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Sample records for adult acute monocytic

  1. Cytarabine With or Without SCH 900776 in Treating Adult Patients With Relapsed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-20

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia

  2. Decitabine, Cytarabine, and Daunorubicin Hydrochloride in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-20

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  3. Diarrhoea in adults (acute)

    PubMed Central

    2008-01-01

    Introduction An estimated 4000 million cases of diarrhoea occurred worldwide in 1996, resulting in 2.5 million deaths. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for acute diarrhoea in adults living in resource-rich countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults from resource-rich countries traveling to resource-poor countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults living in resource-poor countries? What are the effects of treatments for acute severe diarrhoea in adults living in resource-poor countries? We searched: Medline, Embase, The Cochrane Library and other important databases up to January 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 71 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, antimotility agents, antisecretory agents, bismuth subsalicylate, diet, intravenous rehydration, nasogastric tube rehydration, and oral rehydration solutions (amino acid oral rehydration solution, bicarbonate oral rehydration solution, reduced osmolarity oral rehydration solution, rice-based oral rehydration solution, standard oral rehydration solution). PMID:19450323

  4. Diarrhoea in adults (acute)

    PubMed Central

    2011-01-01

    Introduction An estimated 4.6 billion cases of diarrhoea occurred worldwide in 2004, resulting in 2.2 million deaths. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for acute diarrhoea in adults living in resource-rich countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults from resource-rich countries travelling to resource-poor countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults living in resource-poor countries? What are the effects of treatments for acute severe diarrhoea in adults living in resource-poor countries? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 72 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, antimotility agents, antisecretory agents, bismuth subsalicylate, diet, intravenous rehydration, nasogastric tube rehydration, oral rehydration solutions (amino acid oral rehydration solution, bicarbonate oral rehydration solution, reduced osmolarity oral rehydration solution, rice-based oral rehydration solution, standard oral rehydration solution), vitamin A supplementation, and zinc supplementation. PMID:21718555

  5. The Role of Different Monocyte Subsets in the Pathogenesis of Atherosclerosis and Acute Coronary Syndromes.

    PubMed

    Idzkowska, E; Eljaszewicz, A; Miklasz, P; Musial, W J; Tycinska, A M; Moniuszko, M

    2015-09-01

    The inflammation underlying both atherosclerosis and acute coronary syndromes is strongly related to monocyte-related actions. However, different monocyte subsets can play differential roles in the formation and destabilization of atherosclerotic plaque as well as healing of damaged myocardial tissue. Monocytes are currently being divided into three functionally distinct subsets with different levels of CD14 (cluster of differentiation 14) and CD16 expression. Thus, there are classical CD14++CD16-, intermediate CD14++CD16+ and non-classical CD14+CD16++ monocytes. Here, we summarize the current knowledge on complex activities of different monocyte subsets in atherosclerosis and acute coronary syndromes. Moreover, we discuss which monocyte subsets can serve either as predictive biomarkers of cardiovascular risk or as potential targets used in atherosclerosis and its complications. PMID:25997925

  6. Microglia and monocytes synergistically promote the transition from acute to chronic pain after nerve injury

    PubMed Central

    Peng, Jiyun; Gu, Nan; Zhou, Lijun; B Eyo, Ukpong; Murugan, Madhuvika; Gan, Wen-Biao; Wu, Long-Jun

    2016-01-01

    Microglia and peripheral monocytes contribute to hypersensitivity in rodent models of neuropathic pain. However, the precise respective function of microglia and peripheral monocytes has not been investigated in these models. To address this question, here we combined transgenic mice and pharmacological tools to specifically and temporally control the depletion of microglia and monocytes in a mouse model of spinal nerve transection (SNT). We found that although microglia and monocytes are required during the initiation of mechanical allodynia or thermal hyperalgesia, these cells may not be as important for the maintenance of hypersensitivity. Moreover, we demonstrated that either resident microglia or peripheral monocytes are sufficient in gating neuropathic pain after SNT. We propose that resident microglia and peripheral monocytes act synergistically to initiate hypersensitivity and promote the transition from acute to chronic pain after peripheral nerve injury. PMID:27349690

  7. B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction.

    PubMed

    Zouggari, Yasmine; Ait-Oufella, Hafid; Bonnin, Philippe; Simon, Tabassome; Sage, Andrew P; Guérin, Coralie; Vilar, José; Caligiuri, Giuseppina; Tsiantoulas, Dimitrios; Laurans, Ludivine; Dumeau, Edouard; Kotti, Salma; Bruneval, Patrick; Charo, Israel F; Binder, Christoph J; Danchin, Nicolas; Tedgui, Alain; Tedder, Thomas F; Silvestre, Jean-Sébastien; Mallat, Ziad

    2013-10-01

    Acute myocardial infarction is a severe ischemic disease responsible for heart failure and sudden death. Here, we show that after acute myocardial infarction in mice, mature B lymphocytes selectively produce Ccl7 and induce Ly6C(hi) monocyte mobilization and recruitment to the heart, leading to enhanced tissue injury and deterioration of myocardial function. Genetic (Baff receptor deficiency) or antibody-mediated (CD20- or Baff-specific antibody) depletion of mature B lymphocytes impeded Ccl7 production and monocyte mobilization, limited myocardial injury and improved heart function. These effects were recapitulated in mice with B cell-selective Ccl7 deficiency. We also show that high circulating concentrations of CCL7 and BAFF in patients with acute myocardial infarction predict increased risk of death or recurrent myocardial infarction. This work identifies a crucial interaction between mature B lymphocytes and monocytes after acute myocardial ischemia and identifies new therapeutic targets for acute myocardial infarction. PMID:24037091

  8. Asthma in adults (acute)

    PubMed Central

    2011-01-01

    Introduction About 10% of adults have suffered an attack of asthma, and up to 5% of these have severe disease that responds poorly to treatment. Patients with severe disease have an increased risk of death, but patients with mild to moderate disease are also at risk of exacerbations. Most guidelines about the management of asthma follow stepwise protocols. This review does not endorse or follow any particular protocol, but presents the evidence about specific interventions. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute asthma? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 100 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: beta2 agonists (plus ipratropium bromide, pressured metered-dose inhalers, short-acting continuous nebulised, short-acting intermittent nebulised, short-acting iv, and inhaled formoterol); corticosteroids (inhaled); corticosteroids (single oral, combined inhaled, and short courses); education about acute asthma; generalist care; helium–oxygen mixture (heliox); magnesium sulphate (iv and adding isotonic nebulised magnesium to inhaled beta2 agonists); mechanical ventilation; oxygen supplementation (controlled 28% oxygen and controlled 100% oxygen); and specialist care. PMID:21463536

  9. Age-Related Gene Expression Differences in Monocytes from Human Neonates, Young Adults, and Older Adults.

    PubMed

    Lissner, Michelle M; Thomas, Brandon J; Wee, Kathleen; Tong, Ann-Jay; Kollmann, Tobias R; Smale, Stephen T

    2015-01-01

    A variety of age-related differences in the innate and adaptive immune systems have been proposed to contribute to the increased susceptibility to infection of human neonates and older adults. The emergence of RNA sequencing (RNA-seq) provides an opportunity to obtain an unbiased, comprehensive, and quantitative view of gene expression differences in defined cell types from different age groups. An examination of ex vivo human monocyte responses to lipopolysaccharide stimulation or Listeria monocytogenes infection by RNA-seq revealed extensive similarities between neonates, young adults, and older adults, with an unexpectedly small number of genes exhibiting statistically significant age-dependent differences. By examining the differentially induced genes in the context of transcription factor binding motifs and RNA-seq data sets from mutant mouse strains, a previously described deficiency in interferon response factor-3 activity could be implicated in most of the differences between newborns and young adults. Contrary to these observations, older adults exhibited elevated expression of inflammatory genes at baseline, yet the responses following stimulation correlated more closely with those observed in younger adults. Notably, major differences in the expression of constitutively expressed genes were not observed, suggesting that the age-related differences are driven by environmental influences rather than cell-autonomous differences in monocyte development. PMID:26147648

  10. Acute phase protein and antioxidant responses in dogs with experimental acute monocytic ehrlichiosis treated with rifampicin.

    PubMed

    Karnezi, Dimitra; Ceron, Jose J; Theodorou, Konstantina; Leontides, Leonidas; Siarkou, Victoria I; Martinez, Silvia; Tvarijonaviciute, Asta; Harrus, Shimon; Koutinas, Christos K; Pardali, Dimitra; Mylonakis, Mathios E

    2016-02-29

    There is currently lack of information on the changes of acute phase proteins (APP) and antioxidant markers and their clinical relevance as treatment response indicators in canine monocytic ehrlichiosis (CME). The objective of this study was to investigate the patterns of C-reactive protein (CRP), haptoglobin (Hp), ferritin and paraoxonase-1 (PON-1) during treatment of dogs with acute CME with rifampicin. Blood serum samples from ten Beagle dogs with experimental acute CME were retrospectively examined. Five dogs (Group A) were treated with rifampicin (10mg/Kg/24h), per os, for 3 weeks and 5 dogs (Group B) received no treatment (infected controls). Two Beagle dogs served as uninfected controls. Blood serum samples were serially examined prior to Ehrlichia canis inoculation and on post-inoculation days 14, 21, 28, 35 and 42. Significant changes of CRP, Hp, ferritin and PON-1 values were found in the majority of infected dogs. However, their concentrations did not differ between the two groups during the treatment observation period. The results of this study indicate that although several APP and PON-1 tend to significantly change in the majority of dogs with acute CME, they were of limited clinical relevance as treatment response indicators in this experimental setting. PMID:26854345

  11. The impact of Ly6Clow monocytes after cerebral hypoxia-ischemia in adult mice

    PubMed Central

    Michaud, Jean-Philippe; Pimentel-Coelho, Pedro Moreno; Tremblay, Yannick; Rivest, Serge

    2014-01-01

    After an ischemic stroke, mononuclear phagocytic cells such as microglia, macrophages, and monocytes migrate to the lesion site and coordinate an immune response. Monocytes, which are recruited from the bloodstream after ischemic brain injury, can be categorized into two subsets in mice: inflammatory and patrolling monocytes. Although inflammatory monocytes (Ly6Chi) seem to have a protective role in stroke progression, the impact of patrolling monocytes (Ly6Clow) is unknown. To address the role of Ly6Clow monocytes in stroke, we generated bone marrow chimeric mice in which their hematopoietic system was replaced by Nr4a1−/− cells, allowing the complete and permanent ablation of Ly6Clow monocytes without affecting the Ly6Chi subset. We then subjected adult mice to cerebral hypoxia-ischemia using the Levine/Vannucci model. Functional outcomes after stroke such as body weight change, neurologic score, motor functions and spatial learning were not affected. Moreover, depletion in Ly6Clow monocytes did not change significantly the total infarct size, cell loss, atrophy, the number, or the activation state of microglia/macrophages at the lesion site. These data suggest that Ly6Clow patrolling monocytes are redundant in the progression and recovery of ischemic stroke. PMID:24780898

  12. Treatment Options for Adult Acute Myeloid Leukemia

    MedlinePlus

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  13. Stages of Adult Acute Myeloid Leukemia

    MedlinePlus

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  14. Treatment Option Overview (Adult Acute Myeloid Leukemia)

    MedlinePlus

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  15. Monocytic Tissue Transglutaminase in a Rat Model for Reversible Acute Rejection and Chronic Renal Allograft Injury

    PubMed Central

    Zakrzewicz, Anna; Atanasova, Srebrena; Padberg, Winfried

    2015-01-01

    Acute rejection is a major risk factor for chronic allograft injury (CAI). Blood leukocytes interacting with allograft endothelial cells during acute rejection were suggested to contribute to the still enigmatic pathogenesis of CAI. We hypothesize that tissue transglutaminase (Tgm2), a multifunctional protein and established marker of M2 macrophages, is involved in acute and chronic graft rejection. We focus on leukocytes accumulating in blood vessels of rat renal allografts (Fischer-344 to Lewis), an established model for reversible acute rejection and CAI. Monocytes in graft blood vessels overexpress Tgm2 when acute rejection peaks on day 9 after transplantation. Concomitantly, caspase-3 is activated, suggesting that Tgm2 expression is linked to apoptosis. After resolution of acute rejection on day 42, leukocytic Tgm2 levels are lower and activated caspase-3 does not differ among isografts and allografts. Cystamine was applied for 4 weeks after transplantation to inhibit extracellular transglutaminase activity, which did, however, not reduce CAI in the long run. In conclusion, this is the first report on Tgm2 expression by monocytes in vivo. Tgm2 may be involved in leukocytic apoptosis and thus in reversion of acute rejection. However, our data do not support a role of extracellular transglutaminase activity as a factor triggering CAI during self-limiting acute rejection. PMID:26063971

  16. Acute Monocytic Leukemia Masquerading Behçet's Disease-Like Illness at Onset in an Elderly Female

    PubMed Central

    Koba, Shigeru; Sekioka, Toshio; Takeda, Sorou; Miyagawa-Hayashino, Aya; Nishimura, Keisuke

    2016-01-01

    A previously healthy 74-year-old Japanese female was hospitalized with fever and high C-reactive protein. She developed palatal herpangina-like aphthous ulcers, localized intestinal wall thickening, terminal ileum ulcers, and an erythematous acneiform rash; thus Behçet's disease-like illness was suspected. Significant peripheral blood acute monocytosis developed during her hospitalization and acute monocytic leukemia (FAB M5b) with normal karyotype was diagnosed. By immunostaining, the infiltrating cells in the skin and the terminal ileum were identified as monocytic leukemic cells. This case exhibited a unique initial presentation of Behçet's disease-like illness associated with acute monocytic leukemia. PMID:27610252

  17. Acute Monocytic Leukemia Masquerading Behçet's Disease-Like Illness at Onset in an Elderly Female.

    PubMed

    Koba, Shigeru; Sekioka, Toshio; Takeda, Sorou; Miyagawa-Hayashino, Aya; Nishimura, Keisuke; Imashuku, Shinsaku

    2016-01-01

    A previously healthy 74-year-old Japanese female was hospitalized with fever and high C-reactive protein. She developed palatal herpangina-like aphthous ulcers, localized intestinal wall thickening, terminal ileum ulcers, and an erythematous acneiform rash; thus Behçet's disease-like illness was suspected. Significant peripheral blood acute monocytosis developed during her hospitalization and acute monocytic leukemia (FAB M5b) with normal karyotype was diagnosed. By immunostaining, the infiltrating cells in the skin and the terminal ileum were identified as monocytic leukemic cells. This case exhibited a unique initial presentation of Behçet's disease-like illness associated with acute monocytic leukemia. PMID:27610252

  18. General Information about Adult Acute Lymphoblastic Leukemia

    MedlinePlus

    ... Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Lymphoblastic Leukemia Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  19. General Information about Adult Acute Myeloid Leukemia

    MedlinePlus

    ... Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  20. Differential Oxidative Stress Induced by Dengue Virus in Monocytes from Human Neonates, Adult and Elderly Individuals

    PubMed Central

    Valero, Nereida; Mosquera, Jesús; Añez, Germán; Levy, Alegria; Marcucci, Rafael; de Mon, Melchor Alvarez

    2013-01-01

    Changes in immune response during lifespan of man are well known. These changes involve decreased neonatal and elderly immune response. In addition, it has been shown a relationship between immune and oxidative mechanisms, suggesting that altered immune response could be associated to altered oxidative response. Increased expression of nitric oxide (NO) has been documented in dengue and in monocyte cultures infected with different types of dengue virus. However, there is no information about the age-dependent NO oxidative response in humans infected by dengue virus. In this study, monocyte cultures from neonatal, elderly and adult individuals (n = 10 each group) were infected with different dengue virus types (DENV- 1 to 4) and oxidative/antioxidative responses and apoptosis were measured at days 1 and 3 of culture. Increased production of NO, lipid peroxidation and enzymatic and nonenzymatic anti-oxidative responses in dengue infected monocyte cultures were observed. However, neonatal and elderly monocytes had lower values of studied parameters when compared to those in adult-derived cultures. Apoptosis was present in infected monocytes with higher values at day 3 of culture. This reduced oxidant/antioxidant response of neonatal and elderly monocytes could be relevant in the pathogenesis of dengue disease. PMID:24069178

  1. Hippocampal protection in mice with an attenuated inflammatory monocyte response to acute CNS picornavirus infection

    PubMed Central

    Howe, Charles L.; LaFrance-Corey, Reghann G.; Sundsbak, Rhianna S.; Sauer, Brian M.; LaFrance, Stephanie J.; Buenz, Eric J.; Schmalstieg, William F.

    2012-01-01

    Neuronal injury during acute viral infection of the brain is associated with the development of persistent cognitive deficits and seizures in humans. In C57BL/6 mice acutely infected with the Theiler's murine encephalomyelitis virus, hippocampal CA1 neurons are injured by a rapid innate immune response, resulting in profound memory deficits. In contrast, infected SJL and B6xSJL F1 hybrid mice exhibit essentially complete hippocampal and memory preservation. Analysis of brain-infiltrating leukocytes revealed that SJL mice mount a sharply attenuated inflammatory monocyte response as compared to B6 mice. Bone marrow transplantation experiments isolated the attenuation to the SJL immune system. Adoptive transfer of B6 inflammatory monocytes into acutely infected B6xSJL hosts converted these mice to a hippocampal damage phenotype and induced a cognitive deficit marked by failure to recognize a novel object. These findings show that inflammatory monocytes are the critical cellular mediator of hippocampal injury during acute picornavirus infection of the brain. PMID:22848791

  2. Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia.

    PubMed

    Yan, Xiao-Jing; Xu, Jie; Gu, Zhao-Hui; Pan, Chun-Ming; Lu, Gang; Shen, Yang; Shi, Jing-Yi; Zhu, Yong-Mei; Tang, Lin; Zhang, Xiao-Wei; Liang, Wen-Xue; Mi, Jian-Qing; Song, Huai-Dong; Li, Ke-Qin; Chen, Zhu; Chen, Sai-Juan

    2011-04-01

    Abnormal epigenetic regulation has been implicated in oncogenesis. We report here the identification of somatic mutations by exome sequencing in acute monocytic leukemia, the M5 subtype of acute myeloid leukemia (AML-M5). We discovered mutations in DNMT3A (encoding DNA methyltransferase 3A) in 23 of 112 (20.5%) cases. The DNMT3A mutants showed reduced enzymatic activity or aberrant affinity to histone H3 in vitro. Notably, there were alterations of DNA methylation patterns and/or gene expression profiles (such as HOXB genes) in samples with DNMT3A mutations as compared with those without such changes. Leukemias with DNMT3A mutations constituted a group of poor prognosis with elderly disease onset and of promonocytic as well as monocytic predominance among AML-M5 individuals. Screening other leukemia subtypes showed Arg882 alterations in 13.6% of acute myelomonocytic leukemia (AML-M4) cases. Our work suggests a contribution of aberrant DNA methyltransferase activity to the pathogenesis of acute monocytic leukemia and provides a useful new biomarker for relevant cases. PMID:21399634

  3. [Acute epiglottitis in adults].

    PubMed

    Castillo, A

    1992-09-01

    The author presents the clinical history of 14 patients, from 21 to 48 years of age, 10 men and 4 women, with a final diagnosis of acute epiglottitis who were hospitalized at Gorgas Army Hospital or at the San Fernando Clinic. All the patients had pharyngitis and dysphagia, a few with nasal voice, stridor and difficulty breathing, as the chief complaint. All the patients were initially intubated orally for diagnostic purposes and immediately after nasotracheal intubation was done until the patient improved in 2 or 3 days (one patient remained intubated for 5 days). All patients were kept in the Intensive Care Unit and were treated with Ampicillin and Chloramphenicol IV and lately with a second generation cephalosporin (Cefamandole). The patients allergic to Penicillin were treated with Clindamycin and Chloramphenicol. Corticosteroids were not used in any of the patients. There were no sequelae and none of the patients expired. PMID:1439005

  4. Decitabine With or Without Bortezomib in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-03-14

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  5. Functional and morphologic characteristics of the leukemic cells of a patient with acute monocytic leukemia: correlation with clinical features.

    PubMed

    Schiffer, C A; Sanel, F T; Stechmiller, B K; Wiernik, P H

    1975-07-01

    The clinical course of a patient with acute monocytic leukemia and prominent infiltration of the skin and testes is described. In vitro studies demonstrated that the circulating monocyte precursors were capable of adherence to nylon fibers, and phagocytosis of bacteria and latex particles. In vivo, migration of leukemic cells to skin windows was observed. Extreme nuclear folding, marked surface activity, and morphologic features suggesting nuclear and cytoplasmic maturation were seen by light and electron microscopy. The presence of morphologically and functionally more differentiated monocytic cells may account for the marked tiuuse invasion in this patient and, possibly, in other patients with monocytic leukemia. PMID:1055611

  6. Polydatin Induces Apoptosis and Inhibits Growth of Acute Monocytic Leukemia Cells.

    PubMed

    Wang, Chunmei; Luo, Yuan; Lu, Jie; Wang, Yingchao; Sheng, Guangyao

    2016-04-01

    Polydatin (PD), a component isolated from Polygonum cuspidatum, has various activities such as inhibiting platelet aggregation, lowering level of blood lipid, reducing lipid peroxidation, and so on. However, the antitumor activity of PD has been poorly reported. In the present study, effect of PD on cell proliferation was evaluated by Cell Counting Kit-8, and cell cycle and apoptosis were investigated by flow cytometry. Meanwhile, the protein expression level of Bc1-2, Bax, cyclin A, cyclin B, and cyclin D1, which associated with apoptosis and cell cycle were analyzed by Western blotting. Results show that PD could effectively inhibit the growth, arrest cells in S phase, and induce apoptosis of acute monocytic leukemia cell line THP-1; meanwhile, expression of cyclin D1 and Bc1-2 decreased significantly, and expression of Bax and cyclin A increased notably. All results suggest that PD maybe a potential therapeutic strategy for acute monocytic leukemia. PMID:26616494

  7. Acute Exercise-Induced Response of Monocyte Subtypes in Chronic Heart and Renal Failure

    PubMed Central

    Van Craenenbroeck, Amaryllis H.; Hoymans, Vicky Y.; Verpooten, Gert A.; Vrints, Christiaan J.; Couttenye, Marie M.; Van Craenenbroeck, Emeline M.

    2014-01-01

    Purpose. Monocytes (Mon1-2-3) play a substantial role in low-grade inflammation associated with high cardiovascular morbidity and mortality of patients with chronic kidney disease (CKD) and chronic heart failure (CHF). The effect of an acute exercise bout on monocyte subsets in the setting of systemic inflammation is currently unknown. This study aims (1) to evaluate baseline distribution of monocyte subsets in CHF and CKD versus healthy subjects (HS) and (2) to evaluate the effect of an acute exercise bout. Exercise-induced IL-6 and MCP-1 release are related to the Mon1-2-3 response. Methods. Twenty CHF patients, 20 CKD patients, and 15 HS were included. Before and after a maximal cardiopulmonary exercise test, monocyte subsets were quantified by flow cytometry: CD14++CD16−CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2), and CD14+CD16++CCR2− (Mon3). Serum levels of IL-6 and MCP-1 were determined by ELISA. Results. Baseline distribution of Mon1-2-3 was comparable between the 3 groups. Following acute exercise, %Mon2 and %Mon3 increased significantly at the expense of a decrease in %Mon1 in HS and in CKD. This response was significantly attenuated in CHF (P < 0.05). In HS only, MCP-1 levels increased following exercise; IL-6 levels were unchanged. Circulatory power was a strong and independent predictor of the changes in Mon1 (β = −0.461, P < 0.001) and Mon3 (β = 0.449, P < 0.001); and baseline LVEF of the change in Mon2 (β = 0.441, P < 0.001). Conclusion. The response of monocytes to acute exercise is characterized by an increase in proangiogenic and proinflammatory Mon2 and Mon3 at the expense of phagocytic Mon1. This exercise-induced monocyte subset response is mainly driven by hemodynamic changes and not by preexistent low-grade inflammation. PMID:25587208

  8. Idarubicin and Cytarabine With or Without Bevacizumab in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-01-23

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  9. Acute Migraine Treatment in Adults.

    PubMed

    Becker, Werner J

    2015-06-01

    There are many options for acute migraine attack treatment, but none is ideal for all patients. This study aims to review current medical office-based acute migraine therapy in adults and provides readers with an organized approach to this important facet of migraine treatment. A general literature review includes a review of several recent published guidelines. Acetaminophen, 4 nonsteroidal anti-inflammatory drugs (NSAIDs) (ibuprofen, acetylsalicylic acid [ASA], naproxen sodium, and diclofenac potassium), and 7 triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan) have good evidence for efficacy and form the core of acute migraine treatment. NSAID-triptan combinations, dihydroergotamine, non-opioid combination analgesics (acetaminophen, ASA, and caffeine), and several anti-emetics (metoclopramide, domperidone, and prochlorperazine) are additional evidence-based options. Opioid containing combination analgesics may be helpful in specific patients, but should not be used routinely. Clinical features to be considered when choosing an acute migraine medication include usual headache intensity, usual rapidity of pain intensity increase, nausea, vomiting, degree of disability, patient response to previously used medications, history of headache recurrence with previous attacks, and the presence of contraindications to specific acute medications. Available acute medications can be organized into 4 treatment strategies, including a strategy for attacks of mild to moderate severity (strategy one: acetaminophen and/or NSAIDs), a triptan strategy for patients with severe attacks and for attacks not responding to strategy one, a refractory attack strategy, and a strategy for patients with contraindications to vasoconstricting drugs. Acute treatment of migraine attacks during pregnancy, lactation, and for patients with chronic migraine is also discussed. In chronic migraine, it is particularly important that medication

  10. Plasmacytoid Dendritic Cells Control Lung Inflammation and Monocyte Recruitment in Indirect Acute Lung Injury in Mice

    PubMed Central

    Venet, Fabienne; Huang, Xin; Chung, Chun-Shiang; Chen, Yaping; Ayala, Alfred

    2010-01-01

    Indirect acute lung injury (ALI, not caused by a direct insult to the lung) represents the first organ dysfunction in trauma patients, with nonpulmonary sepsis being the most common cause of indirect ALI. Dendritic cells (DCs) are thought to participate in a number of inflammatory lung diseases; however, their role in indirect ALI is currently not established. Using a clinically relevant model of indirect ALI induced in mice by hemorrhagic shock followed 24 hours later by polymicrobial septic challenge, we report that mature DC numbers were markedly increased in the lung during indirect ALI. DC depletion induced a significant increase in indirect ALI severity, which was associated with enhanced lung and plasma proinflammatory cytokine concentration and recruitment of proinflammatory CD115+ monocytes in response to increased lung monocyte chemotactic protein-1 production. Among the different DC subpopulations, plasmacytoid DCs, which were induced and activated in the lung during indirect ALI, were responsible for this effect because their specific depletion reproduced the observations made in DC-depleted mice. As the recruitment of monocytes to the lung plays a central deleterious role in the pathophysiology of indirect ALI, our data therefore position plasmacytoid DCs as important regulators of acute lung inflammation. PMID:20042672

  11. The Kinetics of Circulating Monocyte Subsets and Monocyte-Platelet Aggregates in the Acute Phase of ST-Elevation Myocardial Infarction: Associations with 2-Year Cardiovascular Events.

    PubMed

    Zhou, Xin; Liu, Xin-Lin; Ji, Wen-Jie; Liu, Jun-Xiang; Guo, Zhao-Zeng; Ren, Dong; Ma, Yong-Qiang; Zeng, Shan; Xu, Zhong-Wei; Li, Hong-Xia; Wang, Peizhong Peter; Zhang, Zhuoli; Li, Yu-Ming; Benefield, Brandon C; Zawada, Adam M; Thorp, Edward B; Lee, Daniel C; Heine, Gunnar H

    2016-05-01

    In experimental myocardial infarction (MI), a rise in cell counts of circulating monocyte subsets contributes to impaired myocardial healing and to atherosclerotic plaque destabilization. In humans, the prognostic role of monocyte subsets in patients suffering ST-elevation MI (STEMI) is still unclear. In the present study, we aimed to determine the kinetics of the 3 monocyte subsets (classical CD14++CD16-, intermediate CD14++CD16+, and nonclassical CD14+CD16++ monocytes), as well as the subset-specific monocyte-platelet aggregates (MPA), in acute STEMI followed by primary percutaneous coronary intervention (PCI), and their relationships with cardiovascular outcomes during a 2-year follow-up.Monocyte subsets and MPA were measured in 100 STEMI patients receiving primary PCI on days 1, 2, 3, 5, and 7 of symptom onset, which were compared with 60 stable coronary heart disease patients and 35 healthy volunteers. From day 1 to day 7, significant increases in the counts of CD14++CD16+ monocytes and CD14++CD16+ MPA were observed, with peak levels on day 2. During a median follow-up of 2.0 years, 28 first cardiovascular events (defined as cardiovascular death, nonfatal ischemic stroke, recurrent MI, need for emergency or repeat revascularization, and rehospitalization for heart failure) were recorded. After adjustment for confounders, CD14++CD16+ monocytosis (day 1 [HR: 3.428; 95% CI: 1.597-7.358; P = 0.002], day 2 [HR: 4.835; 95% CI: 1.106-21.13; P = 0.04], day 3 [HR: 2.734; 95% CI: 1.138-6.564; P = 0.02], and day 7 [HR: 2.647; 95% CI: 1.196-5.861; P = 0.02]), as well as increased levels of CD14++CD16+ MPA measured on all time points (days 1, 2, 3, 5, and 7), had predictive values for adverse cardiovascular events.In conclusion, our data show the expansion of the CD14++CD16+ monocyte subset during acute phase of STEMI has predictive values for 2-year adverse cardiovascular outcomes in patients treated with primary PCI. Future studies will be warranted to

  12. The Kinetics of Circulating Monocyte Subsets and Monocyte-Platelet Aggregates in the Acute Phase of ST-Elevation Myocardial Infarction

    PubMed Central

    Zhou, Xin; Liu, Xin-Lin; Ji, Wen-Jie; Liu, Jun-Xiang; Guo, Zhao-Zeng; Ren, Dong; Ma, Yong-Qiang; Zeng, Shan; Xu, Zhong-Wei; Li, Hong-Xia; Wang, Peizhong Peter; Zhang, Zhuoli; Li, Yu-Ming; Benefield, Brandon C.; Zawada, Adam M.; Thorp, Edward B.; Lee, Daniel C.; Heine, Gunnar H.

    2016-01-01

    Abstract In experimental myocardial infarction (MI), a rise in cell counts of circulating monocyte subsets contributes to impaired myocardial healing and to atherosclerotic plaque destabilization. In humans, the prognostic role of monocyte subsets in patients suffering ST-elevation MI (STEMI) is still unclear. In the present study, we aimed to determine the kinetics of the 3 monocyte subsets (classical CD14++CD16–, intermediate CD14++CD16+, and nonclassical CD14+CD16++ monocytes), as well as the subset-specific monocyte–platelet aggregates (MPA), in acute STEMI followed by primary percutaneous coronary intervention (PCI), and their relationships with cardiovascular outcomes during a 2-year follow-up. Monocyte subsets and MPA were measured in 100 STEMI patients receiving primary PCI on days 1, 2, 3, 5, and 7 of symptom onset, which were compared with 60 stable coronary heart disease patients and 35 healthy volunteers. From day 1 to day 7, significant increases in the counts of CD14++CD16+ monocytes and CD14++CD16+ MPA were observed, with peak levels on day 2. During a median follow-up of 2.0 years, 28 first cardiovascular events (defined as cardiovascular death, nonfatal ischemic stroke, recurrent MI, need for emergency or repeat revascularization, and rehospitalization for heart failure) were recorded. After adjustment for confounders, CD14++CD16+ monocytosis (day 1 [HR: 3.428; 95% CI: 1.597–7.358; P = 0.002], day 2 [HR: 4.835; 95% CI: 1.106–21.13; P = 0.04], day 3 [HR: 2.734; 95% CI: 1.138–6.564; P = 0.02], and day 7 [HR: 2.647; 95% CI: 1.196–5.861; P = 0.02]), as well as increased levels of CD14++CD16+ MPA measured on all time points (days 1, 2, 3, 5, and 7), had predictive values for adverse cardiovascular events. In conclusion, our data show the expansion of the CD14++CD16+ monocyte subset during acute phase of STEMI has predictive values for 2-year adverse cardiovascular outcomes in patients treated with primary PCI. Future studies

  13. Acute Shoulder Injuries in Adults.

    PubMed

    Monica, James; Vredenburgh, Zachary; Korsh, Jeremy; Gatt, Charles

    2016-07-15

    Acute shoulder injuries in adults are often initially managed by family physicians. Common acute shoulder injuries include acromioclavicular joint injuries, clavicle fractures, glenohumeral dislocations, proximal humerus fractures, and rotator cuff tears. Acromioclavicular joint injuries and clavicle fractures mostly occur in young adults as the result of a sports injury or direct trauma. Most nondisplaced or minimally displaced injuries can be treated conservatively. Treatment includes pain management, short-term use of a sling for comfort, and physical therapy as needed. Glenohumeral dislocations can result from contact sports, falls, bicycle accidents, and similar high-impact trauma. Patients will usually hold the affected arm in their contralateral hand and have pain with motion and decreased motion at the shoulder. Physical findings may include a palpable humeral head in the axilla or a dimple inferior to the acromion laterally. Reduction maneuvers usually require intra-articular lidocaine or intravenous analgesia. Proximal humerus fractures often occur in older patients after a low-energy fall. Radiography of the shoulder should include a true anteroposterior view of the glenoid, scapular Y view, and axillary view. Most of these fractures can be managed nonoperatively, using a sling, early range-of-motion exercises, and strength training. Rotator cuff tears can cause difficulty with overhead activities or pain that awakens the patient from sleep. On physical examination, patients may be unable to hold the affected arm in an elevated position. It is important to recognize the sometimes subtle signs and symptoms of acute shoulder injuries to ensure proper management and timely referral if necessary. PMID:27419328

  14. Combination Chemotherapy With or Without PSC 833, Peripheral Stem Cell Transplantation, and/or Interleukin-2 in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-06-03

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  15. Bortezomib and Combination Chemotherapy in Treating Younger Patients With Recurrent, Refractory, or Secondary Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-05-13

    Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myelomonocytic Leukemia (M4); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  16. Azacitidine, Mitoxantrone Hydrochloride, and Etoposide in Treating Older Patients With Poor-Prognosis Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-08-18

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  17. Vorinostat in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-04-30

    Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  18. Stages of Adult Acute Lymphoblastic Leukemia

    MedlinePlus

    ... recovery) and treatment options. Adult acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... to radiation may increase the risk of developing ALL. Anything that increases your risk of getting a ...

  19. Treatment Options for Adult Acute Lymphoblastic Leukemia

    MedlinePlus

    ... recovery) and treatment options. Adult acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... to radiation may increase the risk of developing ALL. Anything that increases your risk of getting a ...

  20. Treatment Option Overview (Adult Acute Lymphoblastic Leukemia)

    MedlinePlus

    ... recovery) and treatment options. Adult acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... to radiation may increase the risk of developing ALL. Anything that increases your risk of getting a ...

  1. Posterior reversible encephalopathy syndrome following acute pancreatitis during chemotherapy for acute monocytic leukemia.

    PubMed

    Nishimoto, Mitsutaka; Koh, Hideo; Bingo, Masato; Yoshida, Masahiro; Nanno, Satoru; Hayashi, Yoshiki; Nakane, Takahiko; Nakamae, Hirohisa; Shimono, Taro; Hino, Masayuki

    2014-05-01

    We describe an 18-year-old man with acute leukemia who presented with posterior reversible encephalopathy syndrome (PRES) shortly after developing acute pancreatitis. On day 15 after the third consolidation course with high-dose cytarabine, treatment with broad-spectrum antibiotics was initiated for febrile neutropenia. On day 16, he developed septic shock, and subsequently, acute respiratory distress syndrome (ARDS). After adding vancomycin, micafungin and high-dose methylprednisolone (mPSL) to his treatment regimen, these manifestations subsided. On day 22, he received hemodialysis for drug-induced acute renal failure. On day 24, he developed acute pancreatitis possibly due to mPSL; the following day he had generalized seizures, and was intubated. Cerebrospinal fluid findings were normal. Brain MRI revealed hyperintense signals on FLAIR images and increased apparent diffusion coefficient values in the sub-cortical and deep white matter areas of the bilateral temporal and occipital lobes, indicative of vasogenic edema. Thus, we diagnosed PRES. Blood pressure, seizures and volume status were controlled, with MRI findings showing improvement by day 42. He was extubated on day 32 and discharged on day 49 without complications. Although little is known about PRES following acute pancreatitis, clinicians should be aware that this condition may develop. PMID:24881921

  2. Tipifarnib and Bortezomib in Treating Patients With Acute Leukemia or Chronic Myelogenous Leukemia in Blast Phase

    ClinicalTrials.gov

    2015-04-14

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Blastic Phase; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  3. Differential Induction of Cytokines by Human Neonatal, Adult, and Elderly Monocyte/Macrophages Infected with Dengue Virus

    PubMed Central

    Valero, Nereida; Levy, Alegria; Añez, Germán; Marcucci, Rafael; Alvarez-Mon, Melchor

    2014-01-01

    Abstract Immunosuppressive status against infections in monocytes from neonates and elderly subjects has been reported. The interaction between dengue virus and monocytes/macrophages plays an important role during dengue disease. The aim of this study was to determine the cytokine response of monocytes from individuals with different ages after infection with dengue virus. Monocyte/macrophage cultures from neonatal, adult, and elderly subjects (n=10 each group) were incubated with all four dengue virus types (DENV-1 to -4). After 1 and 3 days of culture, cytokine concentrations (TNF-α, IL-6, and IL-1β) were determined in culture supernatants by enzyme-linked immunosorbant assay. Increased production of all studied cytokines was induced by the different viral types in monocyte/macrophage cultures regardless of their source. However, lower cytokine concentrations were found in neonatal and elderly monocytes. The relative monocyte/macrophage immunosuppressive status observed in neonates and the elderly could be relevant during dengue infection in those age groups and important in innate and adaptive immunity responses against this virus. PMID:24801946

  4. Sorafenib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2013-01-08

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia

  5. Functional characterisation of human pulmonary monocyte-like cells in lipopolysaccharide-mediated acute lung inflammation

    PubMed Central

    2014-01-01

    Background We have previously reported the presence of novel subpopulations of pulmonary monocyte-like cells (PMLC) in the human lung; resident PMLC (rPMLC, HLA-DR+CD14++CD16+cells) and inducible PMLC (iPMLC, HLA-DR+CD14++CD16- cells). iPMLC are significantly increased in bronchoalveolar lavage (BAL) fluid following inhalation of lipopolysaccharide (LPS). We have carried out the first functional evaluation of PMLC subpopulations in the inflamed lung, following the isolation of these cells, and other lineages, from BAL fluid using novel and complex protocols. Methods iPMLC, rPMLC, alveolar macrophages (AM), neutrophils, and regulatory T cells were quantified in BAL fluid of healthy subjects at 9 hours post-LPS inhalation (n = 15). Cell surface antigen expression by iPMLC, rPMLC and AM and the ability of each lineage to proliferate and to undergo phagocytosis were investigated using flow cytometry. Basal cytokine production by iPMLC compared to AM following their isolation from BAL fluid and the responsiveness of both cell types following in vitro treatment with the synthetic corticosteroid dexamethasone were assessed. Results rPMLC have a significantly increased expression of mature macrophage markers and of the proliferation antigen Ki67, compared to iPMLC. Our cytokine data revealed a pro-inflammatory, corticosteroid-resistant phenotype of iPMLC in this model. Conclusions These data emphasise the presence of functionally distinct subpopulations of the monocyte/macrophage lineage in the human lung in experimental acute lung inflammation. PMID:24684897

  6. Lenalidomide in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-07-25

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  7. Colchicine therapy in acute coronary syndrome patients acts on caspase-1 to suppress NLRP3 inflammasome monocyte activation.

    PubMed

    Robertson, Stacy; Martínez, Gonzalo J; Payet, Cloe A; Barraclough, Jennifer Y; Celermajer, David S; Bursill, Christina; Patel, Sanjay

    2016-07-01

    Inflammasome activation, with subsequent release of pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18, has recently been implicated in atherosclerosis-associated inflammation. This study aims to assess in acute coronary syndrome (ACS) patients (1) inflammasome activation in circulating monocytes and (2) whether short-term oral colchicine, a recognized anti-inflammatory agent that has been shown to be cardio-protective in clinical studies, might acutely suppress inflammasome-dependent inflammation. ACS patients (n=21) were randomized to oral colchicine (1 mg followed by 0.5 mg 1 h later) or no treatment, and compared with untreated healthy controls (n=9). Peripheral venous blood was sampled pre- (day 1) and 24 h post- (day 2) treatment. Monocytes were cultured and stimulated with ATP. Analysis of key inflammasome markers was performed by ELISA. IL-1β secretion increased by 580.4% (P<0.01) in ACS patients compared with controls but only with ATP stimulation. Untreated ACS patients secreted significantly higher levels of IL-18 compared with healthy controls independent of ATP stimulation (P<0.05). Colchicine treatment in ACS patients markedly reduced intracellular and secreted levels of IL-1β compared with pre-treatment levels (P<0.05 for both), as well as significantly reducing pro-caspase-1 mRNA levels by 57.7% and secreted caspase-1 protein levels by 30.2% compared with untreated patients (P<0.05 for both). Monocytes from ACS patients are 'primed' to secrete inflammasome-related cytokines and short-term colchicine acutely and markedly suppresses monocyte caspase-1 activity, thereby reducing monocyte secretion of IL-1β. PMID:27129183

  8. Eltrombopag Olamine in Improving Platelet Recovery in Older Patients With Acute Myeloid Leukemia Undergoing Chemotherapy

    ClinicalTrials.gov

    2016-02-17

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia

  9. Lipid emulsions differentially affect LPS-induced acute monocytes inflammation: in vitro effects on membrane remodeling and cell viability.

    PubMed

    Boisramé-Helms, Julie; Delabranche, Xavier; Klymchenko, Andrey; Drai, Jocelyne; Blond, Emilie; Zobairi, Fatiha; Mely, Yves; Hasselmann, Michel; Toti, Florence; Meziani, Ferhat

    2014-11-01

    The aim of this study was to assess how lipid emulsions for parenteral nutrition affect lipopolysaccharide (LPS)-induced acute monocyte inflammation in vitro. An 18 h long LPS induced human monocyte leukemia cell stimulation was performed and the cell-growth medium was supplemented with three different industrial lipid emulsions: Intralipid(®), containing long-chain triglycerides (LCT--soybean oil); Medialipid(®), containing LCT (soybean oil) and medium-chain triglycerides (MCT--coconut oil); and SMOFlipid(®), containing LCT, MCT, omega-9 and -3 (soybean, coconut, olive and fish oils). Cell viability and apoptosis were assessed by Trypan blue exclusion and flow cytometry respectively. Monocyte composition and membrane remodeling were studied using gas chromatography and NR12S staining. Microparticles released in supernatant were measured by prothrombinase assay. After LPS challenge, both cellular necrosis and apoptosis were increased (threefold and twofold respectively) and microparticle release was enhanced (sevenfold) after supplementation with Medialipid(®) compared to Intralipid(®), SMOFlipid(®) and monocytes in the standard medium. The monocytes differentially incorporated fatty acids after lipid emulsion challenge. Finally, lipid-treated cells displayed microparticles characterized by disrupted membrane lipid order, reflecting lipid remodeling of the parental cell plasma membrane. Our data suggest that lipid emulsions differentially alter cell viability, monocyte composition and thereby microparticle release. While MCT have deleterious effects, we have shown that parenteral nutrition emulsion containing LCT or LCT and MCT associated to n-3 and n-9 fatty acids have no effect on endotoxin-induced cell death and inflammation. PMID:25038627

  10. Monocyte Trafficking, Engraftment, and Delivery of Nanoparticles and an Exogenous Gene into the Acutely Inflamed Brain Tissue – Evaluations on Monocyte-Based Delivery System for the Central Nervous System

    PubMed Central

    Kang, Wen; Davy, Philip M. C.; Shi, Yingli; Sun, Si; Allsopp, Richard C.; Lu, Yuanan

    2016-01-01

    The ability of monocytes and monocyte-derived macrophages (MDM) to travel towards chemotactic gradient, traverse tissue barriers, and accumulate precisely at diseased sites makes them attractive candidates as drug carriers and therapeutic gene delivery vehicles targeting the brain, where treatments are often hampered by the blockade of the blood brain barrier (BBB). This study was designed to fully establish an optimized cell-based delivery system using monocytes and MDM, by evaluating their homing efficiency, engraftment potential, as well as carriage and delivery ability to transport nano-scaled particles and exogenous genes into the brain, following the non-invasive intravenous (IV) cell adoptive transfer in an acute neuroinflammation mouse model induced by intracranial injection of Escherichia coli lipopolysaccharides. We demonstrated that freshly isolated monocytes had superior inflamed-brain homing ability over MDM cultured in the presence of macrophage colony stimulating factor. In addition, brain trafficking of IV infused monocytes was positively correlated with the number of adoptive transferred cells, and could be further enhanced by transient disruption of the BBB with IV administration of Mannitol, Bradykinin or Serotonin right before cell infusion. A small portion of transmigrated cells was detected to differentiate into IBA-1 positive cells with microglia morphology in the brain. Finally, with the use of superparamagnetic iron oxide nanoparticles SHP30, the ability of nanoscale agent-carriage monocytes to enter the inflamed brain region was validated. In addition, lentiviral vector DHIV-101 was used to introduce green fluorescent protein (GFP) gene into monocytes, and the exogenous GFP gene was detected in the brain at 48 hours following IV infusion of the transduced monocytes. All together, our study has set up the optimized conditions for the more-in-depth tests and development of monocyte-mediated delivery, and our data supported the notion to use

  11. Choline Magnesium Trisalicylate and Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-08

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  12. Eltrombopag Olamine in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-04-04

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  13. CD4+ CCR5+ and CD4+ CCR3+ lymphocyte subset and monocyte apoptosis in patients with acute visceral leishmaniasis

    PubMed Central

    Potestio, Marcella; D'Agostino, Pietro; Romano, Giuseppina Colonna; Milano, Salvatore; Ferlazzo, Viviana; Aquino, Alessandra; Di Bella, Gloria; Caruso, Rosalba; Gambino, Giuseppe; Vitale, Giustina; Mansueto, Serafino; Cillari, Enrico

    2004-01-01

    The potential involvement of apoptosis in the pathogenesis of visceral leishmaniasis (VL) was examined by studying spontaneous and Leishmania antigen (LAg)-induced apoptosis using cryopreserved peripheral blood mononuclear cells (PBMC) of Sicilian patients with VL. Results indicate that monocytes and T lymphocytes from acute VL patients show a significantly higher level of apoptosis compared with that observed in healed subjects. The percentage of apoptotic cells was higher in monocytes than in T lymphocytes. T cells involved in programmed cell death (PCD) were mainly of the CD4+ phenotype. In particular, the T helper 1-type (Th1) subset, as evaluated by chemokine receptor-5 (CCR5) expression, is involved in this process. Cell death in Th1-type uses a CD95-mediated mechanism. Furthermore, Th1-type CCR5+ cells are prone to cell suicide in an autocrine or paracrine way, as attested by enhanced expression of CD95L in acute VL patients. The reduction in Th1-type cells by apoptosis was confirmed by the decrease in interferon-γ secretion. In conclusion, apoptosis of monocytes, CD4+ and CD4+ CCR5+ T cells could be involved in the failure of cell mediated immunity that is responsible for severe immune-depression in VL. PMID:15379987

  14. Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-03-19

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  15. Peripheral blood lymphocyte to monocyte ratio identifies high-risk adult patients with sporadic Burkitt lymphoma.

    PubMed

    Wang, Liang; Wang, Hua; Xia, Zhong-Jun; Huang, Hui-Qiang; Jiang, Wen-Qi; Lin, Tong-Yu; Lu, Yue

    2015-10-01

    Adult sporadic Burkitt lymphoma (BL) is a rare subtype of lymphoma. In this retrospective study, we investigated the prognostic value of pretreatment lymphocyte to monocyte ratio (LMR) in a cohort of 62 patients. Using LMR <2.6 as the optimal cutoff point, 24 patients (38.7 %) had LMR <2.6. The complete response rates in high-LMR group and low-LMR group were 90.9 and 65.0 %, respectively (P = 0.019). At a median follow-up time of 41 months, the 3-year progression-free survival (PFS) rate and overall survival (OS) rates were 76 and 80 %, respectively. In a multivariate Cox regression model, it was found that the presence of bone marrow infiltration and low LMR were independently adverse prognostic factors for both PFS and OS. In the whole group, the addition of rituximab to treatment did not benefit patients significantly in PFS and OS. In subgroup analysis, in patients with high LMR, addition of rituximab can significantly improve survival outcomes (P = 0.046). In conclusion, we firstly found that low LMR (<2.60) was an independently adverse prognostic factor in adult patients with sporadic BL. Intensive chemotherapy could cure the majority of patients in our study, and the pretreatment LMR might predict the value of rituximab in this age population. PMID:26082333

  16. Alvocidib, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-07-14

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  17. Azacitidine, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With High-Risk Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-01-06

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  18. Clofarabine, Cytarabine, and Filgrastim Followed by Infusion of Non-HLA Matched Ex Vivo Expanded Cord Blood Progenitors in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-08-13

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  19. Lenalidomide in Treating Older Patients With Acute Myeloid Leukemia Who Have Undergone Stem Cell Transplant

    ClinicalTrials.gov

    2015-03-02

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia

  20. Alvocidib, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-06-03

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  1. Omacetaxine Mepesuccinate, Cytarabine, and Decitabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-04-05

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  2. Altered Stress-Induced Regulation of Genes in Monocytes in Adults with a History of Childhood Adversity.

    PubMed

    Schwaiger, Marion; Grinberg, Marianna; Moser, Dirk; Zang, Johannes C S; Heinrichs, Markus; Hengstler, Jan G; Rahnenführer, Jörg; Cole, Steve; Kumsta, Robert

    2016-09-01

    Exposure to serious or traumatic events early in life can lead to persistent alterations in physiological stress response systems, including enhanced cross talk between the neuroendocrine and immune system. These programming effects may be mechanistically involved in mediating the effects of adverse childhood experience on disease risk in adulthood. We investigated hormonal and genome-wide mRNA expression responses in monocytes to acute stress exposure, in a sample of healthy adults (n=30) with a history of early childhood adversity, and a control group (n=30) without trauma experience. The early adversity group showed altered hypothalamus-pituitary-adrenal axis responses to stress, evidenced by lower ACTH and cortisol responses. Analyses of gene expression patterns showed that stress-responsive transcripts were enriched for genes involved in cytokine activity, cytokine-cytokine receptor interaction, chemokine activity, and G-protein coupled receptor binding. Differences between groups in stress-induced regulation of gene transcription were observed for genes involved in steroid binding, hormone activity, and G-protein coupled receptor binding. Transcription factor binding motif analysis showed an increased activity of pro-inflammatory upstream signaling in the early adversity group. We also identified transcripts that were differentially correlated with stress-induced cortisol increases between the groups, enriched for genes involved in cytokine-cytokine receptor interaction and glutamate receptor signaling. We suggest that childhood adversity leads to persistent alterations in transcriptional control of stress-responsive pathways, which-when chronically or repeatedly activated-might predispose individuals to stress-related psychopathology. PMID:27091381

  3. Trebananib With or Without Low-Dose Cytarabine in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-25

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  4. The PU.1-Modulated MicroRNA-22 Is a Regulator of Monocyte/Macrophage Differentiation and Acute Myeloid Leukemia.

    PubMed

    Shen, Chao; Chen, Ming-Tai; Zhang, Xin-Hua; Yin, Xiao-Lin; Ning, Hong-Mei; Su, Rui; Lin, Hai-Shuang; Song, Li; Wang, Fang; Ma, Yan-Ni; Zhao, Hua-Lu; Yu, Jia; Zhang, Jun-Wu

    2016-09-01

    MicroRNA-22 (miR-22) is emerging as a critical regulator in organ development and various cancers. However, its role in normal hematopoiesis and leukaemogenesis remains unclear. Here, we detected its increased expression during monocyte/macrophage differentiation of HL-60, THP1 cells and CD34+ hematopoietic stem/progenitor cells, and confirmed that PU.1, a key transcriptional factor for monocyte/macrophage differentiation, is responsible for transcriptional activation of miR-22 during the differentiation. By gain- and loss-of-function experiments, we demonstrated that miR-22 promoted monocyte/macrophage differentiation, and MECOM (EVI1) mRNA is a direct target of miR-22 and MECOM (EVI1) functions as a negative regulator in the differentiation. The miR-22-mediated MECOM degradation increased c-Jun but decreased GATA2 expression, which results in increased interaction between c-Jun and PU.1 via increasing c-Jun levels and relief of MECOM- and GATA2-mediated interference in the interaction, and thus promoting monocyte/macrophage differentiation. We also observed significantly down-regulation of PU.1 and miR-22 as well as significantly up-regulation of MECOM in acute myeloid leukemia (AML) patients. Reintroduction of miR-22 relieved the differentiation blockage and inhibited the growth of bone marrow blasts of AML patients. Our results revealed new function and mechanism of miR-22 in normal hematopoiesis and AML development and demonstrated its potential value in AML diagnosis and therapy. PMID:27617961

  5. Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia or Acute Leukemia in Remission

    ClinicalTrials.gov

    2016-06-09

    Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Previously Treated Myelodysplastic Syndromes; Secondary Acute Myeloid Leukemia

  6. Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy

    ClinicalTrials.gov

    2016-08-23

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Fungal Infection; Neutropenia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  7. T-cell/myeloid mixed-phenotype acute leukemia with monocytic differentiation and isolated 17p deletion

    PubMed Central

    Lopes, Germison Silva; Leitão, João Paulo de Vasconcelos; Kaufman, Jacques; Duarte, Fernando Barroso; Matos, Daniel Mazza

    2014-01-01

    Mixed phenotype acute leukemia is a rare subtype of leukemia that probably arises from a hematopoietic pluripotent stem cell. The co-expression of two of myeloid, B- or T-lymphoid antigens is the hallmark of this disease. Herein, the case of a 28-year-old female patient is reported who presented with hemoglobin of 5.8 g/dL, white blood cell count of 138 × 109/L and platelet count of 12 × 109/L. The differential count of peripheral blood revealed 96% of blasts. Moreover, the patient presented with lymphadenopathy, splenomegaly and bone marrow infiltration by monocytoid blasts characterized as 7% positivity by Sudan Black cytochemical staining. Immunophenotyping revealed the involvement of blasts of both T- and monocytic lineages. The cytogenetic analysis showed an isolated 17p deletion. Thus, the diagnosis of T-cell/myeloid mixed phenotype acute leukemia was made with two particular rare features, that is, the monocytic differentiation and the 17p deletion as unique cytogenetic abnormalities. The possibility of concomitant expressions of T-cell and monocytic differentiation antigens in the same blast population is hard to explain using the classical model of hematopoiesis. However, recent studies have suggested that myeloid potential persists even when the lineage branches segregate toward B- and T-cells. The role of an isolated 17p deletion in the pathogenesis of this condition is unclear. At present, the patient is in complete remission after an allogeneic stem cell transplantation procedure. PMID:25031170

  8. Aleukemic Leukemia Cutis Manifesting with Disseminated Nodular Eruptions and a Plaque Preceding Acute Monocytic Leukemia: A Case Report

    PubMed Central

    Yonal, Ipek; Hindilerden, Fehmi; Coskun, Raif; Dogan, Oner Ibrahim; Nalcaci, Meliha

    2011-01-01

    Aleukemic leukemia cutis (ALC), a discrete tumor of leukemic cells involving the skin, may be the first manifestation of acute myeloid leukemia, preceding the onset in marrow and blood by months and years. ALC is often difficult to diagnose and is associated with a dismal prognosis. A 63-year-old male presented with nodular swellings on the face, a plaque extending over the right shoulder and multiple enlarged cervical lymph nodes. The skin biopsy of the plaque lesion showed a diffuse neoplastic infiltration extending from the dermis to subcutaneous tissue with diffuse positivity for myeloperoxidase and focal positivity for CD34 on immunohistochemical staining. The diagnosis was leukemia cutis. One month later, acute monocytic leukemia (FAB AML-M5b) was diagnosed. The patient died on the seventh month of diagnosis. PMID:22187541

  9. Donor Stem Cell Transplant in Treating Patients With High Risk Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-08-29

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  10. Erythromycin in acute laryngitis in adults.

    PubMed

    Schalén, L; Eliasson, I; Kamme, C; Schalén, C

    1993-03-01

    Moraxella catarrhalis and Hemophilus influenzae are isolated from the nasopharynx in 50% to 55% and 8% to 15%, respectively, of cases of acute laryngitis in adults. This finding indicates that these organisms, M catarrhalis in particular, are in some way involved in the pathogenesis of the disorder. In the present double-blind, placebo-controlled trial, the effect of erythromycin ethylsuccinate (0.5 g twice a day for 5 days) on the elimination of nasopharyngeal pathogens and reduction of clinical signs of upper respiratory tract infection, as well as on subjective complaints, was evaluated in 106 adults with acute laryngitis. The bacterial isolation rates at presentation were M catarrhalis 50%, H influenzae 18%, and Streptococcus pneumoniae 4%. In the 99 patients who completed the study, the elimination of M catarrhalis after 1 week was better in the erythromycin group (25 of 30 cases) than in the placebo group (6 of 19 cases; p < or = .00038). The elimination of H influenzae was unaffected by erythromycin. Otolaryngologic examination did not reveal any significant group differences regarding laryngitis, pharyngitis, or rhinitis. Voice quality was improved after 1 week, irrespective of treatment. However, as compared to the placebo group, the erythromycin group reported fewer voice complaints after 1 week and fewer coughing complaints after 2 weeks. As acute laryngitis in adults is self-limiting, and subjective symptoms are spontaneously reduced after 1 week in most cases, antibiotic treatment does not seem warranted as a general policy. However, erythromycin may be justified in patients who are professionally dependent on voice function. PMID:8457123

  11. Early Discharge and Outpatients Care in Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia Previously Treated With Intensive Chemotherapy

    ClinicalTrials.gov

    2015-02-05

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia

  12. Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Relapsed or Refractory Acute Leukemia

    ClinicalTrials.gov

    2013-09-27

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Malignant Neoplasm; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia

  13. Ixazomib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-06-24

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  14. AKT Inhibitor MK-2206 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-12-23

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  15. Vorinostat and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2011-11-03

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

  16. Arsenic Trioxide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-09-13

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  17. Combination Chemotherapy With or Without Valspodar in Treating Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-06-03

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

  18. Non-identical twins - microglia and monocyte-derived macrophages in acute injury and autoimmune inflammation.

    PubMed

    Jung, Steffen; Schwartz, Michal

    2012-01-01

    The brain has been commonly regarded as a "tissue behind walls." Appearance of immune cells in the brain has been taken as a sign of pathology. Moreover, since infiltrating monocyte-derived macrophages and activated resident microglia were indistinguishable by conventional means, both populations were considered together as inflammatory cells that should be mitigated. Yet, because the microglia permanently reside in the brain, attributing to them negative properties evoked an ongoing debate; why cells that are supposed to be the brain guardians acquire only destructive potential? Studies over the last two decades in the immune arena in general, and in the context of central nervous system pathology in particular, have resulted in a paradigm shift toward a more balanced appreciation of the contributions of immune cells in the context of brain maintenance and repair, and toward the recognition of distinct roles of resident microglia and infiltrating monocyte-derived macrophages. PMID:22566968

  19. Cystathionine-gamma-lyase gene silencing with siRNA in monocytes/macrophages protects mice against acute pancreatitis.

    PubMed

    Badiei, A; Chambers, S T; Gaddam, R R; Fraser, R; Bhatia, M

    2016-01-01

    Hydrogen sulphide (H2S) is an endogenous inflammatory mediator produced by cystathionine-γ-lyase (CSE) in monocytes/macrophages. To determine the role of H2S and macrophages in inflammation, we used small interference RNA (siRNA) to target the CSE gene and investigated its effect in a mouse model of acute pancreatitis. Acute pancreatitis is characterised by increased levels of plasma amylase, myeloperoxidase (MPO) activity and pro-inflammatory cytokines and chemokines in the pancreas and lung. SiRNA treatment attenuated inflammation in the pancreas and lungs of mice following caerulein-induced acute pancreatitis. MPO activity increased in caerulein-induced acute pancreatitis (16.21 ± 3.571 SD fold increase over control) and treatment with siRNA significantly reduced this (mean 3.555 ± 2.522 SD fold increase over control) (p < 0.0001). Similarly, lung MPO activity increased following treatment with caerulein (3.56 ± 0.941 SD fold increase over control) while siRNA treatment significantly reduced MPO activity (0.8243 ± 0.4353 SD fold increase over control) (p < 0.0001). Caerulein treatment increased plasma amylase activity (7094 ± 207 U/l) and this significantly decreased following siRNA administration (5895 ± 115 U/l) (p < 0.0001). Cytokine and chemokine levels in caerulein-induced acute pancreatitis reduced following treatment with siRNA. For example, siRNA treatment significantly decreased pancreatic and lung monocyte chemoattractant protein (MCP)-1 (169.8 ± 59.75 SD; 90.01 ± 46.97 SD pg/ml, respectively) compared to caerulein-treated mice (324.7 ± 103.9 SD; 222.8 ± 85.37 SD pg/ml, pancreas and lun,g respectively) (p < 0.0001). These findings show a crucial pro-inflammatory role for H2S synthesised by CSE in macrophages in acute pancreatitis and suggest CSE gene silencing with siRNA as a potential therapeutic approach for this condition. PMID:26411454

  20. CPX-351 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2016-04-25

    Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  1. Bortezomib, Daunorubicin, and Cytarabine in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-09-04

    Acute Myeloid Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

  2. Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission

    ClinicalTrials.gov

    2016-01-19

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia

  3. Clofarabine or Daunorubicin Hydrochloride and Cytarabine Followed By Decitabine or Observation in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-09-16

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  4. Consumption of Bifidobacterium lactis Bi-07 by healthy elderly adults enhances phagocytic activity of monocytes and granulocytes.

    PubMed

    Maneerat, Sujira; Lehtinen, Markus J; Childs, Caroline E; Forssten, Sofia D; Alhoniemi, Esa; Tiphaine, Milin; Yaqoob, Parveen; Ouwehand, Arthur C; Rastall, Robert A

    2013-01-01

    Elderly adults have alterations in their gut microbiota and immune functions that are associated with higher susceptibility to infections and metabolic disorders. Probiotics and prebiotics, and their synbiotic combinations are food supplements that have been shown to improve both gut and immune function. The objective of this randomised, double-blind, placebo-controlled, cross-over human clinical trial was to study immune function and the gut microbiota in healthy elderly adults. Volunteers (n 37) consumed prebiotic galacto-oligosaccharides (GOS; 8 g/d), probiotic Bifidobacterium lactis Bi-07 (Bi-07; 10(9) colony-forming units/d), their combination (Bi-07 + GOS) and maltodextrin control (8 g/d) in four 3-week periods separated by 4-week wash-out periods. Immune function was analysed by determining the phagocytic and oxidative burst activity of monocytes and granulocytes, whole-blood response to lipopolysaccharide, plasma chemokine concentrations and salivary IgA levels. Gut microbiota composition and faecal SCFA content were determined using 16S ribosomal RNA fluorescence in situ hybridisation and HPLC, respectively. Primary statistical analyses indicated the presence of carry-over effects and thus measurements from only the first supplementation period were considered valid. Subsequent statistical analysis showed that consumption of Bi-07 improved the phagocytic activity of monocytes (P < 0·001) and granulocytes (P = 0·02). Other parameters were unchanged. We have for the first time shown that the probiotic Bi-07 may provide health benefits to elderly individuals by improving the phagocytic activity of monocytes and granulocytes. The present results also suggest that in the elderly, the effects of some probiotics and prebiotics may last longer than in adults. PMID:25191600

  5. Alvocidib, Cytarabine, and Mitoxantrone Hydrochloride or Cytarabine and Daunorubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-10-10

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  6. Upregulated Expression of A20 on Monocytes is Associated With Increased Severity of Acute-on-Chronic Hepatitis B Liver Failure: A Case-Control Study.

    PubMed

    Guo, Yonghong; He, Yu; Zhang, Ying; Zhou, Yun; Qin, Yuan; Fan, Chao; Ji, Guangxi; Zhang, Peixin; Jia, Zhansheng

    2015-09-01

    A20 expression is increased in various inflammatory diseases. However, the role of A20 in acute-on-chronic liver failure is unknown. This study was to evaluate A20 expression on monocytes and its associations with the severity of acute-on-chronic hepatitis B liver failure (ACHBLF). Thirty-seven patients with ACHBLF, 20 patients with chronic hepatitis B (CHB), and 15 healthy controls (HC) were enrolled in this case-control study. A20-positive monocytes were identified using flow cytometry. Serum levels of interleukin (IL)-10, IL-12p70, and TNF-α were determined using bead cytometry. A20 and IL-10 expressions were examined in THP-1 cells stimulated by lipopolysaccharide (LPS). The frequency of A20+ monocytes was significantly increased in patients with ACHBLF compared with HC (median [interquartile range, IQR]: 15.7 [22.8]% vs 2.5 [4.7]%, P < 0.001). Increased monocyte A20 expression was detected during the progression phase (including the mild/moderate and severe grades of ACHBLF) compared with patients in the recovery phase (both P < 0.05), and in the ACHBLF worsening group compared with patients in the improvement group (P < 0.001). LPS treatment upregulated A20 and IL-10 expressions in THP-1 cells. A20 expression on monocytes from patients with ACHBLF was positively correlated with total bilirubin (r = 0.60, P = 0.0001), direct bilirubin (r = 0.63, P < 0.0001), and MELD score (r = 0.43, P = 0.008), and inversely with prothrombin activity (r = -0.33, P = 0.046). IL-10 and TLR4 expression levels in monocytes, and serum levels of IL-10, IL-12p70, and TNF-α were increased in patients with ACHBLF compared with patients with CHB and HC. Increased A20 expression on monocytes was associated with the severity of ACHBLF. PMID:26426612

  7. MEK Inhibitor MEK162, Idarubicin, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-04-25

    Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  8. Cyclosporine, Pravastatin Sodium, Etoposide, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2012-06-18

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  9. Busulfan, Fludarabine Phosphate, and Anti-Thymocyte Globulin Followed By Donor Stem Cell Transplant and Azacitidine in Treating Patients With High-Risk Myelodysplastic Syndrome and Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-20

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  10. Lithium Carbonate and Tretinoin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-10-19

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  11. Sirolimus, Idarubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-06-03

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

  12. Cholecalciferol in Treating Patients With Acute Myeloid Leukemia Undergoing Intensive Induction Chemotherapy

    ClinicalTrials.gov

    2015-06-18

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

  13. C-Myb(+) erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident macrophages.

    PubMed

    Hoeffel, Guillaume; Chen, Jinmiao; Lavin, Yonit; Low, Donovan; Almeida, Francisca F; See, Peter; Beaudin, Anna E; Lum, Josephine; Low, Ivy; Forsberg, E Camilla; Poidinger, Michael; Zolezzi, Francesca; Larbi, Anis; Ng, Lai Guan; Chan, Jerry K Y; Greter, Melanie; Becher, Burkhard; Samokhvalov, Igor M; Merad, Miriam; Ginhoux, Florent

    2015-04-21

    Although classified as hematopoietic cells, tissue-resident macrophages (MFs) arise from embryonic precursors that seed the tissues prior to birth to generate a self-renewing population, which is maintained independently of adult hematopoiesis. Here we reveal the identity of these embryonic precursors using an in utero MF-depletion strategy and fate-mapping of yolk sac (YS) and fetal liver (FL) hematopoiesis. We show that YS MFs are the main precursors of microglia, while most other MFs derive from fetal monocytes (MOs). Both YS MFs and fetal MOs arise from erythro-myeloid progenitors (EMPs) generated in the YS. In the YS, EMPs gave rise to MFs without monocytic intermediates, while EMP seeding the FL upon the establishment of blood circulation acquired c-Myb expression and gave rise to fetal MOs that then seeded embryonic tissues and differentiated into MFs. Thus, adult tissue-resident MFs established from hematopoietic stem cell-independent embryonic precursors arise from two distinct developmental programs. PMID:25902481

  14. Topical NSAIDs for acute pain in adults

    PubMed Central

    Massey, Thomas; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background Use of topical NSAIDs to treat acute musculoskeletal conditions is widely accepted in some parts of the world, but not in others. Their main attraction is their potential to provide pain relief without associated systemic adverse events. Objectives To review the evidence from randomised, double-blind, controlled trials on the efficacy and safety of topically applied NSAIDs in acute pain. Search methods We searched MEDLINE, EMBASE, The Cochrane Library, and our own in-house database to December 2009. We sought unpublished studies by asking personal contacts and searching on-line clinical trial registers and manufacturers web sites. Selection criteria We included randomised, double-blind, active or placebo (inert carrier)-controlled trials in which treatments were administered to adult patients with acute pain resulting from strains, sprains or sports or overuse-type injuries (twisted ankle, for instance). There had to be at least 10 participants in each treatment arm, with application of treatment at least once daily. Data collection and analysis Two review authors independently assessed trial quality and validity, and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and numbers needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment. Main results Forty-seven studies were included; most compared topical NSAIDs in the form of a gel, spray, or cream with a similar placebo, with 3455 participants in the overall analysis of efficacy. For all topical NSAIDs combined, compared with placebo, the number needed to treat to benefit (NNT) for clinical success, equivalent to 50% pain relief, was 4.5 (3.9 to 5.3) for treatment periods of 6 to 14 days. Topical diclofenac, ibuprofen, ketoprofen, and piroxicam were of similar efficacy, but indomethacin and benzydamine were not significantly better than placebo. Local skin reactions were generally mild and transient, and did not differ from

  15. Ly6C(hi) Monocytes Provide a Link between Antibiotic-Induced Changes in Gut Microbiota and Adult Hippocampal Neurogenesis.

    PubMed

    Möhle, Luisa; Mattei, Daniele; Heimesaat, Markus M; Bereswill, Stefan; Fischer, André; Alutis, Marie; French, Timothy; Hambardzumyan, Dolores; Matzinger, Polly; Dunay, Ildiko R; Wolf, Susanne A

    2016-05-31

    Antibiotics, though remarkably useful, can also cause certain adverse effects. We detected that treatment of adult mice with antibiotics decreases hippocampal neurogenesis and memory retention. Reconstitution with normal gut flora (SPF) did not completely reverse the deficits in neurogenesis unless the mice also had access to a running wheel or received probiotics. In parallel to an increase in neurogenesis and memory retention, both SPF-reconstituted mice that ran and mice supplemented with probiotics exhibited higher numbers of Ly6C(hi) monocytes in the brain than antibiotic-treated mice. Elimination of Ly6C(hi) monocytes by antibody depletion or the use of knockout mice resulted in decreased neurogenesis, whereas adoptive transfer of Ly6C(hi) monocytes rescued neurogenesis after antibiotic treatment. We propose that the rescue of neurogenesis and behavior deficits in antibiotic-treated mice by exercise and probiotics is partially mediated by Ly6C(hi) monocytes. PMID:27210745

  16. Azacitidine and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-12

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  17. Monocyte Phenotype and Polyfunctionality Are Associated With Elevated Soluble Inflammatory Markers, Cytomegalovirus Infection, and Functional and Cognitive Decline in Elderly Adults.

    PubMed

    de Pablo-Bernal, Rebeca Sara; Cañizares, Julio; Rosado, Isaac; Galvá, María Isabel; Alvarez-Ríos, Ana Isabel; Carrillo-Vico, Antonio; Ferrando-Martínez, Sara; Muñoz-Fernández, María Ángeles; Rafii-El-Idrissi Benhnia, Mohammed; Pacheco, Yolanda María; Ramos, Raquel; Leal, Manuel; Ruiz-Mateos, Ezequiel

    2016-05-01

    Monocytes are mediators of the inflammatory response and include three subsets: classical, intermediate, and nonclassical. Little is known about the phenotypical and functional age-related changes in monocytes and their association with soluble inflammatory biomarkers, cytomegalovirus infection, and functional and mental decline. We assayed the activation ex vivo and the responsiveness to TLR2 and TLR4 agonists in vitro in the three subsets and assessed the intracellular production of IL1-alpha (α), IL1-beta (β), IL-6, IL-8, TNF-α, and IL-10 of elderly adults (median 83 [67-90] years old;n= 20) compared with young controls (median 35 [27-40] years old;n= 20). Ex vivo, the elderly adults showed a higher percentage of classical monocytes that expressed intracellular IL1-α (p= .001), IL1-β (p= .001), IL-6 (p= .002), and IL-8 (p= .007). Similar results were obtained both for the intermediate and nonclassical subsets and in vitro. Polyfunctionality was higher in the elderly adults. The functionality ex vivo was strongly associated with soluble inflammatory markers. The activation phenotype was independently associated with the anti-cytomegalovirus IgG levels and with functional and cognitive decline. These data demonstrate that monocytes are key cell candidates for the source of the high soluble inflammatory levels. Our findings suggest that cytomegalovirus infection might be a driving force in the activation of monocytes and is associated with the functional and cognitive decline. PMID:26286603

  18. Veliparib and Topotecan With or Without Carboplatin in Treating Patients With Relapsed or Refractory Acute Leukemia, High-Risk Myelodysplasia, or Aggressive Myeloproliferative Disorders

    ClinicalTrials.gov

    2016-04-05

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Essential Thrombocythemia; Hematopoietic and Lymphoid Cell Neoplasm; Philadelphia Chromosome Negative, BCR-ABL1 Positive Chronic Myelogenous Leukemia; Polycythemia Vera; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Secondary Myelodysplastic Syndrome

  19. Decitabine Followed by Idarubicin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-10-09

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts

  20. Acute Lymphoblastic Leukemia (ALL) Treatment in Adults (Beyond the Basics)

    MedlinePlus

    ... 2016 UpToDate, Inc. Patient information: Acute lymphoblastic leukemia (ALL) treatment in adults (Beyond the Basics) Author Richard ... the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of ...

  1. Inflammatory Transcriptome Profiling of Human Monocytes Exposed Acutely to Cigarette Smoke

    PubMed Central

    Wright, William R.; Parzych, Katarzyna; Crawford, Damian; Mein, Charles; Mitchell, Jane A.; Paul-Clark, Mark J.

    2012-01-01

    Background Cigarette smoking is responsible for 5 million deaths worldwide each year, and is a major risk factor for cardiovascular and lung diseases. Cigarette smoke contains a complex mixture of over 4000 chemicals containing 1015 free radicals. Studies show smoke is perceived by cells as an inflammatory and xenobiotic stimulus, which activates an immune response. The specific cellular mechanisms driving cigarette smoke-induced inflammation and disease are not fully understood, although the innate immune system is involved in the pathology of smoking related diseases. Methodology/Principle findings To address the impact of smoke as an inflammagen on the innate immune system, THP-1 cells and Human PBMCs were stimulated with 3 and 10% (v/v) cigarette smoke extract (CSE) for 8 and 24 hours. Total RNA was extracted and the transcriptome analysed using Illumina BeadChip arrays. In THP-1 cells, 10% CSE resulted in 80 genes being upregulated and 37 downregulated by ≥1.5 fold after 8 hours. In PBMCs stimulated with 10% CSE for 8 hours, 199 genes were upregulated and 206 genes downregulated by ≥1.5 fold. After 24 hours, the number of genes activated and repressed by ≥1.5 fold had risen to 311 and 306 respectively. The major pathways that were altered are associated with cell survival, such as inducible antioxidants, protein chaperone and folding proteins, and the ubiquitin/proteosome pathway. Conclusions Our results suggest that cigarette smoke causes inflammation and has detrimental effects on the metabolism and function of innate immune cells. In addition, THP-1 cells provide a genetically stable alternative to primary cells for the study of the effects of cigarette smoke on human monocytes. PMID:22363418

  2. [Effect of down-regulating mll-af9 gene expression on proliferation of acute monocytic leukemia cell line THP-1].

    PubMed

    Li, Lei; Zhang, Ai-Hua; Liu, Ling-Bo; Bi, Lan; Wang, Li; Zhao, Ya-Jie; Zou, Ping

    2008-04-01

    This study was aimed to investigate the effect of small interfering RNA (siRNA) on the expression of mll-af9 oncogene and the proliferation of human acute monocytic leukemia cell line THP-1. One group of siRNA was designed targeting mll-af9 mRNA and finally obtained by chemosynthesis. Then the obtained siRNA was transfected into cultured human acute monocytic leukemia cell line THP-1 by lipofectamine. Flow cytometry was used to detect siRNA transfection efficiency. The level of mll-af9 mRNA expression was analyzed by reverse transcription polymerase chain reaction (RT-PCR). The cell proliferation rate was assayed by MTT. The change of cell cycles and apoptosis rate was detected by flow cytometry. The results showed that the siRNA transfection efficiency was 69.1%+/-1.8%. The level of mll-af9 mRNA expression was significantly inhibited in siRNA-transfected cells as compared with the controls. mll-af9-targeted siRNA inhibited the proliferation of THP-1 cells and induced cell apoptosis effectively after transfection. The percentage of G0/G1 phase cells significantly increased in siRNA-transfected cells in comparion with the control cells, but the percentage of S phase cells significantly decreased. It is concluded that the mll-af9-targeted siRNA can effectively inhibit the proliferation of human acute monocytic leukemia cell line THP-1. PMID:18426643

  3. Human Monocyte Heat Shock Protein 72 Responses to Acute Hypoxic Exercise after 3 Days of Exercise Heat Acclimation

    PubMed Central

    Lee, Ben J.; Mackenzie, Richard W. A.; Cox, Valerie; James, Rob S.; Thake, Charles D.

    2015-01-01

    The aim of this study was to determine whether short-term heat acclimation (STHA) could confer increased cellular tolerance to acute hypoxic exercise in humans as determined via monocyte HSP72 (mHSP72) expression. Sixteen males were separated into two matched groups. The STHA group completed 3 days of exercise heat acclimation; 60 minutes cycling at 50% V˙O2peak in 40°C 20% relative humidity (RH). The control group (CON) completed 3 days of exercise training in 20°C, 40% RH. Each group completed a hypoxic stress test (HST) one week before and 48 hours following the final day of CON or STHA. Percentage changes in HSP72 concentrations were similar between STHA and CON following HST1 (P = 0.97). STHA induced an increase in basal HSP72 (P = 0.03) with no change observed in CON (P = 0.218). Basal mHSP72 remained elevated before HST2 for the STHA group (P < 0.05) and was unchanged from HST1 in CON (P > 0.05). Percent change in mHSP72 was lower after HST2 in STHA compared to CON (P = 0.02). The mHSP72 response to hypoxic exercise was attenuated following 3 days of heat acclimation. This is indicative of improved tolerance and ability to cope with the hypoxic insult, potentially mediated in part by increased basal reserves of HSP72. PMID:25874231

  4. Cooperation between Monocyte-Derived Cells and Lymphoid Cells in the Acute Response to a Bacterial Lung Pathogen

    PubMed Central

    Brown, Andrew S.; Yang, Chao; Fung, Ka Yee; Bachem, Annabell; Bourges, Dorothée; Bedoui, Sammy; Hartland, Elizabeth L.; van Driel, Ian R.

    2016-01-01

    Legionella pneumophila is the causative agent of Legionnaires’ disease, a potentially fatal lung infection. Alveolar macrophages support intracellular replication of L. pneumophila, however the contributions of other immune cell types to bacterial killing during infection are unclear. Here, we used recently described methods to characterise the major inflammatory cells in lung after acute respiratory infection of mice with L. pneumophila. We observed that the numbers of alveolar macrophages rapidly decreased after infection coincident with a rapid infiltration of the lung by monocyte-derived cells (MC), which, together with neutrophils, became the dominant inflammatory cells associated with the bacteria. Using mice in which the ability of MC to infiltrate tissues is impaired it was found that MC were required for bacterial clearance and were the major source of IL12. IL12 was needed to induce IFNγ production by lymphoid cells including NK cells, memory T cells, NKT cells and γδ T cells. Memory T cells that produced IFNγ appeared to be circulating effector/memory T cells that infiltrated the lung after infection. IFNγ production by memory T cells was stimulated in an antigen-independent fashion and could effectively clear bacteria from the lung indicating that memory T cells are an important contributor to innate bacterial defence. We also determined that a major function of IFNγ was to stimulate bactericidal activity of MC. On the other hand, neutrophils did not require IFNγ to kill bacteria and alveolar macrophages remained poorly bactericidal even in the presence of IFNγ. This work has revealed a cooperative innate immune circuit between lymphoid cells and MC that combats acute L. pneumophila infection and defines a specific role for IFNγ in anti-bacterial immunity. PMID:27300652

  5. Effects of the New Generation Synthetic Reconstituted Surfactant CHF5633 on Pro- and Anti-Inflammatory Cytokine Expression in Native and LPS-Stimulated Adult CD14+ Monocytes

    PubMed Central

    Glaser, Kirsten; Fehrholz, Markus; Curstedt, Tore; Kunzmann, Steffen; Speer, Christian P.

    2016-01-01

    Background Surfactant replacement therapy is the standard of care for the prevention and treatment of neonatal respiratory distress syndrome. New generation synthetic surfactants represent a promising alternative to animal-derived surfactants. CHF5633, a new generation reconstituted synthetic surfactant containing SP-B and SP-C analogs and two synthetic phospholipids has demonstrated biophysical effectiveness in vitro and in vivo. While several surfactant preparations have previously been ascribed immunomodulatory capacities, in vitro data on immunomodulation by CHF5633 are limited, so far. Our study aimed to investigate pro- and anti-inflammatory effects of CHF5633 on native and LPS-stimulated human adult monocytes. Methods Highly purified adult CD14+ cells, either native or simultaneously stimulated with LPS, were exposed to CHF5633, its components, or poractant alfa (Curosurf®). Subsequent expression of TNF-α, IL-1β, IL-8 and IL-10 mRNA was quantified by real-time quantitative PCR, corresponding intracellular cytokine synthesis was analyzed by flow cytometry. Potential effects on TLR2 and TLR4 mRNA and protein expression were monitored by qPCR and flow cytometry. Results Neither CHF5633 nor any of its components induced inflammation or apoptosis in native adult CD14+ monocytes. Moreover, LPS-induced pro-inflammatory responses were not aggravated by simultaneous exposure of monocytes to CHF5633 or its components. In LPS-stimulated monocytes, exposure to CHF5633 led to a significant decrease in TNF-α mRNA (0.57 ± 0.23-fold, p = 0.043 at 4h; 0.56 ± 0.27-fold, p = 0.042 at 14h). Reduction of LPS-induced IL-1β mRNA expression was not significant (0.73 ± 0.16, p = 0.17 at 4h). LPS-induced IL-8 and IL-10 mRNA and protein expression were unaffected by CHF5633. For all cytokines, the observed CHF5633 effects paralleled a Curosurf®-induced modulation of cytokine response. TLR2 and TLR4 mRNA and protein expression were not affected by CHF5633 and Curosurf

  6. The perfect storm: older adults and acute kidney injury.

    PubMed

    Hain, Debra; Paixao, Rute

    2015-01-01

    Older adults have a high risk for acute kidney injury (AKI), often necessitating critical care admission. The majority of older adults live with 1 or more chronic conditions requiring multiple medications, and when faced with acute illness increased vulnerability can lead to poor health outcomes. When combined with circumstances that exacerbate chronic conditions, clinicians may witness the perfect storm. Some factors that contribute to AKI risk include the aging kidney, sepsis, polypharmacy, and nephrotoxic medications and contrast media. This paper discusses specific risks and approaches to care for older adults with AKI who are in critical care. PMID:26039649

  7. The CD14+CD16+ Inflammatory Monocyte Subset Displays Increased Mitochondrial Activity and Effector Function During Acute Plasmodium vivax Malaria

    PubMed Central

    Antonelli, Lis R. V.; Leoratti, Fabiana M. S.; Costa, Pedro A. C.; Rocha, Bruno C.; Diniz, Suelen Q.; Tada, Mauro S.; Pereira, Dhelio B.; Teixeira-Carvalho, Andrea; Golenbock, Douglas T.; Gonçalves, Ricardo; Gazzinelli, Ricardo T.

    2014-01-01

    Infection with Plasmodium vivax results in strong activation of monocytes, which are important components of both the systemic inflammatory response and parasite control. The overall goal of this study was to define the role of monocytes during P. vivax malaria. Here, we demonstrate that P. vivax–infected patients display significant increase in circulating monocytes, which were defined as CD14+CD16− (classical), CD14+CD16+ (inflammatory), and CD14loCD16+ (patrolling) cells. While the classical and inflammatory monocytes were found to be the primary source of pro-inflammatory cytokines, the CD16+ cells, in particular the CD14+CD16+ monocytes, expressed the highest levels of activation markers, which included chemokine receptors and adhesion molecules. Morphologically, CD14+ were distinguished from CD14lo monocytes by displaying larger and more active mitochondria. CD14+CD16+ monocytes were more efficient in phagocytizing P. vivax-infected reticulocytes, which induced them to produce high levels of intracellular TNF-α and reactive oxygen species. Importantly, antibodies specific for ICAM-1, PECAM-1 or LFA-1 efficiently blocked the phagocytosis of infected reticulocytes by monocytes. Hence, our results provide key information on the mechanism by which CD14+CD16+ cells control parasite burden, supporting the hypothesis that they play a role in resistance to P. vivax infection. PMID:25233271

  8. The CD14+CD16+ inflammatory monocyte subset displays increased mitochondrial activity and effector function during acute Plasmodium vivax malaria.

    PubMed

    Antonelli, Lis R V; Leoratti, Fabiana M S; Costa, Pedro A C; Rocha, Bruno C; Diniz, Suelen Q; Tada, Mauro S; Pereira, Dhelio B; Teixeira-Carvalho, Andrea; Golenbock, Douglas T; Gonçalves, Ricardo; Gazzinelli, Ricardo T

    2014-09-01

    Infection with Plasmodium vivax results in strong activation of monocytes, which are important components of both the systemic inflammatory response and parasite control. The overall goal of this study was to define the role of monocytes during P. vivax malaria. Here, we demonstrate that P. vivax-infected patients display significant increase in circulating monocytes, which were defined as CD14(+)CD16- (classical), CD14(+)CD16(+) (inflammatory), and CD14loCD16(+) (patrolling) cells. While the classical and inflammatory monocytes were found to be the primary source of pro-inflammatory cytokines, the CD16(+) cells, in particular the CD14(+)CD16(+) monocytes, expressed the highest levels of activation markers, which included chemokine receptors and adhesion molecules. Morphologically, CD14(+) were distinguished from CD14lo monocytes by displaying larger and more active mitochondria. CD14(+)CD16(+) monocytes were more efficient in phagocytizing P. vivax-infected reticulocytes, which induced them to produce high levels of intracellular TNF-α and reactive oxygen species. Importantly, antibodies specific for ICAM-1, PECAM-1 or LFA-1 efficiently blocked the phagocytosis of infected reticulocytes by monocytes. Hence, our results provide key information on the mechanism by which CD14(+)CD16(+) cells control parasite burden, supporting the hypothesis that they play a role in resistance to P. vivax infection. PMID:25233271

  9. Peripheral Blood Monocytes as Adult Stem Cells: Molecular Characterization and Improvements in Culture Conditions to Enhance Stem Cell Features and Proliferative Potential

    PubMed Central

    Ungefroren, Hendrik; Hyder, Ayman; Schulze, Maren; Fawzy El-Sayed, Karim M.; Grage-Griebenow, Evelin; Nussler, Andreas K.; Fändrich, Fred

    2016-01-01

    Adult stem or programmable cells hold great promise in diseases in which damaged or nonfunctional cells need to be replaced. We have recently demonstrated that peripheral blood monocytes can be differentiated in vitro into cells resembling specialized cell types like hepatocytes and pancreatic beta cells. During phenotypic conversion, the monocytes downregulate monocyte/macrophage differentiation markers, being indicative of partial dedifferentiation, and are partially reprogrammed to acquire a state of plasticity along with expression of various markers of pluripotency and resumption of mitosis. Upregulation of stem cell markers and mitotic activity in the cultures was shown to be controlled by autocrine production/secretion of activin A and transforming growth factor-beta (TGF-β). These reprogrammed monocyte derivatives were termed “programmable cells of monocytic origin” (PCMO). Current efforts focus on establishing culture conditions that increase both the plasticity and proliferation potential of PCMO in order to be able to generate large amounts of blood-derived cells suitable for both autologous and allogeneic therapies. PMID:26798361

  10. Cecocolic Intussusception in Adult Caused by Acute Appendicitis

    PubMed Central

    Lee, Kang Young; Sohn, Seung-Kook

    2014-01-01

    Intussusception in adult is rare. The etiology is different from that of childhood. The most common cause of intussusception in adult is known as malignancy. When dealing with adult intussusception, surgical resection is usually warranted for correct diagnosis and proper treatment. This is a case report of cecocolic intussusception caused by an acute appendicitis in adult. The causes of cecocolic intussusception were reported as appendiceal adenocarcinoma, appendiceal mucocele, appendiceal adenoma, or idiopathic. Although this patient underwent laparoscopic right hemicolectomy under suspicion of malignancy at cecum base, final pathologic diagnosis revealed only acute appendicitis. Thus, the present case emphasizes the importance of prior thorough examinations including colonoscopy when we encounter this rare kind of intussusception in adult. PMID:24826358

  11. Acute myocardial infarction in young adults: causes and management

    PubMed Central

    Osula, S; Bell, G; Hornung, R

    2002-01-01

    The case report in this review illustrates an acute myocardial infarction in a young adult probably due to arterial thrombosis that can be attributed to a hypercoagulable state resulting from the nephrotic syndrome. Although rare, acute myocardial infarction should be considered in young adults presenting with chest pain. A detailed clinical history may help to identify the aetiology, and guide subsequent management, but diagnostic coronary angiography is essential. Careful risk factor modification and treatment of the underlying cause should reduce the incidence of recurrent cardiac events. PMID:11796868

  12. Acute moderate exercise enhances compensatory brain activation in older adults.

    PubMed

    Hyodo, Kazuki; Dan, Ippeita; Suwabe, Kazuya; Kyutoku, Yasushi; Yamada, Yuhki; Akahori, Mitsuya; Byun, Kyeongho; Kato, Morimasa; Soya, Hideaki

    2012-11-01

    A growing number of reports state that regular exercise enhances brain function in older adults. Recently a functional near-infrared spectroscopy (fNIRS) study revealed that an acute bout of moderate exercise enhanced activation of the left dorsolateral prefrontal cortex (L-DLPFC) associated with Stroop interference in young adults. Whether this acute effect is also applicable to older adults was examined. Sixteen older adults performed a color-word matching Stroop task before and after 10 minutes of exercise on a cycle ergometer at a moderate intensity. Cortical hemodynamics of the prefrontal area was monitored with a fNIRS during the Stroop task. We analyzed Stroop interference (incongruent-neutral) as Stroop performance. Though activation for Stroop interference was found in the bilateral prefrontal area before the acute bout of exercise, activation of the right frontopolar area (R-FPA) was enhanced after exercise. In the majority of participants, this coincided with improved performance reflected in Stroop interference results. Thus, an acute bout of moderate exercise improved Stroop performance in older adults, and this was associated with contralateral compensatory activation. PMID:22300952

  13. Epidemiology of Acute Symptomatic Seizures among Adult Medical Admissions

    PubMed Central

    Nwani, Paul Osemeke; Nwosu, Maduaburochukwu Cosmas; Nwosu, Monica Nonyelum

    2016-01-01

    Acute symptomatic seizures are seizures occurring in close temporal relationship with an acute central nervous system (CNS) insult. The objective of the study was to determine the frequency of presentation and etiological risk factors of acute symptomatic seizures among adult medical admissions. It was a two-year retrospective study of the medical files of adults patients admitted with acute symptomatic seizures as the first presenting event. There were 94 cases of acute symptomatic seizures accounting for 5.2% (95% CI: 4.17–6.23) of the 1,802 medical admissions during the period under review. There were 49 (52.1%) males and 45 (47.9%) females aged between 18 years and 84 years. The etiological risk factors of acute symptomatic seizures were infections in 36.2% (n = 34) of cases, stroke in 29.8% (n = 28), metabolic in 12.8% (n = 12), toxic in 10.6% (n = 10), and other causes in 10.6% (n = 10). Infective causes were more among those below fifty years while stroke was more in those aged fifty years and above. CNS infections and stroke were the prominent causes of acute symptomatic seizures. This is an evidence of the “double tragedy” facing developing countries, the unresolved threat of infectious diseases on one hand and the increasing impact of noncommunicable diseases on the other one. PMID:26904280

  14. Current Concepts in Adult Acute Rhinosinusitis.

    PubMed

    Aring, Ann M; Chan, Miriam M

    2016-07-15

    Acute rhinosinusitis is one of the most common conditions that physicians treat in ambulatory care. Most cases of acute rhinosinusitis are caused by viral upper respiratory infections. A meta-analysis based on individual patient data found that common clinical signs and symptoms were not effective for identifying patients with rhinosinusitis who would benefit from antibiotics. C-reactive protein and erythrocyte sedimentation rate are somewhat useful tests for confirming acute bacterial maxillary sinusitis. Four signs and symptoms that significantly increase the likelihood of a bacterial cause when present are double sickening, purulent rhinorrhea, erythrocyte sedimentation rate greater than 10 mm per hour, and purulent secretion in the nasal cavity. Although cutoffs vary depending on the guideline, antibiotic therapy should be considered when rhinosinusitis symptoms fail to improve within seven to 10 days or if they worsen at any time. First-line antibiotics include amoxicillin with or without clavulanate. Current guidelines support watchful waiting within the first seven to 10 days after upper respiratory symptoms first appear. Evidence on the use of analgesics, intranasal corticosteroids, and saline nasal irrigation for the treatment of acute rhinosinusitis is poor. Nonetheless, these therapies may be used to treat symptoms within the first 10 days of upper respiratory infection. Radiography is not recommended in the evaluation of uncomplicated acute rhinosinusitis. For patients who do not respond to treatment, computed tomography of the sinuses without contrast media is helpful to evaluate for possible complications or anatomic abnormalities. Referral to an otolaryngologist is indicated when symptoms persist after maximal medical therapy and if any rare complications are suspected. PMID:27419326

  15. Immunomodulatory effects of adult Haemonchus contortus excretory/secretory products on human monocyte-derived dendritic cells.

    PubMed

    Rehman, Z U; Knight, J S; Koolaard, J; Simpson, H V; Pernthaner, A

    2015-12-01

    The levels of expression of surface molecules and release of cytokines and chemokines of human monocyte-derived dendritic cells were determined after their exposure to adult H. contortus excretory/secretory (ES) products or a combination of ES products and bacterial lipopolysaccharide (LPS). Worm products provoked a weak response and only partial maturation of the dendritic cells, consistent with the hyporesponsiveness and more tolerogenic immune environment present in parasitized animals and humans. Co-stimulation with LPS demonstrated that H. contortus secretions, like those of other helminths, contain immunomodulators capable of reducing some aspects of the strong T(H)1/T(H)2 response evoked by bacterial LPS. There were significant reductions in the release of some cytokine/chemokines by LPS-stimulated mdDCs and a trend (although not significant at P < 0.05) for reduced expression levels of CD40, CD80 and HLA-DR. A prominent feature was the variability in responses of dendritic cells from the four donors, even on different days in repeat experiments, suggesting that generalized conclusions may be difficult to make, except in genetically related animals. Such observations may therefore be applicable only to restricted populations. In addition, previous exposure to parasites in a target population for immunomodulatory therapy may be an important factor in assessing the likelihood of adverse reactions or failures in the treatment to worm therapy. PMID:26457886

  16. Adult Acute Myeloid Leukemia Long-term Survivors

    PubMed Central

    Cheng, M. Jennifer; Hourigan, Christopher S.; Smith, Thomas J.

    2014-01-01

    The number of leukemia patients and survivors is growing. This review summarizes what is known regarding the health related quality of life (HRQOL) and medical complications associated with acute myeloid leukemia (AML) disease and treatment and highlights understudied aspects of adult AML survivorship care, and potential novel areas for intervention. PMID:25243197

  17. MS-275 and GM-CSF in Treating Patients With Myelodysplastic Syndrome and/or Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphocytic Leukemia

    ClinicalTrials.gov

    2013-01-08

    Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  18. SB-715992 in Treating Patients With Acute Leukemia, Chronic Myelogenous Leukemia, or Advanced Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-01-10

    Acute Undifferentiated Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  19. Acute myeloid leukemia in the older adults.

    PubMed

    Almeida, Antonio M; Ramos, Fernando

    2016-01-01

    AML is an aggressive hematological malignancy with highest incidence in the older adults. The adverse features of AML in the elderly, and the frailties and comorbidities frequently present in them, make their management a particularly difficult therapeutic challenge. In this context, it is important to assess carefully patient- as well as disease-associated prognostic features with validated tools. The fittest patients should be considered for curative therapy, such as bone marrow transplantation, whereas low intensity options may be more appropriate for frail patients. Here we review how to assess patients with elderly AML and the treatments options available for them. PMID:27408788

  20. 7-Hydroxystaurosporine and Perifosine in Treating Patients With Relapsed or Refractory Acute Leukemia, Chronic Myelogenous Leukemia or High Risk Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-09-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Neoplasms; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  1. Transplantations in adult acute lymphoblastic leukemia--grounds for optimism?

    PubMed

    Goldstone, Anthony H

    2009-01-01

    The large MRC/ECOG Adult Acute Lymphoblastic Leukemia Study establishes the value of sibling donor allogeneic transplantation in patients with standard risk, demonstrating superior outcome to conventional chemotherapy. The small but significant number of patients having matched unrelated donor transplantations on this study protocol appear to do well and might establish the value of such an approach for those without a sibling. Reduced-intensity conditioning might begin to address the transplantation-related mortality problems of the older patients. The youngest adults might not need to undergo transplantation at all. If they are now treated on pediatric chemotherapy protocols, their outcome appears to improve significantly. PMID:19778843

  2. Multiple Chronic Conditions in Older Adults with Acute Coronary Syndromes.

    PubMed

    Alfredsson, Joakim; Alexander, Karen P

    2016-05-01

    Older adults presenting with acute coronary syndromes (ACSs) often have multiple chronic conditions (MCCs). In addition to traditional cardiovascular (CV) risk factors (ie, hypertension, hyperlipidemia, and diabetes), common CV comorbidities include heart failure, stroke, and atrial fibrillation, whereas prevalent non-CV comorbidities include chronic kidney disease, anemia, depression, and chronic obstructive pulmonary disease. The presence of MCCs affects the presentation (eg, increased frequency of type 2 myocardial infarctions [MIs]), clinical course, and prognosis of ACS in older adults. In general, higher comorbidity burden increases mortality following MI, reduces utilization of ACS treatments, and increases the importance of developing individualized treatment plans. PMID:27113147

  3. Tanespimycin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, Chronic Myelomonocytic Leukemia, or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-09-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  4. Sorafenib in Treating Patients With Refractory or Relapsed Acute Leukemia, Myelodysplastic Syndromes, or Blastic Phase Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2015-04-27

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Blastic Phase; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

  5. Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia in Adults.

    PubMed

    Speziali, Craig; Paulson, Kristjan; Seftel, Matthew

    2016-06-01

    The majority of adults with acute lymphoblastic leukemia will achieve a first complete remission (CR). However relapse is the most common cause of treatment failure. Outcomes after relapse remain poor, with long-term survival in the order of 10 %. Treatment decisions made at the time of first complete remission are thus critical to ensuring long-term survival. Allogeneic hematopoietic cell transplant (HCT) is effective at preventing relapse in many transplant recipients but is also associated with significant treatment related morbidity and mortality. Alternatively, ongoing systemic chemotherapy offers lower toxicity at the expense of increased relapse rates. Over the past decades, both the safety of transplant and the efficacy of non-transplant chemotherapy have improved. Emerging data show substantially improved outcomes for young adults treated with pediatric-inspired chemotherapy regimens that question the role of HCT in the upfront setting. In this review, we review the data supporting the role of allogeneic transplantation in adult acute lymphoblastic leukemia (ALL), and we propose a therapeutic algorithm for upfront therapy of adults with ALL. PMID:26984203

  6. Acute Myeloid Leukemia and Myelodysplastic Syndromes in Older Adults

    PubMed Central

    Klepin, Heidi D.; Rao, Arati V.; Pardee, Timothy S.

    2014-01-01

    Treatment of older adults with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) is challenging because of disease morbidity and associated treatments. Both diseases represent a genetically heterogeneous group of disorders primarily affecting older adults, with treatment strategies ranging from supportive care to hematopoietic stem-cell transplantation. Although selected older adults can benefit from intensive therapies, as a group they experience increased treatment-related morbidity, are more likely to relapse, and have decreased survival. Age-related outcome disparities are attributed to both tumor and patient characteristics, requiring an individualized approach to treatment decision making beyond consideration of chronologic age alone. Selection of therapy for any individual requires consideration of both disease-specific risk factors and estimates of treatment tolerance and life expectancy derived from evaluation of functional status and comorbidity. Although treatment options for older adults are expanding, clinical trials accounting for the heterogeneity of tumor biology and aging are needed to define standard-of-care treatments for both disease groups. In addition, trials should include outcomes addressing quality of life, maintenance of independence, and use of health care services to assist in patient-centered decision making. This review will highlight available evidence in treatment of older adults with AML or MDS and unanswered clinical questions for older adults with these diseases. PMID:25071138

  7. Clofarabine for the treatment of adult acute lymphoid leukemia: the Group for Research on Adult Acute Lymphoblastic Leukemia intergroup.

    PubMed

    Huguet, Françoise; Leguay, Thibaut; Raffoux, Emmanuel; Rousselot, Philippe; Vey, Norbert; Pigneux, Arnaud; Ifrah, Norbert; Dombret, Hervé

    2015-04-01

    Clofarabine, a second-generation purine analog displaying potent inhibition of DNA synthesis and favorable pharmacologic profile, is approved for the treatment of acute lymphoblastic leukemia (ALL) after failure of at least two previous regimens in patients up to 21 years of age at diagnosis. Good neurologic tolerance, synergy with alkylating agents, management guidelines defined through pediatric ALL and adult acute myeloid leukemia, have also prompted its administration in more than 100 adults with Philadelphia chromosome-positive and negative B lineage and T lineage ALL, as single agent (40 mg/m(2)/ day for 5 days), or in combination. In a Group for Research on Adult Acute Lympho- blastic Leukemia (GRAALL) retrospective study of two regimens (clofarabine ± cyclophosphamide + / - etoposide (ENDEVOL) ± mitoxantrone ± asparaginase ± dexamethasone (VANDEVOL)), remission was achieved in 50% of 55 relapsed/refractory patients, and 17-35% could proceed to allogeneic stem cell. Clofarabine warrants further exploration in advanced ALL treatment and bridge-to-transplant. PMID:24996442

  8. Vorinostat, Cytarabine, and Etoposide in Treating Patients With Relapsed and/or Refractory Acute Leukemia or Myelodysplastic Syndromes or Myeloproliferative Disorders

    ClinicalTrials.gov

    2013-05-01

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  9. Knockdown of p54nrb inhibits migration, invasion and TNF-α release of human acute monocytic leukemia THP1 cells.

    PubMed

    Zhang, Xiujuan; Wu, Changli; Xiong, Wei; Chen, Chunling; Li, Rong; Zhou, Guangji

    2016-06-01

    54 kDa nuclear RNA- and DNA-binding protein (p54nrb) which is also called non-POU domain-containing octamer-binding protein (NONO) is known to be multifunctional involved in many nuclear processes. It was shown that p54nrb/NONO was closely related to the occurrence of erythroleukemia. Whether p54nrb/NONO plays a role in progress of human acute monocytic leukemia remains unknown. In the present study, we examined the effects of p54nrb/NONO silencing on the biological characteristics of human acute monocytic leukemia THP1 cells. The results showed that p54nrb was strongly expressed in THP1 cells, and knockdown of p54nrb slightly promoted proliferation and strongly inhibited motility and invasion of THP1 cells. Moreover, knockdown of p54nrb strongly decreased the release of TNF-α from THP1 cells by inhibiting certain process of TNF-α secretion, specially for the release of TNF-α induced by lipopolysaccharide (LPS). Notably, the infection of negative control shRNA-containing lentiviruses promoted the migration and the release of TNF-α induced by LPS in THP1 cells. All the above results demonstrated that p54nrb slightly inhibited THP1 cell proliferation, but significantly promoted migration, invasion and release of TNF-α induced by LPS in THP1 cells. The present study indicates that p54nrb is a powerful molecule involved in the regulation of cell motility and promotes the migration and invasion of THP1 cells, and it is more likely to be involved in the release of inflammatory mediators and the motility of inflammatory cells. PMID:27108701

  10. Adult midgut malrotation presented with acute bowel obstruction and ischemia

    PubMed Central

    Zengin, Akile; Uçar, Bercis İmge; Düzgün, Şükrü Aydın; Bayhan, Zülfü; Zeren, Sezgin; Yaylak, Faik; Şanal, Bekir; Bayhan, Nilüfer Araz

    2016-01-01

    Introduction Intestinal malrotation refers to the partial or complete failure of rotation of midgut around the superior mesenteric vessels in embryonic life. Arrested midgut rotation results due to narrow-based mesentery and increases the risk of twisting midgut and subsequent obstruction and necrosis. Presentation of case 40 years old female patient admitted to emergency service with acute abdomen and computerized tomography scan showed dilated large and small intestine segments with air-fluid levels and twisted mesentery around superior mesenteric artery and vein indicating “whirpool sign”. Discussion Malrotation in adults is a rare cause of midgut volvulus as though it should be considered in differential diagnosis in patients presented with acute abdomen and intestinal ischemia. Even though clinical symptoms are obscure, adult patients usually present with vomiting and recurrent abdominal pain due to chronic partial obstruction. Contrast enhanced radiograph has been shown to be the most accurate method. Typical radiological signs are corkscrew sign, which is caused by the dilatation of various duodenal segments at different levels and the relocation of duodenojejunal junction due to jejunum folding. As malrotation commonly causes intestinal obstruction, patients deserve an elective laparotomy. Conclusion Malrotation should be considered in differential diagnosis in patients presented with acute abdomen and intestinal ischemia. Surgical intervention should be prompt to limit morbidity and mortality. PMID:27015011

  11. Acute Promyelocytic Leukemia (APL): Comparison Between Children and Adults

    PubMed Central

    Testi, Anna Maria; D’Angiò, Mariella; Locatelli, Franco; Pession, Andrea; Lo Coco, Francesco

    2014-01-01

    The outcome of adults and children with Acute Promyelocytic Leukemia (APL) has dramatically changed since the introduction of all trans retinoic acid (ATRA) therapy. Based on the results of several multicenter trials, the current recommendations for the treatment of patients with APL include ATRA and anthracycline-based chemotherapy for the remission induction and consolidation, and ATRA combined with low-dose chemotherapy for maintenance. This has improved the prognosis of APL by increasing the complete remission (CR) rate, actually > 90%, decreasing the induction deaths and by reducing the relapse rate, leading to cure rates nowadays exceeding 80% considering both adults and children.1–9 More recently the combination of ATRA and arsenic trioxide (ATO) as induction and consolidation therapy has been shown to be at least not inferior and possibly superior to ATRA plus chemotherapy in adult patients with APL conventionally defined as non-high risk (Sanz score).10 Childhood APL has customarily been treated on adult protocols. Data from several trials have shown that the overall outcome in pediatric APL appears similar to that reported for the adult population; however, some clinical and therapeutic aspects differ in the two cohorts which require some important considerations and treatment adjustments. PMID:24804005

  12. Topical rubefacients for acute and chronic pain in adults

    PubMed Central

    Matthews, Paul; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background Rubefacients (containing salicylates or nicotinamides) cause irritation of the skin, and are believed to relieve various musculoskeletal pains. They are available on prescription, and are common components in over-the-counter remedies. A non-Cochrane review in 2004 found limited evidence for efficacy. Objectives To review current evidence for efficacy and safety of topically applied rubefacients in acute and chronic painful musculoskeletal conditions in adults. Search methods Cochrane CENTRAL, MEDLINE, EMBASE, the Oxford Pain Relief Database, and reference lists of articles were searched; last search December 2008. Selection criteria Randomised, double blind, placebo or active controlled clinical trials of topical rubefacient for musculoskeletal pain in adults, with at least 10 participants per treatment arm, and reporting outcomes at close to 7 (minimum 3, maximum 10) days for acute conditions and 14 (minimum 7) days or longer for chronic conditions. Data collection and analysis Two review authors independently assessed trials for inclusion and quality, and extracted data. Relative benefit or risk and number needed to treat to benefit or harm (NNT or NNH) were calculated with 95% confidence intervals (CI). Acute and chronic conditions were analysed separately. Main results Six placebo and one active controlled studies (560 and 137 participants) in acute pain, and seven placebo and two active controlled studies (489 and 90 participants) in chronic pain were included. All used topical salicylates. The evidence in acute conditions was not robust; using only better quality, valid studies, there was no difference between topical rubefacient and topical control, though overall, including lower quality studies, the NNT for clinical success compared with placebo was 3.2 (95% CI: 2.4 to 4.9). In chronic conditions the NNT was 6.2 (95% CI: 4.0 to 13) compared with topical placebo. Adverse events and withdrawals occurred more often with rubefacients than placebo

  13. Biology and treatment of adult acute lymphoblastic leukemia.

    PubMed Central

    Levitt, L; Lin, R

    1996-01-01

    The molecular analysis of acute lymphoblastic leukemia (ALL) has provided exciting insights into the pathogenesis of this disease. This disease is heterogenous and can be subtyped based on chromosomal, immunophenotypic, and structural criteria. The varying prognostic implications of different ALL subtypes markedly influence the treatment decisions in adults. Many patients with T-cell ALL can be cured with chemotherapy alone. In contrast, patients with early B-lineage ALL with certain chromosomal abnormalities, especially the Philadelphia chromosome, do not have durable responses to chemotherapy and should receive a bone marrow transplantation if an HLA-matched donor is available. Recent reports have shown improved results for adults with B-cell ALL (Burkitt's) after intensive alternating cycles of chemotherapy containing high doses of methotrexate and cyclophosphamide. Future clinical and laboratory investigation should lead to the development of novel and possibly more effective treatments specifically tailored for different subsets of ALL. PMID:8775728

  14. Correlation between cytotoxicity induced by Pseudomonas aeruginosa clinical isolates from acute infections and IL-1β secretion in a model of human THP-1 monocytes.

    PubMed

    Anantharajah, Ahalieyah; Buyck, Julien M; Faure, Emmanuel; Glupczynski, Youri; Rodriguez-Villalobos, Hector; De Vos, Daniel; Pirnay, Jean-Paul; Bilocq, Florence; Guery, Benoît; Tulkens, Paul M; Mingeot-Leclercq, Marie-Paule; Van Bambeke, Françoise

    2015-10-01

    Type III secretion system (T3SS) in Pseudomonas aeruginosa is associated with poor clinical outcome in acute infections. T3SS allows for injection of bacterial exotoxins (e.g. ExoU or ExoS) into the host cell, causing cytotoxicity. It also activates the cytosolic NLRC4 inflammasome, activating caspase-1, inducing cytotoxicity and release of mature IL-1β, which impairs bacterial clearance. In addition, flagellum-mediated motility has been suggested to also modulate inflammasome response and IL-1β release. Yet the capacity of clinical isolates to induce IL-1β release and its relation with cytotoxicity have never been investigated. Using 20 clinical isolates from acute infections with variable T3SS expression levels and human monocytes, our aim was to correlate IL-1β release with toxin expression, flagellar motility and cytotoxicity. ExoU-producing isolates caused massive cell death but minimal release of IL-1β, while those expressing T3SS but not ExoU (i.e. expressing ExoS or no toxins) induced caspase-1 activation and IL-1β release, the level of which was correlated with cytotoxicity. Both effects were prevented by a specific caspase-1 inhibitor. Flagellar motility was not correlated with cytotoxicity or IL-1β release. No apoptosis was detected. Thus, T3SS cytotoxicity is accompanied by a modification in cytokine balance for P. aeruginosa clinical isolates that do not express ExoU. PMID:26203053

  15. Growth factors in the management of adult acute leukemia.

    PubMed

    Bernstein, S H

    1993-02-01

    This review has explored the various ways that growth factors may be used in the management of adult acute leukemia. Growth factors have the potential to reduce the morbidity and mortality of both induction and postremission therapy by enhancing hematopoietic recovery or, when used as an adjunct to standard antimicrobial therapy, reducing the infectious complications of chemotherapy. In addition, they may have favorable effects on the biology of leukemia either by recruitment of leukemic progenitors into cycle, rendering them more sensitive to the cytotoxic effects of chemotherapy, or by inducing the terminal differentiation of the leukemic clone. Finally, disruption of aberrant growth factor networks, thought to play a role in the pathogenesis of leukemia, may be a therapeutic strategy now that soluble receptors and receptor antagonists to such growth factors as IL-1 are available. Whether growth factors used in such ways will have beneficial, or in fact adverse, effects on the treatment outcome for acute leukemia is not yet known. As such, the use of growth factors in the management of adults with acute leukemia is still experimental and needs to be studied in the context of clinical trials. Perhaps the ultimate benefit to be derived from the study of these growth factors will be a deeper understanding of the genetic perturbations that define the leukemic state. The development of molecular therapeutic techniques, such as gene transfer technology and the use of antisense oligonucleotides, has paralleled our increasing knowledge of cytokines. The hope is that as we come to understand leukemia at the molecular level, we will be able to develop the new therapeutic tools necessary to increase the numbers of patients cured. PMID:8449861

  16. Yolk Sac Macrophages, Fetal Liver, and Adult Monocytes Can Colonize an Empty Niche and Develop into Functional Tissue-Resident Macrophages.

    PubMed

    van de Laar, Lianne; Saelens, Wouter; De Prijck, Sofie; Martens, Liesbet; Scott, Charlotte L; Van Isterdael, Gert; Hoffmann, Eik; Beyaert, Rudi; Saeys, Yvan; Lambrecht, Bart N; Guilliams, Martin

    2016-04-19

    Tissue-resident macrophages can derive from yolk sac macrophages (YS-Macs), fetal liver monocytes (FL-MOs), or adult bone-marrow monocytes (BM-MOs). The relative capacity of these precursors to colonize a niche, self-maintain, and perform tissue-specific functions is unknown. We simultaneously transferred traceable YS-Macs, FL-MOs, and BM-MOs into the empty alveolar macrophage (AM) niche of neonatal Csf2rb(-/-) mice. All subsets produced AMs, but in competition preferential outgrowth of FL-MOs was observed, correlating with their superior granulocyte macrophage-colony stimulating factor (GM-CSF) reactivity and proliferation capacity. When transferred separately, however, all precursors efficiently colonized the alveolar niche and generated AMs that were transcriptionally almost identical, self-maintained, and durably prevented alveolar proteinosis. Mature liver, peritoneal, or colon macrophages could not efficiently colonize the empty AM niche, whereas mature AMs could. Thus, precursor origin does not affect the development of functional self-maintaining tissue-resident macrophages and the plasticity of the mononuclear phagocyte system is largest at the precursor stage. PMID:26992565

  17. Acute leukaemias in adult Ethiopians in a teaching hospital.

    PubMed

    Shamebo, M

    1994-01-01

    Eighty-two consecutive cases of acute leukaemias in adult Ethiopians were admitted to the Tikur Anbessa (Black Lion) Hospital, a teaching and referral hospital in Addis Abeba, Ethiopia, from January 1982 to December 1992. These cases were studied to describe the clinical and haematological findings, response to therapy and prognosis. The age range was 13-78 (mean 29.6) years. The male to female ratio was 1.6:1. Acute myeloblastic (AML) and acute lymphoblastic (ALL) leukaemias occurred in 53.7% and 46.3%, respectively. The commonest symptoms were anaemia, fever and bleeding tendencies. The commonest signs were pallor, fever, sternal tenderness and purpura. Splenomegaly was more commonly seen in ALL patients. The haematological findings were anaemia (mean Hgb 6.35 g%), leucocytosis (mean WBC count 88,507/mm3) and thrombocytopenia (mean platelet count 31,700/mm3). Of the patients eligible for evaluation treated with chemotherapeutic agents, only 38.4% of ALL and 6.2% of AML achieved complete remission. Twenty-seven patients with ALL died from one day to 84 (median 1.0) months after diagnosis. Ten are lost to follow-up from two weeks to 36 (median 2.5) months, one is still alive 40 months after diagnosis. Thirty-nine of the AML patients died from one day to nine (median 0.3) months after diagnosis. Five are lost to follow-up from two weeks to two and a half (median 2.0) months. The causes of death were sepsis and bleeding, separately or in combination. Increasing numbers of acute leukaemia patients are being referred to this centre. Therefore, attempts should be made to equip it for the treatment of such cases. PMID:8187778

  18. Acute coronary syndrome after levamisole-adultered cocaine abuse.

    PubMed

    Michaud, Katarzyna; Grabherr, Silke; Shiferaw, Kebede; Doenz, Franceso; Augsburger, Marc; Mangin, Patrice

    2014-01-01

    Cocaine is a well known trigger of acute coronary syndromes. Over the last 10 years levamisole, a veterinary anthelminthic drug has been increasingly used as an adulterant of cocaine. Levamisole was used to treat pediatric nephritic syndrome and rheumatoid arthritis before being withdrawn from the market due to its significant toxicity, i.e. hematological complications and vasculitis. The major complications of levamisole-adultered cocaine reported up to now are hematological and dermatological. The case reported here is of a 25 year old man with a history of cocaine abuse who died at home after complaining of retrosternal pain. Postmortem CT-angiography, autopsy, and chemical and toxicological analyses were performed. An eroded coronary artery plaque was found at the proximal segment of the left anterior descending coronary artery. Two myocardial infarct scars were present in the left ventricle. Microscopic examination of the coronary artery revealed infiltration of eosinophils into the adventitia and intima. Toxicological examination confirmed the presence of cocaine and its metabolites in the peripheral blood, and of levamisole in the urine and pericardial fluid. Eosinophilic inflammatory coronary artery pathologies have been clinically linked to coronary dissection, hypersensitivity coronary syndrome and vasospastic allergic angina. The coronary pathology in the presented case could be a complication of levamisole-adultered cocaine use, in which an allergic or immune-mediated mechanism might play a role. The rise in cocaine addiction worldwide and the increase of levamisole adulterated cocaine highlights the importance of updating our knowledge of the effects of adultered cocaine abuse. PMID:24365689

  19. Single dose oral ibuprofen for acute postoperative pain in adults

    PubMed Central

    Derry, Christopher J; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background This review updates a 1999 Cochrane review showing that ibuprofen at various doses was effective in postoperative pain in single dose studies designed to demonstrate analgesic efficacy. New studies have since been published. Ibuprofen is one of the most widely used non-steroidal anti-inflammatory (NSAID) analgesics both by prescription and as an over-the-counter medicine. Ibuprofen is used for acute and chronic painful conditions. Objectives To assess analgesic efficacy of ibuprofen in single oral doses for moderate and severe postoperative pain in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to May 2009. Selection criteria Randomised, double blind, placebo-controlled trials of single dose orally administered ibuprofen (any formulation) in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Main results Seventy-two studies compared ibuprofen and placebo (9186 participants). Studies were predominantly of high reporting quality, and the bulk of the information concerned ibuprofen 200 mg and 400 mg. For at least 50% pain relief compared with placebo the NNT for ibuprofen 200 mg (2690 participants) was 2.7 (2.5 to 3.0) and for ibuprofen 400 mg (6475 participants) it was 2.5 (2.4 to 2.6). The proportion with at least 50% pain relief was 46% with 200 mg and 54% with 400 mg. Remedication within 6 hours was less

  20. Respiratory autoresuscitation following severe acute hypoxemia in anesthetized adult rats.

    PubMed

    Krause, A; Nowak, Z; Srbu, R; Bell, H J

    2016-10-01

    In the present study we investigated the pattern and efficacy of respiratory autoresuscitation in spontaneously breathing adult male rats across three separate anesthetic backgrounds. Each animal was administered one of three injectable anesthetics to achieve a surgical plane of anesthesia: ketamine-xylazine (KET, n=10), pentobarbital (PEN, n=10), or urethane (URE, n=10). Animals were tracheostomized and equipped with a femoral artery catheter to record airflow and arterial pressures. In response to a bout of breathing anoxic air, none of the 10 URE animals were able to mount a successful autoresuscitation response. In contrast, all KET and PEN animals survived all four consecutive anoxic exposures, restoring eupneic breathing in all cases. Moreover, only 4/10 URE animals expressed gasping breaths following the onset of respiratory arrest, and these were temporally delayed (p<0.001) and much smaller in volume (P≤0.012) compared to KET and PEN animals. URE animals showed no clear aberrations in their cardiovascular responses to anoxia, with the exception of lower arterial pulse pressures compared to either KET or PEN animals at specific points following RA. Ketamine-xylazine and pentobarbital anesthesia can be reliably and effectively used to create models for the study of autoresuscitation in adult rats. In contrast, urethane causes catastrophic failure of respiratory autoresuscitation, by delaying or outright preventing the elaboration of gasping breaths following anoxia-induced respiratory arrest. The neuronal and synaptic alterations accompanying urethane anesthesia may therefore provide a means of understanding potential pathological alterations in rhythm generation that can predispose the respiratory control system to failed autoresuscitation following an episode of acute severe hypoxemia. PMID:27378495

  1. Rituximab in B-Lineage Adult Acute Lymphoblastic Leukemia.

    PubMed

    Maury, Sébastien; Chevret, Sylvie; Thomas, Xavier; Heim, Dominik; Leguay, Thibaut; Huguet, Françoise; Chevallier, Patrice; Hunault, Mathilde; Boissel, Nicolas; Escoffre-Barbe, Martine; Hess, Urs; Vey, Norbert; Pignon, Jean-Michel; Braun, Thorsten; Marolleau, Jean-Pierre; Cahn, Jean-Yves; Chalandon, Yves; Lhéritier, Véronique; Beldjord, Kheira; Béné, Marie C; Ifrah, Norbert; Dombret, Hervé

    2016-09-15

    Background Treatment with rituximab has improved the outcome for patients with non-Hodgkin's lymphoma. Patients with B-lineage acute lymphoblastic leukemia (ALL) may also have the CD20 antigen, which is targeted by rituximab. Although single-group studies suggest that adding rituximab to chemotherapy could improve the outcome in such patients, this hypothesis has not been tested in a randomized trial. Methods We randomly assigned adults (18 to 59 years of age) with CD20-positive, Philadelphia chromosome (Ph)-negative ALL to receive chemotherapy with or without rituximab, with event-free survival as the primary end point. Rituximab was given during all treatment phases, for a total of 16 to 18 infusions. Results From May 2006 through April 2014, a total of 209 patients were enrolled: 105 in the rituximab group and 104 in the control group. After a median follow-up of 30 months, event-free survival was longer in the rituximab group than in the control group (hazard ratio, 0.66; 95% confidence interval [CI], 0.45 to 0.98; P=0.04); the estimated 2-year event-free survival rates were 65% (95% CI, 56 to 75) and 52% (95% CI, 43 to 63), respectively. Treatment with rituximab remained associated with longer event-free survival in a multivariate analysis. The overall incidence rate of severe adverse events did not differ significantly between the two groups, but fewer allergic reactions to asparaginase were observed in the rituximab group. Conclusions Adding rituximab to the ALL chemotherapy protocol improved the outcome for younger adults with CD20-positive, Ph-negative ALL. (Funded by the Regional Clinical Research Office, Paris, and others; ClinicalTrials.gov number, NCT00327678 .). PMID:27626518

  2. Acute Tryptophan Depletion and Sweet Food Consumption by Overweight Adults

    PubMed Central

    Pagoto, Sherry L.; Spring, Bonnie; McChargue, Dennis; Hitsman, Brian; Smith, Malaina; Appelhans, Bradley; Hedeker, Donald

    2009-01-01

    Serotonergic involvement has been implicated in preferential consumption of treat foods. We tested the effect of acute tryptophan depletion (ATD) on food consumption by overweight and lean adults with and without a history of recurrent major depressive disorder (MDD). ATD and taste-matched placebo challenges were administered double-blind in counter-balanced order. Participants were classified as lean (n = 36) or overweight (n=19) on the basis of body mass index (BMI). Total calorie, carbohydrate, protein, and sweet food consumption were assessed via a test meal 8-hours following ATD. Four food items of comparable palatability were offered as a part of the test: two sweet (one carbohydrate-rich, and one protein-rich) and two non-sweet (one carbohydrate-rich, and one protein-rich). As compared to the placebo challenge, ATD significantly increased sweet calorie intake among overweight participants and increased their propensity to consume sweet food first before any other type of food. Lean participants’ sweet calorie intake and food preference were unaffected by ATD. Findings suggest serotonergic involvement in the sweet food consumption by overweight individuals. PMID:19171315

  3. Dengue NS1 antigen contributes to disease severity by inducing interleukin (IL)-10 by monocytes.

    PubMed

    Adikari, T N; Gomes, L; Wickramasinghe, N; Salimi, M; Wijesiriwardana, N; Kamaladasa, A; Shyamali, N L A; Ogg, G S; Malavige, G N

    2016-04-01

    Both dengue NS1 antigen and serum interleukin (IL)-10 levels have been shown to associate with severe clinical disease in acute dengue infection, and IL-10 has also been shown to suppress dengue-specific T cell responses. Therefore, we proceeded to investigate the mechanisms by which dengue NS1 contributes to disease pathogenesis and if it is associated with altered IL-10 production. Serum IL-10 and dengue NS1 antigen levels were assessed serially in 36 adult Sri Lankan individuals with acute dengue infection. We found that the serum IL-10 levels correlated positively with dengue NS1 antigen levels (Spearman's r = 0·47, P < 0·0001), and NS1 also correlated with annexin V expression by T cells in acute dengue (Spearman's r = 0·63, P = 0·001). However, NS1 levels did not associate with the functionality of T cell responses or with expression of co-stimulatory molecules. Therefore, we further assessed the effect of dengue NS1 on monocytes and T cells by co-culturing primary monocytes and peripheral blood mononuclear cells (PBMC), with varying concentrations of NS1 for up to 96 h. Monocytes co-cultured with NS1 produced high levels of IL-10, with the highest levels seen at 24 h, and then declined gradually. Therefore, our data show that dengue NS1 appears to contribute to pathogenesis of dengue infection by inducing IL-10 production by monocytes. PMID:26621477

  4. What's New in Adult Acute Myeloid Leukemia Research and Treatment?

    MedlinePlus

    ... Topic Additional resources for acute myeloid leukemia What’s new in acute myeloid leukemia research and treatment? Researchers ... benefit from current treatments. Researchers are studying many new chemo drugs for use in AML, including: Sapacitabine, ...

  5. Angiotensin II induces apoptosis of human pulmonary microvascular endothelial cells in acute aortic dissection complicated with lung injury patients through modulating the expression of monocyte chemoattractant protein-1

    PubMed Central

    Wu, Zhiyong; Dai, Feifeng; Ren, Wei; Liu, Huagang; Li, Bowen; Chang, Jinxing

    2016-01-01

    Patients with acute aortic dissection (AAD) usually showed acute lung injury (ALI). However, its pathogenesis is still not well defined. Apoptosis of pulmonary microvascular endothelial cells (PMVECs) is closely related to the alveolus-capillary barrier injury and the increased vascular permeability. In this study, we aim to investigate the human PMVECs (hPMVECs) apoptosis induced by angiotensin II (AngII) and monocyte chemoattractant protein-1 (MCP-1) and their potential interaction in the pathogenesis of AAD complicated with ALI. Fifty-eight newly diagnosed AAD, 12 matched healthy individuals were included. Pulmonary tissues of AAD complicated with lung injury were obtained from 2 cadavers to determine the levels of AngII type 1 receptor (AT1-R) and MCP-1. Serum AngII was measured using commercial ELISA kit. H&E staining and immunohistostaining were performed to determine the expression of AT1-R and MCP-1. For the in vitro experiment, hPMVECs were divided into control, AngII group, AngII+Bindarit group and Bindarit group, respectively. Flow cytometry was performed to analyze the apoptosis in each group. Reverse transcription-polymerase chain reaction was performed to determine the mRNA expression of MCP-1. Western blot analysis was performed to evaluate the expression of MCP-1 and apoptosis related protein. Apoptosis of hPMVECs was observed in the lung tissues in the cadavers with AAD complicated with ALI. Besides, the expression of AT1-R and MCP-1 was remarkably elevated. Compared with normal individuals and the non-lung injury AAD patients, the expression of serum AngII was remarkably elevated in AAD patients complicated with ALI. In vitro experiments showed AngII contributed to the apoptosis and elevation of MCP1 in hPMVECs. Besides, it involved in the down-regulation of Bcl-2 protein, and up-regulation of Bax and Caspase-3. Such phenomenon was completely reversed after administration of MCP-1 inhibitor (Bindarit). The production of MCP-1 and cellular

  6. Single dose oral diclofenac for acute postoperative pain in adults

    PubMed Central

    Derry, Philip; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), available as a potassium salt (immediate-release) or sodium salt (delayed-release). This review updates an earlier review published in The Cochrane Database of Systematic Reviews (Issue 2, 2004) on ‘Single dose oral diclofenac for postoperative pain’. Objectives To assess single dose oral diclofenac for the treatment of acute postoperative pain. Search methods Cochrane CENTRAL, MEDLINE, EMBASE, Biological Abstracts, the Oxford Pain Relief Database, and reference lists of articles were searched; last search December 2008. Selection criteria Randomised, double-blind, placebo-controlled clinical trials of single dose, oral diclofenac (sodium or potassium) for acute postoperative pain in adults. Data collection and analysis Two review authors independently assessed studies for inclusion and quality, and extracted data. The area under the pain relief versus time curve was used to derive the proportion of participants with at least 50% pain relief over 4 to 6 hours, using validated equations. Relative benefit (risk) and number needed to treat to benefit (NNT) were calculated. Information on adverse events, time to remedication, and participants needing additional analgesia was also collected. Main results Fifteen studies (eight additional studies) with 1512 participants more than doubled the information available at each dose. Overall 50% to 60% of participants experienced at least 50% pain relief over 4 to 6 hours at any dose with diclofenac, compared to 10 to 20% with placebo, giving NNTs of about 2.5 for doses of 25 mg to 100 mg (similar to earlier review); no dose response was demonstrated. At 50 mg and 100 mg, NNTs for diclofenac potassium (2.1 (1.8 to 2.4) and 1.9 (1.7 to 2.2)) were significantly lower (better) than for diclofenac sodium (6.7 (4.2 to 17) and 4.5 (3.2 to 7.7)). The median time to use of rescue medication was 2 hours for placebo, 4.3 hours for diclofenac 50 mg and 4.9 hours

  7. Acute rhinosinusitis in adults: an update on current management

    PubMed Central

    Masood, Ajmal; Moumoulidis, Ioannis; Panesar, Jaan

    2007-01-01

    Acute rhinosinusitis is a common disease with worldwide prevalence. It is a significant burden on the health services. It is most commonly caused by viruses and is self‐limiting in nature. The diagnosis of acute rhinosinusitis is clinical and sinus radiography is not indicated routinely. Most cases of acute rhinosinusitis are treated symptomatically. However, symptoms may persist beyond 10 days when secondary bacterial infection prevails. Antibiotics are reserved for moderate or severe cases or when there is development of complications of acute rhinosinusitis. This paper provides an update on the current management of acute rhinosinusitis. PMID:17551072

  8. Oxidative metabolism in cord blood monocytes and monocyte-derived macrophages.

    PubMed Central

    Speer, C P; Ambruso, D R; Grimsley, J; Johnston, R B

    1985-01-01

    Little is known about phagocytosis-associated oxidative metabolism in mononuclear phagocytes from the human neonate. We investigated this phenomenon in monocytes from the cord blood of term newborn infants by measuring generation of superoxide anion (O2-) and hydroxyl radical (X OH) after stimulation with opsonized zymosan or phorbol myristate acetate. Production of these microbicidal oxygen metabolites by monocytes from neonates and healthy adult volunteers was equivalent. When cultured in the presence of the macrophage activator lipopolysaccharide or muramyl dipeptide, monocytes from neonates and adults differentiated into cells with the appearance of macrophages and with an enhanced capacity to release O2- compared with cells cultured in the absence of an activator. Monocyte-derived macrophages from neonates produced only slightly less O2- than did adult cells. Thus, unlike the cord blood neutrophil, which exhibits abnormalities in oxidative metabolism, the cord blood mononuclear phagocyte has a respiratory burst that is quantitatively comparable to that of the adult cell. PMID:2999001

  9. Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Acute Leukemia

    ClinicalTrials.gov

    2013-10-07

    Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  10. Single dose oral analgesics for acute postoperative pain in adults

    PubMed Central

    Moore, R Andrew; Derry, Sheena; McQuay, Henry J; Wiffen, Philip J

    2014-01-01

    Background Thirty-five Cochrane Reviews of randomised trials testing the analgesic efficacy of individual drug interventions in acute postoperative pain have been published. This overview brings together the results of all those reviews and assesses the reliability of available data. Objectives To summarise data from all Cochrane Reviews that have assessed the effects of pharmaceutical interventions for acute pain in adults with at least moderate pain following surgery, who have been given a single dose of oral analgesic taken alone. Methods We identified systematic reviews in The Cochrane Library through a simple search strategy. All reviews were overseen by a single Review Group, had a standard title, and had as their primary outcome numbers of participants with at least 50% pain relief over four to six hours compared with placebo. For individual reviews we extracted the number needed to treat (NNT) for this outcome for each drug/dose combination, and also the percentage of participants achieving at least 50% maximum pain relief, the mean of mean or median time to remedication, the percentage of participants remedicating by 6, 8, 12, or 24 hours, and results for participants experiencing at least one adverse event. Main results The overview included 35 separate Cochrane Reviews with 38 analyses of single dose oral analgesics tested in acute postoperative pain models, with results from about 45,000 participants studied in approximately 350 individual studies. The individual reviews included only high-quality trials of standardised design and outcome reporting. The reviews used standardised methods and reporting for both efficacy and harm. Event rates with placebo were consistent in larger data sets. No statistical comparison was undertaken. There were reviews but no trial data were available for acemetacin, meloxicam, nabumetone, nefopam, sulindac, tenoxicam, and tiaprofenic acid. Inadequate amounts of data were available for dexibuprofen, dextropropoxyphene 130

  11. Acute Psychiatric Hospital Admissions of Adults and Elderly Adults with Mental Retardation.

    ERIC Educational Resources Information Center

    Pary, Robert J.

    1993-01-01

    Examination of the records of 240 inpatients with mental retardation and 7 with autism discharged from a university hospital indicated that elderly adults had more medical problems than did adults, more elderly adults were transferred to a state hospital, and the most common diagnosis in both adults and elderly adults was chronic schizophrenia,…

  12. What's New in Adult Acute Lymphocytic Leukemia (ALL) in Adults Research?

    MedlinePlus

    ... Topic Additional resources for acute lymphocytic leukemia What’s new in acute lymphocytic leukemia research and treatment? Researchers ... have the Philadelphia chromosome. Gene expression profiling This new lab technique is being studied to help identify ...

  13. Increased monocyte tissue factor expression in coronary disease.

    PubMed Central

    Leatham, E. W.; Bath, P. M.; Tooze, J. A.; Camm, A. J.

    1995-01-01

    OBJECTIVE--To investigate whether monocyte expression of tissue factor is increased in patients with acute coronary syndromes and chronic stable angina. DESIGN--Cross sectional study of monocyte tissue factor expression in patients with ischaemic heart disease and control subjects. BACKGROUND--Unstable angina and myocardial infarction are associated with enhanced mononuclear cell procoagulant activity. Procoagulant activity of blood monocytes is principally mediated by tissue factor expression. Tissue factor initiates the coagulation cascade and monocyte tissue factor expression may therefore be increased in these syndromes. METHODS--Monocyte tissue factor expression was measured cytometrically in whole blood flow using a polyclonal rabbit antihuman tissue factor antibody. PATIENTS--30 patients with acute myocardial infarction, 17 with unstable angina, 13 with chronic stable angina, and 11 normal control subjects. RESULTS--Increased proportions of monocytes expressing tissue factor (> 2.5%) were found in none of 11 (0%) normal subjects, five 13 (38%) patients with stable angina, 11 of 17 (64%) patients with unstable angina, and 16 of 30 (53%) patients with myocardial infarction (2P = 0.006). Blood from all subjects showed similar monocyte tissue factor expression similar monocyte tissue factor expression (46.1 (15.1)%) after lipopolysaccharide stimulation. CONCLUSION--Hypercoagulability associated with acute myocardial infarction, unstable angina, and chronic stable angina may be induced by tissue factor expressed on circulating monocytes. PMID:7888247

  14. Monocyte Subpopulations in Angiogenesis

    PubMed Central

    Dalton, Heather J.; Armaiz-Pena, Guillermo; Gonzalez-Villasana, Vianey; Lopez-Berestein, Gabriel; Bar-Eli, Menashe; Sood, Anil K.

    2014-01-01

    Growing understanding of the role of the tumor microenvironment in angiogenesis has brought monocyte-derived cells into focus. Monocyte subpopulations are an increasingly attractive therapeutic target in many pathologic states, including cancer. Before monocyte-directed therapies can be fully harnessed for clinical use, understanding of monocyte-driven angiogenesis in tissue development and homeostasis, as well as malignancy, is required. Here, we provide an overview of the mechanisms by which monocytic subpopulations contribute to angiogenesis in tissue and tumor development, highlight gaps in our existing knowledge, and discuss opportunities to exploit these cells for clinical benefit. PMID:24556724

  15. [Expression of PRAME gene in adult acute leukemia and its significance in prognosis].

    PubMed

    Zhou, Pei-Yi; Li, Wei-Jia; Wei, Cai-Xia; Zhou, Zhi

    2007-12-01

    The study was aimed to investigate the expression of preferentially expressed antigen of melanoma (PRAME) gene in adult acute leukemia and its clinical significance. The expression of the PRAME gene of bone marrow was measured by reverse transcriptase polymerase chain reaction (RT-PCR) in 73 adult newly diagnosed acute leukemia patients, 3 relapsed patients, 7 patients with idiopathic thrombocytopenic purpura (ITP) and 8 healthy donors, as well as two AL cell-lines (K562 and U937). The results indicated that PRAME mRNA was expressed in 42.9% AML patients (n=24) and 20% ALL patients (n=4), also in two leukemia cell-lines K562 and U937, but not in eight health donors and seven ITP patients. PRAME expression not correlated to the white blood count, hemoglobin level, platelet count and the percentage of blasts at diagnosis, yet independent of age, sex, and FAB type. PRAME mRNA expression in complete remission group seems much higher than those in partial complete remission group and death group. The increased levels of expression could be found prior to the relapse in one patient being regularly monitored. PRAME gene was overexpressed in adult acute leukemia patients and leukemia cell-lines. It is concluded that the expression of PRAME is an indicator of favorable prognosis and can be a useful tool for monitoring minimal residual disease (MRD) in adult acute leukemia. Differential expression between adult acute leukemia patients and healthy volunteers suggests that the immunogenic antigens PRAME are potential candidates for immunotherapy in adult acute leukemia. PMID:18088461

  16. A parasite rescue and transformation assay for antileishmanial screening against intracellular Leishmania donovani amastigotes in THP1 human acute monocytic leukemia cell line.

    PubMed

    Jain, Surendra K; Sahu, Rajnish; Walker, Larry A; Tekwani, Babu L

    2012-01-01

    Leishmaniasis is one of the world's most neglected diseases, largely affecting the poorest of the poor, mainly in developing countries. Over 350 million people are considered at risk of contracting leishmaniasis, and approximately 2 million new cases occur yearly(1). Leishmania donovani is the causative agent for visceral leishmaniasis (VL), the most fatal form of the disease. The choice of drugs available to treat leishmaniasis is limited (2);current treatments provide limited efficacy and many are toxic at therapeutic doses. In addition, most of the first line treatment drugs have already lost their utility due to increasing multiple drug resistance (3). The current pipeline of anti-leishmanial drugs is also severely depleted. Sustained efforts are needed to enrich a new anti-leishmanial drug discovery pipeline, and this endeavor relies on the availability of suitable in vitro screening models. In vitro promastigotes (4) and axenic amastigotes assays(5) are primarily used for anti-leishmanial drug screening however, may not be appropriate due to significant cellular, physiological, biochemical and molecular differences in comparison to intracellular amastigotes. Assays with macrophage-amastigotes models are considered closest to the pathophysiological conditions of leishmaniasis, and are therefore the most appropriate for in vitro screening. Differentiated, non-dividing human acute monocytic leukemia cells (THP1) (make an attractive) alternative to isolated primary macrophages and can be used for assaying anti-leishmanial activity of different compounds against intracellular amastigotes. Here, we present a parasite-rescue and transformation assay with differentiated THP1 cells infected in vitro with Leishmania donovani for screening pure compounds and natural products extracts and determining the efficacy against the intracellular Leishmania amastigotes. The assay involves the following steps: (1) differentiation of THP1 cells to non-dividing macrophages, (2

  17. Acute Myeloid Leukemia (AML) Treatment in Adults (Beyond the Basics)

    MedlinePlus

    ... and returned by IV infusion. Because the transplanted stem cells do not come from another person, there is no "graft versus ... leukemia (AML) (The Basics) Patient information: Leukemia in adults (The ... (bone marrow transplantation) (Beyond the Basics) Professional ...

  18. Neuropsychological and psychiatric profiles in acute encephalitis in adults.

    PubMed

    Pewter, Stephen M; Williams, W Huw; Haslam, Catherine; Kay, Janice M

    2007-01-01

    Acute encephalitis is an inflammation of brain tissue that can result from activity in the central nervous system (CNS) of a number of viruses. Although the neurological and psychiatric effects of encephalitis in the acute phase of the illness are well-known (Caroff, Mann, Gliatto, Sullivan, & Campbell, 2001), larger scale studies of the pattern of neuropsychological and psychiatric impairment following recovery from the acute inflammatory phase are less apparent. This paper reports the results of neuropsychological testing with a range of standardised cognitive measures in a case series of long-term post-acute participants. Psychiatric abnormality is examined using the SCL-90-R self-report scale of distress (Derogatis, 1983). We also examined the role of emerging insight in the aetiology of depression in this population. Two clusters of cognitive dysfunction were observed, one group of primarily herpes simplex cases showing a severe generalised deficit across a number of cognitive domains and a second cluster showing a variety of more isolated disorders of executive function. Abnormally high levels of distress were reported by participants, with depression, obsessive-compulsive symptoms, interpersonal sensitivity and phobic anxiety most significantly increased. Depression was found to be least severe in those with most accurate insight into their problems. Examining the correlations between cognitive and psychiatric test results demonstrates a relationship between depression and interpersonal anxiety and specific cognitive measures. Obsessive-compulsive behaviour and phobic anxiety, however, appear to exist independently of the assessed cognitive deficits. PMID:17676531

  19. Fatal measles presenting as acute respiratory distress syndrome in an immunocompetent adult

    PubMed Central

    Karanth, Suman S; Marupudi, Krishna Chaitanya; Gupta, Anurag; Rau, Nileshwar Radhakrishna

    2014-01-01

    Fatal measles is known to occur among immunocompromised adults. We report a rare case of an immunocompetent non-pregnant young lady who suffered from fatal acute respiratory distress syndrome due to measles. Physicians must be vigilant to this deadly presentation of measles even in immunocompetent individuals. We emphasise the inadequacies of vaccination programmes in India reflected not only by the existing high measles-related childhood mortalities, but also an emerging rise in deaths among adults. PMID:25139919

  20. The effect of music on pain and acute confusion in older adults undergoing hip and knee surgery.

    PubMed

    McCaffrey, Ruth; Locsin, Rozzano

    2006-01-01

    The purpose of this study was to examine the effects of music listening in older adults following hip or knee surgery. Acute confusion and pain after surgery can increase length of stay and reduce function. Study results demonstrate a reduction in acute confusion and pain and improved ambulation and higher satisfaction scores in older adults who listened to music. PMID:16974175

  1. Acute renal failure in 2 adult llamas after exposure to Oak trees (Quercus spp.)

    PubMed Central

    Chamorro, Manuel F.; Passler, Thomas; Joiner, Kellye; Poppenga, Robert H.; Bayne, Jenna; Walz, Paul H.

    2013-01-01

    Two adult llamas (Lama glama) previously exposed to oak trees (Quercus spp.) were presented with a history of depression and anorexia. Clinicopathological abnormalities included severe gastroenteritis, acute renal failure, and increased liver enzymes. This is believed to be the first report of oak toxicosis in South American camelids. PMID:23814303

  2. COMPARISON OF THE RESPONSES OF CHILDREN AND ADULTS TO ACUTE OZONE EXPOSURE

    EPA Science Inventory

    The purpose of the paper is to compare the results of two studies in which the respiratory responses of children and adults to acute ozone (O3) exposure were measured. Forty-two 18-30 year old males were exposed for 2.5 hours in a controlled environmental chamber to either 0.0 or...

  3. Clinical Application of the "Scribble Technique" with Adults in an Acute Inpatient Psychiatric Hospital.

    ERIC Educational Resources Information Center

    Hanes, Michael J.

    1995-01-01

    The "scribble technique," described by Florence Cane's book, "The Artist in Each of Us" (1983), has historically been employed by art therapists as a technique to reduce inhibitions and liberate spontaneous imagery from the unconscious. Reviews the technique and presents examples produced by adult patients in an acute inpatient psychiatric ward.…

  4. Uncommon acute neurologic presentation of canine distemper in 4 adult dogs

    PubMed Central

    Galán, Alba; Gamito, Araceli; Carletti, Beatrice E.; Guisado, Alicia; de las Mulas, Juana Martín; Pérez, José; Martín, Eva M.

    2014-01-01

    Four uncommon cases of canine distemper (CD) were diagnosed in vaccinated adult dogs. All dogs had acute onset of neurologic signs, including seizures, abnormal mentation, ataxia, and proprioceptive deficits. Polymerase chain reaction for CD virus was positive on cerebrospinal fluid in 2 cases. Due to rapid deterioration the dogs were euthanized and CD was confirmed by postmortem examination. PMID:24688139

  5. Uncommon acute neurologic presentation of canine distemper in 4 adult dogs.

    PubMed

    Galán, Alba; Gamito, Araceli; Carletti, Beatrice E; Guisado, Alicia; de las Mulas, Juana Martín; Pérez, José; Martín, Eva M

    2014-04-01

    Four uncommon cases of canine distemper (CD) were diagnosed in vaccinated adult dogs. All dogs had acute onset of neurologic signs, including seizures, abnormal mentation, ataxia, and proprioceptive deficits. Polymerase chain reaction for CD virus was positive on cerebrospinal fluid in 2 cases. Due to rapid deterioration the dogs were euthanized and CD was confirmed by postmortem examination. PMID:24688139

  6. ACUTE TOXICITY OF PESTICIDES IN ADULT AND WEANLING RATS

    EPA Science Inventory

    LD sub 50 values were determined for 57 pesticides administered by the oral or dermal route to adult male and female Sherman rats. Nine pesticides tested by the oral route (bufencarb, cacodylic acid, dialifor, deltamethrin, dicamba, diquat, quintozene, phoxim, pyrazon) and 4 test...

  7. ACUTE BEHAVIORAL TOXICITY OF CARBARYL AND PROPOXUR IN ADULT RATS

    EPA Science Inventory

    Motor activity and neuromotor function were examined in adult CD rats exposed to either carbaryl or propoxur, and behavioral effects were compared with the time course of cholinesterase inhibition. Rats received an IP injection of either 0, 2, 4, 6 or 8 mg/kg propoxur or 0, 4, 8,...

  8. Characteristics of acute care utilization of a Delaware adult sickle cell disease patient population.

    PubMed

    Anderson, Nina; Bellot, Jennifer; Senu-Oke, Oluseyi; Ballas, Samir K

    2014-02-01

    Sickle cell disease (SCD) is an inherited blood disorder that is chronic in nature and manifests itself through many facets of the patient's life. Comprehensive specialty centers have the potential to reduce health care costs and improve the quality of care for patients who have chronic medical conditions such as heart failure and SCD. The purpose of this practice inquiry was to analyze de-identified data for acute care episodes involving SCD in order to create a detailed picture of acute care utilization for adult patients in Delaware with SCD from 2007 to 2009. Gaining a better understanding of acute care utilization for adults with SCD may provide evidence to improve access to high-quality health care services for this vulnerable patient population in the state of Delaware. PMID:23965046

  9. Reduced Acute Recovery from Alcohol Impairment in Adults with ADHD

    PubMed Central

    Roberts, Walter; Milich, Richard; Fillmore, Mark T.

    2013-01-01

    Rationale Prior research has found that adults with attention-deficit/hyperactivity disorder (ADHD) show increased sensitivity to the impairing effects of alcohol (Weafer et al. 2009). However, these studies have focused exclusively on the ascending limb of the blood alcohol concentration (BAC) curve, and it is unclear whether these adults continue to show increased sensitivity during the later phase of the dose as BAC is declining. Objective This study tested the hypothesis that those with ADHD would display increased response to alcohol during the ascending limb of the BAC curve and less recovery from the impairing effects during the descending limb. Methods Adult social drinkers with ADHD and control adults completed measures of motor coordination, reaction time, and subjective intoxication twice following 0.64 g/kg alcohol and placebo. The measures were administered during the ascending limb of the BAC curve and again during the descending limb. Results During the ascending limb, alcohol reduced motor coordination, slowed reaction time (RT), and increased self-reports of subjective intoxication. Those with ADHD displayed greater impairment of motor coordination compared with controls. During the descending limb, controls reported diminished subjective intoxication and showed recovery from the impairing effects of alcohol on both their motor coordination and their RT. Those with ADHD showed reduced subjective intoxication and faster RT during this time, but they did not recover motor control. Conclusions The protracted time course of motor impairment in adults with ADHD despite reductions in subjective intoxication may contribute to poor decision making and diminished behavioral control in this group. PMID:23430161

  10. Ethnographic research into nursing in acute adult mental health units: a review.

    PubMed

    Cleary, Michelle; Hunt, Glenn E; Horsfall, Jan; Deacon, Maureen

    2011-01-01

    Acute inpatient mental health units are busy and sometimes chaotic settings, with high bed occupancy rates. These settings include acutely unwell patients, busy staff, and a milieu characterised by unpredictable interactions and events. This paper is a report of a literature review conducted to identify, analyse, and synthesize ethnographic research in adult acute inpatient mental health units. Several electronic databases were searched using relevant keywords to identify studies published from 1990-present. Additional searches were conducted using reference lists. Ethnographic studies published in English were included if they investigated acute inpatient care in adult settings. Papers were excluded if the unit under study was not exclusively for patients in the acute phase of their mental illness, or where the original study was not fully ethnographic. Ten research studies meeting our criteria were found (21 papers). Findings were grouped into the following overarching categories: (1) Micro-skills; (2) Collectivity; (3) Pragmatism; and (4) Reframing of nursing activities. The results of this ethnographic review reveal the complexity, patient-orientation, and productivity of some nursing interventions that may not have been observed or understood without the use of this research method. Additional quality research should focus on redefining clinical priorities and philosophies to ensure everyday care is aligned constructively with the expectations of stakeholders and is consistent with policy and the realities of the organisational setting. We have more to learn from each other with regard to the effective nursing care of inpatients who are acutely disturbed. PMID:21736465

  11. Adult-to-adult living donor liver transplantation for acute liver failure in China

    PubMed Central

    Yuan, Ding; Liu, Fei; Wei, Yong-Gang; Li, Bo; Yan, Lv-Nan; Wen, Tian-Fu; Zhao, Ji-Chun; Zeng, Yong; Chen, Ke-Fei

    2012-01-01

    AIM: To investigate the long-term outcome of recipients and donors of adult-to-adult living-donor liver transplantation (AALDLT) for acute liver failure (ALF). METHODS: Between January 2005 and March 2010, 170 living donor liver transplantations were performed at West China Hospital of Sichuan University. All living liver donor was voluntary and provided informed consent. Twenty ALF patients underwent AALDLT for rapid deterioration of liver function. ALF was defined based on the criteria of the American Association for the Study of Liver Diseases, including evidence of coagulation abnormality [international normalized ratio (INR) ≥ 1.5] and degree of mental alteration without pre-existing cirrhosis and with an illness of < 26 wk duration. We reviewed the clinical indications, operative procedure and prognosis of AALDTL performed on patients with ALF and corresponding living donors. The potential factors of recipient with ALF and corresponding donor outcome were respectively investigated using multivariate analysis. Survival rates after operation were analyzed using the Kaplan-Meier method. Receiver operator characteristic (ROC) curve analysis was undertaken to identify the threshold of potential risk factors. RESULTS: The causes of ALF were hepatitis B (n = 18), drug-induced (n = 1) and indeterminate (n = 1). The score of the model for end-stage liver disease was 37.1 ± 8.6, and the waiting duration of recipients was 5 ± 4 d. The graft types included right lobe (n = 17) and dual graft (n = 3). The mean graft weight was 623.3 ± 111.3 g, which corresponded to graft-to-recipient weight ratio of 0.95% ± 0.14%. The segment Vor VIII hepatic vein was reconstructed in 11 right-lobe grafts. The 1-year and 3-year recipient’s survival and graft survival rates were 65% (13 of 20). Postoperative results of total bilirubin, INR and creatinine showed obvious improvements in the survived patients. However, the creatinine level of the deaths was increased postoperatively

  12. Carbamazepine for acute and chronic pain in adults

    PubMed Central

    Wiffen, Philip J; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background Carbamazepine is used to treat chronic neuropathic pain. Objectives Evaluation of analgesic efficacy and adverse effects of carbamazepine for acute and chronic pain management (except headaches). Search methods Randomised controlled trials (RCTs) of carbamazepine in acute, chronic or cancer pain were identified, searching MEDLINE, EMBASE, SIGLE and Cochrane CENTRAL to June 2010, reference lists of retrieved papers, and reviews. Selection criteria RCTs reporting the analgesic effects of carbamazepine. Data collection and analysis Two authors independently extracted results and scored for quality. Numbers needed to treat to benefit (NNT) or harm (NNH) with 95% confidence intervals (CI) were calculated from dichotomous data for effectiveness, adverse effects and adverse event withdrawal. Issues of study quality, size, duration, and outcomes were examined. Main results Fifteen included studies (12 cross-over design; three parallel-group) with 629 participants. Carbamazepine was less effective than prednisolone in preventing postherpetic neuralgia following acute herpes zoster (1 study, 40 participants). No studies examined acute postoperative pain. Fourteen studies investigated chronic neuropathic pain: two lasted eight weeks, others were four weeks or less (mean 3 weeks, median 2 weeks). Five had low reporting quality. Ten involved fewer than 50 participants; mean and median maximum treatment group sizes were 34 and 29. Outcome reporting was inconsistent. Most placebo controlled studies indicated that carbamazepine was better than placebo. Five studies with 298 participants provided dichotomous results; 70% improved with carbamazepine and 12% with placebo. Carbamazepine at any dose, using any definition of improvement was significantly better than placebo (70% versus 12% improved; 5 studies, 298 participants); relative benefit 6.1 (3.9 to 9.7), NNT 1.7 (1.5 to 2.0). Four studies (188 participants) reporting outcomes equivalent to 50% pain reduction or more

  13. Leukostasis in adult acute hyperleukocytic leukemia: a clinician's digest.

    PubMed

    Ali, Alaa M; Mirrakhimov, Aibek E; Abboud, Camille N; Cashen, Amanda F

    2016-06-01

    Leukostasis is a poorly understood and life-threatening complication of acute hyperleukocytic leukemia. The incidence of hyperleukocytosis and leukostasis differs among various subtypes of leukemias. While the pathophysiology of leukostasis is not fully understood, recent research has elucidated many novel pathways that may have therapeutic implications in the future. Respiratory and neurological compromise represents the classical clinical manifestations of leukostasis. If it is not diagnosed and treated rapidly, the one-week mortality rate is approximately 40%. Targeted induction chemotherapy is an important component of the successful treatment of leukostasis, although other modalities of cytoreduction are being used and investigated. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27018197

  14. Managing the acutely ill adult with sickle cell disease.

    PubMed

    Brown, Marvelle

    Sickle cell disease (SCD) is an autosomal recessively inherited condition, affecting the structure of the haemoglobin. SCD is a long-term chronic condition which is manifested by periods of acute painful sickling crisis, known as vaso-occlusive crisis (VOC) and is the cause of 90% of sickle cell-related hospital admissions. SCD is one of the most common genetic conditions worldwide and in the UK there are approximately 12,500 people living with it (Streetly et al,1997; Howard et al, 2008), making it more common than cystic fibrosis, yet there still remains many challenges in managing these patients when they become acutely ill. Lack of awareness and understanding of the illness, concerns regarding addiction and limited attention to the psycho-social implications of the illness, leads to less than effective care for this patient group when they are hospitalized. The aims of this article are to outline the pathophysiology of SCD, identify the causes of VOC and discuss the key principles of nursing management for patients experiencing a VOC. PMID:22306637

  15. An update of current treatments for adult acute myeloid leukemia

    PubMed Central

    Gardin, Claude

    2016-01-01

    Recent advances in acute myeloid leukemia (AML) biology and its genetic landscape should ultimately lead to more subset-specific AML therapies, ideally tailored to each patient's disease. Although a growing number of distinct AML subsets have been increasingly characterized, patient management has remained disappointingly uniform. If one excludes acute promyelocytic leukemia, current AML management still relies largely on intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), at least in younger patients who can tolerate such intensive treatments. Nevertheless, progress has been made, notably in terms of standard drug dose intensification and safer allogeneic HSCT procedures, allowing a larger proportion of patients to achieve durable remission. In addition, improved identification of patients at relatively low risk of relapse should limit their undue exposure to the risks of HSCT in first remission. The role of new effective agents, such as purine analogs or gemtuzumab ozogamicin, is still under investigation, whereas promising new targeted agents are under clinical development. In contrast, minimal advances have been made for patients unable to tolerate intensive treatment, mostly representing older patients. The availability of hypomethylating agents likely represents an encouraging first step for this latter population, and it is hoped will allow for more efficient combinations with novel agents. PMID:26660429

  16. Higher Early Monocyte and Total Lymphocyte Counts Are Associated with Better Overall Survival after Standard Total Body Irradiation, Cyclophosphamide, and Fludarabine Reduced-Intensity Conditioning Double Umbilical Cord Blood Allogeneic Stem Cell Transplantation in Adults.

    PubMed

    Le Bourgeois, Amandine; Peterlin, Pierre; Guillaume, Thierry; Delaunay, Jacques; Duquesne, Alix; Le Gouill, Steven; Moreau, Philippe; Mohty, Mohamad; Campion, Loïc; Chevallier, Patrice

    2016-08-01

    This single-center retrospective study aimed to report the impact of early hematopoietic and immune recoveries after a standard total body irradiation, cyclophosphamide, and fludarabine (TCF) reduced-intensity conditioning (RIC) regimen for double umbilical cord blood (dUCB) allogeneic stem cell transplantation (allo-SCT) in adults. We analyzed 47 consecutive patients older than 17 years who engrafted after a dUCB TCF allo-SCT performed between January 2006 and April 2013 in our department. Median times for neutrophil and platelet recoveries were 17 (range, 6 to 59) and 37 days (range, 0 to 164), respectively. The 3-year overall (OS) and disease-free survivals, relapse incidence, and nonrelapse mortality were 65.7%, 57.2%, 27.1%, and 19%, respectively. In multivariate analysis, higher day +30 monocyte (≥615/mm(3); hazard ratio [HR], .04; 95% confidence interval [CI], .004 to .36; P < .01) and day +42 lymphocyte (≥395/mm(3); HR, .16; 95% CI, .03 to .78; P = .02) counts were independently associated with better OS. These results suggest that early higher hematopoietic and immune recovery is predictive of survival after dUCB TCF RIC allo-SCT in adults. Factors other than granulocyte colony-stimulating factor, which was used in all cases, favoring expansion of monocytes or lymphocytes, should be tested in the future as part of the UCB transplantation procedure. PMID:27118570

  17. Treatment options for acute uncomplicated cystitis in adults.

    PubMed

    Naber

    2000-08-01

    Urinary tract infection (UTI) is classified as uncomplicated if it occurs in a patient with a structurally and functionally normal urinary tract. Acute uncomplicated cystitis is observed chiefly in women. It needs, however, to be differentiated depending on whether it occurs in premenopausal, postmenopausal or pregnant women. Only a small number of 15-50 year old, otherwise healthy men suffer acute uncomplicated cystitis. In premenopausal, non-pregnant women, single-dose antimicrobial therapy is generally less effective than the same antibiotic used for longer duration. However, most antimicrobial agents given for 3 days are as effective as those given for longer duration, and adverse events tend to be found more often with longer treatment. Trimethoprim (or co-trimoxazole) can be recommended as first-line empirical therapy only in communities with resistance rates of uropathogens to trimethoprim of 10%) of Escherichia coli strains in the community are already resistant to fluoroquinolones, as in Spain, for example. Recurrent UTIs are common among young, healthy women even though they generally have anatomically and physiologically normal urinary tracts. The following prophylactic antimicrobial regimens are recommended: (i) the use of long-term, low-dose prophylactic antimicrobials taken at bedtime; (ii) post-coital prophylaxis for women in whom episodes of infection are associated with sexual intercourse. Other prophylactic methods are not as yet as effective as antimicrobial prophylaxis. PMID:10969048

  18. Treatment options for acute uncomplicated cystitis in adults.

    PubMed

    Naber, K G

    2000-09-01

    Urinary tract infection (UTI) is classified as uncomplicated if it occurs in a patient with a structurally and functionally normal urinary tract. Acute uncomplicated cystitis is observed chiefly in women. It needs, however, to be differentiated depending on whether it occurs in premenopausal, postmenopausal or pregnant women. Only a small number of 15-50 year old, otherwise healthy men suffer acute uncomplicated cystitis. In premenopausal, non-pregnant women, single-dose antimicrobial therapy is generally less effective than the same antibiotic used for longer duration. However, most antimicrobial agents given for 3 days are as effective as those given for longer duration, and adverse events tend to be found more often with longer treatment. Trimethoprim (or co-trimoxazole) can be recommended as first-line empirical therapy only in communities with resistance rates of uropathogens to trimethoprim of < or =10-20%. Otherwise fluoroquinolones are recommended. Alternatives are fosfomycin trometamol or beta-lactams, such as second- or third-generation oral cephalosporins or pivmecillinam, especially when fluoroquinolones are contraindicated or a high proportion (>10%) of Escherichia coil strains in the community are already resistant to fluoroquinolones, as in Spain, for example. Recurrent UTIs are common among young, healthy women even though they generally have anatomically and physiologically normal urinary tracts. The following prophylactic antimicrobial regimens are recommended: (i) the use of long-term, low-dose prophylactic antimicrobials taken at bedtime; (ii) post-coital prophylaxis for women in whom episodes of infection are associated with sexual intercourse. Other prophylactic methods are not as yet as effective as antimicrobial prophylaxis. PMID:11051620

  19. Acute hemicerebellitis in a young adult: a case report and literature review.

    PubMed

    Suzuki, Keisuke; Nakamura, Toshiki; Numao, Ayaka; Fujita, Hiroaki; Komagamine, Tomoko; Nagashima, Takahide; Asakawa, Yohei; Watanabe, Yuji; Takekawa, Hidehiro; Hirata, Koichi

    2014-12-15

    Acute hemicerebellitis, marked by headache with or without cerebellar signs, is a rare clinical entity involving a unilateral cerebellar hemisphere. The pathogenesis of acute hemicerebellitis remains unclear, and the disease rarely occurs in adults. Here, we report an 18-year-old woman who presented with a lack of coordination of the right hand and leg lasting longer than one week, following a pulsatile headache. A neurological examination disclosed ocular dysmetria, right-sided limb ataxia and slight truncal ataxia. Cerebrospinal fluid analysis showed mononuclear pleocytosis. The serology and autoimmune studies were unremarkable. Brain magnetic resonance imaging (MRI) revealed a focal signal change in the right cerebellar hemisphere and vermis. Acute hemicerebellitis was diagnosed, and the patient was treated with intravenous methylprednisolone sodium succinate and acyclovir. Subsequently, the headache resolved, and the cerebellar signs were markedly improved. Twenty days after admission, she became asymptomatic and brain MRI showed resolution of cerebellar hyperintensity on the right side. In conclusion, we identified only 6 additional patients with adult-onset acute hemicerebellitis from previous reports, highlighting the importance of recognizing this rare clinical entity. Its clinical outcome is usually favorable, but in the acute phase, attention should be directed toward clinical symptoms that are suggestive of increased intracranial pressure. PMID:25454647

  20. Acute neuropsychiatric disorders in adolescents and young adults with Down syndrome: Japanese case reports

    PubMed Central

    Akahoshi, Keiko; Matsuda, Hiroshi; Funahashi, Masuko; Hanaoka, Tomoyuki; Suzuki, Yasuyuki

    2012-01-01

    Background: The aim of this study was to evaluate acute neuropsychiatric disorders in adolescents and young adults with Down syndrome. We report 13 Japanese adolescents or young adults with Down syndrome who developed acute neuropsychiatric disorders including withdrawal, depression, obsessive-compulsive behaviors, and occasional delusions or hallucinations. Methods: The following information was collected from each patient: age at onset of acute neuropsychiatric disorder, complications, signs and symptoms, personality traits before the onset of the acute neuropsychiatric disorder, prescribed medications with their respective doses and the response to treatment, and senile changes observed on magnetic resonance imaging or computed tomography. Results: The mean age at onset of these disorders was 21.2 years. Brain imaging showed almost senile changes; patients responded well to low-dose psychotropic therapy. Patients had an onset at a young age and presented with treatable conditions, although the average age of the onset of Alzheimer’s disease is generally over 40 years of age in patients with Down syndrome. Conclusion: These findings suggest that the pathology of acute neuropsychiatric disorder in patients with Down syndrome may be related to presenile changes; however, these disorders present features and a clinical course that is different from those presented in typical Alzheimer’s disease with Down syndrome. PMID:22888254

  1. Recognition of adult and pediatric acute lymphoblastic leukemia blasts by natural killer cells

    PubMed Central

    Torelli, Giovanni F.; Peragine, Nadia; Raponi, Sara; Pagliara, Daria; De Propris, Maria S.; Vitale, Antonella; Bertaina, Alice; Barberi, Walter; Moretta, Lorenzo; Basso, Giuseppe; Santoni, Angela; Guarini, Anna; Locatelli, Franco; Foà, Robin

    2014-01-01

    In this study, we aimed to investigate the pathways of recognition of acute lymphoblastic leukemia blasts by natural killer cells and to verify whether differences in natural killer cell activating receptor ligand expression among groups defined by age of patients, or presence of cytogenetic/molecular aberrations correlate with the susceptibility to recognition and killing. We analyzed 103 newly diagnosed acute lymphoblastic leukemia patients: 46 adults and 57 children. Pediatric blasts showed a significantly higher expression of Nec-2 (P=0.03), ULBP-1 (P=0.01) and ULBP-3 (P=0.04) compared to adult cells. The differential expression of these ligands between adults and children was confined to B-lineage acute lymphoblastic leukemia with no known molecular alterations. Within molecularly defined subgroups of patients, a high surface expression of NKG2D and DNAM1 ligands was found on BCR-ABL+ blasts, regardless of patient age. Accordingly, BCR-ABL+ blasts proved to be significantly more susceptible to natural killer-dependent lysis than B-lineage blasts without molecular aberrations (P=0.03). Cytotoxic tests performed in the presence of neutralizing antibodies indicated a pathway of acute lymphoblastic leukemia cell recognition in the setting of the Nec-2/DNAM-1 interaction. These data provide a biological explanation of the different roles played by alloreactive natural killer cells in pediatric versus adult acute lymphoblastic leukemia and suggest that new natural killer-based strategies targeting specific subgroups of patients, particularly those BCR-ABL+, are worth pursuing further. PMID:24658822

  2. Acute respiratory distress syndrome in an adult patient with a myelodysplastic disorder.

    PubMed

    Pentimone, F; Cini, G; Meola, N; Ferrannini, E

    1983-01-01

    A 58-year-old man was diagnosed to have refractory anaemia with excessive blasts. After 3 1/2 years of relative control on periodic blood transfusions, the patient developed an acute leukaemia. Although the blastic crisis was not extreme (WBC counts less than 100 X 10(9)/l), a severe, intractable respiratory distress syndrome set in and brought the patient to the exitus in a few days. Overt signs of septic shock were absent, as was evidence of any other known cause of adult respiratory distress. Acute pulmonary failure can be the cause of death in leukaemic patients even in the absence of overwhelming sepsis or hyperleucocytosis. PMID:6404107

  3. Pregabalin for acute and chronic pain in adults

    PubMed Central

    Moore, R Andrew; Straube, Sebastian; Wiffen, Philip J; Derry, Sheena; McQuay, Henry J

    2014-01-01

    Background Antiepileptic drugs have been used in pain management since the 1960s. Pregabalin is a recently developed antiepileptic drug also used in management of chronic neuropathic pain conditions. Objectives To assess analgesic efficacy and associated adverse events of pregabalin in acute and chronic pain. Search methods We searched MEDLINE, EMBASE, and CENTRAL to May 2009 for randomised controlled trials (RCTs). Additional studies were identified from the reference lists of retrieved papers and on-line clinical trial databases. Selection criteria Randomised, double blind trials reporting on the analgesic effect of pregabalin, with subjective pain assessment by the patient as either the primary or a secondary outcome. Data collection and analysis Two independent review authors extracted data and assessed trial quality. Numbers-needed-to-treat-to-benefit (NNTs) were calculated, where possible, from dichotomous data for effectiveness, adverse events and study withdrawals. Main results There was no clear evidence of beneficial effects of pregabalin in established acute postoperative pain. No studies evaluated pregabalin in chronic nociceptive pain, like arthritis. Pregabalin at doses of 300 mg, 450 mg, and 600 mg daily was effective in patients with postherpetic neuralgia, painful diabetic neuropathy, central neuropathic pain, and fibromyalgia (19 studies, 7003 participants). Pregabalin at 150 mg daily was generally ineffective. Efficacy was demonstrated for dichotomous outcomes equating to moderate or substantial pain relief, alongside lower rates for lack of efficacy discontinuations with increasing dose. The best (lowest) NNT for each condition for at least 50% pain relief over baseline (substantial benefit) for 600 mg pregabalin daily compared with placebo were 3.9 (95% confidence interval 3.1 to 5.1) for postherpetic neuralgia, 5.0 (4.0 to 6.6) for painful diabetic neuropathy, 5.6 (3.5 to 14) for central neuropathic pain, and 11 (7.1 to 21) for fibromyalgia

  4. Studying nursing interventions in acutely ill, cognitively impaired older adults

    PubMed Central

    McCauley, Kathleen; Bradway, Christine; Hirschman, Karen B; Naylor, Mary D

    2015-01-01

    Background Between one and two of every five hospitalized older adults have cognitive deficits, often not accurately assessed or well managed. Cognitive impairment adds substantially to the complexity of these patients’ care, places them at high risk for poor outcomes and increases the cost of health care. Methods We describe three evidence-based interventions, each capitalizing on the unique contributions of nurses and designed to improve outcomes of hospitalized older adults who have cognitive deficits. Interventions of varying intensity were compared across three hospitals (Phase I) and subsequently within the same hospitals (Phase II). All enrolled patients were screened during their index hospitalizations and cognitive deficits were communicated to relevant health care team members (Augmented Standard Care-ASC, lowest intensity). At one hospital, ASC was the only intervention. Patients at a second hospital also had care influenced by specially prepared registered nurses (Resource Nurse Care-RNC, medium intensity). Finally, patients at third hospital also received advanced practice nurse coordinated care (Transitional Care Model-TCM, higher intensity). In Phase II, newly enrolled patients at these same hospitals all received the TCM. We summarize major themes from review of multiple data sources and researcher recollections related to facilitators and barriers to implementing a complex research study. Findings Effective implementation of the three intervention strategies depended on clinician engagement and communication; degree of participation by nurses in the educational program with subsequent practice improvement; and success of advanced practice nurses in implementing the TCM with both with patients, family caregivers and clinicians. Implications Based on lessons learned in implementing complex research studies within the “real world” of clinical practice settings, recommendations focus on strengthening facilitators, minimizing barriers and gaining

  5. Defining and Treating Older Adults with Acute Myeloid Leukemia Who Are Ineligible for Intensive Therapies

    PubMed Central

    Pettit, Kristen; Odenike, Olatoyosi

    2015-01-01

    Although acute myeloid leukemia (AML) is primarily a disease of older adults (age ≥60 years), the optimal treatment for older adults remains largely undefined. Intensive chemotherapy is rarely beneficial for frail older adults or those with poor-risk disease, but criteria that define fitness and/or appropriateness for intensive chemotherapy remain to be standardized. Evaluation of disease-related and patient-specific factors in the context of clinical decision making has therefore been largely subjective. A uniform approach to identify those patients most likely to benefit from intensive therapies is needed. Here, we review currently available objective measures to define older adults with AML who are ineligible for intensive chemotherapy, and discuss promising investigational approaches. PMID:26697412

  6. Current standard treatment of adult acute promyelocytic leukaemia.

    PubMed

    Lo-Coco, Francesco; Cicconi, Laura; Breccia, Massimo

    2016-03-01

    The outcome of patients with acute promyelocytic leukaemia (APL) has dramatically improved over the last two decades, due to the introduction of combined all-trans retinoic acid (ATRA) and chemotherapy regimens and, more recently, to the advent of arsenic trioxide (ATO). ATRA and anthracycline-based chemotherapy remains a widely used strategy, providing cure rates above 80%, but it is associated with risk of severe infections and occurrence of secondary leukaemias. ATO is the most effective single agent in APL and, used alone or in combination with ATRA or ATRA and reduced-intensity chemotherapy, results in greater efficacy with considerably less haematological toxicity. The toxic profile of ATO includes frequent, but manageable, QTc prolongation and increase of liver enzymes. Two large randomized studies have shown that ATRA + ATO is superior to ATRA + chemotherapy for newly diagnosed low-risk APL resulting in 2-4 year event-free survival rates above 90% and very few relapses. According to real world data, the spectacular progress in APL outcomes reported in clinical trials has not been paralleled by a significant improvement in early death rates, this remains the most challenging issue for the final cure of the disease. PMID:26687281

  7. Novel postremission strategies in adults with acute myeloid leukemia

    PubMed Central

    Lancet, Jeffrey E.; Karp, Judith E.

    2010-01-01

    Purpose of review Given the high rates of relapse in acute myeloid leukemia (AML), there is tremendous opportunity for the development of new therapeutic strategies in the postremission state. Unfortunately, the currently available modalities for postremission therapy, namely chemotherapy, have proven largely ineffective in changing the natural history of AML. The challenges to overcome therapeutic failure in the minimal residual disease status may relate to an incomplete understanding of the mechanisms and cell populations that are directly related to disease relapse as well as suboptimal ability to identify patients at highest risk for relapse. Recent findings Being a heterogeneous disease, relapsed AML is unlikely to emanate from one predominant mechanism; instead, there are likely multiple biologic factors at play that allow for clinical relapse to occur. These factors likely include multidrug resistance proteins, aberrant signal transduction pathways, survival of leukemia stem cells, microenvironmental interactions, and immune tolerance. Many novel strategies are in development that target these mechanisms, ranging from chemotherapeutic modalities, to signal transduction inhibitors, to upregulation of antileukemic immune responses. Summary Understanding the underlying mechanisms of leukemic cell survival and resistance has spurred the development of novel therapeutic approaches to overcome these mechanisms in the hope of eradicating minimal residual disease and improving survival in AML. PMID:19468272

  8. Epidemiology of severe acute respiratory syndrome (SARS): adults and children.

    PubMed

    Zhong, Nan-Shan; Wong, Gary W K

    2004-12-01

    Severe acute respiratory syndrome (SARS) is a newly described respiratory infection with pandemic potential. The causative agent is a new strain of coronavirus most likely originating from wild animals. This disease first emerged in November 2002 in Guangdong Province, China. Early in the outbreak the infection had been transmitted primarily via household contacts and healthcare settings. In late February 2003 the infection was transmitted to Hong Kong when an infected doctor from the mainland visited there. During his stay in Hong Kong at least 17 guests and visitors were infected at the hotel at which he stayed. By modern day air travel, the infection was rapidly spread to other countries including Vietnam, Singapore and Canada by these infected guests. With the implementation of effective control strategies including early isolation of suspected cases, strict infection control measures in the hospital setting, meticulous contact tracing and quarantine, the outbreak was finally brought under control by July 2003. In addition, there were another two events of SARS in China between the end of December 2003 and January 2004 and from March to May 2004; both were readily controlled without significant patient spread. PMID:15531250

  9. Docosahexaenoic acid pretreatment confers protection and functional improvements after acute spinal cord injury in adult rats.

    PubMed

    Figueroa, Johnny D; Cordero, Kathia; Baldeosingh, Keisha; Torrado, Aranza I; Walker, Robert L; Miranda, Jorge D; Leon, Marino De

    2012-02-10

    Currently, few interventions have been shown to successfully limit the progression of secondary damage events associated with the acute phase of spinal cord injury (SCI). Docosahexaenoic acid (DHA, C22:6 n-3) is neuroprotective when administered following SCI, but its potential as a pretreatment modality has not been addressed. This study used a novel DHA pretreatment experimental paradigm that targets acute cellular and molecular events during the first week after SCI in rats. We found that DHA pretreatment reduced functional deficits during the acute phase of injury, as shown by significant improvements in Basso-Beattie-Bresnahan (BBB) locomotor scores, and the detection of transcranial magnetic motor evoked potentials (tcMMEPs) compared to vehicle-pretreated animals. We demonstrated that, at 7 days post-injury, DHA pretreatment significantly increased the percentage of white matter sparing, and resulted in axonal preservation, compared to the vehicle injections. We found a significant increase in the survival of NG2+, APC+, and NeuN+ cells in the ventrolateral funiculus (VLF), dorsal corticospinal tract (dCST), and ventral horns, respectively. Interestingly, these DHA protective effects were observed despite the lack of inhibition of inflammatory markers for monocytes/macrophages and astrocytes, ED1/OX42 and GFAP, respectively. DHA pretreatment induced levels of Akt and cyclic AMP responsive element binding protein (CREB) mRNA and protein. This study shows for the first time that DHA pretreatment ameliorates functional deficits, and increases tissue sparing and precursor cell survival. Further, our data suggest that DHA-mediated activation of pro-survival/anti-apoptotic pathways may be independent of its anti-inflammatory effects. PMID:21970623

  10. Docosahexaenoic Acid Pretreatment Confers Protection and Functional Improvements after Acute Spinal Cord Injury in Adult Rats

    PubMed Central

    Figueroa, Johnny D.; Cordero, Kathia; Baldeosingh, Keisha; Torrado, Aranza I.; Walker, Robert L.; Miranda, Jorge D.

    2012-01-01

    Abstract Currently, few interventions have been shown to successfully limit the progression of secondary damage events associated with the acute phase of spinal cord injury (SCI). Docosahexaenoic acid (DHA, C22:6 n-3) is neuroprotective when administered following SCI, but its potential as a pretreatment modality has not been addressed. This study used a novel DHA pretreatment experimental paradigm that targets acute cellular and molecular events during the first week after SCI in rats. We found that DHA pretreatment reduced functional deficits during the acute phase of injury, as shown by significant improvements in Basso-Beattie-Bresnahan (BBB) locomotor scores, and the detection of transcranial magnetic motor evoked potentials (tcMMEPs) compared to vehicle-pretreated animals. We demonstrated that, at 7 days post-injury, DHA pretreatment significantly increased the percentage of white matter sparing, and resulted in axonal preservation, compared to the vehicle injections. We found a significant increase in the survival of NG2+, APC+, and NeuN+ cells in the ventrolateral funiculus (VLF), dorsal corticospinal tract (dCST), and ventral horns, respectively. Interestingly, these DHA protective effects were observed despite the lack of inhibition of inflammatory markers for monocytes/macrophages and astrocytes, ED1/OX42 and GFAP, respectively. DHA pretreatment induced levels of Akt and cyclic AMP responsive element binding protein (CREB) mRNA and protein. This study shows for the first time that DHA pretreatment ameliorates functional deficits, and increases tissue sparing and precursor cell survival. Further, our data suggest that DHA-mediated activation of pro-survival/anti-apoptotic pathways may be independent of its anti-inflammatory effects. PMID:21970623

  11. Candesartan ameliorates acute myocardial infarction in rats through inducible nitric oxide synthase, nuclear factor‑κB, monocyte chemoattractant protein‑1, activator protein‑1 and restoration of heat shock protein 72.

    PubMed

    Lin, Xuefeng; Wu, Min; Liu, Bo; Wang, Junkui; Guan, Gongchang; Ma, Aiqun; Zhang, Yong

    2015-12-01

    Candesartan, an angiotensin II type 1 receptor antagonist, has a variety of biological activities, including antioxidant, anti‑inflammatory and anticancer activities, with specific pharmacological effects. The present study investigated the mechanisms and protective effect of candesartan on acute myocardial infarction in rats. Male Wistar rats (8‑week‑old) were induced as a model of acute myocardial infarction and treated with candesartan (0.25 mg/kg) for 2 weeks. The present study first measured the activities of casein kinase (CK), the MB isoenzyme of creatine kinase (CK‑MB) and lactate dehydrogenase (LDH), the level of cardiac troponin T (cTnT) and infarct size. Subsequently, western blot analysis was performed to analyze the protein expression levels of inducible nitric oxide synthase (iNOS) and heat shock protein 72 (HSP72) in the rats. An enzyme linked immunosorbent assay was used to detect iNOS and nuclear factor‑κB (NF‑κB) activity. In addition, gene expression levels of monocyte chemotactic protein‑1 (MCP‑1) and activating protein‑1 (AP‑1) were determined using reverse transcription‑quantitative polymerase chain reaction analysis. Finally, the activities of caspase‑3 and caspase‑9 were examined using colorimetric assay kits. In the serum of the rat model of acute myocardial infarction, candesartan significantly increased the activities of CK, CK‑MB and LDH, and the level of cTnT. The infarction size was perfected by candesartan treatment. Candesartan significantly reduced the protein expression and activity of iNOS, the activity of NF‑κB p65, and the gene expression levels of MCP‑1 and AP‑1 in the rat model of acute myocardial infarction. Candesartan increased the protein expression of HSP‑72 in the acute myocardial infarction rat model. However, candesartan did not effect the levels of caspase‑3 or caspase‑9 in the rat model of acute myocardial infarction. These results suggested that candesartan ameliorates

  12. Acute bacterial meningitis in adults: a hospital based study in Yemen.

    PubMed

    Abdulrab, Amin; Algobaty, Faker; Salem, Ahmed K; Mohammed, Y A K

    2010-03-01

    Acute bacterial meningitis is an important cause of mortality and morbidity with high rates of long-term neurological sequelae. To determine the clinical presentation, complications, and outcome of acute meningitis in Yemen, a retrospective study in patients 15 years or older with acute bacterial meningitis who were admitted into Al-Thawra Teaching Hospital in Sana'a from January 2006 to December 2007 was carried out. There were 121 patients with acute bacterial meningitis. Lumbar puncture was performed in 112 (92.6%). The most common pathogen was Streptococcus pneumoniae found in 47.4% of positive cultures, Neisseria meningitidis in 33.9%, and Haemophilus influenzae in 10.2%. The classical triad of acute bacterial meningitis was found in 65% of cases. The mortality rate was 22.3%, with 27 patients dying during hospitalization. S. pneumoniae had a case fatality rate of 35.7%. Frequent complications were impaired consciousness, recurrent convulsion, and chest infection, which occurred in 30.6, 16.5, and 10.7% of the patients, respectively. Risk factors for death among those with acute bacterial meningitis included older age (>or=45 years), altered mental status, chest infection, and S. pneumoniae infection. This study highlights the importance of bacterial meningitis as a serious disease of adults in Yemen and the need for effective methods to prevent its complications. PMID:20332577

  13. Spectral karyotyping reveals a comprehensive karyotype in an adult acute lymphoblastic leukemia

    PubMed Central

    Guo, Bo; Zhu, Hong Li; Li, Su Xia; Lu, Xue Chun; Fan, Hui; Da, Wan Ming

    2012-01-01

    Cytogenetic abnormalities are frequently detected in patients with acute lymphoblastic leukemia (ALL). Comprehensive karyotype was related to poor prognosis frequently in ALL. We present a comprehensive karyotype in an adult ALL by spectral karyotyping (SKY) and R-banding. SKY not only confirmed the abnormalities previously seen by R-banding but also improved comprehensive karyotype analysis with the following result 47,XY,+9, ins(1;5)(q23;q23q34) t(6;7)(q23;p13). Our report demonstrated that SKY is able to provide more information accurately for prediction of disease prognosis in adult ALL with comprehensive karyotype. PMID:27298606

  14. Allogeneic hematopoietic cell transplantation in adult patients with acute lymphoblastic leukemia.

    PubMed

    Marks, David I; Alonso, Laura; Radia, Rohini

    2014-12-01

    This review discusses the use of prognostic factors, patient and donor selection, choice of conditioning regimens, and timing of transplant. It also describes the management of Philadelphia-positive acute lymphocytic leukemia (ALL) and central nervous system disease. All aggressively treated adults with ALL should be considered for allogeneic transplantation and tissue typed at diagnosis. We further suggest that eligible patients be entered into clinical trials (that incorporate transplantation); these unselected prospective outcome data are essential to evaluate the true value of allogeneic transplantation in adults with ALL. PMID:25459175

  15. Forearm and upper-arm oscillometric blood pressure comparison in acutely ill adults.

    PubMed

    Schell, Kathleen; Morse, Kate; Waterhouse, Julie K

    2010-04-01

    When patients' upper arms are not accessible and/or when cuffs do not fit large upper arms, the forearm site is often used for blood pressure (BP) measurement. The purpose of this study is to compare forearm and upper-arm BPs in 70 acutely ill adults, admitted to a community hospital's 14-bed ICU. Using Philips oscillometric monitors, three repeated measures of forearm and upper-arm BPs are obtained with head of bed flat and with head of bed elevated at 30 degrees. Arms are resting on the bed. Paired t tests show statistically significant differences in systolic BPs, diastolic BPs, and mean arterial pressures in the supine and head-elevated positions. Bland-Altman analyses indicate that forearm and upper-arm oscillometric BPs are not interchangeable in acutely ill adults. PMID:20581399

  16. Extracorporeal membrane oxygenation for the treatment of adult sickle cell acute chest syndrome.

    PubMed

    Parhar, Ken; Parizkova, Barbora; Jones, Nicola; Valchanov, Kamen; Fowles, Jo-Anne; Besser, Martin; Telfer, Paul; Kaya, Banu; Vuylsteke, Alain; Rubino, Antonio

    2016-04-01

    Sickle cell disease (SCD) is a hereditary haemoglobinopathy that results in polymerization of haemoglobin molecules and subsequent vaso-occlusion. A common cause of death in adults is acute chest syndrome (AChS) with resulting hypoxemic respiratory failure.Veno-venous extracorporeal membrane oxygenation (VV-ECMO) has been used successfully in acutely reversible respiratory failure when conventional mechanical ventilation has been unable to adequately oxygenate and ventilate in a lung-protective fashion.We present an adult SCD patient with severe respiratory failure due to AChS, successfully treated with VV-ECMO. We also discuss some of the technical challenges and considerations when using ECMO in the SCD patient. PMID:26130498

  17. Efficacy of Retigabine on Acute Limbic Seizures in Adult Rats

    PubMed Central

    Friedman, LK; Slomko, AM; Wongvravit, JP; Naseer, Z; Hu, S; Wan, WY; Ali, SS

    2015-01-01

    Background and Purpose: The efficacy of retigabine (RGB), a positive allosteric modulator of K+ channels indicated for adjunct treatment of partial seizures, was studied in two adult models of kainic acid (KA)-induced status epilepticus to determine it’s toleratbility. Methods: Retigabine was administered systemiclly at high (5 mg/kg) and low (1–2 mg/kg) doses either 30 min prior to or 2 hr after KA-induced status epilepticus. High (1 µg/µL) and low (0.25 µg/µL) concentrations of RGB were also delivered by intrahippocampal microinjection in the presence of KA. Results: Dose-dependent effects of RGB were observed with both models. Lower doses increased seizure behavior latency and reduced the number of single spikes and synchronized burst events in the electroencephalogram (EEG). Higher doses worsened seizure behavior, produced severe ataxia, and increased spiking activity. Animals treated with RGB that were resistant to seizures did not exhibit significant injury or loss in GluR1 expression; however if stage 5–6 seizures were reached, typical hippocampal injury and depletion of GluR1 subunit protein in vulernable pyramidal fields occurred. Conclusions: RGB was neuroprotective only if seizures were significantly attenuated. GluR1 was simultaneously suppressed in the resistant granule cell layer in presence of RGB which may weaken excitatory transmission. Biphasic effects observed herein suggest that the human dosage must be carefully scrutinized to produce the optimal clinical response. PMID:26819936

  18. Review of Acute Traumatic Closed Mallet Finger Injuries in Adults

    PubMed Central

    Salazar Botero, Santiago; Hidalgo Diaz, Juan Jose; Benaïda, Anissa; Collon, Sylvie; Facca, Sybille

    2016-01-01

    In adults, mallet finger is a traumatic zone I lesion of the extensor tendon with either tendon rupture or bony avulsion at the base of the distal phalanx. High-energy mechanisms of injury generally occur in young men, whereas lower energy mechanisms are observed in elderly women. The mechanism of injury is an axial load applied to a straight digit tip, which is then followed by passive extreme distal interphalangeal joint (DIPJ) hyperextension or hyperflexion. Mallet finger is diagnosed clinically, but an X-ray should always be performed. Tubiana's classification takes into account the size of the bony articular fragment and DIPJ subluxation. We propose to stage subluxated fractures as stage III if the subluxation is reducible with a splint and as stage IV if not. Left untreated, mallet finger becomes chronic and leads to a swan-neck deformity and DIPJ osteoarthritis. The goal of treatment is to restore active DIPJ extension. The results of a six- to eight-week conservative course of treatment with a DIPJ splint in slight hyperextension for tendon lesions or straight for bony avulsions depends on patient compliance. Surgical treatments vary in terms of the approach, the reduction technique, and the means of fixation. The risks involved are stiffness, septic arthritis, and osteoarthritis. Given the lack of consensus regarding indications for treatment, we propose to treat all cases of mallet finger with a dorsal glued splint except for stage IV mallet finger, which we treat with extra-articular pinning. PMID:27019806

  19. Acute Whole-Body Vibration does not Facilitate Peak Torque and Stretch Reflex in Healthy Adults

    PubMed Central

    Yeung, Ella W.; Lau, Cheuk C.; Kwong, Ada P.K.; Sze, Yan M.; Zhang, Wei Y.; Yeung, Simon S.

    2014-01-01

    The acute effect of whole-body vibration (WBV) training may enhance muscular performance via neural potentiation of the stretch reflex. The purpose of this study was to investigate if acute WBV exposure affects the stretch induced knee jerk reflex [onset latency and electromechanical delay (EMD)] and the isokinetic knee extensor peak torque performance. Twenty-two subjects were randomly assigned to the intervention or control group. The intervention group received WBV in a semi-squat position at 30° knee flexion with an amplitude of 0.69 mm, frequency of 45 Hz, and peak acceleration of 27.6 m/s2 for 3 minutes. The control group underwent the same semii-squatting position statically without exposure of WBV. Two-way mixed repeated measures analysis of variance revealed no significant group effects differences on reflex latency of rectus femoris (RF) and vastus lateralis (VL; p = 0.934 and 0.935, respectively) EMD of RF and VL (p = 0.474 and 0.551, respectively) and peak torque production (p = 0.483) measured before and after the WBV. The results of this study indicate that a single session of WBV exposure has no potentiation effect on the stretch induced reflex and peak torque performance in healthy young adults. Key Points There is no acute potentiation of stretch reflex right after whole body vibration. Acute whole body vibration does not improve mus-cle peak torque performance in healthy young adults. PMID:24570602

  20. DISTRIBUTION OF [14C]ETHANE DIMENTHANESULFONATE IN IMMATURE AND ADULT MALE RATS FOLLOWING AN ACUTE EXPOSURE

    EPA Science Inventory

    In the adult rat, ethane dimethanesulphonate (EDS) reduces testosterone (T) production by killing Leydig cells. Studies have also shown that acute EDS administration produces transient infertility and epididymal effects. Although these later effects were believed to be indirect r...

  1. Acute dietary nitrate supplementation enhances compensatory vasodilation during hypoxic exercise in older adults

    PubMed Central

    Treichler, David P.; Ganger, Charles T.; Schneider, Aaron C.; Ueda, Kenichi

    2014-01-01

    We have previously demonstrated that aging reduces the compensatory vasodilator response during hypoxic exercise due to blunted nitric oxide (NO) signaling. Recent evidence suggests that NO bioavailability can be augmented by dietary nitrate through the nitrate-nitrite pathway. Thus we tested the hypothesis that acute dietary nitrate supplementation increases the compensatory vasodilator response to hypoxic exercise, particularly in older adults. Thirteen young (25 ± 1 yr) and 12 older (64 ± 2 yr) adults performed rhythmic forearm exercise at 20% of maximum voluntary contraction during normoxia and hypoxia (∼80% O2 saturation); both before (control) and 3 h after beetroot juice (BR) consumption. Forearm vascular conductance (FVC; ml·min−1·100 mmHg−1) was calculated from forearm blood flow (ml/min) and blood pressure (mmHg). Compensatory vasodilation was defined as the relative increase in FVC due to hypoxic exercise (i.e., % increase compared with respective normoxic exercise trial). Plasma nitrite was determined from venous blood samples obtained before the control trials and each of the exercise trials (normoxia and hypoxia) after BR. Consumption of BR increased plasma nitrite in both young and older adults (P < 0.001). During the control condition, the compensatory vasodilator response to hypoxic exercise was attenuated in older compared with young adults (3.8 ± 1.7% vs. 14.2 ± 1.2%, P < 0.001). Following BR consumption, compensatory vasodilation did not change in young (13.7 ± 3.3%, P = 0.81) adults but was substantially augmented in older adults (11.4 ± 2.1%, P < 0.01). Our data suggest that acute dietary nitrate supplementation increases the compensatory vasodilator response to hypoxic exercise in older but not young adults. PMID:25414241

  2. Acute dietary nitrate supplementation enhances compensatory vasodilation during hypoxic exercise in older adults.

    PubMed

    Casey, Darren P; Treichler, David P; Ganger, Charles T; Schneider, Aaron C; Ueda, Kenichi

    2015-01-15

    We have previously demonstrated that aging reduces the compensatory vasodilator response during hypoxic exercise due to blunted nitric oxide (NO) signaling. Recent evidence suggests that NO bioavailability can be augmented by dietary nitrate through the nitrate-nitrite pathway. Thus we tested the hypothesis that acute dietary nitrate supplementation increases the compensatory vasodilator response to hypoxic exercise, particularly in older adults. Thirteen young (25 ± 1 yr) and 12 older (64 ± 2 yr) adults performed rhythmic forearm exercise at 20% of maximum voluntary contraction during normoxia and hypoxia (∼80% O2 saturation); both before (control) and 3 h after beetroot juice (BR) consumption. Forearm vascular conductance (FVC; ml·min(-1)·100 mmHg(-1)) was calculated from forearm blood flow (ml/min) and blood pressure (mmHg). Compensatory vasodilation was defined as the relative increase in FVC due to hypoxic exercise (i.e., % increase compared with respective normoxic exercise trial). Plasma nitrite was determined from venous blood samples obtained before the control trials and each of the exercise trials (normoxia and hypoxia) after BR. Consumption of BR increased plasma nitrite in both young and older adults (P < 0.001). During the control condition, the compensatory vasodilator response to hypoxic exercise was attenuated in older compared with young adults (3.8 ± 1.7% vs. 14.2 ± 1.2%, P < 0.001). Following BR consumption, compensatory vasodilation did not change in young (13.7 ± 3.3%, P = 0.81) adults but was substantially augmented in older adults (11.4 ± 2.1%, P < 0.01). Our data suggest that acute dietary nitrate supplementation increases the compensatory vasodilator response to hypoxic exercise in older but not young adults. PMID:25414241

  3. Results of a phase 1 study utilizing monocyte-derived dendritic cells pulsed with tumor RNA in children and young adults with brain cancer1

    PubMed Central

    Caruso, Denise A.; Orme, Lisa M.; Neale, Alana M.; Radcliff, Fiona J.; Amor, Gerlinda M.; Maixner, Wirginia; Downie, Peter; Hassall, Timothy E.; Tang, Mimi L.K.; Ashley, David M.

    2004-01-01

    We conducted a phase 1 study of 9 pediatric patients with recurrent brain tumors using monocyte-derived dendritic cells pulsed with tumor RNA to produce antitumor vaccine (DCRNA) preparations. The objectives of this study included (1) establishing safety and feasibility and (2) measuring changes in general, antigen-specific, and tumor-specific immune responses after DCRNA. Dendritic cells were derived from freshly isolated monocytes after 7 days of culture with IL-4 and granulocyte-macrophage colony–stimulating factor, pulsed with autologous tumor RNA, and then cryopreserved. Patients received at least 3 vaccines, each consisting of an intravenous and an intra-dermal administration at biweekly intervals. The study showed that this method for producing and administering DCRNA from a single leukapheresis product was both feasible and safe in this pediatric brain tumor population. Immune function at the time of enrollment into the study was impaired in all patients tested. While humoral responses to recall antigens (diphtheria and tetanus) were intact in all patients, cellular responses to mitogen and recall antigens were below normal. Following DCRNA vaccine, 2 of 7 patients showed stable clinical disease and 1 of 7 showed a partial response. Two of 7 patients who were tested showed a tumor-specific immune response to DCRNA. This study showed that DCRNA vaccines are both safe and feasible in children with tumors of the central nervous system with a single leukapheresis. PMID:15279716

  4. A Systematic Review of Music Therapy Practice and Outcomes with Acute Adult Psychiatric In-Patients

    PubMed Central

    Carr, Catherine; Odell-Miller, Helen; Priebe, Stefan

    2013-01-01

    Background and Objectives There is an emerging evidence base for the use of music therapy in the treatment of severe mental illness. Whilst different models of music therapy have been developed in mental health care, none have specifically accounted for the features and context of acute in-patient settings. This review aimed to identify how music therapy is provided for acute adult psychiatric in-patients and what outcomes have been reported. Review Methods A systematic review using medical, psychological and music therapy databases. Papers describing music therapy with acute adult psychiatric in-patients were included. Analysis utilised narrative synthesis. Results 98 papers were identified, of which 35 reported research findings. Open group work and active music making for nonverbal expression alongside verbal reflection was emphasised. Aims were engagement, communication and interpersonal relationships focusing upon immediate areas of need rather than longer term insight. The short stay, patient diversity and institutional structure influenced delivery and resulted in a focus on single sessions, high session frequency, more therapist direction, flexible use of musical activities, predictable musical structures, and clear realistic goals. Outcome studies suggested effectiveness in addressing a range of symptoms, but were limited by methodological shortcomings and small sample sizes. Studies with significant positive effects all used active musical participation with a degree of structure and were delivered in four or more sessions. Conclusions No single clearly defined model exists for music therapy with adults in acute psychiatric in-patient settings, and described models are not conclusive. Greater frequency of therapy, active structured music making with verbal discussion, consistency of contact and boundaries, an emphasis on building a therapeutic relationship and building patient resources may be of particular importance. Further research is required to

  5. Clinical use of blinatumomab for B-cell acute lymphoblastic leukemia in adults

    PubMed Central

    Lee, Kum Ja; Chow, Vivian; Weissman, Ashley; Tulpule, Sunil; Aldoss, Ibrahim; Akhtari, Mojtaba

    2016-01-01

    Adults with relapsed or refractory B-cell acute lymphoblastic leukemia have a dismal prognosis with a short median overall survival that can be measured in months. Because most patients will have chemotherapy-resistant disease, allogeneic hematopoietic stem cell transplantation remains the only potentially curative treatment. Despite advances in current management, patients continue to have poor outcomes and lack of durable responses. Thus, new therapies with alternative modes of actions are currently being investigated. Blinatumomab is a novel bispecific T-cell engager that simultaneously binds CD3-positive cytotoxic T-cells and CD19-positive B-cells, resulting in selective lysis of tumor cells. It has shown promising results in patients with relapsed or refractory acute lymphoblastic leukemia or those achieving hematologic response with persistent minimum residual disease. Future clinical trials will answer questions regarding its optimal place in the treatment paradigm. Dose-limiting toxicities include immunological toxicities and cytokine release syndrome. However, most patients tolerate the therapy relatively well. This review will focus on the pharmacology, clinical efficacy, and safety of blinatumomab in the treatment of adult B-cell acute lymphoblastic leukemia while highlighting its unique drug warnings and toxicity management. PMID:27601914

  6. Clinical use of blinatumomab for B-cell acute lymphoblastic leukemia in adults.

    PubMed

    Lee, Kum Ja; Chow, Vivian; Weissman, Ashley; Tulpule, Sunil; Aldoss, Ibrahim; Akhtari, Mojtaba

    2016-01-01

    Adults with relapsed or refractory B-cell acute lymphoblastic leukemia have a dismal prognosis with a short median overall survival that can be measured in months. Because most patients will have chemotherapy-resistant disease, allogeneic hematopoietic stem cell transplantation remains the only potentially curative treatment. Despite advances in current management, patients continue to have poor outcomes and lack of durable responses. Thus, new therapies with alternative modes of actions are currently being investigated. Blinatumomab is a novel bispecific T-cell engager that simultaneously binds CD3-positive cytotoxic T-cells and CD19-positive B-cells, resulting in selective lysis of tumor cells. It has shown promising results in patients with relapsed or refractory acute lymphoblastic leukemia or those achieving hematologic response with persistent minimum residual disease. Future clinical trials will answer questions regarding its optimal place in the treatment paradigm. Dose-limiting toxicities include immunological toxicities and cytokine release syndrome. However, most patients tolerate the therapy relatively well. This review will focus on the pharmacology, clinical efficacy, and safety of blinatumomab in the treatment of adult B-cell acute lymphoblastic leukemia while highlighting its unique drug warnings and toxicity management. PMID:27601914

  7. NUTRITIONAL THERAPY IN THE TREATMENT OF ACUTE CORROSIVE INTOXICATION IN ADULTS

    PubMed Central

    Chibishev, Andon; Markoski, Velo; Smokovski, Ivica; Shikole, Emilija; Stevcevska, Aleksandra

    2016-01-01

    Introduction: Acute intoxications with corrosive substances can cause severe chemical injuries of the upper gastrointestinal tract, most often located in the mouth, pharynx, esophagus, stomach and duodenum. If a patient survives the acute phase of intoxication, regenerative response may result in esophageal and/or gastric stenosis, and increased risk of esophageal and gastric cancer. Such intoxication may be fatal due to perforation or tracheal necrosis. Enteral nutrition is a nutritional method when nutritional substances are administered through specially designed tubing placed through the nose or percutaneously, directly into the GIT. Aim: The aim of this study is to describe the methods of artificial nutrition in patients with acute corrosive intoxications and the importance of nutritional support in the treatment of these intoxications. Discussion: Nutrition in the treatment of acute corrosive intoxications is one of the most important therapeutic processes that largely contribute to faster recovery of the post-corrosive injuries of upper GIT, stabilization of biologic, immunologic and metabolic parameters, and reduction of length of stay in hospital Aim of the treatment of acute corrosive intoxications is to prevent perforation and progressive fibrosis, and esophageal and gastric stenosis. There are different and often conflicting positions, on the conservative treatment of acute corrosive intoxications in adults. Such treatment mainly consists of anti-secretory treatment, antibiotics and intensive hyper-alimentation, aiming to prevent late post-corrosive intoxications. Conclusion: It is considered that nutritional support plays a major role in maintenance of metabolic processes and prevention of severe metabolic complications that could additionally aggravate the condition and impair the treatment. PMID:27047272

  8. Electrophysiological study of infant and adult rats under acute intoxication with fluoroacetamide.

    PubMed

    Kuznetsov, Sergey V; Jenkins, Richard O; Goncharov, Nikolay V

    2007-01-01

    A study was conducted of acute intoxication of infant and adult Wistar rats with fluoroacetamide (FAA), an inhibitor of oxidative metabolism. FAA was administered orally to adult rats at 1/2 LD(50) and subcutaneously to infant rats at LD(100) or 1/10 LD(50). Electrocardiogram (ECG), respiration and motor activity were registered for 7 days. Clinical analysis of ECG and the heart rate variability (HRV) was carried out to assess the state of the vegetative nervous system. In adult rats, FAA caused marked disturbances in the activity of cardiovascular and respiratory systems, including the development of a potentially lethal acute cor pulmonale. Conversely, there were no significant changes of cardiac function and respiration in infant rats; they died because of extreme emaciation accompanied by retardation of development. In adult rats, bursts of associated cardiac and respiratory tachyarrhythmia, as well as regular high amplitude spasmodic sighs having a deca-second rhythm were observed. In both infant and adult rats, FAA caused short-term enhancement of humoral (metabolic) and sympathetic activities, followed by a gradual and stable predominance of parasympathetic influence on HRV. Under conditions of FAA inhibition of the tricarboxylic acid cycle, the observed physiological reactions may be explained by activation of alternative metabolic pathways. This is also supported by a lack of ontogenetically caused inhibition of spontaneous motor activity in infant rats poisoned with FAA, which highlights the significance of the alternative metabolic pathways for implementation of deca-second and minute rhythms and a lack of a rigid dependence of these rhythms upon activity of neuronal networks. PMID:17351914

  9. A Case of Acute Disseminated Encephalomyelitis in a Middle-Aged Adult

    PubMed Central

    Mahdi, Nicole; Abdelmalik, Peter A.; Curtis, Mark; Bar, Barak

    2015-01-01

    Objectives. Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disorder that is often preceded by infection or recent vaccination. Encephalopathy and focal neurological deficits are usually manifest several weeks after a prodromal illness with rapidly progressive neurologic decline. ADEM is most commonly seen in children and young adults, in which prognosis is favorable, but very few cases have been reported of older adults with ADEM and thus their clinical course is unknown. Methods. Here we present a case of ADEM in a middle-aged adult that recovered well after treatment. Results. A 62-year-old man presented with encephalopathy and rapid neurological decline following a gastrointestinal illness. A brain MRI revealed extensive supratentorial white matter hyperintensities consistent with ADEM and thus he was started on high dose intravenous methylprednisolone. He underwent a brain biopsy showing widespread white matter inflammation secondary to demyelination. At discharge, his neurological exam had significantly improved with continued steroid treatment and four months later, he was able to perform his ADLs. Conclusions. This case of ADEM in a middle-aged adult represents an excellent response to high dose steroid treatment with a remarkable neurological recovery. Thus it behooves one to treat suspected cases of ADEM in an adult patient aggressively, as outcome can be favorable. PMID:26180647

  10. Survival improvements in adolescents and young adults after myeloablative allogeneic transplantation for acute lymphoblastic leukemia.

    PubMed

    Wood, William A; Lee, Stephanie J; Brazauskas, Ruta; Wang, Zhiwei; Aljurf, Mahmoud D; Ballen, Karen K; Buchbinder, David K; Dehn, Jason; Freytes, Cesar O; Lazarus, Hillard M; Lemaistre, Charles F; Mehta, Paulette; Szwajcer, David; Joffe, Steven; Majhail, Navneet S

    2014-06-01

    Adolescents and young adults (AYAs, ages 15 to 40 years) with cancer have not experienced survival improvements to the same extent as younger and older patients. We compared changes in survival after myeloablative allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia (ALL) among children (n = 981), AYAs (n = 1218), and older adults (n = 469) who underwent transplantation over 3 time periods: 1990 to 1995, 1996 to 2001, and 2002 to 2007. Five-year survival varied inversely with age group. Survival improved over time in AYAs and paralleled that seen in children; however, overall survival did not change over time for older adults. Survival improvements were primarily related to lower rates of early treatment-related mortality in the most recent era. For all cohorts, relapse rates did not change over time. A subset of 222 AYAs between the ages of 15 and 25 at 46 pediatric or 49 adult centers were also analyzed to describe differences by center type. In this subgroup, there were differences in transplantation practices among pediatric and adult centers, although HCT outcomes did not differ by center type. Survival for AYAs undergoing myeloablative allogeneic HCT for ALL improved at a similar rate as survival for children. PMID:24607554

  11. A Case of Acute Disseminated Encephalomyelitis in a Middle-Aged Adult.

    PubMed

    Mahdi, Nicole; Abdelmalik, Peter A; Curtis, Mark; Bar, Barak

    2015-01-01

    Objectives. Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disorder that is often preceded by infection or recent vaccination. Encephalopathy and focal neurological deficits are usually manifest several weeks after a prodromal illness with rapidly progressive neurologic decline. ADEM is most commonly seen in children and young adults, in which prognosis is favorable, but very few cases have been reported of older adults with ADEM and thus their clinical course is unknown. Methods. Here we present a case of ADEM in a middle-aged adult that recovered well after treatment. Results. A 62-year-old man presented with encephalopathy and rapid neurological decline following a gastrointestinal illness. A brain MRI revealed extensive supratentorial white matter hyperintensities consistent with ADEM and thus he was started on high dose intravenous methylprednisolone. He underwent a brain biopsy showing widespread white matter inflammation secondary to demyelination. At discharge, his neurological exam had significantly improved with continued steroid treatment and four months later, he was able to perform his ADLs. Conclusions. This case of ADEM in a middle-aged adult represents an excellent response to high dose steroid treatment with a remarkable neurological recovery. Thus it behooves one to treat suspected cases of ADEM in an adult patient aggressively, as outcome can be favorable. PMID:26180647

  12. Acute brain slice methods for adult and aging animals: application of targeted patch clampanalysis and optogenetics

    PubMed Central

    Daigle, Tanya L.; Chen, Qian; Feng, Guoping

    2014-01-01

    Summary The development of the living acute brain slice preparation for analyzing synaptic function roughly a half century ago was a pivotal achievement that greatly influenced the landscape of modern neuroscience. Indeed, many neuroscientists regard brain slices as the gold-standard model system for detailed cellular, molecular, and circuitry level analysis and perturbation of neuronal function. A critical limitation of this model system is the difficulty in preparing slices from adult and aging animals, and over the past several decades few substantial methodological improvements have emerged to facilitate patch clamp analysis in the mature adult stage. In this chapter we describe a robust and practical protocol for preparing brain slices from mature adult mice that are suitable for patch clamp analysis. This method reduces swelling and damage in superficial layers of the slices and improves the success rate for targeted patch clamp recordings, including recordings from fluorescently labeled populations in slices derived from transgenic mice. This adult brain slice method is suitable for diverse experimental applications, including both monitoring and manipulating neuronal activity with genetically encoded calcium indicators and optogenetic actuators, respectively. We describe the application of this adult brain slice platform and associated methods for screening kinetic properties of Channelrhodopsin (ChR) variants expressed in genetically-defined neuronal subtypes. PMID:25023312

  13. Acute Pain and Depressive Symptoms: Independent Predictors of Insomnia Symptoms among Adults with Sickle Cell Disease.

    PubMed

    Moscou-Jackson, Gyasi; Allen, Jerilyn; Kozachik, Sharon; Smith, Michael T; Budhathoki, Chakra; Haywood, Carlton

    2016-02-01

    No studies to date have systematically investigated insomnia symptoms among adults with sickle cell disease (SCD). The purpose of this study was to (1) describe the prevalence of insomnia symptoms and (2) identify biopsychosocial predictors in community-dwelling adults with SCD. Cross-sectional analysis of baseline data from 263 African American adults with SCD (aged 18 years or older). Measures included the Insomnia Severity Index (ISI), Center for Epidemiologic Studies in Depression scale, Urban Life Stress Scale, Brief Pain Inventory, and a chronic pain item. SCD genotype was extracted from the medical record. A slight majority (55%) of the sample reported clinically significant insomnia symptomatology (ISI ≥ 10), which suggests that insomnia symptoms are prevalent among community-dwelling African American adults with SCD. While insomnia symptoms were associated with a number of biopsychosocial characteristics, depressive symptoms and acute pain were the only independent predictors. Given the high number of participants reporting clinically significant insomnia symptoms, nurses should screen for insomnia symptoms and explore interventions to promote better sleep among adults with SCD, with an emphasis on recommending treatment for pain and depression. In addition, current pain and depression interventions in this population could add insomnia measures and assess the effect of the intervention on insomnia symptomatology as a secondary outcome. PMID:26673730

  14. In vitro sensitivity of granulo-monocytic progenitors as a new toxicological cell system and endpoint in the ACuteTox Project

    SciTech Connect

    Cerrato, Laura; Valeri, Antonio; Bueren, Juan A.; Albella, Beatriz

    2009-07-15

    The ACuteTox Project (part of the EU 6th Framework Programme) was started up in January 2005. The aim of this project is to develop a simple and robust in vitro strategy for prediction of human acute systemic toxicity, which could replace animal tests used for regulatory purposes. Our group is responsible for the characterization of the effect of the reference chemicals on the hematopoietic tissue. CFU-GM assay based on the culture of human mononuclear cord blood cells has been used to characterize the effects of the selected compounds on the myeloid progenitors. Previous results have shown the relevance of the CFU-GM assay for the prediction of human acute neutropenia after treatment of antitumoral compounds, and this assay has been recently approved by the ECVAM's Scientific Advisory Committee. Among the compounds included in the study there were pharmaceuticals, environmental pollutants and industrial chemicals. Eleven out of 55 chemicals did not show any cytotoxic effect at the maximum concentration tested. The correlation coefficients of CFU-GM IC50, IC70 and IC90 values with human LC50 values (50% lethal concentration calculated from time-related sublethal and lethal human blood concentrations) were 0.4965, 0.5106 and 0.5142 respectively. Although this correlation is not improve respect to classical in vitro basal cytotoxicity tests such as 3T3 Neutral Red Uptake, chemicals which deviate substantially in the correlation with these assays (colchicine, digoxin, 5-Fluorouracil and thallium sulfate) fitted very well in the linear regression analysis of the CFU-GM progenitors. The results shown in the present study indicate that the sensitivity of CFU-GM progenitors correlates better than the sensitivity of HL-60 cells with human LC50 values and could help to refine the predictability for human acute systemic toxicity when a given chemical may affect to the hematopoietic myeloid system.

  15. Acute symptomatic calcific discitis in adults: a case report and review of literature.

    PubMed

    Shah, A; Botchu, R; Grainger, M F; Davies, A M; James, S L

    2015-12-01

    Symptomatic calcific discitis has been reported in the paediatric population but is a rare entity in adults with only eight cases reported in the English literature. We present a case of adult calcific discitis presenting with acute onset back pain. Radiographs and CT demonstrated central T11-T12 disc calcification with diffuse marrow oedema on subsequent MRI. The patient was referred to our spinal oncology unit due to the extensive marrow oedema as a possible underlying primary bone tumour. Review of the CT confirmed an end-plate defect with herniated calcific nucleus pulposus with no underlying bone lesion. Features were in keeping with acute calcific discitis. The patient was treated symptomatically and made an uneventful recovery. We discuss the characteristic imaging features seen on radiograph, CT and MRI and review the current literature. Calcific discitis is a self-limiting pathology requiring symptomatic management only. Radiologists need to be aware of this rare entity as it can occur in adults and may be mistaken for a more sinister pathology such as infective discitis or a bone tumour and lead to further unnecessary imaging or invasive procedures. PMID:26160461

  16. Viral Infection in Adults with Severe Acute Respiratory Infection in Colombia

    PubMed Central

    Remolina, Yuly Andrea; Ulloa, María Mercedes; Vargas, Hernán; Díaz, Liliana; Gómez, Sandra Liliana; Saavedra, Alfredo; Sánchez, Edgar; Cortés, Jorge Alberto

    2015-01-01

    Objectives To identify the viral aetiology in adult patients with severe acute respiratory infection (SARI) admitted to sentinel surveillance institutions in Bogotá in 2012. Design A cross-sectional study was conducted in which microarray molecular techniques for viral identification were used on nasopharyngeal samples of adult patients submitted to the surveillance system, and further descriptions of clinical features and relevant clinical outcomes, such as mortality, need for critical care, use of mechanical ventilation and hospital stay, were obtained. Setting Respiratory infections requiring hospital admission in surveillance centres in Bogotá, Colombia. Participants Ninety-one adult patients with acute respiratory infection (55% were female). Measurements Viral identification, intensive care unit admission, hospital stay, and mortality. Results Viral identification was achieved for 63 patients (69.2%). Comorbidity was frequently identified and mainly involved chronic pulmonary disease or pregnancy. Influenza, Bocavirus and Adenovirus were identified in 30.8%, 28.6% and 18.7% of the cases, respectively. Admission to the intensive care unit occurred in 42.9% of the cases, while mechanical ventilation was required for 36.3%. The average hospital stay was 9.9 days, and mortality was 15.4%. Antibiotics were empirically used in 90.1% of patients. Conclusions The prevalence of viral aetiology of SARI in this study was high, with adverse clinical outcomes, intensive care requirements and high mortality. PMID:26576054

  17. A Phase II Study Of The Farnesyltransferase Inhibitor ZANESTRA (R115777, NSC #702818, IND #58,359) In Complete Remission Following Induction And/Or Consolidation Chemotherapy In Adults With Poor-Risk Acute Myelogenous Leukemia (AML) And High-Risk Myelodysplasia (MDS)

    ClinicalTrials.gov

    2013-01-08

    Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); de Novo Myelodysplastic Syndromes; Secondary Myelodysplastic Syndromes

  18. Accuracy of ultrasonography in the diagnosis of acute appendicitis in adult patients: review of the literature

    PubMed Central

    2013-01-01

    Background Ultrasound is a widely used technique in the diagnosis of acute appendicitis; nevertheless, its utilization still remains controversial. Methods The accuracy of the Ultrasound technique in the diagnosis of acute appendicitis in the adult patient, as shown in the literature, was searched for. Results The gold standard for the diagnosis of appendicitis still remains pathologic confirmation after appendectomy. In the published literature, graded-compression Ultrasound has shown an extremely variable diagnostic accuracy in the diagnosis of acute appendicitis (sensitivity range from 44% to 100%; specificity range from 47% to 99% ). This is due to many reasons, including lack of operator skill, increased bowel gas content, obesity, anatomic variants, and limitations to explore patients with previuos laparotomies. Conclusions Graded-compression Ultrasound still remains our first-line method in patients referred with clinically suspected acute appendicitis: nevertheless, due to variable diagnostic accuracy, individual skill is requested not only to perform a successful exam, but also in order to triage those equivocal cases that, subsequently, will have to undergo assessment by means of Computed Tomography. PMID:23902717

  19. Right sided transmesentric hernia: A rare cause of acute abdomen in adults

    PubMed Central

    Bharatam, Kaundinya Kiran; Kaliyappa, C.; Reddy, Raja Raghavendra

    2014-01-01

    INTRODUCTION Transmesenteric mesocolic hernias are a rare cause of acute abdomen in adults with few reported cases in published literature. PRESENTATION OF CASE We report a rare case of a 30-year-old male with right-sided transmesenteric hernia of ileum due to a congenital mesocolic defect resulting in acute abdomen, presenting as acute abdomen. The hernia was reduced, small bowel inspected for gangrene and mesenteric hernia repaired, following which the patient made a good recovery and was discharged 5 days later. DISCUSSION The insidious onset of transmesenteric herniae and lack of specific radiological or laboratory investigations reaffirms the importance of surgeons maintaining a high index of suspicion for this surgical emergency. CONCLUSION Transmesentric hernia though rare can present as a case of acute abdomen in an emergency. The diagnosis is purely by a CT scan and close monitoring of the patient's general condition in cases of non-specific abdominal pain is essential to identify the rare deteriorating patient for early surgical intervention and optimal outcome. PMID:25437662

  20. Supervised exercises for adults with acute lateral ankle sprain: a randomised controlled trial

    PubMed Central

    van Rijn, Rogier M; van Os, Anton G; Kleinrensink, Gert-Jan; Bernsen, Roos MD; Verhaar, Jan AN; Koes, Bart W; Bierma-Zeinstra, Sita MA

    2007-01-01

    Background During the recovery period after acute ankle sprain, it is unclear whether conventional treatment should be supported by supervised exercise. Aim To evaluate the short- and long-term effectiveness of conventional treatment combined with supervised exercises compared with conventional treatment alone in patients with an acute ankle sprain. Design Randomised controlled clinical trial. Setting A total of 32 Dutch general practices and the hospital emergency department. Method Adults with an acute lateral ankle sprain consulting general practices or the hospital emergency department were allocated to either conventional treatment combined with supervised exercises or conventional treatment alone. Primary outcomes were subjective recovery (0–10 point scale) and the occurrence of a re-sprain. Measurements were carried out at intake, 4 weeks, 8 weeks, 3 months, and 1 year after injury. Data were analysed using intention-to-treat analyses. Results A total of 102 patients were enrolled and randomised to either conventional treatment alone or conventional treatment combined with supervised exercise. There was no significant difference between treatment groups concerning subjective recovery or occurrence of re-sprains after 3 months and 1-year of follow-up. Conclusion Conventional treatment combined with supervised exercises compared to conventional treatment alone during the first year after an acute lateral ankle sprain does not lead to differences in the occurrence of re-sprains or in subjective recovery. PMID:17925136

  1. A Longitudinal Investigation of Posttraumatic Growth in Adult Patients Undergoing Treatment for Acute Leukemia

    PubMed Central

    Danhauer, Suzanne C.; Russell, Gregory B.; Tedeschi, Richard G.; Jesse, Michelle T.; Vishnevsky, Tanya; Daley, Kristin; Carroll, Suzanne; Triplett, Kelli N.; Calhoun, Lawrence G.; Cann, Arnie; Powell, Bayard L.

    2013-01-01

    An acute leukemia diagnosis can be an extremely stressful experience for most patients. Posttraumatic growth (PTG) is positive psychological change experienced following a struggle with highly challenging life circumstances. The current study is the first longitudinal investigation of predictors of PTG and distress in adult acute leukemia patients undergoing induction chemotherapy. Findings suggest that these patients report PTG, and levels of PTG appear to increase over the weeks following leukemia diagnosis and induction chemotherapy. Variables associated with higher total PTG scores over time included greater number of days from baseline, younger age, and greater challenge to core beliefs. Variables associated with higher distress included greater number of days from baseline, greater perceived cancer threat, higher symptom severity, and lower spiritual well-being. Results underscore the critical role that examination of one’s core beliefs may play in the development of PTG over time. PMID:22739660

  2. Hierarchy in Gene Expression is Predictive of Risk, Progression, and Outcome in Adult Acute Myeloid Leukemia

    PubMed Central

    Tripathi, Shubham; Deem, Michael W.

    2015-01-01

    Cancer progresses with a change in the structure of the gene network in normal cells. We define a measure of organizational hierarchy in gene networks of affected cells in adult acute myeloid leukemia (AML) patients. With a retrospective cohort analysis based on the gene expression profiles of 116 acute myeloid leukemia patients, we find that the likelihood of future cancer relapse and the level of clinical risk are directly correlated with the level of organization in the cancer related gene network. We also explore the variation of the level of organization in the gene network with cancer progression. We find that this variation is non-monotonic, which implies the fitness landscape in the evolution of AML cancer cells is nontrivial. We further find that the hierarchy in gene expression at the time of diagnosis may be a useful biomarker in AML prognosis. PMID:25685944

  3. When is acute persistent cough in school-age children and adults whooping cough?

    PubMed Central

    Philipson, Kathryn; Goodyear-Smith, Felicity; Grant, Cameron C; Chong, Angela; Turner, Nikki; Stewart, Joanna

    2013-01-01

    Background Pertussis is a vaccine modified disease in most age groups and hence subtle in its presentation. Current diagnostic approaches require relatively invasive sampling. Aim To determine the incidence of B. pertussis infection among people aged 5–49 years identified in primary care with acute persistent cough using an oral fluid based diagnostic test. Design and setting Active surveillance of acute persistent cough of 2 weeks duration or greater was established in Auckland, New Zealand from May to October 2011. The 15 participating primary care practices provided care for a socioeconomically diverse population. Method Recent B. pertussis infection was determined by measurement of IgG antibodies to pertussis toxin (PT) in an oral fluid sample. An IgG antibody titre to PT of ≥70 arbitrary units defined recent infection. Participants reported symptoms at presentation and kept a cough diary. Results A total of 226 participants were enrolled: 70 (31%) were children (5–16 years) and 156 (69%) were adults (17–49 years). Oral fluid samples were obtained from 225 participants. Ten per cent (23/225) had recent B. pertussis infection including a larger proportion of children than adults (17% versus 7%, P = 0.003). Neither cough duration nor any individual symptom discriminated between those with and without recent B. pertussis infection. Conclusion Pertussis is a frequent cause of acute persistent cough presenting to primary care. Clinical differentiation of pertussis from other causes of acute persistent cough is difficult. An oral fluid based diagnostic test, which is less invasive than other diagnostic approaches, has high acceptability in primary care. PMID:23972198

  4. Emergency department treatment of adults with acute asthma exacerbations: effect on exhaled nitric oxide levels.

    PubMed

    Silverberg, Jonathan I; Rodenas, Mario; Sinert, Richard; Joks, Rauno

    2012-01-01

    Measurement of exhaled nitric oxide levels (eNO) from asthmatic patients is a noninvasive marker of airway inflammation in both adults and children and has been used as an outpatient measure of asthma control. We examined eNO in acute asthma exacerbations and how it is affected by treatment in the emergency department (ED) setting. Both eNO and peak expiratory flow (PEF) rate were measured at arrival and before discharge for adult asthmatic subjects (n = 28) treated for acute exacerbations in the ED at Kings County Hospital Center during spring and fall pollen seasons. Total serum Immunoglobulin E (IgE), peripheral blood leukocyte numbers, and tobacco smoking history were determined. Routine ED treatment included oral prednisone at 60 mg and inhalation of nebulized albuterol and ipratropium. Both PEF (p = 0.0005) and eNO (p < 0.0001) increased after treatment of subjects. Initial eNO was associated with age (p = 0.0004), absolute eosinophil count (p = 0.003), Asthma Control Test (p = 0.004), and Asthma Quality of Life Questionnaire (p = 0.04). Change in pre- versus posttreatment eNO (ΔeNO) was associated with change in PEF (ΔPEF; p < 0.0001). Initial PEF was associated with oxygen saturation (p < 0.0001). ΔPEF was associated with serum IgE levels. ED visit duration was associated with initial PEF (p = 0.0004), ΔeNO (p = 0.004), and number of albuterol treatments (p = 0.001). These associations remained significant in multivariate models that controlled for demographic factors, asthma control, smoking, and measures of inflammation and ventilation. eNO levels increase after ED treatment of acute asthma exacerbations in adults. Improved ventilation may allow for more accurate measurement of NO produced in inflamed airways. PMID:23394510

  5. Acute plastic bowing of the forearm in adults: a report of two cases.

    PubMed

    Tada, K; Ikeda, K; Tsubouchi, H; Tomita, K

    2008-08-01

    We report 2 adult cases where the diagnosis of acute plastic bowing of the forearm was either delayed or missed. In a 21-year-old man, ulnar bowing was missed and fixation was not performed because the patient had no limitation to his range of movement or pain. In a 24-year-old woman, the presentation of bowing in both the ulna and radius was delayed and corrective osteotomy was necessary for restoration of full range of movement. Prompt diagnosis enables manual reposition for easy restoration of full range of movement. PMID:18725680

  6. The role of Clofarabine in the treatment of adults with acute myeloid leukemia.

    PubMed

    Fozza, Claudio

    2015-03-01

    The therapeutic scenario available for adult patients with acute myeloid leukemia (AML) has shown only partial progresses over the last few years. This is especially true for refractory and relapsed AML whose outcome is still extremely disappointing. In this context Clofarabine has offered new promising perspectives within first and second line protocols. This review will firstly describe the initial development in monotherapy, considering then the different potential combination strategies which include both polichemotherapeutic regimens and less conventional approaches with new generation drugs. The potential use of Clofarabine as induction treatment for patients candidate to stem cell transplantation and within conditioning regimens will be finally evaluated. PMID:25457773

  7. Self-management of acute asthma among low-income urban adults.

    PubMed

    George, Maureen; Campbell, Jacquelyn; Rand, Cynthia

    2009-08-01

    One approach to address asthma disparities has been to create evidence-based guidelines to standardize asthma care and education. However, the adoption of these recommendations has been suboptimal among many providers. As a result, low-income minority patients may not be receiving adequate instruction in asthma self-management. In addition, these patients may fail to follow guideline-based recommendations. We conducted 25 interviews to identify the extent to which urban low-income adults have received training in, and implement, self-management protocols for acute asthma. Twenty-five adults (92% female; 76% African American; mean age 39) were enrolled. Only one subject had received asthma self-management training and only 10 (40%) used short-acting beta-(2) agonist-based (SABA) self-management protocols for the early treatment of acute asthma. No subject used a peak flow meter or an asthma action plan. Most (52%) chose to initially treat acute asthma with complementary and alternative medicine (CAM) despite the availability of SABAs. Importantly, 21 (84%) preferred an integrated approach using both conventional and CAM treatments. Four themes associated with acute asthma self-management emerged from the qualitative analysis. The first theme safety reflected subjects' perception that CAM was safer than SABA. Severity addressed the calculation that subjects made in determining if SABA or CAM was indicated based on the degree of symptoms they were experiencing. The third theme speed and strength of the combination described subjects' belief in the superiority of integrating CAM and SABA for acute asthma self-management. The final themesense of identity spoke to the ability of CAM to provide a customized self-management strategy that subjects desired. It is unclear if subjects' greater use of CAM or delays in using SABA-based self-management protocols were functions of inadequate instruction or personal preference. Regardless, delays in, or under use of, conventional

  8. RBP2 Promotes Adult Acute Lymphoblastic Leukemia by Upregulating BCL2

    PubMed Central

    Wang, Xiaoming; Zhou, Minran; Fu, Yue; Sun, Ting; Chen, Jin; Qin, Xuemei; Yu, Yuan; Jia, Jihui; Chen, Chunyan

    2016-01-01

    Despite recent increases in the cure rate of acute lymphoblastic leukemia (ALL), adult ALL remains a high-risk disease that exhibits a high relapse rate. In this study, we found that the histone demethylase retinoblastoma binding protein-2 (RBP2) was overexpressed in both on-going and relapse cases of adult ALL, which revealed that RBP2 overexpression was not only involved in the pathogenesis of ALL but that its overexpression might also be related to relapse of the disease. RBP2 knockdown induced apoptosis and attenuated leukemic cell viability. Our results demonstrated that BCL2 is a novel target of RBP2 and supported the notion of RBP2 being a regulator of BCL2 expression via directly binding to its promoter. As the role of RBP2 in regulating apoptosis was confirmed, RBP2 overexpression and activation of BCL2 might play important roles in ALL development and progression. PMID:27008505

  9. Aetiology of community-acquired, acute gastroenteritis in hospitalised adults: a prospective cohort study

    PubMed Central

    Jansen, Andreas; Stark, Klaus; Kunkel, Jan; Schreier, Eckart; Ignatius, Ralf; Liesenfeld, Oliver; Werber, Dirk; Göbel, Ulf B; Zeitz, Martin; Schneider, Thomas

    2008-01-01

    Background The aetiology of severe gastroenteritis leading to hospitalisation in adults frequently remains unclear. Our objective was to study the causes and characteristics of community-acquired, acute gastroenteritis in adult hospitalized patients to support the clinical management of these patients. Methods From August 2005 to August 2007, we conducted a prospective cohort study among patients ≥18 y hospitalized with community-acquired gastroenteritis in a university hospital in Berlin, Germany. Stool specimens were examined for 26 gastrointestinal pathogens, supplemented by serologic tests for antibodies to Campylobacter spp., Yersinia spp., and Entamoeba histolytica. Patient data on demographics and clinical presentation were recorded and analyzed. Coexisting medical conditions were assessed using the Charlson Comorbidity Index score. Results Of 132 patients presenting with acute community-acquired gastroenteritis, 104 were included in the study. A non-infectious aetiology was diagnosed in 8 patients (8%). In 79 (82%) of the remaining 96 patients at least one microorganism was identified. Campylobacter spp. (35%) was detected most frequently, followed by norovirus (23%), Salmonella spp. (20%), and rotavirus (15%). In 46% of the patients with Campylobacter spp. infection, the diagnosis was made solely by serology. More than one pathogen was found in seventeen (22%) patients. Simultaneous infection was significantly more likely in patients with rotavirus and salmonella infections (RR 3.6; 95% CI: 1.8–7.4; RR 2.5; 95%CI: 1.2–5.5). Length of hospital stay (median: 5.5 days) was independent of the pathogen, but was associated with coexisting medical conditions (OR 4,8; 95%CI:2,0–11,6). Conclusion Known enteric pathogens were detected in 82% of adult patients who were hospitalized with acute gastroenteritis. We found that currently used culture-based methods may miss a substantial proportion of Campylobacter infections, and additional serological testing for

  10. A scoring system for assessing the severity of acute diarrhea of adult patients

    PubMed Central

    Xiao, Hong-li; Ma, Su-xia; Qi, Hai-yu; Li, Xiaoli; Wang, Yan; Yin, Cheng-hong

    2016-01-01

    BACKGROUND: Diarrhea is frequently seen in developed and developing countries, and severe diarrhea is characterized by the high risk of death. Thus, it is very important to assess the severity of diarrhea early. We conducted a multi-center study to identify risk factors for the severity of diarrhea in adult patients and formulate an adult diarrhea state score (ADSS) for out-patient clinicians. METHODS: A total of 219 adult patients with acute diarrhea were divided into two groups: 132 patients with mild diarrhea and 87 with severe diarrhea. Logistic regression was used to determine risk factors for the severity of diarrhea. The risk factors were assessed and an ADSS was formulated. Receiver operating characteristic (ROC) analysis was made to evaluate the diagnostic accuracy of ADSS, and the Kappa test was used to confirm the diagnostic reliability. RESULTS: Five risk factors for evaluating the severity of diarrhea in adults included age (P<0.05), axillary temperature (P<0.01), mean arterial pressure (P<0.01), white blood cell count (WBC; P<0.01), and WBC in stool (P<0.01). The area under the ROC curve for ADSS was 0.958 when the cut off value was 4 (a sensitivity of 0.909; a specificity of 0.874), and the Kappa value was 0.781 (P<0.05). CONCLUSION: The risk factors associated with the pathogenic condition of diarrhea were identified, quantified and formulated into an ADSS, which has high diagnostic accuracy and reliability for the early identification of patients with severe acute diarrhea. PMID:27313808

  11. Dialysis-requiring acute kidney injury among hospitalized adults with documented hepatitis C Virus infection: a nationwide inpatient sample analysis.

    PubMed

    Nadkarni, G N; Patel, A; Simoes, P K; Yacoub, R; Annapureddy, N; Kamat, S; Konstantinidis, I; Perumalswami, P; Branch, A; Coca, S G; Wyatt, C M

    2016-01-01

    Chronic hepatitis C virus (HCV) infection may cause kidney injury, particularly in the setting of cryoglobulinemia or cirrhosis; however, few studies have evaluated the epidemiology of acute kidney injury in patients with HCV. We aimed to describe national temporal trends of incidence and impact of severe acute kidney injury (AKI) requiring renal replacement 'dialysis-requiring AKI' in hospitalized adults with HCV. We extracted our study cohort from the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project using data from 2004 to 2012. We defined HCV and dialysis-requiring acute kidney injury based on previously validated ICD-9-CM codes. We analysed temporal changes in the proportion of hospitalizations complicated by dialysis-requiring AKI and utilized survey multivariable logistic regression models to estimate its impact on in-hospital mortality. We identified a total of 4,603,718 adult hospitalizations with an associated diagnosis of HCV from 2004 to 2012, of which 51,434 (1.12%) were complicated by dialysis-requiring acute kidney injury. The proportion of hospitalizations complicated by dialysis-requiring acute kidney injury increased significantly from 0.86% in 2004 to 1.28% in 2012. In-hospital mortality was significantly higher in hospitalizations complicated by dialysis-requiring acute kidney injury vs those without (27.38% vs 2.95%; adjusted odds ratio: 2.09; 95% confidence interval: 1.74-2.51). The proportion of HCV hospitalizations complicated by dialysis-requiring acute kidney injury increased significantly between 2004 and 2012. Similar to observations in the general population, dialysis-requiring acute kidney injury was associated with a twofold increase in odds of in-hospital mortality in adults with HCV. These results highlight the burden of acute kidney injury in hospitalized adults with HCV infection. PMID:26189719

  12. Acute myocardial ischemia in adults secondary to missed Kawasaki disease in childhood.

    PubMed

    Rizk, Sherif R Y; El Said, Galal; Daniels, Lori B; Burns, Jane C; El Said, Howaida; Sorour, Khaled A; Gharib, Soliman; Gordon, John B

    2015-02-15

    Coronary artery aneurysms that occur in 25% of untreated Kawasaki disease (KD) patients may remain clinically silent for decades and then thrombose resulting in myocardial infarction. Although KD is now the most common cause of acquired heart disease in children in Asia, the United States, and Western Europe, the incidence of KD in Egypt is unknown. We tested the hypothesis that young adults in Egypt presenting with acute myocardial ischemia may have coronary artery lesions because of KD in childhood. We reviewed a total of 580 angiograms of patients ≤40 years presenting with symptoms of myocardial ischemia. Coronary artery aneurysms were noted in 46 patients (7.9%), of whom 9 presented with myocardial infarction. The likelihood of antecedent KD as the cause of the aneurysms was classified as definite (n = 10), probable (n = 29), or equivocal (n = 7). Compared with the definite and probable groups, the equivocal group had more traditional cardiovascular risk factors, smaller sized aneurysms, and fewer coronary arteries affected. In conclusion, in a major metropolitan center in Egypt, 6.7% of adults aged ≤40 years who underwent angiography for evaluation of possible myocardial ischemia had lesions consistent with antecedent KD. Because of the unique therapeutic challenges associated with these lesions, adult cardiologists should be aware that coronary artery aneurysms in young adults may be because of missed KD in childhood. PMID:25555655

  13. Blueprint for Implementing New Processes in Acute Care: Rescuing Adult Patients With Intraosseous Access.

    PubMed

    Chreiman, Kristen M; Kim, Patrick K; Garbovsky, Lyudmila A; Schweickert, William D

    2015-01-01

    The intraosseous (IO) access initiative at an urban university adult level 1 trauma center began from the need for a more expeditious vascular access route to rescue patients in extremis. The goal of this project was a multidisciplinary approach to problem solving to increase access of IO catheters to rescue patients in all care areas. The initiative became a collaborative effort between nursing, physicians, and pharmacy to embark on an acute care endeavor to standardize IO access. This is a descriptive analysis of processes to effectively develop collaborative strategies to navigate hospital systems and successfully implement multilayered initiatives. Administration should empower nurse to advance their practice to include IO for patient rescue. Intraosseous access may expedite resuscitative efforts in patients in extremis who lack venous access or where additional venous access is required for life-saving therapies. Limiting IO dwell time may facilitate timely definitive venous access. Continued education and training by offering IO skill laboratory refreshers and annual e-learning didactic is optimal for maintaining proficiency and knowledge. More research opportunities exist to determine medication safety and efficacy in adult patients in the acute care setting. PMID:26352658

  14. Adult stem cells for acute lung injury: remaining questions and concerns.

    PubMed

    Zhu, Ying-Gang; Hao, Qi; Monsel, Antoine; Feng, Xiao-Mei; Lee, Jae-Woo

    2013-07-01

    Acute lung injury (ALI) or acute respiratory distress syndrome remains a major cause of morbidity and mortality in hospitalized patients. The pathophysiology of ALI involves complex interactions between the inciting event, such as pneumonia, sepsis or aspiration, and the host immune response resulting in lung protein permeability, impaired resolution of pulmonary oedema, an intense inflammatory response in the injured alveolus and hypoxemia. In multiple preclinical studies, adult stem cells have been shown to be therapeutic due to both the ability to mitigate injury and inflammation through paracrine mechanisms and perhaps to regenerate tissue by virtue of their multi-potency. These characteristics have stimulated intensive research efforts to explore the possibility of using stem or progenitor cells for the treatment of lung injury. A variety of stem or progenitor cells have been isolated, characterized and tested experimentally in preclinical animal models of ALI. However, questions remain concerning the optimal dose, route and the adult stem or progenitor cell to use. Here, the current mechanisms underlying the therapeutic effect of stem cells in ALI as well as the questions that will arise as clinical trials for ALI are planned are reviewed. PMID:23578018

  15. An Extremely Rare Coexistence: Acute Appendicitis and Multiple Intussusceptions in an Adult

    PubMed Central

    Ozan, Ebru; Atac, Gokce Kaan

    2016-01-01

    Summary Background Adult intussusception is a rare phenomenon, acute appendicitis accompanying multiple transient intussusceptions are much more uncommon. Satisfaction and quiting imaging studies after finding an intussusception on ultrasound, may lead diagnostic errors. Radiologists should raise their awareness of imaging findings in intussusception and keep in their mind coexistent troubles in the belly. This unique case presents unusual imaging findings of a rare dual abdominal emergency condition, particularly highlighting the value of abdominal computed tomography. Case Report 32-year-old female was admitted to Emergency Department with complaints of epigastric abdominal pain and vomiting. US identified ‘target’ appereance on left paramedian location at umbilical level. Contrast enhanced abdominal CT not only confirmed the enteric intussusception that was demonstrated on previos US, but also showed additional concomitant intussusceptions and inflamed appendix. Conclusions Adult intussusception is a rare phenomenon, multiple transient intussusceptions are even more uncommon. This unique report adds, precious clinical and imaging findings of acute appendicitis coexisting with multiple spontaneously resolving intussusceptions, to the literature. Physicians should be alerted for accompanying multiple abdominal pathologies and use justification essentials to make their decisions about the selection of the appropriate imaging modality. PMID:27354879

  16. Time-lapse imaging of neuroblast migration in acute slices of the adult mouse forebrain.

    PubMed

    Khlghatyan, Jivan; Saghatelyan, Armen

    2012-01-01

    There is a substantial body of evidence indicating that new functional neurons are constitutively generated from an endogenous pool of neural stem cells in restricted areas of the adult mammalian brain. Newborn neuroblasts from the subventricular zone (SVZ) migrate along the rostral migratory stream (RMS) to their final destination in the olfactory bulb (OB). In the RMS, neuroblasts migrate tangentially in chains ensheathed by astrocytic processes using blood vessels as a structural support and a source of molecular factors required for migration. In the OB, neuroblasts detach from the chains and migrate radially into the different bulbar layers where they differentiate into interneurons and integrate into the existing network. In this manuscript we describe the procedure for monitoring cell migration in acute slices of the rodent brain. The use of acute slices allows the assessment of cell migration in the microenvironment that closely resembling to in vivo conditions and in brain regions that are difficult to access for in vivo imaging. In addition, it avoids long culturing condition as in the case of organotypic and cell cultures that may eventually alter the migration properties of the cells. Neuronal precursors in acute slices can be visualized using DIC optics or fluorescent proteins. Viral labeling of neuronal precursors in the SVZ, grafting neuroblasts from reporter mice into the SVZ of wild-type mice, and using transgenic mice that express fluorescent protein in neuroblasts are all suitable methods for visualizing neuroblasts and following their migration. The later method, however, does not allow individual cells to be tracked for long periods of time because of the high density of labeled cells. We used a wide-field fluorescent upright microscope equipped with a CCD camera to achieve a relatively rapid acquisition interval (one image every 15 or 30 sec) to reliably identify the stationary and migratory phases. A precise identification of the duration of

  17. [Epidemiologic, clinical and cytohematologic characteristics of adult acute lymphoblastic leukemia in Tunisia].

    PubMed

    Elloumi, Moez; Hafsia, Raouf; el Omri, Halima; Souissi, Taoufik; Hafsia, Aicha; Ennabli, Souad; Ben Abdeladhim, Abdeladhim

    2002-04-01

    Through a national retrospective study, the authors report the clinical and hematological characteristics of 124 acute lymphoblastic leukemia of the adult diagnosed during 5 years (1993-1997). The national prevalence is of 0.28/100.000 inhabitants/year. The sex-ratio is of 1.3. Sixty six per cent of patients were 16-35 years of age, and only 10% of them were more than 60 years of age. A tumoral syndrome was present at 71% of the cases with peripheral adenopathies in 55%, splenomegaly in 40%, hepatomegaly in 19% and a mediastinal tumor in 18% of the cases. The bone pain were rarely signaled (10%) and neuro-meningeal affection was found in only 3% of cases. There was no testicular lesions. The white blood cells count was less than 30.000/mm3 in 60% whereas an important hyperleucocytosis superior than 100.103/mm3 was observed in 20% of the cases. Anemia and thrombopenia were noted in 94% and 90% of the cases respectively. Acute lymphoblastic leukemia typing by cytological study of Bone marrow according to the Fransh-American-Britain criteria (FAB) had found 43%, 48% and 4% for type 1,2 and 3 respectively. In 5% of the cases the type of the acute lymphoblastic leukemia was not precised (diagnosis based on the Bone biopsy). PMID:12416355

  18. Rare case of intussusception in an adult with acute myeloid leukemia

    PubMed Central

    Law, Man Fai; Wong, Cheuk Kei; Pang, Chun Yin; Chan, Hay Nun; Lai, Ho Kei; Ha, Chung Yin; Ng, Celia; Yeung, Yiu Ming; Yip, Sze Fai

    2015-01-01

    Intussusception is rarely reported in adult patients with acute leukemia. We report a case of intussusception in a 29-year-old woman with acute myeloid leukemia (AML). She developed right lower quadrant pain, fever, and vomiting on day 16 of induction chemotherapy. Physical examination showed tenderness and guarding at the right lower quadrant of the abdomen. Abdominal computed tomography (CT) showed distension of the cecum and ascending colon, which were filled with loops of small bowel, and herniation of the ileocecal valve into the cecum. We proceeded to laparotomy and revealed ileocecal intussusception with the ileocecal valve as the leading point. The terminal ileum was thickened and invaginated into the cecum, which showed gangrenous changes. Right hemicolectomy was performed and microscopic examination of the colonic tissue showed infiltration of leukemic cells. The patient recovered after the operation and was subsequently able to continue treatment for AML. This case demonstrates that the diagnosis of intussusception is difficult because the presenting symptoms can be non-specific, but abdominal CT can be informative for preoperative diagnosis. Resection of the involved bowel is recommended when malignancy is suspected or confirmed. Intussusception should be considered in any leukemia patients presenting with acute abdomen. A high index of clinical suspicion is important for early diagnosis. PMID:25593499

  19. Prevalence of sapovirus infection among infant and adult patients with acute gastroenteritis in Tehran, Iran

    PubMed Central

    Romani, Sara; Azimzadeh, Pedram; Bozorgi, Sajad Majidizadeh; Zali, Narges; Jadali, Farzaneh

    2012-01-01

    Aim This study investigated the prevalence of sapovirus infections in patient with acute gastroenteritis in Tehran, Iran. Background Sapovirus, a member of the family Caliciviridae is one of the major causative agents of viral gastroenteritis affecting both children and adult individuals. There isn't enough data about prevalence and genotypes of sapovirus infection in Tehran, the capital city of Iran. Patients and methods A total of 42 fecal samples were collected from patients with acute gastroenteritis from May to July 2009. RT nested- PCR was performed for screening. To genotype the sapovirus isolates, some positive samples were subjected to phylogenetic analysis by sequencing of fragments of viral capsid gene region. Results Sapovirus was detected in 5 of 42 stool specimens from patients with acute gastroenteritis. Sapovirus detected in this study was clustered into only one distinct genogroup I/2. Sapovirus GI/2 was predominant. Conclusion Our results show that among the studied viruses responsible for this disease, sapovirus was a major viral isolate virus. PMID:24834197

  20. Technique, outcomes, and acute toxicities in adults treated with proton beam craniospinal irradiation

    PubMed Central

    Barney, Christian L.; Brown, Aaron P.; Grosshans, David R.; McAleer, Mary Frances; de Groot, John F.; Puduvalli, Vinay; Tucker, Susan L.; Crawford, Cody N.; Gilbert, Mark R.; Brown, Paul D.; Mahajan, Anita

    2014-01-01

    Background Proton craniospinal irradiation (p-CSI) has been proposed to reduce side effects associated with CSI. We evaluated acute toxicities and preliminary clinical outcomes in a series of adults treated with p-CSI. Methods We reviewed medical records for 50 patients (aged 16–63 y) with malignancies of varying histologies treated consecutively with vertebral body-sparing p-CSI at MD Anderson Cancer Center from 2007 to 2011. Median CSI and total boost doses were 30.6 and 54 Gy. Forty patients received chemotherapy, varying by histology. Median follow-up was 20.1 months (range, 0.3–59). Results Median doses to the thyroid gland, pituitary gland, hypothalamus, and cochleae were 0.003 Gy–relative biological effectiveness (RBE; range, 0.001–8.5), 36.1 Gy-RBE (22.5–53.0), 37.1 Gy-RBE (22.3–54.4), and 33.9 Gy-RBE (22.2–52.4), respectively. Median percent weight loss during CSI was 1.6% (range, 10% weight loss to 14% weight gain). Mild nausea/vomiting was common (grade 1 = 46%, grade 2 = 20%); however, only 5 patients experienced grade ≥2 anorexia (weight loss >5% baseline weight). Median percent baseline white blood cells, hemoglobin, and platelets at nadir were 52% (range, 13%–100%), 97% (65%–112%), and 61% (10%–270%), respectively. Four patients developed grade ≥3 cytopenias. Overall and progression-free survival rates were 96% and 82%, respectively, at 2 years and 84% and 68% at 5 years. Conclusions This large series of patients treated with p-CSI confirms low rates of acute toxicity, consistent with dosimetric models. Vertebral body-sparing p-CSI is feasible and should be considered as a way to reduce acute gastrointestinal and hematologic toxicity in adults requiring CSI. PMID:24311638

  1. Long-Term Outcome of Critically Ill Adult Patients with Acute Epiglottitis

    PubMed Central

    Hernu, Romain; Baudry, Thomas; Bohé, Julien; Piriou, Vincent; Allaouchiche, Bernard; Disant, François; Argaud, Laurent

    2015-01-01

    Background Acute epiglottitis is a potentially life threatening disease, with a growing incidence in the adult population. Its long-term outcome after Intensive Care Unit (ICU) hospitalization has rarely been studied. Methodology and Principal Findings Thirty-four adult patients admitted for acute epiglottitis were included in this retrospective multicentric study. The mean age was 44±12 years (sex ratio: 5.8). Sixteen patients (47%) had a history of smoking while 8 (24%) had no previous medical history. The average time of disease progression before ICU was 2.6±3.6 days. The main reasons for hospitalization were continuous monitoring (17 cases, 50%) and acute respiratory distress (10 cases, 29%). Microbiological documentation could be made in 9 cases (26%), with Streptococcus spp. present in 7 cases (21%). Organ failure at ICU admission occurred in 8 cases (24%). Thirteen patients (38%) required respiratory assistance during ICU stay; 9 (26%) required surgery. Two patients (6%) died following hypoxemic cardiac arrest. Five patients (15%) had sequelae at 1 year. Patients requiring respiratory assistance had a longer duration of symptoms and more frequent anti inflammatory use before ICU admission and sequelae at 1 year (p<0.05 versus non-ventilated patients). After logistic regression analysis, only exposure to anti-inflammatory drugs before admission was independently associated with airway intervention (OR, 4.96; 95% CI, 1.06-23.16). Conclusions and Significance The profile of the cases consisted of young smoking men with little comorbidity. Streptococcus spp. infection represented the main etiology. Outcome was favorable if early respiratory tract protection could be performed in good conditions. Morbidity and sequelae were greater in patients requiring airway intervention. PMID:25945804

  2. Phase II Trial of Oral Aminopterin for Adults and Children with Refractory Acute Leukemia

    PubMed Central

    Cole, Peter D.; Drachtman, Richard A.; Smith, Angela K.; Cate, Sarah; Larson, Richard A.; Hawkins, Douglas S.; Holcenberg, John; Kelly, Kara; Kamen, Barton A.

    2010-01-01

    Purpose To determine the antileukemic activity of weekly oral aminopterin in patients with refractory acute leukemia; to describe the pharmacodynamic properties of aminopterin; and to contrast the intracellular metabolism of aminopterin and methotrexate by patients’ blasts in vitro. Experimental Design Forty-six patients were enrolled in three strata: children with acute lymphoblastic leukemia (ALL), adults with ALL, and patients with acute myeloid leukemia (AML).Aminopterin was given weekly, in two doses of 2mg/m2, 12 hours apart. Limited sampling pharmacokinetic analysis was done during the first week of therapy. Accumulation of [3H]aminopterin and [3H]methotrexate by leukemic blasts was studied in vitro. Results Six of 22 children with ALL (27%; 95% confidence interval, 8–47%) had clinically significant responses. None of those with AML and only two of 11 adults with ALL had responses meeting protocol definitions, although peripheral blast counts tended to decrease with therapy in all groups. Mucosal toxicity was minimal, even with limited use of leucovorin rescue. Complete bioavailability of aminopterin was confirmed, with a mean area under the curve of 0.52 ± 0.03 µmol hour/L after oral dosing. No relationship between aminopterin pharmacokinetics and response was seen. In vitro, aminopterin showed more consistent metabolism by leukemic blasts to polyglutamates than methotrexate. Lineage-specific differences in the pattern of intracellular antifolylpolyglutamates were observed. Conclusions Weekly oral aminopterin has significant activity among children with refractory ALL. With greater cellular accumulation and metabolism, more reliable bioavailability than methotrexate, and tolerable toxicity at this dose and schedule, aminopterin deserves further study as a potent alternative to methotrexate. PMID:16299240

  3. Proton Beam Craniospinal Irradiation Reduces Acute Toxicity for Adults With Medulloblastoma

    SciTech Connect

    Brown, Aaron P.; Barney, Christian L.; Grosshans, David R.; McAleer, Mary Frances; Groot, John F. de; Puduvalli, Vinay K.; Tucker, Susan L.; Crawford, Cody N.; Khan, Meena; Khatua, Soumen; Gilbert, Mark R.; Brown, Paul D.; Mahajan, Anita

    2013-06-01

    Purpose: Efficacy and acute toxicity of proton craniospinal irradiation (p-CSI) were compared with conventional photon CSI (x-CSI) for adults with medulloblastoma. Methods and Materials: Forty adult medulloblastoma patients treated with x-CSI (n=21) or p-CSI (n=19) at the University of Texas MD Anderson Cancer Center from 2003 to 2011 were retrospectively reviewed. Median CSI and total doses were 30.6 and 54 Gy, respectively. The median follow-up was 57 months (range 4-103) for x-CSI patients and 26 months (range 11-63) for p-CSI. Results: p-CSI patients lost less weight than x-CSI patients (1.2% vs 5.8%; P=.004), and less p-CSI patients had >5% weight loss compared with x-CSI (16% vs 64%; P=.004). p-CSI patients experienced less grade 2 nausea and vomiting compared with x-CSI (26% vs 71%; P=.004). Patients treated with x-CSI were more likely to have medical management of esophagitis than p-CSI patients (57% vs 5%, P<.001). p-CSI patients had a smaller reduction in peripheral white blood cells, hemoglobin, and platelets compared with x-CSI (white blood cells 46% vs 55%, P=.04; hemoglobin 88% vs 97%, P=.009; platelets 48% vs 65%, P=.05). Mean vertebral doses were significantly associated with reductions in blood counts. Conclusions: This report is the first analysis of clinical outcomes for adult medulloblastoma patients treated with p-CSI. Patients treated with p-CSI experienced less treatment-related morbidity including fewer acute gastrointestinal and hematologic toxicities.

  4. Prognostic impact of persistent cytogenetic abnormalities at complete remission in adult patients with acute lymphoblastic leukemia.

    PubMed

    Short, Nicholas J; Kantarjian, Hagop M; Jabbour, Elias J; O'Brien, Susan M; Faderl, Stefan; Burger, Jan A; Garris, Rebecca; Qiao, Wei; Huang, Xuelin; Jain, Nitin; Konopleva, Marina; Kadia, Tapan M; Daver, Naval; Borthakur, Gautam; Cortes, Jorge E; Ravandi, Farhad

    2016-06-01

    In acute myelogenous leukemia, the persistent detection of abnormal cytogenetics at complete remission (ACCR) is associated with inferior outcomes. However, the prognostic significance of ACCR in adult patients with acute lymphoblastic leukemia (ALL) is unknown. We evaluated 272 adult patients with ALL and abnormal cytogenetics at baseline who were treated with frontline induction chemotherapy, achieved complete remission (CR) and had cytogenetic analysis performed at the time of CR. ACCR was observed in 26 patients (9.6%). Median relapse-free survival was 22 months (95% CI, 12 months to not reached) for patients with ACCR vs. 48 months (range, 30-125 months) in patients with normal cytogenetics at CR (NCCR; P = 0.31). Median overall survival also did not differ significantly between the ACCR (99 months [range, 17 months to not reached]) and NCCR groups (67 months [range, 47 months to not reached], P = 0.86). The specificity of ACCR for minimal residual disease (MRD) positivity by multi-parameter flow cytometry (MFC) was 43%, and there was overall poor correlation between these two methods for the detection of residual disease. When patients were stratified by MRD status, the presence or absence of persistent cytogenetic abnormalities at CR did not add additional prognostic information. This study suggests that there is poor association between MRD assessment by MFC and the presence or absence of cytogenetic abnormalities at CR in adult patients with ALL. ACCR was not associated with adverse outcomes in ALL and did not add additional prognostic information when MRD status by MFC was known. PMID:26800008

  5. Distribution of granulocyte-monocyte colony-stimulating factor and its receptor α-subunit in the adult human brain with specific reference to Alzheimer's disease.

    PubMed

    Ridwan, Sami; Bauer, Henrike; Frauenknecht, Katrin; von Pein, Harald; Sommer, Clemens J

    2012-11-01

    Granulocyte-monocyte colony-stimulating factor (GM-CSF) is a member of the hematopoietic growth factor family, promoting proliferation and differentiation of hematopoietic progenitor cells of the myeloid lineage. In recent years, GM-CSF has also proved to be an important neurotrophic factor in the central nervous system (CNS) via binding to the GM-CSF receptor (GM-CSF R). Furthermore, studies on rodent CNS revealed a wide distribution of both the major binding α-subunit of the GM-CSF R (GM-CSF Rα) and its ligand. Since respective data on the expression pattern of these two molecules are still lacking, the present study has been designed to systematically analyze the protein expression of GM-CSF and GM-CSF Rα in the human brain, with particular emphasis on their regulation in Alzheimer's disease (AD). One major finding is that both GM-CSF and GM-CSF Rα were ubiquitously but not uniformly expressed in neurons throughout the CNS. Protein expression of GM-CSF and GM-CSF Rα was not restricted to neurons but also detectable in astrocytes, ependymal cells and choroid plexus cells. Interestingly, distribution and intensity of immunohistochemical staining for GM-CSF did not differ among AD brains and age-matched controls. Concerning GM-CSF Rα, a marked reduction of protein expression was predominantly detected in the hippocampus although a slight reduction was also found in various cortical regions, thalamic nuclei and some brainstem nuclei. Since the hippocampus is one of the target regions of neurodegenerative changes in AD, reduction of GM-CSF Rα, with consecutive downregulation of GM-CSF signaling, may contribute to in the progressive course of neurodegeneration in AD. PMID:22430742

  6. Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia.

    PubMed

    Dhédin, Nathalie; Huynh, Anne; Maury, Sébastien; Tabrizi, Reza; Beldjord, Kheira; Asnafi, Vahid; Thomas, Xavier; Chevallier, Patrice; Nguyen, Stéphanie; Coiteux, Valérie; Bourhis, Jean-Henri; Hichri, Yosr; Escoffre-Barbe, Martine; Reman, Oumedaly; Graux, Carlos; Chalandon, Yves; Blaise, Didier; Schanz, Urs; Lhéritier, Véronique; Cahn, Jean-Yves; Dombret, Hervé; Ifrah, Norbert

    2015-04-16

    Because a pediatric-inspired Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) protocol yielded a markedly improved outcome in adults with Philadelphia chromosome-negative ALL, we aimed to reassess the role of allogeneic stem cell transplantation (SCT) in patients treated in the GRAALL-2003 and GRAALL-2005 trials. In all, 522 patients age 15 to 55 years old and presenting with at least 1 conventional high-risk factor were candidates for SCT in first complete remission. Among these, 282 (54%) received a transplant in first complete remission. At 3 years, posttransplant cumulative incidences of relapse, nonrelapse mortality, and relapse-free survival (RFS) were estimated at 19.5%, 15.5%, and 64.7%, respectively. Time-dependent analysis did not reveal a significant difference in RFS between SCT and no-SCT cohorts. However, SCT was associated with longer RFS in patients with postinduction minimal residual disease (MRD) ≥10(-3) (hazard ratio, 0.40) but not in good MRD responders. In B-cell precursor ALL, SCT also benefitted patients with focal IKZF1 gene deletion (hazard ratio, 0.42). This article shows that poor early MRD response, in contrast to conventional ALL risk factors, is an excellent tool to identify patients who may benefit from allogeneic SCT in the context of intensified adult ALL therapy. Trial GRAALL-2003 was registered at www.clinicaltrials.gov as #NCT00222027; GRAALL-2005 was registered as #NCT00327678. PMID:25587040

  7. Best Practices in Adolescent and Young Adult Patients with Acute Lymphoblastic Leukemia: A Focus on Asparaginase

    PubMed Central

    Boissel, Nicolas

    2015-01-01

    The inclusion of asparaginase in chemotherapy regimens to treat acute lymphoblastic leukemia (ALL) has had a positive impact on survival in pediatric patients. Historically, asparaginase has been excluded from most treatment protocols for adolescent and young adult (AYA) patients because of perceived toxicity in this population, and this is believed to have contributed to poorer outcomes in these patients. However, retrospective analyses over the past 12 years have shown that 2-, 5-, and 7-year overall survival of AYA patients is significantly improved with pediatric versus adult protocols. The addition of asparaginase to adult protocols yielded high rates of first remission and improved survival. However, long-term survival remains lower compared with what has been seen in pediatrics. The notion that asparaginase is poorly tolerated by AYA patients has been challenged in multiple studies. In some, but not all, studies, the incidences of hepatic and pancreatic toxicities were higher in AYA patients, whereas the rates of hypersensitivity reactions did not appear to differ with age. There is an increased risk of venous thromboembolic events, and management with anti-coagulation therapy is recommended. Overall, the risk of therapy-related mortality is low. Together, this suggests that high-intensity pediatric protocols offer an effective and tolerable approach to treating ALL in the AYA population. PMID:26421220

  8. Novel management options for adult patients with progressive acute lymphoblastic leukemia: introduction.

    PubMed

    Wang, Eunice S

    2015-06-01

    Acute lymphoblastic leukemia (ALL) is a heterogeneous hematologic malignancy characterized by highly proliferative immature lymphoid cells in the bone marrow and peripheral blood. In adults, ALL accounts for approximately 20% of all adult leukemias. ALL carries a poor prognosis in adults. The 5-year overall survival is 24% in patients ages 40 to 59 years and 18% in patients ages 60 to 69 years. ALL can be grouped into different categories according to its cell lineage (B cell or T cell), the presence or absence of the Philadelphia chromosome, and various cytogenetic and molecular classifications. A main goal of treatment is to allow the patient to achieve a complete remission and to consolidate this remission with either a maintenance regimen or an allogeneic stem cell transplant. Although the overall rate of complete remission following frontline therapy for newly diagnosed ALL is high, the majority of patients experience a disease relapse. In general, the duration of initial complete remission impacts the patient’s prognosis and response to further therapies. Subsequent treatments must balance the goal of achieving a remission with the need for the patient to maintain or improve quality of life. Recently approved agents, such as blinatumomab and vincristine sulfate liposome injection, offer the promise of a second remission that can serve as a bridge to allogeneic stem cell transplant while still maintaining quality of life. A novel approach using adoptive cellular immunotherapy with chimeric antigen receptor (CAR) T cells is associated with extremely robust responses. PMID:26431322

  9. Comparison of the responses of children and adults to acute ozone exposure

    SciTech Connect

    McDonnell, W.F.; Chapman, R.S.; Horstman, D.H.; Leigh, M.W.; Salaam, S.A.

    1986-07-01

    The purpose of the paper is to compare the results of two studies in which the respiratory responses of children and adults to acute ozone (O/sub 3/) exposure were measured. Forty-two 18-30 year old males were exposed for 2.5 hours in a controlled environmental chamber to either 0.0 or 0.12 ppm O3 while performing intermittent heavy exercise. Twenty-two 8-11 year old males were exposed in a similar manner to both air and 0.12 ppm O3. Measures of respiratory symptoms and function were made before and after exposure. Adults experienced an increase in the symptom cough and decrements in forced vital capacity and some measures of forced expiratory flow. Children experienced similar decrements in pulmonary function, but had no increase in symptoms. The authors concluded that as measured by pulmonary function children appear to be no more responsive to O3 exposure than are adults and may experience fewer symptoms.

  10. Combined Detection of Serum IL-10, IL-17, and CXCL10 Predicts Acute Rejection Following Adult Liver Transplantation

    PubMed Central

    Kim, Nayoung; Yoon, Young-In; Yoo, Hyun Ju; Tak, Eunyoung; Ahn, Chul-Soo; Song, Gi-Won; Lee, Sung-Gyu; Hwang, Shin

    2016-01-01

    Discovery of non-invasive diagnostic and predictive biomarkers for acute rejection in liver transplant patients would help to ensure the preservation of liver function in the graft, eventually contributing to improved graft and patient survival. We evaluated selected cytokines and chemokines in the sera from liver transplant patients as potential biomarkers for acute rejection, and found that the combined detection of IL-10, IL-17, and CXCL10 at 1-2 weeks post-operation could predict acute rejection following adult liver transplantation with 97% specificity and 94% sensitivity. PMID:27498551

  11. Studying Biomarkers in Samples From Younger Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-05-17

    Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies; Childhood Acute Myelomonocytic Leukemia (M4)

  12. [Clinical and epidemiologic characteristics of acute diarrhea in adults at a hospital from Cordoba city].

    PubMed

    Polo Friz, H; Toloza, S; Acosta, H; Toloza, C; Unsain, F; Marconetto, G; Massanet, P; Canova, S; Celli, J; Abdala, O; Gandini, B

    1997-01-01

    The purpose of this work was to assess the clinical and epidemiologic presentation features of adult acute diarrhea in a general hospital form Córdoba City. All the patients older than 14 years old who assisted to the Hospital Nacional de Clínicas Central Guard for acute diarrhea, during the periods: A (15-12-89 to 15-03-90), B (15-12-93 to 15-03-94) and C (15-12-94 to 15-03-95), were included. 594 patients were studied: 337 female (56.7%) and 257 male, 143 in the period A, 250 in B and 201 in C. The means +/- SD age was 34.6 +/- 13.3 and stool loose per day at admission 7.3 +/- 4.7. Eighty six percent of patients presented liquid consistent stool, 89.6% abdominal pain, 44.7% vomiting and 18.8% bloody stools. The rate of patients who consulted Central Guard referring acute diarrhea increased from period A (2.4%) to B (3.61%); p = 0.002 and decreased form B to C (2.85%); p = 0.01. The mean (+/- SD) days transcurred from the beginning of diarrhea episode till consultation was 3.5 +/- 2.7; 2.7 +/- 2.3 y 2.9 +/- 3.5 in the periods A, B and C respectively, statistically significant difference between A and B, p < 0.01. Thirty six percent, 21.1% and 23.1% of patients presented mucus with their stools in the periods A, B and C (p = 0.01), and high temperature 61.1%, 48.1% and 48.5% respectively (p = 0.04). Twenty seven percent of stools samples cultures became positive in the periods A, 17.6% in B and 11.5% in C, statistically significant difference between A and C; p = 0.008. The results show that in a general hospital from Córdoba City the adult acute diarrhea is a frequent cause of consult. In the last years there were modifications in its clinical an epidemiologic presentation features. PMID:10436614

  13. Functional mitochondrial analysis in acute brain sections from adult rats reveals mitochondrial dysfunction in a rat model of migraine

    PubMed Central

    Fried, Nathan T.; Moffat, Cynthia; Seifert, Erin L.

    2014-01-01

    Mitochondrial dysfunction has been implicated in many neurological disorders that only develop or are much more severe in adults, yet no methodology exists that allows for medium-throughput functional mitochondrial analysis of brain sections from adult animals. We developed a technique for quantifying mitochondrial respiration in acutely isolated adult rat brain sections with the Seahorse XF Analyzer. Evaluating a range of conditions made quantifying mitochondrial function from acutely derived adult brain sections from the cortex, cerebellum, and trigeminal nucleus caudalis possible. Optimization of this technique demonstrated that the ideal section size was 1 mm wide. We found that sectioning brains at physiological temperatures was necessary for consistent metabolic analysis of trigeminal nucleus caudalis sections. Oxygen consumption in these sections was highly coupled to ATP synthesis, had robust spare respiratory capacities, and had limited nonmitochondrial respiration, all indicative of healthy tissue. We demonstrate the effectiveness of this technique by identifying a decreased spare respiratory capacity in the trigeminal nucleus caudalis of a rat model of chronic migraine, a neurological disorder that has been associated with mitochondrial dysfunction. This technique allows for 24 acutely isolated sections from multiple brain regions of a single adult rat to be analyzed simultaneously with four sequential drug treatments, greatly advancing the ability to study mitochondrial physiology in adult neurological disorders. PMID:25252946

  14. The prognostic value of glucocorticoid receptors for adult acute lymphoblastic leukemia

    PubMed Central

    EL-Maghraby, Shereen M.; Kandil, Noha S.; El-Bendary, Waleed R.

    2015-01-01

    Background Therapeutic protocols used in adult acute lymphoblastic leukemia (ALL) are widely variable, and glucocorticoids (GCs) are essential components in ALL treatment. Therefore, this study aimed to evaluate the distribution of prominent glucocorticoid receptor (GR) gene polymorphic variants among adult ALL patients. We also investigated the association between GR messenger ribonucleic acid (mRNA) isoform expressions and the response to chemotherapy. Methods Fifty-two newly diagnosed Philadelphia-negative adult ALL patients and 30 healthy control subjects were enrolled in this study. Genotyping was carried out using a polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis. GR mRNA isoform expressions were assayed by quantitative real-time PCR. Results ALL patients in this study had a median age of 34 years (range, 18-75). GRα expression was associated with complete remission (P=0.03), while GRγ mRNA expression was significantly higher in GC resistant patients (P=0.032) and in non-responders (P=0.019). However, there were no significant associations with GC resistance. The BclI polymorphic variant of the GR gene was the most frequent in adult ALL patients and was not associated with the GC response. Both higher GRα expression and lower GRγ expression were associated with achievement of complete remission, while higher GRγ expression was associated with GC-resistance. Conclusion Our data suggest that the level of GR isoform expression may be useful in predicting GC response, achievement of complete remission, and better event-free survival in ALL patients. However, further evaluation with a larger cohort of patients is warranted. PMID:26770951

  15. Regulation of brain water during acute glucose-induced hyperosmolality in ovine fetuses, lambs, and adults.

    PubMed

    Stonestreet, Barbara S; Petersson, Katherine H; Sadowska, Grazyna B; Patlak, Clifford S

    2004-02-01

    We tested the hypothesis that, during acute glucose-induced hyperosmolality, the brain shrinks less than predicted on the basis of an ideal osmometer and that brain volume regulation is present in fetuses, premature and newborn lambs. Brain water responses to glucose-induced hyperosmolality were measured in the cerebral cortex, cerebellum, and medulla of fetuses at 60% of gestation, premature ventilated lambs at 90% of gestation, newborn lambs, and adult sheep. After exposure of the sheep to increases in osmolality with glucose plus NaCl, brain water and electrolytes were measured. The ideal osmometer is a system in which impermeable solutes do not enter or leave in response to an osmotic stress. In the absence of volume regulation, brain solute remains constant as osmolality changes. The osmotically active solute demonstrated direct linear correlations with plasma osmolality in the cerebral cortex of the fetuses at 60% of gestation (r = 0.72, n = 24, P = 0.0001), premature lambs (r = 0.58, n = 22, P = 0.005), newborn lambs (r = 0.57, n = 24, P = 0.004), and adult sheep (r = 0.70, n = 18, P = 0.001). Similar findings were observed in the cerebellum and medulla. Increases in the quantity of osmotically active solute over the range of plasma osmolalities indicate that volume regulation was present in the brain regions of the fetuses, premature lambs, newborn lambs, and adult sheep during glucose-induced hyperosmolality. We conclude that, during glucose-induced hyperosmolality, the brain shrinks less than predicted on the basis of an ideal osmometer and exhibits volume regulation in fetuses at 60% of gestation, premature lambs, newborn lambs, and adult sheep. PMID:14578364

  16. Prevalence, diagnosis, and disease course of pertussis in adults with acute cough: a prospective, observational study in primary care

    PubMed Central

    Teepe, Jolien; Broekhuizen, Berna DL; Ieven, Margareta; Loens, Katherine; Huygen, Kris; Kretzschmar, Mirjam; de Melker, Hester; Butler, Chris C; Little, Paul; Stuart, Beth; Coenen, Samuel; Goossens, Herman; Verheij, Theo JM

    2015-01-01

    Background Most cases of adult pertussis probably remain undiagnosed. Aim To explore the prevalence, diagnosis, and disease course of acute pertussis infection in adult patients presenting with acute cough. Design and setting Prospective observational study between 2007 and 2010 in primary care in 12 European countries. Method Adults presenting with acute cough (duration of ≤28 days) were included. Bordetella pertussis infection was determined by polymerase chain reaction (from nasopharyngeal flocked swabs and sputa) and by measurement of immunoglobulin G antibodies to pertussis toxin (PT) in venous blood at day 28. An antibody titre to PT of ≥125 IU/ml or PCR positive result in a respiratory sample defined recent infection. Patients completed a symptom diary for 28 days. Results Serum and/or respiratory samples were obtained in 3074 patients. Three per cent (93/3074) had recent B. pertussis infection. Prior cough duration >2 weeks discriminated to some extent between those with and without pertussis (adjusted odds ratio 1.89, 95% confidence interval = 1.17 to 3.07; P = 0.010). Median cough duration after presentation was 17 and 12 days in patients with and without pertussis, respectively (P = 0.008). Patients with pertussis had longer duration of phlegm production (P = 0.010), shortness of breath (P = 0.037), disturbed sleep (P = 0.013) and interference with normal activities or work (P = 0.033) after presentation. Conclusion Pertussis infection plays a limited role among adults presenting with acute cough in primary care, but GPs should acknowledge the possibility of pertussis in uncomplicated lower respiratory tract infection. As in children, pertussis also causes prolonged symptoms in adults. However, pertussis is difficult to discern from other acute cough syndromes in adults at first presentation. PMID:26412843

  17. The Effect of Statins Use on the Risk and Outcome of Acute Bacterial Infections in Adult Patients

    PubMed Central

    Ghorbani, Raheb; Afshar, Reza Kiaee

    2015-01-01

    Background Beyond their lipid-lowering abilities, statins have anti-inflammatory and immunomodulatory properties. In view of these effects, a growing interest has emerged in the possible role of statins, in preventing or decreasing morbidity and mortality from infection. Objectives The aim of this study was to determine whether previous statin use is associated with reduced risk of acute bacterial infections and better outcome of these infections. Materials and Methods In this historical cohort study, consecutive adult patients admitted with acute bacterial infection were enrolled. Control group were selected from adult outpatient and without history of acute bacterial infections. Acute bacterial infections included in this study were; pneumonia, acute pyelonephritis, cellulitis and sepsis with unknown origin. Data about baseline characteristics, co-morbidities and statins use of two groups was obtained. Results Finally 144 patients met inclusion criteria and were enrolled. Same numbers of controls were selected. Two groups were matched based on most baseline characteristics and co-morbidities. The patients’ categories were as follows: pneumonia 42.3%, acute pyelonephritis 23.6%, cellulitis 16% and sepsis 18%. From all participants 29.9% of patients and 45.8% controls were statin users. There was significant association between previous statin use and reduced risk of acute bacterial infections (Mantel Haenszel Weighted Odds Ratio=0.51, 95% CI: 0.30-0.85, p=0.009). Duration of hospitalization was significantly shorter in statin users (p=0.002). Hospital mortality rate was lower (14.6%) in statins users when compared with non-users (18.8%) with significant difference (p=0.028). Conclusion Prior therapy with statins is associated with considerably reduced onset of acute bacterial infections and better outcome in adult patients. PMID:26676277

  18. Single dose oral tiaprofenic acid for acute postoperative pain in adults

    PubMed Central

    Moore, R Andrew; Derry, Sheena; Moore, Maura; McQuay, Henry J

    2014-01-01

    Background Tiaprofenic acid is a a non-steroidal anti-inflammatory drug (NSAID). It is widely available around the world, with indications for osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, periarticular disorders, and strains and sprains. This review sought to evaluate the efficacy and safety of oral tiaprofenic acid in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties. Objectives To assess the efficacy of single dose oral tiaprofenic acid in acute postoperative pain, and any associated adverse events. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to June 2009. Selection criteria Randomised, double blind, placebo-controlled trials of single dose orally administered tiaprofenic acid in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. We planned to use area under the “pain relief versus time” curve to derive the proportion of participants with tiaprofenic acid experiencing at least 50% pain relief over 4 to 6 hours, using validated equations; to use number needed to treat to benefit (NNT); the proportion of participants using rescue analgesia over a specified time period; time to use of rescue analgesia; information on adverse events and withdrawals. Main results Not one of eleven studies identified by the searches and examined in detail studied oral tiaprofenic acid against placebo in patients with established postoperative pain and therefore no results are available. Authors’ conclusions In the absence of evidence of efficacy for oral tiaprofenic acid in acute postoperative pain, its use in this indication is not justified at present. Because trials clearly

  19. [Acute abdominal pain in the emergency department - a clinical algorithm for adult patients].

    PubMed

    Trentzsch, H; Werner, J; Jauch, K-W

    2011-04-01

    adult patients with acute abdominal pain. PMID:21424993

  20. Adult onset Still's disease accompanied by acute respiratory distress syndrome: A case report

    PubMed Central

    Xi, Xiao-Tu; Wang, Mao-Jie; Huang, Run-Yue; Ding, Bang-Han

    2016-01-01

    Adult onset Still's disease (AOSD) is a systemic inflammatory disorder characterized by rash, leukocytosis, fever and arthralgia/arthritis. The most common pulmonary manifestations associated with AOSD are pulmonary infiltrates and pleural effusion. The present study describes a 40-year-old male with AOSD who developed fever, sore throat and shortness of breath. Difficulty breathing promptly developed, and the patient was diagnosed with acute respiratory distress syndrome (ARDS). The patient did not respond to antibiotics, including imipenem, vancomycin, fluconazole, moxifloxacin, penicillin, doxycycline and meropenem, but was sensitive to glucocorticoid treatment, including methylprednisolone sodium succinate. ARDS accompanied by AOSD has been rarely reported in the literature. In conclusion, in a patient with ARDS who does not respond to antibiotic treatment, the involvement of AOSD should be considered. PMID:27588099

  1. Hierarchy in gene expression is predictive of risk, progression, and outcome in adult acute myeloid leukemia

    NASA Astrophysics Data System (ADS)

    Tripathi, Shubham; Deem, Michael W.

    2015-02-01

    Cancer progresses with a change in the structure of the gene network in normal cells. We define a measure of organizational hierarchy in gene networks of affected cells in adult acute myeloid leukemia (AML) patients. With a retrospective cohort analysis based on the gene expression profiles of 116 AML patients, we find that the likelihood of future cancer relapse and the level of clinical risk are directly correlated with the level of organization in the cancer related gene network. We also explore the variation of the level of organization in the gene network with cancer progression. We find that this variation is non-monotonic, which implies the fitness landscape in the evolution of AML cancer cells is non-trivial. We further find that the hierarchy in gene expression at the time of diagnosis may be a useful biomarker in AML prognosis.

  2. Does aberrant membrane transport contribute to poor outcome in adult acute myeloid leukemia?

    PubMed Central

    Chigaev, Alexandre

    2015-01-01

    Acute myeloid leukemia in adults is a highly heterogeneous disease. Gene expression profiling performed using unsupervised algorithms can be used to distinguish specific groups of patients within a large patient cohort. The identified gene expression signatures can offer insights into underlying physiological mechanisms of disease pathogenesis. Here, the analysis of several related gene expression clusters associated with poor outcome, worst overall survival and highest rates of resistant disease and obtained from the patients at the time of diagnosis or from previously untreated individuals is presented. Surprisingly, these gene clusters appear to be enriched for genes corresponding to proteins involved in transport across membranes (transporters, carriers and channels). Several ideas describing the possible relationship of membrane transport activity and leukemic cell biology, including the “Warburg effect,” the specific role of chloride ion transport, direct “import” of metabolic energy through uptake of creatine phosphate, and modification of the bone marrow niche microenvironment are discussed. PMID:26191006

  3. Monocyte Heterogeneity: Consequences for Monocyte-Derived Immune Cells

    PubMed Central

    de Vries, Teun J.; Everts, Vincent

    2016-01-01

    Blood monocytes are precursors of dendritic cells, macrophages, and osteoclasts. They are a heterogeneous cell population with differences in size, phenotype, and function. Although monocytes maintain several tissue-specific populations of immune cells in homeostasis, their contribution to populations of dendritic cells, macrophages, and osteoclasts is significantly increased in inflammation. Identification of a growing number of functionally different subsets of cells within populations of monocyte-derived immune cells has recently put monocyte heterogeneity into sharp focus. Here, we summarize recent findings in monocyte heterogeneity and their differentiation into dendritic cells, macrophages, and osteoclasts. We also discuss these advances in the context of the formation of functionally different monocyte-derived subsets of dendritic cells, macrophages, and osteoclasts. PMID:27478854

  4. Clinical significance of monocyte heterogeneity.

    PubMed

    Stansfield, Brian K; Ingram, David A

    2015-01-01

    Monocytes are primitive hematopoietic cells that primarily arise from the bone marrow, circulate in the peripheral blood and give rise to differentiated macrophages. Over the past two decades, considerable attention to monocyte diversity and macrophage polarization has provided contextual clues into the role of myelomonocytic derivatives in human disease. Until recently, human monocytes were subdivided based on expression of the surface marker CD16. "Classical" monocytes express surface markers denoted as CD14(++)CD16(-) and account for greater than 70% of total monocyte count, while "non-classical" monocytes express the CD16 antigen with low CD14 expression (CD14(+)CD16(++)). However, recognition of an intermediate population identified as CD14(++)CD16(+) supports the new paradigm that monocytes are a true heterogeneous population and careful identification of specific subpopulations is necessary for understanding monocyte function in human disease. Comparative studies of monocytes in mice have yielded more dichotomous results based on expression of the Ly6C antigen. In this review, we will discuss the use of monocyte subpopulations as biomarkers of human disease and summarize correlative studies in mice that may yield significant insight into the contribution of each subset to disease pathogenesis. PMID:25852821

  5. Pharmacotherapy of Acute Bipolar Depression in Adults: An Evidence Based Approach.

    PubMed

    Muneer, Ather

    2016-05-01

    In the majority of cases of bipolar disorder, manic episodes are usually brief and typically responsive to currently available psychopharmacological agents. In contrast, depressive manifestations are more prevalent and persistent, and can present as major depressive/mixed episodes or residual interepisode symptoms. The depressive phase is often associated with other neuropsychiatric conditions, such as anxiety spectrum disorders, substance use disorders, stressor-related disorders, and eating disorders. It is viewed as a systemic disease with associated ailments such as metabolic syndrome, diabetes mellitus, and cardiovascular disease. There is an increased rate of mortality not only from suicide, but also from concomitant physical illness. This scenario is made worse by the fact that depressive symptoms, which represent the main disease burden, are often refractory to existing psychotropic drugs. As such, there is a pressing need for novel agents that are efficacious in acute depressive exacerbations, and also have applicable value in preventing recurrent episodes. The rationale of the present review is to delineate the pharmacotherapy of the depressive phase of bipolar disorder with medications for which there is evidence in the form of observational, open-label, or double-blind randomized controlled studies. In the treatment of acute bipolar depression in adults, a comprehensive appraisal of the extant literature reveals that among mood stabilizers, the most robust proof of efficacy exists for divalproex sodium; while atypical antipsychotics, which include olanzapine, quetiapine, lurasidone, and cariprazine, are also effective, as demonstrated in controlled trials. PMID:27274384

  6. Potential for a pluripotent adult stem cell treatment for acute radiation sickness

    PubMed Central

    Rodgerson, Denis O; Reidenberg, Bruce E; Harris, Alan G; Pecora, Andrew L

    2012-01-01

    Accidental radiation exposure and the threat of deliberate radiation exposure have been in the news and are a public health concern. Experience with acute radiation sickness has been gathered from atomic blast survivors of Hiroshima and Nagasaki and from civilian nuclear accidents as well as experience gained during the development of radiation therapy for cancer. This paper reviews the medical treatment reports relevant to acute radiation sickness among the survivors of atomic weapons at Hiroshima and Nagasaki, among the victims of Chernobyl, and the two cases described so far from the Fukushima Dai-Ichi disaster. The data supporting the use of hematopoietic stem cell transplantation and the new efforts to expand stem cell populations ex vivo for infusion to treat bone marrow failure are reviewed. Hematopoietic stem cells derived from bone marrow or blood have a broad ability to repair and replace radiation induced damaged blood and immune cell production and may promote blood vessel formation and tissue repair. Additionally, a constituent of bone marrow-derived, adult pluripotent stem cells, very small embryonic like stem cells, are highly resistant to ionizing radiation and appear capable of regenerating radiation damaged tissue including skin, gut and lung. PMID:24520532

  7. Acute inflammation alters adult hippocampal neurogenesis in a multiple sclerosis mouse model.

    PubMed

    Giannakopoulou, A; Grigoriadis, N; Bekiari, C; Lourbopoulos, A; Dori, I; Tsingotjidou, A S; Michaloudi, H; Papadopoulos, G C

    2013-07-01

    Neural precursor cells (NPCs) located in the subgranular zone (SGZ) of the dentate gyrus (DG) give rise to thousands of new cells every day, mainly hippocampal neurons, which are integrated into existing neuronal circuits. Aging and chronic degenerative disorders have been shown to impair hippocampal neurogenesis, but the consequence of inflammation is somewhat controversial. The present study demonstrates that the inflammatory environment prevailing in the brain of experimental autoimmune encephalomyelitis (EAE) mice enhances the proliferation of NPCs in SGZ of the dorsal DG and alters the proportion between radial glial cells and newborn neuroblasts. The injection protocol of the cell cycle marker bromodeoxyuridine and the immunohistochemical techniques that were employed revealed that the proliferation of NPCs is increased approximately twofold in the SGZ of the dorsal DG of EAE mice, at the acute phase of the disease. However, although EAE animals exhibited significant higher percentage of newborn radial-glia-like NPCs, the mean percentage of newborn neuroblasts rather was decreased, indicating that the robust NPCs proliferation is not followed by a proportional production of newborn neurons. Significant positive correlations were detected between the number of proliferating cells in the SGZ and the clinical score or degree of brain inflammation of diseased animals. Finally, enhanced neuroproliferation in the acute phase of EAE was not found to trigger compensatory apoptotic mechanisms. The possible causes of altered neurogenesis observed in this study emphasize the need to understand more precisely the mechanisms regulating adult neurogenesis under both normal and pathological conditions. PMID:23606574

  8. Unrelated donor transplants in adults with Philadelphia-negative acute lymphoblastic leukemia in first complete remission

    PubMed Central

    Marks, David I.; Pérez, Waleska S.; He, Wensheng; Zhang, Mei-Jie; Bishop, Michael R.; Bolwell, Brian J.; Bredeson, Christopher N.; Copelan, Edward A.; Gale, Robert Peter; Gupta, Vikas; Hale, Gregory A.; Isola, Luis M.; Jakubowski, Ann A.; Keating, Armand; Klumpp, Thomas R.; Lazarus, Hillard M.; Liesveld, Jane L.; Maziarz, Richard T.; McCarthy, Philip L.; Sabloff, Mitchell; Schiller, Gary; Sierra, Jorge; Tallman, Martin S.; Waller, Edmund K.; Wiernik, Peter H.

    2008-01-01

    We report the retrospective outcomes of unrelated donor (URD) transplants in 169 patients with acute lymphoblastic leukemia (ALL) in first complete remission (CR1) who received transplants between 1995 and 2004. Median age was 33 years (range, 16-59 years). A total of 50% had a white blood cell count (WBC) more than 30 × 109/L, 18% extramedullary disease, 42% achieved CR more than 8 weeks from diagnosis, 25% had adverse cytogenetics, and 19% had T-cell leukemia. A total of 41% were HLA well-matched, 41% partially matched with their donors, and 18% were HLA-mismatched. At 54-month median follow-up, incidences of acute grade 2-IV, III to IV, and chronic graft-versus-host disease were 50%, 25%, and 43%, respectively. Five-year treatment-related mortality (TRM), relapse, and overall survival were 42%, 20%, and 39%, respectively. In multivariate analyses, TRM was significantly higher with HLA-mismatched donors and T-cell depletion. Relapse risk was higher if the diagnostic WBC was more than 100 × 109/L. Factors associated with poorer survival included WBC more than 100 × 109/L, more than 8 weeks to CR1, cytomegalovirus seropositivity, HLA mismatching, and T-cell depletion. Nearly 40% of adults with ALL in CR1 survive 5 years after URD transplantation. Relapse risks were modest; TRM is the major cause of treatment failure. Selecting closely HLA-matched URD and reducing TRM should improve results. PMID:18398065

  9. A clinical pathologic study of four adult cases of acute mercury inhalation toxicity

    SciTech Connect

    Kanluen, S.; Gottlieb, C.A. )

    1991-01-01

    We report four cases of fatal mercury vapor inhalation, a rare occurrence. The mercury vapor was released at a private home, where one of the occupants was smelting silver from dental amalgam containing an unknown amount of mercury. Within 24 hours of the incident, all occupants began having shortness of breath necessitating hospital admission. The clinical courses are briefly detailed; however, all included rapid deterioration with respiratory failure. Chest roentgenograms in all four cases were consistent with adult respiratory distress syndrome. All patients were treated with dimercaprol, a mercury chelator, but all died, with survival varying from 9 to 23 days postexposure. Autopsies were performed on all four patients. The lungs in all cases were heavy, firm, and airless. Histologic examination revealed severe diffuse alveolar damage, with variable amounts of fibrosis, conforming with acute lung injury in various stages of organization. Additional postmortem findings included acute proximal renal tubular necrosis, vacuolar hepatoxicity, and a spectrum of central nervous system alterations including multifocal ischemic necrosis, gliosis, and vasculitis.

  10. Blinatumomab: Bridging the Gap in Adult Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia.

    PubMed

    Folan, Stephanie A; Rexwinkle, Amber; Autry, Jane; Bryan, Jeffrey C

    2016-08-01

    Adult patients with acute lymphoblastic leukemia who relapse after frontline therapy have extremely poor outcomes despite advances in chemotherapy and hematopoietic stem cell transplantation. Blinatumomab is a first-in-class bispecific T-cell engager that links T cells to tumor cells leading to T-cell activation and tumor cell lysis. In December 2014, the Food and Drug Administration approved blinatumomab for treatment of relapsed or refractory Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia. In a phase II trial, blinatumomab produced response rates of 43%, and 40% of patients achieving a complete remission proceeded to hematopoietic stem cell transplantation. Early use of blinatumomab was complicated with adverse effects, including cytokine release syndrome and neurotoxicity. Management strategies, including dexamethasone premedication and 2-step dose escalation during the first cycle of blinatumomab, have decreased the incidence and severity of these adverse effects. Blinatumomab currently is being studied for other B-cell malignancies and has the potential to benefit many patients with CD19+ malignancies in the future. PMID:27521320

  11. Novel Cryptic Rearrangements in Adult B-Cell Precursor Acute Lymphoblastic Leukemia Involving the MLL Gene.

    PubMed

    Othman, Moneeb A K; Grygalewicz, Beata; Pienkowska-Grela, Barbara; Rincic, Martina; Rittscher, Katharina; Melo, Joana B; Carreira, Isabel M; Meyer, Britta; Marzena, Watek; Liehr, Thomas

    2015-05-01

    MLL (mixed-lineage-leukemia) gene rearrangements are typical for acute leukemia and are associated with an aggressive course of disease, with a worse outcome than comparable case, and thus require intensified treatment. Here we describe a 69-year-old female with adult B cell precursor acute lymphoblastic leukemia (BCP-ALL) with hyperleukocytosis and immunophenotype CD10- and CD19+ with cryptic MLL rearrangements. G-banding at the time of diagnosis showed a normal karyotype: 46,XX. Molecular cytogenetics using multitude multicolor banding (mMCB) revealed a complex rearrangement of the two copies of chromosome 11. However, a locus-specific probe additionally identified that the MLL gene at 11q23.3 was disrupted, and that the 5' region was inserted into the chromosomal sub-band 4q21; thus the aberration involved three chromosomes and five break events. Unfortunately, the patient died six months after the initial diagnosis from serious infections and severe complications. Overall, the present findings confirm that, by far not all MLL aberrations are seen by routine chromosome banding techniques and that fluorescence in situ hybridization (FISH) should be regarded as standard tool to access MLL rearrangements in patients with BCP-ALL. PMID:25699572

  12. Pharmacotherapy of Acute Bipolar Depression in Adults: An Evidence Based Approach

    PubMed Central

    2016-01-01

    In the majority of cases of bipolar disorder, manic episodes are usually brief and typically responsive to currently available psychopharmacological agents. In contrast, depressive manifestations are more prevalent and persistent, and can present as major depressive/mixed episodes or residual interepisode symptoms. The depressive phase is often associated with other neuropsychiatric conditions, such as anxiety spectrum disorders, substance use disorders, stressor-related disorders, and eating disorders. It is viewed as a systemic disease with associated ailments such as metabolic syndrome, diabetes mellitus, and cardiovascular disease. There is an increased rate of mortality not only from suicide, but also from concomitant physical illness. This scenario is made worse by the fact that depressive symptoms, which represent the main disease burden, are often refractory to existing psychotropic drugs. As such, there is a pressing need for novel agents that are efficacious in acute depressive exacerbations, and also have applicable value in preventing recurrent episodes. The rationale of the present review is to delineate the pharmacotherapy of the depressive phase of bipolar disorder with medications for which there is evidence in the form of observational, open-label, or double-blind randomized controlled studies. In the treatment of acute bipolar depression in adults, a comprehensive appraisal of the extant literature reveals that among mood stabilizers, the most robust proof of efficacy exists for divalproex sodium; while atypical antipsychotics, which include olanzapine, quetiapine, lurasidone, and cariprazine, are also effective, as demonstrated in controlled trials. PMID:27274384

  13. Successful cord blood transplantation in an adult acute lymphoblastic leukemia patient with congenital heart disease.

    PubMed

    Kowata, Shugo; Fujishima, Yukiteru; Suzuki, Yuzo; Tsukushi, Yasuhiko; Oyake, Tatsuo; Togawa, Ryou; Oyama, Kotaro; Ikai, Akio; Ito, Shigeki; Ishida, Yoji

    2016-08-01

    Recent advances in surgical corrections and supportive care for congenital heart disease have resulted in increasing numbers of adult survivors who may develop hematological malignancies. Treatments including chemotherapy for such patients may cause serious hemodynamic or cardiac complications, especially in those receiving stem cell transplantation. We present a 29-year-old woman with acute lymphoblastic leukemia and congenital heart disease. She had been diagnosed with pulmonary atresia with an intact ventricular septum at birth, and the anomaly was surgically corrected according to the Fontan technique at age 9 years. Her induction chemotherapy required modifications due to poor cardiac status with Fontan circulation. However, after surgical procedures including total cavopulmonary connection and aortic valve replacement at first complete remission, her cardiac status was significantly improved. Subsequently, she underwent cord blood stem cell transplantation at the third complete remission. She required intensive supportive care for circulatory failure as a pre-engraftment immune reaction and stage III acute graft versus host disease of the gut, but recovered from these complications. She was discharged on day 239, and remained in complete remission at 1-year post-transplantation. PMID:27599417

  14. Persistent Adult Zebrafish Behavioral Deficits Results from Acute Embryonic Exposure to Gold Nanoparticles

    PubMed Central

    Truong, Lisa; Saili, Katerine S.; Miller, John M.; Hutchison, James E.; Tanguay, Robert L.

    2011-01-01

    As the number of products containing nanomaterials increase, human exposure to nanoparticles (NPs) is unavoidable. Presently, few studies focus on the potential long-term consequences of developmental NP exposure. In this study, zebrafish embryos were acutely exposed to three gold NPs that possess functional groups with differing surface charge. Embryos were exposed to 50 μg/mL of 1.5 nm gold nanoparticles (AuNPs) possessing negatively charged 2-mercaptoethanesulfonic acid (MES) or neutral 2-(2-(2-mercaptoethoxy)ethoxy)ethanol (MEEE) ligands or 10 μg/mL of the AuNPs possessing positively charged trimethylammoniumethanethiol (TMAT). Both MES- and TMAT-AuNP exposed embryos exhibited hypo-locomotor activity, while those exposed to MEEE-AuNPs did not. A subset of embryos that were exposed to 1.5 nm MES- and TMAT-AuNPs during development from 6–120 hours post fertilization were raised to adulthood. Behavioral abnormalities and the number of survivors into adulthood were evaluated at 122 days post fertilization. We found that both treatments induced abnormal startle behavior following a tap stimulus. However, the MES-AuNPs exposed group also exhibited abnormal adult behavior in the light and had a lower survivorship into adulthood. This study demonstrates that acute, developmental exposure to 1.5 nm MES- and TMAT- AuNPs, two NPs differing only in the functional group, affects larval behavior, with behavioral effects persisting into adulthood. PMID:21946249

  15. The relationship between basal and acute HPA axis activity and aggressive behavior in adults

    PubMed Central

    Bertsch, Katja; Kruk, Menno R.; Naumann, Ewald

    2010-01-01

    The hypothalamic–pituitary–adrenal (HPA) axis seems to play a major role in the development, elicitation, and enhancement of aggressive behavior in animals. Increasing evidence suggests that this is also true for humans. However, most human research on the role of the HPA axis in aggression has been focusing on highly aggressive children and adolescent clinical samples. Here, we report on a study of the role of basal and acute HPA axis activity in a sample of 20 healthy male and female adults. We used the Taylor Aggression Paradigm to induce and measure aggression. We assessed the cortisol awakening response as a trait measure of basal HPA axis activity. Salivary free cortisol measures for the cortisol awakening response were obtained on three consecutive weekdays immediately following awakening and 30, 45, and 60 min after. Half of the subjects were provoked with the Taylor Aggression Paradigm to behave aggressively; the other half was not provoked. Acute HPA axis activity was measured four times, once before and three times after the induction of aggression. Basal cortisol levels were significantly and negatively related to aggressive behavior in the provoked group and explained 67% of the behavioral variance. Cortisol levels following the induction of aggression were significantly higher in the provoked group when baseline levels were taken into account. The data implicate that the HPA axis is not only relevant to the expression of aggressive behavior in clinical groups, but also to a large extent in healthy ones. PMID:20333417

  16. High incidence of obesity in young adults after treatment of acute lymphoblastic leukemia in childhood.

    PubMed

    Didi, M; Didcock, E; Davies, H A; Ogilvy-Stuart, A L; Wales, J K; Shalet, S M

    1995-07-01

    To determine whether obesity complicated the treatment of childhood acute lymphoblastic leukemia, we studied the body mass index (BMI) of 63 female when and 51 male patients from the time of diagnosis of acute lymphoblastic leukemia to the time when final height was attained. The BMI z score was calculated for each patient at diagnosis, at end of treatment, and at attainment of final height. Obesity at attainment of final height was defined as a BMI greater than the 85th percentile of the normal reference population. At final height 23 of 51 male (45%) and 30 of 63 female patients (47%) were obese. Girls became obese between diagnosis and the end of chemotherapy (p = 0.02), after which they had no further increase, indicating that chemotherapy may have played a role in their obesity. Boys had a progressive and gradual increase in BMI z score through to attainment of final height. Obesity did not appear to be associated with growth hormone insufficiency, disproportionate growth, or abnormal timing of puberty. We conclude that approximately half the survivors of leukemia in childhood become obese young adults. Many of those treated with the more recent regimens studied are still only in their mid or preteen years and should be advised regarding a more active lifestyle and a healthy diet in an attempt to reduce the incidence of obesity. PMID:7608813

  17. Potential Reparative Role of Resident Adult Renal Stem/Progenitor Cells in Acute Kidney Injury

    PubMed Central

    Sallustio, Fabio; Serino, Grazia; Schena, Francesco Paolo

    2015-01-01

    Abstract Human kidney is particularly susceptible to ischemia and toxins with consequential tubular necrosis and activation of inflammatory processes. This process can lead to the acute renal injury, and even if the kidney has a great capacity for regeneration after tubular damage, in several circumstances, the normal renal repair program may not be sufficient to achieve a successful regeneration. Resident adult renal stem/progenitor cells could participate in this repair process and have the potentiality to enhance the renal regenerative mechanism. This could be achieved both directly, by means of their capacity to differentiate and integrate into the renal tissues, and by means of paracrine factors able to induce or improve the renal repair or regeneration. Recent genetic fate-tracing studies indicated that tubular damage is instead repaired by proliferative duplication of epithelial cells, acquiring a transient progenitor phenotype and by fate-restricted clonal cell progeny emerging from different nephron segments. In this review, we discuss about the properties and the reparative characteristics of high regenerative CD133+/CD24+ cells, with a view to a future application of these cells for the treatment of acute renal injury. PMID:26309808

  18. Mechanism for the acute effects of organophosphate pesticides on the adult 5-HT system.

    PubMed

    Judge, Sarah J; Savy, Claire Y; Campbell, Matthew; Dodds, Rebecca; Gomes, Larissa Kruger; Laws, Grace; Watson, Anna; Blain, Peter G; Morris, Christopher M; Gartside, Sarah E

    2016-02-01

    The neurotransmitter serotonin (5-HT) is involved in mood disorder aetiology and it has been reported that (organophosphate) OP exposure affects 5-HT turnover. The aim of this study was to elucidate the mechanism underlying OP effects on the adult 5-HT system. First, acute in vivo administration of the OP diazinon (0, 1.3, 13 or 39 mg/kg i.p.) to male Hooded Lister rats inhibited the activity of the cholinergic enzyme acetylcholinesterase in blood and in the hippocampus, dorsal raphe nucleus (DRN), striatum and prefrontal cortex. Diazinon-induced cholinesterase inhibition was greatest in the DRN, the brain's major source of 5-HT neurones. Second, acute in vivo diazinon exposure (0 or 39 mg/kg i.p.) increased the basal firing rate of DRN neurones measured ex vivo in brain slices. The excitatory responses of DRN neurones to α1-adrenoceptor or AMPA/kainate receptor activation were not affected by in vivo diazinon exposure but the inhibitory response to 5-HT was attenuated, indicating 5-HT1A autoreceptor down-regulation. Finally, direct application of the diazinon metabolite diazinon oxon to naive rat brain slices increased the firing rate of DRN 5-HT neurones, as did chlorpyrifos-oxon, indicating the effect was not unique to diazinon. The oxon-induced augmentation of firing was blocked by the nicotinic acetylcholine receptor antagonist mecamylamine and the AMPA/kainate glutamate receptor antagonist DNQX. Together these data indicate that 1) acute OP exposure inhibits DRN cholinesterase, leading to acetylcholine accumulation, 2) the acetylcholine activates nicotinic receptors on 5-HT neurones and also on glutamatergic neurones, thus releasing glutamate and activating 5-HT neuronal AMPA/kainate receptors 3) the increase in 5-HT neuronal activity, and resulting 5-HT release, may lead to 5-HT1A autoreceptor down-regulation. This mechanism may be involved in the reported increase in risk of developing anxiety and depression following occupational OP exposure. PMID

  19. Feeding acutely stimulates fibrinogen synthesis in healthy young and elderly adults.

    PubMed

    Caso, Giuseppe; Mileva, Izolda; Kelly, Patricia; Ahn, Hongshik; Gelato, Marie C; McNurlan, Margaret A

    2009-11-01

    Fibrinogen is a positive acute-phase protein and its hepatic synthesis is enhanced following inflammation and injury. However, it is not clear whether fibrinogen synthesis is also responsive to oral nutrients and whether the response to a meal may be affected by age. Our aim in this study was to investigate the acute effect of oral feeding on fibrinogen synthesis in both young and elderly men and women. Fibrinogen synthesis was determined in 3 separate occasions from the incorporation of l[(2)H(5)]phenylalanine (43 mg/kg body weight) in 8 young (21-35 y) and 8 elderly (>60 y) participants following the ingestion of water (control), a complete liquid meal (15% protein, 30% fat, and 55% carbohydrate), or only the protein component of the meal. The ingestion of the complete meal enhanced fibrinogen fractional synthesis rates (FSR) by 17 +/- 6% in the young and by 38 +/- 10% in the elderly participants compared with the water meal (P < 0.02). A comparable stimulation of FSR occurred with only the protein component of the meal in both young (29 +/- 7%) and elderly participants (41 +/- 9%) compared with the water meal (P < 0.005). Similar results were obtained when fibrinogen synthesis was expressed as absolute synthesis rates (i.e. mg.kg(-1).d(-1)). The results demonstrate that fibrinogen synthesis is acutely stimulated after ingestion of a meal and that this effect can be reproduced by the protein component of the meal alone, both in young and elderly adults. PMID:19759246

  20. Feeding Acutely Stimulates Fibrinogen Synthesis in Healthy Young and Elderly Adults12

    PubMed Central

    Caso, Giuseppe; Mileva, Izolda; Kelly, Patricia; Ahn, Hongshik; Gelato, Marie C.; McNurlan, Margaret A.

    2009-01-01

    Fibrinogen is a positive acute-phase protein and its hepatic synthesis is enhanced following inflammation and injury. However, it is not clear whether fibrinogen synthesis is also responsive to oral nutrients and whether the response to a meal may be affected by age. Our aim in this study was to investigate the acute effect of oral feeding on fibrinogen synthesis in both young and elderly men and women. Fibrinogen synthesis was determined in 3 separate occasions from the incorporation of l[2H5]phenylalanine (43 mg/kg body weight) in 8 young (21–35 y) and 8 elderly (>60 y) participants following the ingestion of water (control), a complete liquid meal (15% protein, 30% fat, and 55% carbohydrate), or only the protein component of the meal. The ingestion of the complete meal enhanced fibrinogen fractional synthesis rates (FSR) by 17 ± 6% in the young and by 38 ± 10% in the elderly participants compared with the water meal (P < 0.02). A comparable stimulation of FSR occurred with only the protein component of the meal in both young (29 ± 7%) and elderly participants (41 ± 9%) compared with the water meal (P < 0.005). Similar results were obtained when fibrinogen synthesis was expressed as absolute synthesis rates (i.e. mg·kg−1·d−1). The results demonstrate that fibrinogen synthesis is acutely stimulated after ingestion of a meal and that this effect can be reproduced by the protein component of the meal alone, both in young and elderly adults. PMID:19759246

  1. How I treat acute lymphoblastic leukemia in older adolescents and young adults

    PubMed Central

    Curran, Emily

    2015-01-01

    At the intersection between children and older adults, the care of adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) poses unique challenges and issues beyond those faced by other age groups. Although the survival of AYA patients is inferior to younger children, growing evidence suggests that AYA patients have improved outcomes, with disease-free survival rates of 60% to 70%, when treated with pediatric-based approaches. A holistic approach, incorporating a multidisciplinary team, is a key component of successful treatment of these AYA patients. With the appropriate support and management of toxicities during and following treatment, these regimens are well tolerated in the AYA population. Even with the significant progress that has been made during the last decade, patients with persistence of minimal residual disease (MRD) during intensive therapy still have a poor prognosis. With new insights into disease pathogenesis in AYA ALL and the availability of disease-specific kinase inhibitors and novel targeted antibodies, future studies will focus on individualized therapy to eradicate MRD and result in further improvements in survival. This case-based review will discuss the biology, pharmacology, and psychosocial aspects of AYA patients with ALL, highlighting our current approach to the management of these unique patients. PMID:25805810

  2. Central Nervous System Involvement in Adult Acute Lymphoblastic Leukemia: Diagnostic Tools, Prophylaxis, and Therapy

    PubMed Central

    Del Principe, Maria Ilaria; Maurillo, Luca; Buccisano, Francesco; Sconocchia, Giuseppe; Cefalo, Mariagiovanna; De Santis, Giovanna; Di Veroli, Ambra; Ditto, Concetta; Nasso, Daniela; Postorino, Massimiliano; Refrigeri, Marco; Attrotto, Cristina; Del Poeta, Giovanni; Lo-Coco, Francesco; Amadori, Sergio; Venditti, Adriano

    2014-01-01

    In adult patients with acute lymphoblastic leukemia (ALL), Central Nervous System (CNS) involvement is associated with a very poor prognosis. The diagnostic assessment of this condition relies on the use of neuroradiology, conventional cytology (CC) and flow cytometry (FCM). Among these approaches, which is the gold standard it is still a matter of debate. Neuroradiology and CC have a limited sensitivity with a higher rate of false negative results. FCM demonstrated a superior sensitivity over CC, particularly when low levels of CNS infiltrating cells are present. Although prospective studies of a large series of patients are still awaited, a positive finding by FCM appears to anticipate an adverse outcome even if CC shows no infiltration. Current strategies for adult ALL CNS-directed prophylaxis or therapy involve systemic and intrathecal chemotherapy and radiation therapy. An early and frequent intrathecal injection of cytostatic combined with systemic chemotherapy is the most effective strategy to reduce the frequency of CNS involvement. In patients with CNS overt ALL, at diagnosis or upon relapse, allogeneic hematopoietic stem cell transplantation might be considered. This review discusses risk factors, diagnostic techniques for identification of CNS infiltration and modalities of prophylaxis and therapy to manage it. PMID:25408861

  3. Stepping Back and Listening: Staff Experiences of Using a Coaching Approach in an Acute Rehabilitation Ward for Older Adults.

    PubMed

    Gray, Debra; Ross, Kirsty; Prat-Sala, Merce; Kibble, Sharon; Harden, Beverley

    2016-08-01

    Previous research has highlighted that acute care provision can lead to a loss of confidence, control, and independent functioning in older adult patients. In addition, it is recognized that interactions between patients and health care staff are central to the prevention of functional decline in patients. In this study, we aimed to affect the staff-patient relationship by implementing a coaching intervention in an older adult acute care setting. Here, we report on staff experiences of this coaching approach. Data were collected from 16 members of staff via semi-structured interviews, which were analyzed using thematic analysis. Four themes were identified: Putting a Label on It, Stepping Back and Listening, Identifying the Opportunities, and Working as Team. Our findings show that a coaching approach can be successful in getting staff to reconsider their interactions with patients and to focus on strategies that foster the independence and autonomy of older adult patients. PMID:26481943

  4. Effect of prostaglandin I2 analogs on monocyte chemoattractant protein-1 in human monocyte and macrophage.

    PubMed

    Tsai, Ming-Kai; Hsieh, Chong-Chao; Kuo, Hsuan-Fu; Lee, Min-Sheng; Huang, Ming-Yii; Kuo, Chang-Hung; Hung, Chih-Hsing

    2015-08-01

    Chemokines play essential roles during inflammatory responses and in pathogenesis of inflammatory diseases. Monocyte chemotactic protein-1 (MCP-1) is a critical chemokine in the development of atherosclerosis and acute cardiovascular syndromes. MCP-1, by its chemotactic activity, causes diapedesis of monocytes from the lumen to the subendothelial space that leads to atherosclerotic plaque formation. Prostaglandin I2 (PGI2) analogs are used clinically for patients with pulmonary hypertension and have anti-inflammatory effects. However, little is known about the effect of PGI2 analogs on the MCP-1 production in human monocytes and macrophages. We investigated the effects of three conventional (iloprost, beraprost and treprostinil) and one new (ONO-1301) PGI2 analogs, on the expression of MCP-1 expression in human monocytes and macrophages. Human monocyte cell line, THP-1 cell, was treated with PGI2 analogs after LPS stimulation. Supernatants were harvested to measure MCP-1 levels and measured by ELISA. To explore which receptors involved the effects of PGI2 analogs on the expression of MCP-1 expression, IP and EP, PPAR-α and PPAR-γ receptor antagonists were used. Forskolin, a cAMP activator, was used to further confirm the involvement of cAMP on MCP-1 production in human monocytes. Three PGI2 analogs suppressed LPS-induced MCP-1 production in THP-1 cells and THP-1-induced macrophages. Higher concentrations of ONO-1301 also had the suppressive effect. CAY 10449, an IP receptor antagonist, could reverse the effects on MCP-1 production of iloprost on THP-1 cells. Other reported PGI2 receptor antagonists including EP1, EP2, EP4, PPAR-α and PPAR-γ antagonists could not reverse the effect. Forskolin, a cAMP activator, also suppressed MCP-1 production in THP-1 cells. PGI2 analogs suppressed LPS-induced MCP-1 production in human monocytes and macrophages via the IP receptor and cAMP pathway. The new PGI2 analog (ONO-1301) was not better than conventional PGI2 analog in

  5. Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia.

    PubMed

    Beldjord, Kheira; Chevret, Sylvie; Asnafi, Vahid; Huguet, Françoise; Boulland, Marie-Laure; Leguay, Thibaut; Thomas, Xavier; Cayuela, Jean-Michel; Grardel, Nathalie; Chalandon, Yves; Boissel, Nicolas; Schaefer, Beat; Delabesse, Eric; Cavé, Hélène; Chevallier, Patrice; Buzyn, Agnès; Fest, Thierry; Reman, Oumedaly; Vernant, Jean-Paul; Lhéritier, Véronique; Béné, Marie C; Lafage, Marina; Macintyre, Elizabeth; Ifrah, Norbert; Dombret, Hervé

    2014-06-12

    With intensified pediatric-like therapy and genetic disease dissection, the field of adult acute lymphoblastic leukemia (ALL) has evolved recently. In this new context, we aimed to reassess the value of conventional risk factors with regard to new genetic alterations and early response to therapy, as assessed by immunoglobulin/T-cell receptor minimal residual disease (MRD) levels. The study was performed in 423 younger adults with Philadelphia chromosome-negative ALL in first remission (265 B-cell precursor [BCP] and 158 T-cell ALL), with cumulative incidence of relapse (CIR) as the primary end point. In addition to conventional risk factors, the most frequent currently available genetic alterations were included in the analysis. A higher specific hazard of relapse was independently associated with postinduction MRD level ≥10(-4) and unfavorable genetic characteristics (ie, MLL gene rearrangement or focal IKZF1 gene deletion in BCP-ALL and no NOTCH1/FBXW7 mutation and/or N/K-RAS mutation and/or PTEN gene alteration in T-cell ALL). These 2 factors allowed definition of a new risk classification that is strongly associated with higher CIR and shorter relapse-free and overall survival. These results indicate that genetic abnormalities are important predictors of outcome in adult ALL not fully recapitulated by early response to therapy. Patients included in this study were treated in the multicenter GRAALL-2003 and GRAALL-2005 trials. Both trials were registered at http://www.clinicaltrials.gov as #NCT00222027 and #NCT00327678, respectively. PMID:24740809

  6. Disparities in smoking and acute respiratory illnesses among sexual minority young adults.

    PubMed

    Blosnich, John; Jarrett, Traci; Horn, Kimberly

    2010-10-01

    Morbidity and mortality from cigarette smoking remain major public health issues. Particularly, smoking has been associated with increased risk of acute respiratory illnesses (ARIs). Literature indicates that lesbian, gay, and bisexual (i.e., sexual minority) persons smoke more than the general population. Additionally, young adulthood is the second-most prevalent period of smoking uptake. Given this constellation of risk correlates, the authors examined whether sexual minority young adults experience increased odds of ARIs (i.e., strep throat, bronchitis, sinus infection, and asthma). Using cross-sectional data from the Spring 2006 National College Health Assessment, prevalence estimates of smoking were generated among young adult (age range, 18-24 years) lesbian/gay, bisexual, unsure, and heterosexual college students (n = 75,164). Nested logistic regression analyses were used to examine whether smoking status mediated the risk of ARIs among sexual orientation groups. Compared with heterosexual smokers, gay/lesbian smokers were more likely to have had strep throat, and bisexual smokers were more likely to have had sinus infection, asthma, and bronchitis. Whereas smoking mediated the risk of ARI, sexual minorities still showed higher odds of ARIs after adjustment for smoking. Sexual minority young adults may experience respiratory health disparities that may be linked to their higher smoking rates, and their higher rates of smoking lend urgency to the need for cessation interventions. Future studies are needed to explore whether chronic respiratory disease caused by smoking (i.e., lung cancer, COPD, emphysema) disproportionately affect sexual minority populations. PMID:20496074

  7. Hematogones: a sensitive prognostic factor for Chinese adult patients with acute myeloid leukemia

    PubMed Central

    Li, L.; Fu, R.; Zhang, T.; Xie, X.; Liu, J.; Tao, J.; Song, J.; Liu, H.; Zhang, W.; Lu, W.; Shao, Z.

    2016-01-01

    Background Hematogones (hgs) are normal B-lymphocyte precursors that increase in some hematologic diseases. Many studies indicate that hgs might be a favourable prognostic factor. We thus considered it important to determine whether hgs are also a prognostic factor for Chinese adult patients with acute myeloid leukemia (aml) and whether the hg-positive and hg-negative groups show any serologic or phenotypic differences. Methods Chinese adult aml patients (n = 177) who were all initially hg-negative underwent standard chemotherapy and were thereafter divided into hg-positive and hg-negative groups according to hg levels in bone marrow during their first remission. Results The follow-up study confirmed that survival duration (both leukemia-free and overall) was significantly greater in the hg-positive group than in the hg-negative group and was accompanied by a lower relapse rate. A retrospective study of patient characteristics at the time of first diagnosis revealed some differences between the hg-positive and the hg-negative groups, including elevations in white blood cells, lactate dehydrogenase, and β2-microglobulin in the hg-negative group. Retrospective phenotypic analysis revealed a significantly lower proportion of abnormal chromosome karyotype and CD34 expression in hg-positive patients. Finally, we evaluated whether additional intensive chemotherapy after standard chemotherapy could further increase hgs. Conclusions The present work verified the validity of hgs as a prognostic factor for Chinese adult patients with aml. Compared with hg-negative patients, hg-positive patients not only experienced longer survival and a lower relapse rate, but they also had some serologic and phenotypic characteristics that are all considered indicators of better outcome. Additional intensive chemotherapy could further increase the level of hgs, which might imply better clinical results. PMID:27122980

  8. Antioxidant vitamins reduce acute meal-induced memory deficits in adults with type 2 diabetes.

    PubMed

    Chui, Michael Herman; Greenwood, Carol E

    2008-07-01

    Memory impairment is observed in adults with type 2 diabetes mellitus (T2DM), with further acute deficits after meal ingestion. This study explored whether postprandial oxidative stress was a contributor to these meal-induced memory deficits. Sixteen adults with T2DM (mean age, 63.5 +/- 2.1 years) who were not regularly taking high-dose antioxidant supplements were fed a high-fat meal, the same test meal with vitamins C (1000 mg) and E (800 IU) tablets, or water on 3 separate occasions. After meal ingestion, a battery of cognitive tests were administered, which included measures of delayed verbal memory, assessed at 60 and 105 minutes after meal ingestion. Relative to water consumption, the high-fat meal resulted in poorer performance at 105 minutes postingestion on measures of delayed verbal recall (word list and paragraph recall) and working memory (Digit-Span Forward). Coconsumption of antioxidant vitamins and high-fat meal prevented this meal-induced deficit such that performance on these tasks was indistinguishable from that after water intake. At the same time point, a small but significant improvement on the word-naming and color-naming components of Stroop was observed after meal ingestion, relative to water, irrespective of whether antioxidants were consumed, demonstrating the specificity of meal-induced impairments to memory function. Executive function, assessed by Trails Parts A and B, was not influenced by meal or antioxidant ingestion. In adults with T2DM, coconsumption of antioxidant vitamins minimizes meal-induced memory impairment, implicating oxidative stress as a potential contributor to these decrements. PMID:19083441

  9. Effects of acute and chronic administration of fenproporex on DNA damage parameters in young and adult rats.

    PubMed

    Gonçalves, Cinara L; Rezin, Gislaine T; Ferreira, Gabriela K; Jeremias, Isabela C; Cardoso, Mariane R; Valvassori, Samira S; Munhoz, Bruna J P; Borges, Gabriela D; Bristot, Bruno N; Leffa, Daniela D; Andrade, Vanessa M; Quevedo, João; Streck, Emilio L

    2013-08-01

    Obesity is a chronic and multifactorial disease, whose prevalence is increasing in many countries. Pharmaceutical strategies for the treatment of obesity include drugs that regulate food intake, thermogenesis, fat absorption, and fat metabolism. Fenproporex is the second most commonly consumed amphetamine-based anorectic worldwide; this drug is rapidly converted in vivo into amphetamine, which is associated with neurotoxicity. In this context, the present study evaluated DNA damage parameters in the peripheral blood of young and adult rats submitted to an acute administration and chronic administration of fenproporex. In the acute administration, both young and adult rats received a single injection of fenproporex (6.25, 12.5 or 25 mg/kg i.p.) or vehicle. In the chronic administration, both young and adult rats received one daily injection of fenproporex (6.25, 12.5, or 25 mg/kg i.p.) or Tween for 14 days. 2 h after the last injection, the rats were killed by decapitation and their peripheral blood removed for evaluation of DNA damage parameters by alkaline comet assay. Our study showed that acute administration of fenproporex in young and adult rats presented higher levels of damage index and frequency in the DNA. However, chronic administration of fenproporex in young and adult rats did not alter the levels of DNA damage in both parameters of comet assay. The present findings showed that acute administration of fenproporex promoted damage in DNA, in both young and adult rats. Our results are consistent with other reports which showed that other amphetamine-derived drugs also caused DNA damage. We suggest that the activation of an efficient DNA repair mechanism may occur after chronic exposition to fenproporex. Our results are consistent with other reports that showed some amphetamine-derived drugs also caused DNA damage. PMID:23636618

  10. Perspectives for Monocyte/Macrophage-Based Diagnostics of Chronic Inflammation

    PubMed Central

    Kzhyshkowska, Julia; Gudima, Alexandru; Moganti, Kondaiah; Gratchev, Alexei; Orekhov, Alexander

    2016-01-01

    Summary Low-grade chronic inflammation underlies the development of the most dangerous cardiometabolic disorders including type 2 diabetes and its vascular complications. In contrast to acute inflammation induced by bacteria and viruses, chronic inflammation can be driven by abnormal reaction to endogenous factors, including Th2 cytokines, metabolic factors like advanced glycation end products (AGEs), modified lipoproteins, or hyperglycemia. The key innate immune cells that recognize these factors in blood circulation are monocytes. Inflammatory programming of monocytes which migrate into tissues can, in turn, result into generation of tissue macrophages with pathological functions. Therefore, determination of the molecular and functional phenotype of circulating monocytes is a very promising diagnostic tool for the identification of hidden inflammation, which can precede the development of the pathology. Here we propose a new test system for the identification of inflammatory programming of monocytes: surface biomarkers and ex vivo functional system. We summarize the current knowledge about surface biomarkers for monocyte subsets, including CD16, CCR2, CX3CR1, CD64, stabilin-1 and CD36, and their association with inflammatory human disorders. Furthermore, we present the design of an ex vivo monocyte-based test system with minimal set of parameters as a potential diagnostic tool for the identification of personalized inflammatory responses. PMID:27226789

  11. Perspectives for Monocyte/Macrophage-Based Diagnostics of Chronic Inflammation.

    PubMed

    Kzhyshkowska, Julia; Gudima, Alexandru; Moganti, Kondaiah; Gratchev, Alexei; Orekhov, Alexander

    2016-03-01

    Low-grade chronic inflammation underlies the development of the most dangerous cardiometabolic disorders including type 2 diabetes and its vascular complications. In contrast to acute inflammation induced by bacteria and viruses, chronic inflammation can be driven by abnormal reaction to endogenous factors, including Th2 cytokines, metabolic factors like advanced glycation end products (AGEs), modified lipoproteins, or hyperglycemia. The key innate immune cells that recognize these factors in blood circulation are monocytes. Inflammatory programming of monocytes which migrate into tissues can, in turn, result into generation of tissue macrophages with pathological functions. Therefore, determination of the molecular and functional phenotype of circulating monocytes is a very promising diagnostic tool for the identification of hidden inflammation, which can precede the development of the pathology. Here we propose a new test system for the identification of inflammatory programming of monocytes: surface biomarkers and ex vivo functional system. We summarize the current knowledge about surface biomarkers for monocyte subsets, including CD16, CCR2, CX3CR1, CD64, stabilin-1 and CD36, and their association with inflammatory human disorders. Furthermore, we present the design of an ex vivo monocyte-based test system with minimal set of parameters as a potential diagnostic tool for the identification of personalized inflammatory responses. PMID:27226789

  12. Acute and Chronic Effects of Dietary Lactose in Adult Rats Are not Explained by Residual Intestinal Lactase Activity.

    PubMed

    van de Heijning, Bert J M; Kegler, Diane; Schipper, Lidewij; Voogd, Eline; Oosting, Annemarie; van der Beek, Eline M

    2015-07-01

    Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN) Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control). A 50%-75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed. PMID:26184291

  13. Acute and Chronic Effects of Dietary Lactose in Adult Rats Are not Explained by Residual Intestinal Lactase Activity

    PubMed Central

    van de Heijning, Bert J. M.; Kegler, Diane; Schipper, Lidewij; Voogd, Eline; Oosting, Annemarie; van der Beek, Eline M.

    2015-01-01

    Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN) Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control). A 50%–75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed. PMID:26184291

  14. Combination Chemotherapy With or Without Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-09-09

    Adult Acute Lymphoblastic Leukemia in Remission; Adult B Acute Lymphoblastic Leukemia; Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Adult L1 Acute Lymphoblastic Leukemia; Adult L2 Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  15. Acute and chronic administration of gold nanoparticles cause DNA damage in the cerebral cortex of adult rats.

    PubMed

    Cardoso, Eria; Rezin, Gislaine Tezza; Zanoni, Elton Torres; de Souza Notoya, Frederico; Leffa, Daniela Dimer; Damiani, Adriani Paganini; Daumann, Francine; Rodriguez, Juan Carlos Ortiz; Benavides, Roberto; da Silva, Luciano; Andrade, Vanessa M; da Silva Paula, Marcos Marques

    2014-01-01

    The use of gold nanoparticles is increasing in medicine; however, their toxic effects remain to be elucidated. Studies show that gold nanoparticles can cross the blood-brain barrier, as well as accumulate in the brain. Therefore, this study was undertaken to better understand the effects of gold nanoparticles on rat brains. DNA damage parameters were evaluated in the cerebral cortex of adult rats submitted to acute and chronic administration of gold nanoparticles of two different diameters: 10 and 30nm. During acute administration, adult rats received a single intraperitoneal injection of either gold nanoparticles or saline solution. During chronic administration, adult rats received a daily single injection for 28 days of the same gold nanoparticles or saline solution. Twenty-four hours after either single (acute) or last injection (chronic), the rats were euthanized by decapitation, their brains removed, and the cerebral cortices isolated for evaluation of DNA damage parameters. Our study showed that acute administration of gold nanoparticles in adult rats presented higher levels of damage frequency and damage index in their DNA compared to the control group. It was also observed that gold nanoparticles of 30nm presented higher levels of damage frequency and damage index in the DNA compared to the 10nm ones. When comparing the effects of chronic administration of gold nanoparticles of 10 and 30nm, we observed that occurred significant different index and frequency damage, comparing with control group. However, there is no difference between the 10 and 30nm groups in the levels of DNA damage for both parameters of the Comet assay. Results suggest that gold nanoparticles for both sizes cause DNA damage for chronic as well as acute treatments, although a higher damage was observed for the chronic one. PMID:25847268

  16. Risk Factors for Acute Kidney Injury in Older Adults With Critical Illness: A Retrospective Cohort Study

    PubMed Central

    Kane-Gill, Sandra L.; Sileanu, Florentina E.; Murugan, Raghavan; Trietley, Gregory S.; Handler, Steven M.; Kellum, John A.

    2014-01-01

    Background Risk for acute kidney injury (AKI) in older adults has not been systematically evaluated. We sought to delineate the determinants of risk for AKI in older compared to younger adults. Study Design Retrospective analysis of patients hospitalized in July 2000–September 2008. Setting & Participants We identified all adult patients admitted to an intensive care unit (ICU) (n=45,655) in a large tertiary care university hospital system. We excluded patients receiving dialysis or kidney transplant prior to hospital admission, and patients with baseline creatinine ≥ 4 mg/dl, liver transplantation, indeterminate AKI status, or unknown age, leaving 39,938 patients. Predictor We collected data on multiple susceptibilities and exposures including age, sex, race, body mass, comorbid conditions, severity of illness, baseline kidney function, sepsis, and shock. Outcomes We defined AKI according to KDIGO (Kidney Disease: Improving Global Outcomes) criteria. We examined susceptibilities and exposures across age strata for impact on development of AKI. Measurements We calculated area under the receiver operating characteristic curve (AUC) for prediction of AKI across age groups. Results 25,230 patients (63.2%) were aged 55 years or older. Overall 25,120 patients (62.9%) developed AKI (69.2% aged 55 years or older). Examples of risk factors for AKI in the oldest age category (75 years or older) were drugs (vancomycin, aminoglycosides, nonsteroidal anti-inflammatories), history of hypertension (OR, 1.13; 95% CI, 1.02–1.25) and sepsis (OR, 2.12; 95% CI, 1.68–2.67). Fewer variables remained predictive of AKI as age increased and the model for older patients was less predictive (p<0.001). For the age categories 18–54, 55–64, 65–74, and 75 years or older, the AUCs were 0.744 (95% CI, 0.735–0.752), 0.714 (95% CI, 0.702–0.726), 0.706 (95% CI, 0.693–0.718), and 0.673 (95% CI, 0.661–0.685), respectively. Limitations Analysis may not apply to non-ICU patients

  17. Clinical presentation, etiology, and survival in adult acute encephalitis syndrome in rural Central India

    PubMed Central

    Joshi, Rajnish; Mishra, Pradyumna Kumar; Joshi, Deepti; Santhosh, SR; Parida, M.M.; Desikan, Prabha; Gangane, Nitin; Kalantri, S.P.; Reingold, Arthur; Colford, John M.

    2013-01-01

    Background Acute encephalitis syndrome (AES) is a constellation of symptoms that includes fever and altered mental status. Most cases are attributed to viral encephalitis (VE), occurring either in outbreaks or sporadically. We conducted hospital-based surveillance for sporadic adult-AES in rural Central India in order to describe its incidence, spatial and temporal distribution, clinical profile, etiology and predictors of mortality. Methods All consecutive hospital admissions during the study period were screened to identify adult-AES cases and were followed until 30-days of hospitalization. We estimated incidence by administrative sub-division of residence and described the temporal distribution of cases. We performed viral diagnostic studies on cerebrospinal fluid (CSF) samples to determine the etiology of AES. The diagnostic tests included RT-PCR (for enteroviruses, HSV 1 and 2), conventional PCR (for flaviviruses), CSF IgM capture ELISA (for Japanese encephalitis virus, dengue, West Nile virus, Varicella zoster virus, measles, and mumps). We compared demographic and clinical variables across etiologic subtypes and estimated predictors of 30-day mortality. Results A total of 183 AES cases were identified between January and October 2007, representing 2.38% of all admissions. The incidence of adult AES in the administrative subdivisions closest to the hospital was 16 per 100,000. Of the 183 cases, a non-viral etiology was confirmed in 31 (16.9%) and the remaining 152 were considered as VE suspects. Of the VE suspects, we could confirm a viral etiology in 31 cases: 17 (11.2%) enterovirus; 8 (5.2%) flavivirus; 3 (1.9%) Varicella zoster; 1 (0.6%) herpesvirus; and 2 (1.3%) mixed etiology); the etiology remained unknown in remaining 121 (79.6%) cases. 53 (36%) of the AES patients died; the case fatality proportion was similar in patients with a confirmed and unknown viral etiology (45.1 and 33.6% respectively). A requirement for assisted ventilation significantly

  18. Single dose oral ketoprofen and dexketoprofen for acute postoperative pain in adults

    PubMed Central

    Barden, Jodie; Derry, Sheena; McQuay, Henry J; Moore, R Andrew

    2014-01-01

    Background Ketoprofen is a non-selective non-steroidal anti-inflammatory drug (NSAID) used to treat acute and chronic painful conditions. Dexketoprofen is the (S)-enantiomer, which is believed to confer analgesia. Theoretically dexketoprofen is expected to provide equivalent analgesia to ketoprofen at half the dose, with a consequent reduction in gastrointestinal adverse events. Objectives To assess efficacy, duration of action, and associated adverse events of single dose oral ketoprofen and dexketoprofen in acute postoperative pain in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to August 2009. Selection criteria Randomised, double blind, placebo-controlled trials of single dose orally administered ketoprofen and dexketoprofen in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. Main results Fourteen studies compared ketoprofen (968 participants) at mainly 25 mg and 50 mg with placebo (520 participants). Seven studies compared dexketoprofen (681 participants) at mainly 10 mg to 25 mg with placebo (289 participants). Studies were of adequate reporting quality, and participants had pain following dental, orthopaedic, obstetric, gynaecological and general surgery. There was considerable clinical heterogeneity between studies in dental and other types of surgery, particularly bunionectomy, which limited analysis

  19. Acute and chronic caffeine administration increases physical activity in sedentary adults.

    PubMed

    Schrader, Patrick; Panek, Leah M; Temple, Jennifer L

    2013-06-01

    Caffeine is a commonly used stimulant thought to have ergogenic properties. Most studies on the ergogenic effects of caffeine have been conducted in athletes. The purpose of this study was to test the hypothesis that caffeine reduces ratings of perceived exertion and increases liking of physical activity in sedentary adults. Participants completed treadmill walking at 60% to 70% of their maximal heart rate at baseline and for 6 subsequent visits, during which half of the participants were given caffeine (3 mg/kg) and half given placebo in a sports drink vehicle. To investigate the potential synergistic effects of acute and chronic caffeine on self-determined exercise duration, participants were rerandomized to either the same or different condition for the last visit, creating 4 chronic/acute treatment groups (placebo/placebo, placebo/caffeine, caffeine/placebo, caffeine/caffeine). Participants rated how much they liked the activity and perceived exertion at each visit. There was a main effect of time on liking of physical activity, with liking increasing over time and an interaction of sex and caffeine treatment on liking, with liking of activity increasing in female participants treated with caffeine, but not with placebo. There was no effect of caffeine on ratings of perceived exertion. Individuals who received caffeine on the final test day exercised for significantly longer than those who received placebo. These data suggest that repeated exposure to physical activity significantly increases liking of exercise and reduces ratings of perceived exertion and that caffeine does little to further modify these effects. PMID:23746561

  20. Mechanism for the acute effects of organophosphate pesticides on the adult 5-HT system

    PubMed Central

    Judge, Sarah J.; Savy, Claire Y.; Campbell, Matthew; Dodds, Rebecca; Gomes, Larissa Kruger; Laws, Grace; Watson, Anna; Blain, Peter G.; Morris, Christopher M.; Gartside, Sarah E.

    2016-01-01

    The neurotransmitter serotonin (5-HT) is involved in mood disorder aetiology and it has been reported that (organophosphate) OP exposure affects 5-HT turnover. The aim of this study was to elucidate the mechanism underlying OP effects on the adult 5-HT system. First, acute in vivo administration of the OP diazinon (0, 1.3, 13 or 39 mg/kg i.p.) to male Hooded Lister rats inhibited the activity of the cholinergic enzyme acetylcholinesterase in blood and in the hippocampus, dorsal raphe nucleus (DRN), striatum and prefrontal cortex. Diazinon-induced cholinesterase inhibition was greatest in the DRN, the brain's major source of 5-HT neurones. Second, acute in vivo diazinon exposure (0 or 39 mg/kg i.p.) increased the basal firing rate of DRN neurones measured ex vivo in brain slices. The excitatory responses of DRN neurones to α1-adrenoceptor or AMPA/kainate receptor activation were not affected by in vivo diazinon exposure but the inhibitory response to 5-HT was attenuated, indicating 5-HT1A autoreceptor down-regulation. Finally, direct application of the diazinon metabolite diazinon oxon to naive rat brain slices increased the firing rate of DRN 5-HT neurones, as did chlorpyrifos-oxon, indicating the effect was not unique to diazinon. The oxon-induced augmentation of firing was blocked by the nicotinic acetylcholine receptor antagonist mecamylamine and the AMPA/kainate glutamate receptor antagonist DNQX. Together these data indicate that 1) acute OP exposure inhibits DRN cholinesterase, leading to acetylcholine accumulation, 2) the acetylcholine activates nicotinic receptors on 5-HT neurones and also on glutamatergic neurones, thus releasing glutamate and activating 5-HT neuronal AMPA/kainate receptors 3) the increase in 5-HT neuronal activity, and resulting 5-HT release, may lead to 5-HT1A autoreceptor down-regulation. This mechanism may be involved in the reported increase in risk of developing anxiety and depression following occupational OP exposure. PMID

  1. Genetically Modified T-cell Immunotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-08-10

    Adult Acute Myeloid Leukemia in Remission; Donor; Early Relapse of Acute Myeloid Leukemia; Late Relapse of Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  2. Clinical Profiles and Short-Term Outcomes of Acute Disseminated Encephalomyelitis in Adult Chinese Patients

    PubMed Central

    Yang, Hong-Qi; Zhao, Wen-Cong; Yang, Wei-Min; Li, Yong-Li; Sun, Zhi-Kun; Chen, Shuai

    2016-01-01

    Background and Purpose Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disorder that predominantly affects children. Previous studies have mostly involved children in Western developed countries. Methods This study retrospectively reviewed the clinical profiles of ADEM in adult Chinese patients. Results ADEM occurred during summer and autumn in about two-thirds of the 42 included patients. Prior infection was found in five patients and no preimmunization was recorded. The most frequent clinical presentations were alterations in consciousness (79%) and behavior changes (69%), followed by motor deficits (64%) and fever (50%). About one-quarter (26%) of the patients showed positive results for oligoclonal bands, and about half of them exhibited increases in the IgG index and 24-hour IgG synthesis rate. Magnetic resonance imaging showed white- and gray-matter lesions in 83% and 23% of the patients, respectively. Steroids were the main treatment, and full recovery occurred in 62% of the patients, with residual focal neurological deficits recorded in a few patients. After a mean follow-up period of 3.4 years, two patients exhibited recurrence and one patient exhibited a multiphasic course. One patient was diagnosed with multiple sclerosis (MS). Conclusions With the exception of the seasonal distribution pattern and prior vaccine rate, the clinical profiles of ADEM in adult Chinese patients are similar to those in pediatric populations. No specific markers are available for distinguishing ADEM from MS at the initial presentation. Careful clinical evaluations, cerebrospinal fluid measurements, and neuroradiological examinations with long-term follow-up will aid the correct diagnosis of ADEM. PMID:27449911

  3. Optimised z-axis coverage at multidetector-row CT in adults suspected of acute appendicitis

    PubMed Central

    Brassart, N; Winant, C; Tack, D; Gevenois, P A; De Maertelaer, V

    2013-01-01

    Objective: To compare diagnostic performances of two reduced z-axis coverages to full coverage of the abdomen and pelvis for the diagnosis of acute appendicitis and alternative diseases at unenhanced CT. Methods: This study included 152 adults suspected of appendicitis who were enrolled in two ethical committee-approved previous prospective trials. Based on scans covering the entire abdomen and pelvis (set L), two additional sets of images were generated, each with reduced z-axis coverages: (1) from the top of the iliac crests to the pubis (set S) and (2) from the diaphragmatic crus to the pubis (set M). Two readers independently coded the visualisation of the appendix, measured its diameter and proposed a diagnosis (appendicitis or alternative). Final diagnosis was based on surgical findings or clinical follow-up. Fisher exact and McNemar tests and logistic regression were used. Results: 46 patients had a definite diagnosis of appendicitis and 53 of alternative diseases. The frequency of appendix visualisation was lower for set S than set L for both readers (89% and 84% vs 95% and 91% by Readers A and B, respectively; p=0.021 and 0.022). The probability of giving a correct diagnosis was lower for set S (68%) than set L (78%; odds ratio, 0.611; p=0.008) for both readers, without significant difference between sets L and M (77%, p=0.771); z-axis coverage being reduced by 25% for set M. Conclusion: Coverage from diaphragmatic crus to pubis, but not focused on pelvis only, can be recommended in adults suspected of appendicitis. Advances in knowledge: In suspected appendicitis, CT-coverage can be reduced from diaphragmatic crus to pubis. PMID:23690436

  4. Genomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia

    PubMed Central

    2013-01-01

    BACKGROUND Many mutations that contribute to the pathogenesis of acute myeloid leukemia (AML) are undefined. The relationships between patterns of mutations and epigenetic phenotypes are not yet clear. METHODS We analyzed the genomes of 200 clinically annotated adult cases of de novo AML, using either whole-genome sequencing (50 cases) or whole-exome sequencing (150 cases), along with RNA and microRNA sequencing and DNA-methylation analysis. RESULTS AML genomes have fewer mutations than most other adult cancers, with an average of only 13 mutations found in genes. Of these, an average of 5 are in genes that are recurrently mutated in AML. A total of 23 genes were significantly mutated, and another 237 were mutated in two or more samples. Nearly all samples had at least 1 nonsynonymous mutation in one of nine categories of genes that are almost certainly relevant for pathogenesis, including transcription-factor fusions (18% of cases), the gene encoding nucleophosmin (NPM1) (27%), tumor-suppressor genes (16%), DNA-methylation–related genes (44%), signaling genes (59%), chromatin-modifying genes (30%), myeloid transcription-factor genes (22%), cohesin-complex genes (13%), and spliceosome-complex genes (14%). Patterns of cooperation and mutual exclusivity suggested strong biologic relationships among several of the genes and categories. CONCLUSIONS We identified at least one potential driver mutation in nearly all AML samples and found that a complex interplay of genetic events contributes to AML pathogenesis in individual patients. The databases from this study are widely available to serve as a foundation for further investigations of AML pathogenesis, classification, and risk stratification. (Funded by the National Institutes of Health.) PMID:23634996

  5. Vincristine-induced paralytic ileus during induction therapy of treatment protocols for acute lymphoblastic leukemia in adult patients.

    PubMed

    Yasu, Takeo; Ohno, Nobuhiro; Kawamata, Toyotaka; Kurokawa, Yosuke

    2016-06-01

    Vincristine (VCR) is an important drug used in the treatment of acute lymphoblastic leukemia (ALL). VCR-induced neurotoxicity can manifest as peripheral neuropathy, constipation, or paralytic ileus. While there are some case reports describing VCR-induced paralytic ileus (VIPI) in pediatric ALL, there are fewer publication on adult ALL patients. Therefore, we retrospectively investigated VIPI during induction therapy of treatment protocols for ALL in 19 adult patients. The incidence of VIPI was 32%. VIPI was significantly increased in patients receiving concomitant itraconazole (ITCZ) (p = 0.04). We recommend avoidance of the combination of VCR and ITCZ. PMID:27087157

  6. Fibronectin fragments modulate monocyte VLA-5 expression and monocyte migration.

    PubMed

    Trial, J; Baughn, R E; Wygant, J N; McIntyre, B W; Birdsall, H H; Youker, K A; Evans, A; Entman, M L; Rossen, R D

    1999-08-01

    To identify the mechanisms that cause monocyte localization in infarcted myocardium, we studied the impact of ischemia-reperfusion injury on the surface expression and function of the monocyte fibronectin (FN) receptor VLA-5 (alpha(5)beta(1) integrin, CD49e/CD29). Myocardial infarction was associated with the release of FN fragments into cardiac extracellular fluids. Incubating monocytes with postreperfusion cardiac lymph that contained these FN fragments selectively reduced expression of VLA-5, an effect suppressed by specific immunoadsorption of the fragments. Treating monocytes with purified, 120-kDa cell-binding FN fragments (FN120) likewise decreased VLA-5 expression, and did so by inducing a serine proteinase-dependent proteolysis of this beta(1) integrin. We postulated that changes in VLA-5 expression, which were induced by interactions with cell-binding FN fragments, may alter monocyte migration into tissue FN, a prominent component of the cardiac extracellular matrix. Support for this hypothesis came from experiments showing that FN120 treatment significantly reduced both spontaneous and MCP-1-induced monocyte migration on an FN-impregnated collagen matrix. In vivo, it is likely that contact with cell-binding FN fragments also modulates VLA-5/FN adhesive interactions, and this causes monocytes to accumulate at sites where the fragment concentration is sufficient to ensure proteolytic degradation of VLA-5. PMID:10449434

  7. Antigen Presentation by Monocytes and Monocyte-derived Cells

    PubMed Central

    Randolph, Gwendalyn J.; Jakubzick, Claudia; Qu, Chunfeng

    2008-01-01

    Summary Monocytes are circulating mononuclear phagocytes with a fundamental capacity to differentiate into macrophages. This differentiation can, in the presence of the right environmental cues, be re-directed instead to dendritic cells (DCs). Recent advances have been made in understanding the role of monocytes and their derivatives in presenting antigen to drive immune responses, and we review this topic herein. We briefly discuss the heterogeneity of monocytes in the blood and subsequently raise the possibility that one of the major monocyte phenotypes in the blood corresponds with a population of “blood DCs” previously proposed to drive T-independent antibody reactions in the spleen. Then we evaluate the role of monocytes in T-dependent immunity, considering their role in acquiring antigens for presentation prior to exiting the bloodstream and their ability to differentiate into macrophages versus antigen-presenting DCs. Finally, we review recent literature on the role of monocyte-derived cells in cross-presentation and discuss the possibility that monocyte-derived cells participate critically in processing antigen for cross-priming, even if they do not present that antigen to T cells themselves. PMID:18160272

  8. Phase I study of azacitidine and bortezomib in adults with relapsed or refractory acute myeloid leukemia

    PubMed Central

    Walker, Alison R.; Klisovic, Rebecca B.; Garzon, Ramiro; Schaaf, Larry J.; Humphries, Kristina; Devine, Steven M.; Byrd, John C.; Grever, Michael R.; Marcucci, Guido; Blum, William

    2013-01-01

    We previously reported that bortezomib indirectly modulates transcription of DNA methyltransferase 1 (DNMT). We designed a phase I study of azacitidine (a direct DNMT inhibitor) plus bortezomib in acute myeloid leukemia (AML) to determine safety and tolerability. Twenty-three adults with relapsed/refractory AML received azacitidine 75mg/m2 daily on days 1-7. Bortezomib was dose escalated from 0.7mg/m2 on days 2 and 5 to 1.3mg/m2 on days 2, 5, 9, and 12. The target dose was reached without dose limiting toxicities. Infection and/or febrile neutropenia were frequent. Patients received a median of 2 cycles of therapy (range, 1-12+). Five of 23 patients achieved remission including two with morphologic and cytogenetic complete response (CR) and three with CR and incomplete count recovery (CRi). Of CR/CRi responders with cytogenetic abnormalities at baseline, three of four achieved cytogenetic CR. The combination of azacitidine and bortezomib was tolerable and active in this cohort of poor-risk previously-treated AML patients. PMID:23952243

  9. The Effects of Acute Physical Exercise on Memory, Peripheral BDNF, and Cortisol in Young Adults.

    PubMed

    Hötting, Kirsten; Schickert, Nadine; Kaiser, Jochen; Röder, Brigitte; Schmidt-Kassow, Maren

    2016-01-01

    In animals, physical activity has been shown to induce functional and structural changes especially in the hippocampus and to improve memory, probably by upregulating the release of neurotrophic factors. In humans, results on the effect of acute exercise on memory are inconsistent so far. Therefore, the aim of the present study was to assess the effects of a single bout of physical exercise on memory consolidation and the underlying neuroendocrinological mechanisms in young adults. Participants encoded a list of German-Polish vocabulary before exercising for 30 minutes with either high intensity or low intensity or before a relaxing phase. Retention of the vocabulary was assessed 20 minutes after the intervention as well as 24 hours later. Serum BDNF and salivary cortisol were measured at baseline, after learning, and after the intervention. The high-intensity exercise group showed an increase in BDNF and cortisol after exercising compared to baseline. Exercise after learning did not enhance the absolute number of recalled words. Participants of the high-intensity exercise group, however, forgot less vocabulary than the relaxing group 24 hours after learning. There was no robust relationship between memory scores and the increase in BDNF and cortisol, respectively, suggesting that further parameters have to be taken into account to explain the effects of exercise on memory in humans. PMID:27437149

  10. ALERT--a multiprofessional training course in the care of the acutely ill adult patient.

    PubMed

    Smith, Gary B; Osgood, Vicky M; Crane, Sue

    2002-03-01

    The Acute Life-threatening Events--Recognition and Treatment (ALERT) course is a one-day multidisciplinary course originally designed to give newly qualified doctors and nurses greater confidence and ability in the recognition and management of adult patients who have impending or established critical illness. It may also be suitable for many other groups of health service workers. ALERT was developed using principles common to many advanced life support courses and incorporates aspects of clinical governance, multidisciplinary education and interprofessional working. It incorporates pre-course reading, informal and interactive seminars, practical demonstrations and role-play during clinically based scenarios. A novel aspect of ALERT is that participants undertake role interchange during scenarios, thereby facilitating mutual understanding. At all times during the course, participants are encouraged to reflect on their actions and to pay particular attention to detail. The course focuses on those problems that lead ward nurses to call doctors for assistance, e.g. 'the blue patient', 'the hypotensive patient'. Communication skills are covered frequently in the course, during seminars and scenarios, but also as a specific session that covers three aspects--breaking bad news, writing patient notes and interpersonal/interprofessional communication. PMID:11886734

  11. Recurrent DUX4 fusions in B cell acute lymphoblastic leukemia of adolescents and young adults.

    PubMed

    Yasuda, Takahiko; Tsuzuki, Shinobu; Kawazu, Masahito; Hayakawa, Fumihiko; Kojima, Shinya; Ueno, Toshihide; Imoto, Naoto; Kohsaka, Shinji; Kunita, Akiko; Doi, Koichiro; Sakura, Toru; Yujiri, Toshiaki; Kondo, Eisei; Fujimaki, Katsumichi; Ueda, Yasunori; Aoyama, Yasutaka; Ohtake, Shigeki; Takita, Junko; Sai, Eirin; Taniwaki, Masafumi; Kurokawa, Mineo; Morishita, Shinichi; Fukayama, Masashi; Kiyoi, Hitoshi; Miyazaki, Yasushi; Naoe, Tomoki; Mano, Hiroyuki

    2016-05-01

    The oncogenic mechanisms underlying acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYA; 15-39 years old) remain largely elusive. Here we have searched for new oncogenes in AYA-ALL by performing RNA-seq analysis of Philadelphia chromosome (Ph)-negative AYA-ALL specimens (n = 73) with the use of a next-generation sequencer. Interestingly, insertion of D4Z4 repeats containing the DUX4 gene into the IGH locus was frequently identified in B cell AYA-ALL, leading to a high level of expression of DUX4 protein with an aberrant C terminus. A transplantation assay in mice demonstrated that expression of DUX4-IGH in pro-B cells was capable of generating B cell leukemia in vivo. DUX4 fusions were preferentially detected in the AYA generation. Our data thus show that DUX4 can become an oncogenic driver as a result of somatic chromosomal rearrangements and that AYA-ALL may be a clinical entity distinct from ALL at other ages. PMID:27019113

  12. [Access to medicines prescribed for acute health conditions in adults in South and Northeast Brazil].

    PubMed

    Paniz, Vera Maria Vieira; Cechin, Isabel Carolina Coelho Flores; Fassa, Anaclaudia Gastal; Piccini, Roberto Xavier; Tomasi, Elaine; Thumé, Elaine; Silveira, Denise Silva da; Facchini, Luiz Augusto

    2016-01-01

    This was a cross-sectional study within Brazil's Project for the Expansion and Consolidation of Family Health, 2005, with the objective of universal and free access to the medication prescribed in the last medical appointment for acute health problems and to estimate the degree to which access may have improved with inclusion of the medicines in prevailing policies and programs. The sample included 4,060 adults living in the area of primary health care units in 41 municipalities in South and Northeast Brazil. Access was greater in the South (83.2%) than in the Northeast (71%), and free access was similar (37%), with a greater share by the Family Health Program (FHP) when compared to the traditional model, especially in the Northeast. Some 60% of prescribed medicines and 50% of those on the National List of Essential Medicines (RENAME) were paid for. No variation was observed in the proportion of medicines present on the prevailing RENAME list and access. However, 40% of the medicines that were paid for can currently be obtained through the Popular Pharmacy Program. The latter program appears to emerge as a new way to guarantee access to medicines prescribed in the health system. PMID:27096295

  13. The addition of gemtuzumab ozogamicin to chemotherapy in adult patients with acute myeloid leukemia.

    PubMed

    Kell, Jonathan

    2016-04-01

    The treatment of acute myeloid leukaemia has remained largely unchanged for the last 30 years since the advent of combination chemotherapy with cytarabine arabinoside and daunorubicin with remission rates around 70% but with long term survival still only around 40% in young adults. Doses of chemotherapy have been pushed to the limit of toxicity. Gemtuzumab ozogamicin allows additional chemotherapy to be delivered to the leukaemic cells without significantly adding to toxicity since the active agent is coupled to a monoclonal anti-CD33 antibody. It was approved by the FDA in 2000 for the treatment of elderly patients with relapsed CD33 positive AML at a dose of 9mg/m(2) on two days two weeks apart. Almost at once, questions were raised about its safety, with a particular liver signal, and it was voluntarily withdrawn from practice in 2010. Many groups have been examining the role of gemtuzumab ozogamicin in combination with chemotherapy, usually at lower doses than originally recommended, with varying degrees of success and toxicity and gemtuzumab ozogamicin is now entering a period of rehabilitation. Currently it is only commercially available in Japan although it is currently also available in the UK Bloodwise AML18 study. PMID:26942450

  14. The Effects of Acute Physical Exercise on Memory, Peripheral BDNF, and Cortisol in Young Adults

    PubMed Central

    Röder, Brigitte; Schmidt-Kassow, Maren

    2016-01-01

    In animals, physical activity has been shown to induce functional and structural changes especially in the hippocampus and to improve memory, probably by upregulating the release of neurotrophic factors. In humans, results on the effect of acute exercise on memory are inconsistent so far. Therefore, the aim of the present study was to assess the effects of a single bout of physical exercise on memory consolidation and the underlying neuroendocrinological mechanisms in young adults. Participants encoded a list of German-Polish vocabulary before exercising for 30 minutes with either high intensity or low intensity or before a relaxing phase. Retention of the vocabulary was assessed 20 minutes after the intervention as well as 24 hours later. Serum BDNF and salivary cortisol were measured at baseline, after learning, and after the intervention. The high-intensity exercise group showed an increase in BDNF and cortisol after exercising compared to baseline. Exercise after learning did not enhance the absolute number of recalled words. Participants of the high-intensity exercise group, however, forgot less vocabulary than the relaxing group 24 hours after learning. There was no robust relationship between memory scores and the increase in BDNF and cortisol, respectively, suggesting that further parameters have to be taken into account to explain the effects of exercise on memory in humans. PMID:27437149

  15. Capacity of a natural strain of woodchuck hepatitis virus, WHVNY, to induce acute infection in naive adult woodchucks.

    PubMed

    Freitas, Natalia; Lukash, Tetyana; Dudek, Megan; Litwin, Sam; Menne, Stephan; Gudima, Severin O

    2015-07-01

    Woodchuck hepatitis virus (WHV) is often used as surrogate to study mechanism of HBV infection. Currently, most infections are conducted using strains WHV7 or WHV8 that have very high sequence identity. This study focused on natural strain WHVNY that is more genetically distant from WHV7. Three naive adult woodchucks inoculated with WHVNY developed productive acute infection with long lasting viremia. However, only one of two woodchucks infected with WHV7 at the same multiplicity demonstrated productive liver infection. Quantification of intracellular WHV RNA and DNA replication intermediates; percentages of core antigen-positive hepatocytes; and serum relaxed circular DNA showed that strains WHVNY and WHV7 displayed comparable replication levels and capacities to induce acute infection in naive adult woodchucks. Strain WHVNY was therefore validated as valuable reagent to analyze the mechanism of hepadnavirus infection, especially in co- and super-infection settings, which required discrimination between two related virus genomes replicating in the same liver. PMID:25979221

  16. Acute rhinosinusitis (ARS). Diagnosis and treatment of adults in general practice.

    PubMed

    Hansen, Jens Georg

    2014-02-01

    The idea behind this thesis is to present how ARS and especially acute maxillary sinusitis in adults is diagnosed and treated in general practice. The study extends over many years, beginning with the first survey in 1991. Based on doctors' answers, we then investigated the diagnostic values ​​of the symptoms, signs and examinations which the doctors reported using. All patients over 18 years suspected of acute maxillary sinusitis were included consecutively and only once and, after a clinical examination with the GP, they were offered the opportunity to enter into the prospective study referred to acute CT scan and by changes in the CT, immediately referred to sinus puncture. Both examinations were conducted at Aalborg Hospital. The disease was found most frequently in younger and 2/3 were women. The reason for this gender difference is unknown. We have assessed the diagnostic values of the symptoms, objective findings and investigations ​​using 3 different reference standards: sinus puncture, microbiological diagnosis and CT scan described in three articles. In all examinations, it appeared that the usual signs and symptoms of acute maxillary sinusitis occur almost equally often and with a few exceptions in patients, with and without pus in the sinus cavities. Pain in the sinus cavities occurring in 95% of patients, and only elevated levels of CRP and ESR are significantly and independently associated with pus in the sinus cavities. This finding is surprising, because they are two nonspecific markers. CRP tested by near-patient testing has, within the investigations period, been introduced in general practice, and from 1999 the doctors also get reimbursed for performing the test. We have on this background originally defined a clinical criterion with pain over the sinuses accompanied by elevated values ​​of CRP and/or ESR giving a sensitivity of 0.82, specificity 0.57, ppv 0.68 and npv 0.74. But looking at the ROC curve we suggest that a more clinical

  17. Incorporating measurable ('minimal') residual disease-directed treatment strategies to optimize outcomes in adults with acute myeloid leukemia.

    PubMed

    Pettit, Kristen; Stock, Wendy; Walter, Roland B

    2016-07-01

    Curative-intent therapy leads to complete remissions in many adults with acute myeloid leukemia (AML), but relapse remains common. Numerous studies have unequivocally demonstrated that the persistence of measurable ('minimal') residual disease (MRD) at the submicroscopic level during morphologic remission identifies patients at high risk of disease recurrence and short survival. This association has provided the impetus to customize anti-leukemia therapy based on MRD data, a strategy that is now routinely pursued in acute promyelocytic leukemia (APL). While it is currently uncertain whether this approach will improve outcomes in AML other than APL, randomized studies have validated MRD-based risk-stratified treatment algorithms in acute lymphoblastic leukemia. Here, we review the available studies examining MRD-directed therapy in AML, appraise their strengths and limitations, and discuss avenues for future investigation. PMID:27269126

  18. INCREASES IN ANXIETY-LIKE BEHAVIOR INDUCED BY ACUTE STRESS ARE REVERSED BY ETHANOL IN ADOLESCENT BUT NOT ADULT RATS

    PubMed Central

    Varlinskaya, Elena I.; Spear, Linda P.

    2011-01-01

    Repeated exposure to stressors has been found to increase anxiety-like behavior in laboratory rodents, with the social anxiety induced by repeated restraint being extremely sensitive to anxiolytic effects of ethanol in both adolescent and adult rats. No studies, however, have compared social anxiogenic effects of acute stress or the capacity of ethanol to reverse this anxiety in adolescent and adult animals. Therefore, the present study was designed to investigate whether adolescent [postnatal day (P35)] Sprague-Dawley rats differ from their adult counterparts (P70) in the impact of acute restraint stress on social anxiety and in their sensitivity to the social anxiolytic effects of ethanol. Animals were restrained for 90 min, followed by examination of stress- and ethanol-induced (0, 0.25, 0.5, 0.75, and 1 g/kg) alterations in social behavior using a modified social interaction test in a familiar environment. Acute restraint stress increased anxiety, as indexed by reduced levels of social investigation at both ages, and decreased social preference among adolescents. These increases in anxiety were dramatically reversed among adolescents by acute ethanol. No anxiolytic-like effects of ethanol emerged following restraint stress in adults. The social suppression seen in response to higher doses of ethanol was reversed by restraint stress in animals of both ages. To the extent that these data are applicable to humans, the results of the present study provide some experimental evidence that stressful life events may increase the attractiveness of alcohol as an anxiolytic agent for adolescents. PMID:22024161

  19. Acute stress enhances adult rat hippocampal neurogenesis and activation of newborn neurons via secreted astrocytic FGF2

    PubMed Central

    Kirby, Elizabeth D; Muroy, Sandra E; Sun, Wayne G; Covarrubias, David; Leong, Megan J; Barchas, Laurel A; Kaufer, Daniela

    2013-01-01

    Stress is a potent modulator of the mammalian brain. The highly conserved stress hormone response influences many brain regions, particularly the hippocampus, a region important for memory function. The effect of acute stress on the unique population of adult neural stem/progenitor cells (NPCs) that resides in the adult hippocampus is unclear. We found that acute stress increased hippocampal cell proliferation and astrocytic fibroblast growth factor 2 (FGF2) expression. The effect of acute stress occurred independent of basolateral amygdala neural input and was mimicked by treating isolated NPCs with conditioned media from corticosterone-treated primary astrocytes. Neutralization of FGF2 revealed that astrocyte-secreted FGF2 mediated stress-hormone-induced NPC proliferation. 2 weeks, but not 2 days, after acute stress, rats also showed enhanced fear extinction memory coincident with enhanced activation of newborn neurons. Our findings suggest a beneficial role for brief stress on the hippocampus and improve understanding of the adaptive capacity of the brain. DOI: http://dx.doi.org/10.7554/eLife.00362.001 PMID:23599891

  20. Systematic review of randomised controlled trials of over the counter cough medicines for acute cough in adults

    PubMed Central

    Schroeder, Knut; Fahey, Tom

    2002-01-01

    Objectives To determine whether over the counter cough medicines are effective for acute cough in adults. Design Systematic review of randomised controlled trials. Data sources Search of the Cochrane Acute Respiratory Infections Group specialised register, Cochrane Controlled Trials Register, Medline, Embase, and the UK Department of Health National Research Register in all languages. Included studies All randomised controlled trials that compared oral over the counter cough preparations with placebo in adults with acute cough due to upper respiratory tract infection in ambulatory settings and that had cough symptoms as an outcome. Results 15 trials involving 2166 participants met all the inclusion criteria. Antihistamines seemed to be no better than placebo. There was conflicting evidence on the effectiveness of antitussives, expectorants, antihistamine-decongestant combinations, and other drug combinations compared with placebo. Conclusion Over the counter cough medicines for acute cough cannot be recommended because there is no good evidence for their effectiveness. Even when trials had significant results, the effect sizes were small and of doubtful clinical relevance. Because of the small number of trials in each category, the results have to be interpreted cautiously. What is already know on this topicThe NHS encourages self treatment of acute self limiting illnessesOver the counter cough medicines are commonly used as first line treatment for acute coughWhat this study addsThere is little evidence for or against the effectiveness of over the counter cough medicinesAlthough cough medicines are generally well tolerated, they may be an unnecessary expenseRecommendation of over the counter cough medicines to patients is not justified by current evidence PMID:11834560

  1. A rare presentation of midgut malrotation as an acute intestinal obstruction in an adult: Two case reports and literature review

    PubMed Central

    Singh, Shailendra; Das, Anupam; Chawla, A.S.; Arya, S.V.; Chaggar, Jasneet

    2012-01-01

    INTRODUCTION Midgut malrotation is a congenital anomaly presenting mainly in the childhood. Its presentation as an acute intestinal obstruction is extremely rare in adults usually recognized intra-operatively, therefore a high index of suspicion is always required when dealing with any case of acute intestinal obstruction. PRESENTATION OF CASE We report two cases of young adults who presented with symptoms of acute intestinal obstruction and were diagnosed intra-operatively as cecal volvulus and paraduodenal hernia, respectively, caused by midgut malrotation. Post-operative CT scan confirmed these findings. DISCUSSION Malrotation of the intestinal tract is a product of an aberrant embryology. The presentation of intestinal malrotation in adults is rare (0.2–0.5%). Contrast enhanced CT can show the abnormal anatomic location of a right sided small bowel, a left-sided colon and an abnormal relationship of the superior mesenteric vein (SMV) situated to the left of the superior mesenteric artery (SMA) instead of to the right. CONCLUSION Anomalies like midgut malrotation can present as an operative surprise and awareness regarding these anomalies can help surgeons deal with these conditions. PMID:23123419

  2. An early thymic precursor phenotype predicts outcome exclusively in HOXA-overexpressing adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study

    PubMed Central

    Bond, Jonathan; Marchand, Tony; Touzart, Aurore; Cieslak, Agata; Trinquand, Amélie; Sutton, Laurent; Radford-Weiss, Isabelle; Lhermitte, Ludovic; Spicuglia, Salvatore; Dombret, Hervé; Macintyre, Elizabeth; Ifrah, Norbert; Hamel, Jean-François; Asnafi, Vahid

    2016-01-01

    Gene expression studies have consistently identified a HOXA-overexpressing cluster of T-cell acute lymphoblastic leukemias, but it is unclear whether these constitute a homogeneous clinical entity, and the biological consequences of HOXA overexpression have not been systematically examined. We characterized the biology and outcome of 55 HOXA-positive cases among 209 patients with adult T-cell acute lymphoblastic leukemia uniformly treated during the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003 and -2005 studies. HOXA-positive patients had markedly higher rates of an early thymic precursor-like immunophenotype (40.8% versus 14.5%, P=0.0004), chemoresistance (59.3% versus 40.8%, P=0.026) and positivity for minimal residual disease (48.5% versus 23.5%, P=0.01) than the HOXA-negative group. These differences were due to particularly high frequencies of chemoresistant early thymic precursor-like acute lymphoblastic leukemia in HOXA-positive cases harboring fusion oncoproteins that transactivate HOXA. Strikingly, the presence of an early thymic precursor-like immunophenotype was associated with marked outcome differences within the HOXA-positive group (5-year overall survival 31.2% in HOXA-positive early thymic precursor versus 66.7% in HOXA-positive non-early thymic precursor, P=0.03), but not in HOXA-negative cases (5-year overall survival 74.2% in HOXA-negative early thymic precursor versus 57.2% in HOXA-negative non-early thymic precursor, P=0.44). Multivariate analysis further revealed that HOXA positivity independently affected event-free survival (P=0.053) and relapse risk (P=0.039) of chemoresistant T-cell acute lymphoblastic leukemia. These results show that the underlying mechanism of HOXA deregulation dictates the clinico-biological phenotype, and that the negative prognosis of early thymic precursor acute lymphoblastic leukemia is exclusive to HOXA-positive patients, suggesting that early treatment intensification is currently

  3. Sumatriptan (subcutaneous route of administration) for acute migraine attacks in adults

    PubMed Central

    Derry, Christopher J; Derry, Sheena; Moore, R Andrew

    2014-01-01

    Background Migraine is a highly disabling condition for the individual and also has wide-reaching implications for society, healthcare services, and the economy. Sumatriptan is an abortive medication for migraine attacks, belonging to the triptan family. Subcutaneous administration may be preferable to oral for individuals experiencing nausea and/or vomiting Objectives To determine the efficacy and tolerability of subcutaneous sumatriptan compared to placebo and other active interventions in the treatment of acute migraine attacks in adults. Search methods We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, online databases, and reference lists for studies through 13 October 2011. Selection criteria We included randomised, double-blind, placebo- and/or active-controlled studies using subcutaneous sumatriptan to treat a migraine headache episode, with at least 10 participants per treatment arm. Data collection and analysis Two review authors independently assessed trial quality and extracted data. We used numbers of participants achieving each outcome to calculate relative risk (or ‘risk ratio’) and numbers needed to treat to benefit (NNT) or harm (NNH) compared to placebo or a different active treatment. Main results Thirty-five studies (9365 participants) compared subcutaneous sumatriptan with placebo or an active comparator. Most of the data were for the 6 mg dose. Sumatriptan surpassed placebo for all efficacy outcomes. For sumatriptan 6 mg versus placebo the NNTs were 2.9, 2.3, 2.2, and 2.1 for pain-free at one and two hours, and headache relief at one and two hours, respectively, and 6.1 for sustained pain-free at 24 hours. Results for the 4 mg and 8 mg doses were similar to the 6 mg dose, with 6 mg significantly better than 4 mg only for pain-free at one hour, and 8 mg significantly better than 6 mg only for headache relief at one hour. There was no evidence of increased migraine relief if a second dose of sumatriptan 6

  4. Optical mapping of the electrical activity of isolated adult zebrafish hearts: acute effects of temperature

    PubMed Central

    Lin, Eric; Ribeiro, Amanda; Ding, Weiguang; Hove-Madsen, Leif; Sarunic, Marinko V.; Beg, Mirza Faisal

    2014-01-01

    The zebrafish (Danio rerio) has emerged as an important model for developmental cardiovascular (CV) biology; however, little is known about the cardiac function of the adult zebrafish enabling it to be used as a model of teleost CV biology. Here, we describe electrophysiological parameters, such as heart rate (HR), action potential duration (APD), and atrioventricular (AV) delay, in the zebrafish heart over a range of physiological temperatures (18–28°C). Hearts were isolated and incubated in a potentiometric dye, RH-237, enabling electrical activity assessment in several distinct regions of the heart simultaneously. Integration of a rapid thermoelectric cooling system facilitated the investigation of acute changes in temperature on critical electrophysiological parameters in the zebrafish heart. While intrinsic HR varied considerably between fish, the ex vivo preparation exhibited impressively stable HRs and sinus rhythm for more than 5 h, with a mean HR of 158 ± 9 bpm (means ± SE; n = 20) at 28°C. Atrial and ventricular APDs at 50% repolarization (APD50) were 33 ± 1 ms and 98 ± 2 ms, respectively. Excitation originated in the atrium, and there was an AV delay of 61 ± 3 ms prior to activation of the ventricle at 28°C. APD and AV delay varied between hearts beating at unique HRs; however, APD and AV delay did not appear to be statistically dependent on intrinsic basal HR, likely due to the innate beat-to-beat variability within each heart. As hearts were cooled to 18°C (by 1°C increments), HR decreased by ∼40%, and atrial and ventricular APD50 increased by a factor of ∼3 and 2, respectively. The increase in APD with cooling was disproportionate at different levels of repolarization, indicating unique temperature sensitivities for ion currents at different phases of the action potential. The effect of temperature was more apparent at lower levels of repolarization and, as a whole, the atrial APD was the cardiac parameter most affected by acute

  5. Pulmonary function abnormalities in adult patients with acute exacerbation of bronchiectasis: A retrospective risk factor analysis.

    PubMed

    Ma, Yanliang; Niu, Yuqian; Tian, Guizhen; Wei, Jingan; Gao, Zhancheng

    2015-08-01

    Lung function impairments, especially airflow obstruction, are important features during acute exacerbation in patients with bronchiectasis. Recognition of the risk factors associated with airflow obstruction is important in the management of these exacerbations. The medical records of adult patients admitted to the Peking University People's Hospital, Beijing, China, from 2004 to 2011 with a diagnosis of bronchiectasis were reviewed retrospectively. Univariate and multivariate analyses were used to evaluate the risk factors associated with airflow obstruction. Airflow obstruction was found in 55.6% of 156 patients hospitalized with acute exacerbation of bronchiectasis, and the risk factors associated with airflow obstruction included young age (≤14 years old) at diagnosis (odds ratio (OR) = 3.454, 95% confidence interval (CI) 1.709-6.982, p = 0.001) as well as the presence of chronic obstructive pulmonary disease (COPD; OR = 14.677, 95% CI 5.696-37.819, p = 0.001), asthma (OR = 3.063, 95% CI 1.403-6.690, p = 0.005), and wheezing on auscultation (OR = 3.279, 95% CI 1.495-7.194, p = 0.003). The C-reactive protein (13.9 mg/dl vs. 6.89 mg/dl, p = 0.005), partial pressure of arterial oxygen (66.7 ± 8.57 mmHg vs. 89.56 ± 12.80 mmHg, p < 0.001), and partial pressure of arterial carbon dioxide (40.52 ± 2.77 mmHg vs. 42.87 ± 5.39 mmHg, p = 0.02) profiles were different between patients with or without airflow obstruction. In addition, patients colonized with potential pathogenic microorganisms had a decreased diffusing capacity (56.0% vs. 64.7%, p = 0.04). Abnormal pulmonary function was common in hospitalized patients with bronchiectasis exacerbations. Airflow obstruction was correlated with the patient's age at diagnosis, as well as the presence of combined COPD and asthma, and wheezing on auscultation, which also resulted in more severe systemic inflammation and hypoxemia. PMID:25882894

  6. Aspirin with or without an antiemetic for acute migraine headaches in adults

    PubMed Central

    Kirthi, Varo; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background Migraine is a common, disabling condition and a burden for the individual, health services and society. Many sufferers choose not to, or are unable to, seek professional help and rely on over-the-counter analgesics. Co-therapy with an antiemetic should help to reduce nausea and vomiting commonly associated with migraine headaches. Objectives To determine the efficacy and tolerability of aspirin, alone or in combination with an antiemetic, compared to placebo and other active interventions in the treatment of acute migraine headaches in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies through 10 March 2010. Selection criteria We included randomised, double-blind, placebo- or active-controlled studies using aspirin to treat a discrete migraine headache episode, with at least 10 participants per treatment arm. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and numbers needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment. Main results Thirteen studies (4222 participants) compared aspirin 900 mg or 1000 mg, alone or in combination with metoclopramide 10 mg, with placebo or other active comparators, mainly sumatriptan 50 mg or 100 mg. For all efficacy outcomes, all active treatments were superior to placebo, with NNTs of 8.1, 4.9 and 6.6 for 2-hour pain-free, 2-hour headache relief, and 24-hour headache relief with aspirin alone versus placebo, and 8.8, 3.3 and 6.2 with aspirin plus metoclopramide versus placebo. Sumatriptan 50 mg did not differ from aspirin alone for 2-hour pain-free and headache relief, while sumatriptan 100 mg was better than the combination of aspirin plus metoclopramide for 2-hour pain-free, but not headache relief; there were no data for 24-hour headache relief. Associated symptoms of nausea, vomiting

  7. Acute high-intensity exercise-induced cognitive enhancement and brain-derived neurotrophic factor in young, healthy adults.

    PubMed

    Hwang, Jungyun; Brothers, R Matthew; Castelli, Darla M; Glowacki, Elizabeth M; Chen, Yen T; Salinas, Mandy M; Kim, Jihoon; Jung, Yeonhak; Calvert, Hannah G

    2016-09-01

    Acute exercise can positively impact cognition. The present study examined the effect of acute high-intensity aerobic exercise on prefrontal-dependent cognitive performance and brain-derived neurotrophic factor (BDNF). Fifty-eight young adults were randomly assigned to one of two experimental groups: (a) an acute bout of high-intensity exercise (n=29) or (b) a non-exercise control (n=29). Participants in the exercise group improved performance on inhibitory control in Stroop interference and on cognitive flexibility in Trail Making Test (TMT) Part-B compared with participants in the control group and increased BDNF immediately after exercise. There was a significant relationship between BDNF and TMT Part-B on the pre-post change following exercise. These findings provide support for the association between improved prefrontal-dependent cognitive performance and increased BDNF in response to acute exercise. We conclude that the changes in BDNF concentration may be partially responsible for prefrontal-dependent cognitive functioning following an acute bout of exercise. PMID:27450438

  8. Impaired cardiovascular structure and function in adult survivors of severe acute malnutrition.

    PubMed

    Tennant, Ingrid A; Barnett, Alan T; Thompson, Debbie S; Kips, Jan; Boyne, Michael S; Chung, Edward E; Chung, Andrene P; Osmond, Clive; Hanson, Mark A; Gluckman, Peter D; Segers, Patrick; Cruickshank, J Kennedy; Forrester, Terrence E

    2014-09-01

    Malnutrition below 5 years remains a global health issue. Severe acute malnutrition (SAM) presents in childhood as oedematous (kwashiorkor) or nonoedematous (marasmic) forms, with unknown long-term cardiovascular consequences. We hypothesized that cardiovascular structure and function would be poorer in SAM survivors than unexposed controls. We studied 116 adult SAM survivors, 54 after marasmus, 62 kwashiorkor, and 45 age/sex/body mass index-matched community controls who had standardized anthropometry, blood pressure, echocardiography, and arterial tonometry performed. Left ventricular indices and outflow tract diameter, carotid parameters, and pulse wave velocity were measured, with systemic vascular resistance calculated. All were expressed as SD scores. Mean (SD) age was 28.8±7.8 years (55% men). Adjusting for age, sex, height, and weight, SAM survivors had mean (SE) reductions for left ventricular outflow tract diameter of 0.67 (0.16; P<0.001), stroke volume 0.44 (0.17; P=0.009), cardiac output 0.5 (0.16; P=0.001), and pulse wave velocity 0.32 (0.15; P=0.03) compared with controls but higher diastolic blood pressures (by 4.3; 1.2-7.3 mm Hg; P=0.007). Systemic vascular resistance was higher in marasmus and kwashiorkor survivors (30.2 [1.2] and 30.8 [1.1], respectively) than controls 25.3 (0.8), overall difference 5.5 (95% confidence interval, 2.8-8.4 mm Hg min/L; P<0.0001). No evidence of large vessel or cardiac remodeling was found, except closer relationships between these indices in former marasmic survivors. Other parameters did not differ between SAM survivor groups. We conclude that adult SAM survivors had smaller outflow tracts and cardiac output when compared with controls, yet markedly elevated peripheral resistance. Malnutrition survivors are thus likely to develop excess hypertension in later life, especially when exposed to obesity. PMID:24980666

  9. Diclofenac with or without an antiemetic for acute migraine headaches in adults

    PubMed Central

    Derry, Sheena; Rabbie, Roy; Moore, R Andrew

    2014-01-01

    Background Migraine is a common, disabling condition and a burden for the individual, health services and society. Many sufferers choose not to, or are unable to, seek professional help and rely on over-the-counter (OTC) analgesics. Diclofenac is an established analgesic, and new formulations using the potassium or epolamine salts, which can be dissolved in water, have been developed for rapid absorption, which may be beneficial in acute migraine. Co-therapy with an antiemetic should help to reduce the nausea and vomiting commonly associated with migraine. Objectives To determine the efficacy and tolerability of diclofenac, alone or in combination with an antiemetic, compared to placebo and other active interventions in the treatment of acute migraine headaches in adults. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Relief Database, ClinicalTrials.gov, and reference lists for studies through 27 September 2011. Selection criteria We included randomised, double-blind, placebo- and/or active-controlled studies using self administered diclofenac to treat a migraine headache episode, with at least 10 participants per treatment arm. Data collection and analysis Two review authors independently assessed trial quality and extracted data. We used numbers of participants achieving each outcome to calculate relative risk (or ‘risk ratio’) and numbers needed to treat to benefit (NNT) or harm (NNH) compared to placebo or a different active treatment. Main results Five studies (1356 participants) compared oral diclofenac with placebo, and one also compared it with sumatriptan; none combined diclofenac with a self administered antiemetic. Four studies treated attacks with single doses of medication, and two allowed an optional second dose for inadequate response. Only two studies, with three active treatment arms, provided data for pooled analysis of primary outcomes. For single doses of diclofenac

  10. Cortical activity evoked by an acute painful tissue-damaging stimulus in healthy adult volunteers

    PubMed Central

    Williams, Gemma; Lee, Amy; Meek, Judith; Slater, Rebeccah; Olhede, Sofia; Fitzgerald, Maria

    2013-01-01

    Everyday painful experiences are usually single events accompanied by tissue damage, and yet most experimental studies of cutaneous nociceptive processing in the brain use repeated laser, thermal, or electrical stimulations that do not damage the skin. In this study the nociceptive activity in the brain evoked by tissue-damaging skin lance was analyzed with electroencephalography (EEG) in 20 healthy adult volunteers (13 men and 7 women) aged 21–40 yr. Time-frequency analysis of the evoked activity revealed a distinct late event-related vertex potential (lance event-related potential, LERP) at 100–300 ms consisting of a phase-locked energy increase between 1 and 20 Hz (delta-beta bands). A pairwise comparison between lance and sham control stimulation also revealed a period of ultralate stronger desynchronization after lance in the delta band (1–5 Hz). Skin application of mustard oil before lancing, which sensitizes a subpopulation of nociceptors expressing the cation channel TRPA1, did not affect the ultralate desynchronization but reduced the phase-locked energy increase in delta and beta bands, suggesting a central interaction between different modalities of nociceptive inputs. Verbal descriptor screening of individual pain experience revealed that lance pain is predominantly due to Aδ fiber activation, but when individuals describe lances as C fiber mediated, an ultralate delta band event-related desynchronization occurs in the brain-evoked activity. We conclude that pain evoked by acute tissue damage is associated with distinct Aδ and C fiber-mediated patterns of synchronization and desynchronization of EEG oscillations in the brain. PMID:23427303

  11. Acute lethal graft-versus-host disease stimulates cellular proliferation in the adult rat liver.

    PubMed

    Klein, R M; Clancy, J; Stuart, S

    1982-11-01

    The present investigation was designed to analyse the effects of acute lethal graft-versus-host disease (GVHD) in adult (DA x LEW)F1 rats on cellular proliferation within the liver. The influence of the host thymus on GVHD-induced proliferation was also assessed. From 1-28 days after initiation of GVHD [3H]thymidine ([3H]-TdR) was injected i.v. and rats were killed one hour later. Percentage labelled cells (LI) of periportal infiltrating cells (PIC), hepatocytes (H), and sinusoidal lining cells (SC) were counted. Mean values for control rats were 0.3 +/- 0.1% (H), 0.4 +/- 0.1% (SC) and 0.2 +/- 0.1% (PIC). GVHD rats demonstrated a significant increase in LI of PIC (days 1-21), SC (days 2-17) and H (days 2-17). Most labelled cells in PIC were large lymphocytes. Peak LI values were 7.0 +/- 1.0% PIC (day 17), 6.8 +/- 0.9% SC (day 17), and 5.2 +/- 0.9% H (day 7), with all cellular compartments returning to near normal LI values by day 28. Stimulation of cellular proliferation occurred in all three liver cell compartments in neonatally thymectomized (TXM) rats. The intensity of GVHD-induced cell proliferation was significantly decreased at day 7 in all compartments and PIC was dramatically decreased at day 21 in TXM-GVHD rats as compared to non-TXM-GVHD rats. It is hypothesized that the general stimulation of hepatocyte cell proliferation in GVHD is related to the secretion of lymphokines by primarily donor and secondarily host T cells in the periportal infiltrate. PMID:7172201

  12. Ticagrelor: a review of its use in adults with acute coronary syndromes.

    PubMed

    Dhillon, Sohita

    2015-02-01

    Ticagrelor (Brilique™, Brilinta®), a cyclopentyl-triazolopyrimidine, is an orally active, reversible, and selective adenosine diphosphate (ADP) receptor antagonist indicated for use in patients with acute coronary syndromes (ACS). Ticagrelor has a faster onset of action and provides greater inhibition of platelet aggregation than clopidogrel. In the large well-designed, PLATO study in adult patients with ACS, 12 months' treatment with ticagrelor was more effective than clopidogrel in reducing the incidence of the primary composite endpoint of myocardial infarction, stroke, or cardiovascular (CV) death. Ticagrelor also reduced all-cause mortality relative to clopidogrel, although statistical significance of this was not confirmed in hierarchical testing. Benefit with ticagrelor was seen both in invasively and noninvasively managed patients. Ticagrelor was generally well tolerated and was not associated with an increased risk of major bleeding relative to clopidogrel. However, the incidences of non-coronary artery bypass grafting (CABG)-related bleeding, and major or minor bleeding, as well as some non-hemorrhagic adverse events, including dyspnea (usually of mild or moderate severity) and ventricular pauses (largely asymptomatic) were higher with ticagrelor. In addition, the ATLANTIC study showed that although pre-hospital administration of ticagrelor did not improve pre-percutaneous coronary intervention (PCI) coronary reperfusion in ACS patients relative to in-hospital administration, ticagrelor was safe in both instances, with no significant between-group differences in non-CABG-related major and minor bleeding events. Although further comparative studies with other antiplatelet agents, including prasugrel, are required to position it more definitively, current evidence indicates that ticagrelor is a useful option for the prevention of thrombotic CV events in ACS patients managed invasively or noninvasively. PMID:25672642

  13. Oral processing effort, appetite and acute energy intake in lean and obese adults.

    PubMed

    Mattes, Richard D; Considine, Robert V

    2013-08-15

    Chewing reportedly contributes to satiation and satiety signals. Attempts to document and quantify this have led to small and inconsistent effects. The present trial manipulated oral processing effort though required chewing of gums of different hardness and measured appetitive sensations, energy intake, gastric emptying, GI transit time, and concentrations of glucose, insulin, GLP-1, ghrelin and pancreatic polypeptide. Sixty adults classified by sex and BMI (15 each of lean females, obese females, lean males and obese males) were tested in a randomized, controlled, cross-over trial with three arms. They chewed nothing, soft gum or hard gum for 15 min while sipping grape juice (10% of individual energy needs) containing acetaminophen and lactulose on one day each separated by 7 days. Electromyographic recordings and self-reports were obtained during and after chewing to quantify oral processing effort. Blood was sampled through an indwelling catheter and appetite ratings were obtained at baseline and at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min after chewing initiation. Breath samples were collected at 10 min intervals for the first 2h and at 30 min intervals for the next 2h. No effects of chewing were observed for appetitive sensations or gut peptide concentrations. Energy intake tended to decline in lean and increase in obese participants so that daily energy intake differed significantly between the two groups when chewing either gum, while no difference was observed on the non-chewing day. Serum glucose and insulin were significantly lower at selected time points 90-240 min after chewing compared to baseline and the non-chewing day. These data indicate chewing effort does not affect appetitive sensations or gut peptide secretion, but may exert a small differential effect on acute energy intake in lean and obese individuals and lead to greater post-prandial declines of serum glucose and insulin. The efficacy of gum chewing as a substitute for eating for weight

  14. Acute adult poisoning cases admitted to a university hospital in Tabriz, Iran.

    PubMed

    Islambulchilar, M; Islambulchilar, Z; Kargar-Maher, M H

    2009-04-01

    The aim of our study was to investigate the etiological and demographical characteristics of acute adult poisoning cases admitted to a university hospital in Tabriz, Iran. This retrospective study was performed on 1342 poisoning admissions to a university hospital from 2003 to 2005, by data collection from the medical records of patients. Poisonings were 5.40% of the total admissions. There was a predominance of female patients (55.7%) compared to male patients (44.3%) with a female-to-male ratio of 1.2:1. Most poisonings occurred in the age range of 11-20 years (38.9%). Drugs were the most common cause of poisonings (60.8%). Among the drug poisonings, benzodiazepines (40.31%) were the most frequent agents, followed by antidepressants (31.98%). The seasonal distribution in poisoning patients suggested a peak in spring (28%) and summer (27.5%). In 9.8% of cases accidental and in 90.2% intentional poisonings were evident. Most suicide attempts were made by women (58.51%) and unmarried people (51.4%).The mean duration of hospitalization was 3.02 +/- 2.8 days. There were 28 (2.3%) deaths; the majority (13 cases) was due to pesticides. This was a university hospital-based study, so these results may not be representative of the general population. Despite this drawback, these data still provide important information on the characteristics of the poisoning in this part of Iran. To prevent such poisonings, the community education about the danger of central nervous system-acting drugs and reducing the exposure period of people to pesticides are recommended. PMID:19734268

  15. Acute Resveratrol Consumption Improves Neurovascular Coupling Capacity in Adults with Type 2 Diabetes Mellitus

    PubMed Central

    Wong, Rachel H.X.; Raederstorff, Daniel; Howe, Peter R.C.

    2016-01-01

    Background: Poor cerebral perfusion may contribute to cognitive impairment in type 2 diabetes mellitus (T2DM). We conducted a randomized controlled trial to test the hypothesis that resveratrol can enhance cerebral vasodilator function and thereby alleviate the cognitive deficits in T2DM. We have already reported that acute resveratrol consumption improved cerebrovascular responsiveness (CVR) to hypercapnia. We now report the effects of resveratrol on neurovascular coupling capacity (CVR to cognitive stimuli), cognitive performance and correlations with plasma resveratrol concentrations. Methods: Thirty-six T2DM adults aged 40–80 years were randomized to consume single doses of resveratrol (0, 75, 150 and 300 mg) at weekly intervals. Transcranial Doppler ultrasound was used to monitor changes in blood flow velocity (BFV) during a cognitive test battery. The battery consisted of dual-tasking (finger tapping with both Trail Making task and Serial Subtraction 3 task) and a computerized multi-tasking test that required attending to four tasks simultaneously. CVR to cognitive tasks was calculated as the per cent increase in BFV from pre-test basal to peak mean blood flow velocity and also as the area under the curve for BFV. Results: Compared to placebo, 75 mg resveratrol significantly improved neurovascular coupling capacity, which correlated with plasma total resveratrol levels. Enhanced performance on the multi-tasking test battery was also evident following 75 mg and 300 mg of resveratrol. Conclusion: a single 75 mg dose of resveratrol was able to improve neurovascular coupling and cognitive performance in T2DM. Evaluation of benefits of chronic resveratrol supplementation is now warranted. PMID:27420093

  16. HAG regimen improves survival in adult patients with hypocellular acute myeloid leukemia

    PubMed Central

    Wang, Libing; Gao, Lei; Lü, Shuqin; Xi, Hao; Qiu, Huiying; Chen, Li; Chen, Jie; Ni, Xiong; Xu, Xiaoqian; Zhang, Weiping; Yang, Jianmin; Wang, Jianmin; Song, Xianmin

    2016-01-01

    Background Hypocellular acute myeloid leukemia (Hypo-AML) is a rare disease entity. Studies investigating the biological characteristics of hypo-AML have been largely lacking. We examined the clinical and biological characteristics, as well as treatment outcomes of hypo-AML in our institutes over a seven years period. Design and Methods We retrospectively analyzed data on 631 adult AML patients diagnosed according to the French-American-British (FAB) classification and WHO classification of tumors of haematopoietic and lymphoid tissue, including 43 patients with hypo-AML. Biological variables, treatment outcomes and follow-up data on hypo-AML patients were analyzed. Results Out of 631 AML patients, 47 (7.4%) were diagnosed as hypo-AML, out of which 43 patients were evaluable. Compared with non-hypocellular AML, hypo-AML patients tended to be older (P = 0.05), more likely to present with leukocytopenia (P < 0.01) and anterior hematological diseases (P = 0.02). The overall complete remission (CR) rate, disease free survival (DFS), and overall survival (OS) in hypo-AML patients were comparable to those in non-hypo AML patients. Twenty-seven (62.8%) patients with hypocellular AML were treated with the standard regimen of anthracyclines and cytarabine (XA) (associated CR rate: 51.9%; median OS: 7 months; median DFS: 6.5 months). Sixteen (37.2%) patients were treated with a priming regimen containing homoharringtonine, cytarabine and G-CSF (HAG) (associated CR rate: 81.25%; median OS: 16 months; median DFS: 16 months). Conclusions The overall prognosis of hypo-AML was not inferior to that of non-hypo AML. HAG regimen might increase response rates and improve survival in hypo-AML patients. PMID:26497216

  17. Bone marrow-resident NK cells prime monocytes for regulatory function during infection

    PubMed Central

    Askenase, Michael H.; Han, Seong-Ji; Byrd, Allyson L.; da Fonseca, Denise Morais; Bouladoux, Nicolas; Wilhelm, Christoph; Konkel, Joanne E.; Hand, Timothy W.; Lacerda-Queiroz, Norinne; Su, Xin-Zhuan; Trinchieri, Giorgio; Grainger, John R.; Belkaid, Yasmine

    2015-01-01

    SUMMARY Tissue-infiltrating Ly6Chi monocytes play diverse roles in immunity, ranging from pathogen killing to immune regulation. How and where this diversity of function is imposed remains poorly understood. Here we show that during acute gastrointestinal infection, priming of monocytes for regulatory function preceded systemic inflammation and was initiated prior to bone marrow egress. Notably, natural killer (NK) cell-derived IFN-γ promoted a regulatory program in monocyte progenitors during development. Early bone marrow NK cell activation was controlled by systemic interleukin-12 (IL-12) produced by Batf3-dependent dendritic cells (DC) in the mucosal-associated lymphoid tissue (MALT). This work challenges the paradigm that monocyte function is dominantly imposed by local signals following tissue recruitment, and instead proposes a sequential model of differentiation in which monocytes are pre-emptively educated during development in the bone marrow to promote their tissue-specific function. PMID:26070484

  18. Peroxidatic activity distinct from myeloperoxidase in human monocytes cultured in vitro and in alveolar macrophages.

    PubMed

    Breton-Gorius, J; Vildé, J L; Guichard, J; Vainchenker, W; Basset, F

    1982-01-01

    Human monocytes develop a peroxidatic activity (PA) in rough endoplasmic reticulum (RER) after adherence or after culture in semi-solid medium. This enzyme activity disappears after three days of culture in the majority of macrophages derived from adult monocytes but persists for one week in macrophages derived from neonatal monocytes. The PA is due to an enzyme distinct from myeloperoxidase (MPO), since monocytes from a patient with MPO deficiency develop the same PA as that of normal monocytes after adherence. By its localization and other characteristics, PA of adherent monocytes resembles that of rodent macrophages. We therefore investigated whether human alveolar macrophages exhibit PA, using a sensitive cytochemical method which prevents inhibition by aldehyde in adherent monocytes. In various pathological cases, four types of macrophages could be identified: the majority were peroxidase-negative, a small percentage was of exudate type exhibiting a PA in granules as blood monocytes, while few macrophages were intermediate, possessing only PA in RER i.e. of type resident and a smaller proportion had PA in RER and in granules i.e. exudate-resident macrophages. These findings demonstrate that human macrophages and adherent monocytes may exhibit PA in RER as has been reported for rodent macrophages. The true nature and function of the enzyme responsible for this PA, which is distinct from MPO, remains unknown, but some arguments seem to suggest its role in prostaglandin synthesis. PMID:6283838

  19. High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia

    ClinicalTrials.gov

    2016-05-19

    Acute Leukemia of Ambiguous Lineage; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  20. Targeted Therapy in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Acute Myelogenous Leukemia

    ClinicalTrials.gov

    2016-07-28

    Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia

  1. Acute Phase Proteins and Their Role in Periodontitis: A Review.

    PubMed

    Polepalle, Tejaswin; Moogala, Srinivas; Boggarapu, Shalini; Pesala, Divya Sai; Palagi, Firoz Babu

    2015-11-01

    Acute phase proteins are a class of proteins whose plasma concentration increase (positive acute phase proteins) or decrease (negative acute phase proteins) in response to inflammation. This response is called as the acute phase reaction, also called as acute phase response, which occurs approximately 90 minutes after the onset of a systemic inflammatory reaction. In Periodontitis endotoxins released from gram negative organisms present in the sub gingival plaque samples interact with Toll- like receptors (TLR) that are expressed on the surface of Polymorphonuclear leucocytes (PMNs) and monocytes which are in abundance in periodontal inflammation. The complex formed due to interaction of Endotoxins and TLR activates the Signal transduction pathway in both innate and adaptive immunity resulting in production of Cytokines that co- ordinate the local and systemic inflammatory response. The pro inflammatory cytokines originating at the diseased site activates the liver cells to produce acute phase proteins as a part of non specific response. The production of Acute phase proteins is regulated to a great extent by Cytokines such as IL-1, IL-6, IL-8, TNF-α and to a lesser extent by Glucocorticoid hormones. These proteins bind to bacteria leading to activation of complement proteins that destroys pathogenic organisms. Studies have shown that levels of acute phase proteins are increased in otherwise healthy adults with poor periodontal status. This article highlights about the synthesis, structure, types and function of acute phase proteins and the associated relation of acute phase proteins in Periodontitis. PMID:26674303

  2. Acute Phase Proteins and Their Role in Periodontitis: A Review

    PubMed Central

    Moogala, Srinivas; Boggarapu, Shalini; Pesala, Divya Sai; Palagi, Firoz Babu

    2015-01-01

    Acute phase proteins are a class of proteins whose plasma concentration increase (positive acute phase proteins) or decrease (negative acute phase proteins) in response to inflammation. This response is called as the acute phase reaction, also called as acute phase response, which occurs approximately 90 minutes after the onset of a systemic inflammatory reaction. In Periodontitis endotoxins released from gram negative organisms present in the sub gingival plaque samples interact with Toll- like receptors (TLR) that are expressed on the surface of Polymorphonuclear leucocytes (PMNs) and monocytes which are in abundance in periodontal inflammation. The complex formed due to interaction of Endotoxins and TLR activates the Signal transduction pathway in both innate and adaptive immunity resulting in production of Cytokines that co- ordinate the local and systemic inflammatory response. The pro inflammatory cytokines originating at the diseased site activates the liver cells to produce acute phase proteins as a part of non specific response. The production of Acute phase proteins is regulated to a great extent by Cytokines such as IL-1, IL-6, IL-8, TNF-α and to a lesser extent by Glucocorticoid hormones. These proteins bind to bacteria leading to activation of complement proteins that destroys pathogenic organisms. Studies have shown that levels of acute phase proteins are increased in otherwise healthy adults with poor periodontal status. This article highlights about the synthesis, structure, types and function of acute phase proteins and the associated relation of acute phase proteins in Periodontitis. PMID:26674303

  3. Adolescent mice are less sensitive to the effects of acute nicotine on context pre-exposure than adults.

    PubMed

    Kutlu, Munir Gunes; Braak, David C; Tumolo, Jessica M; Gould, Thomas J

    2016-07-01

    Adolescence is a critical developmental period associated with both increased vulnerability to substance abuse and maturation of certain brain regions important for learning and memory such as the hippocampus. In this study, we employed a hippocampus-dependent learning context pre-exposure facilitation effect (CPFE) paradigm in order to test the effects of acute nicotine on contextual processing during adolescence (post-natal day (PND) 38) and adulthood (PND 53). In Experiment 1, adolescent or adult C57BL6/J mice received either saline or one of three nicotine doses (0.09, 0.18, and 0.36mg/kg) prior to contextual pre-exposure and testing. Our results demonstrated that both adolescent and adult mice showed CPFE in the saline groups. However, adolescent mice only showed acute nicotine enhancement of CPFE with the highest nicotine dose whereas adult mice showed the enhancing effects of acute nicotine with all three doses. In Experiment 2, to determine if the lack of nicotine's effects on CPFE shown by adolescent mice is specific to the age when they are tested, mice were either given contextual pre-exposure during adolescence or adulthood and received immediate shock and testing during adulthood after a 15day delay. We found that both adolescent and adult mice showed CPFE in the saline groups when tested during adulthood. However, like Experiment 1, mice that received contextual pre-exposure during adolescence did not show acute nicotine enhancement except at the highest dose (0.36mg/kg) whereas both low (0.09mg/kg) and high (0.36mg/kg) doses enhanced CPFE in adult mice. Finally, we showed that the enhanced freezing response found with 0.36mg/kg nicotine in the 15-day experiment may be a result of decreased locomotor activity as mice that received this dose of nicotine traveled shorter distances in an open field paradigm. Overall, our results indicate that while adolescent mice showed normal contextual processing when tested both during adolescence and adulthood, they

  4. Gemtuzumab Ozogamicin in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-09-23

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia

  5. Comparative study of quality of life of adult survivors of childhood acute lymphocytic leukemia and Wilms’ tumor

    PubMed Central

    de Souza, Clélia Marta Casellato; Cristofani, Lilian Maria; Cornacchioni, Ana Lucia Beltrati; Odone, Vicente; Kuczynski, Evelyn

    2015-01-01

    Abstract Objective To analyze and compare the health-related quality of life of adult survivors of acute lymphocytic leukemia and Wilms’ tumor amongst themselves and in relation to healthy participants. Methods Ninety participants aged above 18 years were selected and divided into three groups, each comprising 30 individuals. The Control Group was composed of physically healthy subjects, with no cancer history; and there were two experimental groups: those diagnosed as acute lymphocytic leukemia, and those as Wilms’ Tumor. Quality of life was assessed over the telephone, using the Medical Outcomes Study 36-Item Short Form Health Survey. Results Male survivors presented with better results as compared to female survivors and controls in the Vitality domain, for acute lymphocytic leukemia (p=0.042) and Wilms’ tumor (p=0.013). For acute lymphocytic leukemia survivors, in Social aspects (p=0.031), Mental health (p=0.041), and Emotional aspects (p=0.040), the latter also for survivors of Wilms’ tumor (p=0.040). The best results related to the Functional capacity domain were recorded for the experimental group that had a late diagnosis of acute lymphocytic leukemia. There were significant differences between groups except for the Social and Emotional domains for self-perceived health, with positive responses that characterized their health as good, very good, and excellent. Conclusion Survivors of acute lymphocytic leukemia showed no evidence of relevant impairment of health-related quality of life. The Medical Outcomes Study 36-Item Short Form Health Survey (via telephone) can be a resource to access and evaluate survivors. PMID:26537509

  6. Recovery-oriented care in older-adult acute inpatient mental health settings in Australia: an exploratory study.

    PubMed

    McKenna, Brian; Furness, Trentham; Dhital, Deepa; Ireland, Susan

    2014-10-01

    Recovery-oriented care acknowledges the unique journey that consumers lead with the aim of regaining control of their lives in order to live a good life. Recovery has become a dominant policy-directed model of many mental health care organizations, but in older-adult acute mental health inpatient settings, nurses do not have a clear description of how to be recovery-oriented. The aims of this study were to determine the extent to which elements of existing nursing practice resemble the domains of recovery-oriented care and provide a baseline understanding of practice in preparation for transformation to recovery-oriented mental health care provision. An exploratory, qualitative research design was used to meet the research aims. A purposive sample of mental health nurses (N = 12) participated in focus groups in three older-adult inpatient settings in Australia. A general inductive approach was used to analyze the qualitative data. The mental health nurses in this study readily discussed aspects of their current practice within the recovery domains. They described pragmatic ways to promote a culture of hope, collaborative partnerships, meaningful engagement, autonomy and self-determination, and community participation and citizenship. Nurses also discussed challenges and barriers to recovery-oriented care in older-adult acute mental health settings. This study identified a reasonable baseline understanding of practice in preparation for transformation to recovery-oriented older-adult mental healthcare provision. A concerted drive focused on recovery education is required to effectively embed a recovery-orientated paradigm into older-adult mental health settings. PMID:25263738

  7. Bone Marrow MicroRNA-335 Level Predicts the Chemotherapy Response and Prognosis of Adult Acute Myeloid Leukemia

    PubMed Central

    Yingchun, Li; Rong, Zhang; Kun, Yao; Ying, Yang; Zhuogang, Liu

    2015-01-01

    Abstract The aim of this study was to investigate the role of microRNA-335 (miR-335) in determining the treatment response and prognosis in adult acute myeloid leukemia (AML) patients receiving the cytarabine (Ara-C)-based chemotherapy. A total of 204 adult AML patients were collected. The miR-335 levels in serum and bone marrow samples from these patients were determined. All patients received Ara-C-based standard induction chemotherapy regimens. The treatment response to Ara-C-based chemotherapy was evaluated. All patients were followed for prognostic analyses. The levels of miR-335 in bone marrow and serum samples from adult AML patients achieving complete response were significantly higher than those without. The serum miR-335 level was not associated with the chemotherapy response and prognosis in these AML patients. In contrast, high bone marrow miR-335 level was significantly associated with a poor treatment response and also predicted a worse prognosis indicated by the relapse-free survival and overall survival periods in adult AML patients receiving Ara-C-based chemotherapy. Our finding suggests that bone marrow miR-335 level may be used as a marker to predict the chemotherapy response and prognosis in adult AML patients. PMID:26287405

  8. Biologic and clinical characteristics of adolescent and young adult cancers: Acute lymphoblastic leukemia, colorectal cancer, breast cancer, melanoma, and sarcoma.

    PubMed

    Tricoli, James V; Blair, Donald G; Anders, Carey K; Bleyer, W Archie; Boardman, Lisa A; Khan, Javed; Kummar, Shivaani; Hayes-Lattin, Brandon; Hunger, Stephen P; Merchant, Melinda; Seibel, Nita L; Thurin, Magdalena; Willman, Cheryl L

    2016-04-01

    Adolescent and young adult (AYA) patients with cancer have not attained the same improvements in overall survival as either younger children or older adults. One possible reason for this disparity may be that the AYA cancers exhibit unique biologic characteristics, resulting in differences in clinical and treatment resistance behaviors. This report from the biologic component of the jointly sponsored National Cancer Institute and LiveStrong Foundation workshop entitled "Next Steps in Adolescent and Young Adult Oncology" summarizes the current status of biologic and translational research progress for 5 AYA cancers; colorectal cancer breast cancer, acute lymphoblastic leukemia, melanoma, and sarcoma. Conclusions from this meeting included the need for basic biologic, genomic, and model development for AYA cancers as well as translational research studies to elucidate any fundamental differences between pediatric, AYA, and adult cancers. The biologic questions for future research are whether there are mutational or signaling pathway differences (for example, between adult and AYA colorectal cancer) that can be clinically exploited to develop novel therapies for treating AYA cancers and to develop companion diagnostics. Cancer 2016;122:1017-1028. © 2016 American Cancer Society. PMID:26849082

  9. Autologous stem cell transplantation for adult acute leukemia in 2015: time to rethink? Present status and future prospects.

    PubMed

    Gorin, N-C; Giebel, S; Labopin, M; Savani, B N; Mohty, M; Nagler, A

    2015-12-01

    The use of autologous stem cell transplantation (ASCT) as consolidation therapy for adult patients with acute leukemia has declined over time. However, multiple randomized studies in the past have reported lower relapse rates after autologous transplantation compared with chemotherapy and lower non-relapse mortality rates compared with allogeneic transplantation. In addition, quality of life of long-term survivors is better after autologous transplantation than after allogeneic transplantation. Further, recent developments may improve outcomes of autograft recipients. These include the use of IV busulfan and the busulfan+melphalan combination, better detection of minimal residual disease (MRD) with molecular biology techniques, the introduction of targeted therapies and post-transplant maintenance therapy. Therefore, ASCT may nowadays be reconsidered for consolidation in the following patients if and when they reach a MRD-negative status: good- and at least intermediate-1 risk acute myelocytic leukemia in first CR, acute promyelocytic leukemia in second CR, Ph-positive acute lymphocytic leukemia. Conversely, patients with MRD-positive status or high-risk leukemia should not be considered for consolidation with ASCT. PMID:26281031

  10. Developmental differences in EEG and sleep responses to acute ethanol administration and its withdrawal (hangover) in adolescent and adult Wistar rats.

    PubMed

    Ehlers, Cindy L; Desikan, Anita; Wills, Derek N

    2013-12-01

    Age-related differences in sensitivity to the acute effects of alcohol may play an important role in the increased risk for the development of alcoholism seen in teens that begin drinking at an early age. The present study evaluated the acute and protracted (hangover) effects of ethanol in adolescent (P33-P40) and adult (P100-P107) Wistar rats, using the cortical electroencephalogram (EEG). Six minutes of EEG was recorded during waking, 15 min after administration of 0, 1.5, or 3.0 g/kg ethanol, and for 3 h at 20 h post ethanol, during the rats' next sleep cycle. Significantly higher overall frontal and parietal cortical power was seen in a wide range of EEG frequencies in adolescent rats as compared to adult rats in their waking EEG. Acute administration of ethanol did not produce differences between adolescents and adults on behavioral measures of acute intoxication. However, it did produce a significantly less intense acute EEG response to ethanol in the theta frequencies in parietal cortex in the adolescents as compared to the adults. At 20 h following acute ethanol administration, during the rats' next sleep cycle, a decrease in slow-wave frequencies (1-4 Hz) was seen and the adolescent rats were found to display more reduction in the slow-wave frequencies than the adults did. The present study found that adolescent rats, as compared to adults, demonstrate low sensitivity to acute ethanol administration in the theta frequencies and more susceptibility to disruption of slow-wave sleep during hangover. These studies may lend support to the idea that these traits may contribute to increased risk for alcohol use disorders seen in adults who begin drinking in their early teenage years. PMID:24169089

  11. Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults

    PubMed Central

    Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background Migraine is a common, disabling condition and a burden for the individual, health services and society. Many sufferers choose not to, or are unable to, seek professional help and rely on over-the-counter analgesics. Co-therapy with an antiemetic should help to reduce nausea and vomiting commonly associated with migraine. Objectives To determine the efficacy and tolerability of paracetamol (acetaminophen), alone or in combination with an antiemetic, compared to placebo and other active interventions in the treatment of acute migraine in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies through 4 October 2010. Selection criteria We included randomised, double-blind, placebo- or active-controlled studies using self-administered paracetamol to treat a migraine headache episode, with at least 10 participants per treatment arm. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and numbers needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment. Main results Ten studies (2769 participants, 4062 attacks) compared paracetamol 1000 mg, alone or in combination with an antiemetic, with placebo or other active comparators, mainly sumatriptan 100 mg. For all efficacy outcomes paracetamol was superior to placebo, with NNTs of 12, 5.2 and 5.0 for 2-hour pain-free and 1- and 2-hour headache relief, respectively, when medication was taken for moderate to severe pain. Nausea, photophobia and phonophobia were reduced more with paracetamol than with placebo at 2 hours (NNTs of 7 to 11); more individuals were free of any functional disability at 2 hours with paracetamol (NNT 10); and fewer participants needed rescue medication over 6 hours (NNT 6). Paracetamol 1000 mg plus metoclopramide 10 mg was not significantly different from oral sumatriptan

  12. Ibuprofen with or without an antiemetic for acute migraine headaches in adults

    PubMed Central

    Rabbie, Roy; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background Migraine is a common, disabling condition and a burden for the individual, health services and society. Many sufferers do not seek professional help, relying instead on over-the-counter analgesics. Co-therapy with an antiemetic should help to reduce symptoms commonly associated with migraine headaches. Objectives To determine efficacy and tolerability of ibuprofen, alone or in combination with an antiemetic, compared to placebo and other active interventions in the treatment of acute migraine headaches in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies through 22 April 2010. Selection criteria We included randomised, double-blind, placebo- or active-controlled studies using self-administered ibuprofen to treat a migraine headache episode, with at least 10 participants per treatment arm. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and number needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment. Main results Nine studies (4373 participants, 5223 attacks) compared ibuprofen with placebo or other active comparators; none combined ibuprofen with a self-administered antiemetic. All studies treated attacks with single doses of medication. For ibuprofen 400 mg versus placebo, NNTs for 2-hour pain-free (26% versus 12% with placebo), 2-hour headache relief (57% versus 25%) and 24-hour sustained headache relief (45% versus 19%) were 7.2, 3.2 and 4.0, respectively. For ibuprofen 200 mg versus placebo, NNTs for 2-hour pain-free (20% versus 10%) and 2-hour headache relief (52% versus 37%) were 9.7 and 6.3, respectively. The higher dose was significantly better for 2-hour headache relief than the lower dose. Soluble formulations of ibuprofen 400 mg were better than standard tablets for 1-hour, but not 2-hour headache relief

  13. Risk-Based Classification System of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-04-07

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  14. [Double-blind controlled study of the efficacy of nifuroxazide versus placebo in the treatment of acute diarrhea in adults].

    PubMed

    Bourée, P; Chaput, J C; Krainik, F; Michel, H; Trépo, C

    1989-05-01

    In a double-blind, controlled randomized trial, 88 adult patients with acute diarrhea (more than three watery stools per day) received either 400 mg of nifuroxazide twice daily or placebo for 5 days. The mean duration of diarrhea in the nifuroxazide group was 2.09 days versus 3.26 days in the placebo group (p less than 0.004). The number of bowel movements per day diminished and mucus disappeared more quickly in patients treated by nifuroxazide than in patients of the placebo group. Nifuroxazide was well tolerated and no side effects were observed. Nifuroxazide is an effective therapy for acute diarrhea and can be prescribed from the onset of diarrhea without waiting for stool culture results which can be late or negative. PMID:2666238

  15. Adult patients are more catabolic than children during acute phase after burn injury: a retrospective analysis on muscle protein kinetics

    PubMed Central

    Tuvdendorj, Demidmaa; Chinkes, David L.; Zhang, Xiao-Jun; Ferrando, Arny A.; Elijah, Itoro E.; Mlcak, Ronald P.; Finnerty, Celeste C.; Wolfe, Robert R.; Herndon, David N.

    2011-01-01

    Purpose This study was performed to determine if there is an age-related specificity in the response of muscle protein metabolism to severe burn injury during acute hospitalization. This is a retrospective analysis of previously published data. Methods: Nineteen adult and 58 pediatric burn-injured patients (age 43.3 ± 14.3 vs. 7.2 ± 5.3 years, adult vs. children) participated in stable isotope [ring-2H5]phenylalanine (Phe) infusion studies. Femoral arterial and venous blood samples and muscle biopsy samples were collected throughout the study. Data are presented as means ± standard deviation (SD). A p value less than 0.05 was considered statistically significant. Results Muscle net protein balance (NB) was higher in children (adult vs. children, -43 ± 61 vs. 8 ± 68 nmol Phe/min/100 ml leg volume, p < 0.05). Muscle protein fractional synthesis rate (FSR) was higher in children (adult vs. children, 0.11 ± 0.05 vs. 0.16 ± 0.10 %/h, p < 0.05). Leg muscle protein breakdown was not different between the groups (adult vs. children, 179 ± 115 vs. 184 ± 124 nmol Phe/ min/100 ml leg volume, p < 0.05; synthesis rate was 134 ± 96 and 192 ± 128 nmol Phe/min/100 ml leg volume in adults and children, respectively (p = 0.07). Age significantly correlated with muscle protein NB (p = 0.01) and FSR (p = 0.02); but not with breakdown (p = 0.67) and synthesis (p = 0.07) rates measured by using a three-pool model. Conclusion In burn injury, the muscle protein breakdown may be affected to the same extent in adults and children, whereas synthesis may have age-related specificities, resulting in a better but still low NB in children. PMID:21647721

  16. Characterization of Clostridium perfringens in the feces of adult horses and foals with acute enterocolitis

    PubMed Central

    Gohari, Iman Mehdizadeh; Arroyo, Luis; MacInnes, Janet I.; Timoney, John F.; Parreira, Valeria R.; Prescott, John F.

    2014-01-01

    Up to 60% of cases of equine colitis have no known cause. To improve understanding of the causes of acute colitis in horses, we hypothesized that Clostridium perfringens producing enterotoxin (CPE) and/or beta2 toxin (CPB2) are common and important causes of severe colitis in horses and/or that C. perfringens producing an as-yet-undescribed cytotoxin may also cause colitis in horses. Fecal samples from 55 horses (43 adults, 12 foals) with clinical evidence of colitis were evaluated by culture for the presence of Clostridium difficile, C. perfringens, and Salmonella. Feces were also examined by enzyme-linked immunosorbent assay (ELISA) for C. difficile A/B toxins and C. perfringens alpha toxin (CPA), beta2 toxin (CPB2), and enterotoxin (CPE). Five C. perfringens isolates per sample were genotyped for the following genes: cpa, cpb, cpb2 consensus, cpb2 atypical, cpe (enterotoxin), etx (epsilon toxin), itx (iota toxin), netB (necrotic enteritis toxin B), and tpeL (large C. perfringens cytotoxin). The supernatants of these isolates were also evaluated for toxicity for an equine cell line. All fecal samples were negative for Salmonella. Clostridium perfringens and C. difficile were isolated from 40% and 5.4% of samples, respectively. All fecal samples were negative for CPE. Clostridium perfringens CPA and CPB2 toxins were detected in 14.5% and 7.2% of fecal samples, respectively, all of which were culture-positive for C. perfringens. No isolates were cpe, etx, netB, or tpeL gene-positive. Atypical cpb2 and consensus cpb2 genes were identified in 15 (13.6%) and 4 (3.6%) of 110 isolates, respectively. All equine C. perfringens isolates showed far milder cytotoxicity effects than a CPB-producing positive control, although cpb2-positive isolates were slightly but significantly more cytotoxic than negative isolates. Based on this studied population, we were unable to confirm our hypothesis that CPE and CPB2-producing C. perfringens are common in horses with colitis in

  17. Characterization of Clostridium perfringens in the feces of adult horses and foals with acute enterocolitis.

    PubMed

    Gohari, Iman Mehdizadeh; Arroyo, Luis; Macinnes, Janet I; Timoney, John F; Parreira, Valeria R; Prescott, John F

    2014-01-01

    Up to 60% of cases of equine colitis have no known cause. To improve understanding of the causes of acute colitis in horses, we hypothesized that Clostridium perfringens producing enterotoxin (CPE) and/or beta2 toxin (CPB2) are common and important causes of severe colitis in horses and/or that C. perfringens producing an as-yet-undescribed cytotoxin may also cause colitis in horses. Fecal samples from 55 horses (43 adults, 12 foals) with clinical evidence of colitis were evaluated by culture for the presence of Clostridium difficile, C. perfringens, and Salmonella. Feces were also examined by enzyme-linked immunosorbent assay (ELISA) for C. difficile A/B toxins and C. perfringens alpha toxin (CPA), beta2 toxin (CPB2), and enterotoxin (CPE). Five C. perfringens isolates per sample were genotyped for the following genes: cpa, cpb, cpb2 consensus, cpb2 atypical, cpe (enterotoxin), etx (epsilon toxin), itx (iota toxin), netB (necrotic enteritis toxin B), and tpeL (large C. perfringens cytotoxin). The supernatants of these isolates were also evaluated for toxicity for an equine cell line. All fecal samples were negative for Salmonella. Clostridium perfringens and C. difficile were isolated from 40% and 5.4% of samples, respectively. All fecal samples were negative for CPE. Clostridium perfringens CPA and CPB2 toxins were detected in 14.5% and 7.2% of fecal samples, respectively, all of which were culture-positive for C. perfringens. No isolates were cpe, etx, netB, or tpeL gene-positive. Atypical cpb2 and consensus cpb2 genes were identified in 15 (13.6%) and 4 (3.6%) of 110 isolates, respectively. All equine C. perfringens isolates showed far milder cytotoxicity effects than a CPB-producing positive control, although cpb2-positive isolates were slightly but significantly more cytotoxic than negative isolates. Based on this studied population, we were unable to confirm our hypothesis that CPE and CPB2-producing C. perfringens are common in horses with colitis in

  18. A Clinical Audit of the Management of Acute Asthmatic Attacks in Adults and Children Presenting to an Emergency Department

    PubMed Central

    Dasgupta, S; Williams, EW; Walters, C; Eldemire-Shearer, D; Williams-Johnson, J

    2014-01-01

    Objective: To compare the guidelines in the University Hospital of the West Indies (UHWI) acute asthma management protocol with actual practice in the Accident and Emergency Department. Methods: A prospective docket audit was done of all consecutive medical records of patients, presenting with a diagnosed acute asthmatic attack between June 1 and September 30, 2010, to the emergency department of the UHWI. A convenient sample was used. The audit tool used was created from the UHWI protocol for the emergency management of asthma in adults and children, as well as the British Adult Asthma Audit Tool. The audit tool assessed three main sections: initial assessment, initial management, and discharge considerations. Data were coded and entered in Microsoft Excel 2007 and statistical analyses conducted using Stata version 10. Management patterns were compared to the actual protocol and then discussed. Results: A total of 15 864 patients were seen during the study period. Of these, a total of 293 patients were seen for a presentation of acute asthma. More females (57.3%) than males were seen, with the mean age of 33.53 years. Only 31% of patients were given a severity assessment of mild, moderate, or severe. Peak expiratory flow rate (PEFR) was attempted and recorded in 62%, but only 18.1% of patients had both pre and post PEFR done. Only 4.4% of patients were administered nebulizations within the suggested time frame. Positively, 94.2% of patients were given a prescription for inhaled corticosteroids and bronchodilators to continue post-discharge. Conclusion: Acute asthma management still remains an area of medical practice that continues to have long-standing difficulties. Failure to assess and document the severity of asthma attacks along with the under-utilization of PEFR was noted. PMID:25314279

  19. Effectiveness of early discharge planning in acutely ill or injured hospitalized older adults: a systematic review and meta-analysis

    PubMed Central

    2013-01-01

    Background Older age and higher acuity are associated with prolonged hospital stays and hospital readmissions. Early discharge planning may reduce lengths of hospital stay and hospital readmissions; however, its effectiveness with acutely admitted older adults is unclear. Methods In this systematic review, we compared the effectiveness of early discharge planning to usual care in reducing index length of hospital stay, hospital readmissions, readmission length of hospital stay, and mortality; and increasing satisfaction with discharge planning and quality of life for older adults admitted to hospital with an acute illness or injury. We searched the Cochrane Library, DARE, HTA, NHSEED, ACP, MEDLINE, EMBASE, CINAHL, Proquest Dissertations and Theses, PubMed, Web of Science, SciSearch, PEDro, Sigma Theta Tau International’s registry of nursing research, Joanna Briggs Institute, CRISP, OT Seeker, and several internet search engines. Hand-searching was conducted in four gerontological journals and references of all included studies and previous systematic reviews. Two reviewers independently extracted data and assessed risk of bias. Data were pooled using a random-effects meta-analysis. Where meta-analysis was not possible, narrative analysis was performed. Results Nine trials with a total of 1736 participants were included. Compared to usual care, early discharge planning was associated with fewer hospital readmissions within one to twelve months of index hospital discharge [risk ratio (RR) = 0.78, 95% CI = 0.69 − 0.90]; and lower readmission lengths of hospital stay within three to twelve months of index hospital discharge [weighted mean difference (WMD) = −2.47, 95% confidence intervals (CI) = −4.13 − −0.81)]. No differences were found in index length of hospital stay, mortality or satisfaction with discharge planning. Narrative analysis of four studies indicated that early discharge planning was associated with greater overall quality of life and the

  20. [Treatment of acute coronary syndrome in older adults and high-risk patients."When the going gets tough…"].

    PubMed

    Bassanelli, Giorgio; Morici, Nuccia; De Luca, Leonardo; De Servi, Stefano; Savonitto, Stefano

    2015-10-01

    The increasing life expectancy in older adults and the better survival of patients with multiple pathologies require the capability to treat complex clinical conditions with an increased risk of iatrogenic complications. Nevertheless, recent improvements in the pharmacological and interventional treatment of acute coronary syndrome (ACS) have promoted a shift from therapeutic nihilism to a more active management of complex ACS cases. Despite the paucity of specific randomized clinical trials, observational studies seem to show benefit of an early invasive treatment in these patients. This approach requires close cooperation of clinical intensivists, interventional cardiologists and cardiovascular surgeons either in a specialized heart center or in a network of hospitals. PMID:26442976

  1. Prognostic Significance and Treatment Implications of Minimal Residual Disease Studies in Philadelphia-Negative Adult Acute Lymphoblastic Leukemia

    PubMed Central

    Spinelli, Orietta; Tosi, Manuela; Peruta, Barbara; Guinea Montalvo, Marie Lorena; Maino, Elena; Scattolin, Anna Maria; Parolini, Margherita; Viero, Piera; Rambaldi, Alessandro; Bassan, Renato

    2014-01-01

    Acute lymphoblastic leukemia (ALL) is curable in about 40–50% of adult patients, however this is subject to ample variations owing to several host- and disease-related prognostic characteristics. Currently, the study of minimal residual disease (MRD) following induction and early consolidation therapy stands out as the most sensitive individual prognostic marker to define the risk of relapse following the achievement of remission, and ultimately that of treatment failure or success. Because substantial therapeutic advancement is now being achieved using intensified pediatric-type regimens, MRD analysis is especially useful to orientate stem cell transplantation choices. These strategic innovations are progressively leading to greater than 50% cure rates. PMID:25237475

  2. Biomarkers in Bone Marrow Samples From Pediatric Patients With High-Risk Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-05-17

    Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Recurrent Childhood Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  3. ACG Clinical Guideline: Diagnosis, Treatment, and Prevention of Acute Diarrheal Infections in Adults.

    PubMed

    Riddle, Mark S; DuPont, Herbert L; Connor, Bradley A

    2016-05-01

    Acute diarrheal infections are a common health problem globally and among both individuals in the United States and traveling to developing world countries. Multiple modalities including antibiotic and non-antibiotic therapies have been used to address these common infections. Information on treatment, prevention, diagnostics, and the consequences of acute diarrhea infection has emerged and helps to inform clinical management. In this ACG Clinical Guideline, the authors present an evidence-based approach to diagnosis, prevention, and treatment of acute diarrhea infection in both US-based and travel settings. PMID:27068718

  4. A rare case of acute epiglottitis due to Staphylococcus aureus in an adult

    PubMed Central

    Harris, Clare; Sharkey, Lisa; Koshy, George; Simler, Nicola; Karas, Johannis Andreas

    2012-01-01

    Epiglottitis has been mainly associated with childhood infection with Haemophilis influenzae type B but cases of adult epiglottitis are increasing. We report here a case of adult epiglottitis and present evidence that it was caused by Staphylococcus aureus. A 48-year old patient with clinical symptoms of epiglottitis grew Staphylococcus aureus in pure culture from an epiglottal swab. Staphylococcus aureus should be considered as a potential pathogen in adult epiglottitis. PMID:24470933

  5. Entinostat and Clofarabine in Treating Patients With Newly Diagnosed, Relapsed, or Refractory Poor-Risk Acute Lymphoblastic Leukemia or Bilineage/Biphenotypic Leukemia

    ClinicalTrials.gov

    2014-07-16

    Acute Leukemias of Ambiguous Lineage; Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  6. The acute effect of maximal exercise on central and peripheral arterial stiffness indices and hemodynamics in children and adults.

    PubMed

    Melo, Xavier; Fernhall, Bo; Santos, Diana A; Pinto, Rita; Pimenta, Nuno M; Sardinha, Luís B; Santa-Clara, Helena

    2016-03-01

    This study compared the effects of a bout of maximal running exercise on arterial stiffness in children and adults. Right carotid blood pressure and artery stiffness indices measured by pulse wave velocity (PWV), compliance and distensibility coefficients, stiffness index α and β (echo-tracking), contralateral carotid blood pressure, and upper and lower limb and central/aortic PWV (applanation tonometry) were taken at rest and 10 min after a bout of maximal treadmill running in 34 children (7.38 ± 0.38 years) and 45 young adults (25.22 ± 0.91 years) having similar aerobic potential. Two-by-two repeated measures analysis of variance and analysis of covariance were used to detect differences with exercise between groups. Carotid pulse pressure (PP; η(2) = 0.394) increased more in adults after exercise (p < 0.05). Compliance (η(2) = 0.385) decreased in particular in adults and in those with high changes in distending pressure, similarly to stiffness index α and β. Carotid PWV increased more in adults and was related to local changes in PP but not mean arterial pressure (MAP). Stiffness in the lower limbs decreased (η(2) = 0.115) but apparently only in those with small MAP changes (η(2) = 0.111). No significant exercise or group interaction effects were found when variables were adjusted to height. An acute bout of maximal exercise can alter arterial stiffness and hemodynamics in the carotid artery and within the active muscle beds. Arterial stiffness and hemodynamic response to metabolic demands during exercise in children simply reflect their smaller body size and may not indicate a particular physiological difference compared with adults. PMID:26842667

  7. Decitabine in Treating Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-05-18

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  8. 8-Chloro-Adenosine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-05-11

    Recurrent Adult Acute Myeloid Leukemia; Relapsed Adult Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia Arising From Previous Myeloproliferative Disorder

  9. A Critical Role for Monocytes/Macrophages During Intestinal Inflammation-associated Lymphangiogenesis

    PubMed Central

    Becker, Felix; Kurmaeva, Elvira; Gavins, Felicity N. E.; Stevenson, Emily V.; Navratil, Aaron R.; Jin, Long; Tsunoda, Ikuo; Orr, A. Wayne; Alexander, Jonathan S.; Ostanin, Dmitry V.

    2016-01-01

    Background Inflammation-associated lymphangiogenesis (IAL) is frequently observed in inflammatory bowel diseases. IAL is believed to limit inflammation by enhancing fluid and immune cell clearance. Although monocytes/macrophages (MΦ) are known to contribute to intestinal pathology in inflammatory bowel disease, their role in intestinal IAL has never been studied mechanistically. We investigated contributions of monocytes/MΦ to the development of intestinal inflammation and IAL. Methods Because inflammatory monocytes express CC chemokine receptor 2 (CCR2), we used CCR2 diphtheria toxin receptor transgenic (CCR2.DTR) mice, in which monocytes can be depleted by diphtheria toxin injection, and CCR2−/− mice, which have reduced circulating monocytes. Acute or chronic colitis was induced by dextran sodium sulfate or adoptive transfer of CD4+CD45RBhigh T cells, respectively. Intestinal inflammation was assessed by flow cytometry, immunofluorescence, disease activity, and histopathology, whereas IAL was assessed by lymphatic vessel morphology and density. Results We demonstrated that intestinal MΦ expressed vascular endothelial growth factor-C/D. In acute colitis, monocyte-depleted mice were protected from intestinal injury and showed reduced IAL, which was reversed after transfer of wild-type monocytes into CCR2−/− mice. In chronic colitis, CCR2 deficiency did not attenuate inflammation but reduced IAL. Conclusions We propose a dual role of MΦ in (1) promoting acute inflammation and (2) contributing to IAL. Our data suggest that intestinal inflammation and IAL could occur independently, because IAL was reduced in the absence of monocytes/MΦ, even when inflammation was present. Future inflammatory bowel disease therapies might exploit promotion of IAL and suppression of MΦ independently, to restore lymphatic clearance and reduce inflammation. PMID:26950310

  10. The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults.

    PubMed

    McGill, F; Heyderman, R S; Michael, B D; Defres, S; Beeching, N J; Borrow, R; Glennie, L; Gaillemin, O; Wyncoll, D; Kaczmarski, E; Nadel, S; Thwaites, G; Cohen, J; Davies, N W S; Miller, A; Rhodes, A; Read, R C; Solomon, T

    2016-04-01

    Bacterial meningitis and meningococcal sepsis are rare conditions with high case fatality rates. Early recognition and prompt treatment saves lives. In 1999 the British Infection Society produced a consensus statement for the management of immunocompetent adults with meningitis and meningococcal sepsis. Since 1999 there have been many changes. We therefore set out to produce revised guidelines which provide a standardised evidence-based approach to the management of acute community acquired meningitis and meningococcal sepsis in adults. A working party consisting of infectious diseases physicians, neurologists, acute physicians, intensivists, microbiologists, public health experts and patient group representatives was formed. Key questions were identified and the literature reviewed. All recommendations were graded and agreed upon by the working party. The guidelines, which for the first time include viral meningitis, are written in accordance with the AGREE 2 tool and recommendations graded according to the GRADE system. Main changes from the original statement include the indications for pre-hospital antibiotics, timing of the lumbar puncture and the indications for neuroimaging. The list of investigations has been updated and more emphasis is placed on molecular diagnosis. Approaches to both antibiotic and steroid therapy have been revised. Several recommendations have been given regarding the follow-up of patients. PMID:26845731

  11. Gemtuzumab Ozogamicin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Acute Promyelocytic Leukemia

    ClinicalTrials.gov

    2015-07-27

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia

  12. Bilateral acute pyogenic conjunctivitis with iritis induced by unilateral topical application of bacterial peptidoglycan muramyl dipeptide in adult rabbits.

    PubMed

    Langford, Marlyn P; Foreman, Bridgett D; Srur, Lana; Ganley, James P; Redens, Thomas B

    2013-11-01

    The factors responsible for the conjunctivitis and iritis associated with acute ocular infection and post enteric inflammatory disease are not fully known. The pro-inflammatory activity of unilateral topical application of muramyl dipeptide (MDP; the smallest bio-active Gram-positive and Gram-negative bacterial cell wall component) was investigated in adult rabbits. The resultant bilateral conjunctivitis/iritis and pyogenic responses were characterized. Bilateral symptoms were graded by slit lamp examinations; tear fluid, Schirmer tests (tear production), blood and aqueous humor (AH) samples were obtained from MDP-treated and untreated rabbits. MDP concentration, gamma-glutamyltranspeptidase activity (GGT; key enzyme in glutathione recapture, xenobiotic detoxification, eicosanoid synthesis and neutrophil function), protein concentration, and tear cell density, cytology, and immunofluorescent antibody reactivity to GGT and calreticulin (CRT; MDP-binding protein) were determined. MDP was cleared from ipsilateral tears and serum by 6 h, but was undetected in mock-treated contralateral tears. Bilateral signs of acute transient pyogenic conjunctivitis, characterized by tearing, lid edema, conjunctival hyperemia, chemosis and leukocytic infiltrate with iritis (erythema and aqueous flare) were detected. Milder symptoms occurred in the mock-treated contralateral eyes. Bilateral symptoms, tear production, tear protein, GGT activity, and mucopurulent discharge (containing up to 2.5-5.0 × 10(6) cells/mL) were elevated 4-8 h post MDP and resolved to near pre-treatment levels by 24 h. Tear GGT activity and protein levels were higher in MDP-treated and mock-treated contralateral eyes than in eyes of untreated adult rabbits (p's < 0.001). Elevated tear GGT activity was associated with histopathology and increased vascular and epithelial permeability to serum protein, GGT-positive epithelia cells, macrophages and heterophils. Repeat MDP applications induced recurrent

  13. Outcomes after matched unrelated donor versus identical sibling hematopoietic cell transplantation in adults with acute myelogenous leukemia.

    PubMed

    Saber, Wael; Opie, Shaun; Rizzo, J Douglas; Zhang, Mei-Jie; Horowitz, Mary M; Schriber, Jeff

    2012-04-26

    Approximately one-third of patients with an indication for hematopoietic cell transplantation (HCT) have an HLA-matched related donor (MRD) available to them. For the remaining patients, a matched unrelated donor (MUD) is an alternative. Prior studies comparing MRD and MUD HCT provide conflicting results, and the relative efficacy of MRD and MUD transplantation is an area of active investigation. To address this issue, we analyzed outcomes of 2223 adult acute myelogenous leukemia patients who underwent allogeneic HCT between 2002 and 2006 (MRD, n = 624; 8/8 HLA locus matched MUD, n = 1193; 7/8 MUD, n = 406). The 100-day cumulative incidence of grades B-D acute GVHD was significantly lower in MRD HCT recipients than in 8/8 MUD and 7/8 MUD HCT recipients (33%, 51%, and 53%, respectively; P < .001). In multivariate analysis, 8/8 MUD HCT recipients had a similar survival rate compared with MRD HCT recipients (relative risk [RR], 1.03; P = .62). 7/8 MUD HCT recipients had higher early mortality than MRD HCT recipients (RR, 1.40; P < .001), but beyond 6 months after HCT, their survival rates were similar (RR, 0.88; P = .30). These results suggest that transplantation from MUD and MRD donors results in similar survival times for patients with acute myelogenous leukemia. PMID:22327226

  14. Sumatriptan (oral route of administration) for acute migraine attacks in adults

    PubMed Central

    Derry, Christopher J; Derry, Sheena; Moore, R Andrew

    2014-01-01

    Background Migraine is a highly disabling condition for the individual and also has wide-reaching implications for society, healthcare services, and the economy. Sumatriptan is an abortive medication for migraine attacks, belonging to the triptan family. Objectives To determine the efficacy and tolerability of oral sumatriptan compared to placebo and other active interventions in the treatment of acute migraine attacks in adults. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, online databases, and reference lists for studies through 13 October 2011. Selection criteria We included randomised, double-blind, placebo- and/or active-controlled studies using oral sumatriptan to treat a migraine headache episode, with at least 10 participants per treatment arm. Data collection and analysis Two review authors independently assessed trial quality and extracted data. We used numbers of participants achieving each outcome to calculate relative risk (or ‘risk ratio’) and numbers needed to treat to benefit (NNT) or harm (NNH) compared to placebo or a different active treatment. Main results Sixty-one studies (37,250 participants) compared oral sumatriptan with placebo or an active comparator. Most of the data were for the 50 mg and 100 mg doses. Sumatriptan surpassed placebo for all efficacy outcomes. For sumatriptan 50 mg versus placebo the NNTs were 6.1, 7.5, and 4.0 for pain-free at two hours and headache relief at one and two hours, respectively. NNTs for sustained pain-free and sustained headache relief during the 24 hours postdose were 9.5 and 6.0, respectively. For sumatriptan 100 mg versus placebo the NNTs were 4.7, 6.8, 3.5, 6.5, and 5.2, respectively, for the same outcomes. Results for the 25 mg dose were similar to the 50 mg dose, while sumatriptan 100 mg was significantly better than 50 mg for pain-free and headache relief at two hours, and for sustained pain-free during 24 hours. Treating early, during

  15. Suppression of Adult Neurogenesis Increases the Acute Effects of Kainic Acid

    PubMed Central

    Iyengar, Sloka S.; LaFrancois, John J.; Friedman, Daniel; Drew, Liam J.; Denny, Christine A.; Burghardt, Nesha S.; Wu, Melody V.; Hsieh, Jenny; Hen, René; Scharfman, Helen E.

    2016-01-01

    Adult neurogenesis, the generation of new neurons in the adult brain, occurs in the hippocampal dentate gyrus (DG) and the olfactory bulb (OB) of all mammals, but the functions of these new neurons are not entirely clear. Originally, adult-born neurons were considered to have excitatory effects on the DG network, but recent studies suggest a net inhibitory effect. Therefore, we hypothesized that selective removal of newborn neurons would lead to increased susceptibility to the effects of a convulsant. This hypothesis was tested by evaluating the response to the chemoconvulsant kainic acid (KA) in mice with reduced adult neurogenesis, produced either by focal X-irradiation of the DG, or by pharmacogenetic deletion of dividing radial glial precursors. In the first 4 hrs after KA administration, when mice have the most robust seizures, mice with reduced adult neurogenesis had more severe convulsive seizures, exhibited either as a decreased latency to the first convulsive seizure, greater number of convulsive seizures, or longer convulsive seizures. Nonconvulsive seizures did not appear to change or they decreased. Four-21 hrs after KA injection, mice with reduced adult neurogenesis showed more interictal spikes (IIS) and delayed seizures than controls. Effects were greater when the anticonvulsant ethosuximide was injected 30 min prior to KA administration; ethosuximide allows forebrain seizure activity to be more easily examined in mice by suppressing seizures dominated by the brainstem. These data support the hypothesis that reduction of adult-born neurons increases the susceptibility of the brain to effects of KA. PMID:25476494

  16. Contrasting regional Fos expression in adolescent and young adult rats following acute administration of the antidepressant paroxetine.

    PubMed

    Karanges, Emily A; Ramos, Linnet; Dampney, Bruno; Suraev, Anastasia S; Li, Kong M; McGregor, Iain S; Hunt, Glenn E

    2016-03-01

    Adolescents and adults may respond differently to antidepressants, with poorer efficacy and greater probability of adverse effects in adolescents. The mechanisms underlying this differential response are largely unknown, but likely relate to an interaction between the neural effects of antidepressants and brain development. We used Fos immunohistochemistry to examine regional differences in adolescent (postnatal day (PND) 28) and young adult (PND 56) male, Wistar rats given a single injection of the selective serotonin reuptake inhibitor paroxetine (10mg/kg). Paroxetine induced widespread Fos expression in both adolescent and young adult rats. Commonly affected areas include the bed nucleus of the stria terminalis (dorsolateral), medial preoptic area, paraventricular hypothalamic and thalamic nuclei and central nucleus of the amygdala. Fos expression was generally lower in adolescents with significantly greater Fos expression observed in young adults in the prelimbic cortex, supraoptic nucleus, basolateral amygdala, lateral parabrachial and Kölliker-Fuse nuclei. However, a small subset of regions showed greater adolescent Fos expression including the nucleus accumbens shell, lateral habenula and dorsal raphe. Paroxetine increased plasma corticosterone concentrations in young adults, but not adolescents. Plasma paroxetine levels were not significantly different between the age groups. These results indicate a different c-Fos signature of acute paroxetine in adolescent rats, with greater activation in key mesolimbic and serotonergic regions, but a more subdued cortical, brainstem and hypothalamic response. This suggests that the atypical response of adolescents to paroxetine may be related to a blunted neuroendocrine response, combined with insufficient top-down regulation of limbic regions involved in reward and impulsivity. PMID:26876759

  17. Cost-effectiveness and clinical outcomes of double versus single cord blood transplantation in adults with acute leukemia in France

    PubMed Central

    Labopin, Myriam; Ruggeri, Annalisa; Gorin, Norbert Claude; Gluckman, Eliane; Blaise, Didier; Mannone, Lionel; Milpied, Noel; Yakoub-Agha, Ibrahim; Deconinck, Eric; Michallet, Mauricette; Fegueux, Nathalie; Socié, Gerard; Nguyen, Stephanie; Cahn, Jean Yves; de Revel, Thierry; Garnier, Federico; Faucher, Catherine; Taright, Namik; Kenzey, Chantal; Volt, Fernanda; Bertrand, Dominique; Mohty, Mohamad; Rocha, Vanderson

    2014-01-01

    Double cord blood transplantation extends the use of cord blood to adults for whom a single unit is not available, but the procedure is limited by its cost. To evaluate outcomes and cost-effectiveness of double compared to single cord blood transplantation, we analyzed 134 transplants in adults with acute leukemia in first remission. Transplants were performed in France with reduced intensity or myeloablative conditioning regimens. Costs were estimated from donor search to 1 year after transplantation. A Markov decision analysis model was used to calculate quality-adjusted life-years and cost-effectiveness ratio within 4 years. The overall survival at 2 years after single and double cord blood transplants was 42% versus 62%, respectively (P=0.03), while the leukemia-free-survival was 33% versus 53%, respectively (P=0.03). The relapse rate was 21% after double transplants and 42% after a single transplant (P=0.006). No difference was observed for non-relapse mortality or chronic graft-versus-host-disease. The estimated costs up to 1 year after reduced intensity conditioning for single and double cord blood transplantation were € 165,253 and €191,827, respectively. The corresponding costs after myeloablative conditioning were € 192,566 and € 213,050, respectively. Compared to single transplants, double cord blood transplantation was associated with supplementary costs of € 21,302 and € 32,420 up to 4 years, but with increases in quality-adjusted life-years of 0.616 and 0.484, respectively, and incremental cost-effectiveness ratios of € 34,581 and €66,983 in the myeloablative and reduced intensity conditioning settings, respectively. Our results showed that for adults with acute leukemia in first complete remission in France, double cord transplantation is more cost-effective than single cord blood transplantation, with better outcomes, including quality-adjusted life-years. PMID:24143000

  18. Comparison of outcomes after unrelated cord blood and unmanipulated haploidentical stem cell transplantation in adults with acute leukemia.

    PubMed

    Ruggeri, A; Labopin, M; Sanz, G; Piemontese, S; Arcese, W; Bacigalupo, A; Blaise, D; Bosi, A; Huang, H; Karakasis, D; Koc, Y; Michallet, M; Picardi, A; Sanz, J; Santarone, S; Sengelov, H; Sierra, J; Vincent, L; Volt, F; Nagler, A; Gluckman, E; Ciceri, F; Rocha, V; Mohty, M

    2015-09-01

    Outcomes after unmanipulated haploidentical stem cell transplantation (Haplo) and after unrelated cord blood transplantation (UCBT) are encouraging and have become alternative options to treat patients with high-risk acute leukemia without human leukocyte antigen (HLA) matched donor. We compared outcomes after UCBT and Haplo in adults with de novo acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Median follow-up was 24 months. Analysis was performed separately for patients with AML, n=918 (Haplo=360, UCBT=558) and ALL, n=528 (Haplo=158 and UCBT=370). UCBT was associated with delayed engraftment and higher graft failure in both AML and ALL recipients. In multivariate analysis, UCBT was associated with lower incidence of chronic graft-vs-host disease both in the AML group (hazard ratio (HR)=0.63, P=0.008) and in the ALL group (HR=0.58, P=0.01). Not statistically significant differences were observed between Haplo and UCBT for relapse incidence (HR=0.95, P=0.76 for AML and HR=0.82, P=0.31 for ALL), non-relapse mortality (HR=1.16, P=0.47 for AML and HR=1.23, P=0.23 for ALL) and leukemia-free survival (HR 0.78, P=0.78 for AML and HR=1.00, P=0.84 for ALL). There were no statistically differences on main outcomes after unmanipulated Haplo and UCBT, and both approaches are valid for acute leukemia patients lacking a HLA matched donor. Both strategies expand the donor pool for patients in need. PMID:25882700

  19. Evaluation of procalcitonin as a biomarker of diagnosis, severity and postoperative complications in adult patients with acute appendicitis

    PubMed Central

    Vaziri, Mohammad; Ehsanipour, Fahimeh; Pazouki, Abdolreza; Tamannaie, Zeinab; Taghavi, Roohollah; Pishgahroudsari, Mohaddese; Jesmi, Fatemeh; Chaichian, Shahla

    2014-01-01

    Background: Delay in diagnosis and treatment of acute appendicitis (AA) results in an increased rate of perforation, postoperative morbidity, mortality and hospital length of stay. Several biochemical parameters including white blood cell (WBC) count, C-reactive protein (CRP), interleukin-6 (IL6) and Procalcitonin (PCT) have been used to further improve the clinical diagnosis of AA. The aim of this study was to assess the value of procalcitonin as a predictor of diagnosis and severity of appendicitis in order to improve the clinical decision making, since other studies have been unable to demonstrate a diagnostic value for PCT elevation in acute appendicitis. Methods: One-hundred patients who underwent open appendectomy, including 75 men and 25 women with a mean age of 28 years were included in this study. Procalcitonin values were measured by an immunofluorescent method). Serum PCT>0.5 ng/ml was considered positive. The PCT serum values were measured in four different categories, including ˂0.5ng/ml, 0.5-2 ng/ml, 2-10ng/ml and more than 10ng/ml. Results: The sensitivity and specificity of PCT level measurement for acute appendicitis diagnosis were 44% and 100% respectively. The value of PCT increased with the severity of appendicitis and also with the presence of peritonitis and infection, at the site of surgery. Conclusions: Procalcitonin measurement cannot be used as a diagnostic test for adult patients with acute appendicitis and its routine use in such patients is not cost effective and conclusive. Procalcitonin values can be used as a prognostic marker and predictor of infectious complications following surgery and it can help to carry out timely surgical intervention which is highly recommended in patients with PCT values more than 0.5ng/ml. PMID:25405116

  20. Impetigo presenting as an acute necrotizing swelling of the lower lip in an adult patient.

    PubMed

    Ghafoor, Mohammed; Halsnad, Moorthy; Fowell, Christopher; Millar, Brian G

    2012-06-01

    The authors present an unusual case of an acute swelling of the lower lip and septicemia in a 35-year-old, recent immigrant male arriving from India. The patient presented in our emergency department with a 48-hour history of a worsening, painful swelling of the lower lip. On presentation, he was pyrexial and the lip was found to be acutely inflamed with honey-colored crusting, pustular lesions, and induration . A diagnosis of impetigo leading to necrosis of the lip was established, a rare phenomenon potentially resulting in significant tissue destruction. Appropriate medical management achieved a good outcome and prevented disabling tissue loss of the orofacial region. PMID:22677026

  1. Novel biomarkers for early diagnosis of acute kidney injury after cardiac surgery in adults

    PubMed Central

    Kališnik, Jurij Matija

    2016-01-01

    Acute kidney injury after cardiac surgery with cardiopulmonary bypass is a common and serious complication and it is associated with increased morbidity and mortality. Diagnosis of acute kidney injury is based on the serum creatinine levels which rise several hours to days after the initial injury. Thus, novel biomarkers that will enable faster diagnosis are needed in clinical practice. There are numerous urine and serum proteins that indicate kidney injury and are under extensive research. Despite promising basic research results and assembled data, which indicate superiority of some biomarkers to creatinine, we are still awaiting clinical application. PMID:27212976

  2. [Update on current care guidelines. Current care guideline: Acute lower respiratory tract infection in adults].

    PubMed

    Honkanen, Pekka; Broas, Markku; Hedman, Jouni; Jartti, Airi; Järvinen, Asko; Koskela, Markku; Meinander, Tuula; Puolijoki, Hannu; Rautakorpi, Ulla; Syrjälä, Hannu

    2015-01-01

    Pneumonia is recognised in patients suffering from acute cough or deteriorated general condition. Patients with acute cough without pneumonia-related symptoms or clinical findings do not benefit from antimicrobial treatment. Those with suspected or confirmed pneumonia are treated with antibiotics, amoxicillin being the first choice. Most patients with pneumonia can be treated at home. Those with severe symptoms are referred to hospital. Patients are always encouraged to contact his/her physician if the symptoms worsen or do not ameliorate within 2-3 days. Patients aged 50 years or older and smokers are controlled by thoracic radiography in 6-8 weeks. PMID:26237912

  3. Ablation of huntingtin in adult neurons is nondeleterious but its depletion in young mice causes acute pancreatitis.

    PubMed

    Wang, Guohao; Liu, Xudong; Gaertig, Marta A; Li, Shihua; Li, Xiao-Jiang

    2016-03-22

    The Huntington's disease (HD) protein, huntingtin (HTT), is essential for early development. Because suppressing the expression of mutantHTTis an important approach to treat the disease, we must first understand the normal function of Htt in adults versus younger animals. Using inducibleHttknockout mice, we found thatHttdepletion does not lead to adult neurodegeneration or animal death at >4 mo of age, which was also verified by selectively depletingHttin neurons. On the other hand, young Htt KO mice die at 2 mo of age of acute pancreatitis due to the degeneration of pancreatic acinar cells. Importantly, Htt interacts with the trypsin inhibitor, serine protease inhibitor Kazal-type 3 (Spink3), to inhibit activation of digestive enzymes in acinar cells in young mice, and transgenicHTTcan rescue the early death of Htt KO mice. These findings point out age- and cell type-dependent vital functions of Htt and the safety of knocking down neuronal Htt expression in adult brains as a treatment. PMID:26951659

  4. Acute pulmonary function response to ozone in young adults as a function of body mass index

    EPA Science Inventory

    Recent studies have shown enhanced responsiveness to ozone in obese mice. Adiposity has not been examined as a possible modulator of ozone response in humans. We therefore examined the relationship between body mass index and the acute spirometric response to ozone (O(3)) exposur...

  5. The acute treatment of migraine in adults: the american headache society evidence assessment of migraine pharmacotherapies.

    PubMed

    Marmura, Michael J; Silberstein, Stephen D; Schwedt, Todd J

    2015-01-01

    The study aims to provide an updated assessment of the evidence for individual pharmacological therapies for acute migraine treatment. Pharmacological therapy is frequently required for acutely treating migraine attacks. The American Academy of Neurology Guidelines published in 2000 summarized the available evidence relating to the efficacy of acute migraine medications. This review, conducted by the members of the Guidelines Section of the American Headache Society, is an updated assessment of evidence for the migraine acute medications. A standardized literature search was performed to identify articles related to acute migraine treatment that were published between 1998 and 2013. The American Academy of Neurology Guidelines Development procedures were followed. Two authors reviewed each abstract resulting from the search and determined whether the full manuscript qualified for review. Two reviewers studied each qualifying full manuscript for its level of evidence. Level A evidence requires at least 2 Class I studies, and Level B evidence requires 1 Class I or 2 Class II studies. The specific medications - triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan [oral, nasal spray, injectable, transcutaneous patch], zolmitriptan [oral and nasal spray]) and dihydroergotamine (nasal spray, inhaler) are effective (Level A). Ergotamine and other forms of dihydroergotamine are probably effective (Level B). Effective nonspecific medications include acetaminophen, nonsteroidal anti-inflammatory drugs (aspirin, diclofenac, ibuprofen, and naproxen), opioids (butorphanol nasal spray), sumatriptan/naproxen, and the combination of acetaminophen/aspirin/caffeine (Level A). Ketoprofen, intravenous and intramuscular ketorolac, flurbiprofen, intravenous magnesium (in migraine with aura), and the combination of isometheptene compounds, codeine/acetaminophen and tramadol/acetaminophen are probably effective (Level B). The antiemetics prochlorperazine

  6. Changes in Monocyte Functions of Astronauts

    NASA Technical Reports Server (NTRS)

    Kaur, I.; Simons, E.; Castro, V.; Ott, C. Mark; Pierson, Duane L.

    2004-01-01

    Monocyte cell numbers and functions, including phagocytosis, oxidative burst capacity, and degranulation and expression of related surface molecules, were studied in blood specimens from 25 astronauts and 9 healthy control subjects. Blood samples were obtained 10 days before a space flight, 3 hours after landing and 3 days after landing. The number of monocytes in astronauts did not change significantly among the three sample collection periods. Following space flight, the monocytes ability to phagocytize Escherichia coli, to exhibit an oxidative burst, and to degranulate was reduced as compared to monocytes from control subjects. These alterations in monocyte functions after space flight correlated with alterations in the expression of CD32 and CD64.

  7. Acute stress differentially affects spatial configuration learning in high and low cortisol-responding healthy adults

    PubMed Central

    Meyer, Thomas; Smeets, Tom; Giesbrecht, Timo; Quaedflieg, Conny W. E. M.; Merckelbach, Harald

    2013-01-01

    Background Stress and stress hormones modulate memory formation in various ways that are relevant to our understanding of stress-related psychopathology, such as posttraumatic stress disorder (PTSD). Particular relevance is attributed to efficient memory formation sustained by the hippocampus and parahippocampus. This process is thought to reduce the occurrence of intrusions and flashbacks following trauma, but may be negatively affected by acute stress. Moreover, recent evidence suggests that the efficiency of visuo-spatial processing and learning based on the hippocampal area is related to PTSD symptoms. Objective The current study investigated the effect of acute stress on spatial configuration learning using a spatial contextual cueing task (SCCT) known to heavily rely on structures in the parahippocampus. Method Acute stress was induced by subjecting participants (N = 34) to the Maastricht Acute Stress Test (MAST). Following a counterbalanced within-subject approach, the effects of stress and the ensuing hormonal (i.e., cortisol) activity on subsequent SCCT performance were compared to SCCT performance following a no-stress control condition. Results Acute stress did not impact SCCT learning overall, but opposing effects emerged for high versus low cortisol responders to the MAST. Learning scores following stress were reduced in low cortisol responders, while high cortisol-responding participants showed improved learning. Conclusions The effects of stress on spatial configuration learning were moderated by the magnitude of endogenous cortisol secretion. These findings suggest a possible mechanism by which cortisol responses serve an adaptive function during stress and trauma, and this may prove to be a promising route for future research in this area. PMID:23671762

  8. Alcohol-Induced miR-27a Regulates Differentiation and M2 Macrophage Polarization of Normal Human Monocytes

    PubMed Central

    Saha, Banishree; Bruneau, Johanna C.; Kodys, Karen; Szabo, Gyongyi

    2015-01-01

    Alcohol abuse is a leading cause of liver disease characterized by liver inflammation, fatty liver, alcoholic hepatitis, or liver cirrhosis. Immunomodulatory effects of alcohol on monocytes and macrophages contribute to alcoholic liver disease. Alcohol use, an independent risk factor for progression of hepatitis C virus (HCV) infection–mediated liver disease, impairs host defense and alters cytokine production and monocyte/macrophage activation. We hypothesized that alcohol and HCV have synergistic effects on the phenotype and function of monocytes. Our data show that acute alcohol binge drinking in healthy volunteers results in increased frequency of CD16+ and CD68+ and M2-type (CD206+, dendritic cell [DC]-SIGN+–expressing and IL-10–secreting) circulating CD14+ monocytes. Expression of HCV-induced CD68 and M2 markers (CD206 and DC-SIGN) in normal monocytes was further enhanced in the presence of alcohol. The levels of microRNA (miR)-27a was significantly upregulated in monocytes cultured in the presence of alcohol or alcohol and HCV as compared with HCV alone. The functional role of miR-27a in macrophage polarization was demonstrated by transfecting monocytes with an miR-27a inhibitor that resulted in reduced alcohol- and HCV- mediated monocyte activation (CD14 and CD68 expression), polarization (CD206 and DC-SIGN expression), and IL-10 secretion. Over-expression of miR-27a in monocytes enhanced IL-10 secretion via activation of the ERK signaling pathway. We found that miR-27a promoted ERK phosphorylation by downregulating the expression of ERK inhibitor sprouty2 in monocytes. Thus, we identified that sprouty2 is a target of miR-27a in human monocytes. In summary, our study demonstrates the regulatory role of miR-27a in alcohol-induced monocyte activation and polarization. PMID:25716995

  9. Acute Multiple Organ Failure in Adult Mice Deleted for the Developmental Regulator Wt1

    PubMed Central

    Chau, You-Ying; Brownstein, David; Mjoseng, Heidi; Lee, Wen-Chin; Buza-Vidas, Natalija; Nerlov, Claus; Jacobsen, Sten Eirik; Perry, Paul; Berry, Rachel; Thornburn, Anna; Sexton, David; Morton, Nik; Hohenstein, Peter; Freyer, Elisabeth; Samuel, Kay; van't Hof, Rob; Hastie, Nicholas

    2011-01-01

    There is much interest in the mechanisms that regulate adult tissue homeostasis and their relationship to processes governing foetal development. Mice deleted for the Wilms' tumour gene, Wt1, lack kidneys, gonads, and spleen and die at mid-gestation due to defective coronary vasculature. Wt1 is vital for maintaining the mesenchymal–epithelial balance in these tissues and is required for the epithelial-to-mesenchyme transition (EMT) that generates coronary vascular progenitors. Although Wt1 is only expressed in rare cell populations in adults including glomerular podocytes, 1% of bone marrow cells, and mesothelium, we hypothesised that this might be important for homeostasis of adult tissues; hence, we deleted the gene ubiquitously in young and adult mice. Within just a few days, the mice suffered glomerulosclerosis, atrophy of the exocrine pancreas and spleen, severe reduction in bone and fat, and failure of erythropoiesis. FACS and culture experiments showed that Wt1 has an intrinsic role in both haematopoietic and mesenchymal stem cell lineages and suggest that defects within these contribute to the phenotypes we observe. We propose that glomerulosclerosis arises in part through down regulation of nephrin, a known Wt1 target gene. Protein profiling in mutant serum showed that there was no systemic inflammatory or nutritional response in the mutant mice. However, there was a dramatic reduction in circulating IGF-1 levels, which is likely to contribute to the bone and fat phenotypes. The reduction of IGF-1 did not result from a decrease in circulating GH, and there is no apparent pathology of the pituitary and adrenal glands. These findings 1) suggest that Wt1 is a major regulator of the homeostasis of some adult tissues, through both local and systemic actions; 2) highlight the differences between foetal and adult tissue regulation; 3) point to the importance of adult mesenchyme in tissue turnover. PMID:22216009

  10. Alcohol screening for older adults in an acute general hospital: FAST v. MAST-G assessments.

    PubMed

    Knightly, Rachel; Tadros, George; Sharma, Juhi; Duffield, Peter; Carnall, Emma; Fisher, Jacqui; Salman, Shaza

    2016-04-01

    Aims and method Documented prevalence of alcohol misuse among older adult patients at Birmingham Heartlands Hospital is significantly lower than the national prevalence. We aimed to evaluate our alcohol misuse screening protocol for older adults to identify possible shortcomings. Hospital protocol is to screen all adults for alcohol misuse in the accident and emergency (A&E) department using the Fast Alcohol Screening Test (FAST). One hundred consecutive consenting in-patients aged 65-94 admitted via A&E subsequently undertook an additional alcohol screening test (Michigan Alcoholism Screening Test-Geriatric version; MAST-G). Results of the two tests were compared. Results FAST screening was completed for 71 patients and none were FAST-positive for alcohol misuse, yet using MAST-G, 18 patients scored positively for alcohol misuse. FAST screening failed to identify 8 patients with a documented history of alcohol misuse. Clinical implications Older adult alcohol misuse prevalence is significantly underreported using FAST. Screening older adults for alcohol problems requires a different approach to screening the general population. PMID:27087989

  11. Alcohol screening for older adults in an acute general hospital: FAST v. MAST-G assessments

    PubMed Central

    Knightly, Rachel; Tadros, George; Sharma, Juhi; Duffield, Peter; Carnall, Emma; Fisher, Jacqui; Salman, Shaza

    2016-01-01

    Aims and method Documented prevalence of alcohol misuse among older adult patients at Birmingham Heartlands Hospital is significantly lower than the national prevalence. We aimed to evaluate our alcohol misuse screening protocol for older adults to identify possible shortcomings. Hospital protocol is to screen all adults for alcohol misuse in the accident and emergency (A&E) department using the Fast Alcohol Screening Test (FAST). One hundred consecutive consenting in-patients aged 65-94 admitted via A&E subsequently undertook an additional alcohol screening test (Michigan Alcoholism Screening Test-Geriatric version; MAST-G). Results of the two tests were compared. Results FAST screening was completed for 71 patients and none were FAST-positive for alcohol misuse, yet using MAST-G, 18 patients scored positively for alcohol misuse. FAST screening failed to identify 8 patients with a documented history of alcohol misuse. Clinical implications Older adult alcohol misuse prevalence is significantly underreported using FAST. Screening older adults for alcohol problems requires a different approach to screening the general population. PMID:27087989

  12. Yawning, acute stressors, and arousal reduction in Nazca booby adults and nestlings.

    PubMed

    Liang, Amy C; Grace, Jacquelyn K; Tompkins, Emily M; Anderson, David J

    2015-03-01

    Yawning is a familiar and phylogenetically widespread phenomenon, but no consensus exists regarding its functional significance. We tested the hypothesis that yawning communicates to others a transition from a state of physiological and/or psychological arousal (for example, due to action of a stressor) to a more relaxed state. This arousal reduction hypothesis predicts little yawning during arousal and more yawning (above baseline) during and after down-regulation of arousal. Experimental capture-restraint tests with wild adult Nazca boobies (Sula granti), a seabird, increased yawning frequency after release from restraint, but yawning was almost absent during tests. Natural maltreatment by non-parental adults also increased yawning by nestlings, but only after the maltreatment ended and the adult left. CORT (corticosterone) was a logical a priori element of the stress response affecting the stressor-yawning relationship under the arousal reduction hypothesis, and cannot be excluded as such for adults in capture-restraint tests but is apparently unimportant for nestlings being maltreated by adults. The arousal reduction hypothesis unites formerly disparate results on yawning: its socially contagious nature in some taxa, its clear pharmacological connection to the stress response, and its temporal linkage to transitions in arousal between consciousness and sleep. PMID:25498600

  13. Localized CCR2 Activation in the Bone Marrow Niche Mobilizes Monocytes by Desensitizing CXCR4

    PubMed Central

    Park, Jeong Eun; Miller, Richard J.

    2015-01-01

    Inflammatory (classical) monocytes residing in the bone marrow must enter the bloodstream in order to combat microbe infection. These monocytes express high levels of CCR2, a chemokine receptor whose activation is required for them to exit the bone marrow. How CCR2 is locally activated in the bone marrow and how their activation promotes monocyte egress is not understood. Here, we have used double transgenic lines that can visualize CCR2 activation in vivo and show that its chemokine ligand CCL2 is acutely released by stromal cells in the bone marrow, which make direct contact with CCR2-expressing monocytes. These monocytes also express CXCR4, whose activation immobilizes cells in the bone marrow, and are in contact with stromal cells expressing CXCL12, the CXCR4 ligand. During the inflammatory response, CCL2 is released and activates the CCR2 on neighboring monocytes. We demonstrate that acutely isolated bone marrow cells co-express CCR2 and CXCR4, and CCR2 activation desensitizes CXCR4. Inhibiting CXCR4 by a specific receptor antagonist in mice causes CCR2-expressing cells to exit the bone marrow in absence of inflammatory insults. Taken together, these results suggest a novel mechanism whereby the local activation of CCR2 on monocytes in the bone marrow attenuates an anchoring signalling provided by CXCR4 expressed by the same cell and mobilizes the bone marrow monocyte to the blood stream. Our results also provide a generalizable model that cross-desensitization of chemokine receptors fine-tunes cell mobility by integrating multiple chemokine signals. PMID:26029924

  14. Short-term acute effects of gutkha chewing on heart rate variability among young adults: A cross-sectional study

    PubMed Central

    Itagi, Afreen Begum H; Arora, Dimple; Patil, Navin A; Bailwad, Sandeep Anant; Yunus, GY; Goel, Ankit

    2016-01-01

    Background and Objectives: An increase in the consumption of smokeless tobacco has been noticed among high school, college students, and adults. Despite the antiquity and popularity of chewing tobacco in India, its effects have not been investigated systematically in humans. The aim of this study was to investigate acute effects of gutkha chewing on heart rate variability (HRV) among healthy young adults. Materials and Methods: A total of 60 young adult males were included in the study. Each individual was asked to chew tobacco and subjected to HRV analysis. HRV analysis using short-term electrocardiogram recording was used to measure HRV parameters before gutkha chewing and at 5, 15, and 30 min after chewing tobacco. One-way analysis of variance and paired t-test was used to assess changes over time. Results: There was a significant increase in heart rate (HR) during tobacco chewing. Mean HR at baseline measured 73.0 ± 6.2 bpm. There was a rise in mean HR to 83.7 ± 9.1 bpm at 5 min during tobacco chewing and gradual reduction to baseline observed after 15 min followed by no significant change till 30 min. The normalized low-frequency power and LF/high-frequency (HF) power ratio were elevated after 5 min; however, normalized HF power was reduced after 5 min tobacco chewing. Conclusion: Gutkha is closely associated with traditional cardiovascular risk factors as detected by a transient enhancing sympathetic activity during tobacco chewing in the form of increased HRV parameters or an imbalance between sympathetic and parasympathetic neural activity among healthy young adults. PMID:26958522

  15. Effects of acute aerobic exercise on a task-switching protocol and brain-derived neurotrophic factor concentrations in young adults with different levels of cardiorespiratory fitness.

    PubMed

    Tsai, Chia-Liang; Pan, Chien-Yu; Chen, Fu-Chen; Wang, Chun-Hao; Chou, Feng-Ying

    2016-07-01

    What is the central question of this study? Neurocognitive functions can be enhanced by acute aerobic exercise, which could be associated with changes in serum brain-derived neurotrophic factor (BDNF) concentrations. We aimed to explore acute exercise-induced changes in BDNF concentrations, neuropsychological and neurophysiological performances when individuals with different levels of cardiorespiratory fitness performed a cognitive task. What is the main finding and its importance? Only young adults with higher cardiorespiratory fitness could attain switching cost and neurophysiological benefits via acute aerobic exercise. The mechanisms might be fitness dependent. Although acute aerobic exercise could enhance serum BDNF concentrations, changes in peripheral BDNF concentrations could not be the potential factor involved in the beneficial effects on neurocognitive performance. This study investigated the effects of acute aerobic exercise on neuropsychological and neurophysiological performances in young adults with different cardiorespiratory fitness levels when performing a task-switching protocol and explored the potential associations between acute aerobic exercise-induced changes in serum brain-derived neurotrophic factor (BDNF) concentrations and various neurocognitive outcomes. Sixty young adults were categorized into one control group (i.e. non-exercise-intervention; n = 20) and two exercise-intervention (EI) groups [i.e. higher (EIH , n = 20) and lower (EIL , n = 20) cardiorespiratory fitness] according to their maximal oxygen consumption. At baseline and after either an acute bout of 30 min of moderate-intensity aerobic exercise or a control period, the neuropsychological and neurophysiological performances and serum BDNF concentrations were measured when the participants performed a task-switching protocol involving executive control and greater demands on working memory. The results revealed that although acute aerobic exercise decreased reaction

  16. Acute lymphoblastic leukaemia in adults: the case for a strategic shift in study approach.

    PubMed

    Proctor, S J

    1994-10-01

    After 20 years of frantic chemotherapeutic activity, all concerned with adult ALL are now resigned to the fact that only some 20% of the overall adult cases are biologically similar to childhood ALL, and the majority of these are in the adolescent age groups. It is evident that as much effort as possible must be made to dissect out such chemocurable patients from the bulk of patients with adult ALL so that they might obtain cure with conventional chemotherapy, thus avoiding early transplantation or unnecessary intensification. In such a rare disease, unless we organize nationally, and look at population-based studies linked to phase III or phase II studies where appropriate, we are destined not to develop appropriate strategies for treatment of this disease for a long time to come. PMID:7803264

  17. How to Apply the AHS Evidence Assessment of the Acute Treatment of Migraine in Adults to your Patient with Migraine.

    PubMed

    Pringsheim, Tamara; Davenport, William Jeptha; Marmura, Michael J; Schwedt, Todd J; Silberstein, Stephen

    2016-07-01

    The "Acute Treatment of Migraine in Adults: The American Headache Society Evidence Assessment of Migraine Pharmacotherapies" provides levels of evidence for medication efficacy for acute treatment of migraine. The goal of this companion paper is to provide guidance on how to choose between evidence-based treatment options, and, based on the clinical characteristics of the patient and their migraine attacks, to provide guidance on designing an individualized strategy for managing migraine attacks. The acute pharmacological treatments described in the American Headache Society evidence assessment can be divided into those initially taken by the patient during the headache phase of the migraine attack, those taken by the patient later in the attack when initial treatments fail, and those administered intravenously or intramuscularly in urgent care settings. Medications taken initially by patients in the headache phase include nonspecific analgesics such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), triptans, and dihydroergotamine (DHE). A stratified approach to treatment is advised, with the choice of medication based on the patient's treatment needs, taking into consideration the attack severity, presence of associated symptoms such as nausea and vomiting, and the degree of migraine-related disability. Individuals with migraine may find reassurance in having a "back-up plan" in the event of an initial acute treatment failure. For those individuals who had a partial response to the initial acute treatment, a second dose might be indicated. When the initial treatment does not provide meaningful and sustained benefits, a treatment from a different medication class is typically chosen. Depending upon the initial treatment used, this might include NSAIDs, triptans, or DHE. Opioids or acetaminophen in combination with codeine or tramadol can be considered as part of the "back-up plan," provided they are used infrequently. When all patient administered

  18. Flavopiridol induces BCL-2 expression and represses oncogenic transcription factors in leukemic blasts from adults with refractory acute myeloid leukemia

    PubMed Central

    Nelson, Dwella M.; Joseph, Biju; Hillion, Joelle; Segal, Jodi; Karp, Judith E.; Resar, Linda M. S.

    2011-01-01

    Flavopiridol is a cyclin-dependent kinase inhibitor that induces cell cycle arrest, apoptosis, and clinical responses in selected patients with acute myeloid leukemia (AML). A better understanding of the molecular pathways targeted by flavopiridol is needed to design optimal combinatorial therapy. Here, we report that in vivo administration of flavopiridol induced expression of the BCL-2 anti-apoptotic gene in leukemic blasts from adult patients with refractory AML. Moreover, flavopiridol repressed the expression of genes encoding oncogenic transcription factors (HMGA1, STAT3, E2F1) and the major subunit of RNA Polymerase II. Our results provide mechanistic insight into the cellular pathways targeted by flavopiridol and suggest that blocking anti-apoptotic pathways could enhance cytotoxicity and improve outcomes in patients treated with flavopiridol. PMID:21728742

  19. Deletion and deletion/insertion mutations in the juxtamembrane domain of the FLT3 gene in adult acute myeloid leukemia

    PubMed Central

    Deeb, Kristin K.; Smonskey, Matthew T.; DeFedericis, HanChun; Deeb, George; Sait, Sheila N.J.; Wetzler, Meir; Wang, Eunice S.; Starostik, Petr

    2014-01-01

    In contrast to FLT3 ITD mutations, in-frame deletions in the FLT3 gene have rarely been described in adult acute leukemia. We report two cases of AML with uncommon in-frame mutations in the juxtamembrane domain of the FLT3 gene: a 3-bp (c.1770_1774delCTACGinsGT; p.F590_V592delinsLF) deletion/insertion and a 12-bp (c.1780_1791delTTCAGAGAATAT; p.F594_Y597del) deletion. We verified by sequencing that the reading frame of the FLT3 gene was preserved and by cDNA analysis that the mRNA of the mutant allele was expressed in both cases. Given the recent development of FLT3 inhibitors, our findings may be of therapeutic value for AML patients harboring similar FLT3 mutations. PMID:25379410

  20. Paliperidone palmitate injection for the acute and maintenance treatment of schizophrenia in adults

    PubMed Central

    Kim, Shiyun; Solari, Hugo; Weiden, Peter J; Bishop, Jeffrey R

    2012-01-01

    Purpose To review the use of paliperidone palmitate in treatment of patients with schizophrenia. Methods Published clinical trial data for the development and utilization of paliperidone palmitate for the treatment of schizophrenia were assessed in this review. Four short-term, randomized, double-blind, placebo-controlled trials investigated the efficacy of paliperidone palmitate in acute exacerbation of schizophrenia. Paliperidone palmitate was also studied as a maintenance treatment to prevent or delay relapse in stable schizophrenia. In addition, paliperidone palmitate was compared to risperidone long-acting injection for noninferiority in three studies. Results Paliperidone palmitate has been shown to be effective in reducing symptoms as measured by the Positive and Negative Syndrome Scale total scores in the four acute treatment studies. In the maintenance treatment studies, paliperidone palmitate was found to be more effective than placebo in preventing or delaying the time to first relapse in stable schizophrenia patients. In addition, paliperidone palmitate was shown to be noninferior to risperidone long-acting injection in two studies. It was shown to be reasonably well tolerated in all clinical trials. Acute treatment phase should be initiated with a dose of 234 mg on day one and 156 mg on day eight, followed by a recommended monthly maintenance dose of 39–234 mg based on efficacy and tolerability results from the clinical studies. Conclusion Providing an optimal long-term treatment can be challenging. Paliperidone palmitate can be used as an acute treatment even in outpatient setting, and it has shown to be well tolerated by patients. Also, it does not require overlapping oral antipsychotic supplementation while being initiated, and is dosed once per month. PMID:22879739

  1. In vivo imaging reveals a pioneer wave of monocyte recruitment into mouse skin wounds.

    PubMed

    Rodero, Mathieu P; Licata, Fabrice; Poupel, Lucie; Hamon, Pauline; Khosrotehrani, Kiarash; Combadiere, Christophe; Boissonnas, Alexandre

    2014-01-01

    The cells of the mononuclear phagocyte system are essential for the correct healing of adult skin wounds, but their specific functions remain ill-defined. The absence of granulation tissue immediately after skin injury makes it challenging to study the role of mononuclear phagocytes at the initiation of this inflammatory stage. To study their recruitment and migratory behavior within the wound bed, we developed a new model for real-time in vivo imaging of the wound, using transgenic mice that express green and cyan fluorescent proteins and specifically target monocytes. Within hours after the scalp injury, monocytes invaded the wound bed. The complete abrogation of this infiltration in monocyte-deficient CCR2(-/-) mice argues for the involvement of classical monocytes in this process. Monocyte infiltration unexpectedly occurred as early as neutrophil recruitment did and resulted from active release from the bloodstream toward the matrix through microhemorrhages rather than transendothelial migration. Monocytes randomly scouted around the wound bed, progressively slowed down, and stopped. Our approach identified and characterized a rapid and earlier than expected wave of monocyte infiltration and provides a novel framework for investigating the role of these cells during early stages of wound healing. PMID:25272047

  2. Acute exposure to gas-supersaturated water does not affect reproductive success of female adult chinook salmon late in maturation

    USGS Publications Warehouse

    Gale, William L.; Maule, A.G.; Postera, A.; Peters, M.H.

    2004-01-01

    At times, total dissolved gas concentrations in the Columbia and Snake rivers have been elevated due to involuntary spill from high spring runoff and voluntary spill used as a method to pass juvenile salmonids over dams. The goal of this project was to determine if acute exposure to total dissolved gas supersaturation (TDGS) affects the reproductive performance of female chinook salmon late in their maturation. During this study, adult female spring chinook salmon were exposed to mean TDGS levels of 114.1 % to 125.5%. We ended exposures at first mortality, or at the appearance of impending death. Based on this criterion, exposures lasted from 10 to 68 h and were inversely related to TDGS. There was no effect of TDGS on pre-spawning mortality or fecundity when comparing treatment fish to experimental controls or the general hatchery population four to six weeks after exposures. Egg quality, based on egg weight and egg diameter, did not differ between treatment and control fish. Fertilization rate and survival to eyed-stage was high (>94%) for all groups. With the exception of Renibacterium salmoninarum (the causative agent of bacterial kidney disease; BKD), no viral or bacterial fish pathogens were isolated from experimental fish. The prevalence (about 45%) and severity of R. salmoninarum did not differ among the groups or the general hatchery population. We conclude that these acute exposures to moderate levels of gas-supersaturated water-perhaps similar to that experienced by immigrating adult salmon as they approach and pass a hydropower dam on the Columbia River-did not affect reproductive success of female chinook salmon late in their maturation. These results are most applicable to summer and fall chinook salmon, which migrate in the summer/fall and spawn shortly after reaching their natal streams. Published in 2004 by John Wiley and Sons, Ltd.

  3. Preterm infants have deficient monocyte and lymphocyte cytokine responses to group B streptococcus.

    PubMed

    Currie, Andrew J; Curtis, Samantha; Strunk, Tobias; Riley, Karen; Liyanage, Khemanganee; Prescott, Susan; Doherty, Dorota; Simmer, Karen; Richmond, Peter; Burgner, David

    2011-04-01

    Group B streptococcus (GBS) is an important cause of early- and late-onset sepsis in the newborn. Preterm infants have markedly increased susceptibility and worse outcomes, but their immunological responses to GBS are poorly defined. We compared mononuclear cell and whole-blood cytokine responses to heat-killed GBS (HKGBS) of preterm infants (gestational age [GA], 26 to 33 weeks), term infants, and healthy adults. We investigated the kinetics and cell source of induced cytokines and quantified HKGBS phagocytosis. HKGBS-induced tumor necrosis factor (TNF) and interleukin 6 (IL-6) secretion was significantly impaired in preterm infants compared to that in term infants and adults. These cytokines were predominantly monocytic in origin, and production was intrinsically linked to HKGBS phagocytosis. Very preterm infants (GA, <30 weeks) had fewer cytokine-producing monocytes, but nonopsonic phagocytosis ability was comparable to that for term infants and adults. Exogenous complement supplementation increased phagocytosis in all groups, as well as the proportion of preterm monocytes producing IL-6, but for very preterm infants, responses were still deficient. Similar defective preterm monocyte responses were observed in fresh whole cord blood stimulated with live GBS. Lymphocyte-associated cytokines were significantly deficient for both preterm and term infants compared to levels for adults. These findings indicate that a subset of preterm monocytes do not respond to GBS, a defect compounded by generalized weaker lymphocyte responses in newborns. Together these deficient responses may increase the susceptibility of preterm infants to GBS infection. PMID:21300777

  4. Preterm Infants Have Deficient Monocyte and Lymphocyte Cytokine Responses to Group B Streptococcus▿

    PubMed Central

    Currie, Andrew J.; Curtis, Samantha; Strunk, Tobias; Riley, Karen; Liyanage, Khemanganee; Prescott, Susan; Doherty, Dorota; Simmer, Karen; Richmond, Peter; Burgner, David

    2011-01-01

    Group B streptococcus (GBS) is an important cause of early- and late-onset sepsis in the newborn. Preterm infants have markedly increased susceptibility and worse outcomes, but their immunological responses to GBS are poorly defined. We compared mononuclear cell and whole-blood cytokine responses to heat-killed GBS (HKGBS) of preterm infants (gestational age [GA], 26 to 33 weeks), term infants, and healthy adults. We investigated the kinetics and cell source of induced cytokines and quantified HKGBS phagocytosis. HKGBS-induced tumor necrosis factor (TNF) and interleukin 6 (IL-6) secretion was significantly impaired in preterm infants compared to that in term infants and adults. These cytokines were predominantly monocytic in origin, and production was intrinsically linked to HKGBS phagocytosis. Very preterm infants (GA, <30 weeks) had fewer cytokine-producing monocytes, but nonopsonic phagocytosis ability was comparable to that for term infants and adults. Exogenous complement supplementation increased phagocytosis in all groups, as well as the proportion of preterm monocytes producing IL-6, but for very preterm infants, responses were still deficient. Similar defective preterm monocyte responses were observed in fresh whole cord blood stimulated with live GBS. Lymphocyte-associated cytokines were significantly deficient for both preterm and term infants compared to levels for adults. These findings indicate that a subset of preterm monocytes do not respond to GBS, a defect compounded by generalized weaker lymphocyte responses in newborns. Together these deficient responses may increase the susceptibility of preterm infants to GBS infection. PMID:21300777

  5. Types, Risk Factors, Clinical symptoms and Diagnostic Tests of Acute Adult Meningitis in Northern Iran During 2006-2012

    PubMed Central

    Bagheri-Nesami, Masoumeh; Babamahmoodi, Farhang

    2015-01-01

    Background Acute bacterial meningitis is a medical emergency condition that requires prompt diagnosis and treatment and otherwise associated with serious morbidity and mortality. Aim The aim of this study was to assess types, risk factors, clinical symptoms and diagnostic tests of meningitis in hospitalized patients of Mazandaran University of medical sciences hospitals during 2006-2012. Matherials and Methods This is a retrospective descriptive study. Following approval of the ethics committee of Mazandaran University of Medical Sciences, records of adult patients diagnosed with acute meningitis from 2006 to 2012 were extracted from Mazandaran Provincial Health Center and patients attending hospitals affiliated to Mazandaran University of Medical Sciences. Statistical Analysis Data were analyzed with SPSS-16 using descriptive statistics (frequency, mean, standard deviation, and median). Results In this study, of the 137 patients with meningitis, 73 (53.9%) were viral, 61 (46%) bacterial, 1 (0.7%) fungal, and 2 (1.4%) unknown. The majority of risk factors in patients were head trauma, upper respiratory infection, and drug addiction. The most common clinical signs were headache, fever, nausea and vomiting, and stiff neck. Conclusion In this study, the incidence of meningitis was much lower than any other country. It could be due to geographic variation or incomplete recording of patient's data. It is recommended to perform a longitudinal study during the coming years on patients with meningitis. PMID:26155497

  6. [Evaluation of the treat of acute poisoning with chemical compounds among adult inhabitants of Krakow in 1995].

    PubMed

    Kamenczak, A; Pach, K; Kłys, M; Motyka, E

    1997-01-01

    The goal of this study is to evaluate the number and the reasons (poison and structure) of acute poisonings which occurred among Kraków adult inhabitants in the year 1995. Under analysis there were 3003 people treated at the Department of Clinical Toxicology and 210 poisoned who died at the place of accident prior to any treatment was conducted. The group of hospitalized persons consisted of 63.7% men and 36.3% women, and the group of people who died at the place of accident consisted of 89.5% men and of 10.5% women. The overall coefficient of poisonings during the year 1995 was 48.3; for men was 66.7 and 32.5 for women. A drugs (45.1%) followed by ethanol (42.8%) were the most common cause of acute poisonings. The mortality rate of the treated patients was low (0.7%), but while including those people who died at the place of accident prior to any treatment, the mortality rate rose up to 7.2%. That increase in the mortality rate was caused mainly by fatal cases due to ethanol and carbon monoxide poisonings. PMID:9333887

  7. Belatacept for prevention of acute rejection in adult patients who have had a kidney transplant: an update

    PubMed Central

    Wojciechowski, David; Vincenti, Flavio

    2012-01-01

    In June 2011, the US Food and Drug Administration approved belatacept for the prophylaxis of organ rejection in adult kidney transplant recipients. This review discusses the use of belatacept for the prevention of acute rejection as part of a maintenance immunosuppression regimen. Belatacept is a selective costimulation blocker designed to provide effective immunosuppression while avoiding the toxicities associated with calcineurin inhibitors. Phase III trial data have demonstrated that belatacept is noninferior to cyclosporine in 1-year patient and allograft survival. Three-year data demonstrate an ongoing improvement in mean measured glomerular filtration rate in belatacept-treated versus cyclosporine-treated patients. However, the rate of acute rejection was higher in belatacept-treated patients compared with cyclosporine. Specifically, there was a higher incidence of Banff type II rejections in patients treated with belatacept. Despite the higher Banff grade, rejections on belatacept were not associated with other factors associated with poor outcomes, such as the development of donor-specific antibodies or reduced estimated glomerular filtration rate. One safety issue that must be considered when using belatacept is the potential for increased risk of post-transplant lymphoproliferative disease. There were more cases of post-transplant lymphoproliferative disease in belatacept-treated patients, especially in recipients seronegative for Epstein–Barr virus or patients treated with lymphocyte-depleting agents. Therefore, belatacept can be recommended for use in Epstein–Barr virus antibody-positive recipients. PMID:23152668

  8. Sex disparity in childhood and young adult acute myeloid leukemia (AML) survival: Evidence from US population data.

    PubMed

    Hossain, Md Jobayer; Xie, Li

    2015-12-01

    Sex variation has been persistently investigated in studies concerning acute myeloid leukemia (AML) survival outcomes but has not been fully explored among pediatric and young adult AML patients. We detected sex difference in the survival of AML patients diagnosed at ages 0-24 years and explored distinct effects of sex across subgroups of age at diagnosis, race-ethnicity and AML subtypes utilizing the United States Surveillance Epidemiology and End Results (SEER) population based dataset of 4865 patients diagnosed with AML between 1973 and 2012. Kaplan-Meier survival function, propensity scores and stratified Cox proportional hazards regression were used for data analyses. After controlling for other prognostic factors, females showed a significant survival advantage over their male counterparts, adjusted hazard ratio (aHR, 95% confidence interval (CI): 1.09, 1.00-1.18). Compared to females, male patients had substantially increased risk of mortality in the following subgroups of: ages 20-24 years at diagnosis (aHR1.30), Caucasian (1.14), acute promyelocytic leukemia (APL) (1.35), acute erythroid leukemia (AEL) (1.39), AML with inv(16)(p13.1q22) (2.57), AML with minimum differentiation (1.47); and had substantially decreased aHR in AML t(9;11)(p22;q23) (0.57) and AML with maturation (0.82). Overall, females demonstrated increased survival over males and this disparity was considerably large in patients ages 20-24 years at diagnosis, Caucasians, and in AML subtypes of AML inv(16), APL and AEL. In contrast, males with AML t(9;11)(p22;q23), AML with maturation and age at diagnosis of 10-14 years showed survival benefit. Further investigations are needed to detect the biological processes influencing the mechanisms of these interactions. PMID:26520618

  9. Development of clinical practice guidelines for urinary continence care of adult stroke survivors in acute and rehabilitation settings.

    PubMed

    Fisher, Andrea R

    2014-01-01

    This study developed evidence-based clinical practice guidelines for the urinary continence care of adult stroke survivors in acute and rehabilitation settings. The research team conducted a comprehensive review of the literature on urinary continence interventions and outcomes. The team then developed a set of recommendations outlined in the resulting clinical practice guidelines titled Clinical Practice Guidelines (CPGs) for the Urinary Continence Care of Stroke Survivors in Acute and Rehabilitation Settings. The evaluation of the CPGs consisted of a two-part assessment and pilot implementation. An expert panel of 25 local and regional experts in stroke and continence care assessed the proposed CPGs. This assessment consisted of two stages: a) evaluating the guidelines using the Appraisal of Guidelines Research and Evaluation (AGREE) Instrument (http://www. agreetrust.org); and, b) conducting focus groups to identify barriers and facilitators to the implementation of the guidelines using the Ottawa Model of Research Use (OMRU). Results from the expert panel assessments/feedback contributed to the refinement of the CPGs as well as identification and construction of implementation strategies. Two sites conducted a three-month pilot implementation of three recommendations from the CPGs as selected by each site. The two inpatient sites were a rehabilitation setting and a mixed acute and rehabilitation setting. The implementation of the CPGs included the development of learning strategies tailored to the needs of each site and in addition to the creation of an online self-learning portal. This study assessed nurses' knowledge, attitudes, and beliefs regarding urinary continence challenges using a survey before and after the pilot. Chart reviews before and after the pilot implementation audited the nurses' urinary continence practices for patients and uptake of the selected guidelines' recommendations. Study findings suggested the implementation of the CPGs

  10. REPRODUCTIVE EFFECTS OF LOW ACUTE DOSES OF CADMIUM CHLORIDE IN ADULT MALE RATS

    EPA Science Inventory

    Adult male Sprague-Dawley rats were injected sc with cadmium (Cd, as cadmium chloride) in doses ranging from 1.6 to 152 micromol Cd/kg body weight (body wt). Fourteen days after dosing, animals were evaluated for reproductive damage. Evaluations for each animal included tests, se...

  11. S1312, Inotuzumab Ozogamicin and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Leukemia

    ClinicalTrials.gov

    2016-04-14

    Acute Leukemias of Ambiguous Lineage; B-cell Adult Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma

  12. Age-related dynamics of constitutive cytokine transcription levels of feline monocytes.

    PubMed

    Kipar, A; Baptiste, K; Meli, M L; Barth, A; Knietsch, M; Reinacher, M; Lutz, H

    2005-03-01

    Monocytes/macrophages are central mediators of inflammation and immunity and therefore of major interest in the study of immunosenescence. In healthy adult cats, monocytes have been shown to constitutively transcribe pro- and anti-inflammatory cytokines. However, in order to characterize the effect of age, feline monocyte functions were examined for changes in cytokine transcription levels in early stages of immunosenescence. For this purpose, isolated, short-term cultured monocytes from barrier-maintained adult cats of different ages (15 mo to 10 yr) were examined for transcription of IL-1 beta, IL-6, IL-10, IL-12 p40 and TNF-alpha by real-time PCR. Transcription levels of cytokines varied and were generally highest for IL-1 beta. For IL-1 beta, IL-6 and IL-12 p40, both young and old cats exhibited highest levels. The age association was significant. TNF-alpha appeared to be transcribed at similar levels over the examination period, whereas IL-10 tended to decline with age but without any statistical significant differences. The observed age association of the constitutive transcription of some cytokines indicates a drop in monocyte activities from youth to middle age, which is then followed by a (progressive) increase with increasing age. This provides evidence that monocytes are in part responsible for the pro-inflammatory status observed with ageing. PMID:15763402

  13. Management of adult and paediatric acute lymphoblastic leukaemia in Asia: resource-stratified guidelines from the Asian Oncology Summit 2013

    PubMed Central

    Yeoh, Allen EJ; Tan, Daryl; Li, Chi-Kong; Hori, Hiroki; Tse, Eric; Pui, Ching-Hon

    2014-01-01

    The survival rates for both adult and children with acute lymphoblastic leukaemia have improved substantially in recent years with wider use of improved risk-directed therapy and supportive care. In nearly all developed countries, clinical practice guidelines have been formulated by multidisciplinary panels of leukaemia experts, with the goal of providing recommendations on standard treatment approaches based on current evidence. However, those guidelines do not take into account resource limitations in low-income countries, including financial and technical challenges. In Asia, there are huge disparities in economy and infrastructure among the countries, and even among different regions in some large countries. This review summarizes the recommendations developed for Asian countries by a panel of adult and paediatric leukaemia therapists, based on the availability of financial, skill and logistical resources, at a consensus session held as part of the 2013 Asian Oncology Summit in Bangkok, Thailand. The management strategies described here are stratified by a four-tier system (basic, limited, enhanced and maximum) based on the resources available to a particular country or region. PMID:24176570

  14. A six gene expression signature defines aggressive subtypes and predicts outcome in childhood and adult acute lymphoblastic leukemia

    PubMed Central

    Wang, Jin; Mi, Jian-Qing; Debernardi, Alexandra; Vitte, Anne-Laure; Emadali, Anouk; Meyer, Julia A.; Charmpi, Konstantina; Ycart, Bernard; Callanan, Mary B.; Carroll, William L.; Khochbin, Saadi; Rousseaux, Sophie

    2015-01-01

    Abnormal gene expression in cancer represents an under-explored source of cancer markers and therapeutic targets. In order to identify gene expression signatures associated with survival in acute lymphoblastic leukemia (ALL), a strategy was designed to search for aberrant gene activity, which consists of applying several filters to transcriptomic datasets from two pediatric ALL studies. Six genes whose expression in leukemic blasts was associated with prognosis were identified:three genes predicting poor prognosis (AK022211, FASTKD1 and STARD4) and three genes associated with a favorable outcome (CAMSAP1, PCGF6 and SH3RF3). Combining the expression of these 6 genes could successfully predict prognosis not only in the two discovery pediatric ALL studies, but also in two independent validation cohorts of adult patients, one from a publicly available study and one consisting of 62 newly recruited Chinese patients. Moreover, our data demonstrate that our six gene based test is particularly efficient in stratifying MLL or BCR.ABL negative patients. Finally, common biological traits characterizing aggressive forms of ALL in both children and adults were found, including features of dormant hematopoietic stem cells, suggesting new therapeutic strategies. PMID:26001296

  15. Extracorporeal photopheresis for treatment of adults and children with acute GVHD: UK consensus statement and review of published literature.

    PubMed

    Das-Gupta, E; Dignan, F; Shaw, B; Raj, K; Malladi, R; Gennery, A; Bonney, D; Taylor, P; Scarisbrick, J

    2014-10-01

    Extracorporeal photopheresis (ECP) has been used for over 20 years to treat acute GVHD (aGVHD) and chronic GVHD. Evidence on the efficacy of response in aGVHD has continued to accrue and data suggest that there is a good response and prolonged survival in both children and adults with grade II-IV aGVHD. Unlike chronic GVHD where treatment schedules are typically one or two times monthly for 12-18 months, patients with aGVHD respond rapidly to an intense weekly treatment schedule for 8 weeks, typically allowing steroids to be discontinued without flare-ups of aGVHD. Maintenance ECP therapy is generally not required. Many centres across Europe and United States treat aGVHD with ECP as second-line therapy and responses are excellent in a subset of patients. Unlike other second-line therapies, ECP is not immunosuppressive and has no reported drug interactions. Importantly, ECP does not have a negative impact on the graft-versus-malignancy effect of the transplant. This statement aims to select those patients most likely to respond to treatment and summarises treatment and monitoring schedules for the management of aGVHD in adult and paediatric patients to ensure the correct patients are treated with the optimal protocol for efficacy. PMID:24887389

  16. Overview of systematic reviews: yoga as a therapeutic intervention for adults with acute and chronic health conditions.

    PubMed

    McCall, Marcy C; Ward, Alison; Roberts, Nia W; Heneghan, Carl

    2013-01-01

    Objectives. Overview the quality, direction, and characteristics of yoga interventions for treatment of acute and chronic health conditions in adult populations. Methods. We searched for systematic reviews in 10 online databases, bibliographic references, and hand-searches in yoga-related journals. Included reviews satisfy Oxman criteria and specify yoga as a primary intervention in one or more randomized controlled trials for treatment in adults. The AMSTAR tool and GRADE approach evaluated the methodological quality of reviews and quality of evidence. Results. We identified 2202 titles, of which 41 full-text articles were assessed for eligibility and 26 systematic reviews satisfied inclusion criteria. Thirteen systematic reviews include quantitative data and six papers include meta-analysis. The quality of evidence is generally low. Sixteen different types of health conditions are included. Eleven reviews show tendency towards positive effects of yoga intervention, 15 reviews report unclear results, and no, reviews report adverse effects of yoga. Yoga appears most effective for reducing symptoms in anxiety, depression, and pain. Conclusion. Although the quality of systematic reviews is high, the quality of supporting evidence is low. Significant heterogeneity and variability in reporting interventions by type of yoga, settings, and population characteristics limit the generalizability of results. PMID:23762174

  17. Clinical profile of non-traumatic acute abdominal pain presenting to an adult emergency department

    PubMed Central

    Chanana, Lakshay; Jegaraj, Moses A. K.; Kalyaniwala, Kimmin; Yadav, Bijesh; Abilash, Kundavaram

    2015-01-01

    Background: Abdominal pain is one of the most common reasons for presenting to the emergency depatment (ED) and the etiology is varied. Materials and Methods: This prospective observational study was conducted in a large ED of a tertiary care center in India. All patients older than 15 years and presenting with non-traumatic abdominal pain to the ED from May 2012 to October 2012 were recruited and the demographic characteristics, diagnosis and outcome were analyzed. Results: The study cohort included 264 patients over a 6 month period. More than half (55.6%) were aged between 15 and 40 years. There was a male predominance (56.8%). Majority of the patients (76.9%) presented with abdominal pain of less than 72 hour duration. The pain was sudden in onset in 54.9% of patients. Dull type was the most common character of pain (36%) followed by colicky type (22.3%). The most common site of pain was the lower abdomen (45.8%). Upper abdominal pain was seen in 26.9% and the pain was generalized in 27.3% of patients. The common causes were uretericcolic (16.3%), urinary tract infection (12.5%), acute pancreatitis (11%), acute appendicitis (10.6%) and acute gastritis (8%). More than half (51.9%) discharged from ED and 37% of cases were managed by the emergency physicians. Surgical intervention was required in 25.8% of patients. The mortality rate was 2.3%. Conclusions: Abdominal pain is a common ED symptom and clinicians must consider multiple diagnoses, especially those that require immediate intervention to limit morbidity and mortality. PMID:26288785

  18. Role of basiliximab in the prevention of acute cellular rejection in adult to adult living-related liver transplantation: a single center experience

    PubMed Central

    Gruttadauria, S; Mandalà, L; Biondo, D; Spampinato, M; Lamonaca, V; Volpes, R; Vizzini, G; Marsh, JW; Marcos, A; Gridelli, B

    2007-01-01

    We report our single center experience with the use of basiliximab, a chimeric monoclonal antibody directed against the alpha chain of the interleukin-2 (IL-2) receptor (CD25), in combination with a steroid- and tacrolimus-based regimen in adult to adult living-related liver transplantation (ALRLT). Sixty consecutive ALRLTs were analyzed. All patients received two 20-mg doses of basiliximab (days 0 and 4 after transplantation) followed by tacrolimus (0.15 mg/kg/day; 10–15 ng/mL target trough levels) and a dose regimen of steroids (starting with 20 mg iv, switched to po as soon as the patient was able to eat, and weaned off within 1–2 months). Follow-up ranged from 6 to 1699.4 days after transplantation (mean 517.5 days, SD ± 413.4; median 424 days). Of the recipients, 95% remained rejection-free during follow-up, with an actuarial rejection-free probability of 96.61% within 3 months. Three patients had episodes of biopsy-proven acute cellular rejection (ACR). Actuarial patient and graft survival rates at 3 years were 82.09% and 75.61%. Six patients (10%) experienced sepsis. There was no evidence of cytomegalovirus infections or side-effects related to the basiliximab. We found zero de novo malignancy, although we observed 5 patients with metastatic spread of their primary malignancy during the follow-up. Basiliximab in association with tacrolimus and steroids is effective in reducing episodes of ACR and increasing ACR-free survival after ALRLT. PMID:19707350

  19. Differential Responses Between Monocytes and Monocyte-Derived Macrophages for Lipopolysaccharide Stimulation of Calves

    PubMed Central

    Guo, Yijie; Zhao, Guoqi; Tanaka, Sachi; Yamaguchi, Takahiro

    2009-01-01

    In this experiment Toll-like receptor expression pattern in monocytes and monocyte-derived macrophages by lipopolysaccharide (LPS) stimulation was examined. Jugular venous blood was collected from four Japanese calves, and the peripheral blood mononuclear cells (PBMCs) were isolated. The cells were directly used for collecting monocytes by magnetic cell sorting or cultured for 7 days to collect monocyte-derived macrophages in Repcell. Then we analyzed the mRNA expression pattern of TLRs and cytokines in monocytes and monocyte-derived macrophages after LPS stimulation for 24 h. LPS stimulation of both monocytes and monocyte-derived macrophages resulted in an increase in the levels of mRNA transcripts for TNF-α, IL-6 and IL-8. Moreover, TNF-α and IL-6 mRNA expressions were significantly augmented by LPS stimulation in monocyte-derived macrophages. TLRs mRNA expressions were unchanged after LPS stimulation of monocytes, while TLRs mRNA expressions in monocyte-derived macrophages were complicated. TLR1, 3, 5, 8 and 10 were significantly decreased after LPS stimulation and there were no differences in the mRNA expressions of TLR2, 4, 6 and 7 between the groups of control and LPS stimulation. Besides, no expression of TLR9 was found. As antigen presenting cells, monocytes and monocyte-derived macrophages respond differently to LPS, so they may have different functions in the innate immune system. PMID:19567206

  20. Co-existence of PHF6 and NOTCH1 mutations in adult T-cell acute lymphoblastic leukemia

    PubMed Central

    LI, MIN; XIAO, LICHAN; XU, JINGYAN; ZHANG, RUN; GUO, JINGJING; OLSON, JUSTIN; WU, YUJIE; LI, JIANYONG; SONG, CHUNHUA; GE, ZHENG

    2016-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) results from the collaboration of multiple genetic abnormalities in the transformation of T-cell progenitors. Plant homeodomain finger protein 6 (PHF6) has recently been established as a key tumor suppressor, which is mutated in T-ALL; however, the clinical significance of PHF6 mutations has not been fully determined in adult T-ALL. In the present study, amplification of the PHF6 exons was performed, followed by DNA sequencing to identify the genomic mutations and examine the expression of PHF6 in adult patients with T-ALL. The correlation between PHF6 mutations and clinical features was also analyzed using a χ2 test, and between PHF6 mutations and survival curve using the Kaplan-Meier methods. PHF6 mutations were detected in 27.1% of the Chinese adults with T-ALL (16/59), 10 of which were found to be novel mutations. A significantly lower expression level of PHF6 was observed in T-ALL patients with PHF6 mutations compared with those without mutations. Of the observed mutations in PHF6, 6/16 were frame-shift mutations, indicating a PHF6 dysfunction in those patients. Of note, PHF6 mutations were found to be significantly associated with older age, lower hemoglobin levels, higher frequency of CD13 positivity and higher incidence of splenomegaly or lymphadenopathy. Furthermore, PHF6 mutations were found to be significantly correlated with Notch homolog 1, translocation-associated (Drosophila) (NOTCH1) mutations. The patients with T-ALL with co-existence of the two mutations had a significantly shorter event-free survival and a poor prognosis. The present results indicated that PHF6 is inactivated in adult T-ALL, due to its low expression and mutations. The present data indicated the synergistic effect of PHF6 and NOTCH1 mutations, as well as their co-existence, on the oncogenesis of adult T-ALL, and their potential as a prognostic marker for the disease. PMID:27347093

  1. Randomized study of reduced-intensity chemotherapy combined with imatinib in adults with Ph-positive acute lymphoblastic leukemia.

    PubMed

    Chalandon, Yves; Thomas, Xavier; Hayette, Sandrine; Cayuela, Jean-Michel; Abbal, Claire; Huguet, Françoise; Raffoux, Emmanuel; Leguay, Thibaut; Rousselot, Philippe; Lepretre, Stéphane; Escoffre-Barbe, Martine; Maury, Sébastien; Berthon, Céline; Tavernier, Emmanuelle; Lambert, Jean-François; Lafage-Pochitaloff, Marina; Lhéritier, Véronique; Chevret, Sylvie; Ifrah, Norbert; Dombret, Hervé

    2015-06-11

    In this study, we randomly compared high doses of the tyrosine kinase inhibitor imatinib combined with reduced-intensity chemotherapy (arm A) to standard imatinib/hyperCVAD (cyclophosphamide/vincristine/doxorubicin/dexamethasone) therapy (arm B) in 268 adults (median age, 47 years) with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). The primary objective was the major molecular response (MMolR) rate after cycle 2, patients being then eligible for allogeneic stem cell transplantation (SCT) if they had a donor, or autologous SCT if in MMolR and no donor. With fewer induction deaths, the complete remission (CR) rate was higher in arm A than in arm B (98% vs 91%; P = .006), whereas the MMolR rate was similar in both arms (66% vs 64%). With a median follow-up of 4.8 years, 5-year event-free survival and overall survival (OS) rates were estimated at 37.1% and 45.6%, respectively, without difference between the arms. Allogeneic transplantation was associated with a significant benefit in relapse-free survival (hazard ratio [HR], 0.69; P = .036) and OS (HR, 0.64; P = .02), with initial white blood cell count being the only factor significantly interacting with this SCT effect. In patients achieving MMolR, outcome was similar after autologous and allogeneic transplantation. This study validates an induction regimen combining reduced-intensity chemotherapy and imatinib in Ph+ ALL adult patients and suggests that SCT in first CR is still a good option for Ph+ ALL adult patients. This trial was registered at www.clinicaltrials.gov as #NCT00327678. PMID:25878120

  2. [Immunophenotype. Clinical and laboratory features of acute lymphoblastic leukemia in Chile. Study of 500 children and 131 adults].

    PubMed

    Cabrera, M E; Labra, S; Ugarte, S; Matutes, E; Greaves, M F

    1996-03-01

    We describe the clinical features and immunophenotype of 500 children and 131 adults with acute lymphoblastic leukemia (ALL), diagnosed between 1984 and 1993. Cases were classified, according to immunophenotype in B-cell ALL with three subtypes (pro-B or null, common and B) and T-cell ALL. Among children, common ALL accounted for 74% of cases and pro-B all was more common in children of less than one year (14%). B ALL was observed in 2% of children. Ten percent of children, mostly males, had T-cell ALL. The third part of these children had high leukocyte counts and a mediastinal mass. Children from Mapuche origin, compared with Caucasian children had a lower proportion of common ALL (36 and 74% respectively) and a higher proportions of T-cell ALL (41 and 10% respectively). Among adults common ALL was the most common phenotype (72%) followed by T-cell ALL (15%), pro-B ALL (11%) and B-cell ALL (2%). There was a lower incidence of children with common ALL with positive cytoplasmic immunoglobulin compared to North American or European studies (2 and 15-33% respectively) and a higher proportion of adults with common ALL compared with pro-B cell ALL, in contrast to European studies that show a higher proportion of patients with pro-B cell ALL. No other immunophenotypic, clinical or laboratory differences were observed with ALL from developed countries. It is concluded that the immunophenotyping of ALL allows a more precise diagnosis of this disease. PMID:9008940

  3. Cytogenetics Does Not Impact Outcomes in Adult Patients with Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation.

    PubMed

    Aldoss, Ibrahim; Tsai, Ni-Chun; Slovak, Marilyn L; Palmer, Joycelynne; Alvarnas, Joseph; Marcucci, Guido; Forman, Stephen J; Pullarkat, Vinod

    2016-07-01

    The prognostic relevance of cytogenetics at diagnosis on the outcome of allogeneic hematopoietic stem cell transplantation (alloHCT) for adult acute lymphoblastic leukemia (ALL) remains unclear. We retrospectively analyzed outcomes of 333 adult ALL patients who underwent alloHCT at our institution over a 10-year period. Patients were classified according to disease status at transplantation (complete response [CR] 1 [n = 202] or > CR1) and according to cytogenetic risk, defined as good (2%), intermediate (42%), poor (46%), or unknown (10%) based on available outcome data for each of the cytogenetic abnormalities. Three-year overall survival (OS), leukemia-free survival (LFS), and relapse incidence (RI) were 55.7%, 47.9% and 27.5%, respectively; 1-year nonrelapse mortality (NRM) was 17.3%. For patients undergoing alloHCT in CR1, 3-year OS, LFS, and RI were 69.8%, 62.3%, and 17.1%, respectively. In multivariable analysis, cytogenetic risk did not impact OS or LFS for the whole cohort or for patients who underwent transplantation in CR1. Disease status at alloHCT was an independent predictor for LFS (CR1 versus others: hazard ratio [HR], 3.17; P < .01) and OS (CR1 versus others: HR, 2.90; P < .01). Graft-versus-host disease prophylaxis with tacrolimus/sirolimus was associated with a low NRM of 11.5% in the alloHCT recipients in CR1. Our data indicate that cytogenetic risk is not an independent predictor of outcomes in alloHCT performed to treat adult ALL. PMID:27044907

  4. High-Dose Vincristine Sulfate Liposome Injection for Advanced, Relapsed, and Refractory Adult Philadelphia Chromosome–Negative Acute Lymphoblastic Leukemia

    PubMed Central

    O'Brien, Susan; Schiller, Gary; Lister, John; Damon, Lloyd; Goldberg, Stuart; Aulitzky, Walter; Ben-Yehuda, Dina; Stock, Wendy; Coutre, Steven; Douer, Dan; Heffner, Leonard T.; Larson, Melissa; Seiter, Karen; Smith, Scott; Assouline, Sarit; Kuriakose, Philip; Maness, Lori; Nagler, Arnon; Rowe, Jacob; Schaich, Markus; Shpilberg, Ofer; Yee, Karen; Schmieder, Guenter; Silverman, Jeffrey A.; Thomas, Deborah; Deitcher, Steven R.; Kantarjian, Hagop

    2013-01-01

    Purpose Relapsed adult acute lymphoblastic leukemia (ALL) is associated with high reinduction mortality, chemotherapy resistance, and rapid progression leading to death. Vincristine sulfate liposome injection (VSLI), sphingomyelin and cholesterol nanoparticle vincristine (VCR), facilitates VCR dose-intensification and densification plus enhances target tissue delivery. We evaluated high-dose VSLI monotherapy in adults with Philadelphia chromosome (Ph) –negative ALL that was multiply relapsed, relapsed and refractory to reinduction, and/or relapsed after hematopoietic cell transplantation (HCT). Patients and Methods Sixty-five adults with Ph-negative ALL in second or greater relapse or whose disease had progressed following two or more leukemia therapies were treated in this pivotal phase II, multinational trial. Intravenous VSLI 2.25 mg/m2, without dose capping, was administered once per week until response, progression, toxicity, or pursuit of HCT. The primary end point was achievement of complete response (CR) or CR with incomplete hematologic recovery (CRi). Results The CR/CRi rate was 20% and overall response rate was 35%. VSLI monotherapy was effective as third-, fourth-, and fifth-line therapy and in patients refractory to other single- and multiagent reinduction therapies. Median CR/CRi duration was 23 weeks (range, 5 to 66 weeks); 12 patients bridged to a post-VSLI HCT, and five patients were long-term survivors. VSLI was generally well tolerated and associated with a low 30-day mortality rate (12%). Conclusion High-dose VSLI monotherapy resulted in meaningful clinical outcomes including durable responses and bridging to HCT in advanced ALL settings. The toxicity profile of VSLI was predictable, manageable, and comparable to standard VCR despite the delivery of large, normally unachievable, individual and cumulative doses of VCR. PMID:23169518

  5. Acute effect of a high nitrate diet on brain perfusion in older adults

    PubMed Central

    Presley, Tennille D.; Morgan, Ashley R.; Bechtold, Erika; Clodfelter, William; Dove, Robin W.; Jennings, Janine M.; Kraft, Robert A.; King, S. Bruce; Laurienti, Paul J.; Rejeski, W. Jack; Burdette, Jonathan H.; Kim-Shapiro, Daniel B.; Miller, Gary D.

    2010-01-01

    Aims Poor blood flow and hypoxia/ischemia contribute to many disease states and may also be a factor in the decline of physical and cognitive function in aging. Nitrite has been discovered to be a vasodilator that is preferentially harnessed in hypoxia. Thus, both infused and inhaled nitrite are being studied as therapeutic agents for a variety of diseases. In addition, nitrite derived from nitrate in the diet has been shown to decrease blood pressure and improve exercise performance. Thus, dietary nitrate may also be important when increased blood flow in hypoxic or ischemic areas is indicated. These conditions could include age-associated dementia and cognitive decline. The goal of this study was to determine if dietary nitrate would increase cerebral blood flow in older adults. Methods and Results In this investigation we administered a high vs. low nitrate diet to older adults (74.7 ± 6.9 years) and measured cerebral perfusion using arterial spin labeling magnetic resonance imaging. We found that the high nitrate diet did not alter global cerebral perfusion, but did lead to increased regional cerebral perfusion in frontal lobe white matter, especially between the dorsolateral prefrontal cortex and anterior cingulate cortex. Conclusion These results suggest that dietary nitrate may be useful in improving regional brain perfusion in older adults in critical brain areas known to be involved in executive functioning. PMID:20951824

  6. Frequencies of Virus-Specific CD4+ and CD8+ T Lymphocytes Secreting Gamma Interferon after Acute Natural Rotavirus Infection in Children and Adults

    PubMed Central

    Jaimes, María C.; Rojas, Olga Lucía; González, Ana María; Cajiao, Isabela; Charpilienne, Annie; Pothier, Pierre; Kohli, Evelyne; Greenberg, Harry B.; Franco, Manuel A.; Angel, Juana

    2002-01-01

    Human rotavirus-specific CD4+ and CD8+ T-cell responses in peripheral blood lymphocytes were studied using a flow cytometric assay that detects the intracellular accumulation of cytokines after short-term in vitro antigen stimulation. The frequencies of virus-specific T cells that secrete gamma interferon and interleukin-13 (IL-13) were determined in adults and children during the acute or convalescent phase of rotavirus-induced diarrhea, in asymptomatically infected adults and laboratory workers who worked with human stool samples containing rotavirus, and in healthy adults. Significantly higher frequencies of rotavirus-specific interferon gamma-secreting CD8+ and CD4+ T cells, but not IL-13-secreting T cells, were detected in symptomatically infected adults and exposed laboratory workers than in healthy adults and children with acute rotavirus diarrhea. The levels of rotavirus-specific T cells returned to levels found in healthy adults by 32 days after the onset of rotavirus diarrhea in most adult subjects. Children with rotavirus diarrhea had undetectable or very low levels of CD4+ and CD8+ T cells that secrete gamma interferon. Adult cytomegalovirus-seropositive individuals had frequencies of cytomegalovirus-specific T cells that secrete gamma interferon that were approximately 20 times the level of rotavirus-specific T cells. This result suggests that rotavirus is a relatively poor inducer of circulating memory T cells that secrete gamma interferon. The frequencies of gamma interferon-secreting CD4+ and CD8+ T cells and the frequencies of IL-13-secreting CD4+ T cells responding to the T-cell superantigen staphylococcal enterotoxin B (SEB) were lower in children than in adults. In both adults and children, the frequencies of CD4+ cells secreting gamma interferon in response to SEB were higher than the frequencies of cells secreting IL-13. PMID:11967291

  7. Glutaric aciduria type 2 presenting with acute respiratory failure in an adult

    PubMed Central

    Ersoy, Ebru Ortac; Rama, Dorina; Ünal, Özlem; Sivri, Serap; Topeli, Arzu

    2015-01-01

    Glutaric aciduria (GTA) type II can be seen as late onset form with myopathic phenotype. We present a case of a 19-year old female with progressive muscle weakness was admitted in intensive care unit (ICU) with respiratory failure and acute renal failure. Patient was unconscious. Pupils were anisocoric and light reflex was absent. She had hepatomegaly. The laboratory results showed a glucose level of 70 mg/dl and the liver enzymes were high. The patient also had hyponatremia (117 mEq/L) and lactate level of 3.9 mmol/L. Tandem MS and organic acid analysis were compatible with GTA type II. Carnitine 1gr, riboflavin 100 mg and co-enzymeQ10 100 mg was arranged. After four months from beginning of treatment tandem MS results are improved. Respiratory failure, acute renal failure due to profound proximal myopathy can be due to glutaric aciduria type II that responded rapidly to appropriate therapy. PMID:26236614

  8. Glutaric aciduria type 2 presenting with acute respiratory failure in an adult.

    PubMed

    Ersoy, Ebru Ortac; Rama, Dorina; Ünal, Özlem; Sivri, Serap; Topeli, Arzu

    2015-01-01

    Glutaric aciduria (GTA) type II can be seen as late onset form with myopathic phenotype. We present a case of a 19-year old female with progressive muscle weakness was admitted in intensive care unit (ICU) with respiratory failure and acute renal failure. Patient was unconscious. Pupils were anisocoric and light reflex was absent. She had hepatomegaly. The laboratory results showed a glucose level of 70 mg/dl and the liver enzymes were high. The patient also had hyponatremia (117 mEq/L) and lactate level of 3.9 mmol/L. Tandem MS and organic acid analysis were compatible with GTA type II. Carnitine 1gr, riboflavin 100 mg and co-enzymeQ10 100 mg was arranged. After four months from beginning of treatment tandem MS results are improved. Respiratory failure, acute renal failure due to profound proximal myopathy can be due to glutaric aciduria type II that responded rapidly to appropriate therapy. PMID:26236614

  9. DNA Methylation Profiles and Their Relationship with Cytogenetic Status in Adult Acute Myeloid Leukemia

    PubMed Central

    Alvarez, Sara; Suela, Javier; Valencia, Ana; Fernández, Agustín; Wunderlich, Mark; Agirre, Xabier; Prósper, Felipe; Martín-Subero, José Ignacio; Maiques, Alba; Acquadro, Francesco; Rodriguez Perales, Sandra; Calasanz, María José; Roman-Gómez, Jose; Siebert, Reiner; Mulloy, James C.; Cervera, José; Sanz, Miguel Angel; Esteller, Manel; Cigudosa, Juan C.

    2010-01-01

    Background Aberrant promoter DNA methylation has been shown to play a role in acute myeloid leukemia (AML) pathophysiology. However, further studies to discuss the prognostic value and the relationship of the epigenetic signatures with defined genomic rearrangements in acute myeloid leukemia are required. Methodology/Principal Findings We carried out high-throughput methylation profiling on 116 de novo AML cases and we validated the significant biomarkers in an independent cohort of 244 AML cases. Methylation signatures were associated with the presence of a specific cytogenetic status. In normal karyotype cases, aberrant methylation of the promoter of DBC1 was validated as a predictor of the disease-free and overall survival. Furthermore, DBC1 expression was significantly silenced in the aberrantly methylated samples. Patients with chromosome rearrangements showed distinct methylation signatures. To establish the role of fusion proteins in the epigenetic profiles, 20 additional samples of human hematopoietic stem/progenitor cells (HSPC) transduced with common fusion genes were studied and compared with patient samples carrying the same rearrangements. The presence of MLL rearrangements in HSPC induced the methylation profile observed in the MLL-positive primary samples. In contrast, fusion genes such as AML1/ETO or CBFB/MYH11 failed to reproduce the epigenetic signature observed in the patients. Conclusions/Significance Our study provides a comprehensive epigenetic profiling of AML, identifies new clinical markers for cases with a normal karyotype, and reveals relevant biological information related to the role of fusion proteins on the methylation signature. PMID:20808941

  10. Monocyte dysfunction in Sydenham's chorea patients.

    PubMed

    Torres, Karen C; Dutra, Walderez O; de Rezende, Vitor Bortolo; Cardoso, Francisco; Gollob, Kenneth J; Teixeira, Antonio L

    2010-04-01

    Until now, there are no conclusive data about the mechanisms involved in motor symptoms of Sydenham's chorea (SC). Taking into account the autoreactive antibody-mediated hypothesis of SC pathogenesis, the SC may be associated with uncontrolled immune mechanisms. Besides the antibody hypothesis, the innate immune system has been underappreciated. Hence, we evaluated the activation state of monocytes, cells that are precursors of macrophages, to characterize the inflammation profile of patients. We assessed the surface molecules CD80, CD86, and human leukocyte antigen DR expression in patients with SC by flow cytometry analysis. Our results showed a decreased CD14(+) (monocyte) frequency, with concomitant increased CD14(-) frequency inside monocyte population. Although monocyte population showed a decreased human leukocyte antigen DR and CD86 frequencies, the CD14(-) population showed an increased frequency of CD80(+) monocyte from SC compared with controls. These data suggest that monocytes showed a reduced costimulatory potential in SC. PMID:20080141

  11. Systemic levels of G-CSF and interleukin-6 determine the angiogenic potential of bone marrow resident monocytes

    PubMed Central

    Gregory, Alyssa D.; Capoccia, Benjamin J.; Woloszynek, Jill R.; Link, Daniel C.

    2010-01-01

    There is considerable interest in the potential of cell-based approaches to mediate therapeutic angiogenesis for acute and chronic vascular syndromes. Using a mouse model of HLI, we showed previously that adoptive transfer of a small number of donor monocytes enhanced revascularization significantly. Herein, we provide data suggesting that the BM resident monocytes sense systemic signals that influence their future functional capacity. Specifically, following induction of distant ischemia, the angiogenic capacity of BM resident monocytes is reduced markedly. We provide evidence that G-CSF and IL-6 represent such “conditioning” signals. Systemic levels of G-CSF and IL-6 are increased significantly following induction of HLI. Accordingly, BM resident monocytes from ischemic mice exhibited increased pSTAT3 and STAT3 target gene expression. Finally, G-CSFR−/− and IL-6−/− mice were resistant to the deleterious effects of ischemic conditioning on monocyte angiogenic potential. RNA expression profiling suggested that ischemia-conditioned monocytes in the BM up-regulate the well-described M2 polarization markers Chi3l4 and Lrg1. Consistent with this observation, M2-skewed monocytes from SHIP−/− mice also had impaired angiogenic capacity. Collectively, these data show that G-CSF and IL-6 provide signals that determine the angiogenic potential of BM resident monocytes. PMID:20354107

  12. Platelet and monocyte activity markers and mediators of inflammation in Takotsubo cardiomyopathy.

    PubMed

    Pirzer, Rainer; Elmas, Elif; Haghi, Dariusch; Lippert, Christiane; Kralev, Stefan; Lang, Siegfried; Borggrefe, Martin; Kälsch, Thorsten

    2012-03-01

    Patients with Takotsubo cardiomyopathy (TC) often present with symptoms similar to those of myocardial infarction (MI). We analyzed blood concentrations of mediators of inflammation and platelet- and monocyte-activity markers in patients with TC and MI for significant differences. Clinical data of patients with TC (n = 16) and acute MI (n = 16) were obtained. Serial blood samples were taken at the time of hospital admission (t(0)), after 2-4 days (t(1)) and after 4-7 weeks (t(2)), respectively. Plasma concentrations of interleukin (IL)-6, IL-7, soluble CD40 ligand (sCD40L), and monocyte chemotactic protein 1 (MCP-1) were determined with an ELISA. Tissue factor binding on monocytes, platelet-activation marker CD62P, platelet CD40-ligand (CD40L), and platelet-monocyte aggregates were measured using flow cytometry. Expression of CD62P on platelets and IL-6 plasma levels were significantly lower in patients with TC compared to MI at the time of hospital admission. IL-7 plasma levels were significantly elevated in patients with TC compared to patients with MI at 2-4 days after hospital admission. No significant differences were observed concerning sCD40L and MCP-1 plasma levels, tissue factor binding on monocytes, CD40L expression on platelets, and platelet-monocyte aggregates at any point in time. Our results indicate that inflammatory mediators and platelet-activity markers contribute to the differences in the pathogenesis of MI and TC. PMID:21416113

  13. Optimal therapy for adult patients with acute myeloid leukemia in first complete remission.

    PubMed

    Wiernik, Peter H

    2014-06-01

    Although it is absolutely clear that postremission therapy is currently necessary to obtain disease-free long-term survivorship for patients with acute myeloid leukemia (AML) in first complete remission (CR), it is not entirely clear what form that treatment should take. High-dose cytarabine is clearly effective and there definitely is a dose-response relationship for cytarabine and remission duration. High-dose cytarabine is effective for younger patients but not elderly patients. It is effective for patients with favorable cytogenetics but it is not clear whether it is effective for patients with intermediate or unfavorable cytogenetics. Furthermore, it is not clear what the most effective and least toxic dose and schedule of high-dose cytarabine is. PMID:24792016

  14. Adult-onset Invasive Haemophilus influenzae Type f Caused by Acute Lower Leg Cellulitis.

    PubMed

    Usui, Yuko; Kakuta, Risako; Araki, Makoto; Sato, Taigo; Gu, Yoshiaki; Yano, Hisakazu; Taniuchi, Norihide

    2016-01-01

    In Japan, routine Haemophilus influenzae type b (Hib) vaccination began in 2013. Thus, similar to other countries, a strain shift is expected in the near future. We experienced a case of H. influenzae type f (Hif) bacteremia in a 66-year-old man. The primary focus of the infection was the soft tissue of the left lower leg, which is an extremely rare origin in adults. Subsequently, we conducted multilocus sequence typing and identified the strain as sequence type 124, which is the most common invasive strain of Hif worldwide. This case may mark the beginning of an Hif strain shift in Japan. PMID:27374690

  15. Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance

    PubMed Central

    Ivey, Adam; Huntly, Brian J. P.

    2016-01-01

    Recent major advances in understanding the molecular basis of acute myeloid leukemia (AML) provide a double-edged sword. Although defining the topology and key features of the molecular landscape are fundamental to development of novel treatment approaches and provide opportunities for greater individualization of therapy, confirmation of the genetic complexity presents a huge challenge to successful translation into routine clinical practice. It is now clear that many genes are recurrently mutated in AML; moreover, individual leukemias harbor multiple mutations and are potentially composed of subclones with differing mutational composition, rendering each patient’s AML genetically unique. In order to make sense of the overwhelming mutational data and capitalize on this clinically, it is important to identify (1) critical AML-defining molecular abnormalities that distinguish biological disease entities; (2) mutations, typically arising in subclones, that may influence prognosis but are unlikely to be ideal therapeutic targets; (3) mutations associated with preleukemic clones; and (4) mutations that have been robustly shown to confer independent prognostic information or are therapeutically relevant. The reward of identifying AML-defining molecular lesions present in all leukemic populations (including subclones) has been exemplified by acute promyelocytic leukemia, where successful targeting of the underlying PML-RARα oncoprotein has eliminated the need for chemotherapy for disease cure. Despite the molecular heterogeneity and recognizing that treatment options for other forms of AML are limited, this review will consider the scope for using novel molecular information to improve diagnosis, identify subsets of patients eligible for targeted therapies, refine outcome prediction, and track treatment response. PMID:26660431

  16. Monocytes in coronary artery disease and atherosclerosis: where are we now?

    PubMed

    Ghattas, Angie; Griffiths, Helen R; Devitt, Andrew; Lip, Gregory Y H; Shantsila, Eduard

    2013-10-22

    Despite improvements in interventional and pharmacological therapy of atherosclerotic disease, it is still the leading cause of death in the developed world. Hence, there is a need for further development of effective therapeutic approaches. This requires better understanding of the molecular mechanisms and pathophysiology of the disease. Atherosclerosis has long been identified as having an inflammatory component contributing to its pathogenesis, whereas the available therapy primarily targets hyperlipidemia and prevention of thrombosis. Notwithstanding a pleotropic anti-inflammatory effect to some therapies, such as acetyl salicylic acid and the statins, none of the currently approved medicines for management of either stable or complicated atherosclerosis has inflammation as a primary target. Monocytes, as representatives of the innate immune system, play a major role in the initiation, propagation, and progression of atherosclerosis from a stable to an unstable state. Experimental data support a role of monocytes in acute coronary syndromes and in outcome post-infarction; however, limited research has been done in humans. Analysis of expression of various cell surface receptors allows characterization of the different monocyte subsets phenotypically, whereas downstream assessment of inflammatory pathways provides an insight into their activity. In this review we discuss the functional role of monocytes and their different subpopulations in atherosclerosis, acute coronary syndromes, cardiac healing, and recovery with an aim of critical evaluation of potential future therapeutic targets in atherosclerosis and its complications. We will also discuss technical difficulties of delineating different monocyte subpopulations, understanding their differentiation potential and function. PMID:23973684

  17. Loss of extracellular superoxide dismutase leads to acute lung damage in the presence of ambient air: a potential mechanism underlying adult respiratory distress syndrome.

    PubMed

    Gongora, Maria Carolina; Lob, Heinrich E; Landmesser, Ulf; Guzik, Tomasz J; Martin, W David; Ozumi, Kiyoski; Wall, Susan M; Wilson, David Scott; Murthy, Niren; Gravanis, Michael; Fukai, Tohru; Harrison, David G

    2008-10-01

    The extracellular superoxide dismutase 3 (SOD3) is highly expressed in both blood vessels and lungs. In different models of pulmonary injury, SOD3 is reduced; however, it is unclear whether this contributes to lung injury. To study the role of acute SOD3 reduction in lung injury, the SOD3 gene was deleted in adult mice by using the Cre-Lox technology. Acute reduction of SOD3 led to a fivefold increase in lung superoxide, marked inflammatory cell infiltration, a threefold increase in the arterial-alveolar gradient, respiratory acidosis, histological changes similar to those observed in adult respiratory distress syndrome, and 85% mortality. Treatment with the SOD mimetic MnTBAP and intranasal administration of SOD-containing polyketal microparticles reduced mortality, prevented the histological alterations, and reduced lung superoxide levels. To understand how mice with the SOD3 embryonic deletion survived without lung injury, gene array analysis was performed. These data demonstrated the up-regulation of 37 genes and down-regulation of nine genes, including those involved in cell signaling, inflammation, and gene transcription in SOD3-/- mice compared with either mice with acute SOD3 reduction or wild-type controls. These studies show that SOD3 is essential for survival in the presence of ambient oxygen and that acute loss of this enzyme can lead to severe lung damage. Strategies either to prevent SOD3 inactivation or to augment its levels might prove useful in the treatment of acute lung injury. PMID:18787098

  18. Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group

    PubMed Central

    Oriol, Albert; Vives, Susana; Hernández-Rivas, Jesús-María; Tormo, Mar; Heras, Inmaculada; Rivas, Concepción; Bethencourt, Concepción; Moscardó, Federico; Bueno, Javier; Grande, Carlos; del Potro, Eloy; Guardia, Ramon; Brunet, Salut; Bergua, Juan; Bernal, Teresa; Moreno, Maria-José; Calvo, Carlota; Bastida, Pilar; Feliu, Evarist; Ribera, Josep-Maria

    2010-01-01

    Background About one half of adults with acute lymphoblastic leukemia are not cured of the disease and ultimately die. The objective of this study was to explore the factors influencing the outcome of adult patients with relapsed acute lymphoblastic leukemia. Design and Methods We analyzed the characteristics, the outcome and the prognostic factors for survival after first relapse in a series of 263 adult patients with acute lymphoblastic leukemia (excluding those with mature B-cell acute lymphoblastic leukemia) prospectively enrolled in four consecutive risk-adapted PETHEMA trials. Results The median overall survival after relapse was 4.5 months (95% CI, 4–5 months) with a 5-year overall survival of 10% (95% CI, 8%–12%); 45% of patients receiving intensive second-line treatment achieved a second complete remission and 22% (95% CI, 14%–30%) of them remained disease free at 5 years. Factors predicting a good outcome after rescue therapy were age less than 30 years (2-year overall survival of 21% versus 10% for those over 30 years old; P<0.022) and a first remission lasting more than 2 years (2-year overall survival of 36% versus 17% among those with a shorter first remission; P<0.001). Patients under 30 years old whose first complete remission lasted longer than 2 years had a 5-year overall survival of 38% (95% CI, 23%–53%) and a 5-year disease-free survival of 53% (95% CI, 34%–72%). Conclusions The prognosis of adult patients with acute lymphoblastic leukemia who relapse is poor. Those aged less than 30 years with a first complete remission lasting longer than 2 years have reasonable possibilities of becoming long-term survivors while patients over this age or those who relapse early cannot be successfully rescued using the therapies currently available. PMID:20145276

  19. Concealed expansion of immature precursors underpins acute burst of adult HSC activity in foetal liver.

    PubMed

    Rybtsov, Stanislav; Ivanovs, Andrejs; Zhao, Suling; Medvinsky, Alexander

    2016-04-15

    One day prior to mass emergence of haematopoietic stem cells (HSCs) in the foetal liver at E12.5, the embryo contains only a few definitive HSCs. It is thought that the burst of HSC activity in the foetal liver is underpinned by rapid maturation of immature embryonic precursors of definitive HSCs, termed pre-HSCs. However, because pre-HSCs are not detectable by direct transplantations into adult irradiated recipients, the size and growth of this population, which represents the embryonic rudiment of the adult haematopoietic system, remains uncertain. Using a novel quantitative assay, we demonstrate that from E9.5 the pre-HSC pool undergoes dramatic growth in the aorta-gonad-mesonephros region and by E11.5 reaches the size that matches the number of definitive HSCs in the E12.5 foetal liver. Thus, this study provides for the first time a quantitative basis for our understanding of how the large population of definitive HSCs emerges in the foetal liver. PMID:27095492

  20. Concealed expansion of immature precursors underpins acute burst of adult HSC activity in foetal liver

    PubMed Central

    Ivanovs, Andrejs; Zhao, Suling; Medvinsky, Alexander

    2016-01-01

    One day prior to mass emergence of haematopoietic stem cells (HSCs) in the foetal liver at E12.5, the embryo contains only a few definitive HSCs. It is thought that the burst of HSC activity in the foetal liver is underpinned by rapid maturation of immature embryonic precursors of definitive HSCs, termed pre-HSCs. However, because pre-HSCs are not detectable by direct transplantations into adult irradiated recipients, the size and growth of this population, which represents the embryonic rudiment of the adult haematopoietic system, remains uncertain. Using a novel quantitative assay, we demonstrate that from E9.5 the pre-HSC pool undergoes dramatic growth in the aorta-gonad-mesonephros region and by E11.5 reaches the size that matches the number of definitive HSCs in the E12.5 foetal liver. Thus, this study provides for the first time a quantitative basis for our understanding of how the large population of definitive HSCs emerges in the foetal liver. PMID:27095492

  1. Effects of acute hypoxia on the oxygen uptake kinetics of older adults during cycling exercise.

    PubMed

    Zerbini, Livio; Brighenti, Alfredo; Pellegrini, Barbara; Bortolan, Lorenzo; Antonetti, Tommaso; Schena, Federico

    2012-08-01

    Pulmonary oxygen uptake, heart rate (HR), and deoxyhemoglobin (HHb) kinetics were studied in a group of older adults exercising in hypoxic conditions. Fourteen healthy older adults (aged 66 ± 6 years) performed 4 exercise sessions that consisted of (i) an incremental test to exhaustion on a cycloergometer while breathing normoxic room air (fractional inspired oxygen (FiO(2)) = 20.9% O(2)); (ii) an incremental test to exhaustion on a cycloergometer while breathing hypoxic room air (FiO(2) = 15% O(2)); (iii) 3 repeated square wave cycling exercises at moderate intensity while breathing normoxic room air; and (iv) 3 repeated square wave cycling exercises at moderate intensity while breathing hypoxic room air. During all exercise sessions, pulmonary gas exchange was measured breath-by-breath; HHb was determined on the vastus lateralis muscle by near-infrared spectroscopy; and HR was collected beat-by-beat. The pulomary oxygen uptake kinetics became slower in hypoxia (31 ± 9 s) than in normoxia (27 ± 7 s) because of an increased mismatching between O(2) delivery to O(2) utilization at the level of the muscle. The HR and HHb kinetics did not change between hypoxia and normoxia. PMID:22680339

  2. Reasons for and Reservations about Research Participation in Acutely Injured Adults

    PubMed Central

    Irani, Elliane; Richmond, Therese S.

    2014-01-01

    Purpose The purpose of this study was to explore the reasons adult patients seeking emergency department care for minor injuries agree to participate in clinical research and to identify their reservations about participating in a research study. Design and Methods This is a secondary analysis of data from a longitudinal cohort study of 275 adults who sought emergency department care for physical injury and were followed over 12 months. At the final interview, participants were asked open-ended short-answer questions about their perception of participating in the study. Free text responses were analyzed using conventional content analysis. Findings The final sample of 214 participants was equally males and females, predominately Black (54%) and White (42%), with a mean age of 41 years. Six themes about reasons for participation emerged from free text responses: being asked, altruism, potential for personal benefit, financial gain, curiosity, and valuing and/or knowledge of research. Most did not report reservations. Those reservations identified included: time constraints, confidentiality, and whether patients felt well suited to fulfill the study requirements. Conclusion Although injured patients are identified by the research community as vulnerable, they are willing to participate in research studies for diverse reasons and their participation is commonly associated with positive experiences. PMID:25599886

  3. Alemtuzumab and Combination Chemotherapy in Treating Patients With Untreated Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2014-03-20

    Acute Undifferentiated Leukemia; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; L1 Adult Acute Lymphoblastic Leukemia; L1 Childhood Acute Lymphoblastic Leukemia; L2 Adult Acute Lymphoblastic Leukemia; L2 Childhood Acute Lymphoblastic Leukemia; Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  4. CCN1/CYR61-mediated meticulous patrolling by Ly6Clow monocytes fuels vascular inflammation.

    PubMed

    Imhof, Beat A; Jemelin, Stephane; Ballet, Romain; Vesin, Christian; Schapira, Marco; Karaca, Melis; Emre, Yalin

    2016-08-16

    Inflammation is characterized by the recruitment of leukocytes from the bloodstream. The rapid arrival of neutrophils is followed by a wave of inflammatory lymphocyte antigen 6 complex (Ly6C)-positive monocytes. In contrast Ly6C(low) monocytes survey the endothelium in the steady state, but their role in inflammation is still unclear. Here, using confocal intravital microscopy, we show that upon Toll-like receptor 7/8 (TLR7/8)-mediated inflammation of mesenteric veins, platelet activation drives the rapid mobilization of Ly6C(low) monocytes to the luminal side of the endothelium. After repeatedly interacting with platelets, Ly6C(low) monocytes commit to a meticulous patrolling of the endothelial wall and orchestrate the subsequent arrival and extravasation of neutrophils through the production of proinflammatory cytokines and chemokines. At a molecular level, we show that cysteine-rich protein 61 (CYR61)/CYR61 connective tissue growth factor nephroblastoma overexpressed 1 (CCN1) protein is released by activated platelets and enables the recruitment of Ly6C(low) monocytes upon vascular inflammation. In addition endothelium-bound CCN1 sustains the adequate patrolling of Ly6C(low) monocytes both in the steady state and under inflammatory conditions. Blocking CCN1 or platelets with specific antibodies impaired the early arrival of Ly6C(low) monocytes and abolished the recruitment of neutrophils. These results refine the leukocyte recruitment cascade model by introducing endothelium-bound CCN1 as an inflammation mediator and by demonstrating a role for platelets and patrolling Ly6C(low) monocytes in acute vascular inflammation. PMID:27482114

  5. In vivo cerebral incorporation of radiolabeled fatty acids after acute unilateral orbital enucleation in adult hooded Long-Evans rats

    SciTech Connect

    Wakabayashi, S.; Freed, L.M.; Bell, J.M.; Rapoport, S.I.

    1994-03-01

    We examined effects of acute unilateral enucleation on incorporation from blood of intravenously injected unsaturated [1-{sup 14}C]arachidonic acid ([{sup 14}C]AA) and [1-{sup 14}C]docosahexaenoic acid ([{sup 14}C]DHA), and of saturated [9,10-{sup 3}H]palmitic acid ([{sup 3}H]PA), into visual and nonvisual brain areas of awake adult Long-Evans hooded rats. Regional cerebral metabolic rate for glucose (rCMR{sub glc}) values also were assessed with 2-deoxy-D-[1-{sup 14}C]glucose ([{sup 14}C]DG). One day after unilateral enucleation, an awake rat was placed in a brightly lit visual stimulation box with black and white striped walls, and a radiolabeled fatty acid was infused for 5 min or [{sup 14}C]DG was injected as a bolus. [{sup 14}C]DG also was injected in a group of rats kept in the dark for 4 h. Fifteen minutes after starting an infusion of a radiolabeled fatty acid, or 45 min after injecting [{sup 14}C]DG, the rat was killed and the brain was prepared for quantitative autoradiography. Incorporation coefficients k* of fatty acids, or rCMR{sub glc} values, were calculated in homologous brain regions contralateral and ipsilateral to enucleation. As compared with ipsilateral regions, rCMR{sub glc} was reduced significantly (by as much as -39%) in contralateral visual areas, including the superior colliculus, lateral geniculate body, and layers I, IV, and V of the primary (striate) and secondary (association, extrastriate) visual cortices. These results indicate that enucleation acutely reduces neuronal activity in contralateral visual areas of the awake rat and that the reductions are coupled to reduced incorporation of unsaturated fatty acids into sn-2 regions of phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine. Reduced fatty acid incorporation likely reflects reduced activity of phospholipases A{sub 2} and/or phospholipase C. 65 refs., 5 figs., 5 tabs.

  6. Acute {beta}-adrenergic stimulation does not alter mitochondrial protein synthesis or markers of mitochondrial biogenesis in adult men.

    PubMed

    Robinson, Matthew M; Richards, Jennifer C; Hickey, Matthew S; Moore, Daniel R; Phillips, Stuart M; Bell, Christopher; Miller, Benjamin F

    2010-01-01

    Exercise-induced expression of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) is dramatically inhibited in mice pretreated with a beta-adrenergic receptor (beta-AR) antagonist, suggesting that beta-ARs play an important role in the regulation of skeletal muscle PGC-1alpha expression, and potentially, mitochondrial biogenesis. Accordingly, we hypothesized that acute beta-AR stimulation would induce transcriptional pathways involved in skeletal muscle mitochondrial biogenesis in humans. Whole body protein turnover (WBPT), myofibrillar protein synthesis (MyPS), skeletal muscle mitochondrial protein synthesis (MiPS), and mitochondrial biogenic signaling were determined in samples of vastus lateralis obtained on two separate occasions in 10 young adult males following 1 h of continuous intravenous administration of saline (CON) or a nonspecific beta-AR agonist [isoproterenol (ISO): 12 ng.kg fat free mass(-1).min(-1)], combined with coinfusion of [1,2](13)C-leucine. beta-AR stimulation induced appreciable increases in heart rate and systolic blood pressure (both P < 0.001) but did not affect mitochondrial biogenic signaling (no change in PGC-1alpha, TFAM, NRF-1, NRF-2, COX, or NADHox expression via RT-PCR; P > 0.05). Additionally, MiPS [CON: 0.099 +/- 0.028, ISO: 0.074 +/- 0.046 (mean +/- SD); P > 0.05] and MyPS (CON: 0.059 +/- 0.008, ISO: 0.055 +/- 0.009; P > 0.05), as well as measures of WBPT were unaffected. On the basis of this investigation, we conclude that acute intravenous beta-AR stimulation does not increase mitochondrial protein synthesis or biogenesis signals in skeletal muscle. PMID:19907002

  7. Patterns and frequencies of acquired and constitutional uniparental isodisomies in pediatric and adult B-cell precursor acute lymphoblastic leukemia.

    PubMed

    Lundin, Kristina B; Olsson, Linda; Safavi, Setareh; Biloglav, Andrea; Paulsson, Kajsa; Johansson, Bertil

    2016-05-01

    Single nucleotide polymorphism (SNP) arrays are increasingly being used in clinical routine for genetic analysis of pediatric B-cell precursor acute lymphoblastic leukemias (BCP ALL). Because constitutional DNA is not readily available as a control at the time of diagnosis, it is important to be able to distinguish between acquired and constitutional aberrations in a diagnostic setting. In the present study we focused on uniparental isodisomies (UPIDs). SNP array analyses of 143 pediatric and 38 adult B-cell precursor acute lymphoblastic leukemias and matched remission samples revealed acquired whole chromosome or segmental UPIDs (wUPIDs, sUPIDs) in 32 cases (18%), without any age- or gender-related frequency differences. Acquired sUPIDs were larger than the constitutional ones (mean 35.3 Mb vs. 10.7 Mb; P < 0.0001) and were more often terminally located in the chromosomes (69% vs. 4.5%; P < 0.0001). Chromosomes 3, 5, and 9 were most often involved in acquired wUPIDs, whilst recurrent acquired sUPIDs targeted 6p, 9p, 9q, and 14q. The majority (56%) of sUPID9p was associated with homozygous CDKN2A deletions. In pediatric ALL, all wUPIDs were found in high hyperdiploid (51-67 chromosomes) cases and an extended analysis, also including unmatched diagnostic samples, revealed a higher frequency of wUPID-positivity in higher modal number (56-67 chromosomes) than in lower modal number (51-55 chromosomes) high hyperdiploid cases (34% vs. 11%; P = 0.04), suggesting different underlying mechanisms of formation of these subtypes of high hyperdiploidy. © 2016 Wiley Periodicals, Inc. PMID:26773847

  8. Hematopoietic stem cell transplantation in children and young adults with secondary myelodysplastic syndrome and acute myelogenous leukemia after aplastic anemia.

    PubMed

    Yoshimi, Ayami; Strahm, Brigitte; Baumann, Irith; Furlan, Ingrid; Schwarz, Stephan; Teigler-Schlegel, Andrea; Walther, Joachim-Ulrich; Schlegelberger, Brigitte; Göhring, Gudrun; Nöllke, Peter; Führer, Monika; Niemeyer, Charlotte M

    2014-03-01

    Secondary myelodysplastic syndrome and acute myelogenous leukemia (sMDS/sAML) are the most serious secondary events occurring after immunosuppressive therapy in patients with aplastic anemia. Here we evaluate the outcome of hematopoietic stem cell transplantation (HSCT) in 17 children and young adults with sMDS/sAML after childhood aplastic anemia. The median interval between the diagnosis of aplastic anemia and the development of sMDS/sAML was 2.9 years (range, 1.2 to 13.0 years). At a median age of 13.1 years (range, 4.4 to 26.7 years), patients underwent HSCT with bone marrow (n = 6) or peripheral blood stem cell (n = 11) grafts from HLA-matched sibling donors (n = 2), mismatched family donors (n = 2), or unrelated donors (n = 13). Monosomy 7 was detected in 13 patients. The preparative regimen consisted of busulfan, cyclophosphamide, and melphalan in 11 patients and other agents in 6 patients. All patients achieved neutrophil engraftment. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 47%, and that of chronic GVHD was 70%. Relapse occurred in 1 patient. The major cause of death was transplant-related complication (n = 9). Overall survival and event-free survival at 5 years after HSCT were both 41%. In summary, this study indicates that HSCT is a curative therapy for some patients with sMDS/sAML after aplastic anemia. Future efforts should focus on reducing transplantation-related mortality. PMID:24316460

  9. Being in a process of transition to psychosis, as narrated by adults with psychotic illnesses acutely admitted to hospital

    PubMed Central

    Sebergsen, K; Norberg, A; Talseth, A-G

    2014-01-01

    Accessible summary Early intervention to prevent and reduce new episodes of psychosis involves patients, relatives and mental health personnel recognizing the early signs of psychosis. Twelve participants with psychotic illnesses narrated how they experienced becoming psychotic before they were admitted to acute psychiatric wards. The results of this study demonstrate that participants and their close others who sensed, understood and articulated experienced changes as signs of psychosis established a dialogue with mental health personnel and initiated treatment and care. Participants who did not perceive the experienced changes as signs of psychosis articulated the experienced changes as an awareness of a poor health condition and illness. These participants, who had no other people to advocate for them, appeared to experience poor communication and coercion during intervention. Abstract To assist in improving early interventions for psychosis, this study explored how adult people narrated their experience of becoming psychotic, and how contact with mental health personnel was established. Narrative interviews were conducted with 12 participants with psychotic illnesses recruited from acute psychiatric wards. The interviews were content analysed. Participants described being in a process of transition to psychosis as follows: experiencing changes as well-known signs of psychosis, experiencing sudden unexpected changes as signs of psychosis and experiencing unidentified changes as signs of illness. Our results show that participants and their close others who knew the signs of psychosis established a dialogue with mental health personnel and were better equipped to prevent and mitigate the psychosis. Our results demonstrate that participants who did not perceive the signs of psychosis and did not have other people to advocate for them were at risk for delayed treatment, poor communication and coercive interventions. Furthermore, participants who did not know the

  10. Acute gastric volvulus associated with wandering spleen in an adult treated laparoscopically after endoscopic reduction: a case report.

    PubMed

    Omata, Jiro; Utsunomiya, Katsuyuki; Kajiwara, Yoshiki; Takahata, Risa; Miyasaka, Nobuo; Sugasawa, Hidekazu; Sakamoto, Naoko; Yamagishi, Yoji; Fukumura, Makiko; Kitagawa, Daiki; Konno, Mitsuhiko; Okusa, Yasushi; Murayama, Michinori

    2016-12-01

    A 43-year-old female was referred to our hospital for sudden onset of abdominal pain, fullness, and vomiting. Physical examination revealed abdominal distension with mild epigastric tenderness. Abdominal radiography showed massive gastric distension and plain computed tomography (CT) a markedly enlarged stomach filled with gas and fluid. A large volume of gastric contents was suctioned out via a nasogastric (NG) tube. Contrast-enhanced CT showed a grossly distended stomach with displacement of the antrum above the gastroesophageal junction, and the spleen was dislocated inferiorly. Upper gastrointestinal (GI) series showed the greater curvature to be elevated and the gastric fundus to be lower than normal. Acute mesenteroaxial gastric volvulus was diagnosed. GI endoscopy showed a distortion of the gastric anatomy with difficulty intubating the pylorus. Various endoscopic maneuvers were required to reposition the stomach, and the symptoms showed immediate and complete solution. GI fluoroscopy was performed 3 days later. Initially, most of the contrast medium accumulated in the fundus, which was drawn prominently downward, and then began flowing into the duodenum with anteflexion. Elective laparoscopic surgery was performed 1 month later. The stomach was in its normal position, but the fundus was folded posteroinferiorly. The spleen attached to the fundus was normal in size but extremely mobile. We diagnosed a wandering spleen based on the operative findings. Gastropexy was performed for the treatment of gastric volvulus and wandering spleen. The patient remained asymptomatic, and there was no evidence of recurrence during a follow-up period of 24 months. This report describes a rare adult case of acute gastric volvulus associated with wandering spleen. Because delay in treatment can result in lethal complications, it is critical to provide a prompt and correct diagnosis and surgical intervention. We advocate laparoscopic surgery after endoscopic reduction because

  11. Thoracic Society of Australia and New Zealand oxygen guidelines for acute oxygen use in adults: ‘Swimming between the flags’*

    PubMed Central

    Beasley, Richard; Chien, Jimmy; Douglas, James; Eastlake, Leonie; Farah, Claude; King, Gregory; Moore, Rosemary; Pilcher, Janine; Richards, Michael; Smith, Sheree; Walters, Haydn

    2015-01-01

    The purpose of the Thoracic Society of Australia and New Zealand guidelines is to provide simple, practical evidence-based recommendations for the acute use of oxygen in adults in clinical practice. The intended users are all health professionals responsible for the administration and/or monitoring of oxygen therapy in the management of acute medical patients in the community and hospital settings (excluding perioperative and intensive care patients), those responsible for the training of such health professionals, and both public and private health care organizations that deliver oxygen therapy. PMID:26486092

  12. Sources of heterogeneity in human monocyte subsets

    PubMed Central

    Appleby, Laura J.; Nausch, Norman; Midzi, Nicholas; Mduluza, Takafira; Allen, Judith E.; Mutapi, Francisca

    2013-01-01

    Human monocytes are commonly defined and discriminated by the extent of their cell surface expression of CD14 and CD16, with associated differences in function and phenotype related to the intensity of expression of these markers. With increasing interest into the function and behaviour of monocytes, it is important to have a clear understanding of how differing strategies of analysis can affect results and how different protocols and population backgrounds can affect this highly morphogenic cell type. Using PBMCs from populations with differing ethnicities and histories of parasite exposure we have characterized monocyte phenotype based on intensity of CD14 and CD16 expression. Using the surface markers HLA-DR, CCR2 and CX3CR1, we compared monocyte phenotype between populations and further assessed changes in monocytes with freezing and thawing of PBMCs. Our results reveal that there is a progression of surface marker expression based on intensity of CD14 or CD16 expression, stressing the importance of careful gating of monocyte subtypes. Freezing and thawing of the PBMCs has no effect generally on the monocytes, although it does lead to a decrease in CD16 and CX3CR1 expression. We show that there are differences in the monocyte populations based on ethnicity and history of exposure to the common parasites Plasmodium falciparum and Schistosoma haematobium. This study highlights that blood monocytes consist of a continuous population of cells, within which the dominant phenotype may vary dependent on the background of the study population. Comparing results from monocyte studies therefore needs to be done with great care, as ethnic background of donor population, gating strategy and processing of PBMCs may all have an effect on outcome of monocyte phenotype. PMID:23557598

  13. Telomerase expression confers cardioprotection in the adult mouse heart after acute myocardial infarction

    PubMed Central

    Serrano, Rosa; Tejera, Agueda; Ayuso, Eduard; Jimenez, Veronica; Formentini, Ivan; Bobadilla, Maria; Mizrahi, Jacques; de Martino, Alba; Gomez, Gonzalo; Pisano, David; Mulero, Francisca; Wollert, Kai C.; Bosch, Fatima; Blasco, Maria A.

    2016-01-01

    Coronary heart disease is one of the main causes of death in the developed world, and treatment success remains modest, with high mortality rates within 1 year after myocardial infarction (MI). Thus, new therapeutic targets and effective treatments are necessary. Short telomeres are risk factors for age-associated diseases, including heart disease. Here we address the potential of telomerase (Tert) activation in prevention of heart failure after MI in adult mice. We use adeno-associated viruses for cardiac-specific Tert expression. We find that upon MI, hearts expressing Tert show attenuated cardiac dilation, improved ventricular function and smaller infarct scars concomitant with increased mouse survival by 17% compared with controls. Furthermore, Tert treatment results in elongated telomeres, increased numbers of Ki67 and pH3-positive cardiomyocytes and a gene expression switch towards a regeneration signature of neonatal mice. Our work suggests telomerase activation could be a therapeutic strategy to prevent heart failure after MI. PMID:25519492

  14. Acute effects of whole-body vibration on trunk muscle functioning in young healthy adults.

    PubMed

    Ye, Jiajia; Ng, Gabriel; Yuen, Kenneth

    2014-10-01

    The purpose of this study was to explore the immediate effects of different frequencies of whole-body vibration (WBV) on the performance of trunk muscles of healthy young adults. A group of 30 healthy subjects (15 men; 15 women; age, 26.8 ± 3.74 years; body mass index, 21.9 ± 1.802) participated in the study. Each subject received 3 sessions of vibration exercise with different exercise parameters with frequencies of 25 Hz and 40 Hz and sham stimulation in a random order on different days. Before and after each WBV exercise session, subjects were assessed for trunk muscle strength/endurance tests and trunk proprioception tests. There was a significant increase in trunk extensor strength (p ≤ 0.05) after low-frequency (25 Hz) WBV exercise, but high-frequency (40 Hz) vibration exercise had resulted in a significant decrease in trunk extensor endurance (p ≤ 0.05). Statistical gender difference (p = 0.04) was found for trunk extensor endurance with lower WBV training. No change was noted in the trunk proprioception with different frequencies of WBV. In conclusions, the immediate response of the body to WBV was different for low and high frequencies. Low-frequency vibration enhanced trunk extensor strength, but high-frequency vibration would decrease endurance of the trunk extensor muscles. Males are more sensitive than females in trunk extensor endurance for lower frequency WBV exposure. These results indicated that short-term WBV with low frequency was effective to improve trunk extensor strength in healthy adults, and that could be helpful for relevant activities of trunk extensor performing and preventing sport injury. PMID:24714536

  15. Acute flaccid paralysis due to West nile virus infection in adults: A paradigm shift entity

    PubMed Central

    Maramattom, Boby Varkey; Philips, Geetha; Sudheesh, Nittur; Arunkumar, Govindakarnavar

    2014-01-01

    Three cases of acute flaccid paralysis (AFP) with preceding fever are described. One patient had a quadriparesis with a florid meningoencephalitic picture and the other two had asymmetric flaccid paralysis with fasciculations at the onset of illness. Magnetic resonance imaging in two cases showed prominent hyperintensitities in the spinal cord and brainstem with prominent involvement of the grey horn (polio-myelitis). Cerebrospinal fluid (CSF) polymerase chain reaction was positive for West Nile virus (WNV) in the index patient. All three cases had a positive WNV immunoglobulin M antibody in serum/CSF and significantly high titer of WNV neutralizing antibody in serum, clearly distinguishing the infection from other Flaviviridae such as Japanese encephalitis. WNV has been recognized in India for many decades; however, AFP has not been adequately described. WNV is a flavivirus that is spread by Culex mosquitoes while they take blood meals from humans and lineage 1 is capable of causing a devastating neuro-invasive disease with fatal consequences or severe morbidity. We describe the first three laboratory confirmed cases of WNV induced AFP from Kerala and briefly enumerate the salient features of this emerging threat. PMID:24753667

  16. Influence of acute tryptophan depletion on verbal declarative episodic memory in young adult females.

    PubMed

    Helmbold, K; Bubenzer, S; Dahmen, B; Eisert, A; Gaber, T J; Habel, U; Konrad, K; Herpertz-Dahlmann, B; Zepf, F D

    2013-11-01

    Diminished synthesis of the neurotransmitter serotonin (5-HT) in the brain has been linked to disturbed memory processes. The present study investigated the effects of diminished central nervous 5-HT synthesis as achieved by an acute dietary tryptophan depletion (ATD) on verbal declarative episodic memory in young women while controlling for the effects of female sex hormones. Eighteen healthy females (aged 20-31 years) participated in a within-subject repeated measures study, with two separate days of assessment spaced at least one individual menstrual cycle apart. On one day, participants were subjected to ATD, thus lowering central nervous 5-HT synthesis. The other day participants received a tryptophan-balanced amino acid load (BAL = control condition). The study was randomized, counterbalanced and double blind in terms of ATD/BAL administration. Measurements took place in the early follicular phase of the participants' menstrual cycle. Estrogen, FSH and LH levels were assessed at baseline. Verbal declarative episodic memory was assessed using a structured word-learning task. Short-term memory, as indexed by immediate recall, was reduced after ATD intake, whereas delayed recall and recognition after a 25-min delay did not show any differences after intake of ATD or BAL. In young women, verbal short-term memory function was more vulnerable to ATD than consolidation processes. In light of the possible interplay between female sex hormones and 5-HT, further studies comparing different menstrual cycle phases are needed. PMID:24072504

  17. ACUTE CLINICAL LEPTOSPIROSIS (GRIPPOTYPHOSA SEROVAR) IN AN ADULT DROMEDARY CAMEL (CAMELUS DROMEDARIUS).

    PubMed

    Gyimesi, Zoltan S; Burns, Roy B; Erol, Erdal; Bolin, Steven R

    2015-09-01

    A 9-yr-old castrated male dromedary camel (Camelus dromedarius) presented with lethargy and partial anorexia. A diagnostic examination revealed fever, and further workup revealed a neutrophilia, hyperfibrinogenemia, renal azotemia, and a rapid onset of a high Leptospira antibody titer during the acute clinical period (Grippotyphosa serovar). The camel responded clinically to antimicrobial treatment with ceftiofur crystalline free acid injections, but renal azotemia persisted, presumably secondary to chronic renal damage. Subsequent Leptospira polymerase chain reaction testing on urine samples obtained over the following 4 mo revealed no evidence of urinary shedding, so a persistent infection was unlikely. Although often mentioned as a potential cause of reproductive loss, well-documented case reports of clinical leptospirosis in camelids are very rare. In this case, native wildlife contamination of a small watering hole is suspected to have been the source of infection. In response to this experience, the camel and two conspecifics were prescribed a vaccination regimen using an inactivated pentavalent Leptospira vaccine licensed for cattle. PMID:26352970

  18. No Acute Effects of Choline Bitartrate Food Supplements on Memory in Healthy, Young, Human Adults

    PubMed Central

    Lippelt, D. P.; van der Kint, S.; van Herk, K.; Naber, M.

    2016-01-01

    Choline is a dietary component and precursor of acetylcholine, a crucial neurotransmitter for memory-related brain functions. In two double-blind, placebo-controlled cross-over experiments, we investigated whether the food supplement choline bitartrate improved declarative memory and working memory in healthy, young students one to two hours after supplementation. In experiment 1, 28 participants performed a visuospatial working memory task. In experiment 2, 26 participants performed a declarative picture memorization task. In experiment 3, 40 participants performed a verbal working memory task in addition to the visuospatial working memory and declarative picture task. All tasks were conducted approximately 60 minutes after the ingestion of 2.0–2.5g of either choline bitartrate or placebo. We found that choline did not significantly enhance memory performance during any of the tasks. The null hypothesis that choline does not improve memory performance as compared to placebo was strongly supported by Bayesian statistics. These results are in contrast with animal studies suggesting that choline supplementation boosts memory performance and learning. We conclude that choline likely has no acute effects on cholinergic memory functions in healthy human participants. PMID:27341028

  19. No Acute Effects of Choline Bitartrate Food Supplements on Memory in Healthy, Young, Human Adults.

    PubMed

    Lippelt, D P; van der Kint, S; van Herk, K; Naber, M

    2016-01-01

    Choline is a dietary component and precursor of acetylcholine, a crucial neurotransmitter for memory-related brain functions. In two double-blind, placebo-controlled cross-over experiments, we investigated whether the food supplement choline bitartrate improved declarative memory and working memory in healthy, young students one to two hours after supplementation. In experiment 1, 28 participants performed a visuospatial working memory task. In experiment 2, 26 participants performed a declarative picture memorization task. In experiment 3, 40 participants performed a verbal working memory task in addition to the visuospatial working memory and declarative picture task. All tasks were conducted approximately 60 minutes after the ingestion of 2.0-2.5g of either choline bitartrate or placebo. We found that choline did not significantly enhance memory performance during any of the tasks. The null hypothesis that choline does not improve memory performance as compared to placebo was strongly supported by Bayesian statistics. These results are in contrast with animal studies suggesting that choline supplementation boosts memory performance and learning. We conclude that choline likely has no acute effects on cholinergic memory functions in healthy human participants. PMID:27341028

  20. Immunophenotype of adult and childhood acute lymphoblastic leukemia: changes at first relapse and clinico-prognostic implications.

    PubMed

    Guglielmi, C; Cordone, I; Boecklin, F; Masi, S; Valentini, T; Vegna, M L; Ferrari, A; Testi, A M; Foa, R

    1997-09-01

    The immunologic features of leukemic cells at the time of 1st hematologic relapse were compared to those obtained at initial diagnosis in 128 patients (69 children and 59 adults) with acute lymphoblastic leukemia (ALL) treated at a single institution. An immunophenotypic change was observed in 59 cases (46%), more frequently in T (20/25) than in B (39/103) lineage ALL (80 vs 38%, P=0.0008), but with a similar incidence in adults and children. Of these cases, 34 (24 B- and 10 T-ALL) changed at relapse their intralineage subgroup affiliation, although no complete shift from B to T lineage ALL, or vice versa, was observed. The myeloid antigens CD13 and/or CD33 were frequently lost (2/5 cases) or acquired (12/123 cases) at relapse. In 21 cases, the immunophenotype at relapse was more undifferentiated than at diagnosis, while it was more differentiated in 13 cases. Initial treatment intensity or preceding treatment with teniposide did not affect the phenotypic profile at relapse. Complete response (CR) rate to salvage therapy and event-free survival were not influenced by the immunophenotypic shifts, nor by the presence, at relapse, of leukemic cells expressing the myeloid antigens CD13 and/or CD33. Univariate analysis suggested that prognosis after relapse was dependent on the duration of 1st CR, patients' age and immunophenotype at the time of diagnosis, with a worse outcome for patients with T lineage ALL and for patients with the less differentiated subgroup of B lineage ALL (CD19+ and CD10-). Multivariate analysis showed that only two factors, duration of 1st CR and grade of immunologic differentiation at diagnosis, have independent prognostic value in relapsed ALL. PMID:9305605