treated subjects compared with similarly treated patients who did not receive vorinostat. Vorinostat for GVHD prevention is an effective strategy that should be confirmed in a randomized phase 3 study. This trial was registered at as #NCT01790568. © 2017 by The American Society of Hematology.

  13. Chronic effects of arotinolol (S-596) in spontaneously hypertensive rats. (United States)

    Kishi, K; Kawashima, K; Sokabe, H; Saito, K


    Arotinolol (S-596, ARL) is a beta-adrenoceptor blocking drug with weak alpha-adrenoceptor blocking activity, and may be classified into the fourth generation. Antihypertensive effects of ARL were studied for 12 weeks in spontaneously hypertensive (SHR) rats. Propranolol (PPL) was used as the reference drug. ARL (20 and 100 mg/kg per day, p.o.) and PPL (100 mg/kg per day, p.o.) treatments significantly decreased heart rate, within a week after the drug treatments had started and thereafter. Tail blood pressure (BP), determined by prewarming the rat at 50 degrees C for 3 min, was slightly higher in the two ARL treated groups than in the control. Tail BP was slightly lower in the PPL treated group than in the control. Mean BP determined directly at the 12th week was lower in the two ARL and PPL groups than in the control by more than 20 mmHg. Both ARL (100 mg/kg per day) and PPL (100 mg/kg per day) treatments significantly reduced incidences of the vascular lesions, and also prevented the decrease of kidney weights usually associated with mild vascular lesions. Furthermore, these treatments showed a tendency to decrease plasma renin (PRC) and aldosterone (PAC) concentrations determined 20 h after the last administration. As mean BP must be more reliable than tail BP, it was concluded that ARL (20 and 100 mg/kg per day) showed almost the same chronic antihypertensive activity in SHR rats as PPL (100 mg/kg per day). Preventive effects of ARL on development of vascular lesions also supported the above view.

  14. Serum Clusterin as a Prognostic Marker of Chronic Spontaneous Urticaria. (United States)

    Kim, Ji-Hye; Lee, Hyung-Young; Ban, Ga-Young; Shin, Yoo-Seob; Park, Hae-Sim; Ye, Young-Min


    A substantial proportion of patients with chronic spontaneous urticaria (CSU) are refractory to antihistamines. However, identifying the subpopulation whose urticaria is not completely controlled by antihistamines remains difficult. The response of autologous serum skin test (ASST), a clinical test for the detection of basophil histamine-releasing activity upon autoantibodies or autoreactive stimulation, has been suggested as a potential predictor in the control of urticaria. We sought to identify proteins that were differentially expressed in the sera of patients with positive and negative ASST results and to investigate their association with urticaria control.Proteomics analysis was performed using sera from 3 CSU patients with positive ASST results compared with those showing negative ASST results. Seven upregulated and 5 downregulated proteins were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in the ASST-positive group compared with the ASST-negative group.Proteins that were differentially expressed according to the ASST results in CSU patients were classified into 6 groups: apolipoproteins, glycoproteins, modified albumin, haptoglobulin, plectin, and others. Among these, apolipoprotein J or clusterin was validated using an enzyme-linked immunosorbent assay. Clusterin levels in 69 ASST-positive patients were significantly higher than those in 69 ASST-negative patients and in 86 healthy controls (231.2 ± 44.0 vs 210.2 ± 36.1 vs 118.7 ± 71.9 μg/mL, P urticaria would be refractory to antihistamines. Serum clusterin can be a prognostic marker to determine the responsiveness to antihistamine treatment in patients with CSU.

  15. EQ-5D Utilities in Chronic Spontaneous/Idiopathic Urticaria. (United States)

    Hawe, Emma; McBride, Doreen; Balp, Maria-Magdalena; Tian, Haijun; Halliday, Anna; Stull, Donald E


    To obtain utility estimates suitable for use in economic models for chronic spontaneous (idiopathic) urticaria (CSU). Patient-level data from three randomized clinical trials-ASTERIA I, ASTERIA II and GLACIAL-were analysed. Health states were derived from the Urticaria Activity Score over 7 days (UAS7); higher scores denote greater activity. The health state score ranges were urticaria free: 0; well-controlled urticaria: 1-6; mild urticaria: 7-15; moderate urticaria: 16-27; and severe urticaria: 28-42. The mean EQ-5D utilities were calculated for each health state. A mixed model was used to predict the EQ-5D according to UAS7 health states in a pooled data set containing all treatment arms and time points from the three trials. Pooled trial data were validated through visual comparisons and interaction terms. Fixed and random effects for trials and patients were included, along with the following covariates: UAS7 health state at baseline (moderate or severe); presence of angioedema at baseline and during follow-up; duration of CSU; number of previous CSU medications; visit; current treatment; and patient age and sex. There was a consistent improvement in EQ-5D utilities as urticaria activity decreased. The mean utilities ranged from 0.710 (severe urticaria) to 0.780 (moderate urticaria), 0.829 (mild urticaria), 0.862 (well-controlled urticaria) and 0.894 (urticaria free). Sensitivity and subgroup analyses confirmed the robustness of the results. The results suggest that EQ-5D utility scores increase with decreasing urticaria activity. EQ-5D utility scores enable the health-related quality of life of CSU patients to be compared with that of patients with other diseases.

  16. Long-term management of chronic spontaneous urticaria with omalizumab. (United States)

    Pinto Gouveia, M; Gameiro, A; Pinho, A; Gonçalo, M


    Clinical trials have shown the efficacy of omalizumabs efficacy in refractory chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU), but real-life management strategies are lacking. To assess the long-term efficacy and safety of omalizumab, and to identify predictive factors and optimum dosage regimens. This was a prospective study of 13 patients (11 women, 2 men) with severe CSU [weekly urticaria activity score (UAS7) > 28] resistant to anti-H1 antihistamines. Patients were started on omalizumab 150 mg subcutaneously every 4 weeks. Dose and interval between administrations were adjusted according to clinical response (189 administrations; treatment duration range 2-38 months). Mean UAS7 was 36.3 ± 5.4. Of the 13 patients, all had experienced angio-oedema, while in addition, 7 had delayed pressure urticaria (DPU) and 1 had solar urticaria (SU). After omalizumab treatment, 4 (30.8%) of the 13 patients had complete response (CR), and the remaining 8 (61.5%) had partial response. CR was achieved with a dose of 150 mg every 4 (n = 2 patients) or 5 (n = 2) weeks. One of these patients remained disease-free after stopping treatment. Partial responses were achieved with 150 mg every 4 weeks (n = 4) and with 300 mg (n = 4) at intervals of 5 weeks (n = 1), 4 weeks (n = 2) or 3 weeks (n = 1). Only one patient (7.7%) did not show significant improvement, despite a dose of 300 mg every 4 weeks. There were no significant differences in epidemiological, clinical and laboratory data between the different response groups. Only two adverse events were observed: one was mild headache and the other was severe angio-oedema and aggravation of urticaria within 6 h of omalizumab administration. Omalizumab dose and interval between administrations could be individualized for long-term management of CSU. © 2017 British Association of Dermatologists.

  17. Spontaneous Hypoglycemia After Islet Autotransplantation for Chronic Pancreatitis. (United States)

    Lin, Yu Kuei; Faiman, Charles; Johnston, Philip C; Walsh, R Matthew; Stevens, Tyler; Bottino, Rita; Hatipoglu, Betul A


    Spontaneous hypoglycemia has been reported in patients after total pancreatectomy (TP) and islet autotransplantation (IAT) with maintained insulin independence. Details surrounding these events have not been well described. The objective of the study was to determine the frequency and characteristics of spontaneous hypoglycemia in patients undergoing TP-IAT and/or to ascertain predictive or protective factors of its development. This was an observational cohort study in 40 patients who underwent TP-IAT from August 2008 to May 2014, with a median follow-up of 34 months. The study was conducted at a single institution (Cleveland Clinic). Patients included recipients of TP-IAT. The intervention included small, frequent meals in those patients who developed spontaneous hypoglycemia. Incidence of spontaneous hypoglycemia development, characteristics of the patients developing hypoglycemia, and their response to small, frequent meals were measured. Six of 12 patients, who maintained insulin independence, developed spontaneous hypoglycemia. The episodes could be fasting, postprandial, and/or exercise associated, with the frequency ranging from two to three times daily to once every 1-2 weeks. All patients experienced at least one episode that required external assistance, glucagon administration, and/or emergent medical attention. Patients who developed hypoglycemia had a lower median age and tended to have a lower median islet equivalent/kg body weight but a higher median total islet equivalent, body mass index, and homeostatic model assessment for insulin resistance score. All patients who received small, frequent meal intervention had improvement in severity and/or frequency of the hypoglycemic episodes. Spontaneous hypoglycemia is prevalent after TP-IAT. Although the underlying pathophysiology responsible for these hypoglycemia events remains to be elucidated, small, frequent meal intervention is helpful in ameliorating this condition.

  18. A bit of sweetness for GVHD prevention. (United States)

    Mohty, Mohamad; Gaugler, Béatrice


    In this issue of Blood, Parmar et al report on preclinical data suggesting that use of ex vivo fucosylated third-party human regulatory T cells (Tregs) could be an effective strategy for prevention of graft-versus-host disease (GVHD).

  19. cGVHD-Related Caries and Its Shared Features with Other 'Dry-Mouth'-Related Caries. (United States)

    Santos-Silva, Alan Roger; Feio, Patricia do Socorro Queiroz; Vargas, Pablo Agustin; Correa, Maria Elvira Pizzigatti; Lopes, Marcio Ajudarte


    Several systemic diseases and their medical treatment may predispose the development of aggressive dental caries. Head and neck radiotherapy, chemotherapy, Sjögren's syndrome and long-standing treatment with drugs that induce hyposalivation are some of these conditions. The aim of this article is to describe the clinical features of five patients who developed chronic graft-versus-host-disease (cGVHD) as a complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and, in spite of close dental follow-up, subsequently developed rampant caries. In these cases, the restorations showed early failure and the caries still progressed until generalized teeth destruction. The majority of the teeth therefore had to be extracted due to advanced dental caries and rapid clinical progression. Herein the term "cGVHD-related caries" is proposed to describe this under-recognized complication of cancer treatment that may evolve in allo-HSCT recipients that develop cGVHD. This condition is poorly recognized in the literature and may represent the final result of the clustering of oral complications in cGVHD patients, including mucositis, oral pain, hyposalivation, taste loss and oral infections, leading to rampant caries due to impaired oral hygiene and increased intake of highly cariogenic food. Consequently, the knowledge of this oral complication should improve the medical and dental management of cGVHD oral manifestations and improve the quality of life of patients with this post allo-HSCT complication.

  20. Therapy of antihistamine-resistant chronic spontaneous urticaria. (United States)

    Greiwe, Justin; Bernstein, Jonathan A


    Chronic urticaria affects up to 1-3% of the general population and contributes to significant direct and indirect medical costs as well as decreased quality of life, which has a significant economic impact on our health care system. Areas covered: Given the prevalence of this condition on a large sector of the population, finding lasting relief for refractory cases is essential and is the focus of this review. Expert commentary: The choice of appropriate therapy in chronic refractory urticaria is not a 'one-size fits all' approach. Treatment should take multiple factors into consideration including the chronicity of hives, presence of physical urticaria, type of cellular infiltrate on skin histopathology, patient age, concomitant comorbid conditions, as well as patient preference and cost.

  1. Chronic spontaneous urticaria: latest developments in aetiology, diagnosis and therapy (United States)

    Vestergaard, Christian; Deleuran, Mette


    Chronic urticaria is a debilitating disease characterized by itching and hives with or without angioedema lasting for more than 6 weeks. The disease carries a significant emotional and economic burden for the patient and often results in an odyssey between doctors of different specialities. Patients suffering from chronic urticaria are considered more difficult to satisfy, treat and to have a bigger emotional burden than the average patient in dermatology, paediatric and general practice settings. A joint initiative under the Dermatology section of the European Academy of Allergy and Clinical immunology (EAACI), the Global Allergy and Asthma European Network (GA2LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO) has resulted in recently published guidelines for the diagnosis, classification and treatment of chronic urticarial: these guidelines are clinically useful and have a high success rate when followed in daily clinical practice. The treatment of choice for chronic urticaria is still nonsedating antihistamines although other treatments are available, with omalizumab (humanized IgG anti IgE antibodies) as the newest therapy. The pathogenesis of urticaria is poorly understood but autoimmunity is considered as one of the major underlying causes for this disease, although other theories exist. PMID:26568807

  2. Pre-transplantation risk factors to develop sclerotic chronic GvHD after allogeneic HSCT: a multicenter retrospective study from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC). (United States)

    Detrait, M Y; Morisset, S; Peffault de Latour, R; Yakoub-Agha, I; Crocchiolo, R; Tabrizi, R; Bay, J-O; Chevalier, P; Barraco, F; Raus, N; Vigouroux, S; Magro, L; Mohty, M; Milpied, N; Blaise, D; Socié, G; Michallet, M


    Sclerotic chronic GvHD (cGvHD) is one of the most severe complications after allo-hematopoietic stem cell transplantation (HSCT). Risk factors associated with this complication remain not very well defined. With the aim to define a pre-transplantation risk profile, we have conducted a French retrospective analysis in 705 consecutive patients between 2005 and 2010. Analyses to determine pre-transplantation risk factors included as variables: patient and donor age, kind of donor, HLA matching, ABO matching, sex-matching, diagnosis, stem cell source, gender, GvHD prophylaxis and antithymocyte globulin (ATG) in the conditioning regimen. The cumulative incidence of sclerotic cGvHD was 18% (95% CI, 16.6-19.6) 3 years after onset of cGvHD. In univariate analysis, we found a significantly lower number of sclerotic cGvHD form in patients transplanted from cord blood cells (P=0.0021), in patients with a one mismatched donor (P=0.041) and in patients who had received ATG in the conditioning regimen (P=0.002). In multivariate analysis, factors associated with an increased risk of sclerotic cGvHD were young patient age, multiple myeloma and PBSC as the stem cell source. ATG in conditioning regimen and cord blood unit as the stem cell source were associated with a lower risk.

  3. Unmet clinical needs in chronic spontaneous urticaria. A GA(2) LEN task force report(1)

    DEFF Research Database (Denmark)

    Maurer, M; Weller, K; Bindslev-Jensen, Carsten


    autologous serum skin test (autoreactivity). Chronic spontaneous urticaria has major detrimental effects on quality of life, with sleep deprivation and psychiatric comorbidity being frequent. It also has a large impact on society in terms of direct and indirect health care costs as well as reduced...

  4. Omalizumab in patients with chronic spontaneous urticaria : A systematic review and GRADE assessment

    NARCIS (Netherlands)

    Urgert, M. C.; Van Den Elzen, M. T.; Knulst, A. C.; Fedorowicz, Z.; Van Zuuren, E. J.


    Summary Chronic spontaneous urticaria (CSU) is characterized by the occurrence of hives, angio-oedema or both for a period of at least 6 weeks. Many patients remain symptomatic despite treatment with H1 antihistamines, even at higher doses. This systematic review assessed the quality of

  5. Expert opinion : Defining response to omalizumab in patients with chronic spontaneous urticaria

    NARCIS (Netherlands)

    Ferrer, Marta; Boccon-Gibod, Isabelle; Gonçalo, Margarida; İnalöz, Hüseyin Serhat; Knulst, André; Lapeere, Hilde; Parthasaradhi, Anchala; Stingl, Georg; Tagka, Anna; Valenzuela, Fernando; Yeung, Jensen; Thomsen, Simon Francis


    Omalizumab (a recombinant, humanized anti-immunoglobulin-E antibody) has been shown in three pivotal Phase III trials (ASTERIA I, II and GLACIAL) and real-world studies to be effective and well-tolerated for the treatment of chronic spontaneous urticaria (CSU), and is the only licensed third-line

  6. Co-Occurrence of Chronic Spontaneous Urticaria with Immunoglobulin A Deficiency and Autoimmune Diseases. (United States)

    Frossi, Barbara; De Carli, Stefano; Bossi, Fleur; Pucillo, Carlo; De Carli, Marco


    Immunoglobulin (Ig) A deficiency is a primary immunodeficiency in which autoimmunity is frequently observed. Thirty to fifty percent of patients with spontaneous chronic urticaria have autoantibodies that are able to cross-link FcεRI on mast cells and basophils. We investigated whether spontaneous chronic urticaria in patients with IgA deficiency meets the criteria for autoimmunity. Four patients were screened for positivity to a skin prick test and an autologous serum skin test and for the presence of other autoimmune diseases. Patient sera were tested for the ability to activate basophils and mast cells in vitro by measuring surface CD63 expression and β-hexosaminidase release, respectively. The autologous serum test was positive in all patients, and patient sera were found to induce CD63 upregulation on basophils and degranulation of an LAD2 mast cell line. Moreover, all patients were affected by other autoimmune disorders. For the first time, these data point out chronic autoimmune urticaria in subjects with an IgA deficiency and confirm that different autoimmune disorders are common among patients with an IgA deficiency. Patients with chronic autoimmune spontaneous urticaria should be screened for IgA deficiency, especially if they are affected by other autoimmune disorders. Thus, spontaneous urticaria could mirror more complex systemic diseases, such as immune deficiency. © 2016 S. Karger AG, Basel.

  7. Effectiveness and safety of antihistamines up to fourfold or higher in treatment of chronic spontaneous urticaria

    NARCIS (Netherlands)

    van den Elzen, Mignon T; van Os-Medendorp, Harmieke; van den Brink, Imke; van den Hurk, Karin; Kouznetsova, Ouliana I; Lokin, Alexander S H J; Laheij-de Boer, Anna-Marijke; Röckmann, Heike; Bruijnzeel-Koomen, Carla A F M; Knulst, André C


    Background: Treatment with second-generation antihistamines is recommended in patients with chronic spontaneous urticaria (CSU). Some patients remain unresponsive even after up-dosing up to fourfold. Many third line treatment options have limited availability and/or give rise to significant side

  8. A spontaneous mutation characterized by chronic proliferative dermatitis in C57BL mice

    NARCIS (Netherlands)

    HogenEsch, H.; Gijbels, M. J.; Offerman, E.; van Hooft, J.; van Bekkum, D. W.; Zurcher, C.


    Chronic proliferative dermatitis is a new spontaneous mutation in C57BL/Ka mice. Breeding results suggest an autosomal recessive mode of inheritance. Mutant mice develop skin lesions at the age of 5 to 6 weeks. The lesions occur in the ventral and dorsal skin of the body, whereas ears, footpads, and

  9. Spontaneous (Autoimmune) Chronic Urticaria in Children: Current Evidences, Diagnostic Pitfalls and Therapeutic Management. (United States)

    Poddighe, Dimitri; De Amici, Mara; Marseglia, Gian L


    Etiologic diagnosis of pediatric chronic urticaria is quite challenging, as few cases can be associated to specific triggers. Thus, more than 50% of chronic urticaria in children are labeled as idiopathic. Several evidences supported an autoimmune pathogenesis in 30-40% of patients with idiopathic (or spontaneous) chronic urticaria in adults, where the diagnosis of autoimmune chronic urticaria included in vivo and in vitro tests, revealing the presence of autoantibodies against high-affinity IgE receptors mainly. This review aimed at collecting and analyzing all the available evidences on the diagnosis and treatment of autoimmune chronic urticaria in children, including most recent developments and patents. Most pediatric studies relied on autologous serum skin test only, in order to evidence autoimmune urticaria. A complete diagnostic assessment of pediatric autoimmune chronic urticaria, demonstrating an antibodymediated mechanism of disease, might ameliorate the therapeutic management of spontaneous (autoimmune) chronic urticaria in children, supporting the use of omalizumab rather than immuno-suppressive therapy in cases resistant to the firstline treatments.

  10. Successful and Safe Treatment of Chronic Spontaneous Urticaria with Omalizumab in a Woman during Two Consecutive Pregnancies

    Directory of Open Access Journals (Sweden)

    Misbah Nasheela Ghazanfar


    Full Text Available Chronic spontaneous urticaria is an itching skin disease characterised by wheals, angioedema, or both present for more than six weeks. Omalizumab is a humanized anti-IgE monoclonal antibody recently approved for treatment of chronic urticaria. Several randomised controlled trials have investigated the safety, tolerability, and efficacy of omalizumab for chronic urticaria. The safety of omalizumab in pregnancy is not known. We describe a female patient with chronic spontaneous urticaria who was treated with omalizumab continuously through two consecutive pregnancies with convincing results and no apparent toxicity.

  11. Successful and Safe Treatment of Chronic Spontaneous Urticaria with Omalizumab in a Woman during Two Consecutive Pregnancies

    DEFF Research Database (Denmark)

    Ghazanfar, Misbah Nasheela; Thomsen, Simon Francis


    Chronic spontaneous urticaria is an itching skin disease characterised by wheals, angioedema, or both present for more than six weeks. Omalizumab is a humanized anti-IgE monoclonal antibody recently approved for treatment of chronic urticaria. Several randomised controlled trials have investigated...... the safety, tolerability, and efficacy of omalizumab for chronic urticaria. The safety of omalizumab in pregnancy is not known. We describe a female patient with chronic spontaneous urticaria who was treated with omalizumab continuously through two consecutive pregnancies with convincing results...

  12. Decreased spontaneous eye blink rates in chronic cannabis users: evidence for striatal cannabinoid-dopamine interactions.

    Directory of Open Access Journals (Sweden)

    Mikael A Kowal

    Full Text Available Chronic cannabis use has been shown to block long-term depression of GABA-glutamate synapses in the striatum, which is likely to reduce the extent to which endogenous cannabinoids modulate GABA- and glutamate-related neuronal activity. The current study aimed at investigating the effect of this process on striatal dopamine levels by studying the spontaneous eye blink rate (EBR, a clinical marker of dopamine level in the striatum. 25 adult regular cannabis users and 25 non-user controls matched for age, gender, race, and IQ were compared. Results show a significant reduction in EBR in chronic users as compared to non-users, suggesting an indirect detrimental effect of chronic cannabis use on striatal dopaminergic functioning. Additionally, EBR correlated negatively with years of cannabis exposure, monthly peak cannabis consumption, and lifetime cannabis consumption, pointing to a relationship between the degree of impairment of striatal dopaminergic transmission and cannabis consumption history.

  13. Spontaneous choledochal cyst perforation in pregnancy with co-existent chronic pancreatitis. (United States)

    Singh, Harjeet; Gupta, Rahul; Dhaliwal, Lakhbir; Singh, Rajinder


    Choledochal cysts are a congenital disorder of the bile duct, usually presenting in childhood. As they cause weakening of the wall of the bile duct, any distal obstruction, infection or reflux of amylase-rich fluid in the biliary tract can predispose to spontaneous perforation. A 25-year-old pregnant woman at 35 weeks of gestation presented with acute abdominal and fetal distress. On emergency laparotomy, common bile duct perforations were detected. T-tube drainage and caesarean section were performed. A t-tube cholangiogram revealed the diagnosis of a choledochal cyst with an abnormal pancreatobiliary junction and chronic pancreatitis. The patient later underwent cyst excision with Roux en Y hepaticojejunostomy. Spontaneous choledochal cyst perforation in pregnancy can be successfully managed by a two-stage operation. 2014 BMJ Publishing Group Ltd.

  14. H1-antihistamines for chronic spontaneous urticaria: an abridged Cochrane Systematic Review. (United States)

    Sharma, Maulina; Bennett, Cathy; Carter, Ben; Cohen, Stuart N


    Chronic spontaneous urticaria is characterized by recurrent itchy wheals. First-line management is with H1-antihistamines. We sought to conduct a Cochrane Review of H1-antihistamines in the treatment of chronic spontaneous urticaria. A systematic search of major databases for randomized controlled trials was conducted. We included 73 studies with 9759 participants; 34 studies provided outcome data for 23 comparisons. Compared with placebo, cetirizine 10 mg daily in the short and intermediate term (RR 2.72; 95% confidence interval [CI] 1.51-4.91) led to complete suppression of urticaria. Levocetirizine 20 mg daily was effective for short-term use (RR 20.87; 95% CI 1.37-317.60) as was 5 mg for intermediate-term use (RR 52.88; 95% CI 3.31-843.81). Desloratadine 20 mg was effective for the short term (RR 15.97; 95% CI 1.04-245.04) as was 5 mg in the intermediate term (RR 37.00; 95% CI 2.31-593.70). There was no evidence to suggest difference in adverse event rates between treatments. Some methodological limitations were observed. Few studies for each comparison reported outcome data that could be incorporated in meta-analyses. At standard doses, several antihistamines are effective and safe in complete suppression of chronic spontaneous urticaria. Research on long-term treatment using standardized outcome measures and quality of life scores is needed. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  15. Histamine release positive test associates with disease remission in chronic spontaneous urticaria

    DEFF Research Database (Denmark)

    Berti, A; Yacoub, M R; Skov, Per Stahl


    Summary: Background. Histamine release (HR) test has previously been shown to predict the presence of endogenous histamine-releasing factors in chronic spontaneous urticaria (CSU). Objectives and methods. Twenty CSU patients unresponsive to antihistamine treatment were enrolled in order to evaluate...... with a positive HR test had a significant reduction of disease activity (p = 0.003) whereas patients with a negative HR test did not (p > 0.05), leading to disease remission and antihistamine treatment withdrawal in 67% (6/9) of positive HR test patients versus 18% (2/11) of negative HR test patients (p = 0...

  16. Visual diagnosis: Chronic diarrhea and failure to thrive in a 5-year-old girl. (United States)

    Hasosah, Mohammed; Satti, Mohamed; Hayat, Amirshazad


    Chronic GVHD usually develops 100 days after BMT and is a serious and potentially life-threatening long-term complication. Chronic GVHD can occur after previous or ongoing acute GVHD or in patients without a history of acute GVHD (eg, de novo disease) as illustrated by this case. In evaluating a patient presenting with chronic diarrhea more than 100 days after BMT, one must consider a serious underlying illness such as chronic GVHD because it is a major cause of morbidity and mortality of allogeneic stem cell transplantation. As indicated by this case, chronic GVHD can cause diarrhea. Complete evaluation of the diarrhea state should be part of the initial investigation. In many cases, however, the diagnosis of GVHD is not straightforward, and gastrointestinal biopsy and histologic confirmation is often necessary to corroborate a clinical impression of chronic GVHD.

  17. Spontaneous Retroperitoneal Hemorrhage in a Patient with Prolymphocytic Transformation of Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Gwynivere A. Davies


    Full Text Available Prolymphocytic transformation of chronic lymphocytic leukemia is a rare but recognized entity. We present the case of a 76-year-old gentleman with a previous diagnosis of chronic lymphocytic leukemia who presented with fatigue, fever, and a white blood cell count of 500 000 with prolymphocytes on peripheral blood examination. Chlorambucil and dexamethasone were initiated. He developed progressive anemia during his admission with no clear cause on initial CT examination. Bilateral hip pain began several days later and he was unfortunately diagnosed with a large spontaneous retroperitoneal hemorrhage postmortem. This condition is rare and generally occurs in those receiving therapeutic anticoagulation or dialysis, with known bleeding disorders or vascular malformation, none of which were present in our patient. Pathology revealed marked leukemoid engorgement of the vessels of many organs with prolymphocytes. We discuss the potential etiologies and relationships between these critical diagnoses.

  18. A rare life-threatening disease: unilateral kidney compressed by huge chronic spontaneous retroperitoneal hemorrhage

    Directory of Open Access Journals (Sweden)

    Lu HY


    Full Text Available Hao-Yuan Lu,1,* Wei Wei,2,* Qi-Wei Chen,1,* Qing-Gui Meng,1 Gao-Hua Hu,1 Xian-Lin Yi,1,3 Xian-Zhong Bai1 1Department of Urology, Tumor Hospital of Guangxi Medical University and Guangxi Cancer Research Institute, Nanning 530021, China; 2Department of Radiology, Tumor Hospital of Guangxi Medical University and Guangxi Cancer Research Institute, Nanning 530021,China; 3Hubei Engineering Laboratory for Synthetic Microbiology, Wuhan Institute of Biotechnology, Wuhan 430075, China *These authors contributed equally to this work Objectives: To study an uncommon life-threatening disease, spontaneous retroperitoneal and perirenal hemorrhage. Case descriptions: A 69-year-old male presented with pain in the left waist and back of 1 month duration. The renal abscess was suspected by magnetic resonance imaging before operation. The perirenal hematoma was cleaned by operation. In another case, the patient had a functional solitary left kidney compressed by a huge retroperitoneal mass and uropenia appeared. Results: The first patient died of adult respiratory distress syndrome after surgery. The second patient died of cardiac insufficiency and pulmonary embolism on the second day after evacuation of retroperitoneal hematoma. Conclusion: Conservative surgery, such as selective arterial embolization, is a reasonable approach in patients with chronic spontaneous retroperitoneal and perirenal space hemorrhage and with poor general condition. We strongly recommend drainage or interventional therapy, but not a major surgery, in patients with poor condition. Keywords: kidney, spontaneous, retroperitoneal, hemorrhage, surgery

  19. Chronic changes of hematocrit value alter blood pressure and glomerular filtration in spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Milanović S.


    Full Text Available Many studies in hypertensive humans and animals have shown that increased blood viscosity is in direct relation with essential hypertension. The aim of our studies was to investigate the effects of chronic hematocrit value changes on arterial blood pressure and kidney function in genetically induced hypertension. To this end, we studied the effects of several interventions, designed to increase/decrease hematocrit, on hemodynamic parameters, vascular reactivity, glomerular filtration and renal function curve in spontaneously hypertensive rats (SHR. Results of our study show that chronic hematocrit value elevation increases blood pressure and peripheral vascular resistance in SHR. On the other hand, chronic hematocrit lowering elucidates blood pressure and peripheral vascular resistance decrease followed by cardiac output rising. Both hematocrit value changes significantly reduce vasodilatory vascular response. Hematocrit lowering induces acute renal failure. Sodium excretion is shifted to higher blood pressure values in high hematocrit value animals and opposite - lower blood pressure values in low hematocrit value animals. Repeated transfusions develop salt sensitive malignant hypertension in SHR. Further studies are necessary to evaluate the degree of kidney damage after chronic hematocrit value changes in SHR.

  20. Challenge-proven aspirin hypersensitivity in children with chronic spontaneous urticaria. (United States)

    Cavkaytar, Ozlem; Arik Yilmaz, Ebru; Buyuktiryaki, Betul; Sekerel, Bulent E; Sackesen, Cansin; Soyer, Ozge U


    Nonsteroidal anti-inflammatory drug (NSAID) exacerbated cutaneous disease is defined as the exacerbation of wheals and/or angioedema in patients with a history of chronic spontaneous urticaria (CSU). The objective of this study was to define 'aspirin-hypersensitive' children and adolescents in a clearly defined group of patients with CSU and to describe their clinical features. Eighty-one children with a history of CSU were enrolled over a 3-year period. The daily or almost daily (>4 days a week) presence of urticaria was defined as 'chronic persistent urticaria' (CPU), while the presence of urticaria for 2-4 days a week was defined as 'chronic recurrent urticaria' (CRU). Single-blind, placebo-controlled provocation tests (SBPCPTs) with aspirin were performed for children with CSU. Patients with CRU had a longer duration of cutaneous symptoms [1.6 (0.5-4) vs 0.6 (0.3-1.5) years], and stress was less frequently experienced as an eliciting factor in patients with CRU compared with the patients with CPU (P urticaria, determination of NSAID hypersensitivity in a well-controlled clinical setting will help to avoid severe drug hypersensitivity reactions. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Steroid-Refractory Acute GVHD: Predictors and Outcomes

    Directory of Open Access Journals (Sweden)

    Jason R. Westin


    Full Text Available Patients with steroid-resistant acute graft versus host disease (aGVHD have a dismal prognosis, with mortality rates in excess of 90%. We sought to identify a subgroup of patients less likely to benefit from initial therapy with corticosteroids as well as the impact of response on day 14 on outcome. Retrospective evaluation was performed of patients with biopsy-proven aGVHD treated with corticosteroids after allogeneic HSCT at M.D. Anderson Cancer Center from 1998 through 2002 (=287. Overall response to first-line therapy on day 14 was 56%. Grade III-IV aGVHD and hyperacute GVHD were the most significant factors predicting failure. Patients who fail to respond to steroids by day 14 should be considered for clinical trials. Severity of aGVHD, hyperacute GVHD, and sex mismatch could be integrated into prognostic scoring systems which may allow for pretreatment identification of patients unlikely to benefit from standard therapy with corticosteroids.

  2. All trans retinoic acid abrogates spontaneous monocytic growth in juvenile chronic myelomonocytic leukaemia. (United States)

    Cambier, N; Menot, M L; Schlageter, M H; Balitrand, N; Leblanc, T; Bordigoni, P; Rohrlich, P; Lamagnère, J P; Donadieu, J; Herbelin, C; Puissant, C; Gourand, F; Baruchel, A; Chomienne, C


    All trans retinoic acid, the active metabolite of vitamin A, exerts profound effects on cell differentiation. On normal myeloid progenitors, retinoids switch the differentiation program of granulo-macrophagic progenitors towards the granulocytic lineage and consequently reduce CFU-M colony formation. Bone marrow and peripheral blood mononuclear cells from children with Juvenile Chronic Myelomonocytic Leukaemia show typical spontaneous monocytic growth. We questioned whether in this disease, retinoids could switch myelomonocytic growth and inhibit the abnormal CFU-M colony proliferation. Ten JCML samples were studied in the presence of ATRA in methyl cellulose colony assay, before (CFU-C) or after (pre-CFU) liquid suspension culture. In vitro characteristics of JCML such as spontaneous monocytic growth in the absence of growth factor was noted in all patients. In the presence of leucocyte-conditioned medium, nine samples showed only CFU-M growth and one sample CFU-GM growth. Incubation with ATRA inhibited CFU-M colony formation in nine cases. Enhancement of granulocytic differentiation (CFU-G) was noted in nine cases. ATRA also inhibited CD34+ JCML monocytic growth and GM-CSF hypersensitivity. These data suggest that, in JCML progenitors, retinoid pathways are functional and inhibition of immature monocytic progenitors cells may be achieved with retinoids, without impeding granulocytic cell growth.

  3. Mediators of Inflammation and Angiogenesis in Chronic Spontaneous Urticaria: Are They Potential Biomarkers of the Disease?

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    Ilaria Puxeddu


    Full Text Available In chronic spontaneous urticaria (CSU, different pathophysiological mechanisms, potentially responsible for the development of the disease, have been recently described. It is likely that the activation of skin mast cells with consequent release of histamine and other proinflammatory mediators is responsible for vasodilation in the lesional skin of CSU. However, the underlying causes of mast cell activation in the disease are largely unknown and remain to be identified. Thus, in this review, we discuss new insights in the pathogenesis of CSU, focusing on inflammation and angiogenesis. The understanding of these mechanisms will enable the identification of biomarkers useful for the diagnosis, follow-up, and management of CSU and will allow the development of novel, more specific, and patient-tailored therapies.

  4. Adolescent and adult male spontaneous hyperactive rats (SHR) respond differently to acute and chronic methylphenidate (Ritalin). (United States)

    Barron, Elyssa; Yang, Pamela B; Swann, Alan C; Dafny, Nachum


    Eight groups of male adolescent and adult spontaneous hyperactive rats (SHR) were used in a dose response (saline, 0.6, 2.5, and 10 mg/kg) experiment of methylphenidate (MPD). Four different locomotor indices were recorded for 2 hours postinjection using a computerized monitoring system. Acutely, the 0.6 mg/kg dose of MPD did not elicit an increase in locomotor activity in either the adolescent or in the adult male SHR. The 2.5 and the 10.0 mg/kg doses increased activity in the adolescent and the adult rats. Chronically, MPD treatment when comparing adolescent and adult gave the following results: the 0.6 mg/kg dose of MPD failed to cause sensitization in the adolescent group but caused sensitization in the adult group, while the 2.5 and 10 mg/kg both caused sensitization in the adolescent and adult groups.

  5. Long-term Tympanic Membrane Pathology Dynamics and Spontaneous Healing in Chronic Suppurative Otitis Media

    DEFF Research Database (Denmark)

    Jensen, Ramon Gordon; Koch, Anders; Homøe, Preben


    BACKGROUND:: Children in the developing parts of the world have a high prevalence of chronic suppurative otitis media (CSOM). It is estimated that 65 to 330 million people worldwide have CSOM, yet very little is known about the natural course of the disease. The Inuit population of the Arctic......-based cohort of 591 children originally examined during 1993 to 1994 at 3 to 8 years of age. Follow-up was attempted among 348 individuals still living in the areas. Video otoscopy and tympanometry were used. Data on otologic disease, ear surgery, and antibiotic use for otitis media were collected from medical...... of spontaneous healing was not influenced by the age at which CSOM was diagnosed in the initial study. Thirty-nine individuals (17%) had CSOM in either the initial study or at follow-up. Of these, 2 had never received antibiotic treatment for otitis media, and 15 had been treated less than 3 times. Eighty...

  6. Amino acid substitution at peptide-binding pockets of HLA class I molecules increases risk of severe acute GVHD and mortality (United States)

    Wang, Tao; Haagenson, Michael; Spellman, Stephen R.; Askar, Medhat; Battiwalla, Minoo; Baxter-Lowe, Lee Ann; Bitan, Menachem; Fernandez-Viña, Marcelo; Gandhi, Manish; Jakubowski, Ann A.; Maiers, Martin; Marino, Susana R.; Marsh, Steven G. E.; Oudshoorn, Machteld; Palmer, Jeanne; Prasad, Vinod K.; Reddy, Vijay; Ringden, Olle; Saber, Wael; Santarone, Stella; Schultz, Kirk R.; Setterholm, Michelle; Trachtenberg, Elizabeth; Turner, E. Victoria; Woolfrey, Ann E.; Lee, Stephanie J.; Anasetti, Claudio


    HLA disparity has a negative impact on the outcomes of hematopoietic cell transplantation (HCT). We studied the independent impact of amino acid substitution (AAS) at peptide-binding positions 9, 99, 116, and 156, and killer immunoglobulin-like receptor binding position 77 of HLA-A, B, or C, on the risks for grade 3-4 acute graft-versus-host disease (GVHD), chronic GVHD, treatment-related mortality (TRM), relapse, and overall survival. In multivariate analysis, a mismatch at HLA-C position 116 was associated with increased risk for severe acute GVHD (hazard ratio [HR] = 1.45, 95% confidence interval [CI] = 1.15-1.82, P = .0016). Mismatch at HLA-C position 99 was associated with increased transplant-related mortality (HR = 1.37, 95% CI = 1.1-1.69, P = .0038). Mismatch at HLA-B position 9 was associated with increased chronic GVHD (HR = 2.28, 95% CI = 1.36-3.82, P = .0018). No AAS were significantly associated with outcome at HLA-A. Specific AAS pair combinations with a frequency >30 were tested for association with HCT outcomes. Cysteine to tyrosine substitution at position 99 of HLA-C was associated with increased TRM (HR = 1.78, 95% = CI 1.27-2.51, P = .0009). These results demonstrate that donor-recipient mismatch for certain peptide-binding residues of the HLA class I molecule is associated with increased risk for acute and chronic GVHD and death. PMID:23982174

  7. Efficacy and safety of omalizumab in patients with chronic idiopathic/spontaneous urticaria who remain symptomatic on H1 antihistamines

    DEFF Research Database (Denmark)

    Saini, Sarbjit S; Bindslev-Jensen, Carsten; Maurer, Marcus


    ASTERIA I was a 40-week, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of subcutaneous omalizumab as add-on therapy for 24 weeks in patients with chronic idiopathic urticaria/spontaneous urticaria (CIU/CSU) who remained symptomatic despite H1 antihistamine...

  8. Omalizumab in the treatment of chronic spontaneous urticaria – literature review and own experience

    Directory of Open Access Journals (Sweden)

    Joanna Dawicka


    Full Text Available Chronic urticaria is a condition characterized by the appearance of wheals and/or angioedema that last for at least 6 weeks. According to the recent recommendations, if H1-antihistamines used in four times licensed doses remain ineffective, add-on treatment with omalizumab, cyclosporine A or montelukast should be applied. This paper offers a literature review of the studies on using omalizumab in chronic spontaneous urticaria (CSU treatment. Moreover, it presents our own experience with the use of omalizumab in the treatment of two patients with CSU. Both patients were treated with H1-antihistamines in four times licensed doses recommended by European guidelines, oral corticosteroids, montelukast, and methotrexate – all without satisfactory results. During the time of the omalizumab therapy both patients achieved a significant improvement measured by the decrease in the Average Urticaria Activity Score for 7 days (UAS7 – the first patient from 34 to 11.8 points, the second one from 41 to 5.76.

  9. Successful Omalizumab treatment in HIV positive patient with chronic spontaneous urticaria: a case report. (United States)

    Iemoli, E; Niero, F; Borgonovo, L; Cossu, M V; Piconi, S


    We described a case of a 56 year old homosexual HIV positive man who presented a history of CSU since one year (2012). All the allergologic, immunologic and microbiologic tests to evaluate the pathogenesis of wheals resulted negative. Therefore in June 2015 we decided to start therapy with Omalizumab while the patient kept on effective antiretroviral therapy with 310 cells/mm3 TCD4 counts and undetectable HIV viremia. After two monthly subcutaneuous injection of 150 mg of Omalizumab the patient had no more urticarial symptoms. UAS7 (Urticaria Activity Score over 7 days) and Cu-Q2oL (chronic urticarial quality of life questionnaire) dropped respectively to 14 from 42 and to 0 from 40 with increase of TCD4 counts while viral load remained undetectable. In November 2015, i.e. 4 months after the end of Omalizumab therapy, the patient was still asymptomatic with persistent effective immune-virological response to antiretroviral therapy. This case report confirms the excellent tolerability and efficacy of anti-IgE therapy in the treatment of spontaneous chronic urticarial even in an immunodepressed patient for HIV infection. Omalizumab therapy shows a remarkable clinical success and had no effect on peripheral TCD4 counts and HIV viral load.

  10. Justification for IgE as a therapeutic target in chronic spontaneous urticaria. (United States)

    Sánchez-Borges, M; Capriles-Hulet, A; Caballero-Fonseca, F; González-Aveledo, L


    Monoclonal anti-IgE antibodies (omalizumab) are able to induce clinically significant benefits in patients with severe chronic spontaneous urticaria (CS). Those results led clinicians and investigators to reconsider a possible pathogenic role not previously supported for IgE and its receptors in this disease, and to investigate additional approaches for understanding its pathogenesis. IgE antibodies to unknown environmental allergens able to trigger chronic urticaria are not generally regarded as the etiologic factor for the disease. Other proposed mechanisms for the production of wheals and angioedema in CSU include IgG autoantibodies and CD4-positive T cells directed to the high-affinity IgE receptor, autoantibodies to IgE itself, IgE autoantibodies directed to thyroid and nuclear autoantigens, highly cytokinergic IgE, and histamine-releasing factors able to bind to IgE and cause mast cell activation. It is expected that a better knowledge on the mechanisms leading to CSU and the clarification of the immunological effects of anti-IgE will provide novel therapies for this frequent condition.

  11. [A case of bilateral chronic subdural hematoma due to spontaneous intracranial hypotension without orthostatic headache]. (United States)

    Sakakura, Kazuki; Ayuzawa, Satoshi; Masuda, Yosuke; Kin, Hidehiro; Matsumura, Akira


    We herein present a case of bilateral chronic subdural hematoma(bilateral CSDH)caused by spontaneous intracranial hypotension(SIH)without orthostatic headache. A 67-year-old male patient with mild head injury suffered from a chronic, non-postural headache. Computed tomography of the brain showed bilateral CSDH. The hematomas were surgically evacuated using a closed drainage method. His headache immediately disappeared, but it recurred after 2 weeks. We further performed hematoma irrigation;however, his neurological status deteriorated with the development of pneumocephalus. Magnetic resonance imaging with gadolinium-DTPA showed diffuse pachymeningeal enhancement. His cerebrospinal fluid pressure was 3cmH2O, and radioisotope cisternography revealed cerebrospinal fluid leakage at the level of the cervicothoracic transition. No recurrence was found after 6 weeks of horizontal bed rest. The possibility of SIH should be considered in patients with CSDH, especially bilateral CSDH, even in elderly patients with a history of mild head trauma, and absence of orthostatic headache. Closed drainage method may be preferable in cases where surgical treatment is used.

  12. Cost Utility of Omalizumab Compared with Standard of Care for the Treatment of Chronic Spontaneous Urticaria. (United States)

    Graham, Jonathan; McBride, Doreen; Stull, Donald; Halliday, Anna; Alexopoulos, Stamatia Theodora; Balp, Maria-Magdalena; Griffiths, Matthew; Agirrezabal, Ion; Zuberbier, Torsten; Brennan, Alan


    Chronic spontaneous urticaria (CSU) negatively impacts patient quality of life and productivity and is associated with considerable indirect costs to society. The aim of this study was to assess the cost utility of add-on omalizumab treatment compared with standard of care (SOC) in moderate or severe CSU patients with inadequate response to SOC, from the UK societal perspective. A Markov model was developed, consisting of health states based on Urticaria Activity Score over 7 days (UAS7) and additional states for relapse, spontaneous remission and death. Model cycle length was 4 weeks, and total model time horizon was 20 years in the base case. The model considered early discontinuation of non-responders (response: UAS7 ≤6) and retreatment upon relapse (relapse: UAS7 ≥16) for responders. Clinical and cost inputs were derived from omalizumab trials and published sources, and cost utility was expressed as incremental cost-effectiveness ratios (ICERs). Scenario analyses included no early discontinuation of non-responders and an altered definition of response (UAS7 omalizumab was associated with increased costs and benefits relative to SOC. Probabilistic sensitivity analysis supported this result. Productivity inputs were key model drivers, and individual scenarios without early discontinuation of non-responders and adjusted response definitions had little impact on results. ICERs were generally robust to changes in key model parameters and inputs. In this, the first economic evaluation of omalizumab in CSU from a UK societal perspective, omalizumab consistently represented a treatment option with societal benefit for CSU in the UK across a range of scenarios.

  13. Spontaneous Immunity Against the Receptor Tyrosine Kinase ROR1 in Patients with Chronic Lymphocytic Leukemia.

    Directory of Open Access Journals (Sweden)

    Mohammad Hojjat-Farsangi

    Full Text Available ROR1 is a receptor tyrosine kinase expressed in chronic lymphocytic leukemia (CLL and several other malignancies but absent in most adult normal tissues. ROR1 is considered an onco-fetal antigen. In the present study we analysed spontaneous humoral and cellular immunity against ROR1 in CLL patients.Antibodies against ROR1 were analysed in 23 patients and 20 healthy donors by ELISA and Western blot. Purified serum IgG from patients was tested for cytotoxicity against CLL cells using the MTT viability assay. A cellular immune response against ROR1 derived HLA-A2 restricted 9 aa and 16 aa long peptides were analysed using peptide loaded dendritic cells co-cultured with autologous T cells from CLL patients (n = 9 and healthy donors (n = 6. IFN-γ, IL-5 and IL-17A-secreting T cells were assessed by ELISPOT and a proliferative response using a H3-thymidine incorporation assay.The majority of CLL patients had antibodies against ROR1. Significantly higher titers of anti-ROR1 antibodies were noted in patients with non-progressive as compared to progressive disease. The extracellular membrane-close ROR1 KNG domain seemed to be an immunodominant epitope. Ten patients with high titers of anti-ROR1 binding antibodies were tested for cytotoxicity. Five of those had cytotoxic anti-ROR1 antibodies against CLL cells. ROR1-specific IFN-γ and IL-17A producing T cells could be detected in CLL patients, preferentially in non-progressive as compared to patients with progressive disease (p<0.05.ROR1 seemed to spontaneously induce a humoral as well as a T cell response in CLL patients. The data support the notion that ROR1 might be a specific neo-antigen and may serve as a target for immunotherapy.

  14. Similar Efficacy with Omalizumab in Chronic Idiopathic/Spontaneous Urticaria Despite Different Background Therapy. (United States)

    Casale, Thomas B; Bernstein, Jonathan A; Maurer, Marcus; Saini, Sarbjit S; Trzaskoma, Benjamin; Chen, Hubert; Grattan, Clive E; Gimenéz-Arnau, Ana; Kaplan, Allen P; Rosén, Karin


    Data from the 3 omalizumab pivotal trials in patients with chronic idiopathic urticaria/chronic spontaneous urticaria (CIU/CSU) represent the largest database of patients reported to date with refractory disease (omalizumab, n = 733; placebo, n = 242). The objective of this study was to compare results from ASTERIA I and II, which included only approved doses of H1-antihistamine as background therapy based on regulatory authority requirements, to those from GLACIAL, which permitted higher doses of H1-antihistamines as well as other types of background therapy, in a post hoc analysis. Efficacy data from the placebo, omalizumab 150-mg, and omalizumab 300-mg treatment arms of ASTERIA I and II were pooled and analyzed (n = 162 and n = 160, respectively). The 300-mg treatment arm analyses were compared with the analysis of data from GLACIAL (n = 252) using analysis of covariance models. The key efficacy endpoint was change from baseline to week 12 in mean weekly itch severity score (ISS); other endpoints were also evaluated. Safety data were pooled from all 3 studies. Mean ISS was significantly reduced from baseline at week 12 in the pooled ASTERIA I and II omalizumab 150- and 300-mg treatment arms and in the GLACIAL omalizumab 300-mg arm. The weekly ISS reduction magnitude at week 12 was similar between the omalizumab 300-mg groups in the ASTERIA I and II pooled and GLACIAL studies. Similar treatment effect sizes were observed across multiple endpoints. Omalizumab was well tolerated and the adverse-event profile was similar regardless of background therapy for CIU/CSU. The overall safety profile was generally consistent with omalizumab therapy in allergic asthma. Omalizumab 300 mg was safe and effective in reducing CIU/CSU symptoms regardless of background therapy. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Treatment of chronic spontaneous urticaria with a single dose of omalizumab: A study of four cases

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    Radhakrishnan Subramaniyan


    Full Text Available Background: Chronic spontaneous urticaria (CSU has a detrimental effect on patients′ emotional and physical quality of life. Omalizumab, an anti-immunoglobulin E humanized monoclonal antibody, has been shown to be very effective in the treatment of refractory chronic urticaria patients but may not be an economically viable option for all CSU patients. However, we present a case series where a single dose of omalizumab gave sustained relief of symptoms in patients with CSU, which may be an economical option. Aims: The aim of this study is to assess the efficacy of a single dose of omalizumab in the treatment of CSU. Materials and Methods: Four patients of CSU whose disease was not controlled with four times the licensed dose of tablet fexofenadine 180 mg were exhibited one subcutaneous injection of omalizumab and were followed up at 4 weekly intervals for 24 weeks for Weekly Urticaria Activity Score 7 (UAS7 and Dermatology Life Quality Index (DLQI. Results: A sharp decline in UAS7 and DLQI was documented in 7-10 days. The decline was maintained up to 16 weeks in one case and 20 weeks in the other three cases. Both the scores at the end of the follow-up period of 24 weeks were better than the pre-omalizumab scores. Conclusion: The results of this case series indicate the efficacy of a single-dose omalizumab in treating moderate to severe refractory CSU. Further studies are required to identify the minimum frequency of administering omalizumab to effectively control CSU. This would greatly reduce the cost of this novel therapy.

  16. Impact of corticosterone treatment on spontaneous seizure frequency and epileptiform activity in mice with chronic epilepsy.

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    Olagide W Castro

    Full Text Available Stress is the most commonly reported precipitating factor for seizures in patients with epilepsy. Despite compelling anecdotal evidence for stress-induced seizures, animal models of the phenomena are sparse and possible mechanisms are unclear. Here, we tested the hypothesis that increased levels of the stress-associated hormone corticosterone (CORT would increase epileptiform activity and spontaneous seizure frequency in mice rendered epileptic following pilocarpine-induced status epilepticus. We monitored video-EEG activity in pilocarpine-treated mice 24/7 for a period of four or more weeks, during which animals were serially treated with CORT or vehicle. CORT increased the frequency and duration of epileptiform events within the first 24 hours of treatment, and this effect persisted for up to two weeks following termination of CORT injections. Interestingly, vehicle injection produced a transient spike in CORT levels - presumably due to the stress of injection - and a modest but significant increase in epileptiform activity. Neither CORT nor vehicle treatment significantly altered seizure frequency; although a small subset of animals did appear responsive. Taken together, our findings indicate that treatment of epileptic animals with exogenous CORT designed to mimic chronic stress can induce a persistent increase in interictal epileptiform activity.

  17. Autologous serum and plasma skin tests in chronic spontaneous urticaria: A reappraisal

    Directory of Open Access Journals (Sweden)

    Muthu Sendhil Kumaran


    Full Text Available Aim: The objective of this study was to assess autologous serum skin test (ASST vs autologous plasma skin test (APST response in chronic spontaneous urticaria (CSU patients and study the significance of intensity of positive responses in relation to clinicoepidemiological parameters. Materials and Methods: One hundred CSU patients and 100 age and sex-matched controls were recruited. The demographic and clinical features were recorded in all patients and routine investigations were performed. ASST and APST tests were performed as per the standard guidelines. Results: The mean duration of illness was 4.85 ± 5.07 years, 90% patients were APST (+, 68% ASST (+, and 22 patients were only APST (+. Positive predictive value (PPV of ASST and APST was 90.7% and 95.7%, respectively. A significant inverse association was seen between thyroid status and serum IgE levels with APST and ASST positivity. Conclusion: APST appears to have better PPV and high intensity of positive response on autologous tests, and correlates with ANA positivity and angioedema.

  18. Omalizumab therapy for treatment of recalcitrant chronic spontaneous urticaria in an Asian population. (United States)

    Kulthanan, Kanokvalai; Tuchinda, Papapit; Chularojanamontri, Leena; Likitwattananurak, Chayanee; Ungaksornpairote, Chanida


    There are limited data regarding omalizumab in the treatment of recalcitrant chronic spontaneous urticaria (CSU) in Asian populations. This study evaluated the effectiveness and the proper dosage of omalizumab for Asian CSU patients in a real-life setting. We retrospectively reviewed recalcitrant CSU patients seeking treatment at the Skin Allergy Clinic, Siriraj Hospital during the 3-year period. All patients were treated with omalizumab as an add-on therapy. Standard seven-day urticaria activity score (UAS7) and medication score were used to assess omalizumab response. Of 13 patients, 9 patients (70%) responded well to 150 mg omalizumab injection every month, whereas 4 patients requiring updosing to 300 mg. In the 150 mg group, one patient achieved complete symptom control without antihistamine intake. Most of them required antihistamines without prednisolone and ciclosporin. Onset of omalizumab was fast, usually within the first week. Though only two patients in the 300 mg group achieved complete absence of symptoms, ciclosporin and oral corticosteroids could be discontinued. No patients reported adverse effects. Omalizumab at an initial dosage of 150 mg was effective in the treatment of recalcitrant CSU among Asians. Updosing to 300 mg was required to achieve satisfactory outcomes.

  19. Omalizumab for treating chronic spontaneous urticaria: an expert review on efficacy and safety. (United States)

    Giménez-Arnau, Ana M


    Chronic spontaneous urticaria (CSU) is characterized by the recurrence of itchy hives and/or angioedema for greater than six weeks, with no known external trigger. Omalizumab, a humanized, recombinant, monoclonal anti-IgE antibody, is the only approved add-on therapy for H1-antihistamine refractory CSU patients. Areas covered: The objective of this article is to discuss the mechanism of action, pharmacokinetics and pharmacodynamics of omalizumab for the treatment of CSU. The review also summarizes efficacy and safety data from proof-of-concept, phase II (X-CUISITE, MYSTIQUE), and pivotal phase III omalizumab studies (ASTERIA I, ASTERIA II, and GLACIAL). Expert opinion: Omalizumab is a clinically effective and safe biological therapy for treating H1-antihistamine refractory CSU patients. It significantly reduces CSU symptoms (hives, itch and angioedema), and improves patient health-related quality of life. While omalizumab is already integral to the treatment of antihistamine refractory CSU, widespread use will depend on legal and economic factors, as well as improvements in the early and accurate diagnosis of CSU patients who would benefit from treatment.

  20. The Clinical Correlations of Helicobacter pylori Virulence Factors and Chronic Spontaneous Urticaria

    Directory of Open Access Journals (Sweden)

    Yi-Chun Chiu


    Full Text Available Background and Study Aims. The association between Helicobacter pylori (H. pylori and chronic spontaneous urticaria (CSU remains controversial. This study explored the role of H. pylori in CSU among different virulent genotypes patients. Patients and Methods. Patients infected by H. pylori were sorted into two groups as group A (with CSU and group B (without CSU. The tissue materials were taken via endoscopy for polymerase chain reaction study to determine virulence factors. After H. pylori eradication therapy, the eradication rate and response of urticaria were evaluated by using C13-UBT and a three-point scale (complete remission, partial remission, or no improvement. Results. The results were comparable between patients of groups A and B in terms of H. pylori infection rates and eradication rate. Longitudinal follow-up of 23.5 months showed complete remission of urticaria in 63.6% but no improvement in 36.4% of the patients after H. pylori eradication. H. pylori infected patients with different virulence factors such as cytotoxin-associated gene A, vacuolating cytotoxin gene A signal region and middle region have similar remission rates for CSU. Conclusions. Current study suggests that H. pylori may play a role in the development and disease course of CSU but may be irrelevant to different virulent genotypes.

  1. Mechanisms of action that contribute to efficacy of omalizumab in chronic spontaneous urticaria. (United States)

    Kaplan, A P; Giménez-Arnau, A M; Saini, S S


    The monoclonal anti-immunoglobulin E (IgE) antibody, omalizumab, was the first drug approved for use in patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) who remain symptomatic despite H 1 -antihistamine treatment. Omalizumab binds to free IgE, which lowers free IgE levels and causes FcεRI receptors on basophils and mast cells to be downregulated. It has been shown to improve symptoms of CIU/CSU, but its mechanism of action is not currently understood. Potential mechanisms in CIU/CSU include reducing mast cell releasability, reversing basopenia and improving basophil IgE receptor function, reducing activity of IgG autoantibodies against FcεRI and IgE, reducing activity of IgE autoantibodies against an antigen or autoantigen that has yet to be definitively identified, reducing the activity of intrinsically 'abnormal' IgE, and decreasing in vitro coagulation abnormalities associated with disease activity. However, none of these theories alone or in combination fully account for the pattern of symptom improvement seen with omalizumab therapy, and therefore, no one mechanism is likely to be the definitive mechanism of action. Additional research is needed to further clarify the involvement of omalizumab in relieving symptoms associated with the complex, multifactorial pathogenesis of CIU/CSU. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Chronic Subdural Hematoma Associated with Spontaneous Intracranial Hypotension: Therapeutic Strategies and Outcomes of 55 Cases. (United States)

    Takahashi, Koichi; Mima, Tatsuo; Akiba, Yoichi


    Spontaneous intracranial hypotension (SIH) has increasingly been recognized, and it is well known that SIH is sometimes complicated by chronic subdural hematoma (SDH). In this study, 55 cases of SIH with SDH were retrospectively analyzed, focusing on therapeutic strategies and outcomes. Of 169 SIH cases (75 males, 84 females), 55 (36 males, 19 females) were complicated by SDH. SIH was diagnosed based on clinical symptoms, neuroimaging, and/or low cerebrospinal fluid pressure. Presence of orthostatic headache and diffuse meningeal enhancement on magnetic resonance imaging were regarded as the most important criteria. Among 55 SIH with SDH cases, 13 improved with conservative treatment, 25 initially received an epidural blood patch (EBP), and 17 initially underwent irrigation of the hematomas. Of the 25 initially treated with EBP, 7 (28.0%) needed SDH surgery and 18 (72.0%) recovered fully without surgery. Of 17 SDH cases initially treated with surgery, 6 (35.7%) required no EBP therapy and the other 11 (64.3%) needed EBP and/or additional SDH operations. In the latter group, 2 cases had transient severe complications during and after the procedures. One of these 2 cases developed a hoarse voice complication. Despite this single, non-severe complication, all enrolled in this study achieved good outcomes. The present study suggests that patients initially receiving SDH surgery may need additional treatments and may occasionally have complications. If conservative treatment is insufficient, EBP should be performed prior to hematoma irrigation.

  3. Assessment of chronic spontaneous urticaria by serum-induced tumor necrosis factor alpha and matrix metalloproteinase-9 release

    DEFF Research Database (Denmark)

    Falkencrone, Sidsel; Bindslev-Jensen, Carsten; Skov, Per Stahl

    BACKGROUND Previous studies from our group have demonstrated that IgE-mediated basophil activation leads to release of TNFα that in turn can induce matrix metallo-proteinase-9 (MMP-9) release from monocytes. We wished to investigate if serum from chronic spontaneous urticaria-patients with auto-a....... Release levels appeared to be positive correlated to ASST reaction in ASST+ patients but not to disease severity for CSU patients in general....

  4. Effect of Chronic Social Stress on Endothelial Function of the Mesenteric Artery of Normotensive and Spontaneously Hypertensive Rats


    Kaprinay B.; Bernatova I.; Sotnikova R.


    The aim of the work was to study the effect of chronic social stress induced by increased population density, “crowding stress” on blood pressure and endothelial function of arteries of male normotensive Wistar and spontaneously hypertensive (SHR) rats. Based on the results, we assume that social stress-induced reduction in endothelium-dependent relaxation and increased blood pressure of SHR rats is most likely associated with decreased bioavailability of nitric oxide.

  5. A positive serum basophil histamine release assay is a marker for ciclosporin-responsiveness in patients with chronic spontaneous urticaria

    DEFF Research Database (Denmark)

    Iqbal, Kamran; Bhargava, Kapil; Skov, Per Stahl


    ABSTRACT: The electronic records of 398 patients with chronic spontaneous urticaria (CSU) who had had a serum basophil histamine release assay (BHRA) performed as a marker of functional autoantibodies were audited. The BHRA was positive in 105 patients (26.4%). Fifty eight were treated with ciclo...... with ciclosporin because they were H1 anti-histamine unresponsive. CSU patients with a positive BHRA were more likely to respond clinically (P...

  6. A Popular myth - low-histamine diet improves chronic spontaneous urticaria - fact or fiction? (United States)

    Wagner, N; Dirk, D; Peveling-Oberhag, A; Reese, I; Rady-Pizarro, U; Mitzel, H; Staubach, P


    Chronic spontaneous urticaria (CsU) is a frequent dermatological disease that might last for months or years with high impact on quality of life. Known causes are autoreactive phenomena, infections or intolerances, rarely IgE-mediated allergies. One-third of CsU patients benefit from a low-pseudoallergen diet. Additionally, it is often discussed, that reducing histamine ingestion alone might improve clinical symptoms and quality of life in CsU patients despite the uncertain role of the histamine-degrading enzyme diamine oxidase (DAO). Aim of this study was to investigate the impact of low-histamine diet on symptoms and quality of life in patients with CsU. Patients suffering from CsU accompanied by gastrointestinal symptoms were included in the study. They underwent low-histamine diet for at least 3 weeks. During the whole study, urticaria activity score (UAS) was recorded daily in a patient's diary. Quality of life was assessed during screening, baseline and post diet visits by completing questionnaires (DLQI and Cu-Q(2)oL). DAO activity was measured before and after elimination diet. A total of 75% of the patients had a benefit from the low-histamine diet. Thirty-four of 56 patients (61%) reached the primary endpoint of the study, an improvement of UAS 4 of ≥3. Overall, a significant reduction from 9.05 to 4.23 points (P = 0.004) was achieved; the average reduction in a strongly affected subgroup was 8.59 points (P histamine diet is a therapeutically useful, simple and cost-free tool to decrease symptoms and increase quality of life in CsU patients with gastrointestinal involvement. Further research is needed to understand the role of diamine oxidase. © 2016 European Academy of Dermatology and Venereology.

  7. Angioedema in the omalizumab chronic idiopathic/spontaneous urticaria pivotal studies. (United States)

    Zazzali, James L; Kaplan, Allen; Maurer, Marcus; Raimundo, Karina; Trzaskoma, Benjamin; Solari, Paul G; Antonova, Evgeniya; Mendelson, Meryl; Rosén, Karin E


    Angioedema, present in some patients with chronic idiopathic/spontaneous urticaria (CIU/CSU), may have a negative effect on patient quality of life. To describe patient-reported angioedema and its management in the pivotal omalizumab studies (ASTERIA I, ASTERIA II, GLACIAL). Enrolled patients with CIU/CSU remained symptomatic despite treatment with histamine 1 (H 1 )-antihistamines at licensed doses (ASTERIA I, ASTERIA II) or H 1 -antihistamines at up to 4 times the approved dose plus H 2 -antihistamines and/or a leukotriene receptor antagonist (GLACIAL). All studies administered omalizumab (75, 150, or 300 mg in ASTERIA I and ASTERIA II; 300 mg in GLACIAL) or placebo subcutaneously every 4 weeks for at least 12 weeks. Urticaria Patient Daily Diary entries were completed by patients and summarized. At baseline, angioedema prevalence was higher in GLACIAL (53.1%) than in ASTERIA I (47.5%) or ASTERIA II (40.7%). The mean proportion of angioedema-free days during weeks 4 to 12 was greater for patients treated with 300 mg of omalizumab than placebo in ASTERIA I (96.1% vs 88.2%, P angioedema was managed by low-intensity interventions (doing nothing or taking medication). Treatment with 300 mg of omalizumab was efficacious in reducing patient-reported angioedema. Low-intensity interventions were generally used to manage angioedema episodes. Identifiers: NCT01287117 (ASTERIA I), NCT01292473 (ASTERIA II), and NCT01264939 (GLACIAL). Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Efficacy and safety of omalizumab in Japanese and Korean patients with refractory chronic spontaneous urticaria. (United States)

    Hide, Michihiro; Park, Hae-Sim; Igarashi, Atsuyuki; Ye, Young-Min; Kim, Tae-Bum; Yagami, Akiko; Roh, Jooyoung; Lee, Jae-Hyun; Chinuki, Yuko; Youn, Sang Woong; Lee, Soo-Keol; Inomata, Naoko; Choi, Jeong-Hee; Fukunaga, Atsushi; Wang, Junyi; Matsushima, Soichiro; Greenberg, Steve; Khalil, Sam


    Many patients with chronic spontaneous/idiopathic urticaria (CSU/CIU) do not respond adequately to treatment with non-sedating H1 antihistamines (H1AH). There are limited studies on use of omalizumab as add-on therapy for treatment of CSU in an Asian population. The POLARIS study (NCT02329223), representing the first randomized, double-blind, placebo-controlled phase III trial of omalizumab for CSU in an Eastern Asian population, evaluated efficacy and safety of omalizumab as add-on therapy for treatment of CSU. This 26-week multicenter (41 Japanese/Korean sites) study enrolled patients (12-75 years) who were symptomatic despite H1AH treatment. Eligible participants (N=218) were randomized 1:1:1 to receive three subcutaneous injections of omalizumab 300mg, 150mg, or placebo every 4 weeks, followed by 12 weeks of follow-up. Primary outcome was change from baseline to Week 12 (Wk12) in weekly itch severity score (ISS7). Safety was assessed through the summary of adverse events (AEs). Baseline demographics and disease characteristics were generally well balanced across treatment groups. At Wk12, statistically significant decreases from baseline were observed in ISS7 with omalizumab vs placebo (mean changes -10.22, -8.80, and -6.51 for omalizumab 300mg, 150mg and placebo; pomalizumab 300mg, 150mg, and placebo groups, respectively); nasopharyngitis was the most frequently reported AE in all treatment arms. The POLARIS study demonstrates that omalizumab is an efficacious and well-tolerated add-on therapy in Japanese and Korean H1AH-refractory patients with CSU. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Omalizumab for the treatment of chronic spontaneous urticaria: A meta-analysis of randomized clinical trials. (United States)

    Zhao, Zuo-Tao; Ji, Chun-Mei; Yu, Wen-Jun; Meng, Ling; Hawro, Tomasz; Wei, Ji-Fu; Maurer, Marcus


    Chronic spontaneous urticaria (CSU) is defined by itchy hives, angioedema, or both for at least 6 weeks. Omalizumab, an anti-IgE antibody that affects mast cell and basophil function, is a promising new treatment option. As of now, however, the efficacy and safety of different doses of omalizumab used in clinical trials for CSU have not been systematically analyzed and summarized. We sought to assess the efficacy and safety of different doses of omalizumab for the treatment of CSU in a meta-analysis of clinical trial results. Suitable trials were identified by searching PubMed, Medline, Embase, and Web of Science databases and with the help of omalizumab's manufacturers. Only double-blind, randomized, placebo-controlled studies with omalizumab-treated versus placebo-treated patients with CSU were included in this analysis. We identified 7 randomized, placebo-controlled studies with 1312 patients with CSU. Patients treated with omalizumab (75-600 mg every 4 weeks) had significantly reduced weekly itch and weekly wheal scores compared with the placebo group. Omalizumab's effects were dose dependent, with the strongest reduction in weekly itch and weekly wheal scores observed with 300 mg. Rates of complete response were significantly higher in the omalizumab group (relative risk, 4.55; P omalizumab and placebo groups. This meta-analysis provides high-quality evidence for the efficacy and safety of omalizumab in patients with CSU and for treating these patients with 300 mg of omalizumab every 4 weeks. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  10. In chronic spontaneous urticaria, IgE against staphylococcal enterotoxins is common and functional. (United States)

    Altrichter, S; Hawro, T; Liedtke, M; Holtappels, G; Bachert, C; Skov, P S; Maurer, M


    Chronic spontaneous urticaria (CSU) is a frequent disorder with recurrent itchy wheals and/or angioedema. Despite the known effectiveness of omalizumab therapy, the relevant IgE antigens are largely unknown. Recently, increased rates of elevated levels of IgE towards Staphylococcus aureus enterotoxins (SEs) were described in CSU. To assess the prevalence and functional relevance of IgE to SEs in CSU. We investigated serum levels of IgE against SEs in 49 CSU patients and in 15 CSU patients additional specific IgE to SE components and basophil histamine release (BHR). Sera of 15 healthy controls (HCs) served as control group. Twenty-five (51%) of the CSU patients had detectable levels of SE-IgE as compared to 5 (33%) of HCs. Specific IgE to one of the SEs, Staphylococcus enterotoxin B (SEB), was present in 5 (33%) of 15 randomly selected CSU patients vs 3 (20%) of HC. Total IgE serum levels in CSU patients were significantly correlated with SE-IgE (r = .52, P IgE (r = .54, P = .04) serum concentrations. Interestingly, SEB-IgE levels were strongly correlated with disease activity (UASday) in CSU patients (r = .657, P = .01). Furthermore, BHR in response to SEB was significantly higher in basophils loaded with the serum of CSU patients compared to HC (P  .51, P IgE against SEs may contribute to the pathogenesis of CSU in a subpopulation of patients. Its role and relevance in the pathophysiology of CSU need to be further analysed. © 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  11. Prevalence of Inducible Urticaria in Patients with Chronic Spontaneous Urticaria: Associated Risk Factors. (United States)

    Sánchez, Jorge; Amaya, Emerson; Acevedo, Ana; Celis, Ana; Caraballo, Domingo; Cardona, Ricardo

    Information on the prevalence of inducible urticaria (IU) in patients with chronic spontaneous urticaria (CSU) and the factors affecting this prevalence is scarce in the literature. To estimate the frequency of IU in patients with CSU and to explore possible factors associated with CSU. Patients older than 12 years diagnosed with CSU and a control group with no history of urticaria were recruited from 2 different cities. All patients were questioned about triggers associated with exacerbation of urticaria, and challenge tests were performed for symptomatic dermographism, pressure, cold, water, and exercise. Atopy to mites and self-reactivity to autologous serum were evaluated using skin tests. The study population comprised 245 patients with CSU and 127 controls. Of the patients with CSU, 186 (75.9%) reported a physical trigger, although only 89 (36.3%) had a positive challenge test result. The challenge tests showed that symptomatic dermographism was the most common type of IU, affecting 24.8% of the CSU group, followed by cold, which affected 13.4%. In the control group, 3.9% of patients were positive for symptomatic dermographism. People living in Medellín city had a higher frequency of symptomatic dermographism 28.5% (odds ratio, 2.1; 95% CI, 1-4.4; P = .03) and cold urticaria 16.5% (odds ratio, 3.3; 95% CI, 1.125-9.8; P = .02) than did people living in Bogotá (dermographism 14.4% and cold 5.2%). Atopy and self-reactivity were more frequent in patients with CSU than in the control group. Physical triggers must be verified by challenge tests to avoid unnecessary lifestyle restrictions. Environmental factors such as geographical characteristics could play a key role in the development of some types of IU, whereas atopy and self-reactivity are major risk factors for CSU. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  12. Clinical, Laboratory and Bacterial Profile of Spontaneous Bacterial Peritonitis in Chronic Liver Disease Patients

    International Nuclear Information System (INIS)

    Bibi, S.; Ahmed, W.; Arif, A.; Khan, F.; Alam, S. E.


    Objective: To determine the clinical and laboratory features, bacterial profile and antibiotic sensitivity pattern of Spontaneous Bacterial Peritonitis (SBP) in Chronic Liver Disease (CLD) patients presenting at a tertiary care hospital of Karachi. Study Design: Cross-sectional study. Place and Duration of Study: PMRC Centre for Gastroenterology and Hepatology and Jinnah Postgraduate Medical Centre, Karachi, from April 2010 to March 2012. Methodology: CLD patients with ascites were recruited from PMRC Centre for Gastroenterology and Hepatology and Jinnah Postgraduate Medical Centre, Karachi. Basic demographics, symptoms and clinical signs of patients were recorded. Patients with the history of antibiotic use within last 3 days or any intra-abdominal source of infection were excluded. Diagnostic paracentesis was done for ascitic fluid detailed report (D/R) and culture. Blood sample was collected for total leukocyte count, serum proteins and billirubin levels. Results: Out of a total 152 CLD patients, 38 (25%) were diagnosed with SBP. Eight (24.2%) patients presented with classical SBP, 20 (52.6%) had culture negative neutrocytic ascites and 10 (26%) had bacterascites. Fever, abdominal tenderness and constipation were common in SBP patients. Ascitic fluid culture was positive in 19 (50%) patients. E. coli (65%) was the predominant pathogen followed by Enterococcus species (15%). Resistance was high against cephalosporins (78%) and fluoroquinolones (69.6%) and least against amikacin (13%) and meropenem (12%). Conclusion: Ascitic fluid D/R and culture together can lead to the accurate diagnosis of SBP and can guide for the right antibiotic choice as resistance to commonly prescribed antibiotic is common in such patients. (author)

  13. Change of HLA phenotype in postoperative patients developing posttransfusion GVHD and prevention of GVHD by X-ray radiation of blood preparations

    International Nuclear Information System (INIS)

    Ito, Kazuhiko; Norioka, Mihoko; Yoshida, Hisahiro; Fujita, Masahiro; Maruya, Etsuko; Saji, Hiroh; Hosoi, Takemitsu.


    The change of HLA phenotype from heterozygous to homozygous one occurred in two postoperative patients developing posttransfusion GVHD. One haplotype was shared in the homozygous and heterozygous phenotype. A blood donor whose HLA phenotype was identified to the homozygous phenotype of the patient was found. For preventing posttransfusion GVHD, blood preparations to be transfused within 10 days after collection were irradiated in a dose more than 15 Gy. The two patients described above developed GVHD after the transfusion with non-irradiated fresh blood. On the other hand, no patients developed GVHD after the transfusion with irradiated blood. (author)

  14. Spontaneous and indicated preterm delivery risk is increased among overweight and obese women without prepregnancy chronic disease. (United States)

    Kim, S S; Mendola, P; Zhu, Y; Hwang, B S; Grantz, K L


    To investigate the independent impact of prepregnancy obesity on preterm delivery among women without chronic diseases by gestational age, preterm category and parity. A retrospective cohort study. Data from the Consortium on Safe Labor (CSL) in the USA (2002-08). Singleton deliveries at ≥23 weeks of gestation in the CSL (43 200 nulliparas and 63 129 multiparas) with a prepregnancy body mass index (BMI) ≥18.5 kg/m 2 and without chronic diseases. Association of prepregnancy BMI and the risk of preterm delivery was examined using Poisson regression with normal weight as reference. Preterm deliveries were categorised by gestational age (extremely, very, moderate to late) and category (spontaneous, indicated, no recorded indication). Relative risk of spontaneous preterm delivery was increased for extremely preterm among obese nulliparas (1.26, 95% CI: 0.94-1.70 for overweight; 1.88, 95% CI: 1.30-2.71 for obese class I; 1.99, 95% CI: 1.32-3.01 for obese class II/III) and decreased for moderate to late preterm delivery among overweight and obese multiparas (0.90, 95% CI: 0.83-0.97 for overweight; 0.87, 95% CI: 0.78-0.97 for obese class I; 0.79, 95% CI: 0.69-0.90 for obese class II/III). Indicated preterm delivery risk was increased with prepregnancy BMI in a dose-response manner for extremely preterm and moderate to late preterm among nulliparas, as it was for moderate to late preterm delivery among multiparas. Prepregnancy BMI was associated with increased risk of preterm delivery even in the absence of chronic diseases, but the association was heterogeneous by preterm categories, gestational age and parity. Obese nulliparas without chronic disease had higher risk for spontaneous delivery <28 weeks of gestation. © 2017 Royal College of Obstetricians and Gynaecologists.

  15. Non invasive spontaneous dual ventilation in critically ill patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Khaled Hussein


    Conclusion: Non invasive spontaneous dual ventilation using intelligent volume assured pressure support (iVAPS is characterized by stable alveolar ventilation with lower and variable inspiratory pressure and earlier improvement of respiratory acidosis when compared with conventional pressure support.

  16. Chronic administration of the probiotic kefir improves the endothelial function in spontaneously hypertensive rats. (United States)

    Friques, Andreia G F; Arpini, Clarisse M; Kalil, Ieda C; Gava, Agata L; Leal, Marcos A; Porto, Marcella L; Nogueira, Breno V; Dias, Ananda T; Andrade, Tadeu U; Pereira, Thiago Melo C; Meyrelles, Silvana S; Campagnaro, Bianca P; Vasquez, Elisardo C


    The beverage obtained by fermentation of milk with kefir grains, a complex matrix containing acid bacteria and yeasts, has been shown to have beneficial effects in various diseases. However, its effects on hypertension and endothelial dysfunction are not yet clear. In this study, we evaluated the effects of kefir on endothelial cells and vascular responsiveness in spontaneously hypertensive rats (SHR). SHR were treated with kefir (0.3 mL/100 g body weight) for 7, 15, 30 and 60 days and compared with non-treated SHR and with normotensive Wistar-Kyoto rats. Vascular endothelial function was evaluated in aortic rings through the relaxation response to acetylcholine (ACh). The balance between reactive oxygen species (ROS) and nitric oxide (NO) synthase was evaluated through specific blockers in the ACh-induced responses and through flow cytometry in vascular tissue. Significant effects of kefir were observed only after treatment for 60 days. The high blood pressure and tachycardia exhibited by the SHR were attenuated by approximately 15 % in the SHR-kefir group. The impaired ACh-induced relaxation of the aortic rings observed in the SHR (37 ± 4 %, compared to the Wistar rats: 74 ± 5 %), was significantly attenuated in the SHR group chronically treated with kefir (52 ± 4 %). The difference in the area under the curve between before and after the NADPH oxidase blockade or NO synthase blockade of aortic rings from SHR were of approximately +90 and -60 %, respectively, when compared with Wistar rats. In the aortic rings from the SHR-kefir group, these values were reduced to +50 and -40 %, respectively. Flow cytometric analysis of aortic endothelial cells revealed increased ROS production and decreased NO bioavailability in the SHR, which were significantly attenuated by the treatment with kefir. Scanning electronic microscopy showed vascular endothelial surface injury in SHR, which was partially protected following administration of kefir for 60 days. In addition, the

  17. A rapid method of detecting autoantibody against FcεRIα for chronic spontaneous urticaria.

    Directory of Open Access Journals (Sweden)

    Mey-Fann Lee

    Full Text Available BACKGROUND: Chronic spontaneous urticaria (CU is a common skin disorder, with an estimated prevalence of 0.5-1.8% in most populations. Around 30-50% of CU patients have an autoimmune etiology, with autoantibodies (autoAbs against IgE, FcεRIα, and FcεRII/CD23. Although the in vivo autologous serum skin test (ASST and in vitro histamine release/activation assay are the most frequently used screening methods, these two have many limitations and do not directly measure susceptible autoAbs. This study aimed to establish an in vitro rapid screening test using recombinant autoantigen FcεRIα(rFcεRIα to improve the diagnosis of autoimmune urticaria. METHODS: Forty patients with CU and 20 healthy individuals were enrolled. After PCR-based cloning and the production of extracellular fragments of the FcεRIα protein using the E. coli expression system, serum autoAb to rFcεRIα was evaluated using in-house ELISA and rapid immunodot test. RESULTS: In ELISA-based detection, 14 out of 20 CU-ASST(+ patients exhibited anti- FcεRIα responses, whereas five of the 20 CU-ASST(- and two of the 20 non-CU patients showed autoantibody background in the assay. For the immunodot test, 55% (11/20 of the CU-ASST(+ sera exhibited anti-FcεRIα reactivity. There was no false positive among the CU-ASST(- and non-CU groups. Using clinical urticaria plus ASST(+ as the gold standard, in-house ELISA had 70% sensitivity, 82.5% specificity, and positive likelihood ratio of 4, while immunodot had 55% sensitivity, 100% specificity, and positive likelihood ratio >55. CONCLUSIONS: This study has developed a rapid immunodot method with high specificity for detecting autoAb to FcεRIαin patients with CU. Preliminary data indicates that this immunodot technique has the potential to be a routine diagnostic assay for autoimmune CU.

  18. Histopathological and clinical evaluation of chronic spontaneous urticaria patients with neutrophilic and non-neutrophilic cutaneous infiltrate. (United States)

    Martins, Cíntia Freitas; Morais, Karina Lopes; Figueroa, Pamela; Dias, Natasha Favoretto; Valente, Neusa Sakai; Maruta, Celina Wakisaba; Criado, Paulo Ricardo


    Chronic urticaria has an expressive prevalence in general population, especially in adults, and is defined by the presence of intermittent hives for six weeks or longer. Our study aims to characterize the histological patterns of chronic spontaneous urticaria, based on the inflammatory cell infiltrate, and correlate them to laboratory exams. It was performed a retrospective analysis of laboratory, histopathology and direct immunofluorescence data of 93 patients with chronic urticaria. For histopathological analysis, cell count was performed in four fields at high magnification (×400) for each specimen. The resulting cell count medians were submitted to statistical analysis and, then, were correlated to laboratorial findings. We found a female predominance (76.34%) of chronic urticaria cases, and an average age of 42.5 years (SD ± 15). Two histological groups were distinctive: 1) chronic urticaria with predominance of neutrophils or eosinophils - N (%) = 39 (42.4%) - and 2) chronic urticaria with predominance of lymphocytes - N (%) = 53 (57.6%). There was not significant correlation between histological groups and laboratorial tests. Moreover, direct immunofluorescence was positive in 21 (33,87%) from 62 patients. There is not enough scientific evidence to support neutrophilic urticaria as a solid, separate entity. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  19. Timing and duration of omalizumab response in patients with chronic idiopathic/spontaneous urticaria. (United States)

    Kaplan, Allen; Ferrer, Marta; Bernstein, Jonathan A; Antonova, Evgeniya; Trzaskoma, Benjamin; Raimundo, Karina; Rosén, Karin; Omachi, Theodore A; Khalil, Sam; Zazzali, James L


    Few data are available that describe response patterns in patients with chronic idiopathic urticaria (CIU)/chronic spontaneous urticaria (CSU) treated with omalizumab. We sought to describe response patterns by using data from the 3 pivotal omalizumab CIU/CSU trials. Every 4 weeks, randomized patients received dosing with placebo or 75, 150, or 300 mg of omalizumab (ASTERIA I: n = 318, 24 weeks; ASTERIA II: n = 322, 12 weeks) or placebo or 300 mg of omalizumab (GLACIAL: n = 335, 24 weeks). Response was defined as well-controlled urticaria (weekly Urticaria Activity Score [UAS7] ≤ 6) or complete response (UAS7 = 0). Response rates were dose dependent and highest with 300 mg of omalizumab. Some patients responded early (before week 4). At week 12, a higher proportion of patients treated with 300 mg of omalizumab reported a UAS7 ≤ 6 (26.0% [75 mg of omalizumab], 40.0% [150 mg of omalizumab], 51.9% [300 mg of omalizumab], and 11.3% [placebo] for ASTERIA I; 26.8% [75 mg of omalizumab], 42.7% [150 mg of omalizumab], 65.8% [300 mg of omalizumab], and 19.0% [placebo] for ASTERIA II; and 52.4% [300 mg of omalizumab] and 12.0% [placebo] for GLACIAL) or a UAS7 = 0 (11.7% [75 mg of omalizumab], 15.0% [150 mg of omalizumab], 35.8% [300 mg of omalizumab], and 8.8% [placebo] for ASTERIA I; 15.9% [75 mg of omalizumab], 22.0% [150 mg of omalizumab], 44.3% [300 mg of omalizumab], and 5.1% [placebo] for ASTERIA II; and 33.7% [300 mg of omalizumab] and 4.8% [placebo] for GLACIAL). In patients receiving 300 mg of omalizumab with 24 weeks of treatment, median time to achieve a UAS7 ≤ 6 was 6 weeks (ASTERIA I and GLACIAL) and median time to achieve a UAS7 = 0 was 12 or 13 weeks (ASTERIA I and GLACIAL, respectively). Some patients who achieved well-controlled urticaria or complete response sustained response throughout the treatment period. Benefits of omalizumab treatment were evident early (before week 4) in some patients and persisted to week

  20. Umbilical cord blood–derived T regulatory cells to prevent GVHD: kinetics, toxicity profile, and clinical effect (United States)

    Miller, Jeffrey S.; McKenna, David H.; Hippen, Keli L.; DeFor, Todd E.; Sumstad, Darin; Curtsinger, Julie; Verneris, Michael R.; MacMillan, Margaret L.; Levine, Bruce L.; Riley, James L.; June, Carl H.; Le, Chap; Weisdorf, Daniel J.; McGlave, Philip B.; Blazar, Bruce R.; Wagner, John E.


    We studied the safety and clinical outcomes of patients treated with umbilical cord blood (UCB)-derived regulatory T cells (Tregs) that expanded in cultures stimulated with K562 cells modified to express the high-affinity Fc receptor (CD64) and CD86, the natural ligand of CD28 (KT64/86). Eleven patients were treated with Treg doses from 3-100 × 106 Treg/kg. The median proportion of CD4+FoxP3+CD127– in the infused product was 87% (range, 78%-95%), and we observed no dose-limiting infusional adverse events. Clinical outcomes were compared with contemporary controls (n = 22) who received the same conditioning regimen with sirolimus and mycophenolate mofetil immune suppression. The incidence of grade II-IV acute graft-versus-host disease (GVHD) at 100 days was 9% (95% confidence interval [CI], 0-25) vs 45% (95% CI, 24-67) in controls (P = .05). Chronic GVHD at 1 year was zero in Tregs and 14% in controls. Hematopoietic recovery and chimerism, cumulative density of infections, nonrelapse mortality, relapse, and disease-free survival were similar in the Treg recipients and controls. KT64/86-expanded UCB Tregs were safe and resulted in low risk of acute GVHD. PMID:26563133

  1. Umbilical cord blood-derived T regulatory cells to prevent GVHD: kinetics, toxicity profile, and clinical effect. (United States)

    Brunstein, Claudio G; Miller, Jeffrey S; McKenna, David H; Hippen, Keli L; DeFor, Todd E; Sumstad, Darin; Curtsinger, Julie; Verneris, Michael R; MacMillan, Margaret L; Levine, Bruce L; Riley, James L; June, Carl H; Le, Chap; Weisdorf, Daniel J; McGlave, Philip B; Blazar, Bruce R; Wagner, John E


    We studied the safety and clinical outcomes of patients treated with umbilical cord blood (UCB)-derived regulatory T cells (Tregs) that expanded in cultures stimulated with K562 cells modified to express the high-affinity Fc receptor (CD64) and CD86, the natural ligand of CD28 (KT64/86). Eleven patients were treated with Treg doses from 3-100 × 10(6) Treg/kg. The median proportion of CD4(+)FoxP3(+)CD127(-) in the infused product was 87% (range, 78%-95%), and we observed no dose-limiting infusional adverse events. Clinical outcomes were compared with contemporary controls (n = 22) who received the same conditioning regimen with sirolimus and mycophenolate mofetil immune suppression. The incidence of grade II-IV acute graft-versus-host disease (GVHD) at 100 days was 9% (95% confidence interval [CI], 0-25) vs 45% (95% CI, 24-67) in controls (P = .05). Chronic GVHD at 1 year was zero in Tregs and 14% in controls. Hematopoietic recovery and chimerism, cumulative density of infections, nonrelapse mortality, relapse, and disease-free survival were similar in the Treg recipients and controls. KT64/86-expanded UCB Tregs were safe and resulted in low risk of acute GVHD. © 2016 by The American Society of Hematology.

  2. Aberrant spontaneous brain activity in chronic tinnitus patients revealed by resting-state functional MRI

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    Yu-Chen Chen


    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.

  3. Non invasive spontaneous dual ventilation in critically ill patients with chronic obstructive pulmonary disease


    Khaled Hussein


    Background: Effective non-invasive ventilation (NIV) is dependent on optimal ventilator settings for alveolar ventilation. Volume-assured pressure support (VAPS) is a mode of servoventilation, providing constant automatic adjustment of pressure support (PS) to achieve a target ventilation. Our aim is to evaluate the effectiveness of the new dual spontaneous mode of ventilation named intelligent volume assured pressure support (iVAPS) in comparison with conventional pressure support using S/T ...

  4. Chronic hepatitis C virus infection triggers spontaneous differential expression of biosignatures associated with T cell exhaustion and apoptosis signaling in peripheral blood mononucleocytes. (United States)

    Barathan, Muttiah; Gopal, Kaliappan; Mohamed, Rosmawati; Ellegård, Rada; Saeidi, Alireza; Vadivelu, Jamuna; Ansari, Abdul W; Rothan, Hussin A; Ravishankar Ram, M; Zandi, Keivan; Chang, Li Y; Vignesh, Ramachandran; Che, Karlhans F; Kamarulzaman, Adeeba; Velu, Vijayakumar; Larsson, Marie; Kamarul, Tunku; Shankar, Esaki M


    Persistent hepatitis C virus (HCV) infection appears to trigger the onset of immune exhaustion to potentially assist viral persistence in the host, eventually leading to hepatocellular carcinoma. The role of HCV on the spontaneous expression of markers suggestive of immune exhaustion and spontaneous apoptosis in immune cells of chronic HCV (CHC) disease largely remain elusive. We investigated the peripheral blood mononuclear cells of CHC patients to determine the spontaneous recruitment of cellular reactive oxygen species (cROS), immunoregulatory and exhaustion markers relative to healthy controls. Using a commercial QuantiGenePlex(®) 2.0 assay, we determined the spontaneous expression profile of 80 different pro- and anti-apoptotic genes in persistent HCV disease. Onset of spontaneous apoptosis significantly correlated with the up-regulation of cROS, indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2/prostaglandin H synthase (COX-2/PGHS), Foxp3, Dtx1, Blimp1, Lag3 and Cd160. Besides, spontaneous differential surface protein expression suggestive of T cell inhibition viz., TRAIL, TIM-3, PD-1 and BTLA on CD4+ and CD8+ T cells, and CTLA-4 on CD4+ T cells was also evident. Increased up-regulation of Tnf, Tp73, Casp14, Tnfrsf11b, Bik and Birc8 was observed, whereas FasLG, Fas, Ripk2, Casp3, Dapk1, Tnfrsf21, and Cflar were moderately up-regulated in HCV-infected subjects. Our observation suggests the spontaneous onset of apoptosis signaling and T cell exhaustion in chronic HCV disease.

  5. Spontaneous chronic subdural hematoma in a young male patient: case report

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    Full Text Available The chronic subdural hematoma is a common pathology in elderly patients. There is usually a history of head trauma. The diagnosis of chronic subdural hematomas in young patients is very rare and few cases have been reported in the literature. The authors present a case of a patient of 16 years old who presented headache of two months of evolution, which was conducted by tomography diagnosis of chronic subdural hematoma. The patient had no history of mild trauma. Surgical management was performed, showing a satisfactory evolution.

  6. Double valve replacement for acute spontaneous left chordal rupture secondary to chronic aortic incompetence

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    McLenachan Jim


    Full Text Available Abstract A 54 years old male with undiagnosed chronic calcific degenerative aortic valve incompetence presented with acute left anterior chordae tendinae rupture resulting in severe left heart failure and cardiogenic shock. He was successfully treated with emergency double valve replacement using mechanical valves. The pathogenesis of acute rupture of the anterior chordae tendinae, without any evidence of infective endocarditis or ischemic heart disease seems to have been attrition of the subvalvular mitral apparatus by the chronic regurgitant jet of aortic incompetence with chronic volume overload. We review the literature with specific focus on the occurrence of this unusual event.

  7. Spontaneous tension pneumothorax and CO₂ narcosis in a near fatal episode of chronic obstructive pulmonary disease exacerbation. (United States)

    Spindelboeck, Walter; Moser, Adrian


    Exacerbation of chronic obstructive pulmonary disease (COPD) is a disease pattern frequently seen in emergency medical services and intensive care units. Usually, exacerbations of COPD are of infectious origin, and an acute vital threat may take several days to develop. Tension pneumothorax in patients with COPD is a rare and often unexpected cause of acute vital threat. To the best of our knowledge, this is a unique case of CO2 narcosis after spontaneous tension pneumothorax in a patient with COPD. We describe the rapid development of respiratory insufficiency and near fatal pulmonary failure in a 65-year-old female patient with COPD due to spontaneous tension pneumothorax. The patient was in respiratory failure and comatose upon arrival of the emergency service. Before mechanical ventilation, coma could be confirmed to be due to CO2 narcosis caused by exorbitant arterial hypercapnia (PCO2, 193 mm Hg). Pneumothorax was diagnosed in the hospital by chest x-ray and resolved after pleural drainage. The patient could be extubated early and discharged without sequelae. In conclusion, we want to report the occurrence of a tension pneumothorax as an important and potentially overseen condition in patients with COPD with acute respiratory failure. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Influence of renal function on spontaneous dietary intake and on nutritional status of chronic renal insufficiency patients. (United States)

    Duenhas, M R; Draibe, S A; Avesani, C M; Sesso, R; Cuppari, L


    To analyze the spontaneous food intake and the nutritional parameters of patients with different degrees of chronic renal insufficiency (CRI) at the onset of predialysis treatment. Cross-sectional. Outpatient Clinic of the Nephrology Division of Federal University of São Paulo, Brazil. The analysis involved 487 (187 women and 300 men) patients with moderate to advanced CRI who were evaluated in the first visit to the clinic. Patients were divided according to creatinine clearance (CrCl) quartiles. CrCl in the first quartile was lower than 19.9 ml/min/1.73 m(2) and in the fourth one was higher than 43 ml/min/1.73 m(2). Energy intake was significantly (Pprotein intake estimated by protein equivalent of nitrogen appearance (PNA) was significantly lower in the first, second and third quartiles in comparison with the fourth (Prenal function. Standard per cent of triceps skinfold thickness was lower in the first quartile when compared with the fourth one. Compared with the fourth quartile, standard per cent of midarm muscle circumference (MAMC) was lower in the second and in the third quartile. CrCl correlated directly and significantly with PNA (r=0.30; Pprotein intake, CrCl correlated significantly and positively with BMI and MAMC. This study suggests that a spontaneous decrease in energy and protein intake as well as in anthropometric indices follows a decline in renal function in patients with no previous dietary intervention.

  9. Related or not? Development of spontaneous Creutzfeldt-Jakob disease in a patient with chronic, well-controlled HIV: A case report and review of the literature. (United States)

    Babi, M-Alain; Kraft, Bryan D; Sengupta, Sweta; Peterson, Haley; Orgel, Ryan; Wegermann, Zachary; Lugogo, Njira L; Luedke, Matthew W


    We report a novel case of a rare disease: spontaneous Creutzfeldt-Jakob disease in a patient with well-controlled HIV. We explore the relationship between spontaneous Creutzfeldt-Jakob disease and HIV. A 66-year-old man with long-standing, well-controlled HIV infection presented with 3 months of progressive, subacute neurocognitive decline. His symptoms included conceptual apraxia, apathy, memory impairment, and gait disturbance, and were initially attributed to depressive "pseudo-dementia." Unfortunately, the patient's symptoms rapidly progressed and he ultimately succumbed to his illness. Autopsy confirmed the clinical diagnosis of spontaneous Creutzfeldt-Jakob disease. This case highlights spontaneous Creutzfeldt-Jakob disease as a rare terminal illness in the setting of well-controlled chronic HIV. To our knowledge, this is the first report of a patient with chronic and previously well-controlled HIV infection dying from a prion disease. Despite the very different epidemiology and pathophysiology of HIV and spontaneous Creutzfeldt-Jakob disease, this case does raise questions of whether certain host genetic factors could predispose to both conditions, albeit currently, there is no clear causal link between HIV and spontaneous Creutzfeldt-Jakob disease.

  10. Brazilian status in blood irradiation in Graft-Versus-Host Disease (GVHD) prevention

    International Nuclear Information System (INIS)

    Goes, E.G. de; Borges, J.C.; Ghilardi Netto, T.


    A short overview of the Brazilian reality concerning Graft-Versus-Host Disease (GVHD) is presented. Suggestions of policies and procedures to optimise GVHD prevention are reported. A national irradiator device using cobalt teletherapy unit is proposed for irradiation of blood and cellular components

  11. Vorinostat plus tacrolimus/methotrexate to prevent GVHD after myeloablative conditioning, unrelated donor HCT

    NARCIS (Netherlands)

    Choi, S.W.; Braun, T.; Henig, I.; Gatza, E.; Magenau, J.; Parkin, B.; Pawarode, A.; Riwes, M.; Yanik, G.; Dinarello, C.A.; Reddy, P.


    The oral histone deacetylase (HDAC) inhibitor (vorinostat) is safe and results in low incidence of acute graft-versus-host disease (GVHD) after reduced-intensity conditioning, related donor hematopoietic cell transplantation (HCT). However, its safety and efficacy in preventing acute GVHD in

  12. H1-antihistamine up-dosing in chronic spontaneous urticaria: patients' perspective of effectiveness and side effects--a retrospective survey study. (United States)

    Weller, Karsten; Ziege, Claudia; Staubach, Petra; Brockow, Knut; Siebenhaar, Frank; Krause, Karoline; Altrichter, Sabine; Church, Martin K; Maurer, Marcus


    The guidelines recommend that first line treatment of chronic spontaneous urticaria should be second generation non-sedating H(1)-antihistamines with a positive recommendation against the use of old sedating first generation antihistamines. If standard dosing is not effective, increasing the dosage up to four-fold is recommended. The objective of this study was to obtain the chronic spontaneous urticaria-patient perspective on the effectiveness and unwanted effects of H(1)-antihistamines in standard and higher doses. This was a questionnaire based survey, initially completed by 368 individuals. 319 (248 female, 71 male, median age 42 years) had a physician-confirmed diagnosis of chronic spontaneous urticaria and were included in the results. Participants believed standard doses (manufacturers recommended dose) of second generation antihistamines to be significantly (Pdrugs. Furthermore, they believed that second generation drugs caused significantly (Pantihistamines. Three-quarters of the patients stated that they had up-dosed with antihistamines with 40%, 42% and 54% reporting significant added benefit from taking 2, 3 or 4 tablets daily respectively. The number of reports of unwanted effects and sedation following up-dosing were not significantly different from those reported for standard doses. This survey supports the urticaria guidelines recommendations that the first line treatment for chronic spontaneous urticaria should be second generation rather than first generation H(1)-antihistamines and that, if standard dosing is not effective, the dosage should be increased up to four-fold.

  13. Transient hair loss in patients with chronic spontaneous urticaria treated with omalizumab

    DEFF Research Database (Denmark)

    Noshela Ghazanfar, M; Thomsen, S F


    Summary: Omalizumab (anti-IgE) is used as add-on therapy for antihistamine refractory chronic urticaria patients. The most commonly reported adverse effects were headache, arthralgia, upper respiratory infections, fatigue, nausea and injection-site reactions. However, lately a few cases of hair...... loss have been reported. We describe a case of transient hair loss in a young female patient after initiating treatment with omalizumab. Despite this side effect, the patient continued with omalizumab treatment for 10 months with good effect....

  14. Descemet Stripping Endothelial Keratoplasty in a Patient with Keratoglobus and Chronic Hydrops Secondary to a Spontaneous Descemet Membrane Tear

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    Anton M. Kolomeyer


    Full Text Available Purpose. To report the use of Descemet stripping endothelial keratoplasty (DSEK in a patient with keratoglobus and chronic hydrops. Case Report. We describe a case of a 28-year-old man with bilateral keratoglobus and chronic hydrops in the right eye secondary to spontaneous Descemet membrane tear. The patient presented with finger counting (CF vision, itching, foreign body sensation, and severe photophobia in the right eye. Peripheral corneal thinning with central corneal protrusion and Descemet membrane tear spanning from 4 to 7 o'clock was noted on slit lamp examination. The right eye cornea was 15 mm in the horizontal diameter. After a 5.5-month loss to follow-up, the patient presented with discomfort, photophobia, decreasing vision, and tearing in the right eye. Vision was 20/60 with pinhole. 360-degree peripheral corneal ectasia with mild neovascularization and hydrops was present. Over the next few months, the patient complained of photophobia and intermittent eye pain. His vision deteriorated to CF, he developed corneal scarring with bullae, and a DSEK was performed. Eight months postoperatively, best-corrected vision improved to 20/30, cornea was clear, and the DSEK graft was stable. Conclusions. Nonresolving hydrops secondary to Descemet membrane tear in a patient with keratoglobus may result in permanent endothelial cell damage and scar formation. This may be successfully treated with DSEK.

  15. Crosstalk between type II NKT cells and T cells leads to spontaneous chronic inflammatory liver disease. (United States)

    Weng, Xiufang; He, Ying; Visvabharathy, Lavanya; Liao, Chia-Min; Tan, Xiaosheng; Balakumar, Arjun; Wang, Chyung-Ru


    Natural killer T (NKT) cells are CD1d-restricted innate-like T cells that modulate innate and adaptive immune responses. Unlike the well-characterized invariant/type I NKT cells, type II NKT cells with a diverse T cell receptor repertoire are poorly understood. This study defines the pathogenic role of type II NKT cells in the etiology of chronic liver inflammation. Transgenic mice with the Lck promoter directing CD1d overexpression on T cells in Jα18 wild-type (Lck-CD1dTgJα18 + ; type I NKT cell sufficient) and Jα18-deficient (Lck-CD1dTgJα18 o , type I NKT cell deficient) mice were analyzed for liver pathology and crosstalk between type II NKT cells and conventional T cells. CD1d expression on T cells in peripheral blood samples and liver sections from autoimmune hepatitis patients and healthy individuals were also examined. Lck-CD1dTgJα18 o and Lck-CD1dTgJα18 + mice developed similar degrees of liver pathology resembling chronic autoimmune hepatitis in humans. Increased CD1d expression on T cells promoted the activation of type II NKT cells and other T cells. This resulted in T h 1-skewing and impaired T h 2 cytokine production in type II NKT cells. Dysfunction of type II NKT cells was accompanied by conventional T cell activation and pro-inflammatory cytokine production, leading to a hepatic T/B lymphocyte infiltration, elevated autoantibodies and hepatic injury in Lck-CD1dTg mice. A similar mechanism could be extended to humans as CD1d expression is upregulated on activated human T cells and increased presence of CD1d-expressing T cells was observed in autoimmune hepatitis patients. Our data reveals enhanced crosstalk between type II NKT cells and conventional T cells, leading to a T h 1-skewed inflammatory milieu, and consequently, to the development of chronic autoimmune liver disease. Lay summary: CD1d overexpression on T cells enhances crosstalk between type II NKT cells and T cells, resulting in their aberrant activation and leading to the

  16. Influence of spontaneous nystagmus with eyes closed on computerized vestibular exam of patients with chronic peripheral

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    Shin, Elizabeth


    Full Text Available Introduction: The spontaneous nystagmus with eyes closed (NEOF can modify the results obtained during some evidence of vestibular, leading to erroneous conclusions. Objective: To characterize the patients and the type of influence on the evidence of NEOF vectonystagmography digital. Method: Retrospective study based on survey charts of patients with the presence of NEOF vectonystagmography digital, in the Outpatient Equilibriometria UNIFESP-EPM, in the years 2000 to 2007. Comparisons were made between genders, ages, direction, angular velocity of NEOF, completion of entrance examination and its influence on the results of caloric testing. Results: We found 73.7% of the population was female, mean age of 55.08 years; NEOF prevalence of horizontal and angular velocity smaller than 7o/s in 86.7%. 59% had some kind of influence caused by the caloric test NEOF as inversion, hyporeflexia, hyperreflexia, nystagmus directional preponderance (NDP and labyrinthine preponderance (LP changed. The most prevalent findings were normal vestibular tests (EVN and bilateral irritative peripheral vestibular syndrome (BIPVS. 38.7% caloric ice and realized these cases it was possible to reach a conclusion in 79%. Conclusion: The NEOF most common was the horizontal type, with VACL less than 7o/s, influencing the majority of examinations and only the results of caloric testing the air, with reversal of post-caloric nystagmus, hyperreflexia and hyporeflexia, NDP and PL altered; the findings were more prevalent and BIPVS EVN, and the caloric test the influence of ice withdrew NEOF in most individuals, enabling to reach a final conclusion.

  17. Spontaneous chronic subdural hematoma development in chronic myeloid leukemia cases at remission phase under maintenance therapy, management strategy - a series with literature review

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    Raheja Amol


    Full Text Available Chronic subdural hematoma (CSDH is common squeal of trauma and rarely associated with anticoagulant therapy, antiplatelet, chemotherapeutic drugs, arteriovenous malformation, aneurysms and post-craniotomy. However its occurrence is very unusual with systemic haematological malignancy and mostly reported with acute myeloid leukemia; however incidence of SDH occurrence in chronic myelogenous leukemia (CML is very rare. CML is a haematological malignancy characterized by chromosomal alteration, pathologically represents increased proliferation of the granulocytic cell line without loss of capacity to differentiate. CML has three phases - remission phase, accelerated phase and blast crisis. About 85 % of patients present in remission phase of disease and carries a favorable prognosis. As intracranial, subdural hematoma usually occur in the accelerated phase or blast crisis phase or extremely uncommon during chronic remission phase, although only those affected, who are neglecting therapeutic medication or discontinued therapy or rarely as an adverse effect of medications. However, important role of neurosurgeon lies in early detection and correction of platelet count and associated hematological abnormality as quite sizeable proportion of cases may not need surgical intervention instead can be managed conservatively under regular supervision in association with oncologist colleague, but few cases may need urgent surgical intervention. So, selecting a subgroup of CML cases in the remission phase requiring surgical intervention, presenting with CSDH is not only challenging, as failure to make an informed and timely precise decision can lead to catastrophic worse outcome and even mortality. So, purpose of current article is to formulate the management therapeutic plan. Authors report three cases of CML in chronic remission phase, receiving treatment under guidance of Haemto-oncologist at our institute presented with spontaneous chronic SDH. The mean

  18. Improvement of spontaneous language in stroke patients with chronic aphasia treated with music therapy: a randomized controlled trial. (United States)

    Raglio, Alfredo; Oasi, Osmano; Gianotti, Marta; Rossi, Agnese; Goulene, Karine; Stramba-Badiale, Marco


    The aim of this research is to evaluate the effects of active music therapy (MT) based on free-improvisation (relational approach) in addition to speech language therapy (SLT) compared with SLT alone (communicative-pragmatic approach: Promoting Aphasic's Communicative Effectiveness) in stroke patients with chronic aphasia. The experimental group (n = 10) was randomized to 30 MT individual sessions over 15 weeks in addition to 30 SLT individual sessions while the control group (n = 10) was randomized to only 30 SLT sessions during the same period. Psychological and speech language assessment were made before (T0) and after (T1) the treatments. The study shows a significant improvement in spontaneous speech in the experimental group (Aachener Aphasie subtest: p = 0.020; Cohen's d = 0.35); the 50% of the experimental group showed also an improvement in vitality scores of Short Form Health Survey (chi-square test = 4.114; p = 0.043). The current trial highlights the possibility that the combined use of MT and SLT can lead to a better result in the rehabilitation of patients with aphasia than SLT alone.

  19. Basophil FcεRI Expression in Chronic Spontaneous Urticaria: A Potential Immunological Predictor of Response to Omalizumab Therapy

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    Gustavo Deza


    Full Text Available Although the efficacy of omalizumab has been clearly demonstrated in the treatment of chronic spontaneous urticaria (CSU, its mechanism of action, which results in improvement in CSU symptoms, is not entirely understood. This study investigated the effect of omalizumab on expression of the high-affinity IgE receptor (FcεRI on blood basophils from patients with active CSU, and its association with the clinical response. Patients exhibiting significant clinical improvement showed a sharp reduction in the levels of basophil FcεRI after 4 weeks, which was maintained throughout the total duration of the treatment. Such evolution was not observed in non-responder patients. Furthermore, non-responders showed significantly lower baseline levels of FcεRI than responders. Baseline basophil FcεRI expression was found to be a potential immunological predictor of response to omalizumab (100% sensitivity and 73.2% specificity. The results of this study contribute to our knowledge of the therapeutic benefit and mechanism of action of anti-IgE therapy in CSU.

  20. Position statement for the use of omalizumab in the management of chronic spontaneous urticaria in Indian patients

    Directory of Open Access Journals (Sweden)

    Kiran Godse


    Full Text Available Chronic spontaneous urticaria (CSU affects 1% of the world population and also their quality of life, and 50% of these patients are refractory to H1-antihistamines. Omalizumab is a humanized monoclonal anti-IgE antibody that binds with free IgE antibodies and reduces the circulating levels of free IgE. This reduction in free IgE prevents mast-cell degranulation. The EAACI/GA2LEN/EDF/WAO guidelines recommend omalizumab as the third-line of therapy as an add-on to antihistamines. The recommended dose of omalizumab is 300 mg, 4 weekly in the management of CSU refractory to standard of care with H1-antihistamines in adults and adolescents ≥12 years of age. In some patients, a dose of 150 mg may be acceptable. Omalizumab has a good safety profile. However, due to the biologic nature of the drug, all patients administered omalizumab must be observed for 2 h after administration for anaphylactoid reactions. There have been no studies on the effect of impaired renal or hepatic function on the pharmacokinetics of omalizumab. While no particular dose adjustment is recommended, omalizumab should be administered with caution in these patients.

  1. Characterisation of the proximal airway squamous metaplasia induced by chronic tobacco smoke exposure in spontaneously hypertensive rats

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    Foster Martyn


    Full Text Available Abstract Background Continuous exposure to tobacco smoke (TS is a key cause of chronic obstructive pulmonary disease (COPD, a complex multifactorial disease that is difficult to model in rodents. The spontaneously hypertensive (SH rat exhibits several COPD-associated co-morbidities such as hypertension and increased coagulation. We have investigated whether SH rats are a more appropriate animal paradigm of COPD. Methods SH rats were exposed to TS for 6 hours/day, 3 days/week for 14 weeks, and the lung tissues examined by immunohistochemistry. Results TS induced a CK13-positive squamous metaplasia in proximal airways, which also stained for Ki67 and p63. We hypothesise that this lesion arises by basal cell proliferation, which differentiates to a squamous cell phenotype. Differences in staining profiles for the functional markers CC10 and surfactant D, but not phospho-p38, indicated loss of ability to function appropriately as secretory cells. Within the parenchyma, there were also differences in the staining profiles for CC10 and surfactant D, indicating a possible attempt to compensate for losses in proximal airways. In human COPD sections, areas of CK13-positive squamous metaplasia showed sporadic p63 staining, suggesting that unlike the rat, this is not a basal cell-driven lesion. Conclusion This study demonstrates that although proximal airway metaplasia in rat and human are both CK13+ and therefore squamous, they potentially arise by different mechanisms.

  2. Living with Chronic Spontaneous Urticaria in Italy: A Narrative Medicine Project to Improve the Pathway of Patient Care. (United States)

    Cappuccio, Antonietta; Limonta, Tommaso; Parodi, Aurora; Cristaudo, Antonio; Bugliaro, Filomena; Cannavò, Serafinella P; Rossi, Oliviero; Gurioli, Carlotta; Vignoli, Alice; Parente, Roberta; Iemoli, Enrico; Caldarola, Giacomo; De Pità, Ornella; Di Nuzzo, Sergio; Cancian, Mauro; Potenza, Concetta; Caminati, Marco; Stingeni, Luca; Saraceno, Rosita; Trevisini, Sara; Piccirillo, Angelo; Sciarrone, Claudio; Panebianco, Rosanna; Gola, Massimo; Costanzo, Antonio; Grieco, Teresa; Massaroni, Katia; Reale, Luigi; Marini, Maria G


    Chronic spontaneous urticaria (CSU) is perceived as a difficult to manage disease with negative impact on quality of life. The aim of this study was to highlight how to improve the care of people with CSU, using the methodology of narrative medicine. From June 2014 to March 2015, CSU-diagnosed patients and their physicians were asked to record their experiences of the condition in writing. Fourteen healthcare teams participated: 41% considered CSU as a challenge to overcome, while 22% experienced CSU as a big commitment. The number of professional involved was evaluated as insufficient in 11 hospitals. Seventy-five percent of the 190 Italian patients had visited 3 or more physicians before receiving a final diagnosis, with a perceived waste of time and resources. The therapeutic pathways were described as unsatisfactory in 83% of cases. As a result, anger and frustration were life-dominant emotions in 92% of patients. The critical points of the care pathway are related to organizational issues and lack of awareness.

  3. Chronic baroreflex activation restores spontaneous baroreflex control and variability of heart rate in obesity-induced hypertension. (United States)

    Iliescu, Radu; Tudorancea, Ionut; Irwin, Eric D; Lohmeier, Thomas E


    The sensitivity of baroreflex control of heart rate is depressed in subjects with obesity hypertension, which increases the risk for cardiac arrhythmias. The mechanisms are not fully known, and there are no therapies to improve this dysfunction. To determine the cardiovascular dynamic effects of progressive increases in body weight leading to obesity and hypertension in dogs fed a high-fat diet, 24-h continuous recordings of spontaneous fluctuations in blood pressure and heart rate were analyzed in the time and frequency domains. Furthermore, we investigated whether autonomic mechanisms stimulated by chronic baroreflex activation and renal denervation-current therapies in patients with resistant hypertension, who are commonly obese-restore cardiovascular dynamic control. Increases in body weight to ∼150% of control led to a gradual increase in mean arterial pressure to 17 ± 3 mmHg above control (100 ± 2 mmHg) after 4 wk on the high-fat diet. In contrast to the gradual increase in arterial pressure, tachycardia, attenuated chronotropic baroreflex responses, and reduced heart rate variability were manifest within 1-4 days on high-fat intake, reaching 130 ± 4 beats per minute (bpm) (control = 86 ± 3 bpm) and ∼45% and baroreflex activation and renal denervation abolished the hypertension. However, only baroreflex activation effectively attenuated the tachycardia and restored cardiac baroreflex sensitivity and heart rate variability. These findings suggest that baroreflex activation therapy may reduce the risk factors for cardiac arrhythmias as well as lower arterial pressure.

  4. Prediction of the Efficacy of Antihistamines in Chronic Spontaneous Urticaria Based on Initial Suppression of the Histamine- Induced Wheal. (United States)

    Sánchez, J; Zakzuk, J; Cardona, R


    Antihistamines are the first line of treatment for chronic spontaneous urticaria. However, there is no effective method to predict whether an antihistamine will have a beneficial clinical effect or not. To assess whether the change in histamine-induced wheal and flare measurements 24 hours after administration of antihistamine can predict the efficacy of treatment. We performed a multicenter, triple-blind, randomized study. Patients received a daily oral dose of cetirizine, fexofenadine, bilastine, desloratadine, or ebastine over 8 weeks. After 4 weeks, a higher dose of antihistamine was administered to patients who did not experience a clinical response. A histamine skin prick test was carried out at baseline and 24 hours after the first dose of antihistamine. Disease severity (Urticaria Activity Score [UAS]), response to the histamine skin prick test, and impact on the patient's quality of life (Dermatology Life Quality Index [DLQI]) were determined every 2 weeks. The study population comprised 150 patients (30 per group) and 30 controls. Twenty-four hours after administration of antihistamine, inhibition of the histamine wheal by >75% was significantly associated with better UAS and DLQI scores. The safety and efficacy of the 5 antihistamines were similar. After updosing, rates of disease control (DLQI score antihistamines but has limited utility for identifying nonresponders. The clinical significance of these data could be relevant in the search for new urticaria treatment regimens.

  5. Long-term efficacy of omalizumab in seven patients with treatment-resistant chronic spontaneous urticaria. (United States)

    Silva, P M; Costa, A C; Mendes, A; Barbosa, M P


    Monoclonal anti-IgE antibody omalizumab is a promising therapeutic option in patients with chronic urticaria (CU) resistant to non-sedating H1-antihistamines (nsAH). However, data about its long-term efficacy and safety are still scant. We retrospectively analysed the clinical course of patients with severe recalcitrant CU that were treated in our department with omalizumab for a period greater than 24 months. Seven patients (six females, median 43 years) treated for a median of 35 months have been evaluated. Before treatment, all suffered from persistent symptoms despite receiving high doses of nsAH [4×/day], leukotriene antagonists and prednisolone (10-30 mg/day for a median duration of 48 months). Response to treatment was assessed using urticaria activity score (UAS) and a combined symptom/medication score. There was a complete remission of disease in four patients after the first dose of omalizumab. Before the 5th administration, all patients had a UAS of 0. We found a significant improvement in UAS between pre-treatment and first dose (p=0.017) and a gradual decrease in the symptom/medication score over the course of the first five administrations. Tapering of prednisolone was possible in all patients. Administration intervals were gradually increased, although all experienced resurgence of symptoms in cycles greater than six weeks. There were no reported adverse reactions attributable to the drug. Omalizumab was a safe and effective corticosteroid alternative for maintaining long-term remission of symptoms in these patients. Treatment intervals required individual patient-by-patient determination. The drug did not seem to alter the natural history of the disease. Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.

  6. Urinary Fractional Excretion of Phosphorus in Dogs with Spontaneous Chronic Kidney Disease. (United States)

    Martorelli, Cínthia Ribas; Kogika, Márcia Mery; Chacar, Fernanda Chicharo; Caragelasco, Douglas Segalla; de Campos Fonseca Pinto, Ana Carolina Brandão; Lorigados, Carla Aparecida Batista; Andrade, Lúcia Conceição


    The increase of urinary fractional excretion of phosphorus (uFEP) may indicate phosphorus retention before the onset of hyperphosphatemia in the early stages of chronic kidney disease (CKD). The hypothesis of this study is whether uFEP may increase during the early stage of CKD as a compensatory mechanism to prevent hyperphosphatemia as well as whether hyperphosphatemia in the late stages is associated with increase or decrease in uFEP in dogs with naturally occurring CKD; therefore, the aim of this study was to determine the uFEP in CKD dogs with different stages. Forty-nine CKD dogs were included, and they were divided into stage 1 (serum creatinine 5.0 mg/dL), according to the IRIS staging criteria. The stage 3 was subdivided into stage 3-A (serum creatinine 2.1 to 3.5 mg/dL) and stage 3-B (serum creatinine 3.6 to 5.0 mg/dL). The control group comprised 10 dogs, and uFEP ≤ 40% was considered as normal. A progressive increase in uFEP along the progression of CKD was found. However, similar results of uFEP levels were observed in late CKD, since there were no differences between stages 3 (A, B) and 4. Interestingly, some CKD dogs with stage 4 showed normal or reduced uFEP, besides hyperphosphatemia; conversely, some dogs in early CKD had increased uFEP values and normophosphatemia. Our findings suggest that uFEP may act as a compensatory mechanism to avoid the onset of hyperphosphatemia in early CKD, but not in later stages. uFEP assessment may be considered as an additional tool for the diagnostic and monitoring of phosphate disorders in dogs with CKD, since it may help to identify disturbances of phosphorus balance. More studies are needed to elucidate the role of uFEP in phosphorus homeostasis in dogs with CKD.

  7. H1-antihistamine up-dosing in chronic spontaneous urticaria: patients' perspective of effectiveness and side effects--a retrospective survey study.

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    Karsten Weller

    Full Text Available BACKGROUND: The guidelines recommend that first line treatment of chronic spontaneous urticaria should be second generation non-sedating H(1-antihistamines with a positive recommendation against the use of old sedating first generation antihistamines. If standard dosing is not effective, increasing the dosage up to four-fold is recommended. The objective of this study was to obtain the chronic spontaneous urticaria-patient perspective on the effectiveness and unwanted effects of H(1-antihistamines in standard and higher doses. METHODOLOGY/PRINCIPAL FINDINGS: This was a questionnaire based survey, initially completed by 368 individuals. 319 (248 female, 71 male, median age 42 years had a physician-confirmed diagnosis of chronic spontaneous urticaria and were included in the results. Participants believed standard doses (manufacturers recommended dose of second generation antihistamines to be significantly (P<0.005 more effective than first generation drugs. Furthermore, they believed that second generation drugs caused significantly (P<0.001 fewer unwanted effects and caused significantly (P<0.001 less sedation than first generation antihistamines. Three-quarters of the patients stated that they had up-dosed with antihistamines with 40%, 42% and 54% reporting significant added benefit from taking 2, 3 or 4 tablets daily respectively. The number of reports of unwanted effects and sedation following up-dosing were not significantly different from those reported for standard doses. CONCLUSIONS: This survey supports the urticaria guidelines recommendations that the first line treatment for chronic spontaneous urticaria should be second generation rather than first generation H(1-antihistamines and that, if standard dosing is not effective, the dosage should be increased up to four-fold.

  8. Self-reported hair loss in patients with chronic spontaneous urticaria treated with omalizumab: an under-reported, transient side effect? (United States)

    Konstantinou, G N; Chioti, A G; Daniilidis, M


    Omalizumab has been recently approved for treating patients with refractory to H1- antihistamines chronic spontaneous urticaria (CSU). Although hair loss is listed among omalizumab side effects, there are no available data to estimate its frequency. We describe for the first time hair loss as a side effect associated with omalizumab administration in three women, 38, 62 and 70 years old, suffering from refractory to H1-antihistamines CSU. This information was retrieved from their Chronic Urticaria Quality of Life Questionnaires. Despite this side effect, all patients agreed to continue omalizumab regular administration. Hair loss appeared to be transient, lasting up to four months. All cases finally benefited from omalizumab continuation.

  9. MAGIC biomarkers predict long term outcomes for steroid-resistant acute GVHD. (United States)

    Major-Monfried, Hannah; Renteria, Anne S; Pawarode, Attaphol; Reddy, Pavan; Ayuk, Francis; Holler, Ernst; Efebera, Yvonne A; Hogan, William J; Wölfl, Matthias; Qayed, Muna; Hexner, Elizabeth O; Wudhikarn, Kitsada; Ordemann, Rainer; Young, Rachel; Shah, Jay; Hartwell, Matthew J; Chaudhry, Mohammed; Aziz, Mina; Etra, Aaron; Yanik, Gregory A; Kröger, Nicolaus; Weber, Daniela; Chen, Yi-Bin; Nakamura, Ryotaro; Rösler, Wolf; Kitko, Carrie L; Harris, Andrew C; Pulsipher, Michael; Reshef, Ran; Kowalyk, Steven; Morales, George; Torres, Ivan; Özbek, Umut; Ferrara, James L M; Levine, John E


    Acute graft versus host disease (GVHD) is treated with systemic corticosteroid immunosuppression. Clinical response after one week of therapy often guides further treatment decisions, but long term outcomes vary widely between centers and more accurate predictive tests are urgently needed. We analyzed clinical data and blood samples taken after one week of systemic treatment for GVHD from 507 patients from 17 centers of the Mount Sinai Acute GVHD International Consortium (MAGIC), dividing them into test (n=236) and two validation cohorts separated in time (n = 142 and 129, respectively). Initial response to systemic steroids correlated with response at four weeks, one-year non-relapse mortality (NRM) and overall survival (OS). A previously validated algorithm of two MAGIC biomarkers (ST2 and REG3α) consistently separated steroid resistant patients into two groups with dramatically different NRM and OS (p<0.001 for all three cohorts). High biomarker probability, resistance to steroids and GVHD severity (Minnesota risk) were all significant predictors of NRM in multivariate analysis. A direct comparison of receiver operating curves showed the area under the curve for biomarker probability (0.82) was significantly greater than that for steroid response (0.68, p=0.004) and for Minnesota risk (0.72, p=0.005). In conclusion, MAGIC biomarker probabilities generated after one week of systemic treatment for GVHD predict long term outcomes in steroid resistant GVHD better than clinical criteria and should prove useful in developing better treatment strategies. Copyright © 2018 American Society of Hematology.

  10. A Critical Appraisal of Extracorporeal Photopheresis as a Treatment Modality for Acute and Chronic Graft-Versus-Host Disease

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    Hind Rafei


    Full Text Available Although significant advances have been made in the biologic understanding of graft-versus-host disease (GVHD and its treatment options, GVHD remains the single most challenging obstacle to the success of allogeneic hematopoietic cell transplantation (HCT due to high risk of disabling morbidity and mortality. Extracorporeal photopheresis (ECP has promising effects in controlling steroid-refractory GVHD, both acute and chronic, and it has been studied extensively. Its putative immunomodulatory mechanisms, while not immunosuppressive, position ECP as an attractive treatment strategy for GVHD patients who are already receiving global immunosuppression. However, ECP is relatively underutilized due in part to limited access and time commitment. Here, we review the recent findings on the ECP efficacy in both acute and chronic GVHD, primarily for steroid-refractory status, and we critically appraise its benefits. We also explore salient considerations on the optimal use of ECP in the treatment of refractory GVHD.

  11. Short-term spontaneous fluctuations of HBV DNA levels in a Senegalese population with chronic hepatitis B. (United States)

    Maylin, Sarah; Sire, Jean-Marie; Mbaye, Papa Saliou; Simon, François; Sarr, Anna; Evra, Marie-Louise; Fall, Fatou; Daveiga, Jean; Diallo, Aboubakry; Debonne, Jean-Marc; Chartier, Loic; Vray, Muriel


    We evaluated the short-term spontaneous fluctuations of HBV DNA and HBsAg levels in Senegalese patients with chronic infection with hepatitis B virus and normal ALT and determined factors related to these fluctuations. A total of 87 patients with persistent normal ALT values were enrolled in the study. Serum samples were obtained at three different visits, with an interval of 2 months (M0, M2, and M4), and without initiating anti HBV treatment. Levels of HBV DNA, quantitative HBsAg, ALT and AST, genotyping and viral DNA mutations were analyzed. Among the 87 patients, genotype E was predominant (75%). The median HBV DNA level was 2.9 log10 IU/mL [2.2-3.4], 2.7 log10 IU/mL [2.1-3.6] and 2.7 log10 IU/mL [2.1-3.4] at M0, M2 and M4, respectively. The values ranged from <1.1 to 7 log10 IU/mL and 55 (63%) had HBV DNA fluctuations≥0.5 log10 IU/mL between two visits. Patients in whom HBV DNA fluctuated ≥0.5 log10 IU/mL between M0 and M2 also had significant fluctuations between M2 and M4, while patients with stable HBV DNA between M0 and M2 showed a stable viral load between M2 and M4. The only factor found to be associated with HBV DNA fluctuations≥0.5 log10 IU/mL was a low BMI (<21 kg/ m2). HBsAg levels were not correlated with HBV DNA levels. Sixty-three percent of the enrolled Senegalese population showed a large, short-term fluctuation of HBV DNA levels. Such fluctuations may have an impact on therapeutic management, requiring closer monitoring.

  12. Treatment and retreatment with omalizumab in chronic spontaneous urticaria: Real life experience with twenty-five patients. (United States)

    Türk, Murat; Yılmaz, İnsu; Bahçecioğlu, Sakine Nazik


    Previous data have shown the high efficacy of omalizumab in chronic spontaneous urticaria (CSU). However, factors that may be effective on the response to therapy, relapse rates after drug discontinuation, and efficacy of retreatment remain unclear. This study aimed to determine the efficacy of omalizumab in CSU refractory to conventional therapy, to identify possible factors affecting treatment response and relapse, and also to evaluate the efficacy of retreatment on relapsed disease. The data of CSU patients treated with 300 mg/month omalizumab for at least 3 months were retrospectively analyzed. In order to evaluate the efficacy of treatment and retreatment, baseline and follow-up concomitant medication score (CMS) and urticaria activity score (UAS) were calculated. Possible factors affecting treatment response and relapse were identified. Twenty-five patients were included. The median duration of omalizumab therapy was 6 (6-12) months. Of the patients with baseline UAS 6 (5.5-6) and CMS 13 (10-15), 8 (32%) had complete response (UAS = 0) and 2 (8%) were non-responders after 3 months of therapy. None of the complete responders were positive for IgG-anti-TPO. After discontinuation of omalizumab therapy, 11 (61%) patients experienced relapse and 10 of them received retreatment with omalizumab. Half of the patients had complete response, and half had partial response (UAS = 1-4) after retreatment. No treatment related adverse events were documented. Omalizumab has high efficacy in both the treatment and retreatment of CSU; however, relapse rates after discontinuation are high. Autoimmune markers may be helpful in predicting treatment response and relapse. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  13. TP53-induced glycolysis and apoptosis regulator protects from spontaneous apoptosis and predicts poor prognosis in chronic lymphocytic leukemia. (United States)

    Hong, Ming; Xia, Yi; Zhu, Yu; Zhao, Hui-Hui; Zhu, Han; Xie, Yue; Fan, Lei; Wang, Li; Miao, Kou-Rong; Yu, Hui; Miao, Yu-Qing; Wu, Wei; Zhu, Hua-Yuan; Chen, Yao-Yu; Xu, Wei; Qian, Si-Xuan; Li, Jian-Yong


    Circulating chronic lymphocytic leukemia (CLL) cells appear not to be overly utilizing aerobic glycolysis. However, recurrent contact with CLL cells in a stromal microenvironment leads to increased aerobic glycolysis and the cells' overall glycolytic capacity, which promotes cell survival and proliferation. TP53-induced glycolysis and apoptosis regulator (TIGAR) has been directly implicated in cellular metabolism in the control of glycolysis. TIGAR inhibits glycolysis and protects cells from intracellular reactive oxygen species (ROS)-associated apoptosis. TIGAR mRNA expression was investigated by quantitative PCR in 102 newly diagnosed CLL patients. Furthermore, the relationship between the expression of TIGAR and its clinical characteristics and prognosis were investigated. Moreover, we also investigated the correlation between TIGAR expression and apoptosis in primary CLL cells. Our data revealed that TIGAR overexpression was correlated with the protection from spontaneous apoptosis in CLL cells, and is strongly associated with advanced Binet stage, unmutated immunoglobulin heavy-chain variable region (IGHV) status, CD38 positivity, β2-microglobulin and p53 aberrations. Higher expression of TIGAR was associated with shorter treatment-free survival (median: three months vs. 51 months, P=0.0108), worse overall survival (median: 74 months vs. not reached, P=0.0242), and the diverse responses to fludarabine-based chemotherapy. TIGAR expression in patients resistant to chemotherapy was significantly higher than in patients sensitive to chemotherapy (mean: 0.3859±0.1710 vs. 0.0974±0.0291, P=0.0290). Taken together, our findings revealed that high TIGAR expression is closely correlated with worse clinical outcome in CLL patients, and depicted how bioenergetic characteristics could be therapeutically exploited in CLL. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Real-world use of omalizumab in patients with chronic idiopathic/spontaneous urticaria in the United States. (United States)

    Eghrari-Sabet, Jacqueline; Sher, Ellen; Kavati, Abhishek; Pilon, Dominic; Zhdanava, Maryia; Balp, Maria-Magdalena; Lefebvre, Patrick; Ortiz, Benjamin; Bernstein, Jonathan A


    Omalizumab was approved for the treatment of chronic idiopathic urticaria (CIU)/chronic spontaneous urticaria (CSU) in the United States in March 2014. This study sought to describe real-world omalizumab use, in the United States, in a large cohort of patients with CIU/CSU. Patients with CIU/CSU (ages ≥12 years) initiated on omalizumab (index date) with ≥12 months of pre- and postindex data were identified in the an insurance claims data base (January 1, 2013, to July 31, 2016). Treatment patterns, including the dosing regimen and continuous use of omalizumab (no gaps for ≥60 days), were described during the 12-month postindex follow-up period. A total of 1546 patients (mean ± standard deviation [SD] ages, 44 ± 14.5 years; 73.1% women) were identified. Most of the patients (84.5%) were initiated on omalizumab 300-mg dose; 90% maintained the initial dose, 7.5% had a dose increase, and 4.6% had a dose decrease. The mean ± SD omalizumab treatment duration was 9.1 ± 3.8 months, the mean ± SD number of omalizumab administrations was 8.3 ± 4.8, and the mean ± SD administration frequency was 44 ± 29 days. A proportion of the patients continuously treated with omalizumab for 6, 9, and 12 months was 67.3, 54.8, and 47.4%, respectively. Among the patients who discontinued omalizumab for ≥3 months (39.8%), 21% restarted the treatment after a mean ± SD of 4.4 ± 1.3 months. The proportion of patients who used other CIU/CSU-related medications decreased pre- to postindex (94.8 to 81.1%), with the highest decrease observed in oral corticosteroids (75.7 to 49.9%). In this large real-world study, the majority of the patients with CIU/CSU were initiated on a 300-mg omalizumab dose and treated without titration up or down for 9 months on average. Most of the patients were continuously treated with omalizumab for ≥6 months, and one-fourth of the patients who discontinued treatment resumed it. Moreover, compared with baseline levels, the use of other CIU

  15. IL-24 is a common and specific autoantigen of IgE in patients with chronic spontaneous urticaria. (United States)

    Schmetzer, Oliver; Lakin, Elisa; Topal, Fatih A; Preusse, Patricia; Freier, Denise; Church, Martin K; Maurer, Marcus


    The efficacy of omalizumab (anti-IgE) and increased IgE levels in patients with chronic spontaneous urticaria (CSU) suggest autoallergic mechanisms. We sought to identify autoallergic targets of IgE in patients with CSU. Serum samples of patients with CSU together with those of patients with idiopathic anaphylaxis and healthy control subjects (7 of each) were screened for IgE autoantibodies by using an array of more than 9000 proteins. Sera of 1062 patients with CSU and 482 healthy control subjects were used in an IgE-anti-IL-24-specific ELISA to investigate the association of IgE-anti-IL-24 and CSU. By using array analyses, more than 200 IgE autoantigens were found in patients with CSU that were not found in control subjects. Of the 31 IgE autoantigens detected in more than 70% of patients, 8 were soluble or membrane bound and expressed in the skin. Of these, only IgE autoantibodies to IL-24 were found in all patients with CSU. In vitro studies showed IL-24 to release histamine from human mast cells sensitized with purified IgE of patients with CSU but not control subjects. By using ELISA, mean ± SD levels of IgE-anti-IL-24 were 0.52 ± 0.24 IU/mL in patients with CSU and 0.27 ± 0.08 IU/mL in control subjects, with 80% of patients with CSU but only 20% of control subjects having levels greater than 0.33 IU/mL (P IgE-anti-IL-24 showed acceptable predictive properties for CSU, with a likelihood ratio of 3.9. Clinically, IgE-anti-IL-24 levels showed an association with disease activity, as assessed by the urticaria activity score and with reduced basophil counts. Our findings show that patients with CSU frequently exhibit IgE autoantibodies against many autoantigens and that IL-24 is a common, specific, and functional autoantigen of IgE antibodies in patients with CSU. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  16. Assessment of dry eye in a GVHD murine model: Approximation through tear osmolarity measurement. (United States)

    Martínez-Carrasco, Rafael; Sánchez-Abarca, Luis Ignacio; Nieto-Gómez, Cristina; García, Elisabet Martín; Ramos, Teresa L; Velasco, Almudena; Sánchez-Guijo, Fermín; Aijón, José; Hernández-Galilea, Emiliano


    Dry eye disease is one of the most frequent pathological events that take place in the course of the graft versus host disease (GVHD), and is the main cause of deterioration in quality of life for patients. Thus, demonstration of dry eye signs in murine models of oGVHD is crucial for the validation of these models for the study of the disease. Given the increasing evidence that tear osmolarity is an important player of dry eye disease, our purpose in this study was to validate the use of a reliable method to assess tear osmolarity in mice: the electrical impedance method. Then, we wanted to test its utility with an oGVHD model. Tear volume assessment was also performed, using the phenol red thread test. We found differences in tear osmolarity in mice that received a transplant with cells from bone marrow and spleen (the GVHD group) when compared with mice that only received bone marrow cells (the BM group) at day 7 (362 ± 8 mOsm/l and 345 ± 9 mOsm/l respectively; P model mimics the tear film alterations found in human dry eye disease, what contributes to give relevance to this model for the study of GVHD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Superior GVHD-free, relapse-free survival for G-BM to G-PBSC grafts is associated with higher MDSCs content in allografting for patients with acute leukemia

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    Qian Fan


    Full Text Available Abstract Background Granulocyte colony-stimulating factor (G-CSF-mobilized peripheral blood stem cells (G-PBSC has largely replaced unstimulated bone marrow (un-BM for allografting because of accelerated engraftment, but with a higher morbidity and mortality of graft-versus-host-disease (GVHD. Recent studies suggested that G-CSF-primed BM (G-BM had similar engraftment but lower morbidity and mortality of GVHD comparing to G-PBSC. A prospective, randomized, multicenter study was conducted to compare G-BM with G-PBSC as the grafts in allogeneic hematopoietic stem cell transplantation (allo-HSCT for acute leukemia in first complete remission (CR1. Methods Totally 101 adult leukemia in CR1 undergoing HLA-identical sibling transplants were randomized into G-BM or G-PBSC group. The primary study endpoint was GVHD-free/relapse-free survival (GRFS. Results Both the engraftment of neutrophil and platelet were 2 days later in G-BM than in G-PBSC group (P = 0.412, P = 0.39. G-BM group showed significantly lower II–IV acute GVHD (aGVHD and similar III–IV aGVHD compared with G-PBSC group (12.2% vs 28.8% for II–IV, P = 0.048; 4.1% vs 9.6% for III–IV aGVHD, P = 0.267, respectively. The overall cumulative incidence of chronic GVHD (cGVHD at 3 years were 22.3% ± 6.3% and 44.8% ± 7.6% (P = 0.026, respectively, and extensive cGHVD were 4.5% ± 3.1% and 15% ± 5.3% (P = 0.08, respectively, in G-BM and G-PBSC groups. Two groups had similar 3-year relapse, transplant-related mortality (TRM, overall survival (OS, and disease-free survival (DFS (all P > 0.05. G-BM group showed significantly higher probability of GRFS than G-PBSC group (73.5% ± 6.3% vs 55.8% ± 6.9% at 1 year, P = 0.049; 69.0% ± 6.7% vs 49.7% ± 7.0% at 2 and 3 years, P = 0.03, respectively. Graft content analysis revealed statistically higher frequency of myeloid-derived suppressor cells (MDSCs in the G-BM than in G

  18. IgE FcɛR1β polymorphism and risk of developing chronic spontaneous urticaria: A study in an ethnic Kashmiri population. (United States)

    Rasool, R; Shera, I A; Nissar, S; Yousuf, Q; Shah, Z A


    The pathogenesis of chronic spontaneous urticaria involves interplay between the genetic and environmental factors, most of which is still poorly understood. It is well-recognized that 30-40% of chronic spontaneous urticaria is autoimmune in nature. Chronic autoimmune urticaria is caused by anti-FcɛR1β and less frequently, by anti-IgE auto antibodies that lead to mast cell and basophil activation, thereby giving rise to the release of histamine and other proinflammatory mediators. We investigated the association between SNP loci in FcɛR1β and chronic spontaneous urticaria and to see its relation with serum IgE levels in Kashmiri population. The autologous serum skin test was used as a screening test for chronic autoimmune urticaria. PCR-RFLP was used to detect the genotype of the SNP loci. Serum IgE levels were assessed by ELISA kit. No significant difference was found between the study population and control group in genotype distribution (wild and variant) among FcɛR1β loci (P value=0.06, odds ratio=0.29). The frequency of FcɛR1β (C109T) in autologous serum skin test positive chronic autoimmune urticaria patients with the CT genotype was found to be statistically non-significant when compared with the wild genotype (P=0.35). Carriers of FcɛR1β (T allele) had a more significant risk of developing CAU than those with C allele (P=0.01). In our population serum total IgE levels did not find any statistical significance with regard to ASST positive & ASST negative patients (P=0.26). There is statistically no significant association between FcɛR1β gene polymorphism and CSU in Kashmiri population; however, there is a probability of developing CSU in patients carrying FcɛR1β T allele. Furthermore, serum total IgE levels had no significant association with the development of CAU. Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.

  19. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. (United States)

    Di Ianni, Mauro; Falzetti, Franca; Carotti, Alessandra; Terenzi, Adelmo; Castellino, Flora; Bonifacio, Elisabetta; Del Papa, Beatrice; Zei, Tiziana; Ostini, Roberta Iacucci; Cecchini, Debora; Aloisi, Teresa; Perruccio, Katia; Ruggeri, Loredana; Balucani, Chiara; Pierini, Antonio; Sportoletti, Paolo; Aristei, Cynthia; Falini, Brunangelo; Reisner, Yair; Velardi, Andrea; Aversa, Franco; Martelli, Massimo F


    Hastening posttransplantation immune reconstitution is a key challenge in human leukocyte antigen (HLA)-haploidentical hematopoietic stem-cell transplantation (HSCT). In experimental models of mismatched HSCT, T-regulatory cells (Tregs) when co-infused with conventional T cells (Tcons) favored posttransplantation immune reconstitution and prevented lethal graft-versus-host disease (GVHD). In the present study, we evaluated the impact of early infusion of Tregs, followed by Tcons, on GVHD prevention and immunologic reconstitution in 28 patients with high-risk hematologic malignancies who underwent HLA-haploidentical HSCT. We show for the first time in humans that adoptive transfer of Tregs prevented GVHD in the absence of any posttransplantation immunosuppression, promoted lymphoid reconstitution, improved immunity to opportunistic pathogens, and did not weaken the graft-versus-leukemia effect. This study provides evidence that Tregs are a conserved mechanism in humans.

  20. [Spontaneous and mitogen-induced production of proinflammatory cytokines (interleukin-1 and tumor necrosis factor-alpha) in patients with chronic chlamydia infection of urogenital system]. (United States)

    Driians'ka, V Ie; Drannik, H M; Vashchenko, S M; Fesenkova, V I; Papakina, V S


    The article contributes to studying functional activity of mononuclear and macrophage immune cells by spontaneous and induced production of IL-1 and TNF-alpha cytokines in patients with chronic urogenital clamidiosis. The patients with monoinfection were shown to have high level of IL-1 and low level of TNF-alpha, while the patients with mixed infection of urogenital tract presented with the high production of TNF-alpha. The cells activation raise cytokines production not to the level observed among healthy persons. It suggests decreasing compensatory regulation in yet higher activated cells.

  1. Spontaneous intracranial hypotension presenting without orthostatic headache complicated by acute subdural hematoma after drainage for chronic subdural hematoma--case report. (United States)

    Kuramae, Takumi; Inamasu, Joji; Nakagawa, Yu; Nakatsukasa, Masashi


    A 28-year-old man presented with a case of spontaneous intracranial hypotension (SIH) manifesting as a bilateral chronic subdural hematoma (CSDH) without orthostatic headache. He developed life-threatening acute SDH as a complication of CSDH drainage. Neurosurgeons should be aware that SIH patients do not always present with orthostatic headache. Brain magnetic resonance imaging with gadolinium may be recommended for young adults with non-traumatic CSDH before drainage to exclude SIH, even if they do not present with orthostatic headache.

  2. Radiographic features of esophageal involvement in chronic graft-vs. -host disease

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    McDonald, G.B.; Sullivan, K.M.; Plumley, T.F.


    Chronic graft-vs.-host disease (GVHD) is an important late complication of allogeneic bone-marrow transplantation. It resembles several naturally occurring autoimmune diseases and involves the skin, mouth, eyes, liver, and esophagus. The radiographic findings of 14 symptomatic patients with chronic GVHD involving the esophagus were reviewed and found to include webs, ringlike narrowings, and tapering strictures in the mid and upper esophagus. Esophagoscopy revealed characteristic desquamation in the 13 patients studied, but barium studies detected this lesion in only one patient. Knowledge of the site and characteristics of esophageal involvement with chronic GVHD assists the radiologic evaluation of this disorder.

  3. A randomized placebo-controlled double-blind pilot study of methotrexate in the treatment of H1 antihistamine-resistant chronic spontaneous urticaria

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    Vinod K Sharma


    Full Text Available Background: Chronic urticaria not responsive to antihistamines is a difficult disease to manage. Methotrexate has been used in difficult chronic urticarias with some benefit. Objective: To evaluate the efficacy of methotrexate in the treatment of chronic spontaneous urticaria poorly responsive to H1 antihistaminics. Methods: In a randomized double-blind trial at the Department of Dermatology and Venereology of a tertiary care centre, 29 patients with chronic spontaneous urticaria not responding well to H1 antihistaminics were recruited. Patients were randomly allocated to receive either a weekly dose of oral methotrexate 15 mg or placebo (calcium carbonate for a total duration of 12 weeks, after which treatment was stopped and patients were followed up for relapse of urticaria. Each group also received levocetrizine 5 mg once daily for symptom control. Primary outcome measured was a reduction by >2/3 rd of baseline urticaria scores after 12 week therapy. Secondary outcome was a reduction in antihistamine requirement after stopping therapy. Results: Fourteen patients were randomized to the methotrexate group and fifteen patients to the placebo group. Out of 17 patients who completed therapy, the primary outcome was achieved by 3.5 ± 1.9 (out of 10 patients in the methotrexate group and by 3.67 ± 1.03 (out of 7 patients in the placebo group (P > 0.05. Ten patients followed up, after stopping therapy, for a mean period of 3.5 ± 2.4 months; 3 remained in remission and 7 had relapsed. One patient had uncontrollable nausea and vomiting after taking methotrexate and was withdrawn from the study. The placebo group did not experience any side effects. Conclusions: Methotrexate 15 mg weekly for 3 months did not provide any additional benefit over H1 antihistamines in this study but an adequately powered study with longer follow up is required to assess its utility.

  4. Lower incidence of acute GVHD is associated with the rapid recovery of CD4+CD25+CD45RA+ regulatory T cells in patients who received haploidentical allografts from NIMA-mismatched donors: A retrospective (development) and prospective (validation) cohort-based study. (United States)

    Wang, Yu; Zhao, Xiang-Yu; Xu, Lan-Ping; Zhang, Xiao-Hui; Han, Wei; Chen, Huan; Wang, Feng-Rong; Mo, Xiao-Dong; Zhang, Yuan-Yuan; Zhao, Xiao-Su; Y, Kong; Liua, Kai-Yan; Huang, Xiao-Jun; Yu, Xue-Zhong; Chang, Ying-Jun


    To investigate the effects of non-inherited maternal antigen (NIMA) on clinical outcomes and immune recovery, especially of regulatory T cells (Tregs), in patients who underwent unmanipulated haploidentical transplantation. A retrospective cohort (n = 57) and a prospective cohort (n = 88) were included. All patients received haploidentical allografts from sibling donors. Reconstitution of immune subsets, including Tregs, was determined using multicolor flow cytometry. In the retrospective cohort, the cumulative incidence of grades II-IV acute GVHD in patients with NIMA-mismatched donors was significantly lower than that of cases with NIPA-mismatched donors (14.8% vs. 43.30%, p = 0.018). Patients with higher percentages of CD4 + CD25 + CD45RA + T cells (naive Tregs) within CD4 + T cells recovered on day 30 (≥1.55%) experienced a significantly lower incidence of grades II-IV acute GVHD than that of cases with lower percentages of naive Tregs (<1.55%) (13.8% vs. 46.4%, p = 0.010). Multivariate analysis showed that NIMA mismatch and the percentages of naive Tregs were associated with the incidence of grades II-IV acute GVHD [ p = 0.050, and 0.031, respectively]. In the prospective cohort, the association of NIMA mismatch [HR = 0.365, 95% CI, 0.169-0.786, p = 0.010] or higher percentages of naive Tregs recovered on day 30 (≥1.55%) [HR = 0.114, 95% CI, 0.027-0.479, p = 0.003] with a lower cumulative incidence of grades II-IV acute GVHD was further demonstrated. No effects of NIMA mismatch on chronic GVHD, transplant-related mortality, relapse, disease-free survival, or overall survival were found. Our results confirmed the role of NIMA mismatch in acute GVHD and provided the first demonstration, based on clinical data, that recovered Tregs may be involved in the effects of NIMA on acute GVHD in a haploidentical transplant setting.

  5. International, Multicenter Standardization of Acute Graft-versus-Host Disease Clinical Data Collection: A Report from the Mount Sinai Acute GVHD International Consortium. (United States)

    Harris, Andrew C; Young, Rachel; Devine, Steven; Hogan, William J; Ayuk, Francis; Bunworasate, Udomsak; Chanswangphuwana, Chantiya; Efebera, Yvonne A; Holler, Ernst; Litzow, Mark; Ordemann, Rainer; Qayed, Muna; Renteria, Anne S; Reshef, Ran; Wölfl, Matthias; Chen, Yi-Bin; Goldstein, Steven; Jagasia, Madan; Locatelli, Franco; Mielke, Stephan; Porter, David; Schechter, Tal; Shekhovtsova, Zhanna; Ferrara, James L M; Levine, John E


    Acute graft-versus-host disease (GVHD) remains a leading cause of morbidity and nonrelapse mortality after allogeneic hematopoietic cell transplantation. The clinical staging of GVHD varies greatly between transplant centers and is frequently not agreed on by independent reviewers. The lack of standardized approaches to handle common sources of discrepancy in GVHD grading likely contributes to why promising GVHD treatments reported from single centers have failed to show benefit in randomized multicenter clinical trials. We developed guidelines through international expert consensus opinion to standardize the diagnosis and clinical staging of GVHD for use in a large international GVHD research consortium. During the first year of use, the guidance followed discussion of complex clinical phenotypes by experienced transplant physicians and data managers. These guidelines increase the uniformity of GVHD symptom capture, which may improve the reproducibility of GVHD clinical trials after further prospective validation. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  6. Intravital imaging of donor allogeneic effector and regulatory T cells with host dendritic cells during GVHD. (United States)

    Lin, Kaifeng Lisa; Fulton, LeShara M; Berginski, Matthew; West, Michelle L; Taylor, Nicholas A; Moran, Timothy P; Coghill, James M; Blazar, Bruce R; Bear, James E; Serody, Jonathan S


    Graft-versus-host disease (GVHD) is a systemic inflammatory response due to the recognition of major histocompatibility complex disparity between donor and recipient after hematopoietic stem cell transplantation (HSCT). T-cell activation is critical to the induction of GVHD, and data from our group and others have shown that regulatory T cells (Tregs) prevent GVHD when given at the time of HSCT. Using multiphoton laser scanning microscopy, we examined the single cell dynamics of donor T cells and dendritic cells (DCs) with or without Tregs postallogeneic transplantation. We found that donor conventional T cells (Tcons) spent very little time screening host DCs. Tcons formed stable contacts with DCs very early after transplantation and only increased velocity in the lymph node at 20 hours after transplant. We also observed that Tregs reduced the interaction time between Tcons and DCs, which was dependent on the generation of interleukin 10 by Tregs. Imaging using inducible Tregs showed similar disruption of Tcon-DC contact. Additionally, we found that donor Tregs induce host DC death and down-regulate surface proteins required for donor T-cell activation. These data indicate that Tregs use multiple mechanisms that affect host DC numbers and function to mitigate acute GVHD.

  7. IL-10+ regulatory B cells are enriched in cord blood and may protect against cGVHD after cord blood transplantation. (United States)

    Sarvaria, Anushruti; Basar, Rafet; Mehta, Rohtesh S; Shaim, Hila; Muftuoglu, Muharrem; Khoder, Ahmad; Sekine, Takuye; Gokdemir, Elif; Kondo, Kayo; Marin, David; Daher, May; Alousi, Amin M; Alsuliman, Abdullah; Liu, Enli; Oran, Betul; Olson, Amanda; Jones, Roy B; Popat, Uday; Hosing, Chitra; Champlin, Richard; Shpall, Elizabeth J; Rezvani, Katayoun


    Cord blood (CB) offers a number of advantages over other sources of hematopoietic stem cells, including a lower rate of chronic graft-versus-host disease (cGVHD) in the presence of increased HLA disparity. Recent research in experimental models of autoimmunity and in patients with autoimmune or alloimmune disorders has identified a functional group of interleukin-10 (IL-10)-producing regulatory B cells (Bregs) that negatively regulate T-cell immune responses. At present, however, there is no consensus on the phenotypic signature of Bregs, and their prevalence and functional characteristics in CB remain unclear. Here, we demonstrate that CB contains an abundance of B cells with immunoregulatory function. Bregs were identified in both the naive and transitional B-cell compartments and suppressed T-cell proliferation and effector function through IL-10 production as well as cell-to-cell contact involving CTLA-4. We further show that the suppressive capacity of CB-derived Bregs can be potentiated through CD40L signaling, suggesting that inflammatory environments may induce their function. Finally, there was robust recovery of IL-10-producing Bregs in patients after CB transplantation, to higher frequencies and absolute numbers than seen in the peripheral blood of healthy donors or in patients before transplant. The reconstituting Bregs showed strong in vitro suppressive activity against allogeneic CD4(+) T cells, but were deficient in patients with cGVHD. Together, these findings identify a rich source of Bregs and suggest a protective role for CB-derived Bregs against cGVHD development in CB recipients. This advance could propel the development of Breg-based strategies to prevent or ameliorate this posttransplant complication. © 2016 by The American Society of Hematology.

  8. Cytokine and human leukocyte antigen (HLA) profile for graft-versus-host disease (GVHD) after organ transplantation. (United States)

    Chen, Xinhua; Meng, Xueqin; Xu, Yuning; Xie, Haiyang; Yin, Shengyong; Li, Hongchun; Wu, Liming; Zheng, Shusen


    Graft-versus-host disease (GVHD) after liver and kidney transplantation has high mortality and causes diagnostic challenges. This study aims to describe the cytokine and human leukocyte antigen (HLA) profile in the GVHD after liver and kidney transplantation. A high-throughput detection kit was applied and altogether 18 different cytokines were tested simultaneously. GVHD patients included 23 post-liver transplantation patients; 22 post-renal transplantation patients; The control patients include 22 hepatocellular carcinoma (HCC) patients without transplantation and 20 healthy controls. Their HLA characters were compared. The full spectrum of cytokines was present. The inflammatory markers were activated significantly in liver transplantation. The level of inflammatory markers in liver transplantation was higher than that in renal transplantation, HCC or healthy controls. GVHD was associated with the HLA characters; HLA characters are involved in liver GVHD occurrence and act as risk factors. Our findings confirmed that the inflammatory cytokines play a pathogenic role in GVHD and can be used as early diagnostic markers. The HLA mismatch acts as a risk factor in liver transplantation to predict GVHD occurrence.

  9. Night-time sedating H1-antihistamine increases daytime somnolence but not treatment efficacy in chronic spontaneous urticaria: a randomized controlled trial (United States)

    Staevska, M; Gugutkova, M; Lazarova, C; Kralimarkova, T; Dimitrov, V; Zuberbier, T; Church, MK; Popov, TA


    Background Many physicians believe that the most effective way to treat chronic urticaria is to take a nonsedating second-generation H1-antihistamine in the morning and a sedating first-generation H1-antihistamine, usually hydroxyzine, at night to enhance sleep. But is this belief well founded? Objectives To test this belief by comparing the effectiveness and prevalence of unwanted sedative effects when treating patients with chronic spontaneous urticaria (CSU) with levocetirizine 15 mg daily plus hydroxyzine 50 mg at night (levocetirizine plus hydroxyzine) vs. levocetirizine 20 mg daily (levocetirizine monotherapy). Methods In this randomized, double-blind, cross-over study, 24 patients with difficult-to-treat CSU took levocetirizine plus hydroxyzine or levocetirizine monotherapy for periods of 5 days each. At the end of each treatment period, assessments were made of quality of life (Chronic Urticaria Quality of Life Questionnaire, CU-Q2oL), severity of urticaria symptoms (Urticaria Activity Score, UAS), sleep disturbance during the night and daytime somnolence. Results Both treatments significantly decreased UAS, night-time sleep disturbances and CU-Q2oL scores (P urticaria guidelines, which state that first-line treatment for urticaria should be new-generation, nonsedating H1-antihistamines only. PMID:24472058

  10. Homecare-based motor rehabilitation in musculoskeletal chronic graft versus host disease

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    A Tendas


    Full Text Available Chronic graft versus host disease (cGVHD is a frequent complication of allogeneic stem cell transplantation. Extensive musculoskeletal and skin involvement may induce severe functional impairment, disability and quality of life deterioration. Physical rehabilitation is recommended as ancillary therapy in these forms, but experiences are sparse. A 39-year-old man affected by musculoskeletal and skin chronic graft versus host disease (cGVHD was treated with a homecare-based motor rehabilitation program during palliation for disease progression. Significant functional improvement was obtained. Motor rehabilitation should be strongly considered for patients with musculoskeletal cGVHD, both in the palliative and in the curative phase of disease.

  11. Spontaneous Reduction of a Chronic Radial Head Subluxation after open Reduction and Percutaneous Pin Fixation of a Radial Neck Fracture: A Case Report and Review of the Literature (United States)

    Illingworth, Kenneth David; Thompson, Kirk; Lovell, Matthew; McGinty, Jasmin


    Background Fractures of the radial neck in children have shown to account for 5-10% of traumatic elbow injuries in the pediatric population. Chronic dislocation of the radial head with concomitant fracture has been shown to result in progressive deformity and unacceptable loss of motion. Methods In this case report, we describe a patient who sustained a type 2 radial neck fracture with 100% displacement. The patient’s clinical and surgical management will be discussed and a review of the literature is provided as it relates to this particular case. Results The patient underwent open reduction and percutaneous pin fixation of her displaced, dislocated left radial neck fracture in the operating room after multiple failed attempts at closed reduction due to interposition of the annular ligament. Three months after her operation radiographs revealed a well-healed radial neck with no signs of avascular necrosis with an anterior dislocation of her radial head, which was a new finding from her previous radiographs. Fourteen months after her initial injury and operation, radiographs taken at this visit revealed a radial neck fracture that was completely remodeled and had spontaneous relocated and was now aligned with the capitellum without any reduction attempt. Conclusion Closed reduction of displaced radial neck fractures may be unsuccessful and open reduction may be warranted. Excess callus formation post-operatively may have resulted in the radial head subluxation; however there was spontaneous reduction with conservative treatment without a reduction attempt, most likely related to remodeling of the excel callus formation. PMID:24027488

  12. Decreased numbers of chemotactic factor receptors in chronic neutropenia with defective chemotaxis: spontaneous recovery from the neutrophil abnormalities during early childhood

    International Nuclear Information System (INIS)

    Yasui, K.; Yamazaki, M.; Miyagawa, Y.; Komiyama, A.; Akabane, T.


    Childhood chronic neutropenia with decreased numbers of chemotactic factor receptors as well as defective chemotaxis was first demonstrated in an 8-month-old girl. Chemotactic factor receptors on neutrophils were assayed using tritiated N-formyl-methionyl-leucyl-phenylalanine ( 3 H-FMLP). The patient's neutrophils had decreased numbers of the receptors: numbers of the receptors were 20,000 (less than 3 SD) as compared with those of control cells of 52,000 +/- 6000 (mean +/- SD) (n = 10). The neutropenia disappeared spontaneously by 28 months of age parallel with the improvement of chemotaxis and increase in numbers of chemotactic factor receptors. These results demonstrate a transient decrease of neutrophil chemotactic factor receptors as one of the pathophysiological bases of a transient defect of neutrophil chemotaxis in this disorder

  13. The clinical response to omalizumab in chronic spontaneous urticaria patients is linked to and predicted by IgE levels and their change. (United States)

    Ertas, R; Ozyurt, K; Atasoy, M; Hawro, T; Maurer, M


    Omalizumab is an effective and well-tolerated treatment for chronic spontaneous urticaria (CSU). Markers and predictors of response are largely unknown, but needed to optimize omalizumab treatment. Omalizumab targets IgE, and IgE levels may be linked to the effects of treatment. We evaluated whether response rates to treatment with omalizumab in patients with CSU are linked to their baseline IgE levels, their IgE levels after omalizumab treatment, and the ratio of on treatment IgE and baseline IgE levels. Chronic spontaneous urticaria (CSU) patients (n = 113) were treated with omalizumab 300 mg/4 weeks for 12 weeks, when their treatment responses, that is, no, partial, or complete response, were assessed by use of the urticaria activity score, physician and patient visual analog scale, and treatment effectiveness score. Total IgE levels were measured before treatment (bIgE) with omalizumab and 4 weeks thereafter (w4IgE). Nonresponders to omalizumab had significantly lower bIgE levels (17.9, 17.0-55.0 IU/mL) than partial responders (82.0, 46.2-126.5 IU/mL, P = .008) and complete responders (73.7, 19.45-153.8 IU/mL, P = .032). Nonresponders also had lower w4IgE levels and lower ratios of w4IgE/bIgE levels than partial and complete responders (P IgE/bIgE ratios, significantly better than by bIgE levels (P = .016). In CSU, total IgE levels and their change predict the response to treatment with omalizumab. The assessment of pre- and post-treatment IgE levels and their ratio may help to improve the management of CSU in patients who require omalizumab treatment. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  14. IL-17 Genetic and Immunophenotypic Evaluation in Chronic Graft-versus-Host Disease

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    Renata Gonçalves Resende


    Full Text Available Although interleukin-17 (IL-17 is a recently discovered cytokine associated with several autoimmune diseases, its role in the pathogenesis of chronic graft-versus-host disease (cGVHD was not established yet. The objective of this study was to investigate the association of IL17A and IL17F genes polymorphisms and IL-17A and IL-17F levels with cGVHD. IL-17A expression was also investigated in CD4+ T cells of patients with systemic cGVHD. For Part I of the study, fifty-eight allo-HSCT recipients and donors were prospectively studied. Blood samples were obtained to determine IL17A and IL17F genes polymorphisms. Cytokines levels in blood and saliva were assessed by ELISA at days +35 and +100 after HSCT. In Part II, for the immunophenotypic evaluation, eight patients with systemic cGVHD were selected and the expression of IL-17A was evaluated. We found association between recipient AA genotype with systemic cGVHD. No association was observed between IL-17A levels and cGVHD. Lower IL-17A levels in the blood were associated with AA genotype. In flow cytometry analysis, decreased expression of IL-17A was observed in patients with cGVHD after stimulation. In conclusion, IL-17A may have an important role in the development of systemic cGVHD.

  15. Physiochemical disparity of mismatched HLA class I alloantigens and risk of acute GVHD following HSCT. (United States)

    Kosmoliaptsis, V; Jöris, M M; Mallon, D H; Lankester, A C; von dem Borne, P A; Kuball, J; Bierings, M; Cornelissen, J J; Groenendijk-Sijnke, M E; van der Holt, B; Bradley, J A; Oudshoorn, M; van Rood, J J; Taylor, C J; Claas, F H J


    We determined whether assessment of the immunogenicity of individual donor-recipient HLA mismatches based on differences in their amino-acid sequence and physiochemical properties predicts clinical outcome following haematopoietic SCT (HSCT). We examined patients transplanted with 9/10 single HLA class I-mismatched grafts (n=171) and 10/10 HLA-A-, -B-, -C-, -DRB1- and -DQB1-matched grafts (n=168). A computer algorithm was used to determine the physiochemical disparity (electrostatic mismatch score (EMS) and hydrophobic mismatch score (HMS)) of mismatched HLA class I specificities in the graft-versus-host direction. Patients transplanted with HLA-mismatched grafts with high EMS/HMS had increased incidence of ⩾grade II acute GVHD (aGVHD) compared with patients transplanted with low EMS/HMS grafts; patients transplanted with low and medium EMS/HMS grafts had similar incidence of aGVHD to patients transplanted with 10/10 HLA-matched grafts. Mortality was higher following single HLA-mismatched HSCT but was not correlated with HLA physiochemical disparity. Assessment of donor-recipient HLA incompatibility based on physiochemical HLA disparity may enable better selection of HLA-mismatched donors in HSCT.

  16. Serological evidence that activation of ubiquitous human herpesvirus-6 (HHV-6) plays a role in chronic idiopathic/spontaneous urticaria (CIU). (United States)

    Dreyfus, D H


    Acute infection with viral pathogens in the herpesviridae family can trigger acute urticaria, and reactivation of herpesviridae is associated with cutaneous urticarial-like syndromes such as drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DRESS). Reactivation of latent herpesviridae has not been studied systematically in chronic idiopathic/spontaneous urticaria (CIU). This review proposes that CIU is an inflammatory disorder with autoimmune features (termed 'CVU' for chronic viral urticaria), based on serology consistent with the hypothesis that reactivation of a latent herpesvirus or -viruses may play a role in CIU. Serology obtained from a cohort of omalizumab (Xolair)-dependent patients with severe CIU was consistent with previous HHV-6 infection, persistent viral gene expression and replication. CIU patients also exhibited serological evidence of increased immune response to HHV-4 (Epstein-Barr virus, or EBV) but not all CIU patients were infected with EBV. These observations, combined with case reports of CIU response to anti-viral therapy, suggest that HHV-6, possibly interacting with HHV-4 in cutaneous tissues, is a candidate for further prospective study as a co-factor in CIU. © 2015 British Society for Immunology.

  17. Abnormality of spontaneous brain activities in patients with chronic neck and shoulder pain: A resting-state fMRI study. (United States)

    Yu, Cheng-Xin; Ji, Ting-Ting; Song, Hao; Li, Bo; Han, Qiang; Li, Liang; Zhuo, Zhi-Zheng


    Objectives Chronic gneck and shoulder pain (CNSP) is a common clinical symptom of cervical spondylotic radiculopathy. Several studies using resting-state functional magnetic resonance imaging (rs-fMRI) have reported that most chronic pain diseases are accompanied by structural and functional changes in the brain. However, few rs-fMRI studies have examined CNSP. The current study investigated cerebral structural and functional changes in CNSP patients. Methods In total, 25 CNSP patients and 20 healthy volunteers participated in the study. 3D-T1W and rs-fMRI images were acquired. Voxel-based morphometry analysis was applied to structural images, and regional homogeneity (ReHo) was extracted from rs-fMRI. Statistical analysis was performed on post-processing images and ReHo parameter maps. Results The results revealed no significant differences in brain structure between the two groups. In the patient group, ReHo values were significantly increased in the bilateral middle frontal gyrus and decreased in the left insula, superior frontal gyrus, middle cingulate gyrus, supplementary motor area, right postcentral gyrus, and superior parietal lobule. Conclusions This initial structural and rs-fMRI study of CNSP revealed characteristic features of spontaneous brain activity of CNSP patients. These findings may be helpful for increasing our understanding of the neuropathology of CNSP.

  18. Have we made progress in the management of chronic graft-vs-host disease? (United States)

    Lee, Stephanie J


    Chronic graft-vs-host disease (GVHD) is a common long-term complication of allogeneic hematopoietic cell transplant that is associated with very high morbidity and mortality. In order to understand whether we have made progress in the management of chronic GVHD, it is helpful to first propose a definition of meaningful "progress". The following can be considered to be indicators of improved management of chronic GVHD: a decrease in the incidence or severity of chronic GVHD, better efficacy or decreased toxicity of therapies, better quality of life despite chronic GVHD, and improved overall and disease-free survival rates. However, to date, real progress has not been made in these areas, though there are promising new preventive strategies and treatments. Furthermore, a consensus has been reached in the research community about many different issues surrounding chronic GVHD definitions, management, and the conduct of clinical trials. These consensus documents will help to standardize efforts and data collection so that true comparisons can be made in the future and real clinical progress achieved. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. Haploidentical hematopoietic stem cell transplantation in children with high-risk hematologic malignancies: outcomes with two different strategies for GvHD prevention. Ex vivo T-cell depletion and post-transplant cyclophosphamide: 10 years of experience at a single center. (United States)

    Dufort, G; Castillo, L; Pisano, S; Castiglioni, M; Carolina, P; Andrea, I; Simon, E; Zuccolo, S; Schelotto, M; Morosini, F; Pereira, I; Amarillo, P; Silveira, A; Guerrero, L; Ferreira, V; Tiscornia, A; Mezzano, R; Lemos, F; Boggia, B; Quarnetti, A; Decaro, J; Dabezies, A


    Forty patients with high-risk hematologic malignancies, median age 9 years, underwent haploidentical-HSCT from April 2005 to April 2015. Seventeen patients were transplanted with CD3-depleted PBSCs by negative selection (TCD group) following a reduced-intensity conditioning regimen (RIC), and 23 patients received T-cell-replete PBSCs followed by post-transplantation cyclophosphamide (PT-Cy group) after myeloablative conditioning (n=16) or RIC (n=7). Outcomes are reported for the TCD and PT-Cy recipients, respectively. Engraftment was achieved in 88% versus 100%. Median time to neutrophils>500/μL was 10 days versus 15 days. Platelets>20 000/μL occurred at a median of 16 days versus 20 days, respectively. Transplant-related mortality (TRM) was 24% versus 26% at 1 year. The cumulative incidence (CI) of grade III-IV acute GvHD was 7% versus 5%, and chronic GvHD 9% versus 53% (P=0.029). Relapse at 2 years was 31% versus 24%. Actuarial overall survival rates at 2 years were 47% versus 48%. Causes of death were infections (n=3), sinusoidal obstructive syndrome (n=4), acute GvHD (n=2) and relapse (n=9). These results indicate that haploidentical-HSCT is feasible in Uruguay. The TRM rate is of concern and should be the focus of continuing attention. Chronic GvHD risk was higher in the PT-Cy approach, so modifications are justified.

  20. Usefulness of blood irradiation before transfusion to avoid transfusion associated graft versus host disease (TA-GVHD)

    International Nuclear Information System (INIS)

    Takahashi, Koki


    We summarize the pathology of the transfusion associated graft versus host disease (TA-GVHD) and examine the usefulness of the blood irradiation before transfusion as more widely used prophylaxis. The symptom of TA-GVHD was as follows: after (asymptomatic phase) for 1 to 2 weeks after blood transfusion, pyrexia and erythema appeared. Furthermore, hepatic disorder, diarrhea and bloody stool occurred. In no longer time, pancytopenia by aplastic crisis of the bone marrow appeard, and severe granulocytopenia occurred. Finally, by the complication with severe infectious disease such as septicemia, almost all the patients died with in 3 to 4 weeks after blood transfusion. TA-GVHD was found in some patients without immune deficiency syndrome. The cause of the frequent occurrence of the disease in Japan was shown by the probability of the one-way matching analysis. As the countermeasure of TA-GVHD, we examined the effectiveness of the blood irradiation before transfusion under the consideration of the safety and the emergency. After the responder cells were beforehand irradiated with various doses of radiation (X-ray or g-ray), the proliferative response was investigated through the uptake of 3 H-thymidine, and we obtained 15-50 Gy as the optimum dose of the radiation. We discuss the establishment of the countermeasure for the TA-GVHD and the formation of the nationwide support system for TV-GVHD (K.H.). 33 refs

  1. Combined nonlinear metrics to evaluate spontaneous EEG recordings from chronic spinal cord injury in a rat model: a pilot study. (United States)

    Pu, Jiangbo; Xu, Hanhui; Wang, Yazhou; Cui, Hongyan; Hu, Yong


    Spinal cord injury (SCI) is a high-cost disability and may cause permanent loss of movement and sensation below the injury location. The chance of cure in human after SCI is extremely limited. Instead, neural regeneration could have been seen in animals after SCI, and such regeneration could be retarded by blocking neural plasticity pathways, showing the importance of neural plasticity in functional recovery. As an indicator of nonlinear dynamics in the brain, sample entropy was used here in combination with detrended fluctuation analysis (DFA) and Kolmogorov complexity to quantify functional plasticity changes in spontaneous EEG recordings of rats before and after SCI. The results showed that the sample entropy values were decreased at the first day following injury then gradually increased during recovery. DFA and Kolmogorov complexity results were in consistent with sample entropy, showing the complexity of the EEG time series was lost after injury and partially regained in 1 week. The tendency to regain complexity is in line with the observation of behavioral rehabilitation. A critical time point was found during the recovery process after SCI. Our preliminary results suggested that the combined use of these nonlinear dynamical metrics could provide a quantitative and predictive way to assess the change of neural plasticity in a spinal cord injury rat model.

  2. Transcriptional changes associated with reduced spontaneous liver tumor incidence in mice chronically exposed to high dose arsenic. (United States)

    Nelson, Gail M; Ahlborn, Gene J; Allen, James W; Ren, Hongzu; Corton, J Christopher; Waalkes, Michael P; Kitchin, Kirk T; Diwan, Bhalchandra A; Knapp, Geremy; Delker, Don A


    Exposure of male C3H mice in utero (from gestational days 8-18) to 85ppm sodium arsenite via the dams' drinking water has previously been shown to increase liver tumor incidence by 2 years of age. However, in our companion study (Ahlborn et al., 2009), continuous exposure to 85ppm sodium arsenic (from gestational day 8 to postnatal day 365) did not result in increased tumor incidence, but rather in a significant reduction (0% tumor incidence). The purpose of the present study was to examine the gene expression responses that may lead to the apparent protective effect of continuous arsenic exposure. Genes in many functional categories including cellular growth and proliferation, gene expression, cell death, oxidative stress, protein ubiquitination, and mitochondrial dysfunction were altered by continuous arsenic treatment. Many of these genes are known to be involved in liver cancer. One such gene associated with rodent hepatocarcinogenesis, Scd1, encodes stearoyl-CoA desaturase and was down-regulated by continuous arsenic treatment. An overlap between the genes in our study affected by continuous arsenic exposure and those from the literature affected by long-term caloric restriction suggests that reduction in the spontaneous tumor incidence under both conditions may involve similar gene pathways such as fatty acid metabolism, apoptosis, and stress response.

  3. Transcriptional changes associated with reduced spontaneous liver tumor incidence in mice chronically exposed to high dose arsenic

    International Nuclear Information System (INIS)

    Nelson, Gail M.; Ahlborn, Gene J.; Allen, James W.; Ren, Hongzu; Corton, J. Christopher; Waalkes, Michael P.; Kitchin, Kirk T.; Diwan, Bhalchandra A.; Knapp, Geremy; Delker, Don A.


    Exposure of male C3H mice in utero (from gestational days 8-18) to 85 ppm sodium arsenite via the dams' drinking water has previously been shown to increase liver tumor incidence by 2 years of age. However, in our companion study (Ahlborn et al., 2009), continuous exposure to 85 ppm sodium arsenic (from gestational day 8 to postnatal day 365) did not result in increased tumor incidence, but rather in a significant reduction (0% tumor incidence). The purpose of the present study was to examine the gene expression responses that may lead to the apparent protective effect of continuous arsenic exposure. Genes in many functional categories including cellular growth and proliferation, gene expression, cell death, oxidative stress, protein ubiquitination, and mitochondrial dysfunction were altered by continuous arsenic treatment. Many of these genes are known to be involved in liver cancer. One such gene associated with rodent hepatocarcinogenesis, Scd1, encodes stearoyl-CoA desaturase and was down-regulated by continuous arsenic treatment. An overlap between the genes in our study affected by continuous arsenic exposure and those from the literature affected by long-term caloric restriction suggests that reduction in the spontaneous tumor incidence under both conditions may involve similar gene pathways such as fatty acid metabolism, apoptosis, and stress response.

  4. Selective replacement of mitochondrial DNA increases the cardioprotective effect of chronic continuous hypoxia in spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Neckář, Jan; Svatoňová, Anna; Weissová, Romana; Drahota, Zdeněk; Zajíčková, Pavlína; Brabcová, I.; Kolář, D.; Alánová, Petra; Vašinová, Jana; Šilhavý, Jan; Hlaváčková, Markéta; Tauchmannová, Kateřina; Milerová, Marie; Ošťádal, Bohuslav; Červenka, L.; Žurmanová, J.; Kalous, M.; Nováková, Olga; Novotný, J.; Pravenec, Michal; Kolář, František


    Roč. 131, č. 9 (2017), s. 865-881 ISSN 0143-5221 R&D Projects: GA ČR(CZ) GA13-10267S; GA ČR(CZ) GB14-36804G; GA MŠk(CZ) LL1204 Institutional support: RVO:67985823 Keywords : chronic hypoxia * heart * hypertension * ischaemia–reperfusion injury * mitochondrial genome * mitochondrial permeability transition pore Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery OBOR OECD: Physiology (including cytology) Impact factor: 4.936, year: 2016

  5. H1-antihistamine-refractory chronic spontaneous urticaria: it's worse than we thought - first results of the multicenter real-life AWARE study. (United States)

    Maurer, M; Staubach, P; Raap, U; Richter-Huhn, G; Bauer, A; Ruëff, F; Jakob, T; Yazdi, A S; Mahler, V; Wagner, N; Lippert, U; Hillen, U; Schwinn, A; Pawlak, M; Behnke, N; Chaouche, K; Chapman-Rothe, N


    Most data on chronic spontaneous urticaria (CSU) originate from highly selected patient populations treated at specialized centres. Little is known about CSU patient characteristics and the burden of CSU in routine clinical practice. AWARE (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) is an ongoing global study designed to assess chronic urticaria in the real-life setting. To describe the baseline characteristics of the first 1539 German AWARE patients with H1-antihistamine-refractory CSU. This prospective non-interventional study included patients (18-75 years) with a diagnosis of H1-antihistamine-refractory CSU for > 2 months. Baseline demographic and disease characteristics, comorbidities, and pharmacological treatments were recorded. Quality of life (QoL) was assessed using the dermatology life quality index (DLQI), chronic urticaria QoL questionnaire (CU-Q 2 oL), and angioedema QoL questionnaire (AE-QoL, in cases of angioedema). Previous healthcare resource utilization and sick leave data were collected retrospectively. Between March and December 2014, 1539 patients were assessed in 256 sites across Germany. The percentage of females, mean age, and mean body mass index were 70%, 46.3 years, and 27 kg/m 2 , respectively. The mean urticaria control test score was 7.9, one in two patients had angioedema, and the most frequent comorbidities were chronic inducible urticaria (CIndU; 24%), allergic rhinitis (18.2%), hypertension (18.1%), asthma (12%), and depression (9.5%). Overall, 57.6% of patients were receiving at least one pharmacological treatment including second-generation H1-antihistamines (46.3%), first-generation H1-antihistamines (9.1%), and corticosteroids (15.8%). The mean DLQI, total CU-Q 2 oL, and total AE-QoL scores were 8.3, 36.2, and 46.8, respectively. CSU patients reported frequent use of healthcare resources, including emergency services (29.7%), general practitioners (71.9%), and additional allergists or

  6. Improvement in the quality of life of patients with chronic spontaneous urticaria treated with omalizumab in real life. (United States)

    Larrea-Baca, Itzíar; Gurpegui-Resano, María

    Evaluation of the impact on the quality of life (QOL) relating to health in patients with chronic urticaria (CSU) treated with omalizumab. Longitudinal descriptive observational study of quality of life based on18 patients with chronic urticaria ≥12 years treated with omalizumab. Changes in QOL examined at 1 month (T1), at 6 months (T6) and 12 months (T12), by: Visual Analogical Scale (UAS), specific urticaria QOL questionnaire (CU-Q2oL), general health questionnaire (SF-36) and activity of urticaria questionnaire (Score UAS7). The most disabling symptoms for patients were: pruritus (61.1%); decrease in health and physical activity (55.5%), wheals, swelling and nervousness (50%); depression and shame of marks (38.89%); side effects to drugs (33.33%); sleepiness and tiredness (27.78%); work (22.22%); "choosing clothes and pain" 16.67% and social relations (11.11%). Statistically significant differences were observed in T1, T6 and T12. In T1, UAS -4.72 (p=.001); CU-Q2oL -16.38 (p<.001); SF-36 15.44 (p=.006); UAS7 wheals -7.27 (p=.001), UAS7 pruritus -8.72 (p=.003). In T6, UAS -4.26 (p=.001); CU-Q2oL -18.94 (p<.001); SF-36 15.41 (p<.001); UAS7 wheals -7.41 (p=.001), UAS7 pruritus -7.11 (p=.001). In T12 UAS -9.61 (p=.004); CU-Q2oL -21.38 (p=.01); SF-36 17.53 (p=.04); UAS7 wheals -8.23 (p=.004), UAS7 pruritus -10.69 (p=.004). There was a very good response in T1, which was maintained in T6 and T12. Patients with chronic urticaria treated with omalizumab presented good results with a reduction of CUE activity and improvement of their QOL. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  7. Spontaneous pneumothorax

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    Davari R


    Full Text Available A case with bilateral spontaneous pneumothorax was presented. Etiology, mechanism, and treatment were discussed on the review of literature. Spontaneous Pneumothorax is a clinical entity resulting from a sudden non traumatic rupture of the lung. Biach reported in 1880 that 78% of 916 patients with spontaneous pneumothorax had tuberculosis. Kjergaard emphasized 1932 the primary importance of subpleural bleb disease. Currently the clinical spectrum of spontaneous pneumothorax seems to have entered a third era with the recognition of the interstitial lung disease and AIDS as a significant etiology. Standard treatment is including: observation, thoracocentesis, tube thoracostomy. Chemical pleurodesis, bullectomy or wedge resection of lung with pleural abrasion and occasionally pleurectomy. Little information has been reported regarding the efficacy of such treatment in spontaneous pneumothorax secondary to non bleb disease

  8. Chronic cigarette smoking enhances spontaneous release of tumour necrosis factor-α from alveolar macrophages of rats

    Directory of Open Access Journals (Sweden)

    G. P. Pessina


    Full Text Available Some biological effects of chronic cigarette smoking (two cigarettes for 2 h, daily for 4 months in rats were evaluated. During the smoking period, body weight of smoker rats was always significantly lower than that of control rats. Immediately after the last smoking session the carboxyhaemoglobin concentration in the blood was about 8.5% and the polymorphonuclear cells in the bronchoalveolar fluid increased significantly. At the same time, enzymatic analyses on the supernatants of bronchoalveolar fluid revealed a significant increase of β-glucuronidase in the smoker group. Alveolar macrophages, collected 0, 8 and 24 h after the last smoking session, significantly increased the generation of superoxide anion and, after incubation for 24 h at 37° C in a humidified atmosphere, released significantly high amounts of TNF-α. When challenged with lipopolysaccharide, alveolar macrophages of smoker rats released much more TNF-α but, in such a case, TNF-α release was about one half of that observed in the control group. Peritoneal macrophages of both control and smoker rats were unable either to generate high levels of superoxide anion or to release significant amounts of TNF-α. The results clearly demonstrated the activated state of alveolar macrophages and the resting state of peritoneal macrophages.

  9. Effect of omalizumab on angioedema in H1 -antihistamine-resistant chronic spontaneous urticaria patients: results from X-ACT, a randomized controlled trial. (United States)

    Staubach, P; Metz, M; Chapman-Rothe, N; Sieder, C; Bräutigam, M; Canvin, J; Maurer, M


    Chronic spontaneous urticaria (CSU) severely impacts quality of life (QoL), especially in patients with wheals and angioedema. Omalizumab is approved as add-on therapy for CSU patients; however, its effect on patients who are double-positive for wheals and angioedema has not been systematically studied. The primary objective was to evaluate the efficacy of omalizumab vs placebo at week 28 using the Chronic Urticaria Quality of Life (CU-Q2oL) questionnaire. Number of angioedema-burdened days, time interval between successive angioedema episodes, disease activity, angioedema-specific and overall QoL impairment were secondary objectives. X-ACT was a phase III, randomized, double-blind study conducted in 24 centres (Germany), which selectively included CSU patients with angioedema and wheals. Patients were randomized (1 : 1) to omalizumab 300 mg or placebo (every 4 weeks up to week 24) ( number: NCT01723072). Of the 91 patients randomized to omalizumab (n = 44) or placebo (n = 47) at baseline, 68 completed the 28-week treatment phase (omalizumab, 35; placebo, 33). Omalizumab was superior to placebo in improving CU-Q2oL scores at week 28 (P omalizumab (0.3) vs placebo (1.1). The median time to first recurrence of angioedema was 57-63 days with omalizumab and Omalizumab significantly improved angioedema-specific QoL (P omalizumab. Omalizumab was an effective treatment option for patients with moderate-to-severe CSU symptoms and angioedema unresponsive to high doses of antihistamine treatment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Chronic caffeine treatment during prepubertal period confers long-term cognitive benefits in adult spontaneously hypertensive rats (SHR), an animal model of attention deficit hyperactivity disorder (ADHD). (United States)

    Pires, Vanessa A; Pamplona, Fabrício A; Pandolfo, Pablo; Prediger, Rui D S; Takahashi, Reinaldo N


    The spontaneously hypertensive rat (SHR) is frequently used as an experimental model for the study of attention deficit hyperactivity disorder (ADHD) since it displays behavioural and neurochemical features of ADHD. Increasing evidence suggests that caffeine might represent an important therapeutic tool for the treatment of ADHD and we recently demonstrated that the acute administration of caffeine improves several learning and memory impairments in adult SHR rats. Here we further evaluated the potential of caffeine in ADHD therapy. Female Wistar (WIS) and SHR rats were treated with caffeine (3mg/kg, i.p.) or methylphenidate (MPD, 2mg/kg, i.p.) for 14 consecutive days during the prepubertal period (post-natal days 25-38) and they were tested later in adulthood in the object-recognition task. WIS rats discriminated all the objects used, whereas SHR were not able to discriminate pairs of objects with subtle structural differences. Chronic treatment with caffeine or MPD improved the object-recognition deficits in SHR rats. Surprisingly, these treatments impaired the short-term object-recognition ability in adult WIS rats. The present drug effects are independent of changes in locomotor activity, arterial blood pressure and body weight in both rat strains. These findings suggest that chronic caffeine treatment during prepubertal period confers long-term cognitive benefits in discriminative learning impairments of SHR, suggesting caffeine as an alternative therapeutic strategy for the early management of ADHD symptoms. Nevertheless, our results also emphasize the importance of a correct diagnosis and the caution in the use of stimulant drugs such as caffeine and MPD during neurodevelopment since they can disrupt discriminative learning in non-ADHD phenotypes. Copyright 2010 Elsevier B.V. All rights reserved.

  11. Retrospective case note review of chronic spontaneous urticaria outcomes and adverse effects in patients treated with omalizumab or ciclosporin in UK secondary care. (United States)

    Savic, Sinisa; Marsland, Alexander; McKay, David; Ardern-Jones, Michael R; Leslie, Tabi; Somenzi, Olivier; Baldock, Laura; Grattan, Clive


    Omalizumab is approved in the UK as add-on treatment for chronic spontaneous urticaria (CSU) in patients with inadequate response to H1-antihistamines. Ciclosporin is an established but unlicensed 3rd line option for CSU. Two parallel retrospective observational studies were conducted to describe outcomes of treatment and adverse events with omalizumab or ciclosporin for CSU treatment. Data from UK specialist centres prescribing omalizumab (five centres) or ciclosporin (three centres) in CSU patients were collected from hospital records by clinical staff and pooled for analysis. Forty-six patients prescribed omalizumab and 72 patients prescribed ciclosporin were included. Twenty-two (48%) omalizumab-treated patients had paired Urticaria Activity Scores (UAS7), showing a 25.4 point improvement during treatment (P making causality assignment difficult, whereas those for ciclosporin were consistent with its known adverse effect profile. Validated patient-reported measures of disease severity and quality of life should be used routinely in CSU management. Based on clinician comments and DLQI scores, symptoms and quality of life showed a greater improvement in the omalizumab-treated cohort than in the ciclosporin-treated cohort.

  12. Positive impact of omalizumab on angioedema and quality of life in patients with refractory chronic idiopathic/spontaneous urticaria: analyses according to the presence or absence of angioedema. (United States)

    Maurer, M; Sofen, H; Ortiz, B; Kianifard, F; Gabriel, S; Bernstein, J A


    Approximately 50% of patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) report hives and angioedema; some experience hives/angioedema only. Assess omalizumab's effect on angioedema and quality of life (QoL) in subgroups with refractory CIU/CSU: those with and without angioedema. Patients received omalizumab (75, 150 or 300 mg) or placebo every 4 weeks for 12/24 weeks. Angioedema and QoL were assessed [Urticaria Patient Daily Diary and Dermatology Quality of Life Index (DLQI)]. Subgroups were based on the presence/absence of baseline angioedema 7 days prior to randomization. Patients with baseline angioedema randomized to omalizumab 300 mg had a greater reduction in mean weekly incidence of angioedema and mean number of days/week with angioedema vs. placebo at 12 and 24 weeks. A 3.3- to 4.5-point greater mean reduction in DLQI score was achieved with omalizumab 300 mg treatment vs. placebo, above the minimal clinically important difference threshold. Results with lower doses vs. placebo were variable. Compared with placebo, omalizumab 300 mg treatment over 12-24 weeks resulted in marked reduction in incidence and number of days/week with angioedema accompanied by clinically relevant improvement in QoL. © 2016 European Academy of Dermatology and Venereology.

  13. Autoreactive IgE in Chronic Spontaneous/Idiopathic Urticaria and Basophil/Mastocyte Priming Phenomenon, as a Feature of Autoimmune Nature of the Syndrome. (United States)

    Panaszek, Bernard; Pawłowicz, Robert; Grzegrzółka, Jędrzej; Obojski, Andrzej


    Recent years of research have shed a new light on the role of IgE in immune reactions. It seems to be more than just a contribution to immediate type of allergic response. It appears that monomeric IgE may enhance mast cell activity without cross-linking of FcεRI by IgE specific allergen or autoreactive IgG anti-IgE antibodies. Monomeric IgE molecules are heterogeneous concerning their ability to induce survival and activation of mast cells only by binding the IgE to FcεRI, but not affecting degranulation of cells. It also turned out that IgE may react to autoantigens occurring in the blood not only in chronic spontaneous urticaria (CSU) but also in other autoimmune diseases. The aforementioned phenomena may promote the activity of mast cells/basophils in CSU that easily degranulate when influenced by various inner (autoreactive IgG against IgE and FcεRI, autoreactive IgE for self-antigens) and outer factors (cold, heat, pressure) or allergens. These findings forced the new approach to the role of autoimmunity, self-antigens and IgE autoantibodies in the pathology of CSU. CSU put in the scheme of autoreactive IgG and autoreactive IgE seems to be either a kind of an autoimmune disease or a clinical manifestation of some other defined autoimmune diseases or both.

  14. Effectiveness of omalizumab in adolescent and adult patients with chronic idiopathic/spontaneous urticaria: a systematic review of 'real-world' evidence. (United States)

    Bernstein, Jonathan A; Kavati, Abhishek; Tharp, Michael D; Ortiz, Benjamin; MacDonald, Karen; Denhaerynck, Kris; Abraham, Ivo


    Chronic idiopathic/spontaneous urticaria (CIU/CSU) is a dermatological condition characterized by itchy wheals and/or angioedema of continuous or intermittent duration of ≥6 weeks with a high burden of disease and impact on quality of life. Omalizumab is a recombinant humanized monoclonal antibody that inhibits the binding of IgE to high affinity receptors, and is approved for the CIU/CSU indication. The objective of this systematic review was to evaluate and synthesize the evidence on the real-world effectiveness of omalizumab in CIU/CSU in daily clinical practice. Areas covered: This review of 84 observational effectiveness studies covers treatments (dosing, medication use), clinical outcomes (treatment response, disease activity, quality of life), and safety. Expert opinion: The clinical outcomes observed across studies underscore the real-world effectiveness of omalizumab in the management of CIU/CSU. Continued treatment may assist patients showing an initial response to achieve a complete treatment response. Response rates are aligned with observed changes in disease activity, symptom experience, and quality of life, and this across subtypes of CIU/CSU. The positive therapeutic profile is complemented by a positive safety profile. The real-world evidence summarized here points convincingly at the high degree of effectiveness of omalizumab in the treatment of CIU/CSU in daily clinical practice.

  15. Thoracic air-leakage syndrome in allogeneic stem cell transplant recipients as a late complication of chronic graft-versus-host disease: A case report

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    Park, Jae Wook; Kim, Song Soo; Jo, Daeg Yeon; Yun, Hwan Jung; Lee, Hyo Jin; Kim, Jin Hwan [Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon (Korea, Republic of)


    Air-leakage syndrome associated with graft-versus-host disease (GVHD) is a rare complication, but it is also reported as an independent predictor of a worse survival rate after stem cell transplantation. We report two cases of air-leakage syndrome associated with GVHD after allogeneic stem cell transplantation in acute leukemia patients who presented with spontaneous pneumomediastinum and subcutaneous emphysema, and finally death due to respiratory failure seven to eight months later.

  16. CD4+CD25highCD127low Regulatory T Cells in Peripheral Blood Are Not an Independent Factor for Chronic Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Jolanta B. Perz


    Full Text Available Background. The therapeutic efficacy of allogeneic hemopoietic stem cell transplantation (HSCT largely relies on the graft-versus-leukemia (GVL effect. Uncontrolled graft-versus-host disease (GVHD is a feared complication of HSCT. Regulatory T cells (Treg are a subset of CD4+ T-helper cells believed to maintain tolerance after HSCT. It remains unclear whether low peripheral blood Treg have an impact on the risk for acute (aGVHD and chronic GVHD (cGVHD. Methods. In this paper we enumerated the CD4+CD25highCD127low Treg in the peripheral blood of 84 patients after at least 150 days from HSCT and in 20 healthy age-matched controls. Results. Although similar mean lymphocyte counts were found in patients and controls, CD3+CD4+ T-cell counts were significantly lower in patients. Patients also had significantly lower Treg percentages among lymphocytes as compared to controls. Patients with cGVHD had even higher percentages of Treg if compared to patients without cGVHD. In multivariate analysis, Treg percentages were not an independent factor for cGVHD. Conclusions. This paper did not show a relation between deficient peripheral blood Treg and cGVHD, therefore cGVHD does not seem to occur as a result of peripheral Treg paucity.

  17. Adenosine Selectively Depletes Alloreactive T Cells to Prevent GVHD While Conserving Immunity to Viruses and Leukemia. (United States)

    Whitehill, Greg D; Amarnath, Shoba; Muranski, Pawel; Keyvanfar, Keyvan; Battiwalla, Minoo; Barrett, Austin J; Chinnassamy, Dhanalakshmi


    Selective depletion (SD) of alloreactive T cells from allogeneic hematopoeitic stem cell transplants to prevent graft-versus-host disease (GVHD) without compromising immune reconstitution and antitumor responses remains a challenge. Here, we demonstrate a novel SD strategy whereby alloreacting T cells are efficiently deleted ex vivo with adenosine. SD was achieved in human leukocyte antigen (HLA) mismatched cocultures by multiple exposures to 2 mmol/l adenosine over 7 days. Adenosine depleted greater than to 90% of alloproliferating T cells in mismatched, haploidentical, and matched sibling pairs while conserving response to third-party antigens. Alloreactive CD4 and CD8 T cells were targeted for depletion while NK and B cells were preserved. Our novel approach also preserved nonalloreactive naive, central, and effector memory T-cell subsets, Tregs, and notably preserved T-cell responses against DNA viruses that contribute to transplant related mortality after allogeneic hematopoeitic stem cell transplants. Additionally, T cells recognizing leukemia-associated antigens were efficiently generated in vitro from the cell product post-SD. This study is the first to demonstrate that adenosine depletion of alloactivated T cells maintains a complete immune cell profile and recall viral responses. Expansion of tumor antigen-specific subsets postdepletion opens the possibility of generating T-cell products capable of graft-versus-tumor responses without causing GVHD.

  18. Sclerodermatous Chronic Graft-versus-Host Disease Treated With Imatinib: A Dermatological Perspective. (United States)

    Molés-Poveda, P; Montesinos, P; Sanz-Caballer, J; de Unamuno, B; Piñana, J L; Sahuquillo, A; Botella-Estrada, R


    Chronic graft-versus-host disease (cGVHD) is the most important cause of late non-relapse mortality after allogeneic hematopoietic stem cell transplantation. Sclerodermatous cGVHD is usually steroid refractory and remains a therapeutic challenge. Activating antibodies against the PDGFR have been reported in patients with sclerodermatous cGVHD. These antibodies induce PDGFR phosphorylation and lead to fibrosis. There is increasing evidence of successful treatment of sclerodermatous cGVHD with imatinib, a tyrosine kinase inhibitor. To evaluate the response of cutaneous sclerodermatous cGVHD to imatinib. Retrospective study of 18 patients with sclerodermatous cGVHD refractory to immunosuppressants treated with imatinib in a single center. Evaluation of treatment response was performed by clinicians' assessment and patients' subjective response at one, 3, 6, 9, 12 and 18 months after initiation of imatinib. Response was assessed as complete, partial, significant, no change or progression. Tapper off steroids was complete, partial or not possible. In our series, 4 (22%) patients achieved complete response, 9 (50%) patients partial response, 2 (11%) patients significant response, 2 (11%) patients had no change and one (6%) patient progressive disease at last follow-up. Mean time from initiation of imatinib to any degree of response was 2,75 months (range 1-9 months). This study provides further evidence of the role of imatinib for the treatment of steroid refractory sclerodermatous cGVHD. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Evaluation of autologous serum skin test and skin prick test reactivity to house dust mite in patients with chronic spontaneous urticaria.

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    Zhiqiang Song

    Full Text Available BACKGROUND: Chronic spontaneous urticaria (CSU is a common skin disorder with etiology that is not well understood. METHODS: In this study, we evaluated the prevalence of autologous serum skin test (ASST and skin prick testing (SPT to house dust mite (HDM in 862 CSU cases in China. Clinical features, courses and treatment responses were also recorded. RESULTS: The prevalence of positive ASST was 46.3%, and patients aged 30-39 years had the highest positive rate (52.1%. Positive SPT to HDM was seen in 153 patients (17.7% with the highest positive rate (34.2% in patients aged 20 or less. Patients with positive ASST had higher urticaria activity scores (UAS (4.18±0.65 vs. 3.67±0.53 but lower positive rates of HDM (24.6% vs. 37.6%, as compared with those with negative ASST (odds ratio (OR 1.84, 95% CI 1.38-2.47. Patients could be categorized into four groups based on the results of ASST and SPT to HDM and patients with positive ASST and positive SPT to HDM had the highest disease activity scores, experienced higher frequencies of angioedema, diseases duration, and required higher dosage of loratadine every month, compared with other subgroups (P<0.0001. CONCLUSIONS: Patients with CSU showed varied responses of positive ASST and varied sensitivity to HDM, Patients with positive ASST and/or positive SPT had more disease activity compared with patients with negative ASST and/or negative SPT. Further classification can be made based on the result of SPT and ASST.

  20. A 21-35 kDa Mixed Protein Component from Helicobacter pylori Activates Mast Cells Effectively in Chronic Spontaneous Urticaria. (United States)

    Tan, Ran-Jing; Sun, He-Qiang; Zhang, Wei; Yuan, Han-Mei; Li, Bin; Yan, Hong-Tao; Lan, Chun-Hui; Yang, Jun; Zhao, Zhuo; Wu, Jin-Jin; Wu, Chao


    Helicobacter pylori (H. pylori) seem to involve in the etiology of chronic spontaneous urticaria (CSU). But studies of the pathogenic mechanism are very little. In this study, we detected the serum-specific anti-H. pylori IgG and IgE antibodies in 211 CSU and 137 normal subjects by enzyme-linked immunosorbent assay (ELISA), evaluated the direct activation effects of H. pylori preparations and its protein components on human LAD 2 mast cell line in vitro, and analyzed the specific protein ingredients and functions of the most effective H. pylori mixed protein component using liquid chromatography-mass spectrometry and ELISA assay. In CSU patients, the positive rate of anti-H. pylori IgG positive rate was significantly higher than that in normal controls, and the anti-H. pylori IgE levels had no statistical difference between H. pylori-infected patients with and without CSU. Further studies suggested that H. pylori preparations can directly activate human LAD 2 mast cell line in a dose-dependent manner and its most powerful protein component was a mixture of 21-35 kDa proteins. Moreover, the 21-35 kDa mixed protein component mainly contained 23 kinds of proteins, which can stimulate the release of histamine, TNF-a, IL-3, IFN-γ, and LTB4 by LAD 2 cells in a dose-dependent or time-dependent manner. A 21-35 kDa mixed protein component should be regarded as the most promising pathogenic factor contributing to the CSU associated with H. pylori infection. © 2016 John Wiley & Sons Ltd.

  1. An open-label prospective clinical study to assess the efficacy of increasing levocetirizine dose up to four times in chronic spontaneous urticaria not controlled with standard dose. (United States)

    Sharma, Vinod Kumar; Gupta, Vishal; Pathak, Mona; Ramam, M


    The EAACI/GA 2 LEN/EDF/WAO recommendation of increasing antihistamines' dose up to four times in urticaria not adequately controlled with the standard dose is largely based on expert opinion. The objective of this study is to test the current urticaria guidelines of up-dosing antihistamines as second-line treatment. This was an open-label study conducted prospectively on 113 patients with chronic spontaneous urticaria. All patients were treated with sequentially increasing doses of levocetrizine (5 mg, 10 mg, 15 mg and 20 mg/day) every week till the patients became completely asymptomatic or dose of 20 mg/day reached. Urticaria Activity Score (UAS)-7, urticaria-related quality-of-life (CU-Q2oL) and patients' global assessment were used to assess treatment response. Twenty-one (18.58%) patients became asymptomatic with levocetirizine 5 mg/day, while 50 required higher doses of levocetirizine for complete control: 29/92 (31.52%), 6/63 (9.52%) and 15/57 (26.31%) with 10 mg, 15 mg and 20 mg/day, respectively. The percentage of patients experiencing >75% improvement increased with increasing doses of levocetirizine: 26.54%, 53.98%, 60.17% and 69.91% with 5 mg, 10 mg, 15 mg and 20 mg/day, respectively. Sequential up-dosing of levocetirizine produced a progressive improvement in both urticaria control (UAS-7) and quality-of-life (CU-Q2oL) without significantly increasing somnolence. Our results support the current recommendations of increasing antihistamines up to four times the standard dose in patients who fail the first-line treatment.

  2. Lactobacillus rhamnosus GG probiotic enteric regimen does not appreciably alter the gut microbiome or provide protection against GVHD after allogeneic hematopoietic stem cell transplantation. (United States)

    Gorshein, Elan; Wei, Catherine; Ambrosy, Susan; Budney, Shanna; Vivas, Juliana; Shenkerman, Angelika; Manago, Jacqueline; McGrath, Mary Kate; Tyno, Anne; Lin, Yong; Patel, Vimal; Gharibo, Mecide; Schaar, Dale; Jenq, Robert R; Khiabanian, Hossein; Strair, Roger


    Graft-versus-host disease (GVHD) is a major adverse effect associated with allogeneic stem cell transplant. Previous studies in mice indicated that administration of the probiotic Lactobacillus rhamnosus GG can reduce the incidence of GVHD after hematopoietic stem cell transplant. Here we report results from the first randomized probiotic enteric regimen trial in which allogenic hematopoietic stem cell patients were supplemented with Lactobacillus rhamnosus GG. Gut microbiome analysis confirmed a previously reported gut microbiome association with GVHD. However, the clinical trial was terminated when interim analysis did not detect an appreciable probiotic-related change in the gut microbiome or incidence of GVHD. Additional studies are necessary to determine whether probiotics can alter the incidence of GVHD after allogeneic stem cell transplant. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. alpha-1-Antitrypsin (AAT)-modified donor cells suppress GVHD but enhance the GVL effect: a role for mitochondrial bioenergetics

    NARCIS (Netherlands)

    Marcondes, A.M.; Karoopongse, E.; Lesnikova, M.; Margineantu, D.; Welte, T.; Dinarello, C.A.; Hockenbery, D.; Janciauskiene, S.; Deeg, H.J.


    Hematopoietic cell transplantation is curative in many patients. However, graft-versus-host disease (GVHD), triggered by alloreactive donor cells, has remained a major complication. Here, we show an inverse correlation between plasma alpha-1-antitrypsin (AAT) levels in human donors and the

  4. Spontaneous deregulation

    NARCIS (Netherlands)

    Edelman, Benjamin; Geradin, Damien

    Platform businesses such as Airbnb and Uber have risen to success partly by sidestepping laws and regulations that encumber their traditional competitors. Such rule flouting is what the authors call “spontaneous private deregulation,” and it’s happening in a growing number of industries. The authors

  5. Efficacy and Safety of Omalizumab in Patients with Chronic Idiopathic/Spontaneous Urticaria Who Remain Symptomatic on H1 Antihistamines: A Randomized, Placebo-Controlled Study (United States)

    Saini, Sarbjit S; Bindslev-Jensen, Carsten; Maurer, Marcus; Grob, Jean-Jacques; Bülbül Baskan, Emel; Bradley, Mary S; Canvin, Janice; Rahmaoui, Abdelkader; Georgiou, Panayiotis; Alpan, Oral; Spector, Sheldon; Rosén, Karin


    ASTERIA I was a 40-week, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of subcutaneous omalizumab as add-on therapy for 24 weeks in patients with chronic idiopathic urticaria/spontaneous urticaria (CIU/CSU) who remained symptomatic despite H1 antihistamine treatment at licensed doses. Patients aged 12–75 years with CIU/CSU who remained symptomatic despite treatment with approved doses of H1 antihistamines were randomized (1:1:1:1) in a double-blind manner to subcutaneous omalizumab 75 mg, 150 mg, or 300 mg or placebo every 4 weeks for 24 weeks followed by 16 weeks of follow-up. The primary end point was change from baseline in weekly itch severity score (ISS) at week 12. Among randomized patients (N=319: placebo n=80, omalizumab 75 mg n=78, 150 mg n=80, 300 mg n=81), 262 (82.1%) completed the study. Compared with placebo (n=80), mean weekly ISS was reduced from baseline to week 12 by an additional 2.96 points (95% confidence interval (CI): −4.71 to −1.21; P=0.0010), 2.95 points (95% CI: −4.72 to −1.18; P=0.0012), and 5.80 points (95% CI: −7.49 to −4.10; Pomalizumab 75-mg (n=77), 150-mg (n=80), and 300-mg groups (n=81), respectively. The omalizumab 300-mg group met all nine secondary end points, including a significant decrease in the duration of time to reach minimally important difference response (⩾5-point decrease) in weekly ISS (Pomalizumab 75-mg, 150-mg, 300-mg, and placebo groups, respectively, experienced a serious adverse event. Omalizumab 300 mg administered subcutaneously every 4 weeks reduced weekly ISS and other symptom scores versus placebo in CIU/CSU patients who remained symptomatic despite treatment with approved doses of H1 antihistamines. PMID:25046337

  6. Clinical efficacy of omalizumab in chronic spontaneous urticaria is associated with a reduction of FcεRI-positive cells in the skin. (United States)

    Metz, Martin; Staubach, Petra; Bauer, Andrea; Brehler, Randolf; Gericke, Janine; Kangas, Michael; Ashton-Chess, Joanna; Jarvis, Philip; Georgiou, Panayiotis; Canvin, Janice; Hillenbrand, Rainer; Erpenbeck, Veit J; Maurer, Marcus


    Background. Treatment with omalizumab, a humanized recombinant monoclonal anti-IgE antibody, results in clinical efficacy in patients with Chronic Spontaneous Urticaria (CSU). The mechanism of action of omalizumab in CSU has not been elucidated in detail. Objectives. To determine the effects of omalizumab on levels of high affinity IgE receptor-positive (FcεRI + ) and IgE-positive (IgE + ) dermal cells and blood basophils. Treatment efficacy and safety were also assessed. Study design. In a double-blind study, CSU patients aged 18‑75 years were randomized to receive 300 mg omalizumab (n=20) or placebo (n=10) subcutaneously every 4 weeks for 12 weeks. Changes in disease activity were assessed by use of the weekly Urticaria Activity Score (UAS7). Circulating IgE levels, basophil numbers and levels of expression of FcεRI + and IgE + cells in the skin and in blood basophils were determined. Results. Patients receiving omalizumab showed a significantly greater decrease in UAS7 compared with patients receiving placebo. At Week 12 the mean difference in UAS7 between treatment groups was -14.82 (p=0.0027), consistent with previous studies. Total IgE levels in serum were increased after omalizumab treatment and remained elevated up to Week 12. Free IgE levels decreased after omalizumab treatment. Mean levels of FcεRI + skin cells in patients treated with omalizumab 300 mg were decreased at Week 12 compared with baseline in the dermis of both non-lesional and lesional skin, reaching levels comparable with those seen in healthy volunteers (HVs). There were no statistically significant changes in mean FcɛRI + cell levels in the placebo group. Similar results were seen for changes in IgE + cells, although the changes were not statistically significant. The level of peripheral blood basophils increased immediately after treatment start and returned to Baseline values after the follow-up period. The levels of FcεRI and IgE expression on peripheral blood basophils were

  7. Health care burden and treatment patterns in commercially insured children with chronic idiopathic/spontaneous urticaria: A real-world study in the United States. (United States)

    Williams, Paul; Kavati, Abhishek; Pilon, Dominic; Xiao, Yongling; Zhdanava, Maryia; Balp, Maria-Magdalena; Lefebvre, Patrick; Ortiz, Benjamin; Hernandez-Trujillo, Vivian


    Chronic idiopathic urticaria (CIU)/spontaneous urticaria (CSU) is defined by the presence of wheals, angioedema, or both for ≥6 weeks, with or without an identifiable trigger. Real-world health care data among children with CIU/CSU remain scarce. To describe treatment patterns, health care resource utilization (HRU), and costs in pediatric patients with CIU/CSU (<12 years old) and to compare these with pediatric patients without CIU/CSU. A commercial administrative claims data base (September 2013 to June 2016) was used. The CIU/CSU cohort included pediatric patients with either two or more claims for a diagnosis of urticaria ≥6 weeks apart or one or more claims for a diagnosis of urticaria and one or more claims for a diagnosis of angioedema ≥6 weeks apart (index was defined as the first claim). The control cohort comprised pediatric patients without urticaria or angioedema (index randomly assigned). Patients with <6 months of eligibility before and after the index date were excluded. HRU and costs were compared between the cohorts during the observation period after propensity score matching. A total of 6109 pediatric patients with CIU/CSU were selected, and 6107 were 1:1 matched with controls. The patients with CIU/CSU who had a mean ± standard deviation age of 4.58 ± 3.36 years, and 47.9% were girls. CIU/CSU-related medication use increased after diagnosis (e.g., baseline versus 6-month follow-up, 2.2 versus 8.0% for nonsedating prescription H1 antihistamines; 7.4 versus 17.4% for oral corticosteroids). Relative to the controls, the patients with CIU/CSU had higher rates of HRU (incidence rate ratios of 1.71, 2.39, and 2.07 for inpatient, emergency department, and outpatient visits, respectively; all p < 0.01), and higher all-cause per patient per year costs (mean cost differences of $2090, $1606, and $483 for total, medical, and pharmacy costs, respectively; all p < 0.01). This study highlighted unmet needs in pediatric patients with CIU/CSU who had

  8. Hepatitis C virus (HCV) RNA profiles among chronic HIV/HCV-coinfected individuals in ESPRIT; spontaneous HCV RNA clearance observed in nine individuals

    DEFF Research Database (Denmark)

    Grint, D; Tedaldi, Ellen; Peters, L


    OBJECTIVES: Studies have shown that hepatitis C virus (HCV) RNA levels remain stable over time in HIV/HCV-coinfected individuals taking combination antiretroviral therapy (cART), while spontaneous clearance of HCV RNA during the persistent infection phase has been documented only rarely among tho...

  9. UVB pretreatment of rat bone marrow allografts. Prevention of GVHD and induction of allochimerism and donor-specific unresponsiveness

    International Nuclear Information System (INIS)

    Chabot, J.A.; Pepino, P.; Wasfie, T.; Stegall, M.D.; Marboe, C.; Hardy, M.A.


    Ultraviolet B irradiation has been used to pretreat blood and islets to prevent subsequent graft rejection. In this study the optimal dose of UVB irradiation of bone marrow was determined in syngeneic recipients and was subsequently applied to in-vitro treatment of bone marrow allografts. UVB pretreatment of donor bone marrow inoculum led to complete prevention of GVHD in allogeneic rat recipients without major marrow or other toxicity. Long-standing recipients of allogeneic UVB-BM became stable adult chimeras. The recipients of allogeneic BM were populated by donor-type peripheral blood lymphocytes and did not reject host or donor-type heart grafts. The BM allograft recipients were immunocompetent as measured by their ability to normally reject third-party cardiac allografts. We suggest that the prevention of GVHD and induction of stable chimerism in adult recipients of allogeneic UVB-BM may be mediated by suppressor mechanisms

  10. Ocular Surface and Tear Film Characteristics in a Sclerodermatous Chronic Graft-Versus-Host Disease Mouse Model. (United States)

    He, Jingliang; Yamane, Mio; Shibata, Shinsuke; Fukui, Masaki; Shimizu, Eisuke; Yano, Tetsuya; Mukai, Shin; Kawakami, Yutaka; Li, Shaowei; Tsubota, Kazuo; Ogawa, Yoko


    To report the characteristics of the ocular surface in a previously established sclerodermatous chronic graft-versus-host disease (cGVHD) mouse model. The ocular surface features and tear film parameters of the mouse model were assessed by histopathology, immunohistochemistry, electron microscopy, quantitative polymerase chain reaction, and flow cytometry. The mice exhibited loss of body weight and decreased tear secretion (P < 0.001), mimicking the clinical features of patients with cGVHD. Ocular examination demonstrated significant corneal epithelial staining, conjunctival (P < 0.001), and eyelid (P = 0.015) fibrosis compared with the control mice. The density of both goblet cells (P = 0.043) and microvilli was lower (P < 0.001), and the microvilli were shorter (P = 0.007) in the conjunctiva of cGVHD mice than those of the controls. The immunohistochemical studies demonstrated greater expression of CD45, CD4, and CD8 cells in the conjunctiva and eyelid tissues compared with the controls (P < 0.05 for all). In addition, reduced Forkhead box P3 (Foxp3)+ cells were found in both the peripheral blood (P < 0.001) and conjunctiva (P = 0.042) of cGVHD mice compared with the controls. The constellation of these findings suggests that the sclerodermatous cGVHD mouse model well recapitulates ocular manifestations of cGVHD in humans. This model can be used to study the mechanisms involved in the pathogenesis and treatment of chronic ocular graft-versus-host disease.

  11. X-ray irradiation on blood products for the purpose of prevention of PT-GVHD

    International Nuclear Information System (INIS)

    Tayama, Tatsuya; Naohara, Tooru; Haneda, Kenji; Juji, Takeo.


    X-ray irradiation on blood products is a common method to prevent the risk of inducing PT-GVHD, and has recently become to be used in Japan. We have tried X-ray irradiation on WB, CRC and PC using HITACHI X-ray Irradiation Apparatus MBR1520R, and studied its practical usefulness. In case of irradiation on blood bags as the minimum dose of 1,500 rads, these conditions are thought to be practical: 1) the use of 1.0 mm Al filter, 2) the distance of 550 nm from X-ray source, and 3) irradiation on 4 bags at the same time. But, it has also been noticed that total doses and qualities of X-ray absorbed into blood were different between upper and lower side of the bag. Bloods on upper side absorbed much doses and a wide range of X-ray, on the other hand, bloods on lower side absorbed less doses and hard X-ray. In these conditions, irradiated lymphocytes showed a complete inhibition of thymidine uptake in MLC test, still had 15% of activity in PHA stimulation. The qualities of other blood components have not changed before and after irradiation. X-ray irradiation is useful in a routine work of blood center, but problems of proper doses and a uniformity of irradiation are remained to be solved. (author)

  12. Chronic graft versus host disease and nephrotic syndrome. (United States)

    Barbouch, Samia; Gaied, Hanene; Abdelghani, Khaoula Ben; Goucha, Rim; Lakhal, Amel; Torjemen, Lamia; Hamida, Fethi Ben; Abderrahim, Ezzedine; Maiz, Hedi Ben; Adel, Khedher


    Disturbed kidney function is a common complication after bone marrow transplantation. Recently, attention has been given to immune-mediated glomerular damage related to graft versus host disease (GVHD). We describe a 19-year-old woman who developed membranous glomerulonephritis after bone marrow transplantation (BMT). Six months later, she developed soft palate, skin and liver lesions considered to be chronic GVHD. Fifteen months after undergoing BMT, this patient presented with nephrotic syndrome. A renal biopsy showed membranous glomerulonephritis associated with a focal segmental glomerulosclerosis. She was started on corticosteroid treatment with good outcome.

  13. Chronic graft versus host disease and nephrotic syndrome

    Directory of Open Access Journals (Sweden)

    Samia Barbouch


    Full Text Available Disturbed kidney function is a common complication after bone marrow transplantation. Recently, attention has been given to immune-mediated glomerular damage related to graft versus host disease (GVHD. We describe a 19-year-old woman who developed membranous glomerulonephritis after bone marrow transplantation (BMT. Six months later, she developed soft palate, skin and liver lesions considered to be chronic GVHD. Fifteen months after undergoing BMT, this patient presented with nephrotic syndrome. A renal biopsy showed mem-branous glomerulonephritis associated with a focal segmental glomerulosclerosis. She was started on corticosteroid treatment with good outcome.

  14. Donor leukocyte infusions in relapsed Hodgkin's lymphoma following allogeneic stem cell transplantation: CD3+ cell dose, GVHD and disease response. (United States)

    Anderlini, P; Acholonu, S A; Okoroji, G-J; Andersson, B S; Couriel, D R; De Lima, M J; Donato, M L; Khouri, I F; Giralt, S A; Ueno, N T; Champlin, R E


    Nine patients with advanced Hodgkin's lymphoma (HL) who had undergone allogeneic stem cell transplantation (allo-SCT) received donor leukocyte infusions (DLIs) for treatment of persistent or progressive disease (PD). A total of 15 DLIs were performed, with four patients receiving more than one DLI. In four patients, prior salvage chemotherapy was administered. The median CD3+ cell dose administered was 77.5 x 10(6)/kg (range 5-285). GVHD developed in all but one patient. The response rate was 4/9 (44%). Three of these four responders developed GVHD and 3/4 had received chemotherapy. No correlation was observed between CD3+ cell dose infused and disease response. At the latest follow-up, three patients are alive and six have expired (PD n=3, nonrelapse mortality n=3). The median response duration was 7 months (range 4-9), with one response currently ongoing. These data suggest that DLIs for immunotherapy of recurrent HL have significant activity, although they frequently leads to GVHD. The small sample size does not allow any conclusion as to whether chemotherapy administration increases the chance of response. The CD3 cell dose infused does not seem to correlate with disease response.

  15. Murine cytomegalovirus immediate-early 1 gene expression correlates with increased GVHD after allogeneic hematopoietic cell transplantation in recipients reactivating from latent infection.

    Directory of Open Access Journals (Sweden)

    Senthilnathan Palaniyandi

    Full Text Available The success of allogeneic (allo hematopoietic cell transplantation (HCT is limited by its treatment related complications, mostly graft versus host disease (GVHD and fungal and viral infections. CMV reactivation after HCT has been associated with increased morbidity and mortality, and a causal relation between GVHD, immunosuppressive therapy and vice versa has been postulated. Using a low GVHD severity murine HCT model, we assessed the role of MCMV reactivation and GVHD development. BALB/c mice were infected with either murine CMV (MCMV or mock and monitored for 25 weeks to establish latency, followed by sublethal irradiation conditioning and infusion of bone marrow plus splenocytes from either syngeneic (syn BALB/c or allo B10.D2 donors. Engraftment of allo donor cells was confirmed by PCR for D2Mit265 gene product size. Day+100 mortality and overall GVHD severity in allo MCMV pre-infected recipients was higher than in allo mock controls. Pathologic changes of lung and liver GVHD in immediate-early gene 1 (IE1 positive recipients were significantly increased compared to mock controls, and were only slightly increased in IE1 negative. No significant gut injury was seen in any group. Aggravated lung injury in IE1 positive recipients correlated with higher BAL cell counts both for total cells and for CD4+ T cells when compared with mock controls, and also with protein expression of lung IFN-gamma and liver TNF. No evidence for CMV specific morphologic changes was seen on histopathology in any organ of IE1 positive recipients, suggesting that CMV reactivation is related to increased GVHD severity but does not require active CMV disease, strengthening the concept of a reciprocal relationship between CMV and GVHD.

  16. How we treat oral chronic graft-versus-host disease. (United States)

    Treister, Nathaniel; Duncan, Christine; Cutler, Corey; Lehmann, Leslie


    Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic cell transplantation that is associated with a diminished quality of life. The oral cavity is frequently affected, with a wide variety of signs and symptoms that can result in significant short- and long-term complications ranging from mucosal sensitivity and limited oral intake to secondary malignancy and early death. This article provides a comprehensive approach to the diagnosis and clinical management of patients with oral cGVHD, with particular attention to differential diagnosis, control of symptoms, and prevention of and screening for secondary complications. The clinical considerations and recommendations presented are intended to be practical and relevant for all clinicians involved in the care of patients with oral cGVHD, with the ultimate goal of improving care and outcomes.

  17. Evolutionary basis of HLA-DPB1 alleles affects acute GVHD in unrelated donor stem cell transplantation. (United States)

    Morishima, Satoko; Shiina, Takashi; Suzuki, Shingo; Ogawa, Seishi; Sato-Otsubo, Aiko; Kashiwase, Koichi; Azuma, Fumihiro; Yabe, Toshio; Satake, Masahiro; Kato, Shunichi; Kodera, Yoshihisa; Sasazuki, Takehiko; Morishima, Yasuo


    HLA-DPB1 T-cell epitope (TCE) mismatching algorithm and rs9277534 SNP at the 3' untranslated region (3'UTR) in the HLA-DPB1 gene are key factors for transplant-related events in unrelated hematopoietic cell transplantation (UR-HCT). However, the association of these 2 mechanisms has not been elucidated. We analyzed 19 frequent HLA-DPB1 alleles derived from Japanese healthy subjects by next-generation sequencing of the entire HLA-DPB1 gene region and multi-SNP data of the HLA region in 1589 UR-HCT pairs. The risk of acute graft-versus-host disease (aGVHD) was analyzed in 1286 patients with single HLA-DPB1 mismatch UR-HCT. The phylogenetic tree constructed using the entire gene region demonstrated that HLA-DPB1 alleles were divided into 2 groups, HLA-DP2 and HLA-DP5. Although a phylogenetic relationship in the genomic region from exon 3 to 3'UTR (Ex3-3'UTR) obviously supported the division of HLA-DP2 and HLA-DP5 groups, which in exon 2 showed intermingling of HLA-DPB1 alleles in a non-HLA-DP2 and non-HLA-DP5-group manner. Multi-SNP data also showed 2 discriminative HLA-DPB1 groups according to Ex3-3'UTR. Risk of grade 2-4 aGVHD was significantly higher in patient HLA-DP5 group mismatch than patient HLA-DP2 group mismatch (hazard ratio, 1.28; P = .005), regardless of donor mismatch HLA-DP group. Regarding TCE mismatch, increasing risk of aGVHD in patient HLA-DP5 group mismatch and TCE-nonpermissive mismatch were observed only in patients with TCE-permissive mismatch and patient HLA-DP2 group mismatch, respectively. Evolutionary analysis revealed that rs9277534 represented a highly conserved HLA-DPB1 Ex3-3'UTR region and may provoke aGVHD differently to TCE mismatching algorithm, reflecting exon 2 polymorphisms. These findings enrich our understanding of the mechanism of aGVHD in HLA-DPB1 mismatch UR-HCT. © 2018 by The American Society of Hematology.

  18. Mesenchymal stromal cells for treatment of steroid-refractory GvHD: a review of the literature and two pediatric cases

    Directory of Open Access Journals (Sweden)

    Wernicke Caroline M


    Full Text Available Abstract Severe acute graft versus host disease (GvHD is a life-threatening complication after allogeneic hematopoietic stem cell transplantation. Human mesenchymal stromal cells (MSCs play an important role in endogenous tissue repair and possess strong immune-modulatory properties making them a promising tool for the treatment of steroid-refractory GvHD. To date, a few reports exist on the use of MSCs in treatment of GvHD in children indicating that children tend to respond better than adults, albeit with heterogeneous results. We here present a review of the literature and the clinical course of two instructive pediatric patients with acute steroid-refractory GvHD after haploidentical stem cell transplantation, which exemplify the beneficial effects of third-party transplanted MSCs in treatment of acute steroid-refractory GvHD. Moreover, we provide a meta-analysis of clinical studies addressing the outcome of patients with steroid-refractory GvHD and treatment with MSCs in adults and in children (n = 183; 122 adults, 61 children. Our meta-analysis demonstrates that the overall response-rate is high (73.8% and confirms, for the first time, that children indeed respond better to treatment of GvHD with MSCs than adults (complete response 57.4% vs. 45.1%, respectively. These data emphasize the significance of this therapeutic approach especially in children and indicate that future prospective studies are needed to assess the reasons for the observed differential response-rates in pediatric and adult patients.

  19. Spontaneous T-cell responses against the immune check point programmed-death-ligand 1 (PD-L1) in patients with chronic myeloproliferative neoplasms correlate with disease stage and clinical response

    DEFF Research Database (Denmark)

    Holmström, Morten Orebo; Riley, Caroline Hasselbalch; Skov, Vibe


    The Chronic Myeloproliferative Neoplasms (MPN) are cancers characterized by hyperinflammation and immune deregulation. Concurrently, the expression of the immune check point programmed death ligand 1 (PD-L1) is induced by inflammation. In this study we report on the occurrence of spontaneous T cell...... responses against a PD-L1 derived epitope in patients with MPN. We show that 71% of patients display a significant immune response against PD-L1, and patients with advanced MPN have significantly fewer and weaker PD-L1 specific immune responses compared to patients with non-advanced MPN. The PD-L1 specific...... T cell responses are CD4+ T cell responses, and by gene expression analysis we show that expression of PD-L1 is enhanced in patients with MPN. This could imply that the tumor specific immune response in MPN could be enhanced by vaccination with PD-L1 derived epitopes by boosting the anti...

  20. Hemosiderin deposits in chronic graft-vs.-host disease related myopathy. (United States)

    Schmidt-Hieber, Martin; Okuducu, Ali Fuat; Stoltenburg, Gisela; Mackert, Bruno-Marcel; Benzian, Nadia; Thiel, Eckhard; Blau, Igor Wolfgang


    Chronic graft-vs.-host disease (cGVHD) occurs in 20-50% of patients who survive for at least 100 d after allogeneic stem cell transplantation (SCT). cGVHD includes scleroderma-like skin changes, chronic cholangitis, obstructive lung disease and general wasting syndrome. Polymyositis or myopathy are rare manifestations of cGVHD with approximately 40 reported cases. Polymyositis accompanied by hemosiderin deposits in cGVHD has been reported only once, and there are no reports on lipofuscin deposits in skeletal muscle cells in cGVHD. We report here on a 56-yr-old male who underwent allogeneic SCT in 1999 for osteomyelofibrosis and progressive hematopoietic insufficiency. In February 2004, the patient was hospitalized for progressive muscular weakness with loss of the ability to walk. Laboratory tests demonstrated normal values for serum creatine kinase, aldolase and lactic dehydrogenase; the ferritin level was highly elevated. The femoral muscle biopsy showed mostly perifascicular atrophy as well as numerous subsarcolemmal hemosiderin and lipofuscin deposits. Intravenous administration of the chelating agent deferoxamine was ineffective. Three weeks later the patient died of aspiration pneumonia. Interestingly, autopsy disclosed moderate hemosiderin deposits in the liver, the organ usually involved in hemosiderosis.

  1. Hepatitis C virus (HCV) RNA profiles among chronic HIV/HCV-coinfected individuals in ESPRIT; spontaneous HCV RNA clearance observed in nine individuals. (United States)

    Grint, D; Tedaldi, E; Peters, L; Mocroft, A; Edlin, B; Gallien, S; Klinker, H; Boesecke, C; Kokordelis, P; Rockstroh, J K


    Studies have shown that hepatitis C virus (HCV) RNA levels remain stable over time in HIV/HCV-coinfected individuals taking combination antiretroviral therapy (cART), while spontaneous clearance of HCV RNA during the persistent infection phase has been documented only rarely among those with the CC interleukin (IL)-28B genotype. This study describes HCV RNA profiles and factors associated with changes over time in HCV RNA levels in the ESPRIT study. HIV/HCV-coinfected individuals positive for HCV RNA were included in the study. Follow-up was counted from the first HCV RNA positive test and censored at the initiation of interferon-based treatment. HCV RNA and IL-28B measurements were performed in the same reference laboratory. Random effects mixed models were used to analyse changes over time in HCV RNA. A total of 312 ESPRIT patients were included in the study (151 in the arm receiving subcutaneous recombinant IL-2 and 161 in the control arm). Most of the patients were white (89%) and male (76%), and they had a median of 5 HCV RNA measurements per person [interquartile range (IQR) 3-6; range 1-9]. Median follow-up was 5 years (IQR: 2-6 years). At baseline, 96% of patients were taking cART and 93% had undetectable HIV RNA. Mean HCV RNA levels decreased by 13% per year over the study period [95% confidence interval (CI) 8-18%; P < 0.0001]. Baseline HCV RNA levels and the change over time in HCV RNA did not differ by randomization arm (P = 0.16 and P = 0.56, respectively). Nine individuals spontaneously cleared HCV RNA during follow-up [IL-28B genotypes: CC, five patients (56%); CT, four patients (44%)]. HCV RNA levels decreased over time in this population with well-controlled HIV infection. Spontaneous clearance of HCV RNA was documented in five individuals with IL-28B genotype CC and four with the CT genotype. © 2016 British HIV Association.

  2. Antithymocyte globulins and chronic graft-vs-host disease after myeloablative allogeneic stem cell transplantation from HLA-matched unrelated donors: a report from the Sociéte Française de Greffe de Moelle et de Thérapie Cellulaire. (United States)

    Mohty, M; Labopin, M; Balère, M L; Socié, G; Milpied, N; Tabrizi, R; Ifrah, N; Hicheri, Y; Dhedin, N; Michallet, M; Buzyn, A; Cahn, J-Y; Bourhis, J-H; Blaise, D; Raffoux, C; Espérou, H; Yakoub-Agha, I


    This retrospective report assessed the impact of rabbit antithymocyte globulins (ATG), incorporated within a standard myeloablative conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT) using human leukocyte antigen-matched unrelated donors (HLA-MUD), on the incidence of acute and chronic graft-vs-host disease (GVHD). In this series of leukemia patients, 120 patients (70%) did not receive ATG ('no-ATG' group), whereas 51 patients received ATG ('ATG' group). With a median follow-up of 30.3 months, the cumulative incidence of grade 3-4 acute GVHD was 36% in the no-ATG group and 20% in the ATG group (P = 0.11). The cumulative incidence of extensive chronic GVHD was significantly lower in the ATG group as compared to the no-ATG group (4 vs 32%, respectively; P = 0.0017). In multivariate analysis, the absence of use of ATG was the strongest parameter associated with an increased risk of extensive chronic GVHD (relative risk) = 7.14, 95% CI: 1.7-33.3, P = 0.008). At 2 years, the probability of nonrelapse mortality, relapse, overall and leukemia-free survivals was not significantly different between the no-ATG and ATG groups. We conclude that the addition of ATG to GVHD prophylaxis resulted in decreased incidence of extensive chronic GVHD without an increase in relapse or nonrelapse mortality, and without compromising survival after myeloablative allo-SCT from HLA-MUD.

  3. Recruitment of Donor T Cells to the Eyes During Ocular GVHD in Recipients of MHC-Matched Allogeneic Hematopoietic Stem Cell Transplants (United States)

    Herretes, Samantha; Ross, Duncan B.; Duffort, Stephanie; Barreras, Henry; Yaohong, Tan; Saeed, Ali M.; Murillo, Juan C.; Komanduri, Krishna V.; Levy, Robert B.; Perez, Victor L.


    Purpose. The primary objective of the present study was to identify the kinetics and origin of ocular infiltrating T cells in a preclinical model of graft-versus-host disease (GVHD) that induces eye tissue damage. Methods. Graft-versus-host disease was induced using an major histocompatibility complex (MHC)-matched, minor histocompatibility-mismatched hematopoietic stem cell transplant (HSCT) model. This approach, which utilized congenic and EGFP-labeled donor populations, mimics a matched, clinically unrelated donor (MUD) cell transplant. Systemic and ocular GVHD were assessed at varying time points using clinical examination, intravital microscopy, immune phenotype via flow cytometric analyses, and immunohistochemical staining. Results. Following transplant, we observed characteristic changes in GVHD-associated immune phenotype as well as clinical signs present in recipients post transplant. Notably, the kinetics of the systemic changes and the ocular damage paralleled what is observed clinically, including damage to the cornea as well as the conjunctiva and lacrimal gland. Importantly, the infiltrate contained predominantly donor CD4 as well as CD8 T cells with an activated phenotype and macrophages together with effector cytokines consistent with the presence of a TH1 alloreactive population. Conclusions. Overall, the findings here unequivocally demonstrated that donor T cells compose part of the corneal and ocular adnexa infiltrate in animals undergoing ocular GVHD. In total, the results describe a novel and promising preclinical model characterized by both systemic and ocular changes as detected in significant numbers of patients undergoing GVHD following allo-HSCT, which can help facilitate dissecting the underlying immune mechanisms leading to damage associated with ocular GVHD. PMID:25655798

  4. Early and late-onset acute GvHD following hematopoietic cell transplantation: CT features of gastrointestinal involvement with clinical and pathological correlation

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    Brodoefel, H. [Department of Diagnostic Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany)], E-mail:; Bethge, W. [Department of Internal Medicine II, Oncology/Haematology, Eberhard-Karls-University, Otfried-Mueller-Str. 10, 72076 Tuebingen (Germany); Vogel, M.; Fenchel, M. [Department of Diagnostic Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany); Faul, C. [Department of Internal Medicine II, Oncology/Haematology, Eberhard-Karls-University, Otfried-Mueller-Str. 10, 72076 Tuebingen (Germany); Wehrmann, M. [Department of Pathology, Eberhard-Karls-University, Liebermeister-Str. 8, 72076, Tuebingen (Germany); Claussen, C.; Horger, M. [Department of Diagnostic Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany)


    Objective: With the introduction of non-myeloablative hematopoietic cell transplantation, acute graft-versus-host-disease (GvHD) is frequently observed beyond the traditional 100 days cut-off. The aim of this study was to describe and compare CT features of gastrointestinal early and late-onset GvHD and to correlate findings with clinical and pathology grading. Subjects and methods: Abdominal CT scans were obtained in 20 patients with early and 15 with late-onset GvHD. Examinations were assessed for intestinal and extraintestinal abnormalities and findings compared between the two subgroups of GvHD. Distinct CT abnormalities as well as a CT-score integrating multiple pathologies were correlated with gut, clinical or pathology grading. Results: Frequent intestinal abnormalities included wall thickening, abnormal enhancement, and excessive fluid-filling (94%, 89%, and 94%). 86% of patients showed concomitant small and large bowel involvement. A discontinuous distribution was observed in 54%. Bile tract abnormality was the most common extra-intestinal finding (74%). The distribution of pathologies was equal between subgroups of early or late-onset disease. Wall thickening and mucosal attenuation in non-enhanced scans were significantly related to clinical and pathology scores (P {<=} 0.018). Number of abnormal segments, small bowel dilatation, engorgement of the vasa recta, mesenteric fat stranding and ascites were linked to clinical grading (P {<=} 0.019). A CT-score integrating multiple abnormalities was correlated to gut, overall clinical and pathology grading (r = 0.64, 0.57, 0.50). Conclusion: CT morphology of acute GvHD is independent of its time of onset and, thus, facilitates differential diagnosis of late-onset acute GvHD. Correlation of CT morphology with clinical and pathological grading is important in terms of prognosis and may help guiding the therapeutic approach.

  5. Recruitment of Donor T Cells to the Eyes During Ocular GVHD in Recipients of MHC-Matched Allogeneic Hematopoietic Stem Cell Transplants. (United States)

    Herretes, Samantha; Ross, Duncan B; Duffort, Stephanie; Barreras, Henry; Yaohong, Tan; Saeed, Ali M; Murillo, Juan C; Komanduri, Krishna V; Levy, Robert B; Perez, Victor L


    The primary objective of the present study was to identify the kinetics and origin of ocular infiltrating T cells in a preclinical model of graft-versus-host disease (GVHD) that induces eye tissue damage. Graft-versus-host disease was induced using an major histocompatibility complex (MHC)-matched, minor histocompatibility-mismatched hematopoietic stem cell transplant (HSCT) model. This approach, which utilized congenic and EGFP-labeled donor populations, mimics a matched, clinically unrelated donor (MUD) cell transplant. Systemic and ocular GVHD were assessed at varying time points using clinical examination, intravital microscopy, immune phenotype via flow cytometric analyses, and immunohistochemical staining. Following transplant, we observed characteristic changes in GVHD-associated immune phenotype as well as clinical signs present in recipients post transplant. Notably, the kinetics of the systemic changes and the ocular damage paralleled what is observed clinically, including damage to the cornea as well as the conjunctiva and lacrimal gland. Importantly, the infiltrate contained predominantly donor CD4 as well as CD8 T cells with an activated phenotype and macrophages together with effector cytokines consistent with the presence of a TH1 alloreactive population. Overall, the findings here unequivocally demonstrated that donor T cells compose part of the corneal and ocular adnexa infiltrate in animals undergoing ocular GVHD. In total, the results describe a novel and promising preclinical model characterized by both systemic and ocular changes as detected in significant numbers of patients undergoing GVHD following allo-HSCT, which can help facilitate dissecting the underlying immune mechanisms leading to damage associated with ocular GVHD.

  6. The chronic blockade of angiotensin I-converting enzyme eliminates the sex differences of serum cytokine levels of spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Dalpiaz, P.L.M.; Lamas, A.Z.; Caliman, I.F. [Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Medeiros, A.R.S. [Ciências Biológicas e da Saúde, Instituto Federal do Espírito Santo, Vitória, ES (Brazil); Abreu, G.R.; Moysés, M.R. [Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Andrade, T.U. [Departamento de Farmácia, Centro Universitário de Vila Velha, Vila Velha, ES (Brazil); Alves, M.F.; Carmona, A.K. [Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Bissoli, N.S. [Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Vitória, ES (Brazil)


    Sex hormones modulate the action of both cytokines and the renin-angiotensin system. However, the effects of angiotensin I-converting enzyme (ACE) on the proinflammatory and anti-inflammatory cytokine levels in male and female spontaneously hypertensive rats (SHR) are unclear. We determined the relationship between ACE activity, cytokine levels and sex differences in SHR. Female (F) and male (M) SHR were divided into 4 experimental groups each (n = 7): sham + vehicle (SV), sham + enalapril (10 mg/kg body weight by gavage), castrated + vehicle, and castrated + enalapril. Treatment began 21 days after castration and continued for 30 days. Serum cytokine levels (ELISA) and ACE activity (fluorimetry) were measured. Male rats exhibited a higher serum ACE activity than female rats. Castration reduced serum ACE in males but did not affect it in females. Enalapril reduced serum ACE in all groups. IL-10 (FSV = 16.4 ± 1.1 pg/mL; MSV = 12.8 ± 1.2 pg/mL), TNF-α (FSV = 16.6 ± 1.2 pg/mL; MSV = 12.8 ± 1 pg/mL) and IL-6 (FSV = 10.3 ± 0.2 pg/mL; MSV = 7.2 ± 0.2 pg/mL) levels were higher in females than in males. Ovariectomy reduced all cytokine levels and orchiectomy reduced IL-6 but increased IL-10 concentrations in males. Castration eliminated the differences in all inflammatory cytokine levels (IL-6 and TNF-α) between males and females. Enalapril increased IL-10 in all groups and reduced IL-6 in SV rats. In conclusion, serum ACE inhibition by enalapril eliminated the sexual dimorphisms of cytokine levels in SV animals, which suggests that enalapril exerts systemic anti-inflammatory and anti-hypertensive effects.

  7. Chronic graft-versus-host disease of the kidney in patients with allogenic hematopoietic stem cell transplant. (United States)

    Fraile, Pilar; Pilar, Fraile; Vazquez, Lourdes; Lourdes, Vazquez; Caballero, Dolores; Dolores, Caballero; Garcia-Cosmes, Pedro; Pedro, Garcia-Cosmes; López, Lucia; Lucia, López; San Miguel, Jesus; Jesus, San Miguel; Tabernero, Jose Matias; Jose Matias, Tabernero


    Allogenic hematopoietic stem cell transplant (allo-HSCT) is the treatment of choice for several hematological diseases. Although rare, patients could present nephrotic syndrome as a clinical feature of chronic graft-versus-host disease (cGVHD). The objective of our study is to screen patients with allo-HSCT to determine who developed a glomerular pathology in the context of cGVHD. We studied patients who underwent allo-HSCT treatment in our center between October 1995 and October 2012 and who developed glomerular pathology. cGVHD was defined as a pathology when it appeared after 100 d post-allo-HSCT. Five hundred eighty-three allo-HSCT were performed. The prevalence of cGVHD of the kidney was 1.03%. All patients with cGVHD of the kidney were hosts who received peripheral blood from an identical HLA match donor. GVHD prophylaxis with calcineurin inhibitors plus methotrexate was administered in five cases, and prophylaxis with sirolimus was used in another case. cGVHD of the kidney was seen to appear after the removal of the prophylaxis for GVHD, within 33 ± 11.54 months intervals after allo-HSCT in five patients and in another patient, it appeared despite immunosuppressive therapy being administered. All patients had proteinuria, within 11.82 ± 9.03 g/d ranges. The kidney biopsies revealed membranous glomerulonephritis (four patients), focal segmental glomerulonephritis (one patient) and lupus nephropathy class III (one patient). It seems, immunosuppressive therapy achieved complete remission, within the first year of treatment in four patients. Although in three of them, the proteinuria recurred when we tried to remove the therapy; two patients have recently started treatment, being in partial remission now. cGVHD of the kidney is a rare complication after allo-HSCT, related with the removal of the immunosuppression. Monitoring proteinuria in these patients may be useful. In our patients, a complete remission was achieved; although the removal of the

  8. Spontaneous pneumothorax in weightlifters. (United States)

    Marnejon, T; Sarac, S; Cropp, A J


    Spontaneous pneumothorax is infrequently caused by strenuous exertion. To our knowledge there has only been one case of spontaneous pneumothorax associated with weightlifting reported in the medical literature. We describe three consecutive cases of spontaneous pneumothorax associated with weightlifting. We postulate that spontaneous pneumothorax in these patients may be secondary to improper breathing techniques. It is important that physicians and weight trainers be aware of the association between weight lifting and spontaneous pneumothorax and assure that proper instruction is given to athletes who work with weights.

  9. Spontaneous osteonecrosis of the knee

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    Kattapuram, Taj M. [Department of Radiology, Massachusetts General Hospital (United States); Kattapuram, Susan V. [Department of Radiology, Massachusetts General Hospital (United States)], E-mail:


    Spontaneous osteonecrosis of the knee presents with acute onset of severe, pain in elderly patients, usually female and usually without a history of trauma. Originally described as idiopathic osteonecrosis, the exact etiology is still debated. Evidence suggests that an acute fracture occurs as a result of chronic stress or minor trauma to a weakened subchondral bone plate. The imaging characteristics on MR reflect the age of the lesion and the symptoms. More appropriate terminology may be ' subchondral insufficiency fracture of the knee' or 'focal subchondral osteonecrosis'.

  10. Bilateral spontaneous rupture of flexor digitorum profundus tendons.

    LENUS (Irish Health Repository)

    O'Sullivan, S T


    Spontaneous tendon rupture is an unusual condition usually associated with underlying disease processes such as rheumatoid arthritis, chronic renal failure or bony abnormalities of the hand. We report a case of spontaneous, non-concurrent bilateral rupture of flexor profundus tendons in an otherwise healthy individual. Treatment was successful and consisted of a two-stage reconstruction of the ruptured tendon.

  11. The Genotype of the Donor for the (GTn Polymorphism in the Promoter/Enhancer of FOXP3 Is Associated with the Development of Severe Acute GVHD but Does Not Affect the GVL Effect after Myeloablative HLA-Identical Allogeneic Stem Cell Transplantation.

    Directory of Open Access Journals (Sweden)

    Víctor Noriega

    Full Text Available The FOXP3 gene encodes for a protein (Foxp3 involved in the development and functional activity of regulatory T cells (CD4+/CD25+/Foxp3+, which exert regulatory and suppressive roles over the immune system. After allogeneic stem cell transplantation, regulatory T cells are known to mitigate graft versus host disease while probably maintaining a graft versus leukemia effect. Short alleles (≤(GT15 for the (GTn polymorphism in the promoter/enhancer of FOXP3 are associated with a higher expression of FOXP3, and hypothetically with an increase of regulatory T cell activity. This polymorphism has been related to the development of auto- or alloimmune conditions including type 1 diabetes or graft rejection in renal transplant recipients. However, its impact in the allo-transplant setting has not been analyzed. In the present study, which includes 252 myeloablative HLA-identical allo-transplants, multivariate analysis revealed a lower incidence of grade III-IV acute graft versus host disease (GVHD in patients transplanted from donors harboring short alleles (OR = 0.26, CI 0.08-0.82, p = 0.021; without affecting chronic GVHD or graft versus leukemia effect, since cumulative incidence of relapse, event free survival and overall survival rates are similar in both groups of patients.

  12. Efficacy and safety of bilastine in Japanese patients with chronic spontaneous urticaria: A multicenter, randomized, double-blind, placebo-controlled, parallel-group phase II/III study. (United States)

    Hide, Michihiro; Yagami, Akiko; Togawa, Michinori; Saito, Akihiro; Furue, Masutaka


    Bilastine, a novel non-sedating second-generation H 1 -antihistamine, has been widely used in the treatment of allergic rhinoconjunctivitis and urticaria with a recommended dose of 20 mg once daily in most European countries since 2010. We evaluated its efficacy and safety in Japanese patients with chronic spontaneous urticaria (CSU). We conducted a multicenter, randomized, double-blind, placebo-controlled phase II/III study (trial registration No. JapicCTI-142574). Patients (age, 18-74 years) were randomly assigned to receive bilastine 20 mg, 10 mg or placebo once daily for 2 weeks. The primary efficacy endpoint was the change from baseline (Day -3 to 0) in total symptom score (TSS) at 2 weeks (Day 8-14), consisting of the itch and rash scores. A total of 304 patients were randomly allocated to bilastine 20 mg (101 patients), bilastine 10 mg (100 patients), and placebo (103 patients). The changes in TSS at 2 weeks were significantly decreased by bilastine 20 mg than did placebo (p < 0.001), demonstrating the superiority of bilastine 20 mg. Bilastine 10 mg also showed a significant difference from placebo (p < 0.001). The TSS changes for the bilastine showed significant improvement from Day 1, and were maintained during the treatment period. The Dermatology Life Quality Index scores were also improved in bilastine than in placebo. The bilastine treatments were safe and well tolerated. Two-week treatment with bilastine (20 or 10 mg) once daily was effective and tolerable in Japanese patients with CSU, demonstrating an early onset of action. Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  13. Oral chronic graft-versus-host disease in pediatric patients after hematopoietic stem cell transplantation. (United States)

    Treister, Nathaniel S; Woo, Sook-Bin; O'Holleran, Eileen W; Lehmann, Leslie E; Parsons, Susan K; Guinan, Eva C


    Chronic graft-versus-host disease (cGVHD) is a serious and potentially life-threatening complication of hematopoietic stem cell transplantation. This study, which is the largest single-center series of oral disease in pediatric patients with cGVHD, describes the oral findings in 49 consecutive patients seen in a pediatric multidisciplinary cGVHD clinic. All consecutive patients seen at the multidisciplinary pediatric hematopoietic stem cell transplantation/cGVHD clinic at the Dana-Farber Cancer Institute (Boston, MA) from July 2001 through October 2003 were included in this study. Subjective and objective assessments of mucosal, salivary gland, and sclerotic pathology were performed for each patient, and specific therapy was initiated when indicated. Oral mucosal cGVHD was identified in 22 (45%) of 49 patients. Only 4 (8%) of 49 patients reported mouth pain, and all patients reported being able to eat well. All patients who required specific therapy for their oral mucosal cGVHD (45%) were already taking at least 1 immunomodulatory agent; however, efficacy of treatment was difficult to assess because of inconsistent follow-up periods. Subjective and objective salivary gland and sclerotic disease were observed far less often. Oral mucosal pathology is common in these patients, and appropriate diagnosis and management of oral lesions is critical to reduce patient morbidity and to improve quality of life. The apparent lack of salivary gland involvement was notable. Developing validated age-appropriate evaluation strategies and identifying effective treatment guidelines will be invaluable in the future management of these patients.

  14. Quality of life of patients with graft-versus-host disease (GvHD) post-hematopoietic stem cell transplantation. (United States)

    Proença, Sibéli de Fátima Ferraz Simão; Machado, Celina Mattos; Coelho, Raquel de Castro Figueiredo Pereira; Sarquis, Leila Maria Mansano; Guimarães, Paulo Ricardo Bittencourt; Kalinke, Luciana Puchalski


    Assessing the quality of life of adult patients with hematological cancer in the 100 days after transplantation of hematopoietic stem cells and verifying whether the variable graft-versus-host disease (GvHD) is predictive of worse results. An observational correlational and quantitative study with 36 adult participants diagnosed with hematologic cancer who underwent hematopoietic stem cell transplantation from September 2013 to June 2015. The mean age was 37 years, 52.78% were female, and 61.11% were diagnosed with leukemia. Quality of life scores showed a significant impact between pre-transplantation and pre-hospital discharge, and also within the 100 days post-transplantation. The statistical analysis between the scores for the groups with and without GvHD showed a significant difference between the presence of the complication and worse results. Quality of life is altered as a result of hematopoietic stem cells transplantation, especially in patients who have graft-versus-host disease. Avaliar a qualidade de vida de pacientes adultos com câncer hematológico nos 100 dias do transplante de células-tronco hematopoéticas e verificar se a variável doença do enxerto contra o hospedeiro é preditiva de piores resultados. Estudo observacional, correlacional e quantitativo, com 36 participantes adultos, diagnosticados com câncer hematológico que se submeteram ao transplante de células-tronco hematopoéticas de setembro de 2013 a junho de 2015. A média de idade foi 37 anos, 52,78% eram do sexo feminino, e 61,11% com diagnóstico de leucemia. Os escores de qualidade de vida demonstraram impacto significativo entre o pré-transplante e a pré-alta hospitalar e entre os 100 dias pós-transplante. A análise estatística entre os escores dos grupos com e sem doença do enxerto contra o hospedeiro evidenciou significância entre a presença desta complicação e piores resultados. A qualidade de vida é alterada em decorrência do transplante de c

  15. Spontaneous uterine rupture

    African Journals Online (AJOL)

    ABSTRACT. Rupture of a gravid uterus is a surgical emergency. Predisposing factors include a scarred uterus. Spontaneous rupture of an unscarred uterus during pregnancy is a rare occurrence. We hereby present the case of a spontaneous complete uterine rupture at a gestational age of 34 weeks in a 35 year old patient ...

  16. Spontaneous intracranial hypotension.

    LENUS (Irish Health Repository)

    Fullam, L


    INTRODUCTION: Spontaneous\\/primary intracranial hypotension is characterised by orthostatic headache and is associated with characteristic magnetic resonance imaging findings. CASE REPORT: We present a case report of a patient with typical symptoms and classical radiological images. DISCUSSION: Spontaneous intracranial hypotension is an under-recognised cause of headache and can be diagnosed by history of typical orthostatic headache and findings on MRI brain.

  17. Two cases of spontaneous temporal encephalocele. (United States)

    Kamiya, Kouhei; Mori, Harushi; Kunimatsu, Akira; Kawai, Kensuke; Usami, Kenichi; Ohtomo, Kuni


    This is a report of two cases of spontaneous temporal encephalocele: one was anteroinferior and presented with epilepsy; the other was posteroinferior and presented with facial neuritis and labyrinthitis. Spontaneous temporal encephalocele is relatively rare and apparently not familiar to a majority of primary physicians. It may present with a variety of symptoms according to its anatomical location, including cerebrospinal fluid fistulas, recurrent meningitis, chronic otitis media, hearing loss, facial nerve palsy and medically intractable epilepsy. Attention should be paid to this disease entity, as it is easily overlooked in imaging studies and can leave serious neurological deficits. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  18. Chronic Allium sativum administration alters spontaneous ...

    African Journals Online (AJOL)

    Arun Kumar Agnihotri

    may eventually lead to neurodegeneration of the neurons. This is similar to a previous report, where. Nissl loss especially in the high dose groups was also recorded12. The prefrontal cortex of the brain plays a major role in moderating social behaviour, working memory, attention, reward, planning and motivation ...

  19. Comparative analysis of FoxP3(+) regulatory T cells in the target tissues and blood in chronic graft versus host disease. (United States)

    Imanguli, M M; Cowen, E W; Rose, J; Dhamala, S; Swaim, W; Lafond, S; Yagi, B; Gress, R E; Pavletic, S Z; Hakim, F T


    Activation and migration of regulatory T cells (Treg) into tissue is critical in control of inflammation, but has not been examined extensively in chronic graft versus host disease (cGVHD). In parallel studies of tissues and blood, we determined that FoxP3(+) T cells increased in proportion to T effectors (Teff) in tissue infiltrates in oral and cutaneous lichenoid cGVHD. These FoxP3(+) cells expressed distinguishing phenotypic and functional markers of Treg (CD3(+), CD4(+), CD27(+), ICOS(+) and CD39(+)), not found on FoxP3(-) Teff. Both Teff and FoxP3(+) Treg expressed T-bet and the chemokine receptor CXCR3, however, consistent with a common mechanism of chemokine-mediated migration into tissue. Furthermore, functional markers (ICOS and CD39) and chemokine receptors (CXCR3) were both present in a higher proportion of FoxP3(+) cells in tissues than in peripheral blood, consistent with recruitment and activation of Treg in cGVHD target tissues. Finally, the 'activated' CD45RA(-)FoxP3(hi) subset of Treg cells, which highly express functional markers, were found in comparable frequencies in cGVHD patients and normal controls, despite a significant deficit in naive 'resting' Treg. These findings are consistent with Treg capacity to upregulate functional markers and traffick into tissue in cGVHD.

  20. Spontaneous Atraumatic Mediastinal Hemorrhage

    Directory of Open Access Journals (Sweden)

    Morkos Iskander BSc, BMBS, MRCS, PGCertMedEd


    Full Text Available Spontaneous atraumatic mediastinal hematomas are rare. We present a case of a previously fit and well middle-aged lady who presented with acute breathlessness and an increasing neck swelling and spontaneous neck bruising. On plain chest radiograph, widening of the mediastinum was noted. The bruising was later confirmed to be secondary to mediastinal hematoma. This life-threatening diagnostic conundrum was managed conservatively with a multidisciplinary team approach involving upper gastrointestinal and thoracic surgeons, gastroenterologists, radiologists, intensivists, and hematologists along with a variety of diagnostic modalities. A review of literature is also presented to help surgeons manage such challenging and complicated cases.

  1. Post-transplant outcome in chronic myeloid leukemia

    International Nuclear Information System (INIS)

    Raza, S.; Ullah, K.; Ahmed, P.; Kamal, M.K.


    To determine post-transplant survival in chronic myeloid leukaemia patients undergoing allogeneic stem cell transplant. All patients of chronic myeloid leukaemia in chronic phase having HLA identical donor and age under 55 years, normal hepatic, renal and cardiac functions with good performance status were selected. Patients in accelerated phase or blast crisis, poor performance status, impaired hepatic, renal, cardiac functions or pregnancy were excluded. Survival was calculated from the date of transplant to death or last follow-up according to Kaplan-Meier and Cox (proportional hazard) regression analysis methods. Thirty seven patients with chronic myeloid leukaemia underwent allogeneic stem cell transplant from HLA identical sibling donors. Thirty two patients were male and five were females. Median age of patients was 28 years. All patients and donors were CMV positive. Post-transplant complications encountered were acute GvHD (Grade II-IV) (n=13, 35.1%), chronic GvHD in 18.9% (n=7), Veno Occlusive Disease (VOD) in 5.4% (n=2), acute renal failure in 2.7% (n=1), haemorrhagic cystitis in 2.7% (n=1), bacterial infections in 40.5% (n=15), fungal infections in 16.2% (n=6), CMV infection in 5.4% (n=2), tuberculosis in 5.4% (n=2), Herpes Zoster infection 2.7% (n=1) and relapse in 2.7% (n=1). Mortality was observed in 27% (n=10). Major causes of mortality were GvHD, VOD, septicemia, CMV infection and disseminated Aspergillosis. Overall Disease Free Survival (DFS) was 73% with a median duration of follow-up of 47.4 + 12 months. DFS was 81% in standard risk and 54.5% in high-risk group. Results of allogeneic stem cell transplant in standard risk group CML patients were good and comparable with other international centres, however, results in high-risk CML patients need further improvement, although, number of patients in this group is small. (author)

  2. Oral manifestations compatible with chronic graft-versus-host disease in patients with Fanconi anemia. (United States)

    Grein Cavalcanti, Laura; Fuentes Araújo, Renata L; Bonfim, Carmem; Torres-Pereira, Cassius C


    Fanconi anemia (FA) is a genetic disease that is characterized by several congenital abnormalities and progressive bone marrow failure and is associated with an increased susceptibility to malignant disorders. Currently, the only potential cure for hematological disorders is hematopoietic stem cell transplantation (HSCT). However, 1 of the most common complications after HSCT is the development of oral chronic graft-versus-host disease (cGVHD), which is also a risk factor for the development of cancer, particularly oral squamous cell carcinoma. Therefore, the purpose of this study was to describe the prevalence and characteristics of oral manifestations compatible with cGVHD in patients diagnosed with FA according to the National Institutes of Health (NIH) consensus criteria. A total of 96 patients (51 females, 45 males; median age, 16 years) with FA, who were in medical follow-up after HSCT at the outpatient clinic of the bone marrow transplantation unit (Hospital de Clínicas from the Universidade Federal do Paraná) underwent an oral evaluation between January 2013 and December 2013. Post-HSCT periods varied from 1 to 261 months and were divided into 3 periods: immediate post-HSCT period; intermediate post-HSC period, and late post-HSCT period. Among the evaluated patients, 40 of 96 (42%) presented with oral manifestations of cGVHD, with 29 of 40 (73%) of these patients in the late post-HSCT period. NIH scale scores varied from 0 to 10, and lichenoid and hyperkeratotic lesions were the abnormalities most frequently observed (100%). Overall, a high prevalence of oral manifestations was observed for cGVHD patients with FA. These data highlight the importance of monitoring oral manifestations compatible with cGVHD to identify and treat individuals with a higher risk of developing oral cancer. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  3. Spontaneous Appendicocutaneous Fistula I

    African Journals Online (AJOL)

    M T0k0de* MB, BS and. Dr 0. A. AWOj0bi+ FMCS (Nig). ABSTRACT. Ruptured appendicitis is not a common cause of spontaneous enterocutaneous fistula. A case of ruptured retrocaecal appendicitis presenting as an enterocutaneous fistula in a Nigerian woman is presented. The literature on this disorder is also reviewed.

  4. [Spontaneous bacterial peritonitis]. (United States)

    Strauss, Edna; Caly, Wanda Regina


    Spontaneous bacterial peritonitis occurs in 30% of patients with ascites due to cirrhosis leading to high morbidity and mortality rates. The pathogenesis of spontaneous bacterial peritonitis is related to altered host defenses observed in end-stage liver disease, overgrowth of microorganisms, and bacterial translocation from the intestinal lumen to mesenteric lymph nodes. Clinical manifestations vary from severe to slight or absent, demanding analysis of the ascitic fluid. The diagnosis is confirmed by a number of neutrophils over 250/mm3 associated or not to bacterial growth in culture of an ascites sample. Enterobacteriae prevail and Escherichia coli has been the most frequent bacterium reported. Mortality rates decreased markedly in the last two decades due to early diagnosis and prompt antibiotic treatment. Third generation intravenous cephalosporins are effective in 70% to 95% of the cases. Recurrence of spontaneous bacterial peritonitis is common and can be prevented by the continuous use of oral norfloxacin. The development of bacterial resistance demands the search for new options in the prophylaxis of spontaneous bacterial peritonitis; probiotics are a promising new approach, but deserve further evaluation. Short-term antibiotic prophylaxis is recommended for patients with cirrhosis and ascites shortly after an acute episode of gastrointestinal bleeding.

  5. Spontaneous Grammar Explanations. (United States)

    Tjoo, Hong Sing; Lewis, Marilyn


    Describes one New Zealand university language teacher's reflection on her own grammar explanations to university-level students of Bahasa Indonesian. Examines form-focused instruction through the teacher's spontaneous answers to students' questions about the form of the language they are studying. The teacher's experiences show that it takes time…


    African Journals Online (AJOL)


    Spontaneous bacterial peritonitis (SBP) frequent]y occurs in patients with liver cirrhosis and ascites. It is defined as an infection of previously sterile ascitic fluid without any demonstrable intrabdominal source of infection. It is now internationally agreed that a polymorphonuclear (PMN) cell count in the ascitic fluid of over 250 ...

  7. Spontaneous dimensional reduction? (United States)

    Carlip, Steven


    Over the past few years, evidence has begun to accumulate suggesting that spacetime may undergo a "spontaneous dimensional reduction" to two dimensions near the Planck scale. I review some of this evidence, and discuss the (still very speculative) proposal that the underlying mechanism may be related to short-distance focusing of light rays by quantum fluctuations.

  8. High frequency of cutaneous manifestations including vitiligo and alopecia areata in a prospective cohort of patients with chronic graft-vs-host disease (United States)

    Čeović, Romana; Desnica, Lana; Pulanić, Dražen; Serventi Seiwerth, Ranka; Ilić, Ivana; Grce, Magdalena; Mravak Stipetić, Marinka; Klepac Pulanić, Tajana; Bilić, Ervina; Bilić, Ernest; Milošević, Milan; Vrhovac, Radovan; Nemet, Damir; Pavletic, Steven Z


    Aim To determine the frequency and the characteristics of cutaneous manifestations, especially vitiligo and alopecia areata, in patients with chronic graft-vs-host disease (cGVHD). Methods 50 patients with cGVHD were prospectively enrolled in the observational study protocol and evaluated by an experienced dermatologist. The evaluation was focused on the clinical spectrum of skin and adnexal involvement, and the cutaneous GVHD score was determined according to National Institutes of Health (NIH) Consensus criteria. The presence of vitiligo, alopecia, xerosis, nail changes, and dyspigmentation was also assessed. Results Out of 50 cGVHD patients, 28 (56%) had skin involvement, and 27 of them (96%) had hypo and/or hyperpigmentations. 11 patients (39%) had a mild cutaneous NIH cGVHD score, 22% moderate, and 39% severe. 15 (30%) patients had nail changes and 10 (20%) had vitiligo or alopecia areata. Univariate analysis showed that patients with vitiligo/alopecia areata received more lines of prior systemic immunosuppressive therapy (P = 0.043), had lower Karnofsky performance status (P = 0.028), and had a higher B-cell number (P = 0.005), platelet count (P = 0.022), and total protein (P = 0.024). Vitiligo and alopecia areata were associated with higher NIH skin score (P = 0.001), higher intensity of immunosuppressive treatment (P = 0.020), and total body irradiation conditioning (P = 0.040). Multivariate regression model showed that patients with higher NIH skin scoring were 3.67 times more likely to have alopecia and/or vitiligo (odds ratio 3.67; 95% confidence interval 1.26-10.73), controlled for all other factors in the model (age at study entry, number of B-cells, platelet count, and global NIH score). Conclusion These data indicate that vitiligo and alopecia areata occur more frequently in cGVHD than previously reported. PMID:27374824

  9. CD24(hi)CD27⁺ and plasmablast-like regulatory B cells in human chronic graft-versus-host disease. (United States)

    de Masson, Adèle; Bouaziz, Jean-David; Le Buanec, Hélène; Robin, Marie; O'Meara, Alix; Parquet, Nathalie; Rybojad, Michel; Hau, Estelle; Monfort, Jean-Benoît; Branchtein, Mylène; Michonneau, David; Dessirier, Valérie; Sicre de Fontbrune, Flore; Bergeron, Anne; Itzykson, Raphaël; Dhédin, Nathalie; Bengoufa, Djaouida; Peffault de Latour, Régis; Xhaard, Aliénor; Bagot, Martine; Bensussan, Armand; Socié, Gérard


    Interleukin 10 (IL-10)-producing B cells (regulatory B cells [Bregs]) regulate autoimmunity in mice and humans, and a regulatory role of IL-10-producing plasma cells has been described in mice. Dysfunction of B cells that maintain homeostasis may play a role in the pathogenesis of chronic graft-versus-host disease (cGVHD) after allogeneic stem cell transplantation. Here, we found a relation between decreased Breg frequencies and cGVHD severity. An impaired ability of B cells to produce IL-10, possibly linked to poor signal transducer and activator of transcription 3 and extracellular signal-regulated kinase phosphorylation, was found in patients with active cGVHD. IL-10 production was not confined to a single B-cell subset, but enriched in both the CD24(hi)CD27(+) and CD27(hi)CD38(hi) plasmablast B-cell compartments. In vitro plasmablast differentiation increased the frequency of IL-10-producing B cells. We confirmed that allogeneic transplant recipients had an impaired reconstitution of the memory B-cell pool. cGVHD patients had less CD24(hi)CD27(+) B cells and IL-10-producing CD24(hi)CD27(+) B cells. Patients with cGVHD had increased plasmablast frequencies but decreased IL-10-producing plasmablasts. These results suggest a role of CD24(hi)CD27(+) B-cell and plasmablast-derived IL-10 in the regulation of human cGVHD. © 2015 by The American Society of Hematology.

  10. Ex Vivo Expanded Human Non-Cytotoxic CD8+CD45RClow/− Tregs Efficiently Delay Skin Graft Rejection and GVHD in Humanized Mice (United States)

    Bézie, Séverine; Meistermann, Dimitri; Boucault, Laetitia; Kilens, Stéphanie; Zoppi, Johanna; Autrusseau, Elodie; Donnart, Audrey; Nerrière-Daguin, Véronique; Bellier-Waast, Frédérique; Charpentier, Eric; Duteille, Franck; David, Laurent; Anegon, Ignacio; Guillonneau, Carole


    Both CD4+ and CD8+ Tregs play a critical role in the control of immune responses and immune tolerance; however, our understanding of CD8+ Tregs is limited while they are particularly promising for therapeutic application. We report here existence of highly suppressive human CD8+CD45RClow/− Tregs expressing Foxp3 and producing IFNγ, IL-10, IL-34, and TGFβ to mediate their suppressive activity. We demonstrate that total CD8+CD45RClow/− Tregs can be efficiently expanded in the presence of anti-CD3/28 mAbs, high-dose IL-2 and IL-15 and that such expanded Tregs efficiently delay GVHD and human skin transplantation rejection in immune humanized mice. Robustly expanded CD8+ Tregs displayed a specific gene signature, upregulated cytokines and expansion in the presence of rapamycin greatly improved proliferation and suppression. We show that CD8+CD45RClow/− Tregs are equivalent to canonical CD4+CD25highCD127low/− Tregs for suppression of allogeneic immune responses in vitro. Altogether, our results open new perspectives to tolerogenic strategies in human solid organ transplantation and GVHD. PMID:29445370

  11. Patients with Treatment-Requiring Chronic Graft versus Host Disease after Allogeneic Stem Cell Transplantation Have Altered Metabolic Profiles due to the Disease and Immunosuppressive Therapy: Potential Implication for Biomarkers

    Directory of Open Access Journals (Sweden)

    Håkon Reikvam


    Full Text Available Chronic graft versus host disease (cGVHD is a common long-term complication after allogeneic hematopoietic stem cell transplantation. The objective of our study was to compare the metabolic profiles for allotransplant recipients and thereby identify metabolic characteristics of patients with treatment-requiring cGVHD. The study included 51 consecutive patients (29 men and 22 women; median age: 44 years, range: 15–66 years transplanted with peripheral blood stem cells derived from human leukocyte antigen-matched family donors. All serum samples investigated by global metabolomic profiling were collected approximately 1 year posttransplant (median 358 days. Thirty-one of the 51 patients (61% had cGVHD 1 year posttransplant. The affected organs were (number of patients liver/bile duct (23, eyes (15, gastrointestinal tract (14, skin (13, mouth (10, lungs (3, and urogenital tract (1. We compared the metabolic profile for patients with and without cGVHD, and a Random Forrest Classification Analysis then resulted in 75% accuracy in differentiating the two groups. The 30 top-ranked metabolites from this comparison included increased levels of bile acids, several metabolites from the cytokine-responsive kynurenine pathway for tryptophan degradation, pro-inflammatory lipid metabolites, phenylalanine and tyrosine metabolites derived from the gut microbial flora, and metabolites reflecting increased oxidative stress. However, nine of these 30 top-ranked metabolites were probably altered due to cyclosporine or steroid treatment, and we therefore did a hierarchical clustering analysis including all 51 patients but only based on the other 21 cGVHD-specific metabolites. This analysis identified three patient subsets: one cluster included mainly patients without cGVHD and had generally low metabolite levels; another cluster included mainly patients with cGVHD (most patients with at least three affected organs and high metabolite levels, and the last

  12. Spontaneous healing of spontaneous coronary artery dissection. (United States)

    Almafragi, Amar; Convens, Carl; Heuvel, Paul Van Den


    Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome and sudden cardiac death. It should be suspected in every healthy young woman without cardiac risk factors, especially during the peripartum or postpartum periods. It is important to check for a history of drug abuse, collagen vascular disease or blunt trauma of the chest. Coronary angiography is essential for diagnosis and early management. We wonder whether thrombolysis might aggravate coronary dissection. All types of treatment (medical therapy, percutaneous intervention or surgery) improve the prognosis without affecting survival times if used appropriately according to the clinical stability and the angiographic features of the involved coronary arteries. Prompt recognition and targeted treatment improve outcomes. We report a case of SCAD in a young female free of traditional cardiovascular risk factors, who presented six hours after thrombolysis for ST elevation myocardial infarction. Coronary angiography showed a dissection of the left anterior descending and immediate branch. She had successful coronary artery bypass grafting, with complete healing of left anterior descending dissection.

  13. The beneficial effect of chronic graft-versus-host disease on the clinical outcome of transplantation with fludarabine/busulfan-based reduced-intensity conditioning for patients with de novo myelodysplastic syndrome. (United States)

    Cho, Byung-Sik; Kim, Yoo-Jin; Cho, Seok-Goo; Kim, Sung-Yong; Eom, Ki-Seong; Kim, Hee-Je; Lee, Seok; Min, Chang-Ki; Kim, Dong-Wook; Lee, Jong-Wook; Min, Woo-Sung; Kim, Chun-Choo


    Allogeneic hematopoietic stem cell transplantation following reduced-intensity stem cell transplantation (RIST) has enabled the treatment of older or medically infirm patients with myeloid malignancies; however, determining the value of RIST outcomes for myelodysplastic syndrome (MDS) is difficult because of the heterogeneity of the diseases included in most trials. To define the role of RIST in MDS, we performed RIST for 22 consecutive patients who had de novo MDS as classified by World Health Organization (WHO) criteria and who received an allograft with fludarabine/busulfan (Busulfex) or fludarabine/Busulfex/antithymocyte globulin (ATG) conditioning. Nineteen patients (86.4%) achieved engraftment. At a median follow-up of 18.9 months (range, 13.1-24.8 months), the estimated 2-year rates of overall survival, event-free survival (EFS), transplantation-related mortality, and relapse were 78.7%, 67.7%, 12.6%, and 22.5%, respectively. Acute graft-versus-host disease (GVHD) greater than grade II developed in 3 patients (15.8%). Chronic GVHD developed in 10 patients (55.6%), none of whom received ATG as a conditioning regimen. Variables influencing EFS were chronic GVHD, marrow blasts before transplantation, and the WHO criteria. The present study clarifies the benefits of the fludarabine/Busulfex-based conditioning regimen for de novo MDS diagnosed according to the WHO criteria and shows that chronic GVHD appears to have a beneficial effect on survival rates, which are strongly associated with graft-versus-tumor effects.

  14. Spontaneous spinal epidural abscess.

    LENUS (Irish Health Repository)

    Ellanti, P


    Spinal epidural abscess is an uncommon entity, the frequency of which is increasing. They occur spontaneously or as a complication of intervention. The classical triad of fever, back pain and neurological symptoms are not always present. High index of suspicion is key to diagnosis. Any delay in diagnosis and treatment can have significant neurological consequences. We present the case of a previously well man with a one month history of back pain resulting from an epidural abscess.

  15. Simultaneous bilateral primary spontaneous pneumothorax

    Directory of Open Access Journals (Sweden)

    Arife Zeybek


    Full Text Available Simultaneous bilateral primary pneumothorax is a very rare (1.6 / 100,000 and life-threatening condition. Clinical presentation may vary from mild dyspnea to tension pneumothorax. It may be milder particularly in younger patients, but more severe in patients with advanced age, and tube thoracostomy is a life preserver in the latter group. Since mortality and recurrence rates following tube thoracostomy are high, endoscopic approaches to bilateral hemithorax have been reported in literature. Apical wedge resection and pleural procedures are recommended in video thoracoscopy or mini thoracotomy even if no bulla and/or bleb are detected. Bilateral surgical interventions and additional pleural procedures are associated with increased rate of post-operative complications and longer postoperative hospital-stays. As a first-line approach, the surgical method toward any side of lung with air leakage following a previous tube thoracostomy is considered less invasive, especially in younger patients. Here, we present a case of simultaneous bilateral primary spontaneous pneumothorax (SBPSP in a 21-year old male with no history of smoking and chronic pulmonary disease. A unilateral surgical intervention was performed, and no recurrence was observed during 5-year follow up.

  16. Bilateral spontaneous hemotympanum: Case report

    Directory of Open Access Journals (Sweden)

    Economou Nicolas C


    Full Text Available Abstract Background The most common causes of hemotympanum are therapeutic nasal packing, epistaxis, blood disorders and blunt trauma to the head. Hemotympanum is characterized as idiopathic, when it is detected in the presence of chronic otitis media. A rare case of spontaneous bilateral hemotympanum in a patient treated with anticoagulants is presented herein. Case presentation A 72-year-old male presented with acute deterioration of hearing. In the patient's medical history aortic valve replacement 1 year before presentation was reported. Since then he had been administered regularly coumarinic anticoagulants, with INR levels maintained between 3.4 and 4.0. Otoscopy revealed the presence of bilateral hemotympanum. The audiogram showed symmetrical moderately severe mixed hearing loss bilaterally, with the conductive component predominating. Tympanograms were flat bilaterally with absent acoustic reflexes. A computerized tomography scan showed the presence of fluid in the mastoid and middle ear bilaterally. Treatment was conservative and consisted of a 10-day course of antibiotics, anticongestants and temporary interruption of the anticoagulant therapy. After 3 weeks, normal tympanic membranes were found and hearing had returned to previous levels. Conclusion Anticoagulant intake should be included in the differential diagnosis of hemotympanum, because its detection and appropriate treatment may lead to resolution of the disorder.

  17. Cardiac tolerance to ischemia in neonatal spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Charvátová, Z.; Ošťádalová, Ivana; Zicha, Josef; Kuneš, Jaroslav; Maxová, H.; Ošťádal, Bohuslav


    Roč. 61, Suppl.1 (2012), S145-S153 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : neonatal spontaneously hypertensive rats * contractile function * ischemic preconditioning * chronic hypoxia Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.531, year: 2012

  18. Spontaneous Pneumothorax in a Young Child With Pulmonary Tuberculosis. (United States)

    Hulme, Kathryn M; Isaacs, David; Marais, Ben J; Robinson, Paul D


    We report a 2-year old previously healthy boy, who presented with chronic pneumonia. He was diagnosed with culture-confirmed pulmonary tuberculosis. Complications included spontaneous pneumothorax presumed to be secondary to cavity formation and complete sub-segmental airway obstruction that did not resolve with prolonged oral corticosteroid treatment.

  19. Spontaneous Thigh Compartment Syndrome

    Directory of Open Access Journals (Sweden)

    Khan, Sameer K


    Full Text Available A young man presented with a painful and swollen thigh, without any history of trauma, illness, coagulopathic medication or recent exertional exercise. Preliminary imaging delineated a haematoma in the anterior thigh, without any fractures or muscle trauma. Emergent fasciotomies were performed. No pathology could be identified intra-operatively, or on follow-up imaging. A review of thigh compartment syndromes described in literature is presented in a table. Emergency physicians and traumatologists should be cognisant of spontaneous atraumatic presentations of thigh compartment syndrome, to ensure prompt referral and definitive management of this limb-threatening condition. [West J Emerg Med. 2011;12(1:134-138].

  20. Modulation and Apoptosis of Neutrophil Granulocytes by Extracorporeal Photopheresis in the Treatment of Chronic Graft-Versus-Host Disease.

    Directory of Open Access Journals (Sweden)

    Cindy Franklin

    Full Text Available Chronic graft-versus-host disease (cGVHD is a common side effect of allogeneic stem cell transplantation and a major cause of morbidity and mortality in affected patients. Especially skin, eyes and oral mucosa are affected. This can lead to pain and functional impairment. Extracorporeal photopheresis (ECP is an effective immunomodulatory therapy with minimal side effects but its mode of action is still largely unknown. The objective of the present study was to examine the effects of ECP on neutrophil granulocytes in patients with cGVHD. Analysis of leukocytes from cGVHD patients obtained from the ECP device during treatment showed that neutrophil granulocytes account for the majority of cells treated during ECP. Neutrophils from healthy donors treated in vitro with 8-methoxypsoralen and UVA light as well as neutrophils from buffy coats of patients with cGVHD treated by ECP showed increased apoptosis and decreased half-life. In remaining non-apoptotic cells chemoirradiation resulted in loss of activation markers and reduced effector functions. This was accompanied by an increase in extracellular arginase-1 activity. Additional comparison of neutrophils isolated from blood of cGVHD patients before and 24h after ECP revealed a decreased half-life and reduction of effector functions of post-ECP neutrophils ex vivo. These observations strongly suggest that ECP induces both apoptosis and physiological changes in neutrophils and that these changes also take place in vivo. This study is the first to show that ECP modulates apoptosis and inflammatory activity in neutrophil granulocytes, indicating that neutrophils may significantly contribute to the overall immunomodulatory effects attributed to this treatment.

  1. Spontaneous Tumor Lysis Syndrome

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    Alicia C. Weeks MD


    Full Text Available Tumor lysis syndrome (TLS is a known complication of malignancy and its treatment. The incidence varies on malignancy type, but is most common with hematologic neoplasms during cytotoxic treatment. Spontaneous TLS is thought to be rare. This case study is of a 62-year-old female admitted with multisystem organ failure, with subsequent diagnosis of aggressive B cell lymphoma. On admission, laboratory abnormalities included renal failure, elevated uric acid (20.7 mg/dL, and 3+ amorphous urates on urinalysis. Oliguric renal failure persisted despite aggressive hydration and diuretic use, requiring initiation of hemodialysis prior to chemotherapy. Antihyperuricemic therapy and hemodialysis were used to resolve hyperuricemia. However, due to multisystem organ dysfunction syndrome with extremely poor prognosis, the patient ultimately expired in the setting of a terminal ventilator wean. Although our patient did not meet current TLS criteria, she required hemodialysis due to uric acid nephropathy, a complication of TLS. This poses the clinical question of whether adequate diagnostic criteria exist for spontaneous TLS and if the lack of currently accepted guidelines has resulted in the underestimation of its incidence. Allopurinol and rasburicase are commonly used for prevention and treatment of TLS. Although both drugs decrease uric acid levels, allopurinol mechanistically prevents formation of the substrate rasburicase acts to solubilize. These drugs were administered together in our patient, although no established guidelines recommend combined use. This raises the clinical question of whether combined therapy is truly beneficial or, conversely, detrimental to patient outcomes.

  2. Spontaneous prediction error generation in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Yuichi Yamashita

    Full Text Available Goal-directed human behavior is enabled by hierarchically-organized neural systems that process executive commands associated with higher brain areas in response to sensory and motor signals from lower brain areas. Psychiatric diseases and psychotic conditions are postulated to involve disturbances in these hierarchical network interactions, but the mechanism for how aberrant disease signals are generated in networks, and a systems-level framework linking disease signals to specific psychiatric symptoms remains undetermined. In this study, we show that neural networks containing schizophrenia-like deficits can spontaneously generate uncompensated error signals with properties that explain psychiatric disease symptoms, including fictive perception, altered sense of self, and unpredictable behavior. To distinguish dysfunction at the behavioral versus network level, we monitored the interactive behavior of a humanoid robot driven by the network. Mild perturbations in network connectivity resulted in the spontaneous appearance of uncompensated prediction errors and altered interactions within the network without external changes in behavior, correlating to the fictive sensations and agency experienced by episodic disease patients. In contrast, more severe deficits resulted in unstable network dynamics resulting in overt changes in behavior similar to those observed in chronic disease patients. These findings demonstrate that prediction error disequilibrium may represent an intrinsic property of schizophrenic brain networks reporting the severity and variability of disease symptoms. Moreover, these results support a systems-level model for psychiatric disease that features the spontaneous generation of maladaptive signals in hierarchical neural networks.

  3. Prevalence of ocular hypertension and glaucoma in patients with chronic ocular graft-versus-host disease. (United States)

    Saboo, Ujwala S; Amparo, Francisco; Shikari, Hasanain; Dana, Reza


    To evaluate the prevalence of ocular hypertension (OHT) and glaucoma in patients with chronic ocular graft-versus-host disease (GVHD). We performed a retrospective chart review of 218 patients diagnosed with chronic ocular GVHD. Ocular hypertension was defined as intraocular pressure (IOP) ≥ 24 mmHg in either eye without any glaucomatous optic disc changes. Glaucoma suspect was defined as optic disc changes with a cup-to-disc ratio ≥ 0.7 in either eye or asymmetry of ≥ 0.3 between the two eyes. Glaucoma was defined by glaucomatous optic disc changes plus glaucomatous visual field defects in two consecutive reliable visual field tests. The number of cases of ocular hypertension, glaucoma, and glaucoma suspects was evaluated. Thirty-three patients (15 %) were diagnosed with OHT, eight patients (3.6 %) with suspicion of glaucoma, and one patient (0.4 %) with glaucoma. OHT occurred within 6 months of developing ocular GVHD in 60 % of the cases and within the first year in 76 %. High IOP normalized in 67 % of patients when the dosage of topical or systemic corticosteroids was lowered, and 27 % of patients required anti-glaucoma therapy. Ocular hypertension is a common complication in patients with ocular GVHD, with a prevalence of 15 %. The rise in intraocular pressure is often transient and resolves with management of corticosteroids in most cases. However, clinicians should be aware that nearly one-third of the patients with OHT might require anti-glaucoma treatment. The prevalences of glaucoma and suspicion of glaucoma were not higher than in the general population.

  4. Incidences and range of spontaneous findings in the lymphoid and haemopoietic system of control Charles River CD-1 mice (Crl: CD-1(ICR) BR) used in chronic toxicity studies. (United States)

    Bradley, Alys; Mukaratirwa, Sydney; Petersen-Jones, Morven


    The authors performed a retrospective study to determine the incidences and range of spontaneous pathology findings in the lymphoid and haemopoietic systems of control Charles River CD-1 mice (Crl: CD-1(ICR) BR). Data was collected from 2,560 mice from control dose groups (104-week and 80-week carcinogenicity studies; 13-week studies), from regulatory studies evaluated at the authors' laboratory between 2005 and 2010. Lesions of the lymphoid and hematopoietic systems were uncommon in 13-week studies but were of high incidence in the carcinogenicity studies (80- or 104-week duration). The most common finding overall was lymphoid hyperplasia within the spleen, thymus, and lymph nodes. The finding of benign lymphoid hyperplasia of the thymus is unusual in other mouse strains. The most common cause of death in the carcinogenicity studies was lymphoma. It is hoped that the results presented here will provide a useful database of incidental pathology findings in CD-1 mice on carcinogenicity studies.

  5. Spontaneous Intracranial Hypotension

    International Nuclear Information System (INIS)

    Joash, Dr.


    Epidemiology is not only rare but an important cause of new daily persistent headaches among young & middle age individuals. The Etiology & Pathogenesis is generally caused by spinal CSF leak. Precise cause remains largely unknown, underlying structural weakness of spinal meninges is suspected. There are several MR Signs of Intracranial Hypotension that include:- diffuse pachymeningeal (dural) enhancement; bilateral subdural, effusion/hematomas; Downward displacement of brain; enlargement of pituitary gland; Engorgement of dural venous sinuses; prominence of spinal epidural venous plexus and Venous sinus thrombosis & isolated cortical vein thrombosis. The sum of volumes of intracranial blood, CSF & cerebral tissue must remain constant in an intact cranium. Treatment in Many cases can be resolved spontaneously or by use Conservative approach that include bed rest, oral hydration, caffeine intake and use of abdominal binder. Imaging Modalities for Detection of CSF leakage include CT myelography, Radioisotope cisternography, MR myelography, MR imaging and Intrathecal Gd-enhanced MR

  6. Spontaneous wave packet reduction

    International Nuclear Information System (INIS)

    Ghirardi, G.C.


    There are taken into account the main conceptual difficulties met by standard quantum mechanics in dealing with physical processes involving macroscopic system. It is stressed how J.A.Wheeler's remarks and lucid analysis have been relevant to pinpoint and to bring to its extreme consequences the puzzling aspects of quantum phenomena. It is shown how the recently proposed models of spontaneous dynamical reduction represent a consistent way to overcome the conceptual difficulties of the standard theory. Obviously, many nontrivial problems remain open, the first and more relevant one being that of generalizing the model theories considered to the relativistic case. This is the challenge of the dynamical reduction program. 43 refs, 2 figs

  7. Spontaneous compactification to homogeneous spaces

    International Nuclear Information System (INIS)

    Mourao, J.M.


    The spontaneous compactification of extra dimensions to compact homogeneous spaces is studied. The methods developed within the framework of coset space dimensional reduction scheme and the most general form of invariant metrics are used to find solutions of spontaneous compactification equations

  8. Screening for spontaneous preterm birth

    NARCIS (Netherlands)

    van Os, M.A.; van Dam, A.J.E.M.


    Preterm birth is the most important cause of perinatal morbidity and mortality worldwide. In this thesis studies on spontaneous preterm birth are presented. The main objective was to investigate the predictive capacity of mid-trimester cervical length measurement for spontaneous preterm birth in a

  9. Spontaneous Pneumomediastinum: Hamman Syndrome

    Directory of Open Access Journals (Sweden)

    Tushank Chadha, BS


    significant fat stranding. The image also showed an intraluminal stent traversing the gastric antrum and gastric pylorus with no indication of obstruction. Circumferential mural thickening of the gastric antrum and body were consistent with the patient’s history of gastric adenocarcinoma. The shotty perigastric lymph nodes with associated fat stranding, along the greater curvature of the distal gastric body suggested local regional nodal metastases and possible peritoneal carcinomatosis. The thoracic CT scans showed extensive pneumomediastinum that tracked into the soft tissues of the neck, which given the history of vomiting also raised concern for esophageal perforation. There was still no evidence of mediastinal abscess or fat stranding. Additionally, a left subclavian vein port catheter, which terminates with tip at the cavoatrial junction of the superior vena cava can also be seen on the image. Discussion: Spontaneous Pneumomediastinum, also known as Hamman syndrome, is defined by the uncommon incidence of free air in the mediastinum due to the bursting of alveoli, as a result of extended spells of shouting, coughing, or vomiting.1,2 The condition is diagnosed when a clear cause (aerodigestive rupture, barotrauma, infection secondary to gas-forming organisms3 for pneumomediastinum cannot be clearly identified on diagnostic studies. Macklin and Macklin were the first to note the pathogenesis of the syndrome and explained that the common denominator to spontaneous pneumomediastinum was that increased alveolar pressure leads to alveolar rupture.3 Common clinical findings for spontaneous pneumomediastinum include: chest pain, dyspnea, cough, and emesis.4 The condition is not always readily recognized on initial presentation in part for its rare incidence, estimated to be approximately 1 in every 44,500 ED patients3and also because of the non-specific presenting symptoms. For this patient, there was no clear singular cause, and therefore she received care for spontaneous

  10. Three-dimensional structure discrepancy between HLA alleles for effective prediction of aGVHD severity and optimal selection of recipient-donor pairs: a proof-of-concept study. (United States)

    Han, Hongxing; Yuan, Fang; Sun, Yuying; Liu, Jinfeng; Liu, Shuguang; Luo, Yuan; Liang, Fei; Liu, Nan; Long, Juan; Zhao, Xiao; Kong, Fanhua; Xi, Yongzhi


    The optimal selection of recipient-donor pair and accurate prediction of acute graft-versus-host disease (aGVHD) severity are always the two most crucial works in allogeneic hematopoietic stem cell transplantation (allo-HSCT), which currently rests mostly with HLA compatibility, the most polymorphic loci in the human genome, in clinic. Thus, there is an urgent need for a rapid and reliable quantitative system for optimal recipient-donor pairs selection and accurate prediction of aGVHD severity prior to allo-HSCT. For these reasons, we have developed a new selection/prediction system for optimal recipient-donor selection and effective prediction of aGVHD severity based on HLA three-dimensional (3D) structure modeling (HLA-TDSM) discrepancy, and applied this system in a pilot randomized clinical allo-HSCT study. The 37 patient-donor pairs in the study were typed at low- and high-resolution levels for HLA-A/-B/-DRB1/-DQB1 loci. HLA-TDSM system covering the 10000 alleles in HLA class I and II consists of the revised local and coordinate root-mean-square deviation (RMSD) values for each locus. Its accuracy and reliability were confirmed using stably transfected Hmy2.CIR-HLA-B cells, TCR Vβ gene scan, and antigen-specific alloreactive cytotoxic lymphocytes. Based on the preliminary results, we theoretically defined all HLA acceptable versus unacceptable mismatched alleles. More importantly, HLA-TDSM enabled a successful retrospective verification and prospective prediction for aGVHD severity in a pilot randomized clinical allo-HSCT study of 32 recipient-donor transplant pairs. There was a strong direct correlation between single/total revised RMSD and aGVHD severity (92% in retrospective group vs 95% in prospective group). These results seem to be closely related to the 3D structure discrepancy of mismatched HLA-alleles, but not the number or loci of mismatched HLA-alleles. Our data first provide the proof-of-concept that HLA-TDSM is essential for optimal selection of

  11. MR findings in patients with disabling musculocutaneous chronic graft-versus-host disease

    International Nuclear Information System (INIS)

    Horger, M.; Boss, A.; Claussen, C.D.; Bethge, W.; Faul, C.; Vogel, W.; Fierlbeck, G.; Bornemann, A.


    To describe musculocutaneous MR-findings responsible for disability in chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic cell transplantation (HCT). Between June 2005 and February 2008, we performed whole-body musculoskeletal magnetic resonance imaging (MRI; n = 12) or regional MRI (n = 4) in 16 consecutive patients presenting with disabling sclerodermatous cGVHD (e.g., skin edema, fixed deep dermal sclerosis, joint contractures, painful muscular contractures, or myalgia). In all patients, MRI showed musculocutaneous abnormalities reflecting different degrees of inflammation and collagen tissue involvement of the skin (n = 10), subcutaneous fat tissue (n 13), muscle fasciae (n = 16), subfascial muscular septae (n = 6), or findings compatible with myositis (n = 3). The most frequently involved muscle fasciae comprised those of the vastus lateralis muscle (n = 12), biceps femoris muscle (n = 11), gastrocnemius medialis muscle (n = 8), serratus anterior muscle, and latissimus dorsi muscle (each, n = 5). Increased signal of involved tissues on STIR-images and fat-saturated postgadolinium T1-weighted images represented the most frequent MR-signal abnormalities. MR imaging of musculocutaneous cGVHD allows accurate evaluation including assessment of deep tissue infiltration and assists in the differential diagnosis. (orig.)

  12. MR findings in patients with disabling musculocutaneous chronic graft-versus-host disease

    Energy Technology Data Exchange (ETDEWEB)

    Horger, M.; Boss, A.; Claussen, C.D. [Eberhard-Karls-University, Department of Diagnostic Radiology, Tuebingen (Germany); Bethge, W.; Faul, C.; Vogel, W. [Eberhard-Karls-University, Department of Internal Medicine-Oncology, Tuebingen (Germany); Fierlbeck, G. [Eberhard-Karls-University, Department of Dermatology, Tuebingen (Germany); Bornemann, A. [Eberhard-Karls-University, Insitute for Brain Research, Tuebingen (Germany)


    To describe musculocutaneous MR-findings responsible for disability in chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic cell transplantation (HCT). Between June 2005 and February 2008, we performed whole-body musculoskeletal magnetic resonance imaging (MRI; n = 12) or regional MRI (n = 4) in 16 consecutive patients presenting with disabling sclerodermatous cGVHD (e.g., skin edema, fixed deep dermal sclerosis, joint contractures, painful muscular contractures, or myalgia). In all patients, MRI showed musculocutaneous abnormalities reflecting different degrees of inflammation and collagen tissue involvement of the skin (n = 10), subcutaneous fat tissue (n = 13), muscle fasciae (n = 16), subfascial muscular septae (n = 6), or findings compatible with myositis (n = 3). The most frequently involved muscle fasciae comprised those of the vastus lateralis muscle (n = 12), biceps femoris muscle (n = 11), gastrocnemius medialis muscle (n = 8), serratus anterior muscle, and latissimus dorsi muscle (each, n = 5). Increased signal of involved tissues on STIR-images and fat-saturated postgadolinium T1-weighted images represented the most frequent MR-signal abnormalities. MR imaging of musculocutaneous cGVHD allows accurate evaluation including assessment of deep tissue infiltration and assists in the differential diagnosis. (orig.)

  13. Spontaneous breaking of supersymmetry

    Energy Technology Data Exchange (ETDEWEB)

    Zumino, B.


    There has been recently a revival of interest in supersymmetric gauge theories, stimulated by the hope that supersymmetry might help in clarifying some of the questions which remain unanswered in the so called Grand Unified Theories and in particular the gauge hierarchy problem. In a Grand Unified Theory one has two widely different mass scales: the unification mass M approx. = 10/sup 15/GeV at which the unification group (e.g. SU(5)) breaks down to SU(3) x SU(2) x U(1) and the mass approx. = 100 GeV at which SU(2) x U(1) is broken down to the U(1) of electromagnetism. There is at present no theoretical understanding of the extreme smallness of the ratio of these two numbers. This is the gauge hierarchy problem. This lecture attempts to review the various mechanisms for spontaneous supersymmetry breaking in gauge theories. Most of the discussions are concerned with the tree approximation, but what is presently known about radiative correction is also reviewed.

  14. Spontaneous intracranial hypotension

    International Nuclear Information System (INIS)

    Haritanti, A.; Karacostas, D.; Drevelengas, A.; Kanellopoulos, V.; Paraskevopoulou, E.; Lefkopoulos, A.; Economou, I.; Dimitriadis, A.S.


    Spontaneous intracranial hypotension (SIH) is an uncommon but increasingly recognized syndrome. Orthostatic headache with typical findings on magnetic resonance imaging (MRI) are the key to diagnosis. Delayed diagnosis of this condition may subject patients to unnecessary procedures and prolong morbidity. We describe six patients with SIH and outline the important clinical and neuroimaging findings. They were all relatively young, 20-54 years old, with clearly orthostatic headache, minimal neurological signs (only abducent nerve paresis in two) and diffuse pachymeningeal gadolinium enhancement on brain MRI, while two of them presented subdural hygromas. Spinal MRI was helpful in detecting a cervical cerebrospinal fluid leak in three patients and dilatation of the vertebral venous plexus with extradural fluid collection in another. Conservative management resulted in rapid resolution of symptoms in five patients (10 days-3 weeks) and in one who developed cerebral venous sinus thrombosis, the condition resolved in 2 months. However, this rapid clinical improvement was not accompanied by an analogous regression of the brain MR findings that persisted on a longer follow-up. Along with recent literature data, our patients further point out that SIH, to be correctly diagnosed, necessitates increased alertness by the attending physician, in the evaluation of headaches

  15. Spontaneous lateral temporal encephalocele. (United States)

    Tuncbilek, Gokhan; Calis, Mert; Akalan, Nejat


    A spontaneous encephalocele is one that develops either because of embryological maldevelopment or from a poorly understood postnatal process that permits brain herniation to occur. We here report a rare case of lateral temporal encephalocele extending to the infratemporal fossa under the zygomatic arch. At birth, the infant was noted to have a large cystic mass in the right side of the face. After being operated on initially in another center in the newborn period, the patient was referred to our clinic with a diagnosis of temporal encephalocele. He was 6 months old at the time of admission. Computerized tomography scan and magnetic resonance imaging studies revealed a 8 × 9 cm fluid-filled, multiloculated cystic mass at the right infratemporal fossa. No intracranial pathology or connection is seen. The patient was operated on to reduce the distortion effect of the growing mass. The histopathological examination of the sac revealed well-differentiated mature glial tissue stained with glial fibrillary acid protein. This rare clinical presentation of encephaloceles should be taken into consideration during the evaluation of the lateral facial masses in the infancy period, and possible intracranial connection should be ruled out before surgery to avoid complications.

  16. A Single-Center Pilot Prospective Study of Topical Application of Platelet-Derived Eye Drops for Patients with Ocular Chronic Graft-versus-Host Disease. (United States)

    Zallio, Francesco; Mazzucco, Laura; Monaco, Federico; Astori, Maria Rosa; Passera, Roberto; Drago, Giovanna; Tamiazzo, Stefania; Rapetti, Manuela; Dolcino, Daniela; Guaschino, Roberto; Pini, Massimo; Ladetto, Marco


    Ocular involvement of chronic graft-versus-host disease (cGVHD) is a complication that occurs in up to 60% of patients after allogeneic hematopoietic stem cell transplantation. Conventional therapeutic options include medical and surgical procedures that are administered depending on the severity of the condition, but most of them have provided unsatisfactory results and, to date, there is no consensus about treatment. We considered that topical application of a platelet lysate, administered as eye drops, might be considered an alternative worthwhile of investigation to treat ocular surface disorders in patients suffering from cGVHD. Therefore, we conducted a single-center prospective pilot study to assess the efficacy and safety of using eye drops made from reconstituted lysed platelet concentrate. Twenty-six patients with ocular cGVHD were eligible for the study; all but 2 completed their scheduled 1-year treatment and complied with the hematologic and ophthalmic regimen. At their first assessment interviews, after 30 days of treatment, 91% of patients reported an improvement in their symptoms and for 32%, substantive objective differences were measured. Remission of corneal damage was seen for 86% of our cohort, and improved National Institutes of Health scores for 73%, of whom 8% achieved the best score of 0 (ie, non-dry eye). Similar results were seen at later time points. Comparing outcomes for our patient cohort to those determined retrospectively for patients in our institutional database revealed a 5-year overall survival (OS) of 65%. This OS is comparable to patients with limited cGVHD (75%) and is superior to that of patients with nonocular extensive cGVHD or without cGVHD (30% and 59%, respectively) (P = .013). Our results suggest that platelet-derived eye drops are a safe, practical, and well-tolerated therapeutic option that offers substantial benefits for most patients affected by ocular cGVHD at onset. The favorable OS of our patient cohort

  17. Bilateral spontaneous carotid artery dissection. (United States)

    Townend, Bradley Scott; Traves, Laura; Crimmins, Denis


    Bilateral internal carotid artery dissections have been reported, but spontaneous bilateral dissections are rare. Internal carotid artery dissection can present with a spectrum of symptoms ranging from headache to completed stroke. Two cases of spontaneous bilateral carotid artery dissection are presented, one with headache and minimal symptoms and the other with a stroke syndrome. No cause could be found in either case, making the dissections completely spontaneous. Bilateral internal carotid artery dissection (ICAD) should be considered in young patients with unexplained head and neck pain with or without focal neurological symptoms and signs. The increasing availability of imaging would sustain the higher index of suspicion.

  18. [Results of spontaneous NBT-test in influenza patients]. (United States)

    Nagoev, B S; Orazaev, N G


    Assessment of leukocyte activity with spontaneous NBT-test in influenza patients regarding the disease stage, severity, complication and concomitant diseases. 107 influenza patients aged 16-84 years were studied. 70 patients had no complications, 11 patients had early influenzal pneumonia, 26 patients had late viral-bacterial infection. Chronic concomitant diseases were diagnosed in 23 cases. Cytochemical examination of leukocyte activity was made in all the patients using spontaneous NBT-test. In mild influenza NBT-test results were within upper limits of normal value. In alleviation of the symptoms NBT-test parameters were low. In early influenzal and viral-bacterial pneumonia leukocyte activity was high and lowered to normal in late convalescence. Parameters of spontaneous NBT-test in influenzal patients were elevated depending on influenza stage, severity and complications. This fact is of differential-diagnostic importance.

  19. Spontaneous intraorbital hematoma: case report

    Directory of Open Access Journals (Sweden)

    Vinodan Paramanathan


    Full Text Available Vinodan Paramanathan, Ardalan ZolnourianQueen's Hospital NHS Foundation Trust, Burton on Trent, Staffordshire DE13 0RB, UKAbstract: Spontaneous intraorbital hematoma is an uncommon clinical entity seen in ophthalmology practice. It is poorly represented in the literature. Current evidence attributes it to orbital trauma, neoplasm, vascular malformations, acute sinusitis, and systemic abnormalities. A 65-year-old female presented with spontaneous intraorbital hematoma manifesting as severe ocular pains, eyelid edema, proptosis, and diplopia, without a history of trauma. Computer tomography demonstrated a fairly well defined extraconal lesion with opacification of the paranasal sinuses. The principal differential based on all findings was that of a spreading sinus infection and an extraconal tumor. An unprecedented finding of a spontaneous orbital hematoma was discovered when the patient was taken to theater. We discuss the rarity of this condition and its management.Keywords: hemorrhage, ophthalmology, spontaneous, intra-orbital, hematoma

  20. Spontaneous ischaemic stroke in dogs

    DEFF Research Database (Denmark)

    Gredal, Hanne Birgit; Skerritt, G. C.; Gideon, P.


    Translation of experimental stroke research into the clinical setting is often unsuccessful. Novel approaches are therefore desirable. As humans, pet dogs suffer from spontaneous ischaemic stroke and may hence offer new ways of studying genuine stroke injury mechanisms.......Translation of experimental stroke research into the clinical setting is often unsuccessful. Novel approaches are therefore desirable. As humans, pet dogs suffer from spontaneous ischaemic stroke and may hence offer new ways of studying genuine stroke injury mechanisms....

  1. Spontaneity and international marketing performance


    Souchon, Anne L.; Hughes, Paul; Farrell, Andrew M.; Nemkova, Ekaterina; Oliveira, Joao S.


    The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Purpose – The purpose of this paper is to ascertain how today’s international marketers can perform better on the global scene by harnessing spontaneity. Design/methodology/approach – The authors draw on contingency theory to develop a model of the spontaneity – international marketing performance relationship, and identify three potential m...

  2. Nontraumatic spontaneous rupture of the kidney : etiology and CT findings

    International Nuclear Information System (INIS)

    Heo, Tae Haeng; Jeon, Hae Jeong; Shin, Hyun Joon; Kim, Bo Hyun; Cho, Kyoung Sik; Kim, Young Hwa; Kim, Seung Hyup; Park, Churl Min


    To evaluate the usefulness of CT scanning in determining the etiology of spontaneous rupture of the kidney We retrospectively analyzed the CT findings of spontaneous rupture of the kidney in eleven patients, Four were male and seven were female, and they were aged between 20 and 71 (mean, 46.6) years. Both pre- and post-contrast enhanced CT scanning was performed in all patients. Spontaneous renal rupture was induced in seven cases by neoplasms (three angiomyolipomas, three renal cell carcinomas, and one metastatic choriocarcinoma), in three cases by infection or inflammation (acute and chronic pyelonephritis, and renal abscess), and in one, by renal cyst. Common CT findings of rupture of the kidney were the accumulation of high density fluid in the perirenal and anterior pararenal space, and inhomogeneous irregular low density of renal parenchyma and the rupture site. Angiomyolipoma showed fat and an angiomatous component in the lesion, while acute and chronic pyelonephrities revealed thinning of the renal parenchyma and an irregular renal outline. Renal cell carcinoma showed a dense soft tissue mass in the parenchyma. Well-defined, round low-density lesions were noted in the case of renal cyst and renal abscess. CT is very useful in diagnosing and determining the etiology of non-traumatic spontaneous rupture of the kidney and plays an important role in the evaluation of emergency cases

  3. Chronic pancreatitis (United States)

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... abuse over many years. Repeated episodes of acute pancreatitis can lead to chronic pancreatitis. Genetics may be ...

  4. Prospective evaluation of 2 acute graft-versus-host (GVHD) grading systems: a joint Société Française de Greffe de Moëlle et Thérapie Cellulaire (SFGM-TC), Dana Farber Cancer Institute (DFCI), and International Bone Marrow Transplant Registry (IBMTR) prospective study. (United States)

    Cahn, Jean-Yves; Klein, John P; Lee, Stephanie J; Milpied, Noël; Blaise, Didier; Antin, Joseph H; Leblond, Véronique; Ifrah, Norbert; Jouet, Jean-Pierre; Loberiza, Fausto; Ringden, Olle; Barrett, A John; Horowitz, Mary M; Socié, Gérard


    The most commonly used grading system for acute graft-versus-host disease (aGVHD) was introduced 30 years ago by Glucksberg; a revised system was developed by the International Bone Marrow Transplant Registry (IBMTR) in 1997. To prospectively compare the 2 classifications and to evaluate the effect of duration and severity of aGVHD on survival, we conducted a multicenter study of 607 patients receiving T-cell-replete allografts, scored weekly for aGVHD in 18 transplantation centers. Sixty-nine percent of donors were HLA-identical siblings and 28% were unrelated donors. The conditioning regimen included total body irradiation in 442 (73%) patients. The 2 classifications performed similarly in explaining variability in survival by aGVHD grade, although the Glucksberg classification predicted early survival better. There was less physician bias or error in assigning grades with the IBMTR scoring system. With either system, only the maximum observed grade had prognostic significance for survival; neither time of onset nor progression from an initially lower grade of aGVHD was associated with survival once maximum grade was considered. Regardless of scoring system, aGVHD severity accounted for only a small percentage of observed variation in survival. Validity of these results in populations receiving peripheral blood transplants or nonmyeloablative conditioning regimens remains to be tested.

  5. A case of spontaneous ventriculocisternostomy

    International Nuclear Information System (INIS)

    Yamane, Kanji; Yoshimoto, Hisanori; Harada, Kiyoshi; Uozumi, Tohru; Kuwabara, Satoshi.


    The authors experienced a case of spontaneous ventriculocisternostomy diagnosed by CT scan with metrizamide and Conray. Patient was 23-year-old male who had been in good health until one month before admission, when he began to have headache and tinnitus. He noticed bilateral visual acuity was decreased about one week before admission and vomiting appeared two days before admission. He was admitted to our hospital because of bilateral papilledema and remarkable hydrocephalus diagnosed by CT scan. On admission, no abnormal neurological signs except for bilateral papilledema were noted. Immediately, right ventricular drainage was performed. Pressure of the ventricle was over 300mmH 2 O and CSF was clear. PVG and PEG disclosed an another cavity behind the third ventricle, which was communicated with the third ventricle, and occlusion of aqueduct of Sylvius. Metrizamide CT scan and Conray CT scan showed a communication between this cavity and quadrigeminal and supracerebellar cisterns. On these neuroradiological findings, the diagnosis of obstructive hydrocephalus due to benign aqueduct stenosis accompanied with spontaneous ventriculocisternostomy was obtained. Spontaneous ventriculocisternostomy was noticed to produce arrest of hydrocephalus, but with our case, spontaneous regression of such symptoms did not appeared. By surgical ventriculocisternostomy (method by Torkildsen, Dandy, or Scarff), arrest of hydrocephalus was seen in about 50 to 70 per cent, which was the same results as those of spontaneous ventriculocisternostomy. It is concluded that VP shunt or VA shunt is thought to be better treatment of obstructive hydrocephalus than the various kinds of surgical ventriculocisternostomy. (J.P.N.)

  6. Optical antenna enhanced spontaneous emission. (United States)

    Eggleston, Michael S; Messer, Kevin; Zhang, Liming; Yablonovitch, Eli; Wu, Ming C


    Atoms and molecules are too small to act as efficient antennas for their own emission wavelengths. By providing an external optical antenna, the balance can be shifted; spontaneous emission could become faster than stimulated emission, which is handicapped by practically achievable pump intensities. In our experiments, InGaAsP nanorods emitting at ∼ 200 THz optical frequency show a spontaneous emission intensity enhancement of 35 × corresponding to a spontaneous emission rate speedup ∼ 115 ×, for antenna gap spacing, d = 40 nm. Classical antenna theory predicts ∼ 2,500 × spontaneous emission speedup at d ∼ 10 nm, proportional to 1/d(2). Unfortunately, at d antenna efficiency drops below 50%, owing to optical spreading resistance, exacerbated by the anomalous skin effect (electron surface collisions). Quantum dipole oscillations in the emitter excited state produce an optical ac equivalent circuit current, I(o) = qω|x(o)|/d, feeding the antenna-enhanced spontaneous emission, where q|x(o)| is the dipole matrix element. Despite the quantum-mechanical origin of the drive current, antenna theory makes no reference to the Purcell effect nor to local density of states models. Moreover, plasmonic effects are minor at 200 THz, producing only a small shift of antenna resonance frequency.

  7. Assessment of joint and fascia manifestations in chronic graft-versus-host disease. (United States)

    Inamoto, Yoshihiro; Pidala, Joseph; Chai, Xiaoyu; Kurland, Brenda F; Weisdorf, Daniel; Flowers, Mary E D; Palmer, Jeanne; Arai, Sally; Jacobsohn, David; Cutler, Corey; Jagasia, Madan; Goldberg, Jenna D; Martin, Paul J; Pavletic, Steven Z; Vogelsang, Georgia B; Lee, Stephanie J; Carpenter, Paul A


    To investigate the usefulness of various scales for evaluating joint and fascia manifestations in patients with chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation, and to compare the scales in terms of simplicity of use and ability to yield reliable and clinically meaningful results. In a prospective, multicenter, longitudinal, observational cohort of patients with chronic GVHD (n = 567), we evaluated 3 scales proposed for assessing joint status: the National Institutes of Health (NIH) joint/fascia scale, the Hopkins fascia scale, and the Photographic Range of Motion (P-ROM) scale. Ten other scales were also tested for assessment of symptoms, quality of life, and physical functions. Joint and fascia manifestations were present at study enrollment in 164 (29%) of the patients. Limited range of motion was most frequent at the wrists or fingers. Among the 3 joint assessment scales, changes in the NIH scale correlated with both clinician- and patient-perceived improvement of joint and fascia manifestations, with higher sensitivity than the Hopkins fascia scale. Changes in all 3 scales correlated with clinician- and patient-perceived worsening, but the P-ROM scale was the most sensitive in this regard. Onset of joint and fascia manifestations was not associated with subsequent mortality. Joint and fascia manifestations are common in patients with chronic GVHD and should be assessed carefully in these patients. Our results support the use of the NIH joint/fascia scale and P-ROM scale to assess joint and fascia manifestations. The NIH scale better captures improvement, while the P-ROM scale better captures worsening. The utility of these scales could also be tested in the rheumatic diseases. Copyright © 2014 by the American College of Rheumatology.

  8. Joint and fascia manifestations in chronic graft-versus-host disease and their assessment (United States)

    Inamoto, Yoshihiro; Pidala, Joseph; Chai, Xiaoyu; Kurland, Brenda F.; Weisdorf, Daniel; Flowers, Mary E.D.; Palmer, Jeanne; Arai, Sally; Jacobsohn, David; Cutler, Corey; Jagasia, Madan; Goldberg, Jenna D.; Martin, Paul J.; Pavletic, Steven Z.; Vogelsang, Georgia B.; Lee, Stephanie J.; Carpenter, Paul A.


    Objective Joint and fascia manifestations in patients with chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation need to be assessed reliably, simply and in a clinically meaningful way. Methods In a prospective, multicenter, longitudinal, observational cohort of patients with chronic GVHD (n=567), we evaluated 3 scales proposed for assessing joint status: National Institutes of Health (NIH) joint/fascia scale, Hopkins fascia scale and the Photographic Range of Motion (P-ROM) scale. Ten other scales were also tested for assessing symptoms, quality of life and physical functions. Results Joint and fascia manifestations were present at study enrollment in 164 (29%) patients. Limited range of motion was most frequent at wrists or fingers. Among the 3 joint scales, changes in the NIH scale correlated with both clinician and patient-perceived improvement of joint and fascia manifestations with higher sensitivity than the Hopkins fascia scale. Changes in all 3 scales correlated with clinician and patient-perceived worsening but the P-ROM scale was the most sensitive in this regard. Onset of joint and fascia manifestations was not associated with subsequent mortality. Conclusion Joint and fascia manifestations are common and should be assessed carefully in patients with chronic GVHD. Our results support the use of the NIH joint/fascia scale and P-ROM scale to assess joint and fascia manifestations. The NIH scale better captures improvement, while the P-ROM scale better captures worsening. The utility of these scales could also be tested in the rheumatic diseases. PMID:24757155

  9. Successful report of reduced-intensity stem cell transplantation from unrelated umbilical cord blood in a girl with chronic active Epstein-Barr virus infection. (United States)

    Iguchi, Akihiro; Kobayashi, Ryoji; Sato, Tomonobu Z; Nakajima, Masahide; Kaneda, Makoto; Ariga, Tadashi


    We describe an 8-year-old girl with chronic active Epstein-Barr virus (EBV) infection (CAEBV) who was treated successfully by reduced-intensity stem cell transplantation (RIST) from unrelated cord blood (CB). She had been suffering from fever, abdominal pain, and interstitial lymphadenopathy, and CAEBV was diagnosed. After chemotherapy that included etoposide, the amount of EBV decreased transiently below the detection level. However, the disease due to CAEBV worsened despite the chemotherapy, and she finally needed chemotherapy every week. Therefore, instead of conventional myeloablative transplantation, we performed CB transplantation with reduced-intensity conditioning regimens consisting of low-dose total body irradiation, fludarabine, and etoposide. CB, for which human leukocyte antigen (HLA) was 2-loci mismatched on the DR loci from an unrelated donor, was infused after conditioning. Although grade III acute graft-versus-host disease (GVHD) in the gut and chronic GVHD in the lung developed, the symptoms of GVHD disappeared with immunosuppressive therapy. After 15 months, the patient remained a complete chimera, with undetectable levels of EBV in peripheral blood and bone marrow. We conclude that RIST from unrelated CB can be indicated for some cases of CAEBV who are refractory to chemotherapy and have no HLA-matched related and unrelated donors as the source of bone marrow or peripheral blood stem cells.

  10. Spontaneous subcapsular and perirrenal hemorrhage

    International Nuclear Information System (INIS)

    Fuster, M.J.; Saez, J.; Perez-Paya, F.J.; Fernandez, F.


    To assess the role of CT in the etiologic diagnosis of spontaneous subcapsular and perirrenal hemorrhage. The CT findings are described in 13 patients presenting subcapsular and perirrenal hemorrhage. Those patients in whom the bleeding was not spontaneous were excluded. Surgical confirmation was obtained in nine cases. In 11 of the 13 cases (84.6%), involving five adenocarcinomas, five angiomyolipoma, two complicated cysts and one case of panarterities nodosa, CT disclosed the underlying pathology. In two cases (15.4%), it only revealed the extension of the hematoma, but gave no clue to its origin. CT is the technique of choice when spontaneous subcapsular and perirrenal hemorrhage is suspected since, in most cases, it reveals the underlying pathology. (Author)

  11. Spontaneous isolated celiac artery dissection

    Directory of Open Access Journals (Sweden)

    Tuba Cimilli Ozturk


    Full Text Available Dyspepsia with mild, stabbing epigastric discomfort without history of trauma is a very common symptom that emergency physicians see in their daily practice. Vascular emergencies, mostly the aortic dissection and aneurysm, are always described in the differential diagnosis with persistent symptoms. Isolated celiac artery dissection occurring spontaneously is a very rare diagnosis. The involvement of branch vessels is generally observed and patients show various clinical signs and symptoms according to the involved branch vessel. Here we are presenting a case with spontaneous isolated celiac artery dissection, without any branch vessel involvement or visceral damage, detected by computed tomography scans taken on admission.

  12. Spontaneous waves in muscle fibres

    Energy Technology Data Exchange (ETDEWEB)

    Guenther, Stefan; Kruse, Karsten [Department of Theoretical Physics, Saarland University, 66041 Saarbruecken (Germany); Max Planck Institute for the Physics of Complex Systems, Noethnitzer Street 38, 01187 Dresden (Germany)


    Mechanical oscillations are important for many cellular processes, e.g. the beating of cilia and flagella or the sensation of sound by hair cells. These dynamic states originate from spontaneous oscillations of molecular motors. A particularly clear example of such oscillations has been observed in muscle fibers under non-physiological conditions. In that case, motor oscillations lead to contraction waves along the fiber. By a macroscopic analysis of muscle fiber dynamics we find that the spontaneous waves involve non-hydrodynamic modes. A simple microscopic model of sarcomere dynamics highlights mechanical aspects of the motor dynamics and fits with the experimental observations.

  13. Chronic Diarrhea (United States)

    ... infections that cause chronic diarrhea be prevented? Chronic Diarrhea What is chronic diarrhea? Diarrhea that lasts for more than 2-4 ... represent a life-threatening illness. What causes chronic diarrhea? Chronic diarrhea has many different causes; these causes ...

  14. Human Papillomavirus Infection as a Possible Cause of Spontaneous Abortion and Spontaneous Preterm Delivery

    DEFF Research Database (Denmark)

    Ambühl, Lea Maria Margareta; Baandrup, Ulrik; Dybkær, Karen


    , and 10.9% (95% CI; 10.1–11.7) for umbilical cord blood. Summary estimates for HPV prevalence of spontaneous abortions and spontaneous preterm deliveries, in cervix (spontaneous abortions: 24.5%, and pretermdeliveries: 47%, resp.) and placenta (spontaneous abortions: 24.9%, and preterm deliveries: 50......%, resp.), were identified to be higher compared to normal full-term pregnancies (푃 spontaneous abortion, spontaneous preterm...

  15. Spontaneous emission by moving atoms

    International Nuclear Information System (INIS)

    Meystre, P.; Wilkens, M.


    It is well known that spontaneous emission is not an intrinsic atomic property, but rather results from the coupling of the atom to the vacuum modes of the electromagnetic field. As such, it can be modified by tailoring the electromagnetic environment into which the atom can radiate. This was already realized by Purcell, who noted that the spontaneous emission rate can be enhanced if the atom placed inside a cavity is resonant with one of the cavity is resonant with one of the cavity modes, and by Kleppner, who discussed the opposite case of inhibited spontaneous emission. It has also been recognized that spontaneous emission need not be an irreversible process. Indeed, a system consisting of a single atom coupled to a single mode of the electromagnetic field undergoes a periodic exchange of excitation between the atom and the field. This periodic exchange remains dominant as long as the strength of the coupling between the atom and a cavity mode is itself dominant. 23 refs., 6 figs

  16. Spontaneous Development of Moral Concepts (United States)

    Siegal, M.


    Moral competence is more difficult to attain than scientific competence. Since language comprehension plays a central role in conceptual development, and moral language is difficult to learn, there is a common deficiency in moral conceptual development. This suggests a theory of non-spontaneous solutions to moral problems. (Author/MS)

  17. Shell theorem for spontaneous emission

    DEFF Research Database (Denmark)

    Kristensen, Philip Trøst; Mortensen, Jakob Egeberg; Lodahl, Peter


    and therefore is given exactly by the dipole approximation theory. This surprising result is a spontaneous emission counterpart to the shell theorems of classical mechanics and electrostatics and provides insights into the physics of mesoscopic emitters as well as great simplifications in practical calculations....

  18. Prediction of Spontaneous Preterm Birth

    NARCIS (Netherlands)

    Dijkstra, Karolien


    Preterm birth is a leading cause of neonatal morbidity and mortality. It is a major goal in obstetrics to lower the incidence of spontaneous preterm birth (SPB) and related neonatal morbidity and mortality. One of the principal objectives is to discover early markers that would allow us to identify

  19. EAMJ Dec. Spontaneous.indd

    African Journals Online (AJOL)


    Dec 12, 2008 ... surgical abortion at one month gestation without any complication. The second pregnancy which was a year prior resulted in a spontaneous miscarriage at two months followed by evacuation of retained products of conception with no post abortion complications. Antibiotics were taken following both.

  20. Spontaneous fission of superheavy nuclei

    Indian Academy of Sciences (India)

    the Yukawa-plus-exponential potential. The microscopic shell and pairing corrections are obtained using the Strutinsky and BCS approaches and the cranking formulae yield the inertia tensor. Finally, the WKB method is used to calculate penetrabilities and spontaneous fission half-lives. Calculations are performed for the ...

  1. The effects of tricyclic and 'atypical' antidepressants on spontaneous locomotor activity in rodents. (United States)

    Tucker, J C; File, S E


    With the exception of amineptin, buproprion and nomifensine all tricyclic and 'atypical' antidepressants have been reported to reduce spontaneous motor activity in rodents, after both acute and chronic administration. However, with the diversity of chemical actions of these drugs it is unlikely that a single neurochemical mechanism is underlying this one behavioral effect. These widespread sedative effects have implications for interpreting behavioral changes in other test situations, since sedation generally occurs at doses that fall within the dose-range effective in other tests. We also review the effects on spontaneous motor activity of withdrawal from chronic antidepressant treatment.

  2. Spontaneous Retropharyngeal Emphysema: A Case Report | Chi ...

    African Journals Online (AJOL)

    ... is a rare clinical condition in pediatric otolaryngology. The predominant symptoms are sore throat, odynophagia, dysphagia, and neck pain. Here, we report a case of spontaneous retropharyngeal emphysema. Keywords: Iatrogenic injury, retropharyngeal emphysema, spontaneous retropharyngeal emphysem, trauma ...

  3. La maladie de Grisel : Spontaneous atlantoaxial subluxation

    NARCIS (Netherlands)

    Meek, MF; Robinson, PH; Hermens, RAEC

    Objective: "La maladie de Grisel" (Grisel's syndrome) is a spontaneously occurring atlantoaxial subluxation with torticollis. We present a case of atlantoaxial subluxation occurring in a 20-year period of pharyngoplasty surgery. The occurrence of a "spontaneous" atlantoaxial subluxation after oral

  4. Systematics of spontaneous positron lines

    International Nuclear Information System (INIS)

    Mueller, U.; Reus, T. de; Reinhardt, J.; Mueller, B.; Greiner, W.


    Dynamical and spontaneous positron emission are investigated for heavy-ion collisions with long time delay using a semiclassical description. Numerical results and analytical expressions for the characteristic quantities of the resulting spontaneous positron line, i.e., its position, width, and cross section, are compared. The expected behaviour of the line position and cross section and its visibility against the spectrum of dynamically created positrons is discussed in dependence of the united charge Zsub(u) of projectile and target nucleus in a range of systems from Zsub(u)=180 up to Zsub(u)=188. The results are confronted with presently available experimental data, and possible implications on further experiments are worked out. (orig.)

  5. Spontaneous Rotational Inversion in Phycomyces

    KAUST Repository

    Goriely, Alain


    The filamentary fungus Phycomyces blakesleeanus undergoes a series of remarkable transitions during aerial growth. During what is known as the stagea IV growth phase, the fungus extends while rotating in a counterclockwise manner when viewed from above (stagea IVa) and then, while continuing to grow, spontaneously reverses to a clockwise rotation (stagea IVb). This phase lasts for 24-48Ah and is sometimes followed by yet another reversal (stageAIVc) before the overall growth ends. Here, we propose a continuum mechanical model of this entire process using nonlinear, anisotropic, elasticity and show how helical anisotropy associated with the cell wall structure can induce spontaneous rotation and, under appropriate circumstances, the observed reversal of rotational handedness. © 2011 American Physical Society.

  6. Spontaneous regression of colon cancer. (United States)

    Kihara, Kyoichi; Fujita, Shin; Ohshiro, Taihei; Yamamoto, Seiichiro; Sekine, Shigeki


    A case of spontaneous regression of transverse colon cancer is reported. A 64-year-old man was diagnosed as having cancer of the transverse colon at a local hospital. Initial and second colonoscopy examinations revealed a typical cancer of the transverse colon, which was diagnosed as moderately differentiated adenocarcinoma. The patient underwent right hemicolectomy 6 weeks after the initial colonoscopy. The resected specimen showed only a scar at the tumor site, and no cancerous tissue was proven histologically. The patient is alive with no evidence of recurrence 1 year after surgery. Although an antitumor immune response is the most likely explanation, the exact nature of the phenomenon was unclear. We describe this rare case and review the literature pertaining to spontaneous regression of colorectal cancer. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email:

  7. Management of intractable spontaneous epistaxis (United States)

    Rudmik, Luke


    Background: Epistaxis is a common otolaryngology emergency and is often controlled with first-line interventions such as cautery, hemostatic agents, or anterior nasal packing. A subset of patients will continue to bleed and require more aggressive therapy. Methods: Intractable spontaneous epistaxis was traditionally managed with posterior nasal packing and prolonged hospital admission. In an effort to reduce patient morbidity and shorten hospital stay, surgical and endovascular techniques have gained popularity. A literature review was conducted. Results: Transnasal endoscopic sphenopalatine artery ligation and arterial embolization provide excellent control rates but the decision to choose one over the other can be challenging. The role of transnasal endoscopic anterior ethmoid artery ligation is unclear but may be considered in certain cases when bleeding localizes to the ethmoid region. Conclusion: This article will focus on the management of intractable spontaneous epistaxis and discuss the role of endoscopic arterial ligation and embolization as it pertains to this challenging clinical scenario. PMID:22391084

  8. Spontaneous baryogenesis in warm inflation


    Brandenberger, Robert H.; Yamaguchi, Masahide


    We discuss spontaneous baryogenesis in the warm inflation scenario. In contrast with standard inflation models, radiation always exists in the warm inflation scenario, and the inflaton must be directly coupled to it. Also, the transition to the post-inflationary radiation dominated phase is smooth and the entropy is not significantly increased at the end of the period of inflation. In addition, after the period of warm inflation ends, the inflaton does not oscillate coherently but slowly roll...

  9. Chronic Pain (United States)

    ... people who have chronic pain may also have low self-esteem, depression, and anger. Symptoms of chronic pain Chronic ... itself often leads to other symptoms. These include low self-esteem, anger, depression, anxiety, or frustration. What causes chronic ...

  10. Spontaneous Splenic Rupture in Melanoma

    Directory of Open Access Journals (Sweden)

    Hadi Mirfazaelian


    Full Text Available Spontaneous rupture of spleen due to malignant melanoma is a rare situation, with only a few case reports in the literature. This study reports a previously healthy, 30-year-old man who came with chief complaint of acute abdominal pain to emergency room. On physical examination, abdominal tenderness and guarding were detected to be coincident with hypotension. Ultrasonography revealed mild splenomegaly with moderate free fluid in abdominopelvic cavity. Considering acute abdominal pain and hemodynamic instability, he underwent splenectomy with splenic rupture as the source of bleeding. Histologic examination showed diffuse infiltration by tumor. Immunohistochemical study (positive for S100, HMB45, and vimentin and negative for CK, CD10, CK20, CK7, CD30, LCA, EMA, and chromogranin confirmed metastatic malignant melanoma. On further questioning, there was a past history of a nasal dark skin lesion which was removed two years ago with no pathologic examination. Spontaneous (nontraumatic rupture of spleen is an uncommon situation and it happens very rarely due to neoplastic metastasis. Metastasis of malignant melanoma is one of the rare causes of the spontaneous rupture of spleen.


    Directory of Open Access Journals (Sweden)

    O. V. Lovacheva


    Full Text Available Spontaneous pneumothorax was treated by placing two endobronchial valves during rigid bronchoscopy under anesthesia in a patient with severe end-stage chronic obstructive pulmonary disease (an emphysematous phenotype and overall paraseptal emphysema in the presence of grade III respiratory failure, with complicated spontaneous pneumothorax recurring manifold even after surgical treatment for spontaneous pneumothorax. This gave rise to the expansion of the lung that had collapsed within 18 months, to healing of bronchopleural fistula, and to return to normal life.The duration of a follow-up was 1 year with the valves being present in the bronchi and another year after their removal; there was no recurrence of spontaneous pneumothorax. Examination of respiratory function established significant positive changes (forced expiratory volume, vital capacity, and forced vital capacity after one year, then after removal of endobronchial valves. There were more significant positive changes in blood gas composition: normalization of blood oxygen saturation was achieved. 

  12. Fatal Disseminated Tuberculous Peritonitis following Spontaneous Abortion: A Case Report

    Directory of Open Access Journals (Sweden)

    Munire Erman Akar


    Full Text Available We describe a rare case of fatal disseminated tuberculous peritonitis in a young woman with rapid progressive clinical course following spontaneous abortion of 20-week gestation. Clinical and laboratory findings were initially unremarkable. She underwent diagnostic laparoscopy which revealed numerous tiny implants on the peritoneum and viscera. Histopathology showed chronic caseating granulomas, and the tissue culture grew Mycobacterium tuberculosis. At fifth day of the antituberculous treatment multiorgan failure occurred in terms of pulmonary, hepatic, and renal insufficiency. She developed refractory metabolic acidosis with coagulopathy and pancytopenia, and she died of acute respiratory distress syndrome and septic shock on her twelfth day of hospitalization.

  13. Spontaneous oscillations in microfluidic networks (United States)

    Case, Daniel; Angilella, Jean-Regis; Motter, Adilson


    Precisely controlling flows within microfluidic systems is often difficult which typically results in systems being heavily reliant on numerous external pumps and computers. Here, I present a simple microfluidic network that exhibits flow rate switching, bistablity, and spontaneous oscillations controlled by a single pressure. That is, by solely changing the driving pressure, it is possible to switch between an oscillating and steady flow state. Such functionality does not rely on external hardware and may even serve as an on-chip memory or timing mechanism. I use an analytic model and rigorous fluid dynamics simulations to show these results.

  14. General features of spontaneous baryogenesis (United States)

    Arbuzova, Elena


    The classical version of spontaneous baryogenesis is studied in details. It is shown that the relation between the time derivative of the (pseudo)goldstone field and the baryonic chemical potential essentially depends upon the representation chosen for the fermionic fields with non-zero baryonic number (quarks). The kinetic equation, used for the calculations of the cosmological baryon asymmetry, is generalized to the case of non-stationary background. The effects of the finite interval of the integration over time are also included into consideration.

  15. Splenic irradiation before bone marrow transplantation for chronic myeloid leukaemia

    International Nuclear Information System (INIS)

    Gratwohl, A.; Hermans, J.; Biezen, A.V.


    A total of 229 patients with chronic myeloid leukaemia (CML) in chronic phase were randomized between 1986 and 1990 to receive or not receive additional splenic irradiation as part of their conditioning prior to bone marrow transplantation (BMT). Both groups, 115 patients with and 114 patients without splenic irradiation, were very similar regarding distribution of age, sex, donor/recipient sex combination, conditioning, graft-versus-host disease (GvHD) prevention method and blood counts at diagnosis or prior to transplant. 135 patients (59%) are alive as of October 1995 with a minimum follow-up of 5 years. 52 patients have relapsed (23%), 26 patients in the irradiated, 26 patients in the non-irradiated group (n.s.) with a relapse incident at 6 years of 28%. The main risk factor for relapse was T-cell depletion as the method for GvHD prevention, and an elevated basophil count in the peripheral blood prior to transplant. Relapse incidence between patients with or without splenic irradiation was no different in patients at high risk for relapse, e.g. patients transplanted with T-cell-depleted marrows (P = n.s.) and in patients with low risk for relapse, e.g. patients transplanted with non-T-cell-depleted transplants and basophil counts 3% basophils in peripheral blood). In this patient group, relapse incidence was 11% at 6 years with splenic irradiation but 32% in the non-irradiated group (P = 0.05). Transplant-related mortality was similar whether patients received splenic irradiation or not. This study suggests an advantage in splenic irradiation prior to transplantation for CML in this subgroup of patients and illustrates the need for tailored therapy. (Author)

  16. Radiological evaluation of spontaneous pneumoperitoneum

    International Nuclear Information System (INIS)

    Kim, H. S.; Kim, J. D.; Rhee, H. S.


    112 cases of spontaneous penumoperitoneum, the causes of which were confirmed by clinical and surgical procedure at Presbyterian Medical Center from January, 1977 to July, 1981 were reviewed radiologically. The results were as follows: 1. Perforation of duodenal ulcer (46/112: 41.1%), stomach ulcer (22/112: 19.6%), and stomach cancer (11/112: 9.8%) were the three most common causes of spontaneous penumoperitoneum. These were 70.5% of all causes. 2. The most common site of free gas was both subdiaphragmatic areas (46: 41.1%). Others were Rt. subdiaphragmatic only (31: 27.7%), both subdiaphragmatic with subhepatic (16: 14.3%), Rt. subdiaphragmatic with subhepatic (7: 6.2%), Rt. subdiaphragmatic only (5: 4.4%), diffuse in abdomen (4: 3.6%), and subhepatic only (3: 2.7%). So 92.0% (103/112) were located in RUQ. 3. The radiological shape of free gas was classified: crescent (52: 46.4%) of small amount; half-moon (21: 18.8%) of moderate amount; large or diffuse (39: 34.8%) of large amount.4. The age between 31 and 60 occupied 69.1% (77/112), and male was predominant (5.2 times). 5. The patient's position showing free air most frequently was erect

  17. A Case of Multiple Spontaneous Keloid Scars

    Directory of Open Access Journals (Sweden)

    Abdulhadi Jfri


    Full Text Available Keloid scars result from an abnormal healing response to cutaneous injury or inflammation that extends beyond the borders of the original wound. Spontaneous keloid scars forming in the absence of any previous trauma or surgical procedure are rare. Certain syndromes have been associated with this phenomenon, and few reports have discussed the evidence of single spontaneous keloid scar, which raises the question whether they are really spontaneous. Here, we present a 27-year-old mentally retarded single female with orbital hypertelorism, broad nasal bridge, repaired cleft lip and high-arched palate who presented with progressive multiple spontaneous keloid scars in different parts of her body which were confirmed histologically by the presence of typical keloidal collagen. This report supports the fact that keloid scars can appear spontaneously and are possibly linked to a genetic factor. Furthermore, it describes a new presentation of spontaneous keloid scars in the form of multiple large lesions in different sites of the body.

  18. Spontaneity of communication in individuals with autism. (United States)

    Chiang, Hsu-Min; Carter, Mark


    This article provides an examination of issues related to spontaneity of communication in children with autism. Deficits relating to spontaneity or initiation are frequently reported in individuals with autism, particularly in relation to communication and social behavior. Nevertheless, spontaneity is not necessarily clearly conceptualized or measured. Several approaches to conceptualization of communicative spontaneity are examined with a particular focus on the continuum model and how it might be practically applied. A range of possible explanations for deficits in spontaneity of communication in children with autism is subsequently explored, including external factors (highly structured teaching programs, failure to systematically instruct for spontaneity) and intrinsic characteristics (intellectual disability, stimulus overselectivity, weak central coherence). Possible implications for future research are presented.

  19. Autoimmune Demyelinating Polyneuropathy as a Manifestation of Chronic Graft-versus-Host Disease after Adult Cord Blood Transplantation in a Patient with Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Fredrick Hogan


    Full Text Available Immune mediated demyelinating disease after allogeneic stem cell transplantation is a rare entity with unclear etiology. Acute inflammatory demyelinating polyneuropathy (AIDP has been reported after related and adult unrelated allogeneic stem cell transplantation but no such case has been reported after unrelated cord blood transplantation. We hereby present the first case of AIDP after double umbilical cord blood transplantation (DUCBT. A 55-year-old man with chronic lymphocytic leukemia (CLL received a cord blood transplant for relapsed refractory disease with high risk cytogenetics. On day 221, patient presented with skin rash, tingling in both lower extremites, and ascending paralysis that progressed rapidly over the course of 2 days. The workup resulted in a diagnosis of AIDP and administration of intravenous immunoglobulins plus steroids was initiated. Motor and sensory powers were fully recovered and his chronic GVHD was managed for several months with single agent sirolimus.

  20. Outcomes of phacoemulsification in patients with chronic ocular graft-versus-host disease. (United States)

    Saboo, Ujwala S; Amparo, Francisco; Shikari, Hasanain; Jurkunas, Ula V; Dana, Reza


    The purpose of this study was to evaluate the outcomes of phacoemulsification in patients with ocular graft-versus-host disease (GVHD). The occurrence of cataracts, cataract surgery, and its outcomes were analyzed in the medical records of 229 patients (458 eyes) with ocular GVHD. Outcome measures included pre- and postoperative corrected distance visual acuity (CDVA) and the rate of postoperative complications. Of the 458 eyes evaluated, 58 were pseudophakic; from the 400 phakic eyes, 238 (59 %) presented with cataracts and 62 (26 %) underwent cataract surgery. Analysis of postoperative complications and visual outcomes at 1 month was performed in 51 eyes in which detailed surgical and immediate postoperative records were available. Preoperatively, the mean CDVA was 0.67 ± 0.57 LogMAR (Snellen 20/93), improving postoperatively to 0.17 ± 0.18 (Snellen 20/29) at 1 month (P < 0.0001), and to 0.13 ± 0.14 (Snellen 20/26) by the final follow-up visit (P < 0.0001). Postoperative complications included corneal epithelial defects (8 %), filamentary keratitis (6 %), worsening of corneal epitheliopathy (16 %), posterior capsular opacification (18 %), and cystoid macular edema (4 %). A corrected distance visual acuity of 20/30 or better was achieved in 87 % of the eyes; suboptimal CDVA improvement was attributable to severe ocular surface disease, pre-existing advanced glaucoma, and prior macular surgery. Phacoemulsification in patients with chronic ocular GVHD is a safe and efficacious procedure resulting in significant visual improvement. Overall, postoperative adverse events responded well to timely management.

  1. Jupiter scleral lenses in the management of chronic graft versus host disease. (United States)

    Schornack, Muriel M; Baratz, Keith H; Patel, Sanjay V; Maguire, Leo J


    To describe the use of the Jupiter scleral contact lens (Medlens Innovations, Front Royal, VA or Essilor Contact Lens, Inc., Dallas, TX) in the management of ocular manifestations of chronic graft versus host disease (cGVHD). This study is a retrospective case series. Five consecutive patients with severe keratoconjunctivitis sicca (KCS) associated with cGVHD that could not be adequately managed with conventional therapy were evaluated for scleral contact lens wear between January and December 2007. All patients were evaluated with lenses from the standard 18.2 mm Jupiter B diagnostic fitting set. If lenses of standard design failed to provide adequate fit, custom lenses were designed. Three outcome measures were evaluated: the patient's ability to tolerate and successfully handle the lenses, improvement in symptoms of KCS, and improvement in visual acuity. All 5 patients (10 eyes) were successfully fit with Jupiter scleral lenses. Six eyes of 3 patients were successfully fit with lenses of standard design. Standard parameters were altered to achieve adequate fit in 4 eyes of 2 patients. All patients reported subjective improvements in comfort with Jupiter scleral lenses, and best-corrected vision improved in 7 of the 10 eyes fit within the first several months of contact lens wear. The remaining 3 eyes maintained the visual acuity measured before scleral lens wear (20/20 in 2 eyes, 20/40 in 1 eye). Duration of follow-up ranged from 4 to 14 months. Jupiter scleral lenses can relieve symptoms of KCS and may improve vision in patients with cGVHD.

  2. Spontaneous cryptococcal peritonitis in cirrhotic patients.

    Directory of Open Access Journals (Sweden)

    Sungkanuparph S


    Full Text Available Spontaneous bacterial peritonitis is a common complication in patients with cirrhosis and ascites. However, spontaneous peritonitis caused by Cryptococcus neoformans is uncommon. Delayed diagnosis of cryptococcal peritonitis often results in death. We describe three cases of spontaneous cryptococcal peritonitis in patients with decompensated cirrhosis. One case had associated symptomatic human immunodeficiency virus infection. Clinical awareness of this entity may lead to the early diagnosis and proper treatment.

  3. Spontaneous Intracranial Hypotension without Orthostatic Headache

    Directory of Open Access Journals (Sweden)

    Tülay Kansu


    Full Text Available We report 2 cases of spontaneous intracranial hypotension that presented with unilateral abducens nerve palsy, without orthostatic headache. While sixth nerve palsies improved without any intervention, subdural hematoma was detected with magnetic resonance imaging. We conclude that headache may be absent in spontaneous intracranial hypotension and spontaneous improvement of sixth nerve palsy can occur, even after the development of a subdural hematoma

  4. Spontaneous renal hematoma - a case report

    International Nuclear Information System (INIS)

    Obrzut, M.; Obrzut, M.; Homa, J.; Obrzut, B.


    Spontaneous pararenal hematoma is a rare pathology most frequently coexisting with renal tumours, vascular anomalies and inflammatory processes. In some cases one cannot establish its etiology. The paper describes a case of a 58-year-old man with a spontaneous pararenal hematoma and presents a diagnostic algorithm. Ultrasonography and CT play an important role in diagnostics of spontaneous pararenal haemorrhages. These methods enable a precise evaluation of size and location of hematoma and its evolution. (author)

  5. Biomarkers of spontaneous preterm birth

    DEFF Research Database (Denmark)

    Polettini, Jossimara; Cobo, Teresa; Kacerovsky, Marian


    predictors of pregnancy outcome. This systematic review was conducted to synthesize the knowledge on PTB biomarkers identified using multiplex analysis. Three electronic databases (PubMed, EMBASE and Web of Science) were searched for studies in any language reporting the use of multiplex assays for maternal......Despite decades of research on risk indicators of spontaneous preterm birth (PTB), reliable biomarkers are still not available to screen or diagnose high-risk pregnancies. Several biomarkers in maternal and fetal compartments have been mechanistically linked to PTB, but none of them are reliable......) followed by MIP-1β, GM-CSF, Eotaxin, and TNF-RI (two studies) were reported more than once in maternal serum. However, results could not be combined due to heterogeneity in type of sample, study population, assay, and analysis methods. By this systematic review, we conclude that multiplex assays...

  6. Spontaneous Strategies in Innovation Networks

    DEFF Research Database (Denmark)

    Plesner, Ursula; Husted, Emil Krastrup

    and a site ontology, we show how physical sites and objects become constitutive of the inside of virtual worlds through innovation processes. This argument is in line with ANT’s perspective on strategy, where sites and objects are considered a strategically relevant resource in the innovation process...... of materiality in relation to the organization and structuring of virtual worlds. We examine various innovation processes in five Danish entrepreneurial companies where actors continuously struggle to stabilize virtual worlds as platforms for professional communication. With inspiration from actor-network theory....... Empirically, the analysis is founded on descriptive accounts from the five entrepreneurs. By highlighting the spontaneous strategies described by actors, we show how sites and objects are actively used as an element in their strategy, and also how the sites and objects end up facilitating new ways of thinking...

  7. Recurrent spontaneous attacks of dizziness. (United States)

    Lempert, Thomas


    This article describes the common causes of recurrent vertigo and dizziness that can be diagnosed largely on the basis of history. Ninety percent of spontaneous recurrent vertigo and dizziness can be explained by six disorders: (1) Ménière disease is characterized by vertigo attacks, lasting 20 minutes to several hours, with concomitant hearing loss, tinnitus, and aural fullness. Aural symptoms become permanent during the course of the disease. (2) Attacks of vestibular migraine may last anywhere from minutes to days. Most patients have a previous history of migraine headaches, and many experience migraine symptoms during the attack. (3) Vertebrobasilar TIAs affect older adults with vascular risk factors. Most attacks last less than 1 hour and are accompanied by other symptoms from the posterior circulation territory. (4) Vestibular paroxysmia is caused by vascular compression of the eighth cranial nerve. It manifests itself with brief attacks of vertigo that recur many times per day, sometimes with concomitant cochlear symptoms. (5) Orthostatic hypotension causes brief episodes of dizziness lasting seconds to a few minutes after standing up and is relieved by sitting or lying down. In older adults, it may be accompanied by supine hypertension. (6) Panic attacks usually last minutes, occur in specific situations, and are accompanied by choking, palpitations, tremor, heat, and anxiety. Less common causes of spontaneous recurrent vertigo and dizziness include perilymph fistula, superior canal dehiscence, autoimmune inner ear disease, otosclerosis, cardiac arrhythmia, and medication side effects. Neurologists need to venture into otolaryngology, internal medicine, and psychiatry to master the differential diagnosis of recurrent dizziness.

  8. Crows spontaneously exhibit analogical reasoning. (United States)

    Smirnova, Anna; Zorina, Zoya; Obozova, Tanya; Wasserman, Edward


    Analogical reasoning is vital to advanced cognition and behavioral adaptation. Many theorists deem analogical thinking to be uniquely human and to be foundational to categorization, creative problem solving, and scientific discovery. Comparative psychologists have long been interested in the species generality of analogical reasoning, but they initially found it difficult to obtain empirical support for such thinking in nonhuman animals (for pioneering efforts, see [2, 3]). Researchers have since mustered considerable evidence and argument that relational matching-to-sample (RMTS) effectively captures the essence of analogy, in which the relevant logical arguments are presented visually. In RMTS, choice of test pair BB would be correct if the sample pair were AA, whereas choice of test pair EF would be correct if the sample pair were CD. Critically, no items in the correct test pair physically match items in the sample pair, thus demanding that only relational sameness or differentness is available to support accurate choice responding. Initial evidence suggested that only humans and apes can successfully learn RMTS with pairs of sample and test items; however, monkeys have subsequently done so. Here, we report that crows too exhibit relational matching behavior. Even more importantly, crows spontaneously display relational responding without ever having been trained on RMTS; they had only been trained on identity matching-to-sample (IMTS). Such robust and uninstructed relational matching behavior represents the most convincing evidence yet of analogical reasoning in a nonprimate species, as apes alone have spontaneously exhibited RMTS behavior after only IMTS training. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Lessons in IBD Pathogenesis from New Animal Models of Spontaneous Colitis

    Directory of Open Access Journals (Sweden)

    R Balfour Sartor


    Full Text Available The recent explosion of transgenic and targeted gene deleted (knockout [KO] rodents has yielded a number of new animal models of spontaneous, chronic intestinal inflammation that have provided novel insights into the pathogenesis of human inflammatory bowel disease (IBD. Spontaneous colitis resulting from deletion of genes encoding key immunoregulatory cytokines (interleukin [IL]-2, IL-10 and transforming growth factor [TGF]-beta and T cell receptors (TCRs demonstrates that an intact mucosal immune response prevents colitis. The TCR KO model incriminates B lymphocytes in spontaneous colonic inflammation – TCR KO with intact B cells causes colitis, but simultaneous deletion of T and B cells does not. This model and induction of colitis in severe combined immunodeficient (SCID mice by constitution with one T cell subset (CD45RHhi, but prevention by addition of the CD45RBlo subset, strongly suggest that T cell subsets down-regulate inflammation in the normal, immunocompetent host. An essential role for normal luminal bacteria in induction and perpetuation of enterocolitis is provided by the absence of chronic intestinal inflammation in germ-free (sterile IL-2 KO mice and human leukocyte antigen (HLA-B27 transgenic rats, and attenuated inflammation in IL-2 and IL-10 KO mice raised under specific pathogen-free conditions. The fundamental role of host genetic susceptibility in chronic intestinal inflammation and systemic manifestations is established by development of spontaneous colitis and perianal inflammation in C3H/HeJ Bir substrain mice and HLA-B27 transgenic rats.

  10. Stabiliteit spontane taal bij chronische milde afasie

    NARCIS (Netherlands)

    Wolthuis, Nienke; Mendez Orellana, Carolina; Nouwens, Femke; Jonkers, Roel; Visch-Brink, Evy; Bastiaanse, Roelien


    In aphasia, an analysis of spontaneous speech provides opportunities to establish the linguistic and communicative abilities, to create suitable therapy plans and to measure language progress. The current study investigated the stability of spontaneous speech within an interview of ten mild aphasic

  11. Spontaneously broken abelian gauge invariant supersymmetric model

    International Nuclear Information System (INIS)

    Mainland, G.B.; Tanaka, K.

    A model is presented that is invariant under an Abelian gauge transformation and a modified supersymmetry transformation. This model is broken spontaneously, and the interplay between symmetry breaking, Goldstone particles, and mass breaking is studied. In the present model, spontaneously breaking the Abelian symmetry of the vacuum restores the invariance of the vacuum under a modified supersymmetry transformation. (U.S.)

  12. Spontaneous Achilles tendon rupture in alkaptonuria | Mohammed ...

    African Journals Online (AJOL)

    Spontaneous Achilles tendon ruptures are uncommon. We present a 46-year-old man with spontaneous Achilles tendon rupture due to ochronosis. To our knowledge, this has not been previously reported in Sudan literature. The tendon of the reported patient healed well after debridement and primary repairs.

  13. Spontaneous rupture of choledochal cyst: case report

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Ho Seob; Nam, Kyung Jin; Lee, Jin Hwa; Kim, Chan Sung; Choi, Jong Cheol; Oh, Jong Young [Dong-a University College of Medicine, Pusan (Korea, Republic of)


    Spontaneous rupture of a choledochal cyst leading to biliary peritonitis is a rare complication which can be fatal if not promptly diagnosed. The authors report the ultrasound and CT findings of two cases of spontaneous choledochal cystic rupture and the biliary peritonitis which ensued.

  14. Spontaneity and Equilibrium II: Multireaction Systems (United States)

    Raff, Lionel M.


    The thermodynamic criteria for spontaneity and equilibrium in multireaction systems are developed and discussed. When N reactions are occurring simultaneously, it is shown that G and A will depend upon N independent reaction coordinates, ?a (a = 1,2, ..., N), in addition to T and p for G or T and V for A. The general criteria for spontaneity and…

  15. Early pregnancy angiogenic markers and spontaneous abortion

    DEFF Research Database (Denmark)

    Andersen, Louise B; Dechend, Ralf; Karumanchi, S Ananth


    BACKGROUND: Spontaneous abortion is the most commonly observed adverse pregnancy outcome. The angiogenic factors soluble Fms-like kinase 1 and placental growth factor are critical for normal pregnancy and may be associated to spontaneous abortion. OBJECTIVE: We investigated the association between...... maternal serum concentrations of soluble Fms-like kinase 1 and placental growth factor, and subsequent spontaneous abortion. STUDY DESIGN: In the prospective observational Odense Child Cohort, 1676 pregnant women donated serum in early pregnancy, gestational week ..., interquartile range 71-103). Concentrations of soluble Fms-like kinase 1 and placental growth factor were determined with novel automated assays. Spontaneous abortion was defined as complete or incomplete spontaneous abortion, missed abortion, or blighted ovum

  16. Antiviral therapy of chronic hepatitis B.


    Zoulim, Fabien


    Treatment of chronic hepatitis B remains a clinical challenge. Long-term viral suppression is a major goal of antiviral therapy to improve the clinical outcome of the patients. Antiviral treatment of chronic hepatitis B relies currently on immune modulators such as interferon alpha and its pegylated form, and viral polymerase inhibitors. Because of the slow kinetics of viral clearance and the spontaneous viral genome variability, viral mutants resistant to nucleoside analogs may be selected. ...

  17. The (perceived) meaning of spontaneous thoughts. (United States)

    Morewedge, Carey K; Giblin, Colleen E; Norton, Michael I


    Spontaneous thoughts, the output of a broad category of uncontrolled and inaccessible higher order mental processes, arise frequently in everyday life. The seeming randomness by which spontaneous thoughts arise might give people good reason to dismiss them as meaningless. We suggest that it is precisely the lack of control over and access to the processes by which they arise that leads people to perceive spontaneous thoughts as revealing meaningful self-insight. Consequently, spontaneous thoughts potently influence judgment. A series of experiments provides evidence supporting two hypotheses. First, we hypothesize that the more a thought is perceived to be spontaneous, the more it is perceived to provide meaningful self-insight. Participants perceived more spontaneous kinds of thought (e.g., intuition) to reveal greater self-insight than did more controlled kinds of thought in Study 1 (e.g., deliberation). In Studies 2 and 3, participants perceived thoughts with the same content and target to reveal greater self-insight when spontaneously rather than deliberately generated (i.e., childhood memories and impressions formed). Second, we hypothesize that the greater self-insight attributed to thoughts that are (perceived to be) spontaneous leads those thoughts to more potently influence judgment. Participants felt more sexually attracted to an attractive person whom they thought of spontaneously than deliberately in Study 4, and reported their commitment to a current romantic relationship would be more affected by the spontaneous rather than deliberate recollection of a good or bad experience with their romantic partner in Study 5. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  18. Recurrent Corneal Perforation due to Chronic Graft versus Host Disease; a Clinicopathologic Report. (United States)

    Mohammadpour, Mehrdad; Maleki, Siamak; Hashemi, Hassan; Beheshtnejad, Amir Houshang


    To describe a case of chronic graft versus host disease (GVHD) leading to severe dry eye and recurrent corneal perforation in both eyes, its stepwise management and histopathological reports. A 22-year-old woman with a history of thalassemia and subsequent high-dose chemotherapy followed by allogeneic bone marrow transplant (BMT) was referred to Farabi Eye Hospital. Despite aggressive medical and surgical intervention, corneal vascularization in her right eye progressed and led to corneal perforation. Cyanoacrylate glue was applied to seal the perforation, however it recurred. Multilayer amniotic membrane transplantation (AMT) was performed to seal the corneal perforation, which was effective for a short period. Subsequently, the corneal perforation recurred and penetrating keratoplasty was performed. After a few months deep vascularization and descemetocele occurred in the fellow left eye and the patient finally underwent therapeutic lamellar keratoplasty. Patients with GVHD are at risk of severe dry eye and subsequent corneal vascularization. Recurrent and recalcitrant corneal perforation resistant to cyanoacrylate glue and multilayer AMT may occur. Proper systemic and ocular management alongside close collaboration with the hematologist is strongly recommended to control the condition.

  19. Emerging technologies for oral diagnostics: lessons from chronic graft-versus-host disease (United States)

    Mays, Jacqueline W.; Ambatipudi, Kiran S.; Bassim, Carol W.; Melvin, James E.


    Saliva is a protein-rich oral fluid that contains information about systemic and oral-specific disease pathogenesis and diagnosis. Technologies are emerging to improve detection of protein components of human saliva for use not only in biomarker discovery, but also for the illumination of pathways involved in oral disease. These include the optimization of liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) analysis of saliva in health and disease. Downstream of saliva component identification and validation comes the complex task of connecting salivary proteomic data to biological function, disease state, and other clinical patient information in a meaningful way. Augmentation of database information with biological expertise is crucial for effective analysis of potential biomarkers and disease pathways in order to improve diagnosis and identify putative therapeutic targets. This presentation will use LC-MS/MS analysis of saliva from chronic Graft-versus-Host disease (cGVHD) patients to illustrate these principles, and includes a discussion of the complex clinical and diagnostic issues related to proteomics and biomarker research in cGVHD.

  20. Spontaneous Metacognition in Rhesus Monkeys. (United States)

    Rosati, Alexandra G; Santos, Laurie R


    Metacognition is the ability to think about thinking. Although monitoring and controlling one's knowledge is a key feature of human cognition, its evolutionary origins are debated. In the current study, we examined whether rhesus monkeys (Macaca mulatta; N = 120) could make metacognitive inferences in a one-shot decision. Each monkey experienced one of four conditions, observing a human appearing to hide a food reward in an apparatus consisting of either one or two tubes. The monkeys tended to search the correct location when they observed this baiting event, but engaged in information seeking-by peering into a center location where they could check both potential hiding spots-if their view had been occluded and information seeking was possible. The monkeys only occasionally approached the center when information seeking was not possible. These results show that monkeys spontaneously use information about their own knowledge states to solve naturalistic foraging problems, and thus provide the first evidence that nonhumans exhibit information-seeking responses in situations with which they have no prior experience. © The Author(s) 2016.

  1. Spontaneous flocking in human groups. (United States)

    Belz, Michael; Pyritz, Lennart W; Boos, Margarete


    Flocking behaviour, as a type of self-organised collective behaviour, is described as the spatial formation of groups without global control and explicit inter-individual recruitment signals. It can be observed in many animals, such as bird flocks, shoals or herds of ungulates. Spatial attraction between humans as the central component of flocking behaviour has been simulated in a number of seminal models but it has not been detected experimentally in human groups so far. The two other sub-processes of this self-organised collective movement - collision avoidance and alignment - are excluded or held constant respectively in this study. We created a computer-based, multi-agent game where human players, represented as black dots, moved on a virtual playground. The participants were deprived of social cues about each other and could neither communicate verbally nor nonverbally. They played two games: (1) Single Game, where other players were invisible, and (2) Joint Game, where each player could see players' positions in a local radius around himself/herself. We found that individuals approached their neighbours spontaneously if their positions were visible, leading to less spatial dispersion of the whole group compared to moving alone. We conclude that human groups show the basic component of flocking behaviour without being explicitly instructed or rewarded to do so. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Clock frequency estimation under spontaneous emission (United States)

    Qin, Xi-Zhou; Huang, Jia-Hao; Zhong, Hong-Hua; Lee, Chaohong


    We investigate the quantum dynamics of a driven two-level system under spontaneous emission and its application in clock frequency estimation. By using the Lindblad equation to describe the system, we analytically obtain its exact solutions, which show three different regimes: Rabi oscillation, damped oscillation, and overdamped decay. From the analytical solutions, we explore how the spontaneous emission affects the clock frequency estimation. We find that under a moderate spontaneous emission rate, the transition frequency can still be inferred from the Rabi oscillation. Our results enable potential practical applications in frequency measurement and quantum control under decoherence.

  3. Spontaneous Bacterial Peritonitis in Subclinical Hypothyroidism

    Directory of Open Access Journals (Sweden)

    Dalip Gupta


    Full Text Available Hypothyroidism is an uncommon cause of ascites. Here we describe a case of a 75 year-old female patient with spontaneous bacterial peritonitis and subclinical hypothyroidism that resolved with thyroid replacement and antibiotic therapy respectively. Ascitic fluid analysis revealed a gram-positive bacterium on gram staining. A review of the literature revealed just one other reported case of myxoedema ascites with concomitant spontaneous bacterial peritonitis and no case has till been reported of spontaneous bacterial peritonitis in subclinical hypothyroidism.

  4. Spontaneous regression of an invasive thymoma. (United States)

    Yutaka, Yojiro; Omasa, Mitsugu; Shikuma, Kei; Okuda, Masato; Taki, Toshihiko


    Although there are many reports of spontaneous regression of noninvasive thymoma, there are no reports of spontaneous regression of an invasive thymoma. Moreover, the mechanism of the spontaneous regression is still unknown. The present case concerns a 47-year-old man who presented with chest pain. Computed tomography (CT) showed a large anterior mediastinal mass with left pleural effusion that occluded the innominate vein. The tissue obtained by video-assisted thoracic surgery suggested a diagnosis of invasive thymic carcinoma. One month later CT showed prominent regression of the tumor, and the tumor was completely resected. On pathology, the diagnosis was thymoma type B3.

  5. Spontaneous Dissection of the Superior Mesenteric Artery

    International Nuclear Information System (INIS)

    Sheldon, Patrick J.; Esther, James B.; Sheldon, Elana L.; Sparks, Steven R.; Brophy, David P.; Oglevie, Steven B.


    Spontaneous dissection of the superior mesenteric artery (SMA) is a rare occurrence, especially when not associated with aortic dissection. Currently, only 28 cases appear to have been reported. Due to the scarcity of cases in the literature, the natural history of isolated, spontaneous SMA dissection is unclear. CT has been reported to be useful for the initial diagnosis of SMA dissection [2-5]. We present two recent cases of spontaneous SMA dissection in which enhanced spiral CT was instrumental in following the disease process and guiding clinical decision making

  6. Does Spontaneous Favorability to Power (vs. Universalism) Values Predict Spontaneous Prejudice and Discrimination? (United States)

    Souchon, Nicolas; Maio, Gregory R; Hanel, Paul H P; Bardin, Brigitte


    We conducted five studies testing whether an implicit measure of favorability toward power over universalism values predicts spontaneous prejudice and discrimination. Studies 1 (N = 192) and 2 (N = 86) examined correlations between spontaneous favorability toward power (vs. universalism) values, achievement (vs. benevolence) values, and a spontaneous measure of prejudice toward ethnic minorities. Study 3 (N = 159) tested whether conditioning participants to associate power values with positive adjectives and universalism values with negative adjectives (or inversely) affects spontaneous prejudice. Study 4 (N = 95) tested whether decision bias toward female handball players could be predicted by spontaneous attitude toward power (vs. universalism) values. Study 5 (N = 123) examined correlations between spontaneous attitude toward power (vs. universalism) values, spontaneous importance toward power (vs. universalism) values, and spontaneous prejudice toward Black African people. Spontaneous positivity toward power (vs. universalism) values was associated with spontaneous negativity toward minorities and predicted gender bias in a decision task, whereas the explicit measures did not. These results indicate that the implicit assessment of evaluative responses attached to human values helps to model value-attitude-behavior relations. © 2016 The Authors. Journal of Personality Published by Wiley Periodicals, Inc.

  7. Clinical features of ten cases of isolated spontaneous dissection of the superior mesenteric artery

    International Nuclear Information System (INIS)

    Kozuki, Akihito; Shinozaki, Hiroharu; Takasato, Fumika; Kobayashi, Kenji; Kase, Kenichi


    Isolated spontaneous dissection of the superior mesenteric artery (SMA) is a comparatively rare disease, and symptoms vary from acute to chronic abdominal pain to no symptoms. However, it is difficult to diagnose; there is no consensus about medical treatment and the long-term consequences. Isolated spontaneous dissection of the SMA was believed to be a rare disease that required conventional surgery for treatment; however reports of SMA dissection have increased with the progression of diagnostic imaging, and surgery may not always be required. We reviewed 10 cases of isolated spontaneous dissection of the SMA that we experienced between January 1998 and December 2008. We performed conservative medical treatment with anticoagulants in 5 cases, advised bed rest in 4 cases, and performed endovascular treatment in 1 case. None of the cases needed surgery for treatment. There were 3 cases that required continuous administration of long-term anticoagulants or antiplatelet agents. There were no recurrences in a 4-year average observation period. (author)

  8. Clinical features of spontaneous hypothyroidism in one physician’s practice in Jamaica

    Directory of Open Access Journals (Sweden)

    Rosemarie A Wright-Pascoe


    Full Text Available Rosemarie A Wright-PascoeDepartment of Medicine, The University of the West Indies, Kingston, JamaicaObjective: To describe the clinical characteristics of patients with spontaneous hypothyroidism, the frequency of chronic autoimmune thyroiditis, and the thyroid autoantibody most often associated with this condition in a referral population in Jamaica.Methods: A retrospective study of all cases referred to the author’s endocrinology practice from 1995 to 2005 with a diagnosis of spontaneous hypothyroidism was undertaken. The clinical history, examination findings, biochemical test results, thyroid autoimmune antibodies, and imaging data were reviewed.Results: Spontaneous primary hypothyroidism was correctly diagnosed in 53 subjects. Fifty of the patients were females and three were males. Mean age was 43.3 years (range 12–82 years; 24.4% of the patients had a family member with thyroid disease; 27.1% presented because of a goiter; and 54.2% because of symptoms suggestive of hypothyroidism. The thyroid was palpable in 56.3% and thyroid ultrasound was consistent with Hashimoto’s thyroiditis on 64% of occasions. Only 8% of the patients had the atrophic variant of hypothyroidism. Antithyroid peroxidase and antithyroglobulin antibody were positive in 75.8% and 37.5% of patients, respectively. Chronic autoimmune thyroiditis was confirmed in 78.8% of cases.Conclusion: In these cases in Jamaica, spontaneous hypothyroidism was predominantly a female disorder. Chronic autoimmune thyroiditis was the commonest cause, and antithyroid peroxidase antibody was the thyroid antibody most likely to be positive in this population.Keywords: spontaneous hypothyroidism, Jamaican, thyroid autoantibodies, L-thyroxine, autoimmune thyroiditis, Hashimoto’s thyroiditis

  9. Right Diaphragm Spontaneous Rupture: A Surgical Approach

    Directory of Open Access Journals (Sweden)

    Duilio Divisi


    Full Text Available We present a case of spontaneous rupture of the diaphragm, characterized by nonspecific symptoms. The rapid diagnosis and appropriate surgical approach led to a positive resolution of the pathology.

  10. Spontaneous cecal perforation secondary to acute fulminant ...

    African Journals Online (AJOL)

    Spontaneous cecal perforation secondary to acute fulminant gastroenteritis: report of a rare case. Duvuru Ram, Vilvapathy S. Karthikeyan, Sarath C. Sistla, Sheik M. Ali, Parnandi Sridhar, Nagarajan Rajkumar ...

  11. Spontaneous Trait Inferences on Social Media. (United States)

    Levordashka, Ana; Utz, Sonja


    The present research investigates whether spontaneous trait inferences occur under conditions characteristic of social media and networking sites: nonextreme, ostensibly self-generated content, simultaneous presentation of multiple cues, and self-paced browsing. We used an established measure of trait inferences (false recognition paradigm) and a direct assessment of impressions. Without being asked to do so, participants spontaneously formed impressions of people whose status updates they saw. Our results suggest that trait inferences occurred from nonextreme self-generated content, which is commonly found in social media updates (Experiment 1) and when nine status updates from different people were presented in parallel (Experiment 2). Although inferences did occur during free browsing, the results suggest that participants did not necessarily associate the traits with the corresponding status update authors (Experiment 3). Overall, the findings suggest that spontaneous trait inferences occur on social media. We discuss implications for online communication and research on spontaneous trait inferences.

  12. Spontane abdominale arteriovenøse fistler

    DEFF Research Database (Denmark)

    Flarup, S; Lindholt, Jes Sanddal


    Spontaneous arteriovenous fistulas between major abdominal vessels (AAVF) complicates about 1% of abdominal aortic aneurysms. AAVF produces severe circulatory disturbances with high operative mortality. Preoperative diagnosis is important but difficult due to the varied nature of presentation. Fo...

  13. Depressive disorder and grief following spontaneous abortion. (United States)

    Kulathilaka, Susil; Hanwella, Raveen; de Silva, Varuni A


    Abortion is associated with moderate to high risk of psychological problems such as depression, use of alcohol or marijuana, anxiety, depression and suicidal behaviours. The increased risk of depression after spontaneous abortion in Asian populations has not been clearly established. Only a few studies have explored the relationship between grief and depression after abortion. A study was conducted to assess the prevalence and risk factors of depressive disorder and complicated grief among women 6-10 weeks after spontaneous abortion and compare the risk of depression with pregnant women attending an antenatal clinic. Spontaneous abortion group consisted of women diagnosed with spontaneous abortion by a Consultant Obstetrician. Women with confirmed or suspected induced abortion were excluded. The comparison group consisted of randomly selected pregnant, females attending the antenatal clinics of the two hospitals. Diagnosis of depressive disorder was made according to ICD-10 clinical criteria based on a structured clinical interview. This assessment was conducted in both groups. The severity of depressive symptoms were assessed using the Patients Health Questionnaire (PHQ-9). Grief was assessed using the Perinatal Grief Scale which was administered to the women who had experienced spontaneous abortion. The sample consisted of 137 women in each group. The spontaneous abortion group (mean age 30.39 years (SD = 6.38) were significantly older than the comparison group (mean age 28.79 years (SD = 6.26)). There were more females with ≥10 years of education in the spontaneous abortion group (n = 54; SD = 39.4) compared to the comparison group (n = 37; SD = 27.0). The prevalence of depression in the spontaneous abortion group was 18.6 % (95 CI, 11.51-25.77). The prevalence of depression in the comparison group was 9.5 % (95 CI, 4.52-14.46). Of the 64 women fulfilling criteria for grief, 17 (26.6 %) also fulfilled criteria for a depressive episode. The relative risk of

  14. Association between single-nucleotide polymorphisms and early spontaneous hepatitis B virus e antigen seroconversion in children


    Komatsu, Haruki; Murakami, Jun; Inui, Ayano; Tsunoda, Tomoyuki; Sogo, Tsuyoshi; Fujisawa, Tomoo


    Background The disease progression following hepatitis B virus (HBV) infection is associated with single-nucleotide polymorphisms (SNPs). However, the role of SNPs in chronic HBV infection in children remains unclear. Here, we investigate the association between SNPs and early spontaneous hepatitis B e antigen (HBeAg) seroconversion in children with chronic hepatitis B infection. Methods This was a retrospective cohort study. We genotyped seven SNPs in the following genes, interleukin (IL)-10...

  15. Postmenopausal spontaneous uterine perforation: Case report (United States)

    İşlek Seçen, Elçin; Ağış, Hilal; Altunkaya, Canan; Avşar, Ayşe Filiz


    Spontaneous uterine rupture and generalized peritonitis caused by pyometra occurs rarely with high morbidity and mortality. A correct and definite diagnosis can be made with laparotomy or laparoscopy. The clinical findings of perforated pyometra are similar to perforation of the gastrointestinal tract and gynecologic symptoms are less frequent, which makes preoperative diagnosis difficult. We report a case of a patient aged 82 years who underwent surgery for spontaneous uterine rupture and generalized peritonitis as a result of pyometra. PMID:28913055

  16. Endometriosis-related spontaneous diaphragmatic rupture. (United States)

    Triponez, Frédéric; Alifano, Marco; Bobbio, Antonio; Regnard, Jean-François


    Non-traumatic, spontaneous diaphragmatic rupture is a rare event whose pathophysiology is not known. We report the case of endometriosis-related spontaneous rupture of the right diaphragm with intrathoracic herniation of the liver, gallbladder and colon. We hypothesize that the invasiveness of endometriotic tissue caused diaphragm fragility, which finally lead to its complete rupture without traumatic event. The treatment consisted of a classical management of diaphragmatic rupture, with excision of the endometriotic nodule followed by medical ovarian suppression for six months.

  17. Spontaneous regression of metastatic Merkel cell carcinoma.

    LENUS (Irish Health Repository)

    Hassan, S J


    Merkel cell carcinoma is a rare aggressive neuroendocrine carcinoma of the skin predominantly affecting elderly Caucasians. It has a high rate of local recurrence and regional lymph node metastases. It is associated with a poor prognosis. Complete spontaneous regression of Merkel cell carcinoma has been reported but is a poorly understood phenomenon. Here we present a case of complete spontaneous regression of metastatic Merkel cell carcinoma demonstrating a markedly different pattern of events from those previously published.

  18. Spontaneous intracranial epidural hematoma during rivaroxaban treatment

    Energy Technology Data Exchange (ETDEWEB)

    Ruschel, Leonardo Gilmone; Rego, Felipe Marques Monteiro do; Milano, Jeronimo Buzetti; Jung, Gustavo Simiano; Silva Junior, Luis Fernando; Ramina, Ricardo, E-mail: [Instituto de Neurologia de Curitiba (INC), Curitiba, PR (Brazil)


    According to our research, this is the first case described in the literature of spontaneous intracranial epidural hematoma secondary to the use of Xarelto®. Spontaneous intracranial epidural hematomas are rarely described in the literature. They are associated with infectious diseases of the skull, coagulation disorders, vascular malformations of the dura mater and metastasis to the skull. Long-term post-marketing monitoring and independent reports will probably detect the full spectrum of hemorrhagic complications of the use of rivaroxaban. (author)

  19. Spontaneous intracranial epidural hematoma during rivaroxaban treatment. (United States)

    Ruschel, Leonardo Gilmone; Rego, Felipe Marques Monteiro do; Milano, Jerônimo Buzetti; Jung, Gustavo Simiano; Silva, Luis Fernando; Ramina, Ricardo


    According to our research, this is the first case described in the literature of spontaneous intracranial epidural hematoma secondary to the use of Xareltor. Spontaneous intracranial epidural hematomas are rarely described in the literature. They are associated with infectious diseases of the skull, coagulation disorders, vascular malformations of the dura mater and metastasis to the skull. Long-term post-marketing monitoring and independent reports will probably detect the full spectrum of hemorrhagic complications of the use of rivaroxaban.

  20. Chronic cholecystitis (United States)

    Cholecystitis - chronic ... Most of the time, chronic cholecystitis is caused by repeated attacks of acute (sudden) cholecystitis. Most of these attacks are caused by gallstones in the gallbladder. These ...

  1. Chronic Pain (United States)

    ... pain. Psychotherapy, relaxation and medication therapies, biofeedback, and behavior modification may also be employed to treat chronic pain. × ... pain. Psychotherapy, relaxation and medication therapies, biofeedback, and behavior modification may also be employed to treat chronic pain. ...

  2. Chronic Subdural Hematoma Associated with Acute Biphenotypic Leukemia: Case Report


    Besime Utku; Uygar Utku


    Spontaneous chronic subdural hematoma associated with neoplasm is a rare disorder. A rare case of chronic subdural hematoma associated with acute biphenotypic leukemia presented here. A 78-year-old woman who diagnosed as acute biphenotypic leukemia by hematology was complicated with a large chronic subdural hematoma. She presented to our emergency medicine service of hospital with left-sided weakness. Her non-contrast brain computerized tomography scan showed a non-traumatic right-sided, larg...

  3. Spontaneous intraluminal migration of gossypiboma

    Directory of Open Access Journals (Sweden)

    Sebastian Saji


    Full Text Available Retained surgical mops following surgery is an avoidable but serious complication. They are seldom reported because of medicolegal implications but clinicians need to be aware about varied presentations of this entity to avoid unnecessary morbidity. We report a case of a 28-year-old woman who presented with chronic diarrhea and lower abdominal pain due to intraluminal migration of the surgical mop into the sigmoid colon 6 months after myomectomy of the uterus. The possibility of gossypiboma was suggested by the contrast-enhanced CT scan of the abdomen. Flexible sigmoidosocpy showed the remnants of the mop inside the lumen of the sigmoid colon. She underwent laparotomy and removal of the surgical mop and became completely asymptomatic. Though gossypiboma is rare clinicians should keep it in mind in patients who had undergone laparotomy previously.

  4. Dentate gyrus mossy cells control spontaneous convulsive seizures and spatial memory. (United States)

    Bui, Anh D; Nguyen, Theresa M; Limouse, Charles; Kim, Hannah K; Szabo, Gergely G; Felong, Sylwia; Maroso, Mattia; Soltesz, Ivan


    Temporal lobe epilepsy (TLE) is characterized by debilitating, recurring seizures and an increased risk for cognitive deficits. Mossy cells (MCs) are key neurons in the hippocampal excitatory circuit, and the partial loss of MCs is a major hallmark of TLE. We investigated how MCs contribute to spontaneous ictal activity and to spatial contextual memory in a mouse model of TLE with hippocampal sclerosis, using a combination of optogenetic, electrophysiological, and behavioral approaches. In chronically epileptic mice, real-time optogenetic modulation of MCs during spontaneous hippocampal seizures controlled the progression of activity from an electrographic to convulsive seizure. Decreased MC activity is sufficient to impede encoding of spatial context, recapitulating observed cognitive deficits in chronically epileptic mice. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  5. FEL gain optimisation and spontaneous radiation

    Energy Technology Data Exchange (ETDEWEB)

    Bali, L.M.; Srivastava, A.; Pandya, T.P. [Lucknow Univ. (India)] [and others


    Colson have evaluated FEL gains for small deviations from perfect electron beam injection, with radiation of the same polarisation as that of the wiggler fields. We find that for optimum gain the polarisation of the optical field should be the same as that of the spontaneous emission under these conditions. With a helical wiggler the axial oscillations resulting from small departures from perfect electron beam injection lead to injection dependent unequal amplitudes and phases of the spontaneous radiation in the two transverse directions. Viewed along the axis therefore the spontaneous emission is elliptically polarised. The azimuth of the ellipse varies with the difference of phase of the two transverse components of spontaneous emission but the eccentricity remains the same. With planar wigglers the spontaneous emission viewed in the axial direction is linearly polarised, again with an injection dependent azimuth. For optimum coherent gain of a radiation field its polarisation characteristics must be the same as those of the spontaneous radiation with both types of wiggler. Thus, with a helical wiggler and the data reported earlier, an increase of 10% in the FEL gain at the fundamental frequency and of 11% at the fifth harmonic has been calculated in the small gain per pass limit. Larger enhancements in gain may result from more favourable values of input parameters.

  6. Acute otitis media with spontaneous tympanic membrane perforation. (United States)

    Principi, N; Marchisio, P; Rosazza, C; Sciarrabba, C S; Esposito, S


    The principal aim of this review is to present the current knowledge regarding acute otitis media (AOM) with spontaneous tympanic membrane perforation (STMP) and to address the question of whether AOM with STMP is a disease with specific characteristics or a severe case of AOM. PubMed was used to search for all studies published over the past 15 years using the key words "acute otitis media" and "othorrea" or "spontaneous tympanic membrane perforation". More than 250 articles were found, but only those published in English and providing data on aspects related to perforation of infectious origin were considered. Early Streptococcus pneumoniae infection due to invasive pneumococcal strains, in addition to coinfections and biofilm production due mainly to non-typeable Haemophilus influenzae, seem to be precursors of STMP. However, it is unclear why some children have several STMP episodes during the first years of life that resolve without complications in adulthood, whereas other children develop chronic suppurative otitis media. Although specific aetiological agents appear to be associated with an increased risk of AOM with STMP, further studies are needed to determine whether AOM with STMP is a distinct disease with specific aetiological, clinical and prognostic characteristics or a more severe case of AOM than the cases that occur without STMP. Finally, it is important to identify preventive methods that are useful not only in otitis-prone children with uncomplicated AOM, but also in children with recurrent AOM and those who experience several episodes with STMP.

  7. Late spontaneous recanalization of symptomatic atheromatous internal carotid artery occlusion. (United States)

    Delgado, Montserrat G; Vega, Pedro P; Lahoz, Carlos H; Calleja, Sergio


    Definitive treatment of symptomatic atheromatous internal carotid artery occlusion remains controversial, as far as in rare cases, late spontaneous recanalization has been seen. We consecutively studied 182 patients (January 2003 to August 2012) with an ischemic stroke in the internal carotid artery territory and diagnosis of atheromatous internal carotid artery occlusion during hospitalization. Seven patients presented a late spontaneous recanalization (>3 months) of the internal carotid artery. We described therapeutic attitude according to usual care in these patients. The authors attempt to highlight the unusual condition of recanalization after a symptomatic atheromatous chronic internal carotid artery occlusion. If these patients can be treated similar to patients with asymptomatic carotid pathology, then this needs to be clarified. However, due to the risk of ipsi- and contralateral ischemic strokes, revascularization techniques should be considered in certain cases. More studies are needed to establish the most appropriate therapeutical approach in order to avoid arbitrary treatment of these patients. © The Author(s) 2014 Reprints and permissions:

  8. Spontaneous Fluctuations of PO2 in the Rabbit Somatosensory Cortex. (United States)

    Linsenmeier, Robert A; Aksenov, Daniil P; Faber, Holden M; Makar, Peter; Wyrwicz, Alice M


    In many tissues, PO2 fluctuates spontaneously with amplitudes of a few mmHg. Here we further characterized these oscillations. PO2 recordings were made from the whisker barrel cortex of six rabbits with acutely or chronically placed polarographic electrodes. Measurements were made while rabbits were awake and while anesthetized with isoflurane, during air breathing, and during 100% oxygen inspiration. In awake rabbits, 90% of the power was between 0 and 20 cycles per minute (cpm), not uniformly distributed over this range, but with a peak frequently near 10 cpm. This was much slower than heart or respiratory rhythms and is similar to the frequency content observed in other tissues. During hyperoxia, total power was higher than during air-breathing, and the dominant frequencies tended to shift toward lower values (0-10 cpm). These observations suggest that at least the lower frequency fluctuations represent efforts by the circulation to regulate local PO2. There were no consistent changes in total power during 0.5 or 1.5% isoflurane anesthesia, but the power shifted to lower frequencies. Thus, both hyperoxia and anesthesia cause characteristic, but distinct, changes in spontaneous fluctuations. These PO2 fluctuations may be caused by vasomotion, but other factors cannot be ruled out.

  9. Spontaneous Spondylodiscitis - Epidemiology, Clinical Features, Diagnosis and Treatment

    Directory of Open Access Journals (Sweden)

    Petkova Aneta S.


    Full Text Available Spontaneous spondylodiscitis is a rare but serious infectious disease which is a combination of an inflammatory process, involving one or more adjacent vertebral bodies (spondylitis, the intervertebral discs (discitis and finally - the neighboring neural structures. In most cases the condition is due to a hematogenous infection and can affect all regions of the spinal cord, but it is usually localized in the lumbar area. The most common clinical symptom is a pronounced, constant and increasing nocturnal paravertebral pain, while consequently different degrees of residual neurological symptoms from nerve roots and/or spinal cord may appear. The disease course is chronic and the lack of specific symptoms often prolongs the time between its debut and the diagnosis. This delay in diagnosis determines its potentially high morbidity and mortality. Treatment is conservative in cases with no residual neurological symptoms and consists of antibiotic therapy and immobilization. Surgical treatment is necessary in patients with neurological deficit, spinal instability or drug resistance.

  10. Long-term functional outcome of bilateral spontaneous and simultaneous Achilles tendon ruptures.

    LENUS (Irish Health Repository)

    Ellanti, Prasad


    Bilateral simultaneous ruptures are rare comprising less than 1% of all Achilles tendon ruptures. Risk factors for bilateral ruptures include chronic diseases and medications such as corticosteroids and fluoroquinolones. There is little in the literature on the long-term functional outcome of bilateral Achilles tendon ruptures. This article present a series of 3 cases of simultaneous and spontaneous bilateral Achilles tendon ruptures with a minimum of 5-year follow up suggesting a good functional outcome.

  11. Patient-reported outcomes (PROs) in chronic urticaria

    DEFF Research Database (Denmark)

    Moestrup, Kristian; Ghazanfar, Misbah N; Thomsen, Simon F


    Chronic urticaria is an itching skin disease which persists for more than 6 weeks. Chronic urticaria has great impact on the daily life of the patient, and the fluctuating nature of the symptoms complicates the monitoring and treatment of the disease. Currently, there are no reliable biomarkers...... to identify and measure disease activity in chronic spontaneous urticaria. Consequently, use of patient-reported outcomes (PROs) is crucial when evaluating and monitoring different aspects of chronic urticaria such as disease activity/severity, disease control, and quality of life. We present an overview...... of seven different PROs used in chronic urticaria and highlight their strengths, limitations, and use in clinical practice and research....

  12. Spontaneous manifestation of polycystic kidney disease following separation anxiety in a Persian cat. (United States)

    Hosseininejad, M; Hosseini, F


    A 4-year-old female Persian cat was referred with the history of separation from the owner. There was no clinical sign and everything had been reported as normal during the veterinary checkup just before separation and traveling. The history and clinical signs were fit to separation anxiety when the cat referred to us. Ten days after the diagnosis and starting of the treatment for separation anxiety, the cat was referred again with the clinical signs of chronic renal failure. Further assessments showed an inherited polycystic kidney disease. Spontaneous manifestation of polycystic kidney disease after separation anxiety indicate that this phenomenon may cause the chronic process of polycystic kidney disease to promote.

  13. Extracorporeal photopheresis for the treatment of acute and chronic graft-versus-host disease in adults and children: best practice recommendations from an Italian Society of Hemapheresis and Cell Manipulation (SIdEM) and Italian Group for Bone Marrow Transplantation (GITMO) consensus process. (United States)

    Pierelli, Luca; Perseghin, Paolo; Marchetti, Monia; Messina, Chiara; Perotti, Cesare; Mazzoni, Alessandro; Bacigalupo, Andrea; Locatelli, Franco; Carlier, Paolo; Bosi, Alberto


    Extracorporeal photopheresis (ECP) is an effective treatment for both acute and chronic graft-versus-host disease (GVHD) in children and adults. Despite the large use of this treatment, a large heterogeneity in current application of ECP has been reported so far and recent evidence brought novel issues into some specific topics. Consensus-based recommendations ameliorate the appropriateness in daily clinical practice and, in turn, optimize the use of health care resources. Two Italian scientific societies, the Italian Society of Hemapheresis and Cell Manipulation (SIdEM) and the Italian Group for Bone Marrow Transplantation (GITMO), joined to develop and disseminate recommendations on appropriate application of ECP treatment in patients with GVHD. Accordingly, SIdEM and GITMO named an expert panel that first selected 16 questions that were considered relevant for clinical practice: the questions were subsequently addressed through a revision of the available literature and in consensus meetings. The whole group discussed the proposed recommendations according to the nominal group technique. The above-described approach in turn allowed the panel to agree on 47 practice recommendations. SIdEM and GITMO will disseminate such recommendations to the national transplant centers. In conclusion, SIdEM and GITMO have made a scientific effort to provide a useful tool to physicians involved in the field, thus supporting daily clinical practice, as well as strategic decisions in the setting of ECP treatment of GVHD. © 2013 American Association of Blood Banks.

  14. Spontaneous body movements in spatial cognition

    Directory of Open Access Journals (Sweden)

    Sergiu eTcaci Popescu


    Full Text Available People often perform spontaneous body movements during spatial tasks such as giving complex directions or orienting themselves on maps. How are these spontaneous gestures related to spatial problem-solving? We measured spontaneous movements during a perspective-taking task inspired by map reading. Analyzing the motion data to isolate rotation and translation components of motion in specific geometric relation to the task, we found out that most participants executed spontaneous miniature rotations of the head that were significantly related to the main task parameter. These head rotations were as if participants were trying to align themselves with the orientation on the map either in the image plane or on the ground plane, but with tiny amplitudes, typically below 1% of the actual movements. Our results are consistent with a model of sensorimotor prediction driving spatial reasoning. The efference copy of planned movements triggers this prediction mechanism. The movements themselves may then be mostly inhibited; the small spontaneous gestures that we measure are the visible traces of these planned but inhibited actions.

  15. Bilateral spontaneous rupture of 'hale' kidneys

    International Nuclear Information System (INIS)

    Naumov, N.; Zozikov, B.; Otzetov, A.; Kamenova, M.; Martinova, F.; Kalyonski, R.


    A rare case of spontaneous bilateral rupture of the kidneys, occurring consecutively over a one-year period in a young male patient with 'hale' kidneys until then, is described. The patient's past history and thorough examination performed do not justify to assign the case under the heading of some of the etiological factors as the underlying cause of spontaneous kidney rupture. The literature survey on spontaneous bilateral non-tumor ruptures of kidneys shows that over a 20-year period, only 3 cases of bilateral spontaneous ruptures have been reported. It is pointed out that panarteritis nodosa followed by hemorrhagic fever with renal syndrome is the commonest underlying cause of such ruptures. Clinically spontaneous ruptures become manifest with emergency condition presenting severe renal colic, impaired to serious general condition, often with acute abdomen and hemodynamic breakdown, and no past history evidence of renal disease or injury. In the initial phase diagnosing is not always easy; it is usually made on the ground of physical examination and the full range of imaging studies used in urological practice and during operative treatment. Emphasis is laid on the fact that the imaging methods are not invariably sufficient to identify the exact etiological factor giving rise to such a severe condition, but nevertheless these methods have an essential practical bearing on diagnosing a rupture. (authors)

  16. Surgical management of spontaneous hypertensive brainstem hemorrhage

    Directory of Open Access Journals (Sweden)

    Bal Krishna Shrestha


    Full Text Available Spontaneous hypertensive brainstem hemorrhage is the spontaneous brainstem hemorrhage associated with long term hypertension but not having definite focal or objective lesion. It is a catastrophic event which has a poor prognosis and usually managed conservatively. It is not uncommon, especially in eastern Asian populations, accounting approximately for 10% of the intracerebral hemorrhage. Before the advent of computed tomography, the diagnosis of brainstem hemorrhage was usually based on the clinical picture or by autopsy and believed to be untreatable via surgery. The introduction of computed tomography permitted to categorize the subtypes of brainstem hemorrhage with more predicted outcome. Continuous ongoing developments in the stereotactic surgery and microsurgery have added more specific surgical management in these patients. However, whether to manage conservatively or promptly with surgical evacuation of hematoma is still a controversy. Studies have shown that an accurate prognostic assessment based on clinical and radiological features on admission is critical for establishing a reasonable therapeutic approach. Some authors have advocate conservative management, whereas others have suggested the efficacy of surgical treatment in brainstem hemorrhage. With the widening knowledge in microsurgical techniques as well as neuroimaging technology, there seems to have more optimistic hope of surgical management of spontaneous hypertensive brainstem hemorrhage for better prognosis. Here we present five cases of severe spontaneous hypertensive brainstem hemorrhage patients who had undergone surgery; and explore the possibilities of surgical management in patients with the spontaneous hypertensive brainstem hemorrhage.

  17. Cursed lamp: the problem of spontaneous abortion. (United States)

    Simkulet, William


    Many people believe human fetuses have the same moral status as adult human persons, that it is wrong to allow harm to befall things with this moral status, and thus voluntary, induced abortion is seriously morally wrong. Recently, many prochoice theorists have argued that this antiabortion stance is inconsistent; approximately 60% of human fetuses die from spontaneous abortion, far more than die from induced abortion, so if antiabortion theorists really believe that human fetuses have significant moral status, they have strong moral obligations to oppose spontaneous abortion. Yet, few antiabortion theorists devote any effort to doing so. Many prochoice theorists argue that to resolve this inconsistency, antiabortion theorists should abandon their opposition to induced abortion. Here, I argue that those who do not abandon their opposition to induced abortion but continue to neglect spontaneous abortion act immorally. Aristotle argues that moral responsibility requires both control and awareness; I argue that once an antiabortion theorist becomes aware of the frequency of spontaneous abortion, they have a strong moral obligation to redirect their efforts towards combating spontaneous abortion; failure to do so is morally monstrous. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Allogeneic stem cell transplantation for chronic myelomonocytic leukemia: a report from the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire. (United States)

    Park, Sophie; Labopin, Myriam; Yakoub-Agha, Ibrahim; Delaunay, Jacques; Dhedin, Nathalie; Deconinck, Eric; Michallet, Mauricette; Robin, Marie; De Revel, Thierry; Bernard, Marc; Vey, Norbert; Lioure, Bruno; Lapusan, Simona; Tabrizi, Reza; Bourhis, Jean-Henri; Huynh, Anne; Beguin, Yves; Socié, Gérard; Dreyfus, François; Fenaux, Pierre; Mohty, Mohamad


    Chronic myelomonocytic leukemia (CMML) is a severe disease for which allogeneic stem cell transplantation (allo-SCT) remains the only potentially curative treatment. We describe a retrospective study determining prognostic factors for outcome after allo-SCT in consecutive 73 patients with CMML reported to the SFGM-TC registry between 1992 and 2009. At diagnosis, median age was 53 yrs, and 36% patients had palpable splenomegaly (SPM). 48, 13, and 9 patients had good, intermediate, and poor risk karyotype, respectively, according to IPSS, 61% patients had CMML-1, and 39% had CMML-2. 41/31/1 cases had an HLA-identical sibling, an unrelated and haploidentical donor, respectively. 43 patients received reduced-intensity conditioning. With a median follow-up of 23 month, acute grade 2-4 and chronic GVHD developed in 21 and 25 patients, respectively. The 3-year OS, NRM (non-relapse mortality),EFS, and CIR (cumulative incidence of relapse) were 32%, 36%, 29% and 35%, respectively. OS was not influenced by the CR status, marrow blasts% at allo-SCT, prior treatments, and cGVHD. Using multivariate analysis, year of transplant transplantation is a valid treatment option for patients with CMML, and its outcome has improved with YOT > 2004. Splenomegaly seems to be a negative factor of OS and EFS in this series. © 2013 John Wiley & Sons A/S.

  19. Aspectos clínico-hematológicos e lesões vesicais na intoxicação crônica espontânea por Pteridium aquilinum em bovinos Clinical and hematological aspects and urinary bladder lesions in chronic spontaneous poisoning by Pteridium aquilinum in cattle

    Directory of Open Access Journals (Sweden)

    Adriane L. Gabriel


    ão-neoplásicas (6/17, alterações gerais na lâmina própria (6/22 e alterações inflamatórias (5/17. Os achados histológicos das bexigas dos casos de HEB foram classificados da mesma forma, resultando em 19 tipos diferentes de alterações morfológicas. Dessas, 5/19 eram alterações neoplásicas e 14/20, alterações não-neoplásicas (9/14 alterações epiteliais não neoplásicas, 3/14 alterações gerais na lâmina própria e 2/14 alterações inflamatórias. Na HEB, os neoplasmas mesenquimais foram mais freqüentemente observados que os epiteliais, e a maior parte era maligna. A técnica de imuno-histoquímica foi utilizada para caracterizar os aspectos morfológicos, principalmente dos neoplasmas. Através do estudo morfológico concluiu-se que é muito freqüente a ocorrência de lesões vesicais em bovinos com a forma crônica de CCEs no TAS e que essas lesões são idênticas às encontradas nos bovinos com HEB.Spontaneous cases of chronic poisoning by Pteridium aquilinum in cattle were studied. The clinical forms of the disease were squamous cell carcinoma (SCCs of the upper digestive tract (UDT and bovine enzootic hematuria (BEH. The cases were from the midland Region of the Midwest of Rio Grande do Sul State, Brazil, and were submitted to the Laboratório de Patologia Veterinária of the Universidade Federal de Santa Maria. Clinical signs and blood work were evaluated at terminal phase of disease. Cattle with UDT SCCs had progressive weigth loss, ruminal atony, cough, dysphagia, bloating, and regurgitation. In cattle with BEH, hematuria was observed in all cases, followed by progressive weight loss. Non-regenerative anemia was detected in 33.33% of the cattle with UDT SCCs form and in 66.66% of the cattle with BEH form. Changes in white blood count occurred in some cases but drop in lymphocyte numbers was uncommon in both forms of disease. For the morphological study, urinary bladders from 46 cattle with UDT SCCs and 11 cattle with BEH were analyzed. Grossly, 16

  20. Spontaneous Regression of Lumbar Herniated Disc

    Directory of Open Access Journals (Sweden)

    Chun-Wei Chang


    Full Text Available Intervertebral disc herniation of the lumbar spine is a common disease presenting with low back pain and involving nerve root radiculopathy. Some neurological symptoms in the majority of patients frequently improve after a period of conservative treatment. This has been regarded as the result of a decrease of pressure exerted from the herniated disc on neighboring neurostructures and a gradual regression of inflammation. Recently, with advances in magnetic resonance imaging, many reports have demonstrated that the herniated disc has the potential for spontaneous regression. Regression coincided with the improvement of associated symptoms. However, the exact regression mechanism remains unclear. Here, we present 2 cases of lumbar intervertebral disc herniation with spontaneous regression. We review the literature and discuss the possible mechanisms, the precipitating factors of spontaneous disc regression and the proper timing of surgical intervention.

  1. Spontaneous hemothorax: primary pleural epithelioid angiosarcoma

    Directory of Open Access Journals (Sweden)

    Amit Panjwani


    Full Text Available Spontaneous hemothorax is a rare condition seen in coagulation and vascular disorders. Uncommonly, malignant neoplasms may cause spontaneous hemothorax. Primary pleural epithelioid angiosarcomas (excluding the cases with pleuropulmonary or chest wall involvement are extremely rare pleural tumors, which may be mistaken for mesothelioma or adenocarcinoma, and only 19 cases (one of them from India have been reported in the English literature, to date. It commonly occurs in older men, has a nonspecific clinicoradiological presentation, and carries a poor prognosis with no survivors beyond a year of establishing the diagnosis. We report a case of primary pleural epithelioid angiosarcoma presenting as a life-threatening spontaneous hemothorax. We also present a brief literature review on pleural angiosarcoma.

  2. Computed tomographic findings of spontaneous intracranial hemorrhage

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Seung Sook; Kim, Young Sook; Kim, Young Chul [College of Medicine, Chosun University, Kwangju (Korea, Republic of)


    Computed tomography (CT) was a reliable technique to evaluate the exact size and location of spontaneous intracranial hemorrhage and to predict it's prognosis. Fifty-nine cases of spontaneous intracranial hemorrhage were evaluated and reviewed by CT scan. The following results were obtained. 1. The sex ratio of male to female was 1 to 1.4, The highest incidence was in 6th and 7th decades. 2. The most common cause of spontaneous intracranial hemorrhage was hypertension (74.6%), followed by the aneurysm (13.5%), arteriovenous malformation (5.1%), occlusive vascular disease (3.4%), and blood dyscrasia (3.4%). 3. The most common location was basal ganglia and thalamic hemorrhage (37.3%), followed by lobar hemorrhage (27.1%), cerebellar hemorrhage (13.5%), and subarachnoid hemorrhage (11.9%). 4. Primary intraventricular hemorrhage carried the highest mortality. 5. The larger volume of hematoma, the higher the mortality rate.

  3. Spontaneous Perforation of Pyometra: A Case Report

    Directory of Open Access Journals (Sweden)


    Full Text Available Pyometra is the accumulation of purulent material in the uterine cavity. Its reported incidence is 0.01–0.5% in gynecologic patients; however, as far as elderly patients are concerned, its incidence is 13.6% [3]. The most common cause of pyometra is malignant diseases of genital tract and the consequences of their treatment (radiotherapy. Other causes are benign tumors like leiomyoma, endometrial polyps, senile cervicitis, cervical occlusion after surgery, puerperal infections, and congenital cervical anomalies. Spontaneous rupture of the uterus is an extremely rare complication of pyometra. To our knowledge, only 21 cases of spontaneous perforation of pyometra have been reported in English literature since 1980. This paper reports an additional case of spontaneous uterine rupture.

  4. On spontaneous breakdown in Σ-models

    International Nuclear Information System (INIS)

    Ivanov, E.A.


    The group theory aspects of spontaneous breakdown in linear Σ-models are discussed. General conditions are formulated under which multiplet of group G (compact or noncompact) is suitable for constructing the Σ-model with a given subgroup of stability of vacuum. It is shown that the Σ-models of spontaneously broken space-time symmetries can be constructed in general only if some extra coordinates are introduced in addition to an ordinary 4-coordinate xsub(μ). The connection between Σ-models of internal symmetries and appropriate nonlinear realizations has also been investigated

  5. Spontaneous abortion and physical strain around implantation

    DEFF Research Database (Denmark)

    Hjollund, N H; Jensen, Tina Kold; Bonde, Jens Peter


    Existing studies of physical strain and spontaneous abortion are mainly retrospective or based only on pregnancies that have survived the first trimester. Furthermore, almost all studies have relied on averaged measures of physical strain, which tend to blur an effect if peak values during short...... pregnancy the women recorded physical strain prospectively in a structured diary. Physical strain around the time of implantation was associated with later spontaneous abortion. The adjusted risk ratio for women who reported physical strain higher than average at day 6 to 9 after the estimated date...

  6. Need for spontaneous breakdown of chiral symmetry

    International Nuclear Information System (INIS)

    Salomone, A.; Schechter, J.; Tudron, T.


    The question of whether the chiral symmetry of the theory of strong interactions (with massless quarks) is required to be spontaneously broken is examined in the framework of a previously discussed effective Lagrangian for quantum chromodynamics. The assumption that physical masses of the theory be finite leads in a very direct way to the necessity of spontaneous breakdown. This result holds for all N/sub F/> or =2, where N/sub F/ is the number of different flavors of light quarks. The atypical cases N/sub F/ = 1,2 are discussed separately

  7. Spontaneous subdural hematoma associated to Duret hemorrhage

    Directory of Open Access Journals (Sweden)

    William Alves Martins, MD


    Full Text Available Subdural hematoma (SH is a neurosurgical emergency, usually caused by head trauma. Non-traumatic causes include aneurysm or arterial–venous malformation rupture, coagulopathy and others. We report the case of a 66 year-old man who developed apparently unprovoked signs of increased intracranial pressure. Brain computed tomography scan showed an acute spontaneous SH, surgically treated. Throughout surgery, a ruptured cortical artery with intensive bleeding appeared and was cauterized. After surgery, patient remained comatose and a new CT demonstrated Duret hemorrhage at the brainstem. Acute spontaneous SH of arterial origin is rare and highly lethal, in which a good prognosis relies on early diagnosis and treatment.

  8. Primer on spontaneous heating and pyrophoricity

    Energy Technology Data Exchange (ETDEWEB)


    This primer was prepared as an information resource for personnel responsible for operation of DOE nuclear facilities. It has sections on combustion principles, spontaneous heating/ignition of hydrocarbons and organics, pyrophoric gases and liquids, pyrophoric nonmetallic solids, pyrophoric metals (including Pu and U), and accident case studies. Although the information in this primer is not all-encompassing, it should provide the reader with a fundamental knowledge level sufficient to recognize most spontaneous combustion hazards and how to prevent ignition and widespread fires. This primer is provided as an information resource only, and is not intended to replace any fire protection or hazardous material training.

  9. Cavity enhanced rephased amplified spontaneous emission

    International Nuclear Information System (INIS)

    A Williamson, Lewis; J Longdell, Jevon


    Amplified spontaneous emission is usually treated as an incoherent noise process. Recent theoretical and experimental work using rephasing optical pulses has shown that rephased amplified spontaneous emission (RASE) is a potential source of wide bandwidth time-delayed entanglement. Due to poor echo efficiency the plain RASE protocol does not in theory achieve perfect entanglement. Experiments done to date show a very small amount of entanglement at best. Here we show that RASE can, in principle, produce perfect multimode time-delayed two mode squeezing when the active medium is placed inside a Q-switched cavity. (paper)

  10. Spontaneous supersymmetry breaking on the lattice

    Energy Technology Data Exchange (ETDEWEB)

    Wenger, Urs [Albert Einstein Center for Fundamental Physics, Institute for Theoretical Physics, University of Bern, Sidlerstrasse 5, CH-3012 Bern (Switzerland)


    We discuss various strategies for regularising supersymmetric quantum field theories on a space-time lattice. In general, simulations of lattice models with spontaneously broken supersymmetry suffer from a fermion sign problem related to the vanishing of the Witten index. We discuss a novel approach which evades this problem in low dimensions by formulating the path integral on the lattice in terms of fermion loops. Then we present exact results on the spectrum and the Witten index for N=2 supersymmetric quantum mechanics and results from simulations of the spontaneously broken N=1 Wess-Zumino model.

  11. Treatment of refractory chronic urticaria

    Directory of Open Access Journals (Sweden)

    Aayushi Mehta


    Full Text Available Chronic spontaneous urticaria is a distressing disease encountered frequently in clinical practice. The current mainstay of therapy is the use of second-generation, non-sedating antihistamines. However, in patients who do not respond satisfactorily to these agents, a variety of other drugs are used. This article examines the available literature for frequently used agents including systemic corticosteroids, leukotriene receptor antagonists, dapsone, sulfasalazine, hydroxychloroquine, H2 antagonists, methotrexate, cyclosporine A, omalizumab, autologous serum therapy, and mycophenolate mofetil, with an additional focus on publications in Indian literature.

  12. HBV/HCV co-infection is associated with a high level of HCV spontaneous clearance among drug users and blood donors in China. (United States)

    Xiong, H; Rong, X; Wang, M; Xu, R; Huang, K; Liao, Q; Huang, J; Chen, J; Li, C; Tang, X; Shan, Z; Zhang, M; Nelson, K; Fu, Y


    Understanding the biology of spontaneous clearance of hepatitis C virus (HCV) infection could lead to improved strategies to prevent the sequelae associated with chronic HCV infection. Chronic infections with hepatitis virus are very common in China, but the factors associated with spontaneous clearance of HCV have not been adequately studied. We evaluated the spontaneous clearance of HCV among 1918 drug users and 1526 HCV-seropositive blood donors in Guangzhou, China. Among participants who were co-infected with hepatitis B virus (HBV), 41.38% of drug users and 39.47% of blood donors had cleared their HCV infection without antiviral therapy compared to 9.41% of drug users and 16.73% of blood donors who were mono-infected with a single virus (P<.01). The proportion of subjects who had cleared their HCV infection was significantly greater in the co-infected subjects whose serum HBV DNA was greater than 2000IU/mL than those with lower levels. A multiple logistic regression analysis found female gender, IL28B rs8099917 TT genotype, HBV co-infection and blood donors (vs drug users) associated with increased spontaneous clearance of HCV infection. Although acute HCV infections are common in China, the incidence of chronic HCV may be reduced among the high prevalence of chronic HBV and IL28B genotypes associated with spontaneous clearance of HCV in Chinese populations. © 2016 John Wiley & Sons Ltd.

  13. Wheaten ferments spontaneous fermantation in biotechnological methods




    In article are shown results of research of biotechnological properties of wheaten leavens of spontaneous fermentation (in the example of pea-anisetree leaven) and their analysis. Also is established influence of the given type of leavens on the basic biopolymers of the flour, on the property of the pastry and quality of bread from wheaten flour.

  14. Original article Spontaneous Pregnancy Outcome after Surgical ...

    African Journals Online (AJOL)


    Sep 28, 2011 ... Table 2: Spontaneous pregnancy in relation to postoperative semen parameters. (no statistically significant difference), comparable to the mean ages of 22, 28.4 and. 34.9 years, respectively, reported by Bach et al9, Abdel- Meguid et al10 and Baazeem et al11. The mean age of the wives who did or did.

  15. Spontaneous symmetry breakdown in gauge theories

    International Nuclear Information System (INIS)

    Scadron, M.D.


    The dynamical theory of spontaneous breakdown correctly predicts the bound states and relates the order parameters of electron-photon superconductivity and quark-gluon chiral symmetry. A similar statement cannot be made for the standard electro-weak gauge symmetry. (author)

  16. Identical Twin Primigravid Sisters -Spontaneous Labour and ...

    African Journals Online (AJOL)

    We report 2 cases of identical twin sisters, the older sibling getting married 14 months earlier but both got pregnant for their first child at about the same time and were managed by the same Obstetrician and fell into spontaneous labour within a few hours of each other. Both were delivered by emergency caesarean section ...


    Energy Technology Data Exchange (ETDEWEB)



    I explore the regions of quark masses where CP will be spontaneously broken in the strong interactions. The boundaries of these regions are controlled by the chiral anomaly, which manifests itself in ambiguities in the definition of non-degenerate quark masses. In particular, the concept of a single massless quark is ill defined.


    African Journals Online (AJOL)


    Spontaneous fermentation has been identified to improve the quality characteristics of foods derived from them. When combined with cowpea fortification and nixtamalization, it is expected to improve the nutritional, functional, physico-chemical and sensory qualities of maize based foods thereby improving the qualities as ...

  19. Association between Nutritional Status with Spontaneous Abortion

    Directory of Open Access Journals (Sweden)

    Rahimeh Ahmadi


    Full Text Available Background: Spontaneous abortion is the most common adverse pregnancy outcome. We aimed to investigate a possible link between nutrient deficiencies and the risk of spontaneous abortion. Materials and Methods: This case-control study included the case group (n=331 experiencing a spontaneous abortion before 14 weeks of pregnancy and the control group (n=331 who were healthy pregnant women over 14 weeks of pregnancy. The participants filled out Food Frequency Questionnaire (FFQ, in which they reported their frequency of consumption for a given serving of each food item during the past three months, on a daily, weekly or monthly basis. The reported frequency for each food item was converted to a daily intake. Then, consumption of nutrients was compared between the two groups. Results: There are significant differences between the two groups regarding consumed servings/day of vegetables, bread and cereal, meat, poultry, fish, eggs, beans, fats, oils and dairy products (P=0.012, P<0.001, P=0.004, P<0.001, P=0.019, respectively. There are significant differences between the two groups in all micronutrient including folic acid, iron, vitamin C, vitamin B6, vitamin B12 and zinc (P<0.001. Conclusion: Poor nutrientions may be correlated with increased risk of spontaneous abortion

  20. Spontaneous regression of an intraspinal disc cyst

    Energy Technology Data Exchange (ETDEWEB)

    Demaerel, P.; Eerens, I.; Wilms, G. [University Hospital, Leuven (Belgium). Dept. of Radiology; Goffin, J. [Dept. of Neurosurgery, University Hospitals, Leuven (Belgium)


    We present a patient with a so-called disc cyst. Its location in the ventrolateral epidural space and its communication with the herniated disc are clearly shown. The disc cyst developed rapidly and regressed spontaneously. This observation, which has not been reported until now, appears to support focal degeneration with cyst formation as the pathogenesis. (orig.)

  1. Spontaneous rupture of an infected renal cyst

    Energy Technology Data Exchange (ETDEWEB)

    Kopp, W.; Toelly, E.; Ebner, F.; Kullnig, P.


    Spontaneous or traumatic rupture of renal cysts is a rare occurrence. The contents of the cyst can perforate into the renal calyx system or into the perirenal space. Perforation into the peritoneal cavity has also been described (1, 2, 4, 5).

  2. Proteomic Biomarkers for Spontaneous Preterm Birth

    DEFF Research Database (Denmark)

    Kacerovsky, Marian; Lenco, Juraj; Musilova, Ivana


    This review aimed to identify, synthesize, and analyze the findings of studies on proteomic biomarkers for spontaneous preterm birth (PTB). Three electronic databases (Medline, Embase, and Scopus) were searched for studies in any language reporting the use of proteomic biomarkers for PTB published...

  3. Spontaneous emission from saturated parametric amplifiers

    DEFF Research Database (Denmark)

    Rottwitt, Karsten; Ott, Johan Raunkjær; Steffensen, Henrik


    Noise performance of parametric amplifiers is typically calculated assuming un-depleted operation. However, in many applications especially when applied as regenerative amplifiers in systems based on phase shift keyed modulation schemes, this assumption is not valid. Here we show the impact...... on accumulated spontaneous emission for a parametric amplifier operated in saturation....

  4. Spontaneous Non-verbal Counting in Toddlers (United States)

    Sella, Francesco; Berteletti, Ilaria; Lucangeli, Daniela; Zorzi, Marco


    A wealth of studies have investigated numerical abilities in infants and in children aged 3 or above, but research on pre-counting toddlers is sparse. Here we devised a novel version of an imitation task that was previously used to assess spontaneous focusing on numerosity (i.e. the predisposition to grasp numerical properties of the environment)…

  5. Editorial: Spontaneous bacterial peritonitis | Lule | East African ...

    African Journals Online (AJOL)

    Journal Home > Vol 81, No 3 (2004) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Editorial: Spontaneous bacterial peritonitis. GN Lule. Abstract. No Abstract Available. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT ...

  6. Spontaneous conversion of first onset atrial fibrillation

    DEFF Research Database (Denmark)

    Lindberg, Søren Østergaard; Hansen, Sidsel; Nielsen, Tonny


    Background  We studied all patients admitted to hospital with first onset atrial fibrillation (AF) to determine the probability of spontaneous conversion to sinus rhythm and to identify factors predictive of such a conversion. Methods and Results  We retrospectively reviewed charts of 438...

  7. Spontaneous dimensional reduction in quantum gravity (United States)

    Carlip, S.


    Hints from a number of different approaches to quantum gravity point to a phenomenon of “spontaneous dimensional reduction” to two spacetime dimensions near the Planck scale. I examine the physical meaning of the term “dimension” in this context, summarize the evidence for dimensional reduction, and discuss possible physical explanations.

  8. Surgical management of spontaneous ruptured hepatocellular adenoma

    Directory of Open Access Journals (Sweden)

    Marcelo Augusto Fontenelle Ribeiro Junior


    Full Text Available AIMS: Spontaneous ruptured hepatocellular adenoma (SRHA is a rare life-threatening condition that may require surgical treatment to control hemorrhaging and also stabilize the patient. We report a series of emergency surgeries performed at our institution for this condition. METHODS: We reviewed medical records and radiology files of 28 patients (from 1989 to 2006 with a proven diagnosis of hepatocellular adenoma (HA. Three (10.7% of 28 patients had spontaneous ruptured hepatocellular adenoma, two of which were associated with intrahepatic hemorrhage while one had intraperitoneal bleeding. Two patients were female and one was male. Both female patients had a background history of oral contraceptive use. Sudden abdominal pain associated with hemodynamic instability occurred in all patients who suffered from spontaneous ruptured hepatocellular adenoma. The mean age was 41.6 years old. The preoperative assessment included liver function tests, ultrasonography and computed tomography. RESULTS: The surgical approaches were as follows: right hemihepatectomy for controlling intraperitoneal bleeding, and right extended hepatectomy and non-anatomic resection of the liver for intrahepatic hemorrhage. There were no deaths, and the postoperative complications were bile leakage and wound infection (re-operation, as well as intraperitoneal abscess (re-operation and pleural effusion. CONCLUSION: Spontaneous ruptured hepatocellular adenoma may be treated by surgery for controlling hemorrhages and stabilizing the patient, and the decision to operate depends upon both the patient's condition and the expertise of the surgical team.

  9. Spontaneous hedonic reactions to social media cues

    NARCIS (Netherlands)

    Koningsbruggen, G.M. van; Hartmann, T.; Eden, A.; Veling, H.P.


    Why is it so difficult to resist the desire to use social media? One possibility is that frequent social media users possess strong and spontaneous hedonic reactions to social media cues, which, in turn, makes it difficult to resist social media temptations. In two studies (total N = 200), we

  10. Recurrent spontaneous intracerebral hemorrhage associated with ...

    African Journals Online (AJOL)

    Spontaneous intracerebral hemorrhage (ICH) accounts for 15% of stroke cases in the US and Europe and up to 30% in Asian populations. Intracerebral hemorrhage is a relatively uncommon form of stroke-it causes only 10 to 15 percent of all strokes. It is more disabling and has a higher mortality rate than ischemic stroke, ...

  11. Ovarian hyperstimulation syndrome in a spontaneous pregnancy ...

    African Journals Online (AJOL)

    It is known that most cases of Ovarian Hyperstimulation Syndrome (OHSS) are associated with the therapies for ovulation induction. However, OHSS may rarely be associated with a spontaneous ovulatory cycle, usually in the case of multiple gestations, hypothyroidism or polycystic ovary syndrome. We report a case of ...

  12. Spontaneous left main coronary artery dissection

    Directory of Open Access Journals (Sweden)

    Alptug Tokatli


    Full Text Available Spontaneous coronary artery dissection (SCAD is a very rare clinical condition. Physiopathology of SCAD is still mostly unclear. Clinical presentation of SCAD ranges from atypical symptoms to sudden cardiac death. The diagnosis of dissection is generally made by using conventional coronary angiography. Invasive or conservative treatment is reasonable.

  13. Spontaneous extracranial decompression of epidural hematoma

    International Nuclear Information System (INIS)

    Neely, John C.; Jones, Blaise V.; Crone, Kerry R.


    Epidural hematoma (EDH) is a common sequela of head trauma in children. An increasing number are managed nonsurgically, with close clinical and imaging observation. We report the case of a traumatic EDH that spontaneously decompressed into the subgaleal space, demonstrated on serial CT scans that showed resolution of the EDH and concurrent enlargement of the subgaleal hematoma. (orig.)

  14. Spontaneous extracranial decompression of epidural hematoma

    Energy Technology Data Exchange (ETDEWEB)

    Neely, John C. [Marshall University School of Medicine, Huntington, WV (United States); Jones, Blaise V. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Crone, Kerry R. [Cincinnati Children' s Hospital Medical Center, Division of Neurosurgery, Cincinnati, OH (United States)


    Epidural hematoma (EDH) is a common sequela of head trauma in children. An increasing number are managed nonsurgically, with close clinical and imaging observation. We report the case of a traumatic EDH that spontaneously decompressed into the subgaleal space, demonstrated on serial CT scans that showed resolution of the EDH and concurrent enlargement of the subgaleal hematoma. (orig.)

  15. Spontaneous Sourcing among Students Reading Multiple Documents (United States)

    Stromso, Helge I.; Braten, Ivar; Britt, M. Anne; Ferguson, Leila E.


    This study used think-aloud methodology to explore undergraduates' spontaneous attention to and use of source information while reading six documents that presented conflicting views on a controversial social scientific issue in a Google-like environment. Results showed that students explicitly and implicitly paid attention to sources of documents…

  16. Massive Spontaneous Hemothorax, Giant Intrathoracic Meningocele ...

    African Journals Online (AJOL)

    haemothorax associated with von Recklinghausen's disease: Review of occurrence in Japan. Thorax 1997;52:575‑8. 3. Fedoruk LM, English J, Fradet GJ. Spontaneous hemothorax and neurofibromatosis: A review of a lethal combination. Asian Cardiovasc. Thorac Ann 2007;15:342‑4. 4. Conlon NP, Redmond KC, Celi LA.

  17. A Fatal Complication of Dermatomyositis: Spontaneous Pneumomediastinum

    Directory of Open Access Journals (Sweden)

    Ezgi Demirdöğen Çetinoğlu


    Full Text Available Interstitial lung disease (ILD is a negative prognostic factor associated with increased morbidity and mortality in patients with dermatomyositis (DM. Spontaneous pneumomediastinum is a rare complication of DM and it can be fatal. We present a 48-year-old woman with DM and ILD complicated by pneumomediastinum without pneumothorax and subcutaneous emphysema.

  18. Grooming behavior of spontaneously hypertensive rats

    NARCIS (Netherlands)

    Buuse, M. van den; Jong, Wybren de


    In an open field spontaneously hypertensive rats (SHR) exhibited lower scores for grooming when compared to their normotensive controls, the Wistar Kyoto rats (WKY). After i.c.v. injection of 1 μg ACTH1–24 cumulative 50-min grooming scores were lower in SHR. Analysis of subscores indicated that the

  19. Spontaneous abortion and physical strain around implantation

    DEFF Research Database (Denmark)

    Hjollund, N H; Jensen, Tina Kold; Bonde, Jens Peter


    Existing studies of physical strain and spontaneous abortion are mainly retrospective or based only on pregnancies that have survived the first trimester. Furthermore, almost all studies have relied on averaged measures of physical strain, which tend to blur an effect if peak values during short ...

  20. Spontaneous Hedonic Reactions to Social Media Cues. (United States)

    van Koningsbruggen, Guido M; Hartmann, Tilo; Eden, Allison; Veling, Harm


    Why is it so difficult to resist the desire to use social media? One possibility is that frequent social media users possess strong and spontaneous hedonic reactions to social media cues, which, in turn, makes it difficult to resist social media temptations. In two studies (total N = 200), we investigated less-frequent and frequent social media users' spontaneous hedonic reactions to social media cues using the Affect Misattribution Procedure-an implicit measure of affective reactions. Results demonstrated that frequent social media users showed more favorable affective reactions in response to social media (vs. control) cues, whereas less-frequent social media users' affective reactions did not differ between social media and control cues (Studies 1 and 2). Moreover, the spontaneous hedonic reactions to social media (vs. control) cues were related to self-reported cravings to use social media and partially accounted for the link between social media use and social media cravings (Study 2). These findings suggest that frequent social media users' spontaneous hedonic reactions in response to social media cues might contribute to their difficulties in resisting desires to use social media.

  1. Spontaneous electric fields in solid films: spontelectrics

    DEFF Research Database (Denmark)

    Field, David; Plekan, Oksana; Cassidy, Andrew


    When dipolar gases are condensed at sufficiently low temperature onto a solid surface, they form films that may spontaneously exhibit electric fields in excess of 108V/m. This effect, called the ‘spontelectric effect’, was recently revealed using an instrument designed to measure scattering...

  2. Spontaneous Retroperitoneal Hemorrhage from Adrenal Artery Aneurysm

    International Nuclear Information System (INIS)

    Gonzalez Valverde, F.M.; Balsalobre, M.; Torregrosa, N.; Molto, M.; Gomez Ramos, M.J.; Vazquez Rojas, J.L.


    Spontaneous adrenal hemorrhage is a very rare but serious disorder of the adrenal gland that can require emergent treatment. We report on a 42-year-old man who underwent selective angiography for diagnosis and treatment of retroperitoneal hemorrhage from small adrenal artery aneurysm. This case gives further details about the value of transluminal artery embolization in the management of visceral aneurysm rupture

  3. Individual differences in spontaneous analogical transfer. (United States)

    Kubricht, James R; Lu, Hongjing; Holyoak, Keith J


    Research on analogical problem solving has shown that people often fail to spontaneously notice the relevance of a semantically remote source analog when solving a target problem, although they are able to form mappings and derive inferences when given a hint to recall the source. Relatively little work has investigated possible individual differences that predict spontaneous transfer, or how such differences may interact with interventions that facilitate transfer. In this study, fluid intelligence was measured for participants in an analogical problem-solving task, using an abridged version of the Raven's Progressive Matrices (RPM) test. In two experiments, we systematically compared the effect of augmenting verbal descriptions of the source with animations or static diagrams. Solution rates to Duncker's radiation problem were measured across varying source presentation conditions, and participants' understanding of the relevant source material was assessed. The pattern of transfer was best fit by a moderated mediation model: the positive impact of fluid intelligence on spontaneous transfer was mediated by its influence on source comprehension; however, this path was in turn modulated by provision of a supplemental animation via its influence on comprehension of the source. Animated source depictions were most beneficial in facilitating spontaneous transfer for those participants with low scores on the fluid intelligence measure.

  4. Spontaneous regression of a mandibular arteriovenous malformation

    Directory of Open Access Journals (Sweden)

    Scott B. Raymond, MD, PhD


    Full Text Available Mandibular arteriovenous malformations (AVMs are rare lesions that may initially present as catastrophic bleeding during dental surgical procedures. Owing to the significant risk of bleeding, most mandibular AVMs are treated definitively by resection or embolization. In this report, we describe a mandibular AVM that spontaneously regressed after biopsy.

  5. Unified gauge theories with spontaneous symmetry breaking

    International Nuclear Information System (INIS)

    MacDowell, S.W.


    Unified gauge theories with spontaneous symmetry breaking are studied with a view to renormalize quantum field theory. Georgi-Glashow and Weinberg-Salam models to unify weak and electromagnetic interactions are discussed in detail. Gauge theories of strong interactions are also considered [pt

  6. Influence of spontaneous fermentation on some quality ...

    African Journals Online (AJOL)

    Spontaneous fermentation has been identified to improve the quality characteristics of foods derived from them. When combined with cowpea fortification and nixtamalization, it is expected to improve the nutritional, functional, physico- chemical and sensory qualities of maize based foods thereby improving the qualities as ...

  7. Maternal Factors Associated With Early Spontaneous Singleton ...

    African Journals Online (AJOL)

    Background: Knowledge of the maternal factors predisposing to preterm deliveries should affect the anticipatory care of mothers at risk of delivering preterm babies and improve perinatal outcome. Objective: To determine the maternal socio-biological characteristics associated with the delivery of early spontaneous ...


    NARCIS (Netherlands)


    A class of spontaneously broken field theories is proposed, and the occurrence of their periodic, classical solutions is investigated in detail. The emergence of multiple solutions is observed, their normal modes of oscillation are studied, and the bifurcations of the classical energy functional are

  9. The changes of spontaneous motility in chick embryos after blockade of NO-synthase. (United States)

    Sedlácek, J


    The consequences of the blockade of NO-synthase (NOS) for the development, frequency and reactivity of spontaneous motility were investigated in chick embryos aged 4-19 day of incubation. 1. Acute NOS blockade evoked by N-nitro-L-arginine- methylester (L-NAME) (20 mg/kg egg weight-e.w.) caused on day 17 of incubation the short-lasting depression of spontaneous motility to 50% of resting motor activity. L-NAME was in spinal embryos without any effect. Chronic application of L-NAME (1.70 mg/kg e.w./24 h) from day 4 of incubation led after the first 4 days of continual supply to the development of reduced spontaneous motility on one hand, on the other hand it changed the efficacy of central activatory (NMDA, pentylenetetrazole) and inhibitory drugs (ketamine, glycine). L-NAME and L-arginine in different mutual combinations manifested in 17-day-old embryos their typical effect, though the depressory effect of L-NAME took a swifter course than the activatory effect of L-arginine. 2. Aminoguanidine (AmG) (9.8 and 20 mg/kg e.w.) evoked from day 17 of incubation the significant biphasic change of spontaneous motility only: initial depression was replaced by later activation. AmG was in spinal embryos without effect again. Chronic application of AmG (5.29 +/- 0.51 mg/kg e.w./24 h) showed in 17-day-old embryos a reduction of resting motility dependent on the duration of AmG influence during incubation. Another expression was the changed reactivity of spontaneous motility to some centrally effective drugs (ketamine, NMDA, D-cycloserine, glycine, pentylenetetrazole). 3. 7-nitroindazole (7-NIZ) (15 and 30 mg/kg e.w.) caused the significant decrease of spontaneous motility in chick embryos already from day 15 of incubation; the depression after the lower dosis had an interrupted course, whereas after the higher dosis it was a continuous one. 7-NIZ blocked in 17-day-old embryos the activatory effect of L-arginine, reduced the paroxysmal activation of motility evoked by NMDA and

  10. Spontaneous sensorimotor coupling with multipart music. (United States)

    Hurley, Brian K; Martens, Peter A; Janata, Petr


    Music often evokes spontaneous movements in listeners that are synchronized with the music, a phenomenon that has been characterized as being in "the groove." However, the musical factors that contribute to listeners' initiation of stimulus-coupled action remain unclear. Evidence suggests that newly appearing objects in auditory scenes orient listeners' attention, and that in multipart music, newly appearing instrument or voice parts can engage listeners' attention and elicit arousal. We posit that attentional engagement with music can influence listeners' spontaneous stimulus-coupled movement. Here, 2 experiments-involving participants with and without musical training-tested the effect of staggering instrument entrances across time and varying the number of concurrent instrument parts within novel multipart music on listeners' engagement with the music, as assessed by spontaneous sensorimotor behavior and self-reports. Experiment 1 assessed listeners' moment-to-moment ratings of perceived groove, and Experiment 2 examined their spontaneous tapping and head movements. We found that, for both musically trained and untrained participants, music with more instruments led to higher ratings of perceived groove, and that music with staggered instrument entrances elicited both increased sensorimotor coupling and increased reports of perceived groove. Although untrained participants were more likely to rate music as higher in groove, trained participants showed greater propensity for tapping along, and they did so more accurately. The quality of synchronization of head movements with the music, however, did not differ as a function of training. Our results shed new light on the relationship between complex musical scenes, attention, and spontaneous sensorimotor behavior.

  11. Spontaneous perirenal urinoma induced by NSAID-associated acute interstitial nephritis

    Directory of Open Access Journals (Sweden)

    Chang H


    Full Text Available Hsiu-Wen Chang,1 Chia-Hao Kuei,2 Chin-Feng Tseng,1 Yi-Chou Hou,3 Ying-Lan Tseng1 1Department of Internal Medicine, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, Xin-dian District, New Taipei City, Taiwan, Republic of China; 2Division of Urology, Department of Surgery, Cardinal Tien Hospital, New Taipei City, Taiwan, Republic of China; 3Department of Internal Medicine, Cardinal Tien Hospital An-Kang Branch, School of Medicine, Fu-Jen Catholic University, Xin-dian District, New Taipei City, Taiwan, Republic of China Abstract: Urinoma, defined as the urine leakage beyond the urinary tract, is commonly induced by blunt trauma or urinary tract obstruction by stone, intra-abdominal malignancy, or retroperitoneal fibrosis. Spontaneous urinoma is rare and parenchymal pathologic change is rarely mentioned when urinoma is found. We present a case of a 28-year-old woman with bilateral flank pain induced by spontaneous urinoma. The lady received chronic analgesics because of migraine. After intravenous ketorolac injection, bilateral perirenal urinoma developed. Renal biopsy showed acute interstitial nephritis associated with nonsteroid anti-inflammatory drug (NSAID. After discontinuing the medication, urinoma subsided, and the patient was discharged with normal serum creatinine. This was the first case of urinoma induced by NSAID-related interstitial nephritis, and pathophysiology and management of spontaneous urinoma are discussed. Keywords: spontaneous urinoma, NSAID, interstitial nephritis, acute kidney injury, ketorolac

  12. Socioeconomic position and the risk of spontaneous abortion

    DEFF Research Database (Denmark)

    Norsker, Filippa Nyboe; Espenhain, Laura; rogvi, Sofie


    To investigate the relationship between different indicators of socioeconomic position and the risk of spontaneous abortion.......To investigate the relationship between different indicators of socioeconomic position and the risk of spontaneous abortion....

  13. [Bacterial vaginosis and spontaneous preterm birth]. (United States)

    Brabant, G


    To determine if bacterial vaginosis is a marker for risk of spontaneous preterm delivery and if its detection and treatment can reduce this risk. Consultation of the database Pubmed/Medline, Science Direct, and international guidelines of medical societies. Bacterial vaginosis (BV) is a dysbiosis resulting in an imbalance in the vaginal flora through the multiplication of anaerobic bacteria and jointly of a disappearance of well-known protective Lactobacilli. His diagnosis is based on clinical Amsel criteria and/or a Gram stain with establishment of the Nugent score. The prevalence of the BV extraordinarily varies according to ethnic and/or geographical origin (4-58 %), in France, it is close to 7 % in the first trimester of pregnancy (EL2). The link between BV and spontaneous premature delivery is low with an odds ratio between 1.5 and 2 in the most recent studies (EL3). Metronidazole or clindamycin is effective to treat BV (EL3). It is recommended to prescribe one of these antibiotics in the case of symptomatic BV (Professional Consensus). The testing associated with the treatment of BV in the global population showed no benefit in the prevention of the risk of spontaneous preterm delivery (EL2). Concerning low-risk asymptomatic population (defined by the absence of antecedent of premature delivery), it has been failed profit to track and treat the BV in the prevention of the risk of spontaneous preterm delivery (EL1). Concerning the high-risk population (defined by a history of preterm delivery), it has been failed profit to track and treat the VB in the prevention of the risk of spontaneous preterm delivery (EL3). However, in the sub population of patients with a history of preterm delivery occurred in a context of materno-fetal bacterial infection, there may be a benefit to detect and treat early and systematically genital infection, and in particular the BV (Professional Consensus). The screening and treatment of BV during pregnancy in asymptomatic low

  14. Management and treatment of chronic urticaria (CU). (United States)

    Maurer, M; Church, M K; Gonçalo, M; Sussman, G; Sánchez-Borges, M


    Developments increasing our understanding of chronic urticaria have resulted in the simplification and improvement of available treatments. Currently, many treatments target mast cell mediators, but we can now disrupt mast cell activation with the anti-IgE antibody omalizumab, which has markedly advanced the treatment landscape for patients with difficult-to-treat urticaria. Current guidelines provide a framework for the management and treatment of patients with CU but, as each patient is different, knowledge and experience of specialist dermatologists and allergists are key to effective pharmacotherapy. This article reviews the different therapeutic options for patients with chronic spontaneous urticaria (also called chronic idiopathic urticaria) or chronic inducible urticaria and discusses management of special populations or special circumstances related to CU. © 2015 European Academy of Dermatology and Venereology.


    Directory of Open Access Journals (Sweden)

    О. Nesterenko


    Full Text Available The essence and the genesis of spontaneous order are disclosed in the context of critical analysis of constructivism. The author’s approach to the definition of the characteristic features of the spontaneous order is proposed. The dichotomy of the order is revealed towards the economic sphere in form of spontaneous order and organization.

  16. [Spontaneous renal artery dissection: a case report]. (United States)

    Maehana, Takeshi; Nishida, Sachiyo; Shindo, Tetsuya; Miyamoto, Shintaro; Muranaka, Takashi; Suzuki, Kazuhiro; Yanase, Masahiro


    A 65-year-old female was admitted to our hospital complaining of left upper abdominal pain. Although the symptom improved with observation, serum creatinine rose to 2.0 mg/dl. Slight atrophy of the left kidney was seen on abdominal plain computed tomography. In order to examine the possibility of renal infarction from thrombosis with angiography, we consulted the department of cardiovascular medicine. Even though we did not detect thrombosis with left renal angiography or intravascular ultrasound, there was a dissection finding localized at the left renal artery. Based on this finding, we made a diagnosis of spontaneous renal artery dissection and performed stent placement. Spontaneous renal artery dissection is extremely rare and the frequency of occurrence is reported to be less than 0.05%. Recently, however the frequency of detection has risen with the development of clinical imaging. We must keep in mind that the condition has the possibility of leading to renal blood circulation disorders.

  17. Thermal influences on spontaneous rock dome exfoliation (United States)

    Collins, Brian D.; Stock, Greg M.; Eppes, Martha C.; Lewis, Scott W.; Corbett, Skye C.; Smith, Joel B.


    Rock domes, with their onion-skin layers of exfoliation sheets, are among the most captivating landforms on Earth. Long recognized as integral in shaping domes, the exact mechanism(s) by which exfoliation occurs remains enigmatic, mainly due to the lack of direct observations of natural events. In August 2014, during the hottest days of summer, a granitic dome in California, USA, spontaneously exfoliated; witnesses observed extensive cracking, including a ~8000 kg sheet popping into the air. Subsequent exfoliation episodes during the following two summers were recorded by instrumentation that captured—for the first time—exfoliation deformation and stress conditions. Here we show that thermal cycling and cumulative dome surface heating can induce subcritical cracking that culminates in seemingly spontaneous exfoliation. Our results indicate that thermal stresses—largely discounted in dome formation literature—can play a key role in triggering exfoliation and therefore may be an important control for shaping domes worldwide.

  18. Spontaneous abortion and physical strain around implantation

    DEFF Research Database (Denmark)

    Hjøllund, Niels Henrik Ingvar; Jensen, T.K.; Bonde, J.P.


    Existing studies of physical strain and spontaneous abortion are mainly retrospective or based only on pregnancies that have survived the first trimester. Furthermore, almost all studies have relied on averaged measures of physical strain, which tend to blur an effect if peak values during short...... time periods are the relevant measure. We followed a cohort of first pregnancy planners from termination of birth control until pregnancy for a maximum of six menstrual cycles. The analyses include 181 pregnancies, of which 32 were subclinical pregnancies detected by hCG analysis only. During early...... pregnancy the women recorded physical strain prospectively in a structured diary. Physical strain around the time of implantation was associated with later spontaneous abortion. The adjusted risk ratio for women who reported physical strain higher than average at day 6 to 9 after the estimated date...

  19. Spontaneous Enterocutaneous Fistula Resulting from Richter's Hernia. (United States)

    Hajong, Ranendra; Khongwar, Donkupar; Komut, Ojing; Naku, Narang; Baru, Kappa


    Richter's hernia is due to the entrapment of a part of circumference of the bowel wall. As the bowel continuity is maintained, the patients usually do not have intestinal obstruction. Some patients with Richter's hernia may present with enterocutaneous fistula either spontaneous or due to surgical intervention mistaking the obstructed hernia to be inguinal abscess. This is more so in developing countries due to lack of awareness among the masses or due to the delay in seeking medical attention. Presenting here is a case of a 53-year-old male patient with enterocutaneous fistula which occurred spontaneously and sought medical attention only after about three years of repeated discharge of yellowish fluid from the left inguinal region. Magnetic resonance fistulogram confirmed the diagnosis of enterocutaneous fistula. Laparotomy with resection and primary anastomosis of the fistulous bowel was done. Patient recovered uneventfully without any complications or recurrence.

  20. Spontaneous Coronary Artery Dissection and Pregnancy. (United States)

    Naderi, Sahar


    Spontaneous coronary artery dissection (SCAD) is a non-atherosclerotic, non-traumatic cause of coronary artery dissection. SCAD is the most common cause of myocardial infarction in pregnancy or the postpartum period and results in significant cardiovascular morbidity and mortality in the pregnant population. It is important to consider pregnancy-associated spontaneous coronary artery dissection (PASCAD) high on the differential for a pregnant woman who presents with symptoms consistent with acute coronary syndrome. Management of these patients requires a thoughtful, multidisciplinary approach, with consideration of conservative management if possible. Counseling regarding future pregnancies is also critical and requires compassionate care. Given our limited understanding of SCAD, including PASCAD, more data and research are needed to help guide diagnosis, management, and determination of prognosis.

  1. Spontaneous stress fractures of the femoral neck

    International Nuclear Information System (INIS)

    Dorne, H.L.; Lander, P.H.


    The diagnosis of spontaneous stress fractures of the femoral neck, a form of insufficiency stress fracture, can be missed easily. Patients present with unremitting hip pain without a history of significant trauma or unusual increase in daily activity. The initial radiographic features include osteoporosis, minor alterations of trabecular alignment, minimal extracortical or endosteal reaction, and lucent fracture lines. Initial scintigraphic examinations performed in three of four patients showed focal increased radionuclide uptake in two and no focal abnormality in one. Emphasis is placed on the paucity of early findings. Evaluation of patients with persistent hip pain requires a high degree of clinical suspicion and close follow-up; the sequelae of undetected spontaneous fractures are subcapital fracture with displacement, angular deformity, and a vascular necrosis of the femoral head

  2. Motivational Projections of Russian Spontaneous Speech

    Directory of Open Access Journals (Sweden)

    Galina M. Shipitsina


    Full Text Available The article deals with the semantic, pragmatic and structural features of words, phrases, dialogues motivation, in the contemporary Russian popular speech. These structural features are characterized by originality and unconventional use. Language material is the result of authors` direct observation of spontaneous verbal communication between people of different social and age groups. The words and remarks were analyzed in compliance with the communication system of national Russian language and cultural background of popular speech. Studies have discovered that in spoken discourse there are some other ways to increase the expression statement. It is important to note that spontaneous speech identifies lacunae in the nominative language and its vocabulary system. It is proved, prefixation is also effective and regular way of the same action presenting. The most typical forms, ways and means to update language resources as a result of the linguistic creativity of native speakers were identified.

  3. Spontaneous pneumomediastinum due to paralytic rabies

    Directory of Open Access Journals (Sweden)

    Wuping Wang


    Full Text Available Rabies is a fatal disease resulting from rabies virus infection, causing severe neurological symptoms and ultimately death by destroying the nervous system. In general, a patient tends to see a neurologist or an infectious diseases physician, with very common and typical discipline-related signs and symptoms, such as hydrophobia, aerophobia, and mental disorders. However, we reported a rabies patient who was first admitted to see a thoracic surgeon with spontaneous pneumomediastinum.

  4. Spontaneous pneumomediastinum due to paralytic rabies

    Directory of Open Access Journals (Sweden)

    Wuping Wang

    Full Text Available Rabies is a fatal disease resulting from rabies virus infection, causing severe neurological symptoms and ultimately death by destroying the nervous system. In general, a patient tends to see a neurologist or an infectious diseases physician, with very common and typical discipline-related signs and symptoms, such as hydrophobia, aerophobia, and mental disorders. However, we reported a rabies patient who was first admitted to see a thoracic surgeon with spontaneous pneumomediastinum.

  5. Self energy QED: Multipole spontaneous emission

    International Nuclear Information System (INIS)

    Salamin, Y.I.


    Within the context of Barut's self-field approach, we write the exact expression of the spontaneous atomic decay rate (Phys. Rev. A37, 2284 (1988)), in the long wavelength approximation, in terms of electric- and magnetic-like multipole contributions which are related to the matrix elements of the transition charge and current distributions of the relativistic electron. A number of features of these expressions are discussed and their generalization to interacting composite systems is also pointed out. (author). 8 refs

  6. Quantum mechanics with spontaneous localization and experiments

    International Nuclear Information System (INIS)

    Benatti, F.; Grassi, R.


    We examine from an experimental point of view the recently proposed models of spontaneous reduction. We compare their implications about decoherence with those of environmental effects. We discuss the treatment, within the considered models, of the so called quantum telegraph phenomenon and we show that, contrary to what has been recently stated, no problems are met. Finally, we review recent interesting work investigating the implications of dynamical reduction for the proton decay. (author). 16 refs, 4 figs, 3 tabs

  7. Spontaneous atlantoaxial subluxation associated with tonsillitis


    Shunmugam, Meenalochani; Poonnoose, Santosh


    Atlantoaxial subluxation is a rare condition and requires a high index of suspicion to diagnose and treat in order to avoid long-term sequelae. Here, we present a case of late presentation of a nontraumatic rotatory subluxation of the atlantoaxial joint or atlantoaxial rotatory subluxation. A 17-year-old girl presented 3 months after the onset of nonspecific upper limb sensory symptoms which eventually settled spontaneously. Initial conservative management by the general practitioner had no e...

  8. Ear infection - chronic (United States)

    Middle ear infection - chronic; Otitis media - chronic; Chronic otitis media; Chronic ear infection ... blocked, fluid can build up. When this happens, infection can occur. A chronic ear infection develops when ...

  9. Chronic kidney disease (United States)

    Kidney failure - chronic; Renal failure - chronic; Chronic renal insufficiency; Chronic kidney failure; Chronic renal failure ... that you do not have symptoms until your kidneys have almost ... end-stage renal disease (ESRD). At this stage, the kidneys are ...

  10. Spontaneous Regression of a Cervical Disk Herniation

    Directory of Open Access Journals (Sweden)

    Emre Delen


    Full Text Available A 54 years old female patient was admitted to our outpatient clinic with a two months history of muscle spasms of her neck and pain radiating to the left upper extremity. Magnetic resonance imaging had shown a large left-sided paracentral disk herniation at the C6-C7 disk space (Figure 1. Neurological examination showed no obvious neurological deficit. She received conservative treatment including bed rest, rehabilitation, and analgesic drugs. After 13 months, requested by the patient, a second magnetic resonance imaging study showed resolution of the disc herniation.(Figure 2 Although the literature contains several reports about spontaneous regression of herniated lumbar disc without surgical intervention, that of phenomenon reported for herniated cervical level is rare, and such reports are few[1]. In conclusion, herniated intervertebral disc have the potential to spontaneously regress independently from the spine level. With further studies, determining the predictive signs for prognostic evaluation for spontaneous regression which would yield to conservative treatment would be beneficial.

  11. Spontaneously emerging cortical representations of visual attributes (United States)

    Kenet, Tal; Bibitchkov, Dmitri; Tsodyks, Misha; Grinvald, Amiram; Arieli, Amos


    Spontaneous cortical activity-ongoing activity in the absence of intentional sensory input-has been studied extensively, using methods ranging from EEG (electroencephalography), through voltage sensitive dye imaging, down to recordings from single neurons. Ongoing cortical activity has been shown to play a critical role in development, and must also be essential for processing sensory perception, because it modulates stimulus-evoked activity, and is correlated with behaviour. Yet its role in the processing of external information and its relationship to internal representations of sensory attributes remains unknown. Using voltage sensitive dye imaging, we previously established a close link between ongoing activity in the visual cortex of anaesthetized cats and the spontaneous firing of a single neuron. Here we report that such activity encompasses a set of dynamically switching cortical states, many of which correspond closely to orientation maps. When such an orientation state emerged spontaneously, it spanned several hypercolumns and was often followed by a state corresponding to a proximal orientation. We suggest that dynamically switching cortical states could represent the brain's internal context, and therefore reflect or influence memory, perception and behaviour.

  12. Spontaneous Large Serous Retinal Pigment Epithelial Tear

    Directory of Open Access Journals (Sweden)

    Voraporn Chaikitmongkol


    Full Text Available Purpose: To report cases of spontaneous retinal pigment epithelial (RPE tear complicating serous pigment epithelial detachment (PED. Methods: The records of 3 Asian patients with spontaneous giant RPE tear were reviewed retrospectively by including clinical presentation, angiography, optical coherence tomography, fundus autofluorescence imaging, and visual outcome. Results: Three patients (4 eyes were included in this study, with a mean age of 48.3 (42–56 years, and a mean follow-up period of 7.75 (4–18 months. Fundus examination in all patients showed giant RPE tear associated with bullous PED. Two cases had a history of prior corticosteroid use, and 1 had no history of medication use. All 3 patients developed spontaneous resolution of subretinal fluid with no treatment. However, in patients who used corticosteroids, initial progression of the tear and subretinal fluid were observed despite ceasing medication. On subsequent follow-up, an incomplete RPE regeneration was demonstrated by fundus autofluorescence imaging, and choroidal neovascularization developed in 1 patient. Conclusion: Large PED with RPE tear is a rare manifestation. When the fovea is spared, visual prognosis is favorable. No specific treatment is required, but careful choroidal neovascularization monitoring should be performed.

  13. Spontaneous fission of the heaviest elements

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, D.C.


    Although spontaneous fission was discovered in /sup 238/U in 1940, detailed studies of the process were first made possible in the 1960's with the availability of milligram quantities of /sup 252/Cf. The advent of solid-state detectors made it possible to perform measurements of coincident fission fragments from even very short-lived spontaneous fission activities or those available in only very small quantities. Until 1971 it was believed that the main features of the mass and kinetic-energy distributions were essentially the same as those for thermal neutron-induced fission and that all low-energy fission proceeded via asymmetric mass division with total kinetic energies which could be derived by linear extrapolation from those of lighter elements. In 1971, measurements of /sup 257/Fm showed an increase in symmetric mass division with anomalously high TKE's. Subsequent experiments showed that in /sup 258/Fm and /sup 259/Fm, the most probable mass split was symmetric with very high total kinetic energy. Measurements for the heavier elements have shown symmetric mass distributions with both high and low total kinetic energies. Recent results for spontaneous fission properties of the heaviest elements are reviewed and compared with theory. 31 refs., 8 figs., 1 tab.

  14. Spontaneous Coronary Artery Dissection Associated With Pregnancy. (United States)

    Tweet, Marysia S; Hayes, Sharonne N; Codsi, Elisabeth; Gulati, Rajiv; Rose, Carl H; Best, Patricia J M


    Spontaneous coronary artery dissection (SCAD) is the most common cause of pregnancy-associated myocardial infarction and remains poorly characterized. This study sought to assess presentation, clinical factors, and outcomes of pregnancy-associated spontaneous coronary artery dissection (P-SCAD) compared with spontaneous coronary artery dissection not associated with pregnancy (NP-SCAD). A Mayo Clinic registry was established in 2010 to include comprehensive retrospective and prospective SCAD data. Records were reviewed to identify women who were pregnant or ≤12 weeks postpartum at time of SCAD. Complete records were available for 323 women; 54 women met criteria for P-SCAD (4 during pregnancy) and they were compared with 269 women with NP-SCAD. Most events occurred within the first month postpartum (35 of 50). Compared with NP-SCAD, P-SCAD patients more frequently presented with ST-segment elevation myocardial infarction (57% vs. 36%; p = 0.009), left main or multivessel SCAD (24% vs. 5%; p vs. 14%; p = 0.0027, respectively), and left ventricular function ≤35% (26% vs. 10%; p = 0.0071). Among women with imaging of other vascular territories, P-SCAD was less likely with a diagnosis of fibromuscular dysplasia and extracoronary vascular abnormalities (42% vs. 64%; p = 0.047; and 46% vs. 77%; p = 0.0032, respectively). Compared with U.S. birth data, women with P-SCAD were more often multiparous (p = 0.0167), had a history of infertility therapies (p = 0.0004), and had pre-eclampsia (p = 0.001). On long-term follow-up (median 2.3 years) recurrent SCAD occurred in 51 patients, with no difference in the Kaplan Meier 5-year recurrence rates (10% vs. 23%; p = 0.18). P-SCAD patients had more acute presentations and high-risk features than women with NP-SCAD did. The highest frequency of P-SCAD occurred during the first postpartum month and P-SCAD patients less often had extracoronary vascular abnormalities. Hormonal, hemodynamic variations, and yet

  15. Natural History of Progression of Chronic Kidney Disease in Stages ...

    African Journals Online (AJOL)

    Introduction: Patients with chronic kidney disease (CKD) often continue to progress spontaneously towards end stage renal disease (ESRD). In this report we studied the natural history of progression of CKD in a cohort of patients with stage 4 and 5 CKD. Methods: We retrospectively studied a cohort of patients in stage 4 ...

  16. Spontaneous Coronary Artery Dissection: A Rare Manifestation of Alport Syndrome (United States)

    Sethi, Prince; Steffen, Kelly; Jonsson, Orvar; Petrasko, Marian


    Alport syndrome (AS) is a genetic disorder due to inheritance of genetic mutations which lead to production of abnormal type IV collagen. AS has been associated with renal, auditory, and ocular diseases due to the presence of abnormal alpha chains of type IV collagen in the glomerulus, cochlea, cornea, lens, and retina. The resulting disorder includes hereditary nephritis, corneal opacities, anterior lenticonus, fleck retinopathy, temporal retinal thinning, and sensorineural deafness. Aortic and aortic valve pathologies have been described as extrarenal manifestations of AS in multiple case reports. One case report described intramural hematoma of the coronary artery. We report the first case of true spontaneous coronary artery dissection (SCAD) with an intimal flap as a very rare manifestation of AS. The patient is a 36-year-old female with history of AS with chronic kidney disease, hypertension, and obesity who presented to the emergency room with acute onset of substernal chest pain radiating to her neck and arms. Troponin was elevated, and ECG showed transient 1 mm ST-segment elevation in the inferior leads. Subsequent coronary angiography revealed localized dissection of the left circumflex artery. Percutaneous coronary angioplasty was performed and her symptoms improved. This case illustrates that SCAD may be a manifestation of AS patients with chest pain. PMID:28884028

  17. Spontaneous Coronary Artery Dissection: A Rare Manifestation of Alport Syndrome

    Directory of Open Access Journals (Sweden)

    Amornpol Anuwatworn


    Full Text Available Alport syndrome (AS is a genetic disorder due to inheritance of genetic mutations which lead to production of abnormal type IV collagen. AS has been associated with renal, auditory, and ocular diseases due to the presence of abnormal alpha chains of type IV collagen in the glomerulus, cochlea, cornea, lens, and retina. The resulting disorder includes hereditary nephritis, corneal opacities, anterior lenticonus, fleck retinopathy, temporal retinal thinning, and sensorineural deafness. Aortic and aortic valve pathologies have been described as extrarenal manifestations of AS in multiple case reports. One case report described intramural hematoma of the coronary artery. We report the first case of true spontaneous coronary artery dissection (SCAD with an intimal flap as a very rare manifestation of AS. The patient is a 36-year-old female with history of AS with chronic kidney disease, hypertension, and obesity who presented to the emergency room with acute onset of substernal chest pain radiating to her neck and arms. Troponin was elevated, and ECG showed transient 1 mm ST-segment elevation in the inferior leads. Subsequent coronary angiography revealed localized dissection of the left circumflex artery. Percutaneous coronary angioplasty was performed and her symptoms improved. This case illustrates that SCAD may be a manifestation of AS patients with chest pain.

  18. A polymorphism near IL28B is associated with spontaneous clearance of acute hepatitis C virus and jaundice. (United States)

    Tillmann, Hans L; Thompson, Alex J; Patel, Keyur; Wiese, Manfred; Tenckhoff, Hannelore; Nischalke, Hans D; Lokhnygina, Yuliya; Kullig, Ulrike; Göbel, Uwe; Capka, Emanuela; Wiegand, Johannes; Schiefke, Ingolf; Güthoff, Wolfgang; Grüngreiff, Kurt; König, Ingrid; Spengler, Ulrich; McCarthy, Jeanette; Shianna, Kevin V; Goldstein, David B; McHutchison, John G; Timm, Jörg; Nattermann, Jacob


    A single nucleotide polymorphism (SNP) upstream of the IL28B gene has been associated with response of patients with chronic hepatitis C to therapy with pegylated interferon and ribavirin and also with spontaneous clearance of acute hepatitis C in a heterogeneous population. We analyzed the association between IL28B and the clinical presentation of acute hepatitis C virus (HCV) infection in a homogeneous population. We analyzed the SNP rs12979860 in 190 women from the German anti-D cohort (infected with HCV genotype 1b via contaminated rhesus prophylaxis) and its association with spontaneous clearance. Clinical data were available in 136 women with acute infection who were also evaluated for IL28B genotype. Based on results of a TaqMan polymerase chain reaction assay, the rs12979860 SNP genotypes studied were C/C, C/T, or T/T. Spontaneous clearance was more common in patients with the C/C genotype (43/67; 64%) compared with C/T (22/90; 24%) or T/T (2/33; 6%) (P Jaundice during acute infection was more common among patients with C/C genotype (32.7%) than non-C/C patients (with C/T or T/T) (16.1%; P = .032). In C/C patients, jaundice during acute infection was not associated with an increased chance of spontaneous clearance (56.3%) compared with those without jaundice (60.6%). In contrast, in non-C/C patients, jaundice was associated with a higher likelihood of spontaneous clearance (42.9%) compared with those without jaundice (13.7%). The SNP rs12979860 upstream of IL28B is associated with spontaneous clearance of HCV. Women with the C/T or T/T genotype who did not develop jaundice had a lower chance of spontaneous clearance of HCV infection. Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

  19. [Chronic diarrhea]. (United States)

    Stelzer, Teresa; Heuss, Ludwig Theodor


    Defined by lasting more than four weeks - is a common but often challenging clinical scenario. It is important to be aware that diarrhoea means different things to different patients. The evaluation of chronic diarrhoea depends on taking an excellent history and careful physical examination as well as planning investigations thoughtfully. Functional diarrhea ist the most common cause of chronic diarrhea in the developed countries and motility disorders are more common than inflammatory, osmotic or secretory causes. In some cases categorizing patients by their stool characteristics can be helpful in directing further evaluation.

  20. [Spontaneous rupture of biceps brachii tendon; ultrasound diagnosis in emergency, apropose of two cases. Updating results of surgical repair]. (United States)

    Russo, Antonella


    The rupture of the biceps tendon has either thraumatic or spontaneous degenerative etiology. Degenerative tears can occur during physiological abduction of shoulder, just it has been verified in woman affected by arthromyalgic chronic pain, due to arthrosis, or lifting light weight, like the second case showed Clinical suspect has been confirmed by ultrasound in emergency, validating surgical decision, that's the only treatment for this kind of pathology (arthroscopic or wide open surgery).

  1. Multiple genetic switches spontaneously modulating bacterial mutability

    Directory of Open Access Journals (Sweden)

    Johnston Randal N


    Full Text Available Abstract Background All life forms need both high genetic stability to survive as species and a degree of mutability to evolve for adaptation, but little is known about how the organisms balance the two seemingly conflicting aspects of life: genetic stability and mutability. The DNA mismatch repair (MMR system is essential for maintaining genetic stability and defects in MMR lead to high mutability. Evolution is driven by genetic novelty, such as point mutation and lateral gene transfer, both of which require genetic mutability. However, normally a functional MMR system would strongly inhibit such genomic changes. Our previous work indicated that MMR gene allele conversion between functional and non-functional states through copy number changes of small tandem repeats could occur spontaneously via slipped-strand mis-pairing during DNA replication and therefore may play a role of genetic switches to modulate the bacterial mutability at the population level. The open question was: when the conversion from functional to defective MMR is prohibited, will bacteria still be able to evolve by accepting laterally transferred DNA or accumulating mutations? Results To prohibit allele conversion, we "locked" the MMR genes through nucleotide replacements. We then scored changes in bacterial mutability and found that Salmonella strains with MMR locked at the functional state had significantly decreased mutability. To determine the generalizability of this kind of mutability 'switching' among a wider range of bacteria, we examined the distribution of tandem repeats within MMR genes in over 100 bacterial species and found that multiple genetic switches might exist in these bacteria and may spontaneously modulate bacterial mutability during evolution. Conclusions MMR allele conversion through repeats-mediated slipped-strand mis-pairing may function as a spontaneous mechanism to switch between high genetic stability and mutability during bacterial evolution.

  2. Being Spontaneous: The Future of Telehealth Implementation? (United States)

    Mars, Maurice; Scott, Richard E


    The smartphone simplifies interprofessional communication, and smartphone applications can facilitate telemedicine activity. Much has been written about the steps that need to be followed to implement and establish a successful telemedicine service that is integrated into everyday clinical practice. A traditional and systematic approach has evolved incorporating activities such as strategy development, needs assessment, business cases and plans, readiness assessment, implementation plans, change management interventions, and ongoing monitoring and evaluation. This "best practice" has been promoted in the telehealth literature for many years. In contrast, several recent initiatives have arisen without any such formal undertakings. This article describes the strengths and weaknesses of two "spontaneous" telemedicine services in dermatology and burn management that have evolved in South Africa. Two spontaneous services were identified and reviewed. In one unsolicited service, doctors at rural referring hospitals have been taking photographs of skin lesions and sending them with a brief text message history to dermatologists using the instant messaging smartphone app, WhatsApp. In the other, burns service, admissions to the burns unit or the clinic were triaged by telephonic description of the case and completion of a preadmission questionnaire. More recently, management and referral decisions are made only after completion of the questionnaire and subsequent submission of photographs of the burn sent by WhatsApp, with the decision transmitted by text message. Although efficient and effective, potential legal and ethical shortcomings have been identified. These "spontaneous" telehealth services challenge traditional best practice, yet appear to lead to truly integrated practice and, therefore, are successful and warrant further study.


    Directory of Open Access Journals (Sweden)

    O. V. Smirnova


    Full Text Available Chronic gastritis is the most common disease of gastro-intestinal tract. Precancerous potential is among most important epidemiological features of chronic gastritis. Immune system plays a distinct role in transformation from precancerous state to malignancy. In this context, the aim of our work was a study of spontaneous and induced chemiluminescence activity of neutrophilic granulocytes in patients with chronic superficial gastritis, chronic atrophic gastritis and gastric cancer. The work presents results of comprehensive laboratory examination of patients with chronic gastritis (CG (a total of 85 persons. 25 patients with chronic atrophic gastritis (CAG, and 50 patients with gastric cancer (GC at the age of 19 to 70 years were enrolled. Control group included 115 healthy donors without gastrointestinal complaints at the age of 19 to 67 years. The study was performed with venous blood samples taken from cubital vein into Vacutainer tubes with sodium heparin (5 U/mL prior to starting any pathogenic treatment. Evaluation of spontaneous and induced chemiluminescence was performed for 90 minutes at a 36-channel “CL 3606” chemiluminescence analyzer (Russia. In our study, patients with gastric cancer showed clear unidirectional changes in chemiluminescent activity of neutrophilic granulocytes (NG. When measuring spontaneous and induced NG chemiluminescence, we diagnosed a decreased phagocytic activity characterized by prolonged time-to-peak and area under the curve for spontaneous and induced CL, thus presuming longer activation time required in cases of reduced phagocytic function. The NG activity in patients with chronic gastritis is not impaired, but, similar changes of time-to-peak and area under were detected. Chemiluminescent activity of NG is increased in the group of CAG patients, and, considering similar changes in activation time and area under the curve, NG also produce greater amount of reactive oxygen species. Thus, for all H

  4. Angyomatous vocal polypus: a complete spontaneous regression

    Directory of Open Access Journals (Sweden)

    Edmir Américo Lourenço

    Full Text Available The authors describe a male patient who had malignant lymphoma seven years ago which remitted with chemotherapy.Two years ago he developed dysphonia. An unilateral, pediculate smooth red lesion on the right vocal fold was later discovered. Even without benefit of medicamentosus treatment, the patient refused surgery. In a reevaluation using rigid telescopy of the larynx two years later, the lesion had disappeared, completely and spontaneously. As there are no existing publications on this topic, this case report is an alert that surgery should be recommended with extreme caution in this type of vocal disease.

  5. Cerebrovascular gene expression in spontaneously hypertensive rats

    DEFF Research Database (Denmark)

    Grell, Anne-Sofie; Frederiksen, Simona Denise; Edvinsson, Lars


    in the middle cerebral arteries from hypertensive compared to normotensive rats. The gene expression of 72 genes was decreased and the gene expression of 97 genes was increased. The following genes with a fold difference ≥1.40 were verified by quantitative PCR; Postn, Olr1, Fas, Vldlr, Mmp2, Timp1, Serpine1......, Mmp11, Cd34, Ptgs1 and Ptgs2. The gene expression of Postn, Olr1, Fas, Vldlr, Mmp2, Timp1 and Serpine1 and the protein expression of LOX1 (also known as OLR1) were significantly increased in the middle cerebral arteries from spontaneously hypertensive rats compared to Wistar-Kyoto rats. In conclusion...

  6. Spontaneous light emission from fibers in MINOS

    International Nuclear Information System (INIS)

    Avvakumov, S.; Barrett, W.L.; Belias, T.; Bower, C.; Erwin, A.; Kordosky, M.; Lang, K.; Lee, R.; Liu, J.; Miller, W.; Mualem, L.; Nichol, R.; Nelson, J.; Pearce, G.; Proga, M.; Rebel, B.; Ruddick, K.; Smith, C.; Thomas, J.; Vahle, P.; Webb, R.


    We report on the observation and measurements of unexpected background rates in the MINOS Far Detector. The noise level at the Far Detector is significantly greater than that expected from natural radioactivity and intrinsic photomultiplier dark current. We have conducted a series of additional tests which demonstrate that the excess rate is caused by spontaneous light emission in the wavelength-shifting fibers, which are used to read out signals from scintillator strips. This noise due to fibers exhibits an exponential fall off with time with a decay time constant of the order of 100 days

  7. Fracture of maternal sternum during spontaneous delivery. (United States)

    Stubert, J; Gerber, B


    We report of a maternal sternal fracture during a spontaneous delivery in a 31-year-old primipara without a suitable trauma. The putative mechanism of fracture was strong hyperflexion of the thoracic spine and additional cervical flexion with pushing the chin to the thorax due to active management of labour. The history of the healthy woman was free of related risk factors. A possible promoting factor might be pregnancy-induced bone loss. Although there were clear symptoms, the diagnosis of the fracture was delayed by a week because nobody took account of such a possibility.

  8. Chronic gastritis (United States)

    Sipponen, Pentti; Maaroos, Heidi-Ingrid


    Abstract Prevalence of chronic gastritis has markedly declined in developed populations during the past decades. However, chronic gastritis is still one of the most common serious pandemic infections with such severe killing sequelae as peptic ulcer or gastric cancer. Globally, on average, even more than half of people may have a chronic gastritis at present. Helicobacter pylori infection in childhood is the main cause of chronic gastritis, which microbial origin is the key for the understanding of the bizarre epidemiology and course of the disease. A life-long and aggressive inflammation in gastritis results in destruction (atrophic gastritis) of stomach mucosa with time (years and decades). The progressive worsening of atrophic gastritis results subsequently in dysfunctions of stomach mucosa. Atrophic gastritis will finally end up in a permanently acid-free stomach in the most extreme cases. Severe atrophic gastritis and acid-free stomach are the highest independent risk conditions for gastric cancer known so far. In addition to the risks of malignancy and peptic ulcer, acid-free stomach and severe forms of atrophic gastritis may associate with failures in absorption of essential vitamins, like vitamin B12, micronutrients (like iron, calcium, magnesium and zinc), diet and medicines. PMID:25901896

  9. Chronic gastritis. (United States)

    Sipponen, Pentti; Maaroos, Heidi-Ingrid


    Prevalence of chronic gastritis has markedly declined in developed populations during the past decades. However, chronic gastritis is still one of the most common serious pandemic infections with such severe killing sequelae as peptic ulcer or gastric cancer. Globally, on average, even more than half of people may have a chronic gastritis at present. Helicobacter pylori infection in childhood is the main cause of chronic gastritis, which microbial origin is the key for the understanding of the bizarre epidemiology and course of the disease. A life-long and aggressive inflammation in gastritis results in destruction (atrophic gastritis) of stomach mucosa with time (years and decades). The progressive worsening of atrophic gastritis results subsequently in dysfunctions of stomach mucosa. Atrophic gastritis will finally end up in a permanently acid-free stomach in the most extreme cases. Severe atrophic gastritis and acid-free stomach are the highest independent risk conditions for gastric cancer known so far. In addition to the risks of malignancy and peptic ulcer, acid-free stomach and severe forms of atrophic gastritis may associate with failures in absorption of essential vitamins, like vitamin B12, micronutrients (like iron, calcium, magnesium and zinc), diet and medicines.

  10. Chronic Meningococcaemia

    African Journals Online (AJOL)

    clinical features, complications, laboratory findings and treatment of this condition are discussed. The resemblance, both clinically and histologically, to allergic vasculitis is stressed. S. Air. Med. J., 48, 2154 (1974). Chronic meningococcaemia is an uncommon condition today, but was well recognised in the early decades of.

  11. Spontaneous cooperation for prosocials, but not for proselfs: Social value orientation moderates spontaneous cooperation behavior (United States)

    Mischkowski, Dorothee; Glöckner, Andreas


    Cooperation is essential for the success of societies and there is an ongoing debate whether individuals have therefore developed a general spontaneous tendency to cooperate or not. Findings that cooperative behavior is related to shorter decision times provide support for the spontaneous cooperation effect, although contrary results have also been reported. We show that cooperative behavior is better described as person × situation interaction, in that there is a spontaneous cooperation effect for prosocial but not for proself persons. In three studies, one involving population representative samples from the US and Germany, we found that cooperation in a public good game is dependent on an interaction between individuals’ social value orientation and decision time. Increasing deliberation about the dilemma situation does not affect persons that are selfish to begin with, but it is related to decreasing cooperation for prosocial persons that gain positive utility from outcomes of others and score high on the related general personality trait honesty/humility. Our results demonstrate that the spontaneous cooperation hypothesis has to be qualified in that it is limited to persons with a specific personality and social values. Furthermore, they allow reconciling conflicting previous findings by identifying an important moderator for the effect. PMID:26876773

  12. Spontaneous pneumothorax in paracoccidioidomycosis patients from an endemic area in Midwestern Brazil. (United States)

    Cabrera, Lucas G G; Santos, Aline F; Andrade, Ursulla V; Guedes, Carlos Ivan A; Oliveira, Sandra M V L; Chang, Marilene R; Mendes, Rinaldo P; Paniago, Anamaria M M


    Paracoccidioidomycosis (PCM) is the most important systemic mycosis in Latin America. About 80% of PCM patients are present with its chronic form. The lungs are affected in most patients with the chronic form; however, pleural involvement has rarely been reported. We describe nine cases of PCM that presented with lung involvement and spontaneous pneumothorax. All patients, except one whose condition was not investigated, were smokers. PCM was diagnosed during the pneumothorax episode in three patients, and from 3 to 16 years before the pneumothorax episode in six patients. A total of six patients underwent chest drainage and one died as a direct result of the pneumothorax. We suggest that pneumothorax, although rare, should be considered in PCM patients who present with suddenly worsening dyspnoea. PCM should also be investigated in cases of pneumothorax in adult men from mycosis-endemic areas. © 2016 Blackwell Verlag GmbH.

  13. Impairments of spontaneous and deliberative mentalizing co-occur, yet dissociate, in schizophrenia. (United States)

    Langdon, Robyn; Flynn, Michaela; Connaughton, Emily; Brüne, Martin


    goal-driven behaviours. These impairments were even more pronounced when participants were instructed to think of the stimuli as people, suggesting that perceiving others in social roles does not prompt people with schizophrenia to anthropomorphize about others as agents motivated by their own inner worlds. Impairments of spontaneous mentalizing were found to co-occur independently with explicit mentalizing deficits in schizophrenia, consistent with the claim that humans can access two distinct systems for understanding others' minds. Findings suggest that interventions to improve conscious deliberative mentalizing in schizophrenia may not be enough; we also need to target implicit mentalizing processes. Limitations The patient sample was chronic and only mildly symptomatic. As such, findings cannot be generalized to other stages and phases of the illness. All patients were also medicated, allowing for the possibility that automatic responses to socially salient stimuli may have been pharmacologically attenuated. Future research may examine whether unmedicated young people at ultra-high risk of psychosis show a similar profile of mentalizing impairment. Future work may also examine whether impairments of deliberative and spontaneous mentalizing associate differentially with social functioning and different cognitive domains in schizophrenia. © 2017 The British Psychological Society.

  14. Spontaneous regression of intracranial malignant lymphoma

    International Nuclear Information System (INIS)

    Kojo, Nobuto; Tokutomi, Takashi; Eguchi, Gihachirou; Takagi, Shigeyuki; Matsumoto, Tomie; Sasaguri, Yasuyuki; Shigemori, Minoru.


    In a 46-year-old female with a 1-month history of gait and speech disturbances, computed tomography (CT) demonstrated mass lesions of slightly high density in the left basal ganglia and left frontal lobe. The lesions were markedly enhanced by contrast medium. The patient received no specific treatment, but her clinical manifestations gradually abated and the lesions decreased in size. Five months after her initial examination, the lesions were absent on CT scans; only a small area of low density remained. Residual clinical symptoms included mild right hemiparesis and aphasia. After 14 months the patient again deteriorated, and a CT scan revealed mass lesions in the right frontal lobe and the pons. However, no enhancement was observed in the previously affected regions. A biopsy revealed malignant lymphoma. Despite treatment with steroids and radiation, the patient's clinical status progressively worsened and she died 27 months after initial presentation. Seven other cases of spontaneous regression of primary malignant lymphoma have been reported. In this case, the mechanism of the spontaneous regression was not clear, but changes in immunologic status may have been involved. (author)

  15. Spontaneous bending of pre-stretched bilayers. (United States)

    DeSimone, Antonio


    We discuss spontaneously bent configurations of pre-stretched bilayer sheets that can be obtained by tuning the pre-stretches in the two layers. The two-dimensional nonlinear plate model we use for this purpose is an adaptation of the one recently obtained for thin sheets of nematic elastomers, by means of a rigorous dimensional reduction argument based on the theory of Gamma-convergence (Agostiniani and DeSimone in Meccanica. doi:10.1007/s11012-017-0630-4, 2017, Math Mech Solids. doi:10.1177/1081286517699991, arXiv:1509.07003, 2017). We argue that pre-stretched bilayer sheets provide us with an interesting model system to study shape programming and morphing of surfaces in other, more complex systems, where spontaneous deformations are induced by swelling due to the absorption of a liquid, phase transformations, thermal or electro-magnetic stimuli. These include bio-mimetic structures inspired by biological systems from both the plant and the animal kingdoms.

  16. Surgery for spontaneous intracerebral hemorrhage: Emerging trends

    Directory of Open Access Journals (Sweden)

    Girish Menon


    Full Text Available In spite of advances in imaging and surgical techniques, spontaneous intracerebral hemorrhage (SICH has defied attempts to find a scientifically proven effective therapy. The pathophysiology of SICH suggests that early removal of the clot with minimal additional surgical trauma should prove beneficial. Trials in this direction have been few, and for some unknown reason, surgery has not proved to be superior to best medical management in most of these trials. This has led to substantial variability in the management of ICH throughout the world, and the treatment of SICH remains a controversy. SICH encompasses spectra of possible clot locations with varying volumes. Surgery so far has been reserved only for patients with large hematomas and impending brain herniation. Critical analysis of the earlier studies has now shown that surgery does help in clots in certain locations and of particular volume and when done at an optimal time. Poor grade patients with large hematomas, earlier considered poor surgical candidates are being taken up for aggressive decompressive craniectomies with fair results. In addition, minimally invasive surgical techniques complemented by thrombolytic techniques seem to providing surprisingly good results. Overall surgery seems to be going through a period of renaissance with respect to primary spontaneous ICHs.

  17. Spontaneous unscheduled DNA synthesis in human lymphocytes

    International Nuclear Information System (INIS)

    Forell, B.; Myers, L.S. Jr.; Norman, A.


    The rate of spontaneous unscheduled DNA synthesis in human lymphocytes was estimated from measurements of tritiated thymidine incorporation into double-stranded DNA (ds-DNA) during incubation of cells in vitro. The contribution of scheduled DNA synthesis to the observed incorporation was reduced by inhibiting replication with hydroxyurea and by separating freshly replicated single-stranded DNA (ss-DNA) from repaired ds-DNA by column chromatography. The residual contribution of scheduled DNA synthesis was estimated by observing effects on thymidine incorporation of: (a) increasing the rate of production of apurinic sites, and alternatively, (b) increasing the number of cells in S-phase. Corrections based on estimates of endogenous pool size were also made. The rate of spontaneous unscheduled DNA synthesis is estimated to be 490 +- 120 thymidine molecules incorporated per cell per hour. These results compare favorably with estimates made from rates of depurination and depyrimidination of DNA, measured in molecular systems if we assume thymidine is incorporated by a short patch mechanism which incorporates an average of four bases per lesion

  18. Spontaneous ad hoc mobile cloud computing network. (United States)

    Lacuesta, Raquel; Lloret, Jaime; Sendra, Sandra; Peñalver, Lourdes


    Cloud computing helps users and companies to share computing resources instead of having local servers or personal devices to handle the applications. Smart devices are becoming one of the main information processing devices. Their computing features are reaching levels that let them create a mobile cloud computing network. But sometimes they are not able to create it and collaborate actively in the cloud because it is difficult for them to build easily a spontaneous network and configure its parameters. For this reason, in this paper, we are going to present the design and deployment of a spontaneous ad hoc mobile cloud computing network. In order to perform it, we have developed a trusted algorithm that is able to manage the activity of the nodes when they join and leave the network. The paper shows the network procedures and classes that have been designed. Our simulation results using Castalia show that our proposal presents a good efficiency and network performance even by using high number of nodes.

  19. Spontaneous and stimulated emission from quasifree electrons (United States)

    Friedman, A.; Gover, A.; Kurizki, G.; Ruschin, S.; Yariv, A.


    This article presents a unified formulation and review of an extensive class of radiation effects and devices based on free or quasifree electrons. The effects and devices reviewed include slow-wave radiators [such as Čerenkov, Smith-Purcell, and TWT (traveling-wave tube) effects and devices], periodic bremsstrahlung radiators [such as undulator radiation, magnetic bremsstrahlung FEL's (free-electron lasers), and coherent bremsstrahlung in the crystal lattice], and transverse-binding radiators [such as the CRM (cyclotron resonance maser) and channeling radiation]. Starting from a general quantum-electrodynamic model, both quantum and classical effects and operating regimes of these radiation devices are described. The article provides a unified physical description of the interaction kinematics, and presents equations for the characterization of spontaneous and stimulated radiative emission in these various effects and devices. Universal relations between the spontaneous and stimulated emission parameters are revealed and shown to be related (in the quantum limit) to Einstein relations for atomic radiators and (in the classical limit) to the relations derived by Madey for magnetic bremsstrahlung FEL for on-axis radiative emission. Examples for the application of the formulation are given, estimating the feasibility of channeling radiation x-ray laser and optical regime Smith-Purcell FEL, and deriving the gain equations of magnetic bremsstrahlung FEL and CRM for arbitrary electron propagation direction, structure (wiggler) axis, and radiative emission angle.

  20. Progesterone to prevent spontaneous preterm birth (United States)

    Romero, Roberto; Yeo, Lami; Chaemsaithong, Piya; Chaiworapongsa, Tinnakorn; Hassan, Sonia


    Summary Preterm birth is the leading cause of perinatal morbidity and mortality worldwide, and its prevention is an important healthcare priority. Preterm parturition is one of the ‘great obstetrical syndromes’ and is caused by multiple etiologies. One of the mechanisms of disease is the untimely decline in progesterone action, which can be manifested by a sonographic short cervix in the midtrimester. The detection of a short cervix in the midtrimester is a powerful risk factor for preterm delivery. Vaginal progesterone can reduce the rate of preterm delivery by 45%, and the rate of neonatal morbidity (admission to neonatal intensive care unit, respiratory distress syndrome, need for mechanical ventilation, etc.). To prevent one case of spontaneous preterm birth birth in women with a short cervix both with and without a prior history of preterm birth. In patients with a prior history of preterm birth, vaginal progesterone is as effective as cervical cerclage to prevent preterm delivery. 17α-Hydroxyprogesterone caproate has not been shown to be effective in reducing the rate of spontaneous preterm birth in women with a short cervix. PMID:24315687

  1. Microchimerism after induced or spontaneous abortion. (United States)

    Sato, Tomoko; Fujimori, Keiya; Sato, Akira; Ohto, Hitoshi


    To investigate fetomaternal microchimerism in women with induced abortion or spontaneous pregnancy loss. Peripheral blood samples were obtained from 76 healthy women who underwent dilation and curettage in the first trimester but had never had an abortion or male delivery before. Samples were collected at three time points: just before, 7 days after, and 30 days after abortion. Y chromosome-specific, nested polymerase chain reaction targeting the sex-determining region of Y (SRY) was used to test DNA extracted from buffy coat cells. DNA was also extracted from the chorion to determine sex. The sensitivity of our assay allowed detection of approximately one male cell in 100,000 female cells. Thirty-six male and 40 female chorions were obtained. Male DNA was found in 52.8% of women who had a male chorion before abortion, decreasing to 5.6% at 7 days after abortion. At 30 days after abortion, no male DNA was detected. Male DNA was never detected at any point from women with a female chorion. Fetal cells in the maternal circulation are undetectable 30 days after induced abortion or spontaneous pregnancy loss. Fetal cells may be harbored in maternal organs.

  2. Body Mass Index and spontaneous miscarriage.

    LENUS (Irish Health Repository)

    Turner, Michael J


    OBJECTIVE: We compared the incidence of spontaneous miscarriage in women categorised as obese, based on a Body Mass Index (BMI) >29.9 kg\\/m(2), with women in other BMI categories. STUDY DESIGN: In a prospective observational study conducted in a university teaching hospital, women were enrolled at their convenience in the first trimester after a sonogram confirmed an ongoing singleton pregnancy with fetal heart activity present. Maternal height and weight were measured digitally and BMI calculated. Maternal body composition was measured by advanced bioelectrical impedance analysis. RESULTS: In 1200 women, the overall miscarriage rate was 2.8% (n=33). The mean gestational age at enrolment was 9.9 weeks. In the obese category (n=217), the miscarriage rate was 2.3% compared with 3.3% in the overweight category (n=329), and 2.3% in the normal BMI group (n=621). There was no difference in the mean body composition parameters, particularly fat mass parameters, between those women who miscarried and those who did not. CONCLUSIONS: In women with sonographic evidence of fetal heart activity in the first trimester, the rate of spontaneous miscarriage is low and is not increased in women with BMI>29.9 kg\\/m(2) compared to women in the normal BMI category.

  3. Brain MRI findings of spontaneous intracranial hypotension

    Energy Technology Data Exchange (ETDEWEB)

    Park, Won Kyu; Byun, Woo Mok; Cho, Jae Ho; Cho Kil Ho; Hwang, Mi Soo; Park, Bok Hwan [Yeungnam Univ. College of Medicine, Taegu (Korea, Republic of); Joo, Yang Gu [Keimyoung Univ. College of Medicine, Taegu (Korea, Republic of); Lee, Sang Jin [Soonchunhyang Univ. College of Medicine, Seoul (Korea, Republic of)


    To evaluate brain MRI findings of spontaneous intracranial hypotension. A retrospective review of MRI findings was conducted on six patients with clinically proven spontaneous intracranial hypotension; no patient had a history of previous spinal puncture. Follow-up MRI was available in two patients, and to detect CSF leakage, radio-nuclide cisternography(n=3D5), myelography(n=3D1), and MR myelography(n=3D1) were performed. On contrast-enhanced T1WI, diffuse dural enhancement was seen in all cases, subdural hematoma or hygroma was seen in four cases, pituitary gland prominence in four, dural sinus dilatation in four, downward displacement of the cerebellar tonsil in two, downward displacement of the iter in one, and suprasellar and prepontine cistern effacement in two. In no patient was abnormal CSF leakage found. Although dural enhancement, as seen on MRI, is not specific, diffuse enhancement of the dura mater accompanied by subdural hematoma, hygroma, pituitary gland prominence, dural sinus dilatation, downward displacement of the cerebellar tonsil, or suprasellar and prepontine cistern effacement can strongly suggest intracranial hypotension.=20.

  4. In vitro evaluation of heat and moisture exchangers designed for spontaneously breathing tracheostomized patients. (United States)

    Brusasco, Claudia; Corradi, Francesco; Vargas, Maria; Bona, Margherita; Bruno, Federica; Marsili, Maria; Simonassi, Francesca; Santori, Gregorio; Severgnini, Paolo; Kacmarek, Robert M; Pelosi, Paolo


    Heat and moisture exchangers (HMEs) are commonly used in chronically tracheostomized spontaneously breathing patients, to condition inhaled air, maintain lower airway function, and minimize the viscosity of secretions. Supplemental oxygen (O2) can be added to most HMEs designed for spontaneously breathing tracheostomized patients. We tested the efficiency of 7 HMEs designed for spontaneously breathing tracheostomized patients, in a normothermic model, at different minute ventilations (VE) and supplemental O2 flows. HME efficiency was evaluated using an in vitro lung model at 2 VE (5 and 15 L/min) and 4 supplemental O2 flows (0, 3, 6, and 12 L/min). Wet and dry temperatures of the inspiratory flow were measured, and absolute humidity was calculated. In addition, HME efficiency at 0, 12, and 24 h use was evaluated, as well as resistance to flow at 0 and 24 h. The progressive increase in O2 flow from 0 to 12 L/min was associated with a reduction in temperature and absolute humidity. Under the same conditions, this effect was greater at lower VE. The HME with the best performance provided an absolute humidity of 26 mg H2O/L and a temperature of 27.8 °C. No significant changes in efficiency or resistance were detected during the 24 h evaluation. The efficiency of HMEs in terms of temperature and absolute humidity is significantly affected by O2 supplementation and V(E).

  5. [A Case of Spontaneous Cerebrospinal Fluid Leak Associated with Cervical Spondylosis]. (United States)

    Arai, Atsushi; Miyamoto, Hirohito; Shiomi, Ryoji; Tatsumi, Shotaro; Kohmura, Eiji


    Spontaneous cerebrospinal fluid leak and intracranial hypotension associated with cervical spondylosis have rarely been observed, and only a few cases are reported. A 69-year-old woman, previously treated for rectal and thyroid cancer, complained of a non-postural persistent headache. The patient regularly practiced aerobic exercise, but a month earlier she had started experiencing headache and neck pain while exercising. Computed tomography(CT)showed bilateral chronic subdural hematomas, and magnetic resonance imaging(MRI)revealed diffuse dural enhancement and tonsillar herniation. We drained the subdural hematomas and replaced the ventricular reservoir to safely access the cerebrospinal fluid space. After surgery, the persistent headache disappeared for several days, but a postural headache emerged. CT myelogram showed extradural accumulation of the contrast medium at the C2-5 level with cervical spondylosis. The patient was treated with conservative therapy of bed rest and intravenous fluid hydration for two weeks, and the headache improved. CT myelogram after treatment showed no extradural accumulation of the contrast medium. Spontaneous cerebrospinal fluid leak associated with cervical spondylosis could be induced by the repeated minor mechanical stress caused by physical exercise. Therefore, the possibility that non-postural persistent headache may be caused by spontaneous cerebrospinal fluid leak should not be underestimated.

  6. Spontaneous third ventriculostomy 8 years after diagnosis of obstructive hydrocephalus. (United States)

    Öğrenci, Ahmet; Ekşi, Murat Şakir; Koban, Orkun


    Spontaneous ventriculostomy is spontaneous rupture of membranes separating the ventricular system from the subarachnoid space in patients with chronic obstructive hydrocephalus that ends with resolution of symptoms. We present a case of spontaneous third ventriculostomy occurred in a 19-year-old girl 8 years after the initial diagnosis of hydrocephalus. An 11-year-old girl applied to the clinic with intermittent headaches. She was neurologically stable with no visual problems. On her brain MRI, obstructive hydrocephalus was observed. Cerebrospinal fluid diversion procedures were recommended, yet the family denied any interventional procedure. She had routine follow-ups with occasional clinical admissions because of ongoing intermittent headaches. On her last clinical visit, 8 years after the first one, she was in well condition with improvement in her headache in the last 4 months. Her new brain MRI showed an active CSF flow between the basal cistern and the third ventricle. In patients with aqueductal stenosis and without any other mass lesion, wait and see protocol might be conveyed in case of mild symptoms of hydrocephalus. However, there is need for large-scaled studies to make a more comprehensive statement for benign obstructive hydrocephalus cases.

  7. Maternal smoking predicts the risk of spontaneous abortion

    DEFF Research Database (Denmark)

    Nielsen, Ann; Hannibal, Charlotte Gerd; Lindekilde, Bodil Eriksen


    BACKGROUND: Few studies have examined smoking prior to pregnancy and the occurrence of spontaneous abortion, as most studies have addressed the risk of spontaneous abortion in relation to smoking during pregnancy. However, results are not entirely consistent. The aim of the present study...... was to assess the risk of spontaneous abortion considering smoking prior to pregnancy. METHODS: We performed a nested case-control study using prospective data from a population-based cohort comprising 11,088 women aged 20-29 years. From this cohort, women who experienced either a spontaneous abortion (n=343......) or who gave birth (n=1,578) during follow-up were selected. Associations between self-reported smoking at enrollment and subsequent spontaneous abortion were analyzed by means of multiple logistic regression. RESULTS: The risk of spontaneous abortion in relation to pre-pregnancy smoking showed a clear...

  8. Maternal underweight and the risk of spontaneous abortion

    DEFF Research Database (Denmark)

    Helgstrand, Stine; Andersen, Anne-Marie Nybo


    BACKGROUND: To evaluate the risk of spontaneous abortion in relation to maternal pre-pregnant underweight. METHODS: The study was designed as a cohort study within the framework of the Danish National Birth Cohort (DNBC). The participants were a total of 23 821 women recruited consecutively...... spontaneous abortion. Relative risk of spontaneous abortion was calculated as Hazard Ratios using Cox regression with delayed entry. RESULTS: The outcome measure was spontaneous abortion. The hazard ratio for spontaneous abortion in women with a pre-pregnant body mass index (BMI) below 18.5 was 1.24 (95......% confidence limits 0.95-1.63) compared to women with pre-pregnant BMI 18.5-24.9. Women with a BMI of 25 or more had a smaller increase in risk of spontaneous abortion. Adjustment for maternal age, parity, previous miscarriages, and lifestyle factors did not affect the estimates substantially, neither did...

  9. Spontaneous resolution of a herniated fragment cervical disc


    METE, Mesut; SAVRAN, Mehmet; DEMİRÇİVİ ÖZER, Füsun; DURANSOY, Yusuf Kurtuluş


    ABSTRACT Although the spontaneous resolution of herniated nucleus pulposus is a well known phe¬nomenon in lumbar disc herniations, it is rarely encountered in the cervical region. The spontaneous resolution of a herniated cervical disc in a woman is reported to describe a rare occurrence of spontaneous regression of a cervical herniated nucleus pulposus and to discuss its mechanism. A woman with a large and fragment herniated cervical disc refused to undergo operation and was followed-up ...

  10. Biomarkers of Spontaneous Recovery from Traumatic Spinal Cord Injury (United States)


    inflammation. 15. SUBJECT TERMS traumatic spinal cord injury, spinal cord , spontaneous recovery, functional recovery, inflammation, biomarkers, trauma 16...Award Number: W81XWH-15-1-0614 TITLE: Biomarkers of Spontaneous Recovery from Traumatic Spinal Cord Injury PRINCIPAL INVESTIGATOR: Ona Bloom...SUBTITLE 5a. CONTRACT NUMBER W81XWH-15-1-0614 W81XWH-15-1-0614 Biomarkers of Spontaneous Recovery from Traumatic Spinal Cord Injury 5b. GRANT NUMBER

  11. Chronic motor tic disorder (United States)

    Chronic vocal tic disorder; Tic - chronic motor tic disorder ... Chronic motor tic disorder is more common than Tourette syndrome . Chronic tics may be forms of Tourette syndrome. Tics usually start at ...

  12. Chronic Pancreatitis in Children (United States)

    ... Information Children/Pediatric Chronic Pancreatitis in Children Chronic Pancreatitis in Children What symptoms would my child have? ... will develop diabetes in adolescence. Who gets chronic pancreatitis? Those at risk for chronic pancreatitis are children ...

  13. Chronic obstructive pulmonary disease (United States)

    COPD; Chronic obstructive airways disease; Chronic obstructive lung disease; Chronic bronchitis; Emphysema; Bronchitis - chronic ... The best test for COPD is a lung function test called spirometry . ... into a small machine that tests lung capacity. The results can ...

  14. About Chronic Kidney Disease (United States)

    ... Advocacy Donate A to Z Health Guide About Chronic Kidney Disease Tweet Share Print Email Chronic kidney disease (CKD) ... Learn about Glomerular Filtration Rate (GFR) What is chronic kidney disease (CKD)? Chronic kidney disease includes conditions that damage ...

  15. Chronic myelogenous leukemia (CML) (United States)

    CML; Chronic myeloid leukemia; Chronic granulocytic leukemia; Leukemia - chronic granulocytic ... Kantarjian H, Cortes J. Chronic myeloid leukemia. In: Niederhuber JE, ... Oncology . 5th ed. Philadelphia, PA: Elsevier; 2014:chap ...

  16. Identification of the transcripts associated with spontaneous HCV clearance in individuals co-infected with HIV and HCV

    Directory of Open Access Journals (Sweden)

    Yue Chen


    Full Text Available Abstract Background Infection with human immunodeficiency virus (HIV influences the outcome and natural disease progression of hepatitis C virus (HCV infection. While the majority of HCV mono-infected and HCV/HIV co-infected subjects develop chronic HCV infection, 20–46% of mono- and co-infected subjects spontaneously clear HCV infection. The mechanism underlying viral clearance is not clearly understood. Analysis of differential cellular gene expression (mRNA between HIV-infected patients with persistent HCV infection or spontaneous clearance could provide a unique opportunity to decipher the mechanism of HCV clearance. Methods Plasma RNA from HIV/HCV co-infected subjects who cleared HCV and those who remained chronically infected with HCV was sequenced using Ion Torrent technology. The sequencing results were analyzed to identify transcripts that are associated with HCV clearance by measuring differential gene expression in HIV/HCV co-infected subjects who cleared HCV and those who remained chronically infected with HCV. Results We have identified plasma mRNA, the levels of which are significantly elevated (at least 5 fold, False Discovery Rate (FDR <0.05 before HCV infection in subjects who cleared HCV compared to those who remained chronically infected. Upon further analysis of these differentially expressed genes, before and after HCV infection, we found that before HCV infection 12 genes were uniquely upregulated in the clearance group compared to the chronically infected group. Importantly, a number of these 12 genes and their upstream regulators (such as CCL3, IL17D, LBP, SOCS3, NFKBIL1, IRF are associated with innate immune response functions. Conclusions These results suggest that subjects who spontaneously clear HCV may express these unique genes associated with innate immune functions.

  17. Spontaneous regression of a lumbar disc herniation: case report

    Directory of Open Access Journals (Sweden)

    Mostarchid Brahim El


    Full Text Available Lumbar disc herniation is a common disease that induces back pain and radicular pain. Some cases require conservative treatment or at times relived spontaneously. Spontaneous regression of disc herniation is an atypical clinical presentation, and it has been recognized with the advancement of recent advances in imaging techniques. We present a 35-year-old woman presented a spontaneous regression of a lumbar disc herniation with good outcome after intensive physical therapy program. Spontaneous regression of disc herniation is thought to occur via an inflammatory reaction with molecular mechanisms of phagocytic processes.

  18. Spontaneous closure of an ileostomy: A rare occurrence

    Directory of Open Access Journals (Sweden)

    Ashish Saxena


    CONCLUSION: Further research is warranted to understand the mechanism behind spontaneous regression of a stoma. Relationship between this event and intestinal tuberculosis or ATT needs to be analysed.

  19. Spontaneous regression of metastases from malignant melanoma: a case report

    DEFF Research Database (Denmark)

    Kalialis, Louise V; Drzewiecki, Krzysztof T; Mohammadi, Mahin


    A case of a 61-year-old male with widespread metastatic melanoma is presented 5 years after complete spontaneous cure. Spontaneous regression occurred in cutaneous, pulmonary, hepatic and cerebral metastases. A review of the literature reveals seven cases of regression of cerebral metastases......; this report is the first to document complete spontaneous regression of cerebral metastases from malignant melanoma by means of computed tomography scans. Spontaneous regression is defined as the partial or complete disappearance of a malignant tumour in the absence of all treatment or in the presence...

  20. Dorsomedial prefontal cortex supports spontaneous thinking per se. (United States)

    Raij, T T; Riekki, T J J


    Spontaneous thinking, an action to produce, consider, integrate, and reason through mental representations, is central to our daily experience and has been suggested to serve crucial adaptive purposes. Such thinking occurs among other experiences during mind wandering that is associated with activation of the default mode network among other brain circuitries. Whether and how such brain activation is linked to the experience of spontaneous thinking per se remains poorly known. We studied 51 healthy subjects using a comprehensive experience-sampling paradigm during 3T functional magnetic resonance imaging. In comparison with fixation, the experiences of spontaneous thinking and spontaneous perception were related to activation of wide-spread brain circuitries, including the cortical midline structures, the anterior cingulate cortex and the visual cortex. In direct comparison of the spontaneous thinking versus spontaneous perception, activation was observed in the anterior dorsomedial prefrontal cortex. Modality congruence of spontaneous-experience-related brain activation was suggested by several findings, including association of the lingual gyrus with visual in comparison with non-verbal-non-visual thinking. In the context of current literature, these findings suggest that the cortical midline structures are involved in the integrative core substrate of spontaneous thinking that is coupled with other brain systems depending on the characteristics of thinking. Furthermore, involvement of the anterior dorsomedial prefrontal cortex suggests the control of high-order abstract functions to characterize spontaneous thinking per se. Hum Brain Mapp 38:3277-3288, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  1. [Acute states in gastroenterology: spontaneous bacterial peritonitis and the acute intestinal pseudoobstruction syndrome]. (United States)

    Lukás, K


    Our article concentrates on two acute states, which develop less dramatically but their after-effects may be very serious: Spontaneous bacterial peritonitis and Ogilvie's syndrome. Spontaneous bacterial peritonitis is a bacterial infection of the ascitic fluid without any intraperitoneal source of infection. Ascites is a condition of the disease but need not be clinically manifested. Spontaneous bacterial peritonitis comes usually during heavy hepatic impairment. Diagnosis can be set according: 1. Positive cultivation of ascitic fluid, 2. PMN levels higher than 250/mm3, 3. No infection, which may require a surgical intervention is apparent. Liver disease, which brings about the spontaneous bacterial peritonitis can be: 1. Chronic (e.g. alcoholic cirrhosis), 2. Subacute (e.g. alcoholic hepatitis), 3. Acute (e.g. fulminant hepatic failure). Mortality of this form of peritonitis can reach up to 46%. The most frequent etiological factor is alcohol and viral hepatitis, the most frequent agents are E. coli and Klebsiella pneumoniae. The disease is most effectively cured by cefalosporins of the third generation. With inadequate treatment, prognosis may be poor. Intestinal pseudoobstruction syndrome has clinical symptomatology of a serious impairment with ileus without signs of any mechanical intestinal obstruction. Syndrome can be classified according to its development: 1. Acute form--acute intestinal pseudoobstruction syndrome--Ogilvie's syndrome, 2. Chronic form--chronic intestinal pseudoobstruction syndrome. Pathogenic mechanism of the syndrome is not known. The disease is related to immobility, administration of some drugs, electrolyte imbalance and concomitant diseases (most frequently malignant tumors). Clinical symptomatology dominates nausea, vomiting, diffuse abdominal pain, constipation or diarrhoea. For diagnostics the first step should be termination of all medication, which could have causing affects, then taking native abdominal X-ray picture where gaseous

  2. [Spontaneous antepartal RhD alloimmunization]. (United States)

    Studničková, M; Holusková, I; Durdová, V; Kratochvílová, T; Strašilová, P; Marková, I; Lubušký, M


    Assess the incidence of spontaneous antepartal RhD alloimmunization in RhD negative pregnant women with an RhD positive fetus. Clinical study. Department of Obstetrics and Gynecology, Medical School and University Hospital Olomouc. A total of 906 RhD negative women with an RhD positive fetus and without the presence of anti-Dalloantibodies at the beginning of pregnancy were examined. Always it was a singleton pregnancy, RhD blood group of the pregnant women was assessed in the 1st trimester of pregnancy, RhD status of the fetus was determined after delivery. Screening for irregular antierythrocyte antibodies was performed in all women in the 1st trimester of pregnancy, at 28-32 weeks gestation and immediately prior to delivery at 38-42 weeks gestation. Screening for irregular antierythrocyte antibodies was performed also at 6 months following delivery in all cases of positive antibodies before delivery. Antibody screening was performed using the indirect antiglobulin (LISS/NAT) and enzyme (papain) test with their subsequent identification using a panel of reference erythrocytes by column agglutination method Dia-Med. After delivery, the volume of fetomaternal hemorrhage was assesed in all RhD negative women and RhD alloimmunization prophylaxis was performed by administering the necessary IgG anti-D dose; none of the women were administered IgG anti-D antepartally. During screening for irregular antierythrocyte antibodies at 28-32 weeks gestation, anti-D alloantibodies were diagnosed in 0.2% of the women (2/906); immediately prior to the delivery at 38-42 weeks gestation, anti-D alloantibodies were diagnosed in 2.3% of the women (21/906) and repeatedly even at 6 months following delivery (21/157). In 82.7% of the women (749/906), examination at 6 months following delivery was not performed, therefore in these women spontaneous antepartal RhD alloimmunization cannot reliably be ruled out. Alloimmunization may not be diagnosed yet at term of delivery. If anti

  3. Japanese macaque encephalomyelitis: a spontaneous multiple sclerosis-like disease in a nonhuman primate (United States)

    Axthelm, Michael K.; Bourdette, Dennis N.; Marracci, Gail H.; Su, Weiping; Mullaney, Elizabeth T.; Manoharan, Minsha; Kohama, Steven G.; Pollaro, Jim; Witkowski, Ellen; Wang, Paul; Rooney, William D.; Sherman, Lawrence S.; Wong, Scott W.


    Objective To describe Japanese macaque encephalomyelitis (JME), a spontaneous inflammatory demyelinating disease occurring in the Oregon National Primate Research Center’s (ONPRC) colony of Japanese macaques (JM, Macaca fuscata). Methods JM with neurologic impairment were removed from the colony, evaluated and treated with supportive care. Animals were humanely euthanized and their central nervous system (CNS) examined. Results ONPRC’s JM colony was established in 1965 and no cases of JME occurred until 1986. Since 1986, 56 JM spontaneously developed a disease characterized clinically by paresis of one or more limbs, ataxia or ocular motor paresis. Most animals were humanely euthanized during their initial episode. Three recovered, later relapsed and were then euthanized. There was no gender predilection and the median age for disease was 4 years. Magnetic resonance imaging of eight cases of JME revealed multiple gadolinium enhancing T1-weighted hyperintensities in the white matter of the cerebral hemispheres, brainstem, cerebellum and cervical spinal cord. The CNS of monkeys with JME contained multifocal plaque-like demyelinated lesions of varying ages, including acute and chronic, active demyelinating lesions with macrophages and lymphocytic periventricular infiltrates, and chronic, inactive demyelinated lesions. A previously undescribed gamma-herpesvirus was cultured from acute JME white matter lesions. Cases of JME continue to affect 1–3% of the ONPRC colony per year. Interpretation JME is a unique spontaneous disease in a nonhuman primate that has similarities with multiple sclerosis (MS) and is associated with a novel simian herpesvirus. Elucidating the pathogenesis of JME may shed new light on MS and other human demyelinating diseases. PMID:21674589

  4. On the influence of ultraviolet radiation on spontaneous tumors in NMRI mice

    International Nuclear Information System (INIS)

    Koenigsmann, G.; Kinkel, H.J.; Bocionek, P.; Wolff, F.


    During a period of 12 and 15 months respectively, female NMRI mice were irradiated twelve hours per day with specific parts of the ultraviolet spectrum (three groups, each comprising 100 animals: non-irradiated control group, animals irradiated with B units, animals irradiated with A/B units). No considerable influence of the chronic exposure to ultraviolet radiation could be demonstrated with regard to the development of the body weight and the hematologic condition. Group B had the same rate of spontaneous tumors of the respiratory tract as the control group; this rate was higher in group A/B. As to the development of spontaneous tumors in the lymphatic tissues, there seems to be a dependence on radiation: the animals of group B presented a slightly higher, those of group A/B a higher development than the animals of the nonirradiated control group. It cannot be definitely clarified yet to what extent this increased tumor rate was additionally induced by the higher environmental temperature or other influences involved by experiment. Harding-Passey melanomas were inoculated in NMRI mice and, 48 hours later, they were exposed to defined emission spectra within the natural ultraviolet spectrum. The exposed animals showed a slower growth of the transplanted tumors than the non-exposed animals, and especially the animals exposed to UVB radiation had a longer survival time. This chronic irradiation test was carried out in order to examine the influence of defined emission spectra on autochthonous tumors in NMRI mice and on their spontaneous tumor rate and blood count. (orig.) [de

  5. Cerebrovascular gene expression in spontaneously hypertensive rats

    DEFF Research Database (Denmark)

    Grell, Anne-Sofie; Frederiksen, Simona Denise; Edvinsson, Lars


    Hypertension is a hemodynamic disorder and one of the most important and well-established risk factors for vascular diseases such as stroke. Blood vessels exposed to chronic shear stress develop structural changes and remodeling of the vascular wall through many complex mechanisms. However...

  6. Histopathological findings in chronic tendon disorders. (United States)

    Järvinen, M; Józsa, L; Kannus, P; Järvinen, T L; Kvist, M; Leadbetter, W


    Tendon injuries and other tendon disorders represent a common diagnostic and therapeutic challenge in sports medicine, resulting in chronic and long-lasting problems. Tissue degeneration is a common finding in many sports-related tendon complaints. In the great majority of spontaneous tendon ruptures, chronic degenerative changes are seen at the rupture site of the tendon (1). Systemic diseases and diseases specifically deteriorating the normal structure of the tendon (i.e. foreign bodies, and metabolic, inherited and infectious tendon diseases) are only rarely the cause of tendon pathology. Inherited diseases, such as various hereditary diseases with disturbed collagen metabolism and characteristic pathological structural alterations (Ehlers-Danlos syndrome, Marfani syndrome, homocystinuria (ochronosis)), represent approximately 1% of the causes of chronic tendon complaints (2), whereas foreign bodies are somewhat more common and are found in less than 10% of all chronic tendon problems (1). Rheumatoid arthritis and sarcoidosis are typical systemic diseases that cause chronic inflammation in tendon and peritendinous tissues. Altogether, these 'specific' disorders represented less than 2% of the pathological alterations found in the histological analysis of more than 1000 spontaneously ruptured tendons (1, 3, 4). In this material, degenerative changes were seen in a great majority of the tendons, indicating that a spontaneous tendon rupture is a typical clinical end-state manifestation of a degenerative process in the tendon tissue. The role of overuse in the pathogenesis of chronic tendon injuries and disorders is not completely understood. It has been speculated that when tendon is overused it becomes fatigued and loses its basal reparative ability, the repetitive microtraumatic processes thus overwhelming the ability of the tendon cells to repair the fiber damage. The intensive repetitive activity, which often is eccentric by nature, may lead to cumulative

  7. Chronic idiopathic angioedema: a single center experience. (United States)

    Eli, Magen; Joseph, Mishal; Kuznik, Boris; Menachem, Schlesinger


    Chronic idiopathic angioedema (CIA) is defined as three or more episodes of angioedema in a period of > 6 months without a clear etiology. In the study, we tried to explore clinical and laboratory characteristics of patients with CIA unaccompanied by urticaria. We retrospectively reviewed clinical and laboratory characteristics of 1238 patients with chronic urticaria and/or angioedema referred to our allergy clinic. Eight hundred and forty-one (67.9%) subjects had chronic urticaria without angioedema (CU Group), 323 (26.1%) had both urticaria and angioedema (CU + CA group), and 74 (5.9%) had chronic angioedema without urticaria (CA). In 29 (39.2%) cases of CA, no etiologic factor of angioedema was discovered, thus the patients were defined as having chronic idiopathic angioedema (CIA Group). Twenty-two (75.8%) subjects had antihistamine-responsive CIA and seven (24.1%) had antihistamine-unresponsive CIA. There were no statistically significant differences in clinical (except of urticarial eruptions) and laboratory characteristics between CU, CA + CU, and CIA groups. Antihistamine responsive and antihistamine-unresponsive CIA groups had no distinguishable clinical or laboratory features. We suppose that CIA, at least its antihistamine-responsive form, represents a rare form of chronic spontaneous urticaria. The reasons why in CIA there are no other clinical signs of mast cell/basophil activation, such as pruritus, urticarial, and dermatographism, are largely unknown and have to be elucidated in future studies. © 2014 The International Society of Dermatology.

  8. Traceability of biopharmaceuticals in spontaneous reporting systems

    DEFF Research Database (Denmark)

    Vermeer, Niels S; Straus, Sabine M J M; Mantel-Teeuwisse, Aukje K


    , including spontaneous reporting systems (SRSs), in which reports of ADRs are collected. OBJECTIVE: The aim of this study was to explore the current status of traceability of biopharmaceuticals in the US and the EU up to patient level in SRSs. DESIGN AND SETTING: A cross-sectional study was conducted over......BACKGROUND: Adverse drug reactions (ADRs) of biopharmaceuticals can be batch or product specific, resulting from small differences in the manufacturing process. Detailed exposure information should be readily available in systems for postmarketing safety surveillance of biopharmaceuticals...... the period 2004-2010, including ADR reports from two major SRSs: the FDA Adverse Event Reporting System (FAERS) in the US and EudraVigilance (EV) in the EU. MAIN OUTCOME MEASURES: The availability of batch numbers was determined for biopharmaceuticals, and compared with small molecule drugs...

  9. Spontaneously abandoned settlements in Serbia: Part 2

    Directory of Open Access Journals (Sweden)

    Milošević Marko V.


    Full Text Available This is the second part of the article “Spontaneously abandoned settlements in Serbia”, the first part of which was published in No. 60-2 of this Journal. Geomorphological indicators pointing at unsustainability of the studied settlements are singled out. The indicators are classified as morphometric (quantitative and morphologic (qualitative. Geomorphometry has been used for determination of quantitative indicators. The coefficient of settlement isolation (Ki is defined, which is a product of road coefficient (Kr and real relative height (RRH. Morphological indicators refer to the position of a settlement on a certain geomorphological unit (ridge, valley, valley side, as well as to the geomorphological homogeneity of space, determined by geomorphological mapping. The defined indicators of unsustainability are presented in detail as a case study of the abandoned village Smilov Laz, in the municipality of Novi Pazar.

  10. Spontaneous galactosylation of agalactoglycoproteins in colostrum. (United States)

    Oubihi, M; Kitajima, K; Aoki, N; Matsuda, T


    We have found that spontaneous galactosylation of GlcNAc residues occurs in bovine colostrum, but not in dialyzed colostrum, without adding UDP-Gal as a donor substrate. UDP-Gal was shown to be present in bovine colostrum at a level ranging from 200 to 600 microM. When a tracer UDP-[(14)C]Gal was added to the dialyzed colostrum together with a Gal beta1,4-specific beta-galactosidase, remarkable incorporation of radioactivity into 24-28 kDa and 33 kDa RCA1-positive glycoproteins was demonstrated by SDS-PAGE/autoradiography. Some 100-140 kDa agalactoglycoproteins of a CHO mutant cell line were also galactosylated on a blotted membrane by the incubation in the colostrum.

  11. Pneumomediastin spontané chez un asthmatique (United States)

    Elmoqaddem, Amine; Serghini, Issam; Janah, Hicham; Chouikh, Chakib; Alaoui, Amine; Bensghir, Mustapha


    Le pneumomédiastin spontané est une pathologie rare. Il se voit surtout chez l’adulte jeune. Sa survenue brutale est caractéristique, associant une douleur thoracique, un emphysème sous-cutané et une dyspnée. Nous rapportons l’observation d’un pneumomédiastin, chez un patient de 24 ans asthmatique déclenché suite à un effort de toux. Le patient s’est présenté dans un tableau d’insuffisance respiratoire aigue avec une douleur thoracique retrosternale. La radiographie pulmonaire a confirmé le diagnostic de pneumomédiastin. L’évolution a été favorable en 4 jours après exsufflation, oxygénothérapie et traitement médical conventionnel. PMID:28292057

  12. Constrained Gauge Fields from Spontaneous Lorentz Violation

    CERN Document Server

    Chkareuli, J L; Jejelava, J G; Nielsen, H B


    Spontaneous Lorentz violation realized through a nonlinear vector field constraint of the type $A_{\\mu}^{2}=M^{2}$ ($M$ is the proposed scale for Lorentz violation) is shown to generate massless vector Goldstone bosons, gauging the starting global internal symmetries in arbitrary relativistically invariant theories. The gauge invariance appears in essence as a necessary condition for these bosons not to be superfluously restricted in degrees of freedom, apart from the constraint due to which the true vacuum in a theory is chosen by the Lorentz violation. In the Abelian symmetry case the only possible theory proves to be QED with a massless vector Goldstone boson naturally associated with the photon, while the non-Abelian symmetry case results in a conventional Yang-Mills theory. These theories, both Abelian and non-Abelian, look essentially nonlinear and contain particular Lorentz (and $CPT$) violating couplings when expressed in terms of the pure Goldstone vector modes. However, they do not lead to physical ...

  13. Spontaneous unilamellar polymer vesicles in aqueous solution. (United States)

    Kim, Tae-Hwan; Song, Chaeyeon; Han, Young-Soo; Jang, Jong-Dae; Choi, Myung Chul


    A unilamellar polymeric vesicle is a self-assembled structure of a block copolymer that forms a spherical single bilayer structure with a hydrophobic interlayer and a hydrophilic surface. Due to their enhanced colloidal stability and mechanical property, controllable surface functionality, or tunable membrane thickness, polymeric vesicles are useful in nano and bio-science, providing potential applications as nanosized carriers for catalysts, drugs, and enzymes. For fabrication of a unilamellar vesicle, however, preparative procedures with a few steps are inherently required. Herein, without complicated preparative procedures, we report spontaneous unilamellar polymeric vesicles with nanometer sizes (small angle neutron scattering and cryo-TEM, resulting in a phase diagram drawn as a function of temperature and the 5mS concentration. Interestingly the critical temperature for the micelle-to-vesicle phase transition was easily controlled by varying the 5mS concentration, i.e. it was decreased with increasing the 5mS concentration.

  14. Spontaneous jamming in one-dimensional systems (United States)

    O'Loan, O. J.; Evans, M. R.; Cates, M. E.


    We study the phenomenon of jamming in driven diffusive systems. We introduce a simple microscopic model in which jamming of a conserved driven species is mediated by the presence of a non-conserved quantity, causing an effective long-range interaction of the driven species. We study the model analytically and numerically, providing strong evidence that jamming occurs; however, this proceeds via a strict phase transition (with spontaneous symmetry breaking) only in a prescribed limit. Outside this limit, the nearby transition (characterised by an essential singularity) induces sharp crossovers and transient coarsening phenomena. We discuss the relevance of the model to two physical situations: the clustering of buses, and the clogging of a suspension forced along a pipe.

  15. Spontaneous aortic dissecting hematoma in two dogs. (United States)

    Boulineau, Theresa Marie; Andrews-Jones, Lydia; Van Alstine, William


    This report describes 2 cases of spontaneous aortic dissecting hematoma in young Border Collie and Border Collie crossbred dogs. Histology was performed in one of the cases involving an unusual splitting of the elastin present within the wall of the aorta, consistent with elastin dysplasia as described in Marfan syndrome in humans. The first case involved a young purebred Border Collie that died suddenly and the second case involved a Border Collie crossbred dog that died after a 1-month history of seizures. Gross lesions included pericardial tamponade with dissection of the ascending aorta in the former case and thoracic cavity hemorrhage, mediastinal hematoma, and aortic dissection in the latter. Histologic lesions in the case of the Border Collie crossbred dog included a dissecting hematoma of the ascending aorta with elastin dysplasia and right axillary arterial intimal proliferation.

  16. A Young Man with Bilateral Spontaneous Pneumothorax

    Directory of Open Access Journals (Sweden)

    Liese Lieve Willemien Verhaert


    Full Text Available Case. A 33-year-old male nonsmoker presented with sudden onset of dyspnoea and thoracic pain. Chest radiograph showed a left-sided pneumothorax. Few days later he developed a right-sided pneumothorax. He had a positive family history of pneumothorax. High-resolution computed tomography of the chest showed multiple pulmonary cysts predominantly located in the lower lung regions. We suspected Birt-Hogg-Dubé syndrome (BHD. Conclusion. Birt-Hogg-Dubé syndrome is a rare autosomal dominant inherited genodermatosis and characterised by clinical manifestations including hamartomas of the skin, renal tumors, and pulmonary cysts with spontaneous pneumothorax. BHD is probably underdiagnosed because of the wide variability in its clinical expression. It is important to recognize these patients because of the possibility of developing renal cancer.

  17. Constrained gauge fields from spontaneous Lorentz violation

    DEFF Research Database (Denmark)

    Chkareuli, J. L.; Froggatt, C. D.; Jejelava, J. G.


    Spontaneous Lorentz violation realized through a nonlinear vector field constraint of the type AµAµ=M2 (M is the proposed scale for Lorentz violation) is shown to generate massless vector Goldstone bosons, gauging the starting global internal symmetries in arbitrary relativistically invariant...... theories. The gauge invariance appears in essence as a necessary condition for these bosons not to be superfluously restricted in degrees of freedom, apart from the constraint due to which the true vacuum in a theory is chosen by the Lorentz violation. In the Abelian symmetry case the only possible theory...... couplings when expressed in terms of the pure Goldstone vector modes. However, they do not lead to physical Lorentz violation due to the simultaneously generated gauge invariance. Udgivelsesdato: June 11...

  18. Spontaneous Esophageal Injury: Esophageal Intramural Hematoma

    Directory of Open Access Journals (Sweden)

    Yu-Hui Chiu


    Full Text Available Acute chest pain can indicate a life-threatening condition and it is important for physicians to diagnose and treat it as a matter of urgency. We report 1 rare case of esophageal intramural hematoma (IMH that presented with chest pain at the emergency department and which was initially clinically suspected to be due to aortic dissection. The case was diagnosed preoperatively by multidetector computed tomography. Esophageal IMH may represent an intermediate stage between Mallory-Weiss tear (mucosal and Boerhaave's syndrome (transmural. Multidetector computed tomography is a useful noninvasive imaging modality for accurate diagnosis of these spontaneous intramural and transmural ruptures of the esophagus, and aids in the differential diagnosis of aortic and other mediastinal diseases with acute chest pain.

  19. Spontaneous spherical symmetry breaking in atomic confinement (United States)

    Sveshnikov, Konstantin; Tolokonnikov, Andrey


    The effect of spontaneous breaking of initial SO(3) symmetry is shown to be possible for an H-like atom in the ground state, when it is confined in a spherical box under general boundary conditions of "not going out" through the box surface (i.e. third kind or Robin's ones), for a wide range of physically reasonable values of system parameters. The most novel and nontrivial result, which has not been reported previously, is that such an effect takes place not only for attractive, but also for repulsive interactions of atomic electrons with the cavity environment. Moreover, in the limit of a large box size R ≫ aB the regime of an atom, soaring over a plane with boundary condition of "not going out", is reproduced, rather than a spherically symmetric configuration, which would be expected on the basis of the initial SO(3) symmetry of the problem.

  20. Spontaneous Heterotopic Triplet Pregnancy With Tubal Rupture

    Directory of Open Access Journals (Sweden)

    Lima Arsala MBBS, BBMedSci


    Full Text Available The recent increase in heterotopic pregnancies has been largely attributed to the increased use of assisted reproduction technologies. We report the rare case of a multiparous woman with a spontaneous conception resulting in a triplet heterotopic pregnancy: a twin intrauterine pregnancy and a single right tubal ectopic pregnancy. Heterotopic pregnancy is a rare and potentially life-threatening condition in which simultaneous gestations occur at 2 or more implantation sites. It is infrequent in natural conception cycles, occurring in 1:30 000 pregnancies. However, the prevalence is rising with the increased use of assisted reproduction techniques to that of 1:100 to 1:500 in these patient subgroups, highlighting the need to incorporate it into a clinician’s diagnostic algorithm.