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 ...

Mouse xenograft modeling of human adult acute lymphoblastic leukemia provides mechanistic insights into adult LIC biology

PubMed Central

Dey, Aditi; Castleton, Anna Z.; Schwab, Claire; Samuel, Edward; Sivakumaran, Janani; Beaton, Brendan; Zareian, Nahid; Zhang, Christie Yu; Rai, Lena; Enver, Tariq; Moorman, Anthony V.; Fielding, Adele K.

2014-01-01

The distinct nature of acute lymphoblastic leukemia (ALL) in adults, evidenced by inferior treatment outcome and different genetic landscape, mandates specific studies of disease-initiating mechanisms. In this study, we used NOD/LtSz-scid IL2Rγ nullc (NSG) mouse xenotransplantation approaches to elucidate leukemia-initiating cell (LIC) biology in primary adult precursor B (pre-B) ALL to optimize disease modeling. In contrast with xenografting studies of pediatric ALL, we found that modification of the NSG host environment using preconditioning total body irradiation (TBI) was indispensable for efficient engraftment of adult non-t(4;11) pre-B ALL, whereas t(4;11) pre-B ALL was successfully reconstituted without this adaptation. Furthermore, TBI-based xenotransplantation of non-t(4;11) pre-B ALL enabled detection of a high frequency of LICs (<1:6900) and permitted frank leukemic engraftment from a remission sample containing drug-resistant minimal residual disease. Investigation of TBI-sensitive stromal-derived factor-1/chemokine receptor type 4 signaling revealed greater functional dependence of non-t(4;11) pre-B ALL on this niche-based interaction, providing a possible basis for the differential engraftment behavior. Thus, our studies establish the optimal conditions for experimental modeling of human adult pre-B ALL and demonstrate the critical protumorogenic role of microenvironment-derived SDF-1 in regulating adult pre-B LIC activity that may present a therapeutic opportunity. PMID:24825861

Immature MEF2C-dysregulated T-cell leukemia patients have an early T-cell precursor acute lymphoblastic leukemia gene signature and typically have non-rearranged T-cell receptors

PubMed Central

Zuurbier, Linda; Gutierrez, Alejandro; Mullighan, Charles G.; Canté-Barrett, Kirsten; Gevaert, A. Olivier; de Rooi, Johan; Li, Yunlei; Smits, Willem K.; Buijs-Gladdines, Jessica G.C.A.M.; Sonneveld, Edwin; Look, A. Thomas; Horstmann, Martin; Pieters, Rob; Meijerink, Jules P.P.

2014-01-01

Three distinct immature T-cell acute lymphoblastic leukemia entities have been described including cases that express an early T-cell precursor immunophenotype or expression profile, immature MEF2C-dysregulated T-cell acute lymphoblastic leukemia cluster cases based on gene expression analysis (immature cluster) and cases that retain non-rearranged TRG@ loci. Early T-cell precursor acute lymphoblastic leukemia cases exclusively overlap with immature cluster samples based on the expression of early T-cell precursor acute lymphoblastic leukemia signature genes, indicating that both are featuring a single disease entity. Patients lacking TRG@ rearrangements represent only 40% of immature cluster cases, but no further evidence was found to suggest that cases with absence of bi-allelic TRG@ deletions reflect a distinct and even more immature disease entity. Immature cluster/early T-cell precursor acute lymphoblastic leukemia cases are strongly enriched for genes expressed in hematopoietic stem cells as well as genes expressed in normal early thymocyte progenitor or double negative-2A T-cell subsets. Identification of early T-cell precursor acute lymphoblastic leukemia cases solely by defined immunophenotypic criteria strongly underestimates the number of cases that have a corresponding gene signature. However, early T-cell precursor acute lymphoblastic leukemia samples correlate best with a CD1 negative, CD4 and CD8 double negative immunophenotype with expression of CD34 and/or myeloid markers CD13 or CD33. Unlike various other studies, immature cluster/early T-cell precursor acute lymphoblastic leukemia patients treated on the COALL-97 protocol did not have an overall inferior outcome, and demonstrated equal sensitivity levels to most conventional therapeutic drugs compared to other pediatric T-cell acute lymphoblastic leukemia patients. PMID:23975177

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

PubMed

Khlghatyan, Jivan; Saghatelyan, Armen

2012-09-12

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

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

Acute lymphoblastic leukemia: a comprehensive review and 2017 update

PubMed Central

Terwilliger, T; Abdul-Hay, M

2017-01-01

Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults, with an incidence of over 6500 cases per year in the United States alone. The hallmark of ALL is chromosomal abnormalities and genetic alterations involved in differentiation and proliferation of lymphoid precursor cells. In adults, 75% of cases develop from precursors of the B-cell lineage, with the remainder of cases consisting of malignant T-cell precursors. Traditionally, risk stratification has been based on clinical factors such age, white blood cell count and response to chemotherapy; however, the identification of recurrent genetic alterations has helped refine individual prognosis and guide management. Despite advances in management, the backbone of therapy remains multi-agent chemotherapy with vincristine, corticosteroids and an anthracycline with allogeneic stem cell transplantation for eligible candidates. Elderly patients are often unable to tolerate such regimens and carry a particularly poor prognosis. Here, we review the major recent advances in the treatment of ALL. PMID:28665419

GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boku, Shuken, E-mail: shuboku@med.hokudai.ac.jp; Nakagawa, Shin; Takamura, Naoki

2013-05-17

Highlights: •GDNF has no effect on ADP proliferation and apoptosis. •GDNF increases ADP differentiation into astrocyte. •A specific inhibitor of STAT3 decreases the astrogliogenic effect of GDNF. •STAT3 knockdown by lentiviral shRNA vector also decreases the astrogliogenic effect of GDNF. •GDNF increases the phosphorylation of STAT3. -- Abstract: While the pro-neurogenic actions of antidepressants in the adult hippocampal dentate gyrus (DG) are thought to be one of the mechanisms through which antidepressants exert their therapeutic actions, antidepressants do not increase proliferation of neural precursor cells derived from the adult DG. Because previous studies showed that antidepressants increase the expression andmore » secretion of glial cell line-derived neurotrophic factor (GDNF) in C6 glioma cells derived from rat astrocytes and GDNF increases neurogenesis in adult DG in vivo, we investigated the effects of GDNF on the proliferation, differentiation and apoptosis of cultured neural precursor cells derived from the adult DG. Data showed that GDNF facilitated the differentiation of neural precursor cells into astrocytes but had no effect on their proliferation or apoptosis. Moreover, GDNF increased the phosphorylation of STAT3, and both a specific inhibitor of STAT3 and lentiviral shRNA for STAT3 decreased their differentiation into astrocytes. Taken together, our findings suggest that GDNF facilitates astrogliogenesis from neural precursor cells in adult DG through activating STAT3 and that this action might indirectly affect neurogenesis.« less

Tumor suppressors BTG1 and IKZF1 cooperate during mouse leukemia development and increase relapse risk in B-cell precursor acute lymphoblastic leukemia patients.

PubMed

Scheijen, Blanca; Boer, Judith M; Marke, René; Tijchon, Esther; van Ingen Schenau, Dorette; Waanders, Esmé; van Emst, Liesbeth; van der Meer, Laurens T; Pieters, Rob; Escherich, Gabriele; Horstmann, Martin A; Sonneveld, Edwin; Venn, Nicola; Sutton, Rosemary; Dalla-Pozza, Luciano; Kuiper, Roland P; Hoogerbrugge, Peter M; den Boer, Monique L; van Leeuwen, Frank N

2017-03-01

Deletions and mutations affecting lymphoid transcription factor IKZF1 (IKAROS) are associated with an increased relapse risk and poor outcome in B-cell precursor acute lymphoblastic leukemia. However, additional genetic events may either enhance or negate the effects of IKZF1 deletions on prognosis. In a large discovery cohort of 533 childhood B-cell precursor acute lymphoblastic leukemia patients, we observed that single-copy losses of BTG1 were significantly enriched in IKZF1 -deleted B-cell precursor acute lymphoblastic leukemia ( P =0.007). While BTG1 deletions alone had no impact on prognosis, the combined presence of BTG1 and IKZF1 deletions was associated with a significantly lower 5-year event-free survival ( P =0.0003) and a higher 5-year cumulative incidence of relapse ( P =0.005), when compared with IKZF1 -deleted cases without BTG1 aberrations. In contrast, other copy number losses commonly observed in B-cell precursor acute lymphoblastic leukemia, such as CDKN2A/B, PAX5, EBF1 or RB1 , did not affect the outcome of IKZF1 -deleted acute lymphoblastic leukemia patients. To establish whether the combined loss of IKZF1 and BTG1 function cooperate in leukemogenesis, Btg1 -deficient mice were crossed onto an Ikzf1 heterozygous background. We observed that loss of Btg1 increased the tumor incidence of Ikzf1 +/- mice in a dose-dependent manner. Moreover, murine B cells deficient for Btg1 and Ikzf1 +/- displayed increased resistance to glucocorticoids, but not to other chemotherapeutic drugs. Together, our results identify BTG1 as a tumor suppressor in leukemia that, when deleted, strongly enhances the risk of relapse in IKZF1 -deleted B-cell precursor acute lymphoblastic leukemia, and augments the glucocorticoid resistance phenotype mediated by the loss of IKZF1 function. Copyright© Ferrata Storti Foundation.

Opposing Effects of α2- and β-Adrenergic Receptor Stimulation on Quiescent Neural Precursor Cell Activity and Adult Hippocampal Neurogenesis

PubMed Central

Prosper, Boris W.; Marathe, Swanand; Husain, Basma F. A.; Kernie, Steven G.; Bartlett, Perry F.; Vaidya, Vidita A.

2014-01-01

Norepinephrine regulates latent neural stem cell activity and adult hippocampal neurogenesis, and has an important role in modulating hippocampal functions such as learning, memory and mood. Adult hippocampal neurogenesis is a multi-stage process, spanning from the activation and proliferation of hippocampal stem cells, to their differentiation into neurons. However, the stage-specific effects of noradrenergic receptors in regulating adult hippocampal neurogenesis remain poorly understood. In this study, we used transgenic Nestin-GFP mice and neurosphere assays to show that modulation of α2- and β-adrenergic receptor activity directly affects Nestin-GFP/GFAP-positive precursor cell population albeit in an opposing fashion. While selective stimulation of α2-adrenergic receptors decreases precursor cell activation, proliferation and immature neuron number, stimulation of β-adrenergic receptors activates the quiescent precursor pool and enhances their proliferation in the adult hippocampus. Furthermore, our data indicate no major role for α1-adrenergic receptors, as we did not observe any change in either the activation and proliferation of hippocampal precursors following selective stimulation or blockade of α1-adrenergic receptors. Taken together, our data suggest that under physiological as well as under conditions that lead to enhanced norepinephrine release, the balance between α2- and β-adrenergic receptor activity regulates precursor cell activity and hippocampal neurogenesis. PMID:24922313

Loss of p19Arf in a Rag1−/− B-cell precursor population initiates acute B-lymphoblastic leukemia

PubMed Central

Hauer, Julia; Mullighan, Charles; Morillon, Estelle; Wang, Gary; Bruneau, Julie; Brousse, Nicole; Lelorc'h, Marc; Romana, Serge; Boudil, Amine; Tiedau, Daniela; Kracker, Sven; Bushmann, Frederic D.; Borkhardt, Arndt; Fischer, Alain; Hacein-Bey-Abina, Salima

2011-01-01

In human B-acute lymphoblastic leukemia (B-ALL), RAG1-induced genomic alterations are important for disease progression. However, given that biallelic loss of the RAG1 locus is observed in a subset of cases, RAG1's role in the development of B-ALL remains unclear. We chose a p19Arf−/−Rag1−/− mouse model to confirm the previously published results concerning the contribution of CDKN2A (p19ARF /INK4a) and RAG1 copy number alterations in precursor B cells to the initiation and/or progression to B-acute lymphoblastic leukemia (B-ALL). In this murine model, we identified a new, Rag1-independent leukemia-initiating mechanism originating from a Sca1+CD19+ precursor cell population and showed that Notch1 expression accelerates the cells' self-renewal capacity in vitro. In human RAG1-deficient BM, a similar CD34+CD19+ population expressed p19ARF. These findings suggest that combined loss of p19Arf and Rag1 results in B-cell precursor leukemia in mice and may contribute to the progression of precursor B-ALL in humans. PMID:21622646

Acute necrotising ulcerative gingivitis in an immunocompromised young adult

PubMed Central

Hu, Jessie; Kent, Paul; Lennon, Joshua M; Logan, Latania K

2015-01-01

Acute necrotising ulcerative gingivitis is an acute onset disease characterised by ulceration, necrosis, pain and bleeding in gingival surfaces. It is predominantly seen in severely malnourished children and young adults with advanced HIV infection. We present a unique presentation in a young adult with high-grade osteogenic sarcoma. PMID:26376700

High CD45 surface expression determines relapse risk in children with precursor B-cell and T-cell acute lymphoblastic leukemia treated according to the ALL-BFM 2000 protocol

PubMed Central

Cario, Gunnar; Rhein, Peter; Mitlöhner, Rita; Zimmermann, Martin; Bandapalli, Obul R.; Romey, Renja; Moericke, Anja; Ludwig, Wolf-Dieter; Ratei, Richard; Muckenthaler, Martina U.; Kulozik, Andreas E.; Schrappe, Martin; Stanulla, Martin; Karawajew, Leonid

2014-01-01

Further improvement of outcome in childhood acute lymphoblastic leukemia could be achieved by identifying additional high-risk patients who may benefit from intensified treatment. We earlier identified PTPRC (CD45) gene expression as a potential new stratification marker and now analyzed the prognostic relevance of CD45 protein expression. CD45 was measured by flow cytometry in 1065 patients treated according to the ALL-BFM-2000 protocol. The 75th percentile was used as cut-off to distinguish a CD45-high from a CD45-low group. As mean CD45 expression was significantly higher in T-cell acute lymphoblastic leukemia than in B-cell-precursor acute lymphoblastic leukemia (P<0.0001), the analysis was performed separately in both groups. In B-cell-precursor acute lymphoblastic leukemia we observed a significant association of a high CD45 expression with older age, high initial white blood cell count, ETV6/RUNX1 negativity, absence of high hyperdiploidy (P<0.0001), MLL/AF4 positivity (P=0.002), BCR/ABL1 positivity (P=0.007), prednisone poor response (P=0.002) and minimal residual disease (P<0.0001). In T-cell acute lymphoblastic leukemia we observed a significant association with initial white blood cell count (P=0.0003), prednisone poor response (P=0.01), and minimal residual disease (P=0.02). Compared to CD45-low patients, CD45-high patients had a lower event-free survival rate (B-cell-precursor acute lymphoblastic leukemia: 72±3% versus 86±1%, P<0.0001; T-cell acute lymphoblastic leukemia: 60±8% versus 78±4%, P=0.02), which was mainly attributable to a higher cumulative relapse incidence (B-cell-precursor acute lymphoblastic leukemia: 22±3% versus 11±1%, P<0.0001; T-cell acute lymphoblastic leukemia: 31±8% versus 11±3%, P=0.003) and kept its significance in multivariate analysis considering sex, age, initial white blood cell count, and minimal residual disease in B-cell-precursor- and T-cell acute lymphoblastic leukemia, and additionally presence of ETV6/RUNX1

High CD45 surface expression determines relapse risk in children with precursor B-cell and T-cell acute lymphoblastic leukemia treated according to the ALL-BFM 2000 protocol.

PubMed

Cario, Gunnar; Rhein, Peter; Mitlöhner, Rita; Zimmermann, Martin; Bandapalli, Obul R; Romey, Renja; Moericke, Anja; Ludwig, Wolf-Dieter; Ratei, Richard; Muckenthaler, Martina U; Kulozik, Andreas E; Schrappe, Martin; Stanulla, Martin; Karawajew, Leonid

2014-01-01

Further improvement of outcome in childhood acute lymphoblastic leukemia could be achieved by identifying additional high-risk patients who may benefit from intensified treatment. We earlier identified PTPRC (CD45) gene expression as a potential new stratification marker and now analyzed the prognostic relevance of CD45 protein expression. CD45 was measured by flow cytometry in 1065 patients treated according to the ALL-BFM-2000 protocol. The 75(th) percentile was used as cut-off to distinguish a CD45-high from a CD45-low group. As mean CD45 expression was significantly higher in T-cell acute lymphoblastic leukemia than in B-cell-precursor acute lymphoblastic leukemia (P<0.0001), the analysis was performed separately in both groups. In B-cell-precursor acute lymphoblastic leukemia we observed a significant association of a high CD45 expression with older age, high initial white blood cell count, ETV6/RUNX1 negativity, absence of high hyperdiploidy (P<0.0001), MLL/AF4 positivity (P=0.002), BCR/ABL1 positivity (P=0.007), prednisone poor response (P=0.002) and minimal residual disease (P<0.0001). In T-cell acute lymphoblastic leukemia we observed a significant association with initial white blood cell count (P=0.0003), prednisone poor response (P=0.01), and minimal residual disease (P=0.02). Compared to CD45-low patients, CD45-high patients had a lower event-free survival rate (B-cell-precursor acute lymphoblastic leukemia: 72 ± 3% versus 86 ± 1%, P<0.0001; T-cell acute lymphoblastic leukemia: 60 ± 8% versus 78 ± 4%, P=0.02), which was mainly attributable to a higher cumulative relapse incidence (B-cell-precursor acute lymphoblastic leukemia: 22 ± 3% versus 11 ± 1%, P<0.0001; T-cell acute lymphoblastic leukemia: 31 ± 8% versus 11 ± 3%, P=0.003) and kept its significance in multivariate analysis considering sex, age, initial white blood cell count, and minimal residual disease in B-cell-precursor- and T-cell acute lymphoblastic leukemia, and additionally

Adult subependymal neural precursors, but not differentiated cells, undergo rapid cathodal migration in the presence of direct current electric fields.

PubMed

Babona-Pilipos, Robart; Droujinine, Ilia A; Popovic, Milos R; Morshead, Cindi M

2011-01-01

The existence of neural stem and progenitor cells (together termed neural precursor cells) in the adult mammalian brain has sparked great interest in utilizing these cells for regenerative medicine strategies. Endogenous neural precursors within the adult forebrain subependyma can be activated following injury, resulting in their proliferation and migration toward lesion sites where they differentiate into neural cells. The administration of growth factors and immunomodulatory agents following injury augments this activation and has been shown to result in behavioural functional recovery following stroke. With the goal of enhancing neural precursor migration to facilitate the repair process we report that externally applied direct current electric fields induce rapid and directed cathodal migration of pure populations of undifferentiated adult subependyma-derived neural precursors. Using time-lapse imaging microscopy in vitro we performed an extensive single-cell kinematic analysis demonstrating that this galvanotactic phenomenon is a feature of undifferentiated precursors, and not differentiated phenotypes. Moreover, we have shown that the migratory response of the neural precursors is a direct effect of the electric field and not due to chemotactic gradients. We also identified that epidermal growth factor receptor (EGFR) signaling plays a role in the galvanotactic response as blocking EGFR significantly attenuates the migratory behaviour. These findings suggest direct current electric fields may be implemented in endogenous repair paradigms to promote migration and tissue repair following neurotrauma.

Stages of Adult Acute Myeloid Leukemia

MedlinePlus

... in the past. Having had treatment for childhood acute lymphoblastic leukemia (ALL) in the past. Being exposed to radiation from an atomic bomb or to the chemical benzene . Having a history of a blood disorder such as myelodysplastic syndrome . Signs and symptoms of adult AML include fever, ...

Advances in adult acute lymphoblastic leukemia therapy.

PubMed

Aldoss, Ibrahim; Stein, Anthony S

2018-05-01

Progress in adult acute lymphoblastic leukemia (ALL) treatment has been met with challenge until recently. A steady improvement in outcomes is being witnessed among adults with ALL, and it will be enhanced further with early referral of newly diagnosed ALL patients to specialized centers, enrolling more ALL adults in clinical trials, adopting pediatric-inspired ALL regimens in younger adults, tailoring treatments according to minimal residual disease response and disease genetics, incorporating novel therapies and tyrosine kinase inhibitors in frontline regimens, early referral to transplant when indicated, expanding the donor pool, and developing more effective salvage therapies for relapsed/refractory ALL. In this review, we will discuss the most significant advances in treating adult ALL observed in the last five years that have the potential to enhance adult ALL treatment and outcome.

Household Air Pollution and Acute Lower Respiratory Infections in Adults: A Systematic Review.

PubMed

Jary, Hannah; Simpson, Hope; Havens, Deborah; Manda, Geoffrey; Pope, Daniel; Bruce, Nigel; Mortimer, Kevin

2016-01-01

Household air pollution from solid fuel burning kills over 4 million people every year including half a million children from acute lower respiratory infections. Although biologically plausible, it is not clear whether household air pollution is also associated with acute lower respiratory infections in adults. We systematically reviewed the literature on household air pollution and acute lower respiratory infection in adults to identify knowledge gaps and research opportunities. Ten bibliographic databases were searched to identify studies of household air pollution and adult acute lower respiratory infection. Data were extracted from eligible studies using standardised forms. From 4617 titles, 513 abstracts and 72 full-text articles were reviewed. Eight studies met the inclusion criteria of which 2 found a significant adjusted increased risk of acute lower respiratory infection, 2 identified a univariate association whilst 4 found no significant association. Study quality was generally limited. Heterogeneity in methods and findings precluded meta-analysis. A systematic review of the literature found limited evidence for an association between household air pollution and risk of acute lower respiratory infection in adults. Additional research, with carefully defined exposure and outcome measures, is required to complete the risk profile caused by household air pollution in adults. CRD42015028042.

Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manceur, Aziza P.; Donnelly Centre, University of Toronto, Toronto, Ontario; Tseng, Michael

2011-09-10

The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B)more » inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.« less

Acute gastroenteritis associated with rotavirus in adults.

PubMed

del Refugio González-Losa, M; Polanco-Marín, G G; Manzano-Cabrera, L; Puerto-Solís, M

2001-01-01

Rotavirus (RV) is an important cause of acute infectious diarrhea in children all over the world. In adults, RV infection tends to be subclinical; however, outbreaks of gastroenteritis have been reported in emergency situations and in closed communities. The aim of this study was to characterize electrophoretically and antigenically the strains of rotavirus that caused acute gastroenteritis in adults and correlate them with the clinical manifestations. A laboratory-based survey was carried out in which fecal samples from 44 patients over 18 years of age with acute gastroenteritis were studied. Polyacrylamide gels electrophoresis and immunoenzymatic assay with specific antibodies to group A rotavirus, serotypes G1-4, P1A, and P1B were carried out on all the samples. Twenty-eight (63.63%) of the 44 samples were positive for group A rotavirus. Of these, 19 (68%) had long pattern and nine (32%) short pattern. Of all positive samples, 15 (54%) were serotype G1, seven (25%) were G2, two (7%) were G4, and four (14%) had no monoclonal reaction; all were serotype P1A. Among the patients with RV infection, 13 (46.4%) required hospitalization and the remaining 15 (53.6%) showed moderate symptoms. The strains that infected the adults were electrophoretically and antigenically the same as those that infected infants in Mérida, Yucatán over the last 10 years. No relationship between the severity of the symptoms and any specific serotype was found.

CD200/BTLA deletions in pediatric precursor B-cell acute lymphoblastic leukemia treated according to the EORTC-CLG 58951 protocol

PubMed Central

Ghazavi, Farzaneh; Clappier, Emmanuelle; Lammens, Tim; Suciu, Stefan; Caye, Aurélie; Zegrari, Samira; Bakkus, Marleen; Grardel, Nathalie; Benoit, Yves; Bertrand, Yves; Minckes, Odile; Costa, Vitor; Ferster, Alina; Mazingue, Françoise; Plat, Geneviève; Plouvier, Emmanuel; Poirée, Marilyne; Uyttebroeck, Anne; van der Werff-ten Bosch, Jutte; Yakouben, Karima; Helsmoortel, Hetty; Meul, Magali; Van Roy, Nadine; Philippé, Jan; Speleman, Frank; Cavé, Hélène; Van Vlierberghe, Pieter; De Moerloose, Barbara

2015-01-01

DNA copy number analysis has been instrumental for the identification of genetic alterations in B-cell precursor acute lymphoblastic leukemia. Notably, some of these genetic defects have been associated with poor treatment outcome and might be relevant for future risk stratification. In this study, we characterized recurrent deletions of CD200 and BTLA genes, mediated by recombination-activating genes, and used breakpoint-specific polymerase chain reaction assay to screen a cohort of 1154 cases of B-cell precursor acute lymphoblastic leukemia uniformly treated according to the EORTC-CLG 58951 protocol. CD200/BTLA deletions were identified in 56 of the patients (4.8%) and were associated with an inferior 8-year event free survival in this treatment protocol [70.2% ± 1.2% for patients with deletions versus 83.5% ± 6.4% for non-deleted cases (hazard ratio 2.02; 95% confidence interval 1.23–3.32; P=0.005)]. Genetically, CD200/BTLA deletions were strongly associated with ETV6-RUNX1-positive leukemias (P<0.0001), but were also identified in patients who did not have any genetic abnormality that is currently used for risk stratification. Within the latter population of patients, the presence of CD200/BTLA deletions was associated with inferior event-free survival and overall survival. Moreover, the multivariate Cox model indicated that these deletions had independent prognostic impact on event-free survival when adjusting for conventional risk criteria. All together, these findings further underscore the rationale for copy number profiling as an important tool for risk stratification in human B-cell precursor acute lymphoblastic leukemia. This trial was registered at www.ClinicalTrials.gov as #NCT00003728. PMID:26137961

CD200/BTLA deletions in pediatric precursor B-cell acute lymphoblastic leukemia treated according to the EORTC-CLG 58951 protocol.

PubMed

Ghazavi, Farzaneh; Clappier, Emmanuelle; Lammens, Tim; Suciu, Stefan; Caye, Aurélie; Zegrari, Samira; Bakkus, Marleen; Grardel, Nathalie; Benoit, Yves; Bertrand, Yves; Minckes, Odile; Costa, Vitor; Ferster, Alina; Mazingue, Françoise; Plat, Geneviève; Plouvier, Emmanuel; Poirée, Marilyne; Uyttebroeck, Anne; van der Werff-Ten Bosch, Jutte; Yakouben, Karima; Helsmoortel, Hetty; Meul, Magali; Van Roy, Nadine; Philippé, Jan; Speleman, Frank; Cavé, Hélène; Van Vlierberghe, Pieter; De Moerloose, Barbara

2015-10-01

DNA copy number analysis has been instrumental for the identification of genetic alterations in B-cell precursor acute lymphoblastic leukemia. Notably, some of these genetic defects have been associated with poor treatment outcome and might be relevant for future risk stratification. In this study, we characterized recurrent deletions of CD200 and BTLA genes, mediated by recombination-activating genes, and used breakpoint-specific polymerase chain reaction assay to screen a cohort of 1154 cases of B-cell precursor acute lymphoblastic leukemia uniformly treated according to the EORTC-CLG 58951 protocol. CD200/BTLA deletions were identified in 56 of the patients (4.8%) and were associated with an inferior 8-year event free survival in this treatment protocol [70.2% ± 1.2% for patients with deletions versus 83.5% ± 6.4% for non-deleted cases (hazard ratio 2.02; 95% confidence interval 1.23-3.32; P=0.005)]. Genetically, CD200/BTLA deletions were strongly associated with ETV6-RUNX1-positive leukemias (P<0.0001), but were also identified in patients who did not have any genetic abnormality that is currently used for risk stratification. Within the latter population of patients, the presence of CD200/BTLA deletions was associated with inferior event-free survival and overall survival. Moreover, the multivariate Cox model indicated that these deletions had independent prognostic impact on event-free survival when adjusting for conventional risk criteria. All together, these findings further underscore the rationale for copy number profiling as an important tool for risk stratification in human B-cell precursor acute lymphoblastic leukemia. This trial was registered at www.ClinicalTrials.gov as #NCT00003728. Copyright© Ferrata Storti Foundation.

Blinatumomab activity in a patient with Down syndrome B-precursor acute lymphoblastic leukemia.

PubMed

Wadhwa, Aman; Kutny, Matthew A; Xavier, Ana C

2018-02-01

Persistent minimal residual disease (MRD) after consolidation may indicate chemotherapy insensitivity in B-precursor acute lymphoblastic leukemia (BP-ALL). Given the strong association of MRD and outcome in non-Down syndrome (non-DS) BP-ALL, it is likely that MRD levels are also of prognostic significance in DS BP-ALL. We report here the successful use of blinatumomab, a bispecific T-cell engager antibody construct, in a patient with DS BP-ALL and persistent MRD at the end of consolidation. Blinatumomab has been shown to have excellent results in patients with relapsed/refractory BP-ALL. This patient had no significant toxicity and achieved MRD negativity after only one cycle of blinatumomab. © 2017 Wiley Periodicals, Inc.

Interleukin-6 Regulates Adult Neural Stem Cell Numbers during Normal and Abnormal Post-natal Development.

PubMed

Storer, Mekayla A; Gallagher, Denis; Fatt, Michael P; Simonetta, Jaclin V; Kaplan, David R; Miller, Freda D

2018-05-08

Circulating systemic factors can regulate adult neural stem cell (NSC) biology, but the identity of these circulating cues is still being defined. Here, we have focused on the cytokine interleukin-6 (IL-6), since increased circulating levels of IL-6 are associated with neural pathologies such as autism and bipolar disorder. We show that IL-6 promotes proliferation of post-natal murine forebrain NSCs and that, when the IL-6 receptor is inducibly knocked out in post-natal or adult neural precursors, this causes a long-term decrease in forebrain NSCs. Moreover, a transient circulating surge of IL-6 in perinatal or adult mice causes an acute increase in neural precursor proliferation followed by long-term depletion of adult NSC pools. Thus, IL-6 signaling is both necessary and sufficient for adult NSC self-renewal, and acute perturbations in circulating IL-6, as observed in many pathological situations, have long-lasting effects on the size of adult NSC pools. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Identification of residual leukemic cells by flow cytometry in childhood B-cell precursor acute lymphoblastic leukemia: verification of leukemic state by flow-sorting and molecular/cytogenetic methods.

PubMed

Øbro, Nina F; Ryder, Lars P; Madsen, Hans O; Andersen, Mette K; Lausen, Birgitte; Hasle, Henrik; Schmiegelow, Kjeld; Marquart, Hanne V

2012-01-01

Reduction in minimal residual disease, measured by real-time quantitative PCR or flow cytometry, predicts prognosis in childhood B-cell precursor acute lymphoblastic leukemia. We explored whether cells reported as minimal residual disease by flow cytometry represent the malignant clone harboring clone-specific genomic markers (53 follow-up bone marrow samples from 28 children with B-cell precursor acute lymphoblastic leukemia). Cell populations (presumed leukemic and non-leukemic) were flow-sorted during standard flow cytometry-based minimal residual disease monitoring and explored by PCR and/or fluorescence in situ hybridization. We found good concordance between flow cytometry and genomic analyses in the individual flow-sorted leukemic (93% true positive) and normal (93% true negative) cell populations. Four cases with discrepant results had plausible explanations (e.g. partly informative immunophenotype and antigen modulation) that highlight important methodological pitfalls. These findings demonstrate that with sufficient experience, flow cytometry is reliable for minimal residual disease monitoring in B-cell precursor acute lymphoblastic leukemia, although rare cases require supplementary PCR-based monitoring.

Management and treatment of relapsed or refractory Ph(-) B-precursor ALL: a web-based, double-blind survey of EU clinicians.

PubMed

Saltman, Deborah; Barlev, Arie; Seshagiri, Divyagiri; Katsoulis, Ioannis; Lin, Vincent; Barber, Beth

2015-10-24

The prognosis for adult patients with Ph(-) B-precursor acute lymphoblastic leukaemia (ALL) who are refractory to treatment or experience relapse (R/R), is poor; over 90% of these patients die from the disease, typically within a few months. While there are some national guidelines published for the treatment of adult patients with ALL, and local working group recommendations do exist, there is very little detail and no preferred treatment regimens for adult patients with R/R Ph(-) B-precursor ALL. The aim of this study was to describe current real-world clinical practice in Europe for the management and treatment of adult R/R Ph(-) B-precursor ALL. A web-based, double-blind survey was conducted in November/December 2013 in France, Germany, Italy, Spain, and the UK. The survey was developed following consultation with specialist clinicians and a critical review of published literature. Eligible clinicians (15 per country) were board-certified in haemato-oncology or haematology; had at least 4 years of experience in their current role and had treated at least five patients with adult ALL in the 36 months before the survey, including at least one with R/R Ph(-) B-precursor ALL. Clinicians across the five countries consulted 16 guidelines and local working group recommendations for the diagnosis and treatment of R/R Ph(-) B-precursor ALL. Thirty three regimens for salvage therapy were reported; the most frequently cited was augmented hyper-CVAD (15%), with vincristine the most commonly used agent. Salvage therapy regimens involved a range of agents, and most respondents reported using at least one cytotoxic agent; across respondents 10 different cytotoxic agents were cited. All respondents reported that toxicity was common for the regimens they used to treat R/R Ph(-) B-precursor ALL. This study provides evidence of current management and treatment patterns of R/R Ph(-) B-precursor ALL in the real-world clinical practice in Europe. The approach to the treatment of R

CD19 CAR T Cells for B Cell Malignancies After Allogeneic Transplant

ClinicalTrials.gov

2017-02-14

Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia

A high throughput drug screening assay to identify compounds that promote oligodendrocyte differentiation using acutely dissociated and purified oligodendrocyte precursor cells.

PubMed

Lariosa-Willingham, Karen D; Rosler, Elen S; Tung, Jay S; Dugas, Jason C; Collins, Tassie L; Leonoudakis, Dmitri

2016-09-05

Multiple sclerosis is caused by an autoimmune response resulting in demyelination and neural degeneration. The adult central nervous system has the capacity to remyelinate axons in part through the generation of new oligodendrocytes (OLs). To identify clinical candidate compounds that may promote remyelination, we have developed a high throughput screening (HTS) assay to identify compounds that promote the differentiation of oligodendrocyte precursor cells (OPCs) into OLs. Using acutely dissociated and purified rat OPCs coupled with immunofluorescent image quantification, we have developed an OL differentiation assay. We have validated this assay with a known promoter of differentiation, thyroid hormone, and subsequently used the assay to screen the NIH clinical collection library. We have identified twenty-seven hit compounds which were validated by dose response analysis and the generation of half maximal effective concentration (EC50) values allowed for the ranking of efficacy. The assay identified novel promoters of OL differentiation which we attribute to (1) the incorporation of an OL toxicity pre-screen to allow lowering the concentrations of toxic compounds and (2) the utilization of freshly purified, non-passaged OPCs. These features set our assay apart from other OL differentiation assays used for drug discovery efforts. This acute primary OL-based differentiation assay should be of use to those interested in screening large compound libraries for the identification of drugs for the treatment of MS and other demyelinating diseases.

Acute peripheral neuropathy in adults. Guillain-Barré syndrome and related disorders.

PubMed

Pascuzzi, R M; Fleck, J D

1997-08-01

Acute paralysis in adults has an extensive assortment of etiologies. Guillian-Barré syndrome is the most common cause of acute neuropathy in adults. This review emphasizes pathophysiology, clinical features, differential diagnosis, and a practical approach to the laboratory work-up for patients with suspected Guillian-Barré syndrome. The current status of immunotherapy is reviewed.

Acute lymphoblastic leukemia in adolescents and young adults.

PubMed

Ribera, Josep-Maria; Oriol, Albert

2009-10-01

Today, long-term survival is achieved in more than 80% of children 1 to 10 years old with acute lymphoblastic leukemia (ALL). However, cure rates for adults and adolescents and young adults (AYA) with ALL remain relatively low, at only 40% to 50%. Age is a continuous prognostic variable in ALL, with no single age at which prognosis deteriorates markedly. Within childhood ALL populations, older children have shown inferior outcomes, whereas younger adults have shown superior outcomes among adult ALL patients. The type of treatment (pediatric-based versus adult-based) for AYA has recently been a matter of debate. In this article the biology and treatment of ALL in AYA is reviewed.

An unusual case of acute parotitis in a young adult.

PubMed

Sehic, Azra; Haenig, Caitlin; Spear, Francis

2017-08-01

Acute bacterial parotitis is uncommon in young adults. Infection with Serratia marcescens is even rarer and usually found in hospitalized patients. This case report focuses on a young woman with acute bacterial parotitis caused by S. marcescens that required a longer-than-normal course of antibiotics.

Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)—Health Professional Version

Cancer.gov

Adult Acute Lymphoblastic Leukemia (ALL; also called acute lymphocytic leukemia) is an aggressive cancer that can progress quickly without treatment. Treatments include chemotherapy, radiation therapy, stem cell transplant, and targeted therapy. Get detailed information about the molecular genetics, prognosis, and treatment of ALL in this clinician summary.

Treatment Option Overview (Adult Acute Myeloid Leukemia)

MedlinePlus

... in the past. Having had treatment for childhood acute lymphoblastic leukemia (ALL) in the past. Being exposed to radiation from an atomic bomb or to the chemical benzene . Having a history of a blood disorder such as myelodysplastic syndrome . Signs and symptoms of adult AML include fever, ...

Treatment Options for Adult Acute Myeloid Leukemia

MedlinePlus

... in the past. Having had treatment for childhood acute lymphoblastic leukemia (ALL) in the past. Being exposed to radiation from an atomic bomb or to the chemical benzene . Having a history of a blood disorder such as myelodysplastic syndrome . Signs and symptoms of adult AML include fever, ...

Morphological and immunological criteria of minimal residual disease detection in children with B-cell precursors acute lymphoblastic leukemia

NASA Astrophysics Data System (ADS)

Beznos, O. A.; Grivtsova, L. Yu; Popa, A. V.; Shervashidze, M. A.; Serebtyakova, I. N.; Tupitsyn, N. N.; Selchuk, V. U.; Grebennikova, O. P.; Titova, G. V.

2018-01-01

One of the key factors of prognosis and risk stratification in patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is minimal residual disease (MRD). Identification of MRD on the day 15th is one of the most significant in prognosis of the disease. We compared data of a morphological and flow cytometry results of assessment of a bone marrow (BM) at the day 15th of induction chemotherapy in children with BCP-ALL.

Increased KPI containing amyloid precursor protein in experimental autoimmune encephalomyelitis brains.

PubMed

Beilin, Orit; Karussis, Dimitrios M; Korczyn, Amos D; Gurwitz, David; Aronovich, Ramona; Mizrachi-Kol, Rachel; Chapman, Joab

2007-04-16

Amyloid precursor protein can be translated from three alternatively spliced mRNAs. We measured levels of amyloid precursor protein isoforms containing the Kunitz protease inhibitor domain (KPIAPP), and amyloid precursor protein without the Kunitz protease inhibitor domain (KPIAPP) in brain homogenates of acute experimental autoimmune encephalomyelitis mice. At the preclinical phase of the disease, both KPIAPP and KPIAPP levels were significantly higher in homogenates from brains of autoimmune encephalomyelitis mice, whereas at the acute phase of the disease only KPIAPP remained significantly elevated compared with controls. At the recovery phase, no differences were observed between the groups. The early and isoform-specific elevation of KPIAPP in autoimmune encephalomyelitis mice suggests a possible role for amyloid precursor protein in the immune response mediating the disease.

Prone Positioning Improves Oxygenation in Adult Burn Patients with Severe Acute Respiratory Distress Syndrome

DTIC Science & Technology

2012-01-01

Prone positioning improves oxygenation in adult burn patients with severe acute respiratory distress syndrome Diane F. Hale, MD, Jeremy W. Cannon, MD...Kevin K. Chung, MD, San Antonio, Texas BACKGROUND: Prone positioning (PP) improves oxygenation and may provide a benefit in patients with acute... positioning improves oxygenation in adult burn patients with severe acute respiratory distress syndrome 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM

The genomic landscape of acute lymphoblastic leukemia in children and young adults.

PubMed

Mullighan, Charles G

2014-12-05

Our understanding of the genetic basis of childhood acute lymphoblastic leukemia (ALL) has been greatly advanced by genomic profiling and sequencing studies. These efforts have characterized the genetic basis of recently described and poorly understood subtypes of ALL, including early T-cell precursor ALL, Philadelphia chromosome-like (Ph-like) ALL, and ALL with intrachromosomal amplification of chromosome 21, and have identified several rational therapeutic targets in high-risk ALL, notably ABL1-class and JAK-STAT inhibitors in Ph-like ALL. Deep sequencing studies are also refining our understanding of the genetic basis of clonal heterogeneity and relapse. These studies have elucidated the nature of clonal evolution during disease progression and identified genetic changes that confer resistance to specific therapeutic agents, including CREBBP and NT5C2. Genomic profiling has also identified common and rare inherited genetic variants that influence the risk of developing leukemia. These efforts are now being extended to ALL in adolescents and adults with the goal of fully defining the genetic landscape of ALL to further improve treatment outcomes in high-risk populations. © 2014 by The American Society of Hematology. All rights reserved.

Acute Myeloid Leukemia in Adolescents and Young Adults Treated in Pediatric and Adult Departments in the Nordic Countries.

PubMed

Wennström, Lovisa; Edslev, Pernille Wendtland; Abrahamsson, Jonas; Nørgaard, Jan Maxwell; Fløisand, Yngvar; Forestier, Erik; Gustafsson, Göran; Heldrup, Jesper; Hovi, Liisa; Jahnukainen, Kirsi; Jonsson, Olafur Gisli; Lausen, Birgitte; Palle, Josefine; Zeller, Bernward; Holmberg, Erik; Juliusson, Gunnar; Stockelberg, Dick; Hasle, Henrik

2016-01-01

Studies on adolescents and young adults with acute lymphoblastic leukemia suggest better results when using pediatric protocols for adult patients, while corresponding data for acute myeloid leukemia (AML) are limited. We investigated disease characteristics and outcome for de novo AML patients 10-30 years old treated in pediatric or adult departments. We included 166 patients 10-18 years of age with AML treated according to the pediatric NOPHO-protocols (1993-2009) compared with 253 patients aged 15-30 years treated in hematology departments (1996-2009) in the Nordic countries. The incidence of AML was 4.9/million/year for the age group 10-14 years, 6.5 for 15-18 years, and 6.9 for 19-30 years. Acute promyelocytic leukemia (APL) was more frequent in adults and in females of all ages. Pediatric patients with APL had similar overall survival as pediatric patients without APL. Overall survival at 5 years was 60% (52-68%) for pediatric patients compared to 65% (58-70%) for adult patients. Cytogenetics and presenting white blood cell count were the only independent prognostic factors for overall survival. Age was not an independent prognostic factor. No difference was found in outcome for AML patients age 10-30 years treated according to pediatric as compared to adult protocols. © 2015 Wiley Periodicals, Inc.

Treatment of Young Adults with Acute Lymphoblastic Leukemia.

PubMed

Kansagra, Ankit; Litzow, Mark

2017-06-01

Young adults with acute lymphoblastic leukemia are a distinctive category of patients, with substantial difference in disease biology and response to therapy; hence, they pose unique challenges and issues beyond those faced by children and older adults. Despite inferior survival compared to children, there is growing evidence to suggest that young adults have improved outcomes when treated with pediatric-based approaches. With better supportive care and toxicity management and multidisciplinary team and approach, we have made great improvement in outcomes of young adults with ALL. However, despite significant progress, patients with persistence of minimal residual disease have a poor prognosis. This review discusses current controversies in the management of young adults with ALL, outcomes following pediatric and adult protocols, and the role of allogeneic stem cell transplantation. We also explore recent advances in disease monitoring and highlight our approach to incorporation of novel therapies in the management of young adults with ALL.

Potential use of CD40 ligand for immunotherapy of childhood B-cell precursor acute lymphoblastic leukaemia.

PubMed

D'Amico, Giovanna; Marin, Virna; Biondi, Andrea; Bonamino, Martin Hernán

2004-09-01

Around 20% of children affected by B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) still experience a recurrence of the disease after diagnosis, despite a significant improvement in the cure rate (80%). Moreover, standard therapies have high and often unacceptable acute and chronic organ toxicity, with an increased risk for secondary malignancies. Therefore, new strategies are needed to improve overall survival and decrease treatment-associated morbidity. Recent in-vitro and in-vivo studies have demonstrated that CD40 engagement improves tumour immunogenicity and, consequently, generates a strong antitumour immune response. The CD40-CD40 ligand (CD40L) system is of pivotal importance in the immune response via interactions between T cells and antigen-presenting cells. The general aim of this chapter is to review the feasibility of developing cellular strategies to increase childhood BCP-ALL immunogenicity, and the potential use of CD40L as a new strategy to induce an antileukaemia immune response in BCP-ALL.

Acute hematogenous septic arthritis of the knee in adults.

PubMed

Sreenivas, T; Nataraj, A R; Menon, Jagdish

2013-10-01

To evaluate the factors associated with acute hematogenous septic arthritis of the knee in adults and to assess the outcome after open knee arthrotomy. We performed a prospective evaluation of 26 adult patients with acute nongonococcal septic arthritis of the knee presenting within 7 days. All patients underwent open knee arthrotomy, and final evaluation by means of Knee society score of the affected knee was compared with the contra lateral normal knee. The average duration of symptoms at the time of presentation was 3.9 days. Staphylococcus aureus was the commonest bacteria isolated in 17 (65.4 %) patients. The average duration of follow-up in our study was 18.5 months. In our study, Knee society score decreases as the age of the patient advances (P < 0.05) and also it was found to be low (P < 0.05) in the affected knee as compared to contra lateral normal knee. Our study shows that age of the patient at presentation is critical as it shows significant reduction in knee score. This explains that the septic arthritis may contribute to the progression of age-related degeneration of the knee joint. There appears to be no definite contributing factors or conditions associated with acute hematogenous septic arthritis of the knee in adults, although further study may be warranted regarding this matter.

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. © 2015 by The American Society of Hematology.

Acute lymphoblastic leukemia in adults

PubMed Central

Ribera, Josep-Maria

2011-01-01

Acute lymphoblastic leukemia (ALL) is the most frequent neoplastic disease in children, being a rare disease in adults. Many of the advances in pediatric ALL have been through modifications in the doses and schedules of available agents as opposed to the introduction of new compounds. In recent years some improvements in the outcome of ALL in adults have occurred. Application of pediatric regimens to young and middle-aged adults shows promise to improve outcome. Advances in the supportive care of patients undergoing allogeneic stem cell transplantation (SCT), the use of alternative sources of hematopoietic stem cells and the use of reduced-intensity conditioning regimens will expand the number of patients who can benefit from this therapeutic modality. The evaluation of minimal residual disease will further stratify risk classification and redefine the role of therapeutic modalities such as SCT or biologic agents. New drugs such as thyrosin kinase inhibitors or monoclonal antibodies have led to incremental improvements in outcome. Advances in the genetic and epigenetic mechanisms of the disease provide hope that targeted therapies can more effectively treat the disease with less toxicity. PMID:22053271

Adolescents and young adults with acute lymphoblastic leukemia.

PubMed

Stock, Wendy

2010-01-01

During the last decade, increasing attention has been paid to a unique group of patients with acute lymphoblastic leukemia (ALL) who lie at the crossroad of therapeutic care by pediatric and adult hematologists/oncologists. ALL is a disease that affects infants, children, adolescents, and adult patients. With current therapies, the vast majority of children with ALL are now long-term survivors; unfortunately, the same good results have not yet been obtained for adults with ALL. This review will describe current controversies surrounding the treatment of adolescents and young adults with ALL--a group who finds themselves in the transition from "pediatric" to "adult" treatment approaches. The review focuses on recent insights into disease biology, prognostic factors, and treatment outcomes that have led to a series of prospective clinical trials specifically designed for adolescents and younger adults (AYAs) with ALL. These trials have been designed to provide important new clinical, psychosocial, and biological insights, and to further improve the survival of this challenging and unique group of patients.

Seroprevalence and disease burden of acute hepatitis A in adult population in South Korea.

PubMed

Yoon, Jin Gu; Choi, Min Joo; Yoon, Jae Won; Noh, Ji Yun; Song, Joon Young; Cheong, Hee Jin; Kim, Woo Joo

2017-01-01

Adult seroprevalence of HAV is decreasing in developed countries including South Korea, due to general sanitation improvement. Although hepatitis A vaccination was introduced in South Korea more than 20 years ago, recent infection rates have not decreased. In this study, we investigate the seroprevalence of anti-HAV IgG, and estimate the national disease burden of acute hepatitis A in adult population. Seroprevalence data were collected from health promotion center of Korea University Guro Hospital, in Seoul, Korea from 2010 to 2014. Data from adults (≥20-years) being tested for anti-HAV IgG were included. In addition, epidemiological and clinical data of patients diagnosed with acute hepatitis A from 2009 to 2013, were collected from Korean Statistical Information Service (KOSIS) and the National Health Insurance Service (NHIS) database. Data were stratified and compared by age groups. A total of 11,177 subjects were tested for anti-HAV IgG from 2010 to 2014. Age-related seroprevalence showed relatively low seropositivity in young adults. Incidence of acute hepatitis A was highest in 2009 and lowest in 2013. When categorized by age group, adults in their 20s and 30s had more HAV infections and related-admissions than older adults. However, ICU admission rate and average insurance-covered cost was high in older adults. The anti-HAV IgG seropositivity in Korean younger adult population was low while the incidence of acute hepatitis A was high, especially in the 20-39 aged. However, a substantial number of older adults were infected, and required more intensive procedures and incurred higher insurance-covered medical costs.

Seroprevalence and disease burden of acute hepatitis A in adult population in South Korea

PubMed Central

Choi, Min Joo; Yoon, Jae Won; Noh, Ji Yun; Song, Joon Young; Cheong, Hee Jin; Kim, Woo Joo

2017-01-01

Background Adult seroprevalence of HAV is decreasing in developed countries including South Korea, due to general sanitation improvement. Although hepatitis A vaccination was introduced in South Korea more than 20 years ago, recent infection rates have not decreased. In this study, we investigate the seroprevalence of anti-HAV IgG, and estimate the national disease burden of acute hepatitis A in adult population. Methods Seroprevalence data were collected from health promotion center of Korea University Guro Hospital, in Seoul, Korea from 2010 to 2014. Data from adults (≥20-years) being tested for anti-HAV IgG were included. In addition, epidemiological and clinical data of patients diagnosed with acute hepatitis A from 2009 to 2013, were collected from Korean Statistical Information Service (KOSIS) and the National Health Insurance Service (NHIS) database. Data were stratified and compared by age groups. Results A total of 11,177 subjects were tested for anti-HAV IgG from 2010 to 2014. Age-related seroprevalence showed relatively low seropositivity in young adults. Incidence of acute hepatitis A was highest in 2009 and lowest in 2013. When categorized by age group, adults in their 20s and 30s had more HAV infections and related-admissions than older adults. However, ICU admission rate and average insurance-covered cost was high in older adults. Conclusion The anti-HAV IgG seropositivity in Korean younger adult population was low while the incidence of acute hepatitis A was high, especially in the 20–39 aged. However, a substantial number of older adults were infected, and required more intensive procedures and incurred higher insurance-covered medical costs. PMID:29065115

Acute Moderate Exercise Improves Mnemonic Discrimination in Young Adults

PubMed Central

Suwabe, Kazuya; Hyodo, Kazuki; Byun, Kyeongho; Ochi, Genta; Yassa, Michael A.; Soya, Hideaki

2018-01-01

Increasing evidence suggests that regular moderate exercise increases neurogenesis in the dentate gyrus (DG) of the hippocampus and improves memory functions in both humans and animals. The DG is known to play a role in pattern separation, which is the ability to discriminate among similar experiences, a fundamental component of episodic memory. While long-term voluntary exercise improves pattern separation, there is little evidence of alterations in DG function after an acute exercise session. Our previous studies showing acute moderate exercise-enhanced DG activation in rats, and acute moderate exercise-enhanced prefrontal activation and executive function in humans, led us to postulate that acute moderate exercise may also activate the hippocampus, including more specifically the DG, thus improving pattern separation. We thus investigated the effects of a 10-min moderate exercise (50% V̇O2peak) session, the recommended intensity for health promotion, on mnemonic discrimination (a behavioral index of pattern separation) in young adults. An acute bout of moderate exercise improved mnemonic discrimination performance in high similarity lures. These results support our hypothesis that acute moderate exercise improves DG-mediated pattern separation in humans, proposing a useful human acute-exercise model for analyzing the neuronal substrate underlying acute and regular exercise-enhanced episodic memory based on the hippocampus. PMID:27997992

Alterations of the bone marrow stromal microenvironment in adult patients with acute myeloid and lymphoblastic leukemias before and after allogeneic hematopoietic stem cell transplantation.

PubMed

Shipounova, Irina N; Petinati, Nataliya A; Bigildeev, Alexey E; Drize, Nina J; Sorokina, Tamara V; Kuzmina, Larisa A; Parovichnikova, Elena N; Savchenko, Valeri G

2017-02-01

Bone marrow (BM) derived adult multipotent mesenchymal stromal cells (MMSCs) and fibroblast colony-forming units (CFU-Fs) of 20 patients with acute myeloid leukemia (AML) and 15 patients with acute lymphoblastic leukemia (ALL) before and during 1 year after receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) were studied. The growth characteristics of MMSCs of all patients before allo-HSCT were not altered; however, relative expression level (REL) of some genes in MMSCs, but not in CFU-Fs, from AML and ALL patients significantly changed. After allo-HSCT, CFU-F concentration and MMSC production were significantly decreased for 1 year; REL of several genes in MMSCs and CFU-F-derived colonies were also significantly downregulated. Thus, chemotherapy that was used for induction of remission did not impair the function of stromal precursors, but gene expression levels were altered. Allo-HSCT conditioning regimens significantly damaged MMSCs and CFU-Fs, and the effect lasted for at least 1 year.

Platelet indices and netrophil to lymphocyte ratio in adults with acute appendicitis.

PubMed

Kostakis, I D; Machairas, N; Damaskos, C; Doula, C; Tsaparas, P; Charalampoudis, P; Spartalis, E; Sotiropoulos, G C; Kouraklis, G

2016-03-01

A study was performed in adults with acute appendicitis and matched controls to assess the utility of the platelet indices and neutrophil to lymphocyte ratio, as a diagnostic adjunct. Data were retrospectively collected from a complete blood count test of 155 adult patients (72 men and 83 women) with histologically proven acute appendicitis upon admission, and of 50 healthy adults (20 men and 30 women). The parameters for white blood cells and platelets were compared between the two groups, and for each gender separately. A higher white blood cell count, neutrophil count, neutrophil percentage, neutrophil to lymphocyte ratio and lower lymphocyte percentage was reported in patients with acute appendicitis than that in the healthy controls, with high areas under the curve (AUC), sensitivities, specifi cities, positive predictive values (PPVs) and moderate negative predictive values (NPVs). The lymphocyte count was lower in patients than it was in the healthy controls. The platletcrit was lower in the female patients than that in the female controls, whereas a difference was not detected in the male participants. Differences were not detected with regard to platelet count, mean platelet volume and platelet distribution width for both genders. The neutrophil to lymphocyte ratio increases and lymphocyte percentage decreases in acute appendicitis, and can be used as an additional diagnostic marker. Plateletcrit, and therefore total platelet mass, is reduced in women with acute appendicitis, indicating the involvement of platelets in its pathophysiology. However, it is neither a reliable predictor or excluder of the disease.

Pure erythroid leukemia following precursor B-cell lymphoblastic leukemia.

PubMed

Xu, Min; Finn, Laura S; Tsuchiya, Karen D; Thomson, Blythe; Pollard, Jessica; Rutledge, Joe

2012-01-01

Therapy-related acute myeloid leukemia is an unfortunate sequel to current multimodal intensive chemotherapy. The patient described was diagnosed with pure erythroleukemia, AML-M6b, during therapy for precursor B-cell acute lymphoblastic leukemia. To the best of our knowledge, this is the first report of this unusual association.

Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)—Health Professional Version

Cancer.gov

Adult acute lymphoblastic leukemia (ALL) treatment options include chemotherapy, radiation therapy, stem cell transplant, and targeted therapy. Get detailed information about the molecular genetics, prognosis, and treatment of ALL in this summary for clinicians.

Acute moderate exercise improves mnemonic discrimination in young adults.

PubMed

Suwabe, Kazuya; Hyodo, Kazuki; Byun, Kyeongho; Ochi, Genta; Yassa, Michael A; Soya, Hideaki

2017-03-01

Increasing evidence suggests that regular moderate exercise increases neurogenesis in the dentate gyrus (DG) of the hippocampus and improves memory functions in both humans and animals. The DG is known to play a role in pattern separation, which is the ability to discriminate among similar experiences, a fundamental component of episodic memory. While long-term voluntary exercise improves pattern separation, there is little evidence of alterations in DG function after an acute exercise session. Our previous studies showing acute moderate exercise-enhanced DG activation in rats, and acute moderate exercise-enhanced prefrontal activation and executive function in humans, led us to postulate that acute moderate exercise may also activate the hippocampus, including more specifically the DG, thus improving pattern separation. We thus investigated the effects of a 10-min moderate exercise (50% V̇O 2peak ) session, the recommended intensity for health promotion, on mnemonic discrimination (a behavioral index of pattern separation) in young adults. An acute bout of moderate exercise improved mnemonic discrimination performance in high similarity lures. These results support our hypothesis that acute moderate exercise improves DG-mediated pattern separation in humans, proposing a useful human acute-exercise model for analyzing the neuronal substrate underlying acute and regular exercise-enhanced episodic memory based on the hippocampus. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Effect of acute moderate exercise on induced inflammation and arterial function in older adults.

PubMed

Ranadive, Sushant Mohan; Kappus, Rebecca Marie; Cook, Marc D; Yan, Huimin; Lane, Abbi Danielle; Woods, Jeffrey A; Wilund, Kenneth R; Iwamoto, Gary; Vanar, Vishwas; Tandon, Rudhir; Fernhall, Bo

2014-04-01

Acute inflammation reduces flow-mediated vasodilatation and increases arterial stiffness in young healthy individuals. However, this response has not been studied in older adults. The aim of this study, therefore, was to evaluate the effect of acute induced systemic inflammation on endothelial function and wave reflection in older adults. Furthermore, an acute bout of moderate-intensity aerobic exercise can be anti-inflammatory. Taken together, we tested the hypothesis that acute moderate-intensity endurance exercise, immediately preceding induced inflammation, would be protective against the negative effects of acute systemic inflammation on vascular function. Fifty-nine healthy volunteers between 55 and 75 years of age were randomized to an exercise or a control group. Both groups received a vaccine (induced inflammation) and sham (saline) injection in a counterbalanced crossover design. Inflammatory markers, endothelial function (flow-mediated vasodilatation) and measures of wave reflection and arterial stiffness were evaluated at baseline and at 24 and 48 h after injections. There were no significant differences in endothelial function and arterial stiffness between the exercise and control group after induced inflammation. The groups were then analysed together, and we found significant differences in the inflammatory markers 24 and 48 h after induction of acute inflammation compared with sham injection. However, flow-mediated vasodilatation, augmentation index normalized for heart rate (AIx75) and β-stiffness did not change significantly. Our results suggest that acute inflammation induced by influenza vaccination did not affect endothelial function in older adults.

Acute lymphoblastic leukemia in adolescents and young adults.

PubMed

Burke, Patrick W; Douer, Dan

2014-01-01

The cure rate of acute lymphoblastic leukemia (ALL) in children is 80%, compared to less than half in adults. A major proportion of this cure rate drop occurs in adolescents and young adults (AYAs). The age range defining this population varies between studies, biological characteristics are different from both younger children and older adults, and AYAs are treated either by pediatric or adult oncologists, who often apply different treatment approaches to the same ALL patient population. The outcome of AYAs aged 15-21 years treated by more contemporary pediatric protocols is similar to that of younger children but is inferior when using adult regimens. This motivated studying AYA patients, including those above the age of 21 years, with pediatric or 'pediatrics-inspired' regimens that intensified nonmyelosuppressive drugs such as vincristine, steroids and asparaginase, with very promising preliminary results. Discovering new mutations in AYA ALL will help stratify patients into risk subgroups and identify targets for novel agents. This, together with fine-tuning pediatric chemotherapy principles will hopefully finally decrease the cure rate gap between children and AYAs - and even older adults. © 2014 S. Karger AG, Basel.

Acute retinal necrosis as a novel complication of chickenpox in adults.

PubMed Central

Matsuo, T; Koyama, M; Matsuo, N

1990-01-01

Three patients in their 20s suffered from chickenpox while in an immunocompromised state: one in pregnancy, one during a long course of corticosteroid for severe nephrotic syndrome, and the third with repeated upper airway infection due to bronchiectasis. They developed acute retinal necrosis about three weeks after the onset of chickenpox. Since acute retinal necrosis threatens sight, this unusual complication of chickenpox in adults needs serious consideration. Images PMID:2378860

JAK2 aberrations in childhood B-cell precursor acute lymphoblastic leukemia

PubMed Central

de Goffau-Nobel, Willemieke; Hoogkamer, Alex Q.; Boer, Judith M.; Boeree, Aurélie; van de Ven, Cesca; Koudijs, Marco J.; Besselink, Nicolle J.M.; de Groot-Kruseman, Hester A.; Zwaan, Christian Michel; Horstmann, Martin A.; Pieters, Rob; den Boer, Monique L.

2017-01-01

JAK2 abnormalities may serve as target for precision medicines in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In the current study we performed a screening for JAK2 mutations and translocations, analyzed the clinical outcome and studied the efficacy of two JAK inhibitors in primary BCP-ALL cells. Importantly, we identify a number of limitations of JAK inhibitor therapy. JAK2 mutations mainly occurred in the poor prognostic subtypes BCR-ABL1-like and non- BCR-ABL1-like B-other (negative for sentinel cytogenetic lesions). JAK2 translocations were restricted to BCR-ABL1-like cases. Momelotinib and ruxolitinib were cytotoxic in both JAK2 translocated and JAK2 mutated cells, although efficacy in JAK2 mutated cells highly depended on cytokine receptor activation by TSLP. However, our data also suggest that the effect of JAK inhibition may be compromised by mutations in alternative survival pathways and microenvironment-induced resistance. Furthermore, inhibitors induced accumulation of phosphorylated JAK2Y1007, which resulted in a profound re-activation of JAK2 signaling upon release of the inhibitors. This preclinical evidence implies that further optimization and evaluation of JAK inhibitor treatment is necessary prior to its clinical integration in pediatric BCP-ALL. PMID:29163799

Flavopiridol in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia

ClinicalTrials.gov

2013-06-03

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; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia

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. © 2014 by The American Society of Hematology.

British Thoracic Society Quality Standards for acute non-invasive ventilation in adults

PubMed Central

Davies, Michael; Allen, Martin; Bentley, Andrew; Bourke, Stephen C; Creagh-Brown, Ben; D’Oliveiro, Rachel; Glossop, Alastair; Gray, Alasdair; Jacobs, Phillip; Mahadeva, Ravi; Moses, Rachael; Setchfield, Ian

2018-01-01

Introduction The purpose of the quality standards document is to provide healthcare professionals, commissioners, service providers and patients with a guide to standards of care that should be met for the provision of acute non-invasive ventilation in adults together with measurable markers of good practice. Methods Development of British Thoracic Society (BTS) Quality Standards follows the BTS process of quality standard production based on the National Institute for Health and Care Excellence process manual for the development of quality standards. Results 6 quality statements have been developed, each describing a standard of care for the provision of acute non-invasive ventilation in the UK, together with measurable markers of good practice. Conclusion BTS Quality Standards for acute non-invasive ventilation in adults form a key part of the range of supporting materials that the Society produces to assist in the dissemination and implementation of guideline’s recommendations. PMID:29636979

Genetically distinct leukemic stem cells in human CD34− acute myeloid leukemia are arrested at a hemopoietic precursor-like stage

PubMed Central

Quek, Lynn; Garnett, Catherine; Karamitros, Dimitris; Stoilova, Bilyana; Doondeea, Jessica; Kennedy, Alison; Metzner, Marlen; Ivey, Adam; Sternberg, Alexander; Hunter, Hannah; Price, Andrew; Virgo, Paul; Grimwade, David; Freeman, Sylvie; Russell, Nigel; Mead, Adam

2016-01-01

Our understanding of the perturbation of normal cellular differentiation hierarchies to create tumor-propagating stem cell populations is incomplete. In human acute myeloid leukemia (AML), current models suggest transformation creates leukemic stem cell (LSC) populations arrested at a progenitor-like stage expressing cell surface CD34. We show that in ∼25% of AML, with a distinct genetic mutation pattern where >98% of cells are CD34−, there are multiple, nonhierarchically arranged CD34+ and CD34− LSC populations. Within CD34− and CD34+ LSC–containing populations, LSC frequencies are similar; there are shared clonal structures and near-identical transcriptional signatures. CD34− LSCs have disordered global transcription profiles, but these profiles are enriched for transcriptional signatures of normal CD34− mature granulocyte–macrophage precursors, downstream of progenitors. But unlike mature precursors, LSCs express multiple normal stem cell transcriptional regulators previously implicated in LSC function. This suggests a new refined model of the relationship between LSCs and normal hemopoiesis in which the nature of genetic/epigenetic changes determines the disordered transcriptional program, resulting in LSC differentiation arrest at stages that are most like either progenitor or precursor stages of hemopoiesis. PMID:27377587

Guidelines for the Antibiotic Use in Adults with Acute Upper Respiratory Tract Infections

PubMed Central

Park, Chan-Soon; Kim, Jae Wook; Hwang, Kyurin; Lee, Sei Young; Kim, Tae Hoon; Park, Do-Yang; Kim, Hyun Jun; Kim, Dong-Young; Lee, Hyun Jong; Shin, Hyun-Young; You, Yong Kyu; Park, Dong-Ah

2017-01-01

These guidelines were developed as part of the 2016 Policy Research Servicing Project by the Korea Centers for Disease Control and Prevention. A multidisciplinary approach was taken to formulate this guideline to provide practical information about the diagnosis and treatment of adults with acute upper respiratory tract infection, with the ultimate aim to promote the appropriate use of antibiotics. The formulation of this guideline was based on a systematic literature review and analysis of the latest research findings to facilitate evidence-based practice, and focused on key questions to help clinicians obtain solutions to clinical questions that may arise during the care of a patient. These guidelines mainly cover the subjects on the assessment of antibiotic indications and appropriate selection of antibiotics for adult patients with acute pharyngotonsillitis or acute sinusitis. PMID:29299900

Unrelated umbilical cord blood transplant for adult acute lymphoblastic leukemia in first and second complete remission: a comparison with allografts from adult unrelated donors

PubMed Central

Marks, David I.; Woo, Kwang Ahn; Zhong, Xiaobo; Appelbaum, Frederick R.; Bachanova, Veronika; Barker, Juliet N.; Brunstein, Claudio G.; Gibson, John; Kebriaei, Partow; Lazarus, Hillard M.; Olsson, Richard; Perales, Miguel-Angel; Pidala, Joseph; Savani, Bipin; Rocha, Vanderson; Eapen, Mary

2014-01-01

Allogeneic hematopoietic cell transplantation has an established role in the treatment of adults with acute lymphoblastic leukemia whose survival when recipients of grafts from adult unrelated donors approaches that of recipients of grafts from sibling donors. Our aim was to determine the role of mismatched unrelated cord blood grafts in transplantation for 802 adults with acute lymphoblastic leukemia in first or second complete remission. Using Cox regression we compared outcomes after 116 mismatched single or double cord blood transplants, 546 peripheral blood progenitor cell transplants and 140 bone marrow transplants. The characteristics of the recipients and their diseases were similar except cord blood recipients were younger, more likely to be non-Caucasians and more likely to have a low white blood cell count at diagnosis. There were differences in donor-recipient human leukocyte antigen-match depending on the source of the graft. Most adult donor transplants were matched at the allele-level considering human leukocyte antigens-A, -B, -C and –DRB1. In contrast, most cord blood transplants were mismatched and considered antigen-level matching; 57% were mismatched at two loci and 29% at one locus whereas only 29% of adult donor transplants were mismatched at one locus and none at two loci. There were no differences in the 3-year probabilities of survival between recipients of cord blood (44%), matched adult donor (44%) and mismatched adult donor (43%) transplants. Cord blood transplants engrafted slower and were associated with less grade 2–4 acute but similar chronic graft-versus-host disease, relapse, and transplant-related mortality. The survival of cord blood graft recipients was similar to that of recipients of matched or mismatched unrelated adult donor grafts and so cord blood should be considered a valid alternative source of stem cells for adults with acute lymphoblastic leukemia in the absence of a matched unrelated adult donor. PMID:24056817

Neuropsychiatric symptoms are common in immunocompetent adult patients with Toxoplasma gondii acute lymphadenitis.

PubMed

Wong, Weng Kit; Upton, Arlo; Thomas, Mark G

2013-05-01

Chronic toxoplasmosis has been shown to be strongly associated with a range of neuropsychiatric effects including schizophrenia and suicide. However there have not been any prospective, community-based studies of the neuropsychiatric effects of acute toxoplasmosis in adult immunocompetent patients. Adult patients with a positive serum IgM anti-Toxoplasma gondii test result, in the context of an acute illness with lymphadenopathy, were invited to complete a questionnaire seeking information relating to the nature, severity, and duration of symptoms in the months following the diagnosis of acute toxoplasmosis. Laboratory testing identified a total of 187 adults who had a positive serum IgM anti-T. gondii test result between 1 January and 30 November 2011. Consent to contact 108/187 (58%) patients was provided by their family doctor; 37 (34%) of these 108 patients completed and returned the questionnaire. Questionnaires from the 31/108 (29%) patients who reported swollen lymph nodes during their illness were included in the study. Fatigue (90%), headache (74%), difficulty concentrating (52%), and muscle aches (52%) were the most commonly reported symptoms. These symptoms commonly persisted for at least 4 weeks. Twenty-seven of 31 (87%) subjects reported a moderate or severe reduction in their overall physical and mental health during the first 2 months of illness. Acute toxoplasmosis in immunocompetent adults commonly causes moderately severe neuropsychiatric symptoms that might result from replication of the organism in the central nervous system with consequent effects on brain function. Patients should be advised that such symptoms are common and reassured that they usually resolve completely within a few months.

[Study on Precursors for Synthesis of Anthraquinone Metabolites from Rheum tanguticum].

PubMed

Hasi, Qi-mei-ge; Lj, Hai-ling; Cheng, Yan; Menggen, Qi-qi-ge; Zhang, Yang

2015-01-01

To explore the potential precursors of the anthraquinone metabolites from Rheum tanguticum and preliminanly identify the synthesis pathway thereof. Sterile seedlings sprouted from the seeds of Rheum tanguticum were chosen as materials for inducing callus. The effects of different precursors and feeding duration on the callus of Rheum tanguticum and the anthraquinone yield in adult rheum were studied. The greatest improvement of anthraquinone yield was achieved by acetic acid, increasing 43. 9% for the callus and 45. 8% in the adult rheum; the second greatest improvement was achieved by malonic acid, increasing 15. 8% for the callus and only 3. 6% in the adult rheum. The yield of anthraquinone was not influenced significantly by benzoic acid and p-benzoquinone, and in contrast, was inhibited in some degree by shikimic acid and α-ketoglutaric acid. A suitable feeding duration was 36 h, which worked well for the effects of precursors. The precursor for synthesis of anthraquinone metabolites from Rheum tan- guticum is acetic acid, which improves the yields of callus and anthraquinone in adult rheum, concluding that the anthraquinone metabolites are synthesized via polyketone pathway.

The experience of acute leukaemia in adult patients: a qualitative thematic synthesis.

PubMed

Papadopoulou, Constantina; Johnston, Bridget; Themessl-Huber, Markus

2013-10-01

The aim of this review was to systematically identify and synthesise all qualitative evidence on how adult patients diagnosed with acute leukaemia experience living with their illness. A systematic search strategy was developed comprising of two search strings: i) acute leukaemia and ii) qualitative methodology. The search strategy was run in seven electronic databases (Medline, CINAHL, PsychINFO, EMBASE, BNI & Archive, SSCI and ASSIA). Nine qualitative studies in adult patients with acute leukaemia, published in peer reviewed journals between 01/1990 and 01/2013 were included in the final sample. The qualitative thematic synthesis resulted in the development of a conceptual model describing a person's path to build a renewed self. Following the initial blow of diagnosis with the range of initial reactions, patients with acute leukaemia are living in a contracting world; they have to deal with the life in hospital, the several losses and the impact of their illness on their emotions and interpersonal relationships. Several factors take up a buffering role at that stage: coping, support, information and hope. Finally, patients accommodate acute leukaemia in their lives through re-evaluating personal values and assigning new meaning to their experience. Results from this thematic synthesis are indicative of the impact of acute leukaemia on patients' lives and the processes they use to make sense and accommodate the illness in their life. Increasing our understanding of these processes is warranted to improve patient care. Copyright © 2013. Published by Elsevier Ltd.

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.

Blinatumomab vs historical standard therapy of adult relapsed/refractory acute lymphoblastic leukemia

PubMed Central

Gökbuget, N; Kelsh, M; Chia, V; Advani, A; Bassan, R; Dombret, H; Doubek, M; Fielding, A K; Giebel, S; Haddad, V; Hoelzer, D; Holland, C; Ifrah, N; Katz, A; Maniar, T; Martinelli, G; Morgades, M; O'Brien, S; Ribera, J-M; Rowe, J M; Stein, A; Topp, M; Wadleigh, M; Kantarjian, H

2016-01-01

We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24% (95% CI: 20–27%) and a median OS of 3.3 months (95% CI: 2.8–3.6) in the historical cohort compared with a CR/CRh rate of 43% (95% CI: 36–50%) and a median OS of 6.1 months (95% CI: 4.2–7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR=2.68, 95% CI: 1.67–4.31) and improved OS (HR=0.536, 95% CI: 0.394–0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data. PMID:27662202

Blinatumomab vs historical standard therapy of adult relapsed/refractory acute lymphoblastic leukemia.

PubMed

Gökbuget, N; Kelsh, M; Chia, V; Advani, A; Bassan, R; Dombret, H; Doubek, M; Fielding, A K; Giebel, S; Haddad, V; Hoelzer, D; Holland, C; Ifrah, N; Katz, A; Maniar, T; Martinelli, G; Morgades, M; O'Brien, S; Ribera, J-M; Rowe, J M; Stein, A; Topp, M; Wadleigh, M; Kantarjian, H

2016-09-23

We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24% (95% CI: 20-27%) and a median OS of 3.3 months (95% CI: 2.8-3.6) in the historical cohort compared with a CR/CRh rate of 43% (95% CI: 36-50%) and a median OS of 6.1 months (95% CI: 4.2-7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR=2.68, 95% CI: 1.67-4.31) and improved OS (HR=0.536, 95% CI: 0.394-0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data.

Removal of the precursors of N-nitrosodiethylamine (NDEA), an emerging disinfection byproduct, in drinking water treatment process and its toxicity to adult zebrafish (Danio rerio).

PubMed

Zheng, Jian; Lin, Tao; Chen, Wei

2018-01-01

N-nitrosodiethylamine (NDEA) is one of the emerging nitrogenous disinfection byproducts with probable cytotoxicity, genotoxicity, and carcinogenesis. Its potential toxicological effects have received extensive attention but remain to be poorly understood. In this study, changes in NDEA precursors in drinking water treatment process were studied using the trial of its formation potential (FP), and the toxicity induced by NDEA to adult zebrafish was investigated. NDEA FP in the raw water of Taihu Lake ranged from 46.9 to 68.3 ng/L. The NDEA precursors were removed effectively by O 3 /BAC process. Hydrophilic fraction and low-molecular-weight fraction (<1 kDa) had the highest NDEA FP. The toxicity results demonstrated that the acute lethal concentration of NDEA causing 50% mortality in 96 h (96-h LC50) was 210.4 mg/L, and NDEA was more likely to be accumulated in kidney, followed by liver and gill. NDEA induced oxidative stress and antioxidant defense to zebrafish metabolism system at concentrations over 5 μg/L. After a 42-day exposure, a significant DNA damage was observed in zebrafish liver cells at NDEA concentrations beyond 500 μg/L. This study investigated NDEA properties in both engineering prospective and toxicity evaluation, thus providing comprehensive information on its control in drinking water treatment process and its toxicity effect on zebrafish as a model animal. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bortezomib with chemotherapy is highly active in advanced B-precursor acute lymphoblastic leukemia: Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Study.

PubMed

Messinger, Yoav H; Gaynon, Paul S; Sposto, Richard; van der Giessen, Jeannette; Eckroth, Elena; Malvar, Jemily; Bostrom, Bruce C

2012-07-12

Therapy of relapsed pediatric acute lymphoblastic leukemia (ALL) is hampered by low remission rates and high toxicity, especially in second and subsequent relapses. Our phase 1 study, T2005-003, showed that the combination of bortezomib with vincristine, dexamethasone, pegylated asparaginase, and doxorubicin had acceptable toxicity. We report the phase 2 expansion of this combination in patients with relapsed ALL who failed 2-3 previous regimens. Twenty-two patients with relapsed ALL were treated with bortezomib combined with this regimen; their ages ranged from 1 to 22 years, and they had either B-precursor ALL (n = 20) or T-cell ALL (n = 2). Grade 3 peripheral neuropathy developed in 2 (9%) patients. After 3 patients died from bacterial infections, treatment with vancomycin, levofloxacin, and voriconazole prophylaxis resulted in no further infectious mortality in the last 6 patients. Fourteen patients achieved complete remission (CR), and 2 achieved CR without platelet recovery, for an overall 73% response rate, meeting predefined criteria allowing for early closure. B-precursor patients faired best, with 16 of 20 (80%) CR + CR without platelet recovery, whereas the 2 patients with T-cell ALL did not respond. Thus, this combination of bortezomib with chemotherapy is active in B-precursor ALL, and prophylactic antibiotics may be useful in reducing mortality. Bortezomib merits further evaluation in combination therapy in pediatric B-precursor ALL. This study is registered at http://www.clinicaltrials.gov as NCT00440726.

Evaluation of adults with acute viral hepatitis a and review of the literature.

PubMed

Tekin, R; Yolbas, I; Dal, T; Demirpençe, Ö; Kaya, S; Bozkurt, F; Deveci, Ö; Çelen, M K; Tekin, A

2013-01-01

In developing countries HAV infection is very common in the first years of life and it is often asymptomatic. However especially in regions of intermediate endemicity, exposure to the virus may delay and outbreaks of hepatitis A may be encountered in adults. The aim of this study is to evaluate the clinical and laboratory findings and risk factors of adults with acute viral hepatitis A. In present study we evaluated 203 patient with acute viral hepatitis A, who were admitted to four different hospitals of three cities of Turkey between January 2000-December 2011, retrospectively. The diagnosis of acute viral hepatitis A was performed by laboratory findings and clinically. In a total of 203 patients, 120 (59.1%) patients were male and 83 (40.9%) were female. Mean age of cases with acute viral hepatitis A was 24.7 +11.8 years (ranged 15 to 82 years old). Acute viral hepatitis A were seen in patient who were 15-20 years and 21-30 years old, commonly. Jaundice (74%), fatigue (68%), nausea- vomiting (56%) and dark urine (48%) were the most common symptoms in cases. Prolonged cholestasis (6.8%) was the most common atypical manifestation. Prolonged jaundice was more frequent in the cases with positive HBsAg (P < 0.001). Acute viral hepatitis A can cause atypical presentations such as prolonged cholestasis, acute kidney injury and fulminant hepatitis. Some precautions such as routine vaccination program, improvement of hygiene conditions and informing people about it, should be taken for reducing of acute viral hepatitis A infection incidence.

Evaluation of Adult Acute Scrotum in the Emergency Room: Clinical Characteristics, Diagnosis, Management, and Costs.

PubMed

Lorenzo, Laura; Rogel, Ramon; Sanchez-Gonzalez, Jose V; Perez-Ardavin, Javier; Moreno, Elena; Lujan, Saturnino; Broseta, Enrique; Boronat, Francisco

2016-08-01

To evaluate the clinic characteristics, diagnosis, management, and costs of the adult acute scrotum in the emergency room (ER). Acute scrotum is a syndrome characterized by intense, acute scrotal pain that may be accompanied by other symptoms. It is usual in children and commonly found as well in adults, with different causal pathologies between these groups. Between November 2013 and September 2014, 669 cases of adult acute scrotum who presented to our ER were prospectively analyzed. Patients under 15 years of age were excluded. Patient age, reason for consultation, investigations performed, final diagnosis, management, and costs were evaluated. For the statistical analysis, the Mann-Whitney, Kruskal-Wallis U, and chi-square tests were used. A total of 669 cases of acute scrotum were analyzed. The mean age at presentation was 40.2 ± 17.3 years. The most presented diagnoses were orchiepididymitis (28.7%), epididymitis (28.4%), symptoms of uncertain etiology (25.1%), and orchitis (10.3%). Diagnostic tests were carried out in 57.8% of cases. Most cases were treated as outpatients (94.2%), with 5.83% admitted and 1% undergoing surgical treatment. Overall, 13.3% of patients represented to the ER. Abnormal results in blood and urine tests were more common among older patients and infectious pathologies. The average cost generated by an acute scrotum ER consult was 195.03€. Infectious pathologies are the most common causes of acute scrotum at ER. Abnormal blood and urine tests are unusual and are more common in older patients and infectious pathologies. Copyright © 2016 Elsevier Inc. All rights reserved.

Perceived Benefits and Barriers to Exercise for Recently Treated Adults With Acute Leukemia.

PubMed

Leak Bryant, Ashley; Walton, AnnMarie L; Pergolotti, Mackenzi; Phillips, Brett; Bailey, Charlotte; Mayer, Deborah K; Battaglini, Claudio

2017-07-01

To explore perceived exercise benefits and barriers in adults with acute leukemia who recently completed an inpatient exercise intervention during induction therapy.
. Descriptive, exploratory design using semistructured interviews.
. Inpatient hematology/oncology unit at North Carolina Cancer Hospital in Chapel Hill.
. 6 adults with acute leukemia aged 35-67 years.
. Content analyses of semistructured interviews that were conducted with each participant prior to hospital discharge.
. Most participants were not meeting the recommended physical activity levels of 150 minutes of moderate-intensity exercise per week before their diagnosis. Patients were highly pleased with the exercise intervention and the overall program. Common barriers to exercise were anxiety and aches and pains.
. Overall, participants experienced physical and psychological benefits with the exercise intervention with no adverse events from exercising regularly during induction chemotherapy. Referrals for cancer rehabilitation management will lead to prolonged recovery benefits.
. Findings inform the nurses' role in encouraging and supporting adults with acute leukemia to exercise and be physically active during their hospitalization. Nurses should also be responsible for assisting patients with physical function activities to increase mobility and enhance overall health-related quality of life.

Deletions of the long arm of chromosome 5 define subgroups of T-cell acute lymphoblastic leukemia

PubMed Central

La Starza, Roberta; Barba, Gianluca; Demeyer, Sofie; Pierini, Valentina; Di Giacomo, Danika; Gianfelici, Valentina; Schwab, Claire; Matteucci, Caterina; Vicente, Carmen; Cools, Jan; Messina, Monica; Crescenzi, Barbara; Chiaretti, Sabina; Foà, Robin; Basso, Giuseppe; Harrison, Christine J.; Mecucci, Cristina

2016-01-01

Recurrent deletions of the long arm of chromosome 5 were detected in 23/200 cases of T-cell acute lymphoblastic leukemia. Genomic studies identified two types of deletions: interstitial and terminal. Interstitial 5q deletions, found in five cases, were present in both adults and children with a female predominance (chi-square, P=0.012). Interestingly, these cases resembled immature/early T-cell precursor acute lymphoblastic leukemia showing significant down-regulation of five out of the ten top differentially expressed genes in this leukemia group, including TCF7 which maps within the 5q31 common deleted region. Mutations of genes known to be associated with immature/early T-cell precursor acute lymphoblastic leukemia, i.e. WT1, ETV6, JAK1, JAK3, and RUNX1, were present, while CDKN2A/B deletions/mutations were never detected. All patients had relapsed/resistant disease and blasts showed an early differentiation arrest with expression of myeloid markers. Terminal 5q deletions, found in 18 of patients, were more prevalent in adults (chi-square, P=0.010) and defined a subgroup of HOXA-positive T-cell acute lymphoblastic leukemia characterized by 130 up- and 197 down-regulated genes. Down-regulated genes included TRIM41, ZFP62, MAPK9, MGAT1, and CNOT6, all mapping within the 1.4 Mb common deleted region at 5q35.3. Of interest, besides CNOT6 down-regulation, these cases also showed low BTG1 expression and a high incidence of CNOT3 mutations, suggesting that the CCR4-NOT complex plays a crucial role in the pathogenesis of HOXA-positive T-cell acute lymphoblastic leukemia with terminal 5q deletions. In conclusion, interstitial and terminal 5q deletions are recurrent genomic losses identifying distinct subtypes of T-cell acute lymphoblastic leukemia. PMID:27151989

Deletions of the long arm of chromosome 5 define subgroups of T-cell acute lymphoblastic leukemia.

PubMed

La Starza, Roberta; Barba, Gianluca; Demeyer, Sofie; Pierini, Valentina; Di Giacomo, Danika; Gianfelici, Valentina; Schwab, Claire; Matteucci, Caterina; Vicente, Carmen; Cools, Jan; Messina, Monica; Crescenzi, Barbara; Chiaretti, Sabina; Foà, Robin; Basso, Giuseppe; Harrison, Christine J; Mecucci, Cristina

2016-08-01

Recurrent deletions of the long arm of chromosome 5 were detected in 23/200 cases of T-cell acute lymphoblastic leukemia. Genomic studies identified two types of deletions: interstitial and terminal. Interstitial 5q deletions, found in five cases, were present in both adults and children with a female predominance (chi-square, P=0.012). Interestingly, these cases resembled immature/early T-cell precursor acute lymphoblastic leukemia showing significant down-regulation of five out of the ten top differentially expressed genes in this leukemia group, including TCF7 which maps within the 5q31 common deleted region. Mutations of genes known to be associated with immature/early T-cell precursor acute lymphoblastic leukemia, i.e. WT1, ETV6, JAK1, JAK3, and RUNX1, were present, while CDKN2A/B deletions/mutations were never detected. All patients had relapsed/resistant disease and blasts showed an early differentiation arrest with expression of myeloid markers. Terminal 5q deletions, found in 18 of patients, were more prevalent in adults (chi-square, P=0.010) and defined a subgroup of HOXA-positive T-cell acute lymphoblastic leukemia characterized by 130 up- and 197 down-regulated genes. Down-regulated genes included TRIM41, ZFP62, MAPK9, MGAT1, and CNOT6, all mapping within the 1.4 Mb common deleted region at 5q35.3. Of interest, besides CNOT6 down-regulation, these cases also showed low BTG1 expression and a high incidence of CNOT3 mutations, suggesting that the CCR4-NOT complex plays a crucial role in the pathogenesis of HOXA-positive T-cell acute lymphoblastic leukemia with terminal 5q deletions. In conclusion, interstitial and terminal 5q deletions are recurrent genomic losses identifying distinct subtypes of T-cell acute lymphoblastic leukemia. Copyright© Ferrata Storti Foundation.

Acute Cholecystitis Caused by Ceftriaxone Stones in an Adult

PubMed Central

Becker, Christian D.; Fischer, Robert A.

2009-01-01

Acute cholecystitis is a major health problem. There are multiple etiologies to be considered and early recognition of the condition is important to optimize management and outcome. We report the first case in the medical literature of symptomatic acute cholecystitis triggered by ceftriaxone-associated gallbladder sludge formation and, importantly, solid ceftriaxone gallstone formation in an adult patient with underlying mineral and pigment cholecystolithiasis, necessitating cholecystectomy. This case serves as a reminder for physicians to keep this uncommon cause of cholecystolithiasis and cholecystitis in mind in patients who receive prolonged ceftriaxone therapy. These patients should be cautioned to promptly report to their physicians any signs or symptoms of cholecystitis in order to ensure timely and appropriate evaluation. PMID:19707473

Antibiotics for acute maxillary sinusitis in adults.

PubMed

Ahovuo-Saloranta, Anneli; Rautakorpi, Ulla-Maija; Borisenko, Oleg V; Liira, Helena; Williams, John W; Mäkelä, Marjukka

2014-02-11

Sinusitis is one of the most common diagnoses among adults in ambulatory care, accounting for 15% to 21% of all adult outpatient antibiotic prescriptions. However, the role of antibiotics for sinusitis is controversial. To assess the effects of antibiotics in adults with acute maxillary sinusitis by comparing antibiotics with placebo, antibiotics from different classes and the side effects of different treatments. We searched CENTRAL 2013, Issue 2, MEDLINE (1946 to March week 3, 2013), EMBASE (1974 to March 2013), SIGLE (OpenSIGLE, later OpenGrey (accessed 15 January 2013)), reference lists of the identified trials and systematic reviews of placebo-controlled studies. We also searched for ongoing trials via ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP). We imposed no language or publication restrictions. Randomised controlled trials (RCTs) comparing antibiotics with placebo or antibiotics from different classes for acute maxillary sinusitis in adults. We included trials with clinically diagnosed acute sinusitis, confirmed or not by imaging or bacterial culture. Two review authors independently screened search results, extracted data and assessed trial quality. We calculated risk ratios (RRs) for differences between intervention and control groups in whether the treatment failed or not. All measures are presented with 95% confidence intervals (CIs). We conducted the meta-analyses using either the fixed-effect or random-effects model. In meta-analyses of the placebo-controlled studies, we combined data across antibiotic classes. Primary outcomes were clinical failure rates at 7 to 15 days and 16 to 60 days follow-up. We used GRADEpro to assess the quality of the evidence. We included 63 studies in this updated review; nine placebo-controlled studies involving 1915 participants (seven of the studies clearly conducted in primary care settings) and 54 studies comparing different classes of antibiotics (10 different comparisons

Poor Self-Reported Sleep Quality Predicts Mortality within One Year of Inpatient Post-Acute Rehabilitation among Older Adults

PubMed Central

Martin, Jennifer L.; Fiorentino, Lavinia; Jouldjian, Stella; Mitchell, Michael; Josephson, Karen R.; Alessi, Cathy A.

2011-01-01

Study Objective: To evaluate the association between self-reported sleep quality among older adults during inpatient post-acute rehabilitation and one-year survival. Design: Prospective, observational cohort study. Setting: Two inpatient post-acute rehabilitation sites (one community and one Veterans Administration). Participants: Older patients (aged ≥ 65 years, n = 245) admitted for inpatient post-acute rehabilitation. Interventions: None. Measurements and Results: Within one year of post-acute rehabilitation, 57 participants (23%) were deceased. Cox proportional hazards models showed that worse Pittsburgh Sleep Quality Index (PSQI) total scores during the post-acute care stay were associated with increased mortality risk when controlling for amount of rehabilitation therapy received, comorbidities, and cognitive functioning (Hazard ratio [95% CI] = 1.11 [1.02-1.20]). Actigraphically estimated sleep was unrelated to mortality risk. Conclusions: Poorer self-reported sleep quality, but not objectively estimated sleep parameters, during post-acute rehabilitation was associated with shorter survival among older adults. This suggests self-reported poor sleep may be an important and potentially modifiable risk factor for negative outcomes in these vulnerable older adults. Studies of interventions to improve sleep quality during inpatient rehabilitation should therefore be undertaken, and the long-term health benefits of improved sleep should be explored. Citation: Martin JL; Fiorentino L; Jouldjian S; Mitchell M; Josephson KR; Alessi CA. Poor self-reported sleep quality predicts mortality within one year of inpatient post-acute rehabilitation among older adults. SLEEP 2011;34(12):1715-1721. PMID:22131610

Mutations in TP53 and JAK2 are independent prognostic biomarkers in B-cell precursor acute lymphoblastic leukaemia.

PubMed

Forero-Castro, Maribel; Robledo, Cristina; Benito, Rocío; Bodega-Mayor, Irene; Rapado, Inmaculada; Hernández-Sánchez, María; Abáigar, María; Maria Hernández-Sánchez, Jesús; Quijada-Álamo, Miguel; María Sánchez-Pina, José; Sala-Valdés, Mónica; Araujo-Silva, Fernanda; Kohlmann, Alexander; Luis Fuster, José; Arefi, Maryam; de Las Heras, Natalia; Riesco, Susana; Rodríguez, Juan N; Hermosín, Lourdes; Ribera, Jordi; Camos Guijosa, Mireia; Ramírez, Manuel; de Heredia Rubio, Cristina Díaz; Barragán, Eva; Martínez, Joaquín; Ribera, José M; Fernández-Ruiz, Elena; Hernández-Rivas, Jesús-María

2017-07-11

In B-cell precursor acute lymphoblastic leukaemia (B-ALL), the identification of additional genetic alterations associated with poor prognosis is still of importance. We determined the frequency and prognostic impact of somatic mutations in children and adult cases with B-ALL treated with Spanish PETHEMA and SEHOP protocols. Mutational status of hotspot regions of TP53, JAK2, PAX5, LEF1, CRLF2 and IL7R genes was determined by next-generation deep sequencing in 340 B-ALL patients (211 children and 129 adults). The associations between mutation status and clinicopathological features at the time of diagnosis, treatment outcome and survival were assessed. Univariate and multivariate survival analyses were performed to identify independent prognostic factors associated with overall survival (OS), event-free survival (EFS) and relapse rate (RR). A mutation rate of 12.4% was identified. The frequency of adult mutations was higher (20.2% vs 7.6%, P=0.001). TP53 was the most frequently mutated gene (4.1%), followed by JAK2 (3.8%), CRLF2 (2.9%), PAX5 (2.4%), LEF1 (0.6%) and IL7R (0.3%). All mutations were observed in B-ALL without ETV6-RUNX1 (P=0.047) or BCR-ABL1 fusions (P<0.0001). In children, TP53mut was associated with lower OS (5-year OS: 50% vs 86%, P=0.002) and EFS rates (5-year EFS: 50% vs 78.3%, P=0.009) and higher RR (5-year RR: 33.3% vs 18.6% P=0.037), and was independently associated with higher RR (hazard ratio (HR)=4.5; P=0.04). In adults, TP53mut was associated with a lower OS (5-year OS: 0% vs 43.3%, P=0.019) and a higher RR (5-year RR: 100% vs 61.4%, P=0.029), whereas JAK2mut was associated with a lower EFS (5-year EFS: 0% vs 30.6%, P=0.035) and a higher RR (5-year RR: 100% vs 60.4%, P=0.002). TP53mut was an independent risk factor for shorter OS (HR=2.3; P=0.035) and, together with JAK2mut, also were independent markers of poor prognosis for RR (TP53mut: HR=5.9; P=0.027 and JAK2mut: HR=5.6; P=0.036). TP53mut and JAK2mut are potential biomarkers associated

Acute Effects of Walking Exercise on Stair Negotiation in Sedentary and Physically Active Older Adults.

PubMed

Kunzler, Marcos R; da Rocha, Emmanuel S; Bobbert, Maarten F; Duysens, Jacques; Carpes, Felipe P

2017-07-01

In negotiating stairs, low foot clearance increases the risk of tripping and a fall. Foot clearance may be related to physical fitness, which differs between active and sedentary participants, and be acutely affected by exercise. Impaired stair negotiation could be an acute response to exercise. Here we determined acute changes in foot clearances during stair walking in sedentary (n = 15) and physically active older adults (n = 15) after prolonged exercise. Kinematic data were acquired during negotiation with a 3-steps staircase while participants walked at preferred speed, before and after 30 min walking at preferred speed and using a treadmill. Foot clearances were compared before and after exercise and between the groups. Sedentary older adults presented larger (0.5 cm for lead and 2 cm for trail leg) toe clearances in ascent, smaller (0.7 cm) heel clearance in the leading foot in descent, and larger (1 cm) heel clearance in the trailing foot in descent than physically active. Sedentary older adults negotiate stairs in a slightly different way than active older adults, and 30 min walking at preferred speed does not affect clearance in stair negotiation.

Post-traumatic stress disorder symptoms in family caregivers of adult patients with acute leukemia from a dyadic perspective.

PubMed

Jia, Mutian; Li, Jie; Chen, Chunyan; Cao, Fenglin

2015-12-01

Acute leukemia is a fatal disease in adults that not only affects the patients who suffer from it but also their family caregivers. No studies have investigated post-traumatic stress disorder symptoms (PTSS) in family caregivers of adult patients with acute leukemia using a matched sample. The current study examined PTSS in adult patients with acute leukemia and their family caregivers and investigated the factors associated with caregivers' PTSS. A total of 163 patient-caregiver dyads completed questionnaires assessing their PTSS, psychological resilience, and perceived social support. Hierarchical linear regression was used to explore the related factors of caregivers' PTSS. More caregivers than patients met caseness criteria for PTSS (36.8% vs. 18.4%, p < 0.001). Among caregivers, being more closely related to the patients (e.g., spouses and parents), having patients with higher PTSS and having lower psychological resilience were independently associated with more severe PTSS. Caregivers of acute leukemia patients had significantly more severe PTSS than did their patients. This study is the first to investigate PTSS among family caregivers of adult patients with acute leukemia and its related factors in a matched sample. More attention should be paid to the caregivers of patients with acute leukemia to minimize their PTSS and thus improve mental health of caregivers and reduce potential negative consequences for the patients themselves. Copyright © 2015 John Wiley & Sons, Ltd.

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.

SYK as a New Therapeutic Target in B-Cell Precursor Acute Lymphoblastic Leukemia

PubMed Central

Uckun, Fatih M.; Qazi, Sanjive

2014-01-01

The identification of SYK as a master regulator of apoptosis controlling the activation of the PI3-K/AKT, NFκB, and STAT3 pathways—three major anti-apoptotic signaling pathways in B-lineage leukemia/lymphoma cells—prompts the hypothesis that rationally designed inhibitors targeting SYK may overcome the resistance of malignant B-lineage lymphoid cells to apoptosis and thereby provide the foundation for more effective multi-modality treatment regimens for poor prognosis B-precursor acute lymphoblastic leukemia (BPL). In recent preclinical proof-of-concept studies, a liposomal nanoparticle (LNP) formulation of a SYK substrate-binding site inhibitor, known as C61, has been developed as a nanomedicine candidate against poor prognosis and relapsed BPL. This nanoscale formulation of C61 exhibited a uniquely favorable pharmacokinetics and safety profile in mice, induced apoptosis in radiation-resistant primary leukemic cells taken directly from BPL patients as well as in vivo clonogenic BPL xenograft cells, destroyed the leukemic stem cell fraction of BPL blasts, and exhibited potent in vivo anti-leukemic activity in xenograft models of aggressive BPL. Further development of C61-LNP may provide the foundation for new and effective treatment strategies against therapy-refractory BPL. PMID:24851191

Child maltreatment, attention networks, and potential precursors to borderline personality disorder

PubMed Central

ROGOSCH, FRED A.; CICCHETTI, DANTE

2006-01-01

Potential precursors to borderline personality disorder (BPD) were investigated in a sample of 185 maltreated and 175 nonmaltreated school-aged children attending a summer camp research program. Self-report, peer-report, and counselor-report measures were utilized to assess developmental constructs conceptualized to constitute vulnerability for later emerging BPD. These areas, including personality features, representational models of self, parent, and peers, interpersonal relationship difficulties with peers and adults, and suicidal/self-harm behavior, were used to develop a BPD precursors composite. Additionally, the efficiency of three attention networks was assessed with a computerized task. Maltreated children had higher mean scores on the BPD precursors composite, and children classified as having high levels of these precursors were more prevalent in the maltreatment group. No maltreatment group differences were found for the efficiency of the three attention networks; however, children with high levels of BPD precursors evinced less efficient processing of the conflict attention network, comparable to findings observed among adult patients with BPD. Child maltreatment and efficiency of the conflict attention network independently predicted scores on the BPD precursors composite. Experiential and biological contributions to risk for BPD and recommendations for prevention and intervention are discussed. PMID:16613431

Pericardial Tamponade in an Adult Suffering from Acute Mumps Infection

PubMed Central

Flieger, Robert Rainer; Mankertz, Annette; Yilmaz, Kadir; Roepke, Torsten Kai

2016-01-01

Here, we report a case of a 51-year-old man with acute pericardial tamponade requiring emergency pericardiocentesis after he suffered from sore throat, headache, malaise, and sweats for two weeks. Serological analyses revealed increased mumps IgM and IgG indicating an acute mumps infection whereas other bacterial and viral infections were excluded. In addition, MRI revealed atypical swelling of the left submandibular gland. Whereas mumps has become a rare entity in children due to comprehensive vaccination regimens in western civilizations, our case highlights mumps as an important differential diagnosis also in adults, where the virus can induce life-threatening complications such as pericardial tamponade. PMID:27818687

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

Acute Sarcopenia Secondary to Hospitalisation - An Emerging Condition Affecting Older Adults

PubMed Central

Welch, Carly; K. Hassan-Smith, Zaki; A. Greig, Carolyn; M. Lord, Janet; A. Jackson, Thomas

2018-01-01

There has been increasing interest and research into sarcopenia in community-dwelling older adults since the European Working Group on Sarcopenia in Older People (EWGSOP) agreed a consensus definition in 2010. Sarcopenia has been defined as loss of muscle mass with loss of muscle function (strength or physical performance), with measurements two Standard Deviations (SDs) below the mean of a young reference population. This definition does not necessitate longitudinal measurements, or the absence of acute illness and diagnosis can be made from single measurements. We hypothesise that hospitalisation, due to a combination of acute inflammatory burden and muscle disuse, leads to an acute decline in muscle mass and function and may lead to some individuals meeting criteria for sarcopenia, acutely, based on the EWGSOP definition. This may be partially recoverable or may lead to increased risk of developing sarcopenia long-term. We have denoted the term “acute sarcopenia” to refer to acute loss of muscle mass and function associated with hospitalisation. This review discusses some of the current available research in this context and also identifies some of the knowledge gaps and potential areas for future research. PMID:29392090

Patient-accident-fracture (PAF) classification of acute distal radius fractures in adults.

PubMed

Herzberg, G; Galissard, T; Burnier, M

2018-05-19

There is not enough evidence in the literature to support the use of any classification system for distal radius fractures (DRF) in adults. However, there is a need for identification of more homogeneous groups of patients with DRF so that the extent of preoperative workup and sophistication of treatment would best match the needs of the patient. The authors propose an innovative method to analyse and stratify acute DRF in adults. A one-page chart includes criteria related to the patient (P), the energy of the accident (A) and the pathology of the fracture (F). Analysis of the pathology includes not only the distal radius itself but also the associated ulnar and carpal lesions. Radiological suspicion of associated carpal of distal radio-ulnar joint ligamentous injuries is included in the analysis. The preliminary results of the use of this chart in 1610 consecutive adult patients (16-102 years) with unilateral acute DRF are presented. A total of six homogeneous groups of patients are described, and the relevance of this classification regarding the therapeutic options is discussed.

Acute pain in children and adults with sickle cell disease: management in the absence of evidence-based guidelines.

PubMed

Field, Joshua J; Knight-Perry, Jessica E; Debaun, Michael R

2009-05-01

Acute, vaso-occlusive pain is the most characteristic complication of sickle cell disease (SCD). Although there has been rigorous work examining the pathogenesis of vaso-occlusion, fewer studies have focused on approaches to the clinical management of acute pain. In this review, we will examine the epidemiology and management strategies of acute pain events and we will identify limitations in the best available studies. Most acute pain events in adults with SCD are managed at home without physician contact. Prior descriptions of the natural history of pain episodes from the Cooperative Study of Sickle Cell Disease relied on physician contact, limiting the generalizability of these findings to current practice. Patient-controlled analgesia has replaced on-demand therapy to become the standard for management of severe pain events in children and adults with SCD requiring hospital admission. Unfortunately, most clinical practice guidelines for the management of acute pain are not based on randomized clinical trials. As a result, our practice of pain management is primarily limited to expert opinion and inferences from observational studies. Additional clinical trials in management of acute pain in children and adults with SCD are critical for the development of evidence-based guidelines.

Pediatric precursor B acute lymphoblastic leukemia: are T helper cells the missing link in the infectious etiology theory?

PubMed

Bürgler, Simone; Nadal, David

2017-12-01

Precursor B acute lymphoblastic leukemia (BCP-ALL), the most common childhood malignancy, arises from an expansion of malignant B cell precursors in the bone marrow. Epidemiological studies suggest that infections or immune responses to infections may promote such an expansion and thus BCP-ALL development. Nevertheless, a specific pathogen responsible for this process has not been identified. BCP-ALL cells critically depend on interactions with the bone marrow microenvironment. The bone marrow is also home to memory T helper (Th) cells that have previously expanded during an immune response in the periphery. In secondary lymphoid organs, Th cells can interact with malignant cells of mature B cell origin, while such interactions between Th cells and malignant immature B cell in the bone marrow have not been described yet. Nevertheless, literature supports a model where Th cells-expanded during an infection in early childhood-migrate to the bone marrow and support BCP-ALL cells as they support normal B cells. Further research is required to mechanistically confirm this model and to elucidate the interaction pathways between leukemia cells and cells of the tumor microenvironment. As benefit, targeting these interactions could be included in current treatment regimens to increase therapeutic efficiency and to reduce relapses.

Antibiotic use among older adults on an acute care general surgery service

PubMed Central

Pollmann, André S.; Bailey, Jon G.; Davis, Philip J.B.; Johnson, Paul M.

2017-01-01

Background Antibiotics play an important role in the treatment of many surgical diseases that affect older adults, and the potential for inappropriate use of these drugs is high. Our objective was to describe antibiotic use among older adults admitted to an acute care surgery service at a tertiary care teaching hospital. Methods Detailed data regarding diagnosis, comorbidities, surgery and antibiotic use were retrospectively collected for patients 70 years and older admitted to an acute care surgery service. We evaluated antibiotic use (perioperative prophylaxis and treatment) for appropriateness based on published guidelines. Results During the study period 453 patients were admitted to the acute care surgery service, and 229 underwent surgery. The most common diagnoses were small bowel obstruction (27.2%) and acute cholecystitis (11.0%). In total 251 nonelective abdominal operations were performed, and perioperative antibiotic prophylaxis was appropriate in 49.5% of cases. The most common prophylaxis errors were incorrect timing (15.5%) and incorrect dose (12.4%). Overall 206 patients received treatment with antibiotics for their underlying disease process, and 44.2% received appropriate first-line drug therapy. The most common therapeutic errors were administration of second- or third-line antibiotics without indication (37.9%) and use of antibiotics when not indicated (12.1%). There was considerable variation in the duration of treatment for patients with the same diagnoses. Conclusion Inappropriate antibiotic use was common among older patients admitted to an acute care surgery service. Quality improvement initiatives are needed to ensure patients receive optimal care in this complex hospital environment. PMID:28930045

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

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

2017-06-16

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

Preliminary evidence of attenuated blood pressure reactivity to acute stress in adults following a recent marital separation.

PubMed

Grinberg, Austin M; O'Hara, Karey L; Sbarra, David A

2018-03-01

This study explores cardiovascular reactivity during an acute-stress task in a sample of recently separated adults. In a cross-sectional design, we examined the association between adults' subjective separation-related distress and changes in heart rate and blood pressure across the acute-stress laboratory paradigm in a sample of 133 (n = 49 men) recently separated adults. Heart rate (HR) and Blood pressure (BP) were recorded across a resting baseline period, a math stressor task, and a recovery period. Multilevel analyses revealed that adults who reported greater separation-related distress exhibited higher initial BP and a slower linear increase in BP across the study period. In addition, adults reporting greater separation-related distress evidenced significantly slower declines in diastolic blood pressure (DBP) following the acute-stress task. HR reactivity was not moderated by separation-related distress. In recently separated adults, preliminary evidence suggests that the context of the stressors may reveal differential patterns of problematic reactivity (exaggerated or blunted responding). Greater emotional intrusion and hyperactivity symptoms may index increased risk for blunted cardiovascular reactivity to general stressors. This pattern of reactivity is consistent with models of allostatic load that emphasise the deleterious effect of hyporesponsivity to environmental demands.

Chemo-sensitivity in a panel of B-cell precursor acute lymphoblastic leukemia cell lines, YCUB series, derived from children.

PubMed

Goto, Hiroaki; Naruto, Takuya; Tanoshima, Reo; Kato, Hiromi; Yokosuka, Tomoko; Yanagimachi, Masakatsu; Fujii, Hisaki; Yokota, Shumpei; Komine, Hiromi

2009-10-01

Sensitivity to 10 anticancer drugs was evaluated in 6 childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cell lines. Authenticity of newly established cell lines was confirmed by genomic fingerprinting. The line YCUB-5R established at relapse was more resistant to 4-hydroperoxy-cyclophosphamide, cytarabine, L-asparaginase, topotecan, fludarabine, and etoposide than YCUB-5 from the same patient at diagnosis. Of the drugs tested, etoposide and SN-38 (irinotecan) showed highest efficacy in the panel, with 50% growth inhibition at 0.22-1.8 microg/ml and 0.57-3.6 ng/ml, respectively. This cell line panel offers an in vitro model for the development of new therapies for childhood BCP-ALL.

Targeted Therapy in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Acute Myelogenous Leukemia

ClinicalTrials.gov

2018-04-13

Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia

Localization of the putative precursor of Alzheimer's disease-specific amyloid at nuclear envelopes of adult human muscle.

PubMed Central

Zimmermann, K; Herget, T; Salbaum, J M; Schubert, W; Hilbich, C; Cramer, M; Masters, C L; Multhaup, G; Kang, J; Lemaire, H G

1988-01-01

Cloning and sequence analysis revealed the putative amyloid A4 precursor (pre-A4) of Alzheimer's disease to have characteristics of a membrane-spanning glycoprotein. In addition to brain, pre-A4 mRNA was found in adult human muscle and other tissues. We demonstrate by in situ hybridization that pre-A4 mRNA is present in adult human muscle, in cultured human myoblasts and myotubes. Immunofluorescence with antipeptide antibodies shows the putative pre-A4 protein to be expressed in adult human muscle and associated with some but not all nuclear envelopes. Despite high levels of a single 3.5-kb pre-A4 mRNA species in cultured myoblasts and myotubes, the presence of putative pre-A4 protein could not be detected by immunofluorescence. This suggests that putative pre-A4 protein is stabilized and therefore functioning in the innervated muscle tissue but not in developing, i.e. non-innervated cultured muscle cells. The selective localization of the protein on distinct nuclear envelopes could reflect an interaction with motor endplates. Images PMID:2896589

Acute parvovirus B19 infection in adults: a retrospective study of 49 cases.

PubMed

Rodríguez Bandera, A I; Mayor Arenal, M; Vorlicka, K; Ruiz Bravo-Burguilllos, E; Montero Vega, D; Vidaurrázaga Díaz-Arcaya, C

2015-01-01

Our aim was to describe the epidemiologic, clinical, and laboratory characteristics of acute parvovirus B19 infection in adults. This study describes all cases of acute parvovirus B19 infection in patients older than 18 years of age who were treated at Hospital Universitario La Paz in Madrid, Spain, in 2012. Forty-nine adults were treated for acute parvovirus B19 infection. Most were young women who were infected in the spring or early summer. In over half the cases skin lesions were key diagnostic signs.We saw the full range of types of rash of purplish exanthems that were fairly generalized; vasculitis was relatively common (in >18%). Mild or moderate abnormalities in blood counts and indicators of liver dysfunction resolved spontaneously in all but 2 immunocompromised patients, who developed chronic anemia. This is the largest case series of acute parvovirus B19 infection published to date. This infection should be suspected on observing signs of purplish skin rashes, no matter the location or pattern of distribution, or vasculitis, especially if accompanied by fever and joint pain in young women in the spring. Measures to avoid infection should be recommended to individuals at risk. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

Extracorporeal Life Support for Severe Acute Respiratory Distress Syndrome in Adults

PubMed Central

Hemmila, Mark R.; Rowe, Stephen A.; Boules, Tamer N.; Miskulin, Judiann; McGillicuddy, John W.; Schuerer, Douglas J.; Haft, Jonathan W.; Swaniker, Fresca; Arbabi, Saman; Hirschl, Ronald B.; Bartlett, Robert H.

2004-01-01

Objective: Severe acute respiratory distress syndrome (ARDS) is associated with a high level of mortality. Extracorporeal life support (ECLS) during severe ARDS maintains oxygen and carbon dioxide gas exchange while providing an optimal environment for recovery of pulmonary function. Since 1989, we have used a protocol-driven algorithm for treatment of severe ARDS, which includes the use of ECLS when standard therapy fails. The objective of this study was to evaluate our experience with ECLS in adult patients with severe ARDS with respect to mortality and morbidity. Methods: We reviewed our complete experience with ELCS in adults from January 1, 1989, through December 31, 2003. Severe ARDS was defined as acute onset pulmonary failure, with bilateral infiltrates on chest x-ray, and PaO2/fraction of inspired oxygen (FiO2) ratio ≤100 or A-aDO2 >600 mm Hg despite maximal ventilator settings. The indication for ECLS was acute severe ARDS unresponsive to optimal conventional treatment. The technique of ECLS included veno-venous or veno-arterial vascular access, lung “rest” at low FiO2 and inspiratory pressure, minimal anticoagulation, and optimization of systemic oxygen delivery. Results: During the study period, ECLS was used for 405 adult patients age 17 or older. Of these 405 patients, 255 were placed on ECLS for severe ARDS refractory to all other treatment. Sixty-seven percent were weaned off ECLS, and 52% survived to hospital discharge. Multivariate logistic regression analysis identified the following pre-ELCS variables as significant independent predictors of survival: (1) age (P = 0.01); (2) gender (P = 0.048); (3) pH ≤7.10 (P = 0.01); (4) PaO2/FiO2 ratio (P = 0.03); and (5) days of mechanical ventilation (P < 0.001). None of the patients who survived required permanent mechanical ventilation or supplemental oxygen therapy. Conclusion: Extracorporeal life support for severe ARDS in adults is a successful therapeutic option in those patients who do not

Alternative donor transplantation for adults with acute leukemia.

PubMed

Appelbaum, Frederick R

2014-01-01

Allogeneic hematopoietic cell transplantation (HCT) from a matched related donor (MRD) is the preferred therapy for many adults with acute leukemia. Yet most patients do not have matched siblings, and the numbers who do will continue to drop as the average number of children per couple in the United States continues to decline. Recent reports show little difference in the outcomes of matched related and matched unrelated transplants for acute leukemia. Additionally, survival rates at 3-5 years after transplant appear to be generally similar following matched related, matched unrelated, single antigen mismatched unrelated, double cord blood and, perhaps even after haplo-identical transplants. Nevertheless, there are differences between stem cell sources that should be considered in the choice of donor. The following review provides some perspective on the identification of the best stem cell sources for patients who do not have matches within their families. Copyright © 2014 Elsevier Ltd. All rights reserved.

Differences in disease features between childhood-onset and adult-onset systemic lupus erythematosus patients presenting with acute abdominal pain.

PubMed

Tu, Yu-Ling; Yeh, Kuo-Wei; Chen, Li-Chen; Yao, Tsung-Chieh; Ou, Liang-Shiou; Lee, Wen-I; Huang, Jing-Long

2011-04-01

Abdominal pain in systemic lupus erythematosus (SLE) patients has rarely been analyzed in pediatric populations. We planned to investigate the potential differences between childhood-onset and adult-onset SLE patients who were hospitalized because of acute abdominal pain. A retrospective study including 23 childhood-onset SLE patients with 38 admissions and 88 adult-onset SLE patients with 108 admissions from 1999 to 2008 were conducted in our hospital. All of them had the chief complaint of diffuse abdominal pain. The etiologies of acute abdominal pain in adult-onset SLE patients were more diverse than childhood-onset SLE patients. The most common cause of acute abdominal pain in SLE patients was lupus mesenteric vasculitis (LMV) (18.5%), followed by acute gastroenteritis (14.4%), pancreatitis (10.3%), appendicitis (7.5%), and cholecystitis (6.2%). Compared with adults, children were admitted more often due to LMV (31.6% versus 13.9%; P = 0.016), had more frequently recurrent episodes (39.1% versus 14.8%; P = 0.009), and were more often treated with immunosuppressive agents (31.6% versus 7.4%; P < 0.001) at the time of admission. The overall case fatality rate of acute abdomen in SLE patients was 9.4%. The extra-gastrointestinal symptoms, laboratory evaluation, disease activity, and organ damage measured by the SLE Disease Activity Index and outcomes were comparable between children and adults. Various etiologies of acute abdominal pain should be considered in SLE patients. LMV is the most common cause of acute abdomen in childhood-onset SLE patients with low mortality and morbidity provided by prompt diagnosis and timely administration of high-dose intravenous corticosteroids after excluding real surgical abdomen. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Veliparib and Temozolomide in Treating Patients With Acute Leukemia

ClinicalTrials.gov

2018-04-20

Accelerated Phase of Disease; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; Adult Acute Promyelocytic Leukemia With PML-RARA; Adult B Acute Lymphoblastic Leukemia; Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; Adult T Acute Lymphoblastic Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Blastic Phase; Chronic Myelomonocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

Acute effect of mineralocorticoid receptor antagonism on vascular function in healthy older adults.

PubMed

Hwang, Moon-Hyon; Yoo, Jeung-Ki; Luttrell, Meredith; Kim, Han-Kyul; Meade, Thomas H; English, Mark; Talcott, Susanne; Jaffe, Iris Z; Christou, Demetra D

2016-01-01

Mineralocorticoid receptor (MR) activation by aldosterone may regulate vascular function in health or contribute to vascular dysfunction in cardiovascular disease. Whether the effects are beneficial or detrimental to vascular function appear to be dependent on the integrity of the vascular endothelium and whether the responses are short-term or chronic. Acute modulation of MR activation has resulted in conflicting outcomes on vascular function in young healthy adults. Little is known about the vascular role of aldosterone and MR activation in healthy human aging. The primary objective of this study was to examine whether acute inhibition of MR by the selective antagonist eplerenone, influences vascular function in healthy older adults. We performed a randomized, double-blind, placebo-controlled crossover study in 22 adults (61±1 years; mean±SE, 53-79 years) who were free from overt clinical cardiovascular disease. We measured brachial artery flow-mediated endothelium-dependent dilation and endothelium-independent dilation to sublingual nitroglycerin (0.4 mg) following eplerenone (100 mg/dose, 2 doses, 24h between doses) or placebo. In response to acute MR antagonism, flow-mediated dilation decreased by 19% (from 6.9±0.5 to 5.6±0.6%, P=0.02; placebo vs. eplerenone). Endothelial nitric oxide synthase (eNOS) activity also decreased following MR antagonism based on the ratio of phosphorylated eNOS(Ser1177) to total eNOS (1.53±0.08 vs. 1.29±0.06, P=0.02). Nitroglycerin-induced dilation and blood pressure were unaffected (nitroglycerin-induced dilation: 21.9±1.9 vs. 21.0±1.5%, P=0.5 and systolic/diastolic blood pressure: 135/77±4/2 vs. 134/77±4/2 mmHg, P≥0.6). In conclusion, acute MR antagonism impairs vascular endothelial function in healthy older adults without influencing vascular smooth muscle responsiveness to exogenous nitric oxide or blood pressure. Copyright © 2015 Elsevier Inc. All rights reserved.

An Acute Bout of Exercise Improves the Cognitive Performance of Older Adults.

PubMed

Johnson, Liam; Addamo, Patricia K; Selva Raj, Isaac; Borkoles, Erika; Wyckelsma, Victoria; Cyarto, Elizabeth; Polman, Remco C

2016-10-01

There is evidence that an acute bout of exercise confers cognitive benefits, but it is largely unknown what the optimal mode and duration of exercise is and how cognitive performance changes over time after exercise. We compared the cognitive performance of 31 older adults using the Stroop test before, immediately after, and at 30 and 60 min after a 10 and 30 min aerobic or resistance exercise session. Heart rate and feelings of arousal were also measured before, during, and after exercise. We found that, independent of mode or duration of exercise, the participants improved in the Stroop Inhibition task immediately postexercise. We did not find that exercise influenced the performance of the Stroop Color or Stroop Word Interference tasks. Our findings suggest that an acute bout of exercise can improve cognitive performance and, in particular, the more complex executive functioning of older adults.

Anti-CD22-chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia.

PubMed

Haso, Waleed; Lee, Daniel W; Shah, Nirali N; Stetler-Stevenson, Maryalice; Yuan, Constance M; Pastan, Ira H; Dimitrov, Dimiter S; Morgan, Richard A; FitzGerald, David J; Barrett, David M; Wayne, Alan S; Mackall, Crystal L; Orentas, Rimas J

2013-02-14

Immune targeting of B-cell malignancies using chimeric antigen receptors (CARs) is a promising new approach, but critical factors impacting CAR efficacy remain unclear. To test the suitability of targeting CD22 on precursor B-cell acute lymphoblastic leukemia (BCP-ALL), lymphoblasts from 111 patients with BCP-ALL were assayed for CD22 expression and all were found to be CD22-positive, with median CD22 expression levels of 3500 sites/cell. Three distinct binding domains targeting CD22 were fused to various TCR signaling domains ± an IgG heavy chain constant domain (CH2CH3) to create a series of vector constructs suitable to delineate optimal CAR configuration. CARs derived from the m971 anti-CD22 mAb, which targets a proximal CD22 epitope demonstrated superior antileukemic activity compared with those incorporating other binding domains, and addition of a 4-1BB signaling domain to CD28.CD3 constructs diminished potency, whereas increasing affinity of the anti-CD22 binding motif, and extending the CD22 binding domain away from the membrane via CH2CH3 had no effect. We conclude that second-generation m971 mAb-derived anti-CD22 CARs are promising novel therapeutics that should be tested in BCP-ALL.

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

Tipifarnib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

ClinicalTrials.gov

2013-02-01

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; 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); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Tipifarnib in Treating Patients With Acute Myeloid Leukemia in Remission

ClinicalTrials.gov

2018-03-20

Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Megakaryoblastic 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; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Myelodysplastic Syndrome With Excess Blasts; Recurrent Adult Acute Myeloid Leukemia

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

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.

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

Event-Related Potential responses to the acute and chronic effects of alcohol in adolescent and adult Wistar rats

PubMed Central

Ehlers, Cindy L.; Desikan, Anita; Wills, Derek N.

2014-01-01

Background The present study explored the hypothesis that adolescent ethanol exposure may cause long lasting changes in ethanol sensitivity by exploring the age-related effects of acute alcohol on intoxication and on event-related potential (ERP) responses to acoustic stimuli in ethanol naïve adolescent and adult male Wistar rats and in adult rats that were exposed to chronic ethanol/control conditions during adolescence. Methods Ethanol naïve adolescent (postnatal day 32 (PD32)) and adult male rats (PD99) were included in the first study. In a second study, rats were exposed to 5 weeks of ethanol vapor (Blood ethanol concentrations @ 175 mg%) or air from PD24 to PD59 and allowed to mature until PD90. In both studies rats were implanted with cortical recording electrodes, and the effects of acute ethanol (0.0, 1.5, and 3.0 g/kg) on behavioral and ERP responses were assessed. Results Adolescents were found to have higher amplitude and longer latency P3a and P3b components at baseline as compared to adult rats, and ethanol was found to produce a robust dose-dependent increase in the latency of the P3a and P3b components of the auditory ERP recorded in cortical sites in both adolescents and adults. However, ethanol produced significantly larger delays in P3a and P3b latencies in adults as compared to adolescents. Acute ethanol administration was also found to produce a robust dose dependent increase in the latency of the P3a and P3b components in adult animals exposed to ethanol vapor as adolescents and air exposed controls; however, larger acute ethanol-induced increases in P3a and P3b latencies were seen in controls as compared to adolescent vapor exposed rats. Conclusions Adolescent rats have a less intense P3 latency response to acute ethanol administration when compared to adult rats. Exposure to chronic ethanol during adolescence can cause “retention” of the adolescent phenotype of reduced P3 latency sensitivity to ethanol. PMID:24483322

Coordinated Regulation of Niche and Stem Cell Precursors by Hormonal Signaling

PubMed Central

Gancz, Dana; Lengil, Tamar; Gilboa, Lilach

2011-01-01

Stem cells and their niches constitute units that act cooperatively to achieve adult body homeostasis. How such units form and whether stem cell and niche precursors might be coordinated already during organogenesis are unknown. In fruit flies, primordial germ cells (PGCs), the precursors of germ line stem cells (GSCs), and somatic niche precursors develop within the larval ovary. Together they form the 16–20 GSC units of the adult ovary. We show that ecdysone receptors are required to coordinate the development of niche and GSC precursors. At early third instar, ecdysone receptors repress precocious differentiation of both niches and PGCs. Early repression is required for correct morphogenesis of the ovary and for protecting future GSCs from differentiation. At mid-third instar, ecdysone signaling is required for niche formation. Finally, and concurrent with the initiation of wandering behavior, ecdysone signaling initiates PGC differentiation by allowing the expression of the differentiation gene bag of marbles in PGCs that are not protected by the newly formed niches. All the ovarian functions of ecdysone receptors are mediated through early repression, and late activation, of the ecdysone target gene broad. These results show that, similar to mammals, a brain-gland-gonad axis controls the initiation of oogenesis in insects. They further exemplify how a physiological cue coordinates the formation of a stem cell unit within an organ: it is required for niche establishment and to ensure that precursor cells to adult stem cells remain undifferentiated until the niches can accommodate them. Similar principles might govern the formation of additional stem cell units during organogenesis. PMID:22131903

Comparing the effects of an acute bout of physical exercise with an acute bout of interactive mental and physical exercise on electrophysiology and executive functioning in younger and older adults.

PubMed

Dimitrova, Julia; Hogan, Michael; Khader, Patrick; O'Hora, Denis; Kilmartin, Liam; Walsh, Jane C; Roche, Richard; Anderson-Hanley, Cay

2017-10-01

Physical exercise has been shown to improve cognitive and neural functioning in older adults. The current study compared the effects of an acute bout of physical exercise with a bout of interactive mental and physical exercise (i.e., "exergaming") on executive (Stroop) task performance and event-related potential (ERP) amplitudes in younger and older adults. Results revealed enhanced executive task performance in younger and older adults after exercise, with no differences in performance between exercise conditions. Stroop (RT) performance in older adults improved more than in younger adults from pre- to post-exercise. A significant increase in EEG amplitude from pre- to post-exercise was found at the Cz site from 320 to 700 ms post-stimulus for both younger and older adults, with older adults demonstrating a larger Stroop interference effect. While younger adults exhibited overall greater EEG amplitudes than older adults, they showed no differences between congruent and incongruent trials (i.e., minimal interference). Compared to peers with higher BMI (body mass index), older adults with lower BMI showed a greater reduction in Stroop interference effects from pre- to post-exercise. The beneficial effects of an acute bout of physical exercise on cognitive and neural functioning in younger and older adults were confirmed, with no difference between standard exercise and exergaming. Findings suggest that BMI, sometimes used as a proxy for fitness level, may modulate benefits that older adults derive from an acute bout of exercise. Findings have implications for future research that seeks to investigate unique effects of exergaming when compared to standard physical exercise.

huJCAR014 CAR-T Cells in Treating Adult Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma or Acute Lymphoblastic Leukemia

ClinicalTrials.gov

2018-05-25

Adult B Acute Lymphoblastic Leukemia; BCL2 Gene Rearrangement; BCL6 Gene Rearrangement; CD19 Positive; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; MYC Gene Rearrangement; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Adult Acute Lymphoblastic Leukemia; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia | Office of Cancer Genomics

Cancer.gov

Publication Abstract:  Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is characterized by a gene-expression profile similar to that of BCR-ABL1-positive ALL, alterations of lymphoid transcription factor genes, and a poor outcome. The frequency and spectrum of genetic alterations in Ph-like ALL and its responsiveness to tyrosine kinase inhibition are undefined, especially in adolescents and adults. We performed genomic profiling of 1725 patients with precursor B-cell ALL and detailed genomic analysis of 154 patients with Ph-like ALL.

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

PubMed

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

2015-10-01

Most cases of adult pertussis probably remain undiagnosed. To explore the prevalence, diagnosis, and disease course of acute pertussis infection in adult patients presenting with acute cough. Prospective observational study between 2007 and 2010 in primary care in 12 European countries. 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. 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. 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. © British Journal of General Practice 2015.

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

Systemic antibiotics for symptomatic apical periodontitis and acute apical abscess in adults.

PubMed

Cope, Anwen; Francis, Nick; Wood, Fiona; Mann, Mala K; Chestnutt, Ivor G

2014-06-26

Dental pain can have a considerable detrimental effect on an individual's quality of life. Symptomatic apical periodontitis and acute apical abscess are common causes of dental pain and arise from an inflamed or necrotic dental pulp, or infection of the pulpless root canal system. Clinical guidelines recommend that the first-line treatment for teeth with symptomatic apical periodontitis or an acute apical abscess should be removal of the source of inflammation or infection by local, operative measures, and that systemic antibiotics are currently only recommended for situations where there is evidence of spreading infection (cellulitis, lymph node involvement, diffuse swelling) or systemic involvement (fever, malaise). Despite this, there is evidence that dentists continue to prescribe antibiotics for these conditions. There is concern that this could contribute to the development of antibiotic-resistant bacterial colonies both within the individual and within the community as a whole. To evaluate the effects of systemic antibiotics provided with or without surgical intervention (such as extraction, incision and drainage of a swelling or endodontic treatment), with or without analgesics, for symptomatic apical periodontitis or acute apical abscess in adults. We searched the following electronic databases: Cochrane Oral Health Group's Trials Register (to 1 October 2013); Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 9); MEDLINE via OVID (1946 to 1 October 2013); EMBASE via OVID (1980 to 1 October 2013) and CINAHL via EBSCO (1980 to 1 October 2013). We searched the World Health Organization (WHO) International Trials Registry Platform and the US National Institutes of Health Trials Registry (ClinicalTrials.gov) on 1 October 2013 to identify ongoing trials. We searched for grey literature using OpenGrey (to 1 October 2013) and ZETOC Conference Proceedings (1993 to 1 October 2013). We placed no restrictions on the language or date of

Acute effects of exercise and active video games on adults' reaction time and perceived exertion.

PubMed

Guzmán, José F; López-García, Jesús

2016-11-01

The purpose of the present study was to examine the acute effects of resting, aerobic exercise practised alone, and aerobic exercise with active video games (AVG), on complex reaction time (CRT) and the post-exercise acute rate of perceived exertion (RPE) in young healthy adults. The experimental group was composed of 92 healthy young adults, 78 males and 13 females (age M = 21.9 ± 2.7 years) who completed two sessions, A and B. In session A, participants rode 30 min on an ergometer, while in session B they exercised for 30 min on an ergometer while playing an AVG on a Wii. The control group was composed of 30 young adults, 26 males and 4 females (age M = 21.4 ± 2.9 years) who rested for 30 min. In each session, a CRT task was performed before and after exercising or resting, and post-exercise global RPE was noted. Repeated measures general linear model (GLM) and Wilcoxon tests were performed. (1) Both aerobic exercise alone and aerobic exercise combined with AVG improved CRT, while resting did not; (2) aerobic exercise combined with AVG did not improve CRT more than aerobic exercise only; and (3) RPE was lower after aerobic exercise combined with AVG compared with aerobic exercise only. In young adults, exercise produces acute benefits on CRT, and practising exercise with AVG helps to decrease RPE.

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

Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation

ClinicalTrials.gov

2017-03-27

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); B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Essential Thrombocythemia; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

PARP activity and inhibition in fetal and adult oligodendrocyte precursor cells: Effect on cell survival and differentiation.

PubMed

Baldassarro, Vito A; Marchesini, Alessandra; Giardino, Luciana; Calzà, Laura

2017-07-01

Poly (ADP-ribose) polymerase (PARP) family members are ubiquitously expressed and play a key role in cellular processes, including DNA repair and cell death/survival balance. Accordingly, PARP inhibition is an emerging pharmacological strategy for cancer and neurodegenerative diseases. Consistent evidences support the critical involvement of PARP family members in cell differentiation and phenotype maturation. In this study we used an oligodendrocyte precursor cells (OPCs) enriched system derived from fetal and adult brain to investigate the role of PARP in OPCs proliferation, survival, and differentiation. The PARP inhibitors PJ34, TIQ-A and Olaparib were used as pharmacological tools. The main results of the study are: (i) PARP mRNA expression and PARP activity are much higher in fetal than in adult-derived OPCs; (ii) the culture treatment with PARP inhibitors is cytotoxic for OPCs derived from fetal, but not from adult, brain; (iii) PARP inhibition reduces cell number, according to the inhibitory potency of the compounds; (iv) PARP inhibition effect on fetal OPCs is a slow process; (v) PARP inhibition impairs OPCs maturation into myelinating OL in fetal, but not in adult cultures, according to the inhibitory potency of the compounds. These results have implications for PARP-inhibition therapies for diseases and lesions of the central nervous system, in particular for neonatal hypoxic/ischemic encephalopathy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

[Clinical and cytological differences in adult acute lymphatic and acute undifferentiated leukemia].

PubMed

Abbrederis, K; Schmalzl, F

1976-01-01

The usefulness for clinical purposes of the distinction of acute undifferentiated (AUL) and acute lymphocytic leukemia (ALL) is suggested by the following observations: 1. Maturation from AUL to ALL has not been observed. Transformation of ALL to AUL has been reported i.e. less of cytoplasmic polysaccharides; however this seems rather to be the effect of cytotoxic therapy and not a real change of the cytological type. 2. Significant differences among ALL and AUL can be noted as far as the therapeutic response is concerned: All of the 9 patients with ALL but only 2 out of 9 patients with AUL went into remission. The mean survival of the cases with ALL amounts to 34, that of AUL only to 4 months. Out of the patients with ALL 4 patients are still alive in persistant first remission after 77, 57, 36 and 28 months. 3. ALL occurs most frequently in young adults (mean age of 21 patients: 31.7 years): AUL is more frequent in elderly patients (Mean age of 18 patients: 57.6 years). 4. In our material ALL did never occur consequent to a typical preluekemic stage, which was followed either by myeloblastic, monocytic, erythroleukemic or undifferentiated leukemias.

Protocol to Isolate a Large Amount of Functional Oligodendrocyte Precursor Cells from the Cerebral Cortex of Adult Mice and Humans

PubMed Central

Medina-Rodríguez, Eva María; Arenzana, Francisco Javier; Bribián, Ana; de Castro, Fernando

2013-01-01

During development, oligodendrocytes are generated from oligodendrocyte precursor cells (OPCs), a cell type that is a significant proportion of the total cells (3-8%) in the adult central nervous system (CNS) of both rodents and humans. Adult OPCs are responsible for the spontaneous remyelination that occurs in demyelinating diseases like Multiple Sclerosis (MS) and they constitute an interesting source of cells for regenerative therapy in such conditions. However, there is little data regarding the neurobiology of adult OPCs isolated from mice since an efficient method to isolate them has yet to be established. We have designed a protocol to obtain viable adult OPCs from the cerebral cortex of different mouse strains and we have compared its efficiency with other well-known methods. In addition, we show that this protocol is also useful to isolate functional OPCs from human brain biopsies. Using this method we can isolate primary cortical OPCs in sufficient quantities so as to be able to study their survival, maturation and function, and to facilitate an evaluation of their utility in myelin repair. PMID:24303061

Protocol to isolate a large amount of functional oligodendrocyte precursor cells from the cerebral cortex of adult mice and humans.

PubMed

Medina-Rodríguez, Eva María; Arenzana, Francisco Javier; Bribián, Ana; de Castro, Fernando

2013-01-01

During development, oligodendrocytes are generated from oligodendrocyte precursor cells (OPCs), a cell type that is a significant proportion of the total cells (3-8%) in the adult central nervous system (CNS) of both rodents and humans. Adult OPCs are responsible for the spontaneous remyelination that occurs in demyelinating diseases like Multiple Sclerosis (MS) and they constitute an interesting source of cells for regenerative therapy in such conditions. However, there is little data regarding the neurobiology of adult OPCs isolated from mice since an efficient method to isolate them has yet to be established. We have designed a protocol to obtain viable adult OPCs from the cerebral cortex of different mouse strains and we have compared its efficiency with other well-known methods. In addition, we show that this protocol is also useful to isolate functional OPCs from human brain biopsies. Using this method we can isolate primary cortical OPCs in sufficient quantities so as to be able to study their survival, maturation and function, and to facilitate an evaluation of their utility in myelin repair.

A Rare Cause of Acute Abdomen: Diagnosis and Management of Adult Colonic Intussusception.

PubMed

Sertkaya, Mehmet; Emre, Arif; Pircanoglu, Eyüp Mehmet; Yazar, Fatih Mehmet; Tepe, Murat; Cengiz, Emrah; Isler, Ali; Vicdan, Halit

2016-01-01

Intussusception in adults is very rarely seen, and this cause acute abdomen. A computed tomography (CT) scan, clinical suspicion, history, and a physical examination are important for the diagnosis. We present two cases of colonic intussusceptions induced by lipoma. The cases had similar locations, diagnoses, and management. Both lipomas were located close to the cecum in the ascending colon, and a right segmental colon resection was performed in both cases. The follow-up of both cases was uneventful. Although benign lesions can cause colonic intussusception, the high incidence of malignancy in colonic lesions should always be considered. Therefore, oncologic surgical procedures should be applied. The definitive diagnosis can be made by histopathology. Sertkaya M, Emre A, Pircanoglu EM, Yazar FM, Tepe M, Cengiz E, Isler A, Vicdan H. A Rare cause of Acute Abdomen: Diagnosis and Management of Adult Colonic Intussusception. Euroasian J Hepato-Gastroenterol 2016;6(2):179-182.

Polymorphisms in the methylenetetrahydrofolate reductase gene are associated with susceptibility to acute leukemia in adults

PubMed Central

Skibola, Christine F.; Smith, Martyn T.; Kane, Eleanor; Roman, Eve; Rollinson, Sara; Cartwright, Raymond A.; Morgan, Gareth

1999-01-01

Reduction of 5,10-methylenetetrahydrofolate (methyleneTHF), a donor for methylating dUMP to dTMP in DNA synthesis, to 5-methyltetrahydrofolate (methylTHF), the primary methyl donor for methionine synthesis, is catalyzed by 5,10-methylenetetrahydrofolate reductase (MTHFR). A common 677 C → T polymorphism in the MTHFR gene results in thermolability and reduced MTHFR activity that decreases the pool of methylTHF and increases the pool of methyleneTHF. Recently, another polymorphism in MTHFR (1298 A → C) has been identified that also results in diminished enzyme activity. We tested whether carriers of these variant alleles are protected from adult acute leukemia. We analyzed DNA from a case–control study in the United Kingdom of 308 adult acute leukemia patients and 491 age- and sex-matched controls. MTHFR variant alleles were determined by a PCR-restriction fragment length polymorphism assay. The MTHFR 677TT genotype was lower among 71 acute lymphocytic leukemia (ALL) cases compared with 114 controls, conferring a 4.3-fold decrease in risk of ALL [odds ratio (OR = 0.23; 95% CI = 0.06–0.81]. We observed a 3-fold reduction in risk of ALL in individuals with the MTHFR 1298AC polymorphism (OR = 0.33; 95% CI = 0.15–0.73) and a 14-fold decreased risk of ALL in those with the MTHFR 1298CC variant allele (OR = 0.07; 95% CI = 0.00–1.77). In acute myeloid leukemia, no significant difference in MTHFR 677 and 1298 genotype frequencies was observed between 237 cases and 377 controls. Individuals with the MTHFR 677TT, 1298AC, and 1298CC genotypes have a decreased risk of adult ALL, but not acute myeloid leukemia, which suggests that folate inadequacy may play a key role in the development of ALL. PMID:10536004

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. Copyright © 2015 the American Physiological Society.

Decitabine and Bortezomib in Treating Patients With Acute Myeloid Leukemia

ClinicalTrials.gov

2014-11-06

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

Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia

ClinicalTrials.gov

2017-04-05

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; 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); Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

VpreB gene expression in hematopoietic malignancies: a lineage- and stage-restricted marker for B-cell precursor leukemias.

PubMed

Bauer, S R; Kubagawa, H; Maclennan, I; Melchers, F

1991-09-15

We show here that analysis of VpreB gene transcription can be a specific way to identify acute leukemias of cells at very early stages of B-cell development. Northern blot analysis of RNAs from 63 leukemia samples showed that VpreB RNA was present in malignancies of precursor B cells, the expression being a feature of both common acute lymphoblastic leukemia (ALL) (CD10+) and null ALL (CD10-). It was absent from malignancies of mature B cells (surface Ig positive), from acute leukemias of the T-cell lineage and granulocyte-macrophage lineages, and from normal tonsil B and T lymphocytes. Chronic myeloid leukemia blast crises of the B-precursor-cell type expressed the VpreB gene while myeloid blast crises did not. VpreB RNA was also expressed in the neoplastic cells of one of three patients with acute undifferentiated leukemias. These data show that VpreB RNA expression is a marker of the malignant forms of precursor B cells, and that it appears at least as early as cytoplasmic CD22 and CD19 in tumors of the B-cell lineage.

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

Anti-CD22–chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia

PubMed Central

Haso, Waleed; Lee, Daniel W.; Shah, Nirali N.; Stetler-Stevenson, Maryalice; Yuan, Constance M.; Pastan, Ira H.; Dimitrov, Dimiter S.; Morgan, Richard A.; FitzGerald, David J.; Barrett, David M.; Wayne, Alan S.; Mackall, Crystal L.

2013-01-01

Immune targeting of B-cell malignancies using chimeric antigen receptors (CARs) is a promising new approach, but critical factors impacting CAR efficacy remain unclear. To test the suitability of targeting CD22 on precursor B-cell acute lymphoblastic leukemia (BCP-ALL), lymphoblasts from 111 patients with BCP-ALL were assayed for CD22 expression and all were found to be CD22-positive, with median CD22 expression levels of 3500 sites/cell. Three distinct binding domains targeting CD22 were fused to various TCR signaling domains ± an IgG heavy chain constant domain (CH2CH3) to create a series of vector constructs suitable to delineate optimal CAR configuration. CARs derived from the m971 anti-CD22 mAb, which targets a proximal CD22 epitope demonstrated superior antileukemic activity compared with those incorporating other binding domains, and addition of a 4-1BB signaling domain to CD28.CD3ζ constructs diminished potency, whereas increasing affinity of the anti-CD22 binding motif, and extending the CD22 binding domain away from the membrane via CH2CH3 had no effect. We conclude that second-generation m971 mAb-derived anti-CD22 CARs are promising novel therapeutics that should be tested in BCP-ALL. PMID:23243285

Perceived social support among adults seeking care for acute respiratory tract infections in US EDs.

PubMed

Levin, Sara K; Metlay, Joshua P; Maselli, Judith H; Kersey, Ayanna S; Camargo, Carlos A; Gonzales, Ralph

2009-06-01

Emergency departments (EDs) provide a disproportionate amount of care to disenfranchised and vulnerable populations. We examined social support levels among a diverse population of adults seeking ED care for acute respiratory tract infections. A convenience sample of adults seeking care in 1 of 15 US EDs was telephone interviewed 1 to 6 weeks postvisit. The Multidimensional Scale of Perceived Social Support (7-point Likert) assessed social support across 3 domains: friends, family, and significant others. Higher scores indicate higher support. Of 1104 subjects enrolled, 704 (64%) completed the follow-up interview. Factor analysis yielded 3 factors. Mean social support score was 5.54 (SD 1.04). Female sex, greater household income, and better health status were independently associated with higher levels of social support. Social support levels among adults seeking care in the ED for acute respiratory tract infections are similar to general population cohorts, suggesting that social support is not a strong determinant of health care seeking in EDs.

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

ClinicalTrials.gov

2018-05-16

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

Effect of acute aerobic exercise on vaccine efficacy in older adults.

PubMed

Ranadive, Sushant Mohan; Cook, Marc; Kappus, Rebecca Marie; Yan, Huimin; Lane, Abbi Danielle; Woods, Jeffery A; Wilund, Kenneth R; Iwamoto, Gary; Vanar, Vishwas; Tandon, Rudhir; Fernhall, Bo

2014-03-01

The most effective way of avoiding influenza is through influenza vaccination. However, the vaccine is ineffective in about 25% of the older population. Immunosenescence with advancing age results in inadequate protection from disease because of ineffective responses to vaccination. Recently, a number of strategies have been tested to improve the efficacy of a vaccine in older adults. An acute bout of moderate aerobic exercise may increase the efficacy of the vaccine in young individuals, but there are limited efficacy data in older adults who would benefit most. This study sought to evaluate whether acute moderate-intensity endurance exercise immediately before influenza vaccination would increase the efficacy of the vaccine. Fifty-nine healthy volunteers between 55 and 75 yr of age were randomly allocated to an exercise or control group. Antibody titers were measured at baseline before exercise and 4 wk after vaccination. C-reactive protein (CRP) and interleukin-6 (IL-6) were measured at 24 and 48 h after vaccination. Delta CRP and IL-6 at 24 and 48 h were significantly higher after vaccination as compared to the sham injection. There were no differences in the levels of antibody titers against the H3N2 influenza strain between groups. However, women in the exercise group had a significantly higher antibody response against the H1N1 influenza strain as compared to the men, probably because of lower prevaccine titers. There were no significant differences in seroprotection between groups. Acute moderate aerobic exercise was not immunostimulatory in healthy older men but may serve as a vaccine adjuvant in older women.

The Clinical Spectrum of Renal Insufficiency During Acute Glomerulonephritis in the Adult

PubMed Central

Lemieux, Guy; Cuvelier, Amedee A.; Lefebvre, Rene

1967-01-01

Twenty-seven adults with acute poststreptococcal glomerulonephritis were divided into two groups according to the severity of reduction in renal function: (1) 14 patients with mild depression of renal function, and (2) 13 patients with more severe renal insufficiency. In the first group the outcome was favourable, with complete clinical recovery in 11 patients. Only two patients in the second group have recovered. Five have died of renal failure and in six the chronic stage has developed. The most notable histopathological lesion observed in this group of patients was severe proliferative glomerulonephritis with a large number of epithelial crescents. According to the mode of development and time of onset of renal failure, these 13 patients could be divided into three sub-groups: (1) early renal failure without oliguria (three patients), (2) early renal failure with severe oliguria or anuria (three patients) and (3) delayed renal failure (seven patients). Although there are exceptions, the development of renal insufficiency in an adult patient suffering from acute glomerulonephritis is usually associated with a guarded prognosis. ImagesFig. 2 PMID:6021561

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

ClinicalTrials.gov

2018-05-24

Acute Myeloid Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; 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

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

[Genotypes of rhinoviruses in children and adults patients with acute respiratory tract infections].

PubMed

Demirkan, Eda; Kırdar, Sevin; Ceylan, Emel; Yenigün, Ayşe; Kurt Ömürlü, İmran

2017-10-01

Rhinovirus (RV) is one of the most frequent causative agent of acute respiratory tract infections in the world. The virus may cause a mild cold, as well as more serious clinical symptoms in patients with immune system deficiency or comorbidities. Rhinoviruses have been identified by molecular methods under three types: RV-A, RV-B and RV-C. In most of the cases, it was reported that RV-A and RV-C were related with lower respiratory tract infections and asthma exacerbations, while RV-B was rarely reported in lower respiratory tract infections. The main objective of this study was to investigate RV species by sequence analysis in nasopharyngeal samples in pediatric and adult patients who were admitted to hospital with acute respiratory tract infections and to establish the relationship between species and age, gender and clinical diagnosis of the patients. Secondly, it was planned to emphasize the efficiency of the sequence analysis method in the determination of RV species. One hundred twenty seven patients (children and adults) who were followed up with acute respiratory tract infections in our university hospital were evaluated between January 2014 and January 2016. Viral loads were determined by quantitative real-time PCR in RV positive patients detected by a commercial kit in nasopharyngeal swab specimens. Thirty-one samples whose viral loads could not be determined were excluded from the study. The remaining 96 samples (50 children and 46 adults) were retested by conventional PCR using the target of VP4/VP2 gene region. A total of 65 samples (32 adults and 33 children) with the bands (549 bp) corresponding to the VP4/VP2 gene regions after the conventional PCR were analyzed by DNA sequencing. A phylogenetic tree was constructed using the neighbour-joining method. After sequence analysis it was determined that 28 (43.07%) were RV-A, 7 (10.76%) were RV-B and 28 (43.07%) were RV-C; and moreover one of each enterovirus (EV) species EV-D68 (1.53%) and EV-C (1

[The role of endothelial cells and endothelial precursor cells in angiogenesis].

PubMed

Poreba, Małgorzata; Usnarska-Zubkiewicz, Lidia; Kuliczkowski, Kazimierz

2006-01-01

Endothelium plays a key role in maintenance of vascular homeostasis in human organism. According to new data endothelial cells and hematopoietic cells have a common precursor in prenatal life--a hemangioblast, which explains the fact of sharing the same determinants on the surface of both type of cells. Circulating endothelial precursors were identified in adults and this suggests that hemangioblasts may be present not only during embriogenesis. In some clinical situations the increased numbers of endothelial cells and endothelial precursors were noted, and especially in patients with neoplastic diseases, which is probably the result of increased angiogenesis. Endothelial precursors are thought to be the promice for therapeutic purposes in future--to increase local angiogenesis.

AR-42 and Decitabine in Treating Patients With Acute Myeloid Leukemia

ClinicalTrials.gov

2018-03-12

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); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

GAS6/Mer axis regulates the homing and survival of the E2A/PBX1 positive B-cell precursor acute lymphoblastic leukemia in the bone marrow niche

PubMed Central

Shiozawa, Yusuke; Pedersen, Elisabeth A.; Taichman, Russell S.

2009-01-01

Despite improvements in current combinational chemotherapy regimens, the prognosis of the (1;19)(q23;p13) translocation (E2A/PBX1) positive B-cell precursor acute lymphoblastic leukemia (ALL) is poor in pediatric leukemia patients. In this study, we examined the roles of GAS6/Mer axis in the interactions between E2A/PBX1 positive B-cell precursor ALL cells and the osteoblastic niche in the bone marrow. The data show that primary human osteoblasts secrete GAS6 in response to the Mer-over-expressed E2A/PBX1 positive ALL cells through MAPK signaling pathway and that leukemia cells migrate toward GAS6 using pathways activated by Mer. Importantly, GAS6 supports the survival and prevents apoptosis from chemotherapy of E2A/PBX1 positive ALL cells by inducing dormancy. Together, these data suggest that GAS6/Mer axis regulates the homing and survival of the E2A/PBX1 positive B-cell precursor ALL in the bone marrow niche. PMID:19922767

Analysis of acute naproxen administration on memory in young adults: A randomized, double-blind, placebo-controlled study.

PubMed

Wilson, Jack H; Criss, Amy H; Spangler, Sean A; Walukevich, Katherine; Hewett, Sandra

2017-10-01

Nonsteroidal anti-inflammatory drugs work by non-selectively inhibiting cyclooxygenase enzymes. Evidence indicates that metabolites of the cyclooxygenase pathway play a critical role in the process of learning and memory. We evaluated whether acute naproxen treatment impairs short-term working memory, episodic memory, or semantic memory in a young, healthy adult population. Participants received a single dose of placebo or naproxen (750 mg) in random order separated by 7-10 days. Two hours following administration, participants completed five memory tasks. The administration of acute high-dose naproxen had no effect on memory in healthy young adults.

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

ClinicalTrials.gov

2017-02-01

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

Acute stress disorder in older, middle-aged and younger adults in reaction to the second Lebanon war.

PubMed

Cohen, Miri

2008-01-01

To compare rate of acute stress disorder (ASD) and intensity of acute stress symptoms (ASS) in younger, middle-aged and older Israeli citizens exposed to missile attacks during the second Lebanon war. A telephone survey of a random sample of residents in the northern area of Israel was conducted in July 2006, during the third week of Lebanon war. Respondents were divided into groups aged 18-40, 41-69 and 70+. ASD and ASS were measured by the Acute Stress Interview questionnaire and by war-related exposure variables and demographic data. Exposure variables were similar in the three age groups. Older respondents reported lower intensity of ASS and obtained lower means for each of the symptoms criteria than the young adults, while the middle-aged adults were in between the younger and the older group. ASD criteria were met by 13.2% of the younger, 4.7% of middle-aged and 4.3% of older respondents (p > 0.05), and subsyndromal ASD was found in 20.5%, 14.1% and 4.4% (p < 0.05) respectively. Twenty-two percent of ASS variance was explained by younger age, female gender and higher perceived proximity to missile falling. Older adults reacted to the war situation with lower level of acute stress symptoms. Long-term effects of war on different age groups should be further studied.

EFFECTS OF AGE AND ACUTE MUSCLE FATIGUE ON REACTIVE POSTURAL CONTROL IN HEALTHY ADULTS

PubMed Central

Papa, Evan V.; Foreman, K. Bo; Dibble, Lee E.

2015-01-01

BACKGROUND Falls can cause moderate to severe injuries such as hip fractures and head trauma in older adults. While declines in muscle strength and sensory function contribute to increased falls in older adults, skeletal muscle fatigue is often overlooked as an additional contributor to fall risk. The purpose of this investigation was to examine the effects of acute lower extremity muscle fatigue and age on reactive postural control in healthy adults. METHODS A sample of 16 individuals participated in this study (8 healthy older adults and 8 healthy young persons). Whole body kinematic and kinetic data were collected during anterior and posterior reproducible fall tests before (T0) and immediately after (T1) eccentric muscle fatiguing exercise, as well as after 15-minutes (T15) and 30-minutes (T30) of rest. FINDINGS Lower extremity joint kinematics of the stepping limb during the support (landing) phase of the anterior fall were significantly altered by the presence of acute muscle fatigue. Step velocity was significantly decreased during the anterior falls. Statistically significant main effects of age were found for step length in both fall directions. Effect sizes for all outcomes were small. No statistically significant interaction effects were found. INTERPRETATION Muscle fatigue has a measurable effect on lower extremity joint kinematics during simulated falls. These alterations appear to resolve within 15 minutes of recovery. The above deficits, coupled with a reduced step length, may help explain the increased fall risk in older adults. PMID:26351001

Effects of age and acute muscle fatigue on reactive postural control in healthy adults.

PubMed

Papa, Evan V; Foreman, K Bo; Dibble, Leland E

2015-12-01

Falls can cause moderate to severe injuries such as hip fractures and head trauma in older adults. While declines in muscle strength and sensory function contribute to increased falls in older adults, skeletal muscle fatigue is often overlooked as an additional contributor to fall risk. The purpose of this investigation was to examine the effects of acute lower extremity muscle fatigue and age on reactive postural control in healthy adults. A sample of 16 individuals participated in this study (8 healthy older adults and 8 healthy young persons). Whole body kinematic and kinetic data were collected during anterior and posterior reproducible fall tests before (T0) and immediately after (T1) eccentric muscle fatiguing exercise, as well as after 15-min (T15) and 30-min (T30) of rest. Lower extremity joint kinematics of the stepping limb during the support (landing) phase of the anterior fall were significantly altered by the presence of acute muscle fatigue. Step velocity was significantly decreased during the anterior falls. Statistically significant main effects of age were found for step length in both fall directions. Effect sizes for all outcomes were small. No statistically significant interaction effects were found. Muscle fatigue has a measurable effect on lower extremity joint kinematics during simulated falls. These alterations appear to resolve within 15 min of recovery. The above deficits, coupled with a reduced step length, may help explain the increased fall risk in older adults. Copyright © 2015 Elsevier Ltd. All rights reserved.

Patient-Reported Symptoms and Quality of Life in Adults With Acute Leukemia: A Systematic Review

PubMed Central

Bryant, Ashley Leak; Walton, AnnMarie L.; Shaw-Kokot, Julia; Mayer, Deborah K.; Reeve, Bryce B.

2018-01-01

Purpose/Objectives Systematically summarize findings from research conducted on adult acute leukemia survivors as they relate to symptoms and quality of life (QOL). Data Sources Systematic review of the literature from 1990–2013 found in the PubMed, PsycINFO®, EMBASE, and CINAHL® databases, as well as manual searches. Data Synthesis The review identified 16 quantitative studies and 1 qualitative study published from 1990–2013 that used a self-reported QOL or symptom questionnaire. Fatigue was the most commonly assessed and reported symptom, followed by depression. Conclusions Acute leukemia and its treatment have a significant impact in all QOL domains. Future studies should include longitudinal research, more than one recruitment site, increased minority representation, and home-based exercise interventions as ways to improve all domains of QOL. Implications for Nursing This review increases awareness of commonly reported symptoms faced by adults with acute leukemia. Oncology nurses are central in monitoring and reporting symptoms to the interdisciplinary team that may contribute to changes in function, with the overall goal of optimizing QOL over time. PMID:25806895

Proton Beam Craniospinal Irradiation Reduces Acute Toxicity for Adults With Medulloblastoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, Aaron P.; Barney, Christian L.; Grosshans, David R.

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% weightmore » 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.« less

Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

ClinicalTrials.gov

2013-01-08

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 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

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

The Effects of Acute Dopamine Precursor Depletion on the Cognitive Control Functions of Performance Monitoring and Conflict Processing: An Event-Related Potential (ERP) Study.

PubMed

Larson, Michael J; Clayson, Peter E; Primosch, Mark; Leyton, Marco; Steffensen, Scott C

2015-01-01

Studies using medications and psychiatric populations implicate dopamine in cognitive control and performance monitoring processes. However, side effects associated with medication or studying psychiatric groups may confound the relationship between dopamine and cognitive control. To circumvent such possibilities, we utilized a randomized, double-blind, placebo-controlled, within-subjects design wherein participants were administered a nutritionally-balanced amino acid mixture (BAL) and an amino acid mixture deficient in the dopamine precursors tyrosine (TYR) and phenylalanine (PHE) on two separate occasions. Order of sessions was randomly assigned. Cognitive control and performance monitoring were assessed using response times (RT), error rates, the N450, an event-related potential (ERP) index of conflict monitoring, the conflict slow potential (conflict SP), an ERP index of conflict resolution, and the error-related negativity (ERN) and error positivity (Pe), ERPs associated with performance monitoring. Participants were twelve males who completed a Stroop color-word task while ERPs were collected four hours following acute PHE and TYR depletion (APTD) or balanced (BAL) mixture ingestion in two separate sessions. N450 and conflict SP ERP amplitudes significantly differentiated congruent from incongruent trials, but did not differ as a function of APTD or BAL mixture ingestion. Similarly, ERN and Pe amplitudes showed significant differences between error and correct trials that were not different between APTD and BAL conditions. Findings indicate that acute dopamine precursor depletion does not significantly alter cognitive control and performance monitoring ERPs. Current results do not preclude the role of dopamine in these processes, but suggest that multiple methods for dopamine-related hypothesis testing are needed.

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

[Management of acute and severe complications in adults with cystic fibrosis].

PubMed

Chapron, J; Zuber, B; Kanaan, R; Hubert, D; Desmazes-Dufeu, N; Mira, J-P; Dusser, D; Burgel, P-R

2011-04-01

The natural history of cystic fibrosis (CF) may be associated both with acute respiratory complications (respiratory exacerbations, haemoptysis, pneumothorax) and with non-respiratory complications (distal intestinal obstruction syndrome, dehydration) that may result in hospitalizations. The aim of this article is to describe the main therapeutic approaches that are adopted in the management of acute complications occurring in CF adults, and to discuss indications for admission of these patients to intensive care units. Adult CF patients admitted to intensive care unit often benefit from antibiotic courses adapted to their chronic bronchial infection, especially when the hospitalization is related to respiratory disease (including haemoptysis and pneumothorax). Nutritional support, including hypercaloric diet, control of hyperglycemia and pancreatic enzyme supplementation is warranted. The recommended therapy for major haemoptysis is bronchial artery embolization. Patient with significant pneumothorax should have a chest tube inserted, while the treatment of distal intestinal obstruction syndrome will most often be medical. In case of respiratory failure, non-invasive ventilation is the preferred mode of ventilatory support because invasive ventilation is associated with poor outcomes. Therapeutic options should always have been discussed between the patient, family members and the CF medical team to allow for informed decision making. Copyright © 2011 SPLF. Published by Elsevier Masson SAS. All rights reserved.

An antigen shared by human granulocytes, monocytes, marrow granulocyte precursors and leukemic blasts.

PubMed

Shumak, K H; Rachkewich, R A

1983-01-01

An antibody to human granulocytes was raised in rabbits by immunization with granulocytes pretreated with rabbit antibody to contaminating antigens. The antibody reacted not only with granulocytes but also with monocytes and bone marrow granulocyte precursors including colony-forming units in culture (CFU-C). In tests with leukemic cells, the antibody reacted with blasts from most (8 of 9) patients with acute myelomonoblastic leukemia and from some patients with acute myeloblastic leukemia, morphologically undifferentiated acute leukemia and chronic myelogenous leukemia in blast crisis. The antibody did not react with blasts from patients with acute lymphoblastic leukemia nor with leukemic cells from patients with chronic lymphocytic leukemia.

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

ClinicalTrials.gov

2018-04-23

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

Brain-Derived Neurotrophic Factor Induces Cell Survival and the Migration of Murine Adult Hippocampal Precursor Cells During Differentiation In Vitro.

PubMed

Ortiz-López, Leonardo; Vega-Rivera, Nelly Maritza; Babu, Harish; Ramírez-Rodríguez, Gerardo Bernabé

2017-01-01

The generation of new neurons during adulthood involves local precursor cell migration and terminal differentiation in the dentate gyrus. These events are influenced by the hippocampal microenvironment. Brain-derived neurotrophic factor (BDNF) is relevant for hippocampal neuronal development and behavior. Interestingly, studies that have been performed in controlled in vitro systems that involve isolated precursor cells that were derived from the dentate gyrus (AHPCs) have shown that BDNF induces the activation of the TrkB receptor and, consequentially, might activate signaling pathways that favor survival and neuronal differentiation. Based on the fact that the cellular events of AHPCs that are induced by single factors can be studied in this controlled in vitro system, we investigated the ability of BDNF and the involvement of protein kinase C (PKC), as one of the TrkB-downstream activated signaling proteins, in the regulation of migration, here reflected by motility, of AHPCs. Precursor cells were cultured following a concentration-response curve (1-640 ng/ml) for 24 or 96 h. We found that BDNF favored cell survival without altering the viability under culture proliferative conditions of the AHPCs. Concomitantly, glial- and neuronal-differentiated precursor cells increased as a consequence of survival promoted by BDNF. Additionally, pharmacological approaches showed that BDNF (40 ng/ml)-induced migration of AHPCs was blocked with the compounds K252a and GF109203x, which prevent the activation of TrkB and PKC, respectively. The results indicate that in the in vitro migration of differentiated AHPCs it is involved the BDNF and TrkB cascade. Our results provide additional information about the mechanism by which BDNF impacts adult neurogenesis in the hippocampus.

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

ClinicalTrials.gov

2018-01-02

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

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

Sustainability of Evidence-Based Acute Pain Management Practices for Hospitalized Older Adults.

PubMed

Shuman, Clayton J; Xie, Xian-Jin; Herr, Keela A; Titler, Marita G

2017-11-01

Little is known regarding sustainability of evidence-based practices (EBPs) following implementation. This article reports sustainability of evidence-based acute pain management practices in hospitalized older adults following testing of a multifaceted Translating Research Into Practice (TRIP) implementation intervention. A cluster randomized trial with follow-up period was conducted in 12 Midwest U.S. hospitals (six experimental, six comparison). Use of evidence-based acute pain management practices and mean pain intensity were analyzed using generalized estimating equations across two time points (following implementation and 18 months later) to determine sustainability of TRIP intervention effects. Summative Index scores and six of seven practices were sustained. Experimental and comparison group differences for mean pain intensity over 72 hours following admission were sustained. Results revealed most evidence-based acute pain management practices were sustained for 18 months following implementation. Further work is needed to identify factors affecting sustainability of EBPs to guide development and testing of sustainability strategies.

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

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

ClinicalTrials.gov

2017-02-14

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

Single dose oral flurbiprofen for acute postoperative pain in adults

PubMed Central

Sultan, Asquad; McQuay, Henry J; Moore, R Andrew; Derry, Sheena

2014-01-01

Background Flurbiprofen is a non-selective non-steroidal anti-inflammatory drug (NSAID), related to ibuprofen and naproxen, used to treat acute and chronic painful conditions. There is no systematic review of its use in acute postoperative pain. Objectives To assess efficacy, duration of action, and associated adverse events of single dose oral flurbiprofen in acute postoperative pain in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to January 2009. Selection criteria Randomised, double blind, placebo-controlled trials of single dose orally administered flurbiprofen 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 (RR) 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 Eleven studies compared flurbiprofen (699 participants) with placebo (362 participants) in studies lasting 6 to 12 hours. Studies were of adequate reporting quality, and most participants had pain following dental extractions. The dose of flurbiprofen used was 25 mg to 100 mg, with most information for 50 mg and 100 mg. The NNT for at least 50% pain relief over 4 to 6 hours for flurbiprofen 50 mg compared with placebo (692 participants) was 2.7 (2.3 to 3.3) and for 100 mg (416 participants) it was 2.5 (2.0 to 3.1). With flurbiprofen 50 mg and 100 mg 65% to 70% of participants experienced at least 50% pain relief, compared with 25% to 30% with placebo. Rescue medication was used by 25

The Feasibility of performing resistance exercise with acutely ill hospitalized older adults

PubMed Central

Mallery, Laurie H; MacDonald, Elizabeth A; Hubley-Kozey, Cheryl L; Earl, Marie E; Rockwood, Kenneth; MacKnight, Chris

2003-01-01

Background For older adults, hospitalization frequently results in deterioration of mobility and function. Nevertheless, there are little data about how older adults exercise in the hospital and definitive studies are not yet available to determine what type of physical activity will prevent hospital related decline. Strengthening exercise may prevent deconditioning and Pilates exercise, which focuses on proper body mechanics and posture, may promote safety. Methods A hospital-based resistance exercise program, which incorporates principles of resistance training and Pilates exercise, was developed and administered to intervention subjects to determine whether acutely-ill older patients can perform resistance exercise while in the hospital. Exercises were designed to be reproducible and easily performed in bed. The primary outcome measures were adherence and participation. Results Thirty-nine ill patients, recently admitted to an acute care hospital, who were over age 70 [mean age of 82.0 (SD= 7.3)] and ambulatory prior to admission, were randomized to the resistance exercise group (19) or passive range of motion (ROM) group (20). For the resistance exercise group, participation was 71% (p = 0.004) and adherence was 63% (p = 0.020). Participation and adherence for ROM exercises was 96% and 95%, respectively. Conclusion Using a standardized and simple exercise regimen, selected, ill, older adults in the hospital are able to comply with resistance exercise. Further studies are needed to determine if resistance exercise can prevent or treat hospital-related deterioration in mobility and function. PMID:14531932

Role of the Cellular Prion Protein in Oligodendrocyte Precursor Cell Proliferation and Differentiation in the Developing and Adult Mouse CNS

PubMed Central

Bribián, Ana; Gavín, Rosalina; Reina, Manuel; García-Verdugo, José Manuel; Torres, Juan María; de Castro, Fernando; del Río, José Antonio

2012-01-01

There are numerous studies describing the signaling mechanisms that mediate oligodendrocyte precursor cell (OPC) proliferation and differentiation, although the contribution of the cellular prion protein (PrPc) to this process remains unclear. PrPc is a glycosyl-phosphatidylinositol (GPI)-anchored glycoprotein involved in diverse cellular processes during the development and maturation of the mammalian central nervous system (CNS). Here we describe how PrPc influences oligodendrocyte proliferation in the developing and adult CNS. OPCs that lack PrPc proliferate more vigorously at the expense of a delay in differentiation, which correlates with changes in the expression of oligodendrocyte lineage markers. In addition, numerous NG2-positive cells were observed in cortical regions of adult PrPc knockout mice, although no significant changes in myelination can be seen, probably due to the death of surplus cells. PMID:22529900

Decitabine in Treating Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia

ClinicalTrials.gov

2013-09-27

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); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

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

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

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

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

ClinicalTrials.gov

2017-05-30

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

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

ClinicalTrials.gov

2018-04-20

Acute Myeloid 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 t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; 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

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

ClinicalTrials.gov

2017-04-25

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

Exploring how nurses assess, monitor and manage acute pain for adult critically ill patients in the emergency department: protocol for a mixed methods study.

PubMed

Varndell, Wayne; Fry, Margaret; Elliott, Doug

2017-08-01

Many critically ill patients experience moderate to severe acute pain that is frequently undetected and/or undertreated. Acute pain in this patient cohort not only derives from their injury and/or illness, but also as a consequence of delivering care whilst stabilising the patient. Emergency nurses are increasingly responsible for the safety and wellbeing of critically ill patients, which includes assessing, monitoring and managing acute pain. How emergency nurses manage acute pain in critically ill adult patients is unknown. The objective of this study is to explore how emergency nurses manage acute pain in critically ill patients in the Emergency Department. In this paper, we provide a detailed description of the methods and protocol for a multiphase sequential mixed methods study, exploring how emergency nurses assess, monitor and manage acute pain in critically ill adult patients. The objective, method, data collection and analysis of each phase are explained. Justification of each method and data integration is described. Synthesis of findings will generate a comprehensive picture of how emergency nurses' perceive and manage acute pain in critically ill adult patients. The results of this study will form a knowledge base to expand theory and inform research and practice.

Acute chest pain after bench press exercise in a healthy young adult.

PubMed

Smereck, Janet A; Papafilippaki, Argyro; Sudarshan, Sawali

2016-01-01

Bench press exercise, which involves repetitive lifting of weights to full arm extension while lying supine on a narrow bench, has been associated with complications ranging in acuity from simple pectoral muscle strain, to aortic and coronary artery dissection. A 39-year-old man, physically fit and previously asymptomatic, presented with acute chest pain following bench press exercise. Diagnostic evaluation led to the discovery of critical multivessel coronary occlusive disease, and subsequently, highly elevated levels of lipoprotein (a). Judicious use of ancillary testing may identify the presence of "high-risk" conditions in a seemingly "low-risk" patient. Emergency department evaluation of the young adult with acute chest pain must take into consideration an extended spectrum of potential etiologies, so as to best guide appropriate management.

Disability in older adults with acute low back pain: the study Back Complaints in the Elderly - (Brazil).

PubMed

Aguiar, Alessandra Regina Silva Araujo; Ribeiro-Samora, Giane Amorim; Pereira, Leani Souza Maximo; Godinho, Larissa Birro; Assis, Marcella Guimarães

The increase in the older adult and oldest old population in Brazil is growing. This phenomenon may be accompanied by an increase in musculoskeletal symptoms such as low back pain. This condition is usually associated with disability. To verify the association between pain intensity and disability in older adults with acute low back pain and assess whether these variables differ depending on the age group and marital status. This is a cross-sectional study conducted with 532 older adults with acute low back pain episodes. Pain intensity was assessed through the Numeric Pain Scale and disability through the Late Life Function and Disability Instrument, which shows two dimensions: "frequency" and "limitation" in performing activities. The association between pain and disability was analyzed. For the interaction effect between age groups and marital status, we found that the oldest old living with a partner performed activities of the personal domain less often compared to the oldest old living alone. The oldest old group living with a partner had a lower frequency of performing activities, but did not report feeling limited. The association of pain with disability was minimal (rho<0.20) and thus considered irrelevant. Disability in older adults with acute low back pain was influenced by the interaction between age groups and marital status and is not associated with pain intensity. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Dasatinib, Cytarabine, and Idarubicin in Treating Patients With High-Risk Acute Myeloid Leukemia

ClinicalTrials.gov

2018-05-04

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

Identification of ETV6-RUNX1-like and DUX4-rearranged subtypes in paediatric B-cell precursor acute lymphoblastic leukaemia.

PubMed

Lilljebjörn, Henrik; Henningsson, Rasmus; Hyrenius-Wittsten, Axel; Olsson, Linda; Orsmark-Pietras, Christina; von Palffy, Sofia; Askmyr, Maria; Rissler, Marianne; Schrappe, Martin; Cario, Gunnar; Castor, Anders; Pronk, Cornelis J H; Behrendtz, Mikael; Mitelman, Felix; Johansson, Bertil; Paulsson, Kajsa; Andersson, Anna K; Fontes, Magnus; Fioretos, Thoas

2016-06-06

Fusion genes are potent driver mutations in cancer. In this study, we delineate the fusion gene landscape in a consecutive series of 195 paediatric B-cell precursor acute lymphoblastic leukaemia (BCP ALL). Using RNA sequencing, we find in-frame fusion genes in 127 (65%) cases, including 27 novel fusions. We describe a subtype characterized by recurrent IGH-DUX4 or ERG-DUX4 fusions, representing 4% of cases, leading to overexpression of DUX4 and frequently co-occurring with intragenic ERG deletions. Furthermore, we identify a subtype characterized by an ETV6-RUNX1-like gene-expression profile and coexisting ETV6 and IKZF1 alterations. Thus, this study provides a detailed overview of fusion genes in paediatric BCP ALL and adds new pathogenetic insights, which may improve risk stratification and provide therapeutic options for this disease.

Management of Adults With Acute Migraine in the Emergency Department: The American Headache Society Evidence Assessment of Parenteral Pharmacotherapies.

PubMed

Orr, Serena L; Friedman, Benjamin W; Christie, Suzanne; Minen, Mia T; Bamford, Cynthia; Kelley, Nancy E; Tepper, Deborah

2016-06-01

To provide evidence-based treatment recommendations for adults with acute migraine who require treatment with injectable medication in an emergency department (ED). We addressed two clinically relevant questions: (1) Which injectable medications should be considered first-line treatment for adults who present to an ED with acute migraine? (2) Do parenteral corticosteroids prevent recurrence of migraine in adults discharged from an ED? The American Headache Society convened an expert panel of authors who defined a search strategy and then performed a search of Medline, Embase, the Cochrane database and clinical trial registries from inception through 2015. Identified articles were rated using the American Academy of Neurology's risk of bias tool. For each medication, the expert panel determined likelihood of efficacy. Recommendations were created accounting for efficacy, adverse events, availability of alternate therapies, and principles of medication action. The search identified 68 unique randomized controlled trials utilizing 28 injectable medications. Of these, 19 were rated class 1 (low risk of bias), 21 were rated class 2 (higher risk of bias), and 28 were rated class 3 (highest risk of bias). Metoclopramide, prochlorperazine, and sumatriptan each had multiple class 1 studies supporting acute efficacy, as did dexamethasone for prevention of headache recurrence. All other medications had lower levels of evidence. Intravenous metoclopramide and prochlorperazine, and subcutaneous sumatriptan should be offered to eligible adults who present to an ED with acute migraine (Should offer-Level B). Dexamethasone should be offered to these patients to prevent recurrence of headache (Should offer-Level B). Because of lack of evidence demonstrating efficacy and concern about sub-acute or long-term sequelae, injectable morphine and hydromorphone are best avoided as first-line therapy (May avoid-Level C). © 2016 American Headache Society.

Lead decreases cell survival, proliferation, and neuronal differentiation of primary cultured adult neural precursor cells through activation of the JNK and p38 MAP kinases

PubMed Central

Engstrom, Anna; Wang, Hao; Xia, Zhengui

2015-01-01

Adult hippocampal neurogenesis is the process whereby adult neural precursor cells (aNPCs) in the subgranular zone (SGZ) of the dentate gyrus (DG) generate adult-born, functional neurons in the hippocampus. This process is modulated by various extracellular and intracellular stimuli, and the adult-born neurons have been implicated in hippocampus-dependent learning and memory. However, studies on how neurotoxic agents affect this process and the underlying mechanisms are limited. The goal of this study was to determine whether lead, a heavy metal, directly impairs critical processes in adult neurogenesis and to characterize the underlying signaling pathways using primary cultured SGZ-aNPCs isolated from adult mice. We report here that lead significantly increases apoptosis and inhibits proliferation in SGZ-aNPCs. In addition, lead significantly impairs spontaneous neuronal differentiation and maturation. Furthermore, we found that activation of the c-Jun NH2-terminal kinase (JNK) and p38 mitogen activated protein (MAP) kinase signaling pathways are important for lead cytotoxicity. Our data suggest that lead can directly act on adult neural stem cells and impair critical processes in adult hippocampal neurogenesis, which may contribute to its neurotoxicity and adverse effects on cognition in adults. PMID:25967738

Adult neurogenesis and the vascular Nietzsche.

PubMed

Palmer, Theo D

2002-06-13

Adult neurogenesis is mediated by immature neural precursors that divide within the residual germinal matrices of the brain. In the paper by in this issue of Neuron, the "cause and effect" of adult neurogenesis takes a major step forward with the description of a vascular signaling network that influences neuronal precursor migration and fate.

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

Brain-Derived Neurotrophic Factor Promotes Vasculature-Associated Migration of Neuronal Precursors toward the Ischemic Striatum

PubMed Central

Grade, Sofia; Weng, Yuan C.; Snapyan, Marina; Kriz, Jasna; Malva, João O.; Saghatelyan, Armen

2013-01-01

Stroke induces the recruitment of neuronal precursors from the subventricular zone (SVZ) into the ischemic striatum. In injured areas, de-routed neuroblasts use blood vessels as a physical scaffold to their migration, in a process that resembles the constitutive migration seen in the rostral migratory stream (RMS). The molecular mechanism underlying injury-induced vasculature-mediated migration of neuroblasts in the post-stroke striatum remains, however, elusive. Using adult mice we now demonstrate that endothelial cells in the ischemic striatum produce brain-derived neurotrophic factor (BDNF), a neurotrophin that promotes the vasculature-mediated migration of neuronal precursors in the RMS, and that recruited neuroblasts maintain expression of p75NTR, a low-affinity receptor for BDNF. Reactive astrocytes, which are widespread throughout the damaged area, ensheath blood vessels and express TrkB, a high-affinity receptor for BDNF. Despite the absence of BDNF mRNA, we observed strong BDNF immunolabeling in astrocytes, suggesting that these glial cells trap extracellular BDNF. Importantly, this pattern of expression is reminiscent of the adult RMS, where TrkB-expressing astrocytes bind and sequester vasculature-derived BDNF, leading to the entry of migrating cells into the stationary phase. Real-time imaging of cell migration in acute brain slices revealed a direct role for BDNF in promoting the migration of neuroblasts to ischemic areas. We also demonstrated that cells migrating in the ischemic striatum display higher exploratory behavior and longer stationary periods than cells migrating in the RMS. Our findings suggest that the mechanisms involved in the injury-induced vasculature-mediated migration of neuroblasts recapitulate, at least partially, those observed during constitutive migration in the RMS. PMID:23383048

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

Sex impacts the flow-mediated dilation response to acute aerobic exercise in older adults.

PubMed

Yoo, Jeung-Ki; Pinto, Michelle M; Kim, Han-Kyul; Hwang, Chueh-Lung; Lim, Jisok; Handberg, Eileen M; Christou, Demetra D

2017-05-01

There is growing evidence of sex differences in the chronic effect of aerobic exercise on endothelial function (flow-mediated dilation; FMD) in older adults, but whether there are sex differences also in the acute effect of aerobic exercise on FMD in older adults is unknown. The purpose of this study was to test the hypothesis that sex modulates the FMD response to acute aerobic exercise in older adults. Thirteen older men and fifteen postmenopausal women (67±1 vs. 65±2years, means±SE, P=0.6), non-smokers, free of major clinical disease, participated in this randomized crossover study. Brachial artery FMD was measured: 1) prior to exercise; 2) 20min after a single bout of high-intensity interval training (HIIT; 40min; 4×4 intervals 90% peak heart rate (HRpeak)), moderate-intensity continuous training (MICT; 47min 70% HRpeak) and low-intensity continuous training (LICT; 47min 50% HRpeak) on treadmill; and 3) following 60-min recovery from exercise. In older men, FMD was attenuated by 45% following HIIT (5.95±0.85 vs. 3.27±0.52%, P=0.003) and by 37% following MICT (5.97±0.87 vs. 3.73±0.47%, P=0.03; P=0.9 for FMD response to HIIT vs. MICT) and was normalized following 60-min recovery (P=0.99). In postmenopausal women, FMD did not significantly change in response to HIIT (4.93±0.55 vs. 6.31±0.57%, P=0.14) and MICT (5.32±0.62 vs. 5.60±0.68%, P=0.99). In response to LICT, FMD did not change in postmenopausal women nor older men (5.21±0.64 vs. 6.02±0.73%, P=0.7 and 5.70±0.80 vs. 5.55±0.67%, P=0.99). In conclusion, sex and exercise intensity influence the FMD response to acute aerobic exercise in older adults. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Increases in anxiety-like behavior induced by acute stress are reversed by ethanol in adolescent but not adult rats.

PubMed

Varlinskaya, Elena I; Spear, Linda P

2012-01-01

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. Copyright © 2011 Elsevier Inc. All rights reserved.

Selinexor and Chemotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

ClinicalTrials.gov

2018-04-02

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); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

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

ClinicalTrials.gov

2017-06-12

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

Nanoscale liposomal formulation of a SYK P-site inhibitor against B-precursor leukemia

PubMed Central

Qazi, Sanjive; Cely, Ingrid; Sahin, Kazim; Shahidzadeh, Anoush; Ozercan, Ibrahim; Yin, Qian; Gaynon, Paul; Termuhlen, Amanda; Cheng, Jianjun

2013-01-01

We report preclinical proof of principle for effective treatment of B-precursor acute lymphoblastic leukemia (ALL) by targeting the spleen tyrosine kinase (SYK)–dependent antiapoptotic blast cell survival machinery with a unique nanoscale pharmaceutical composition. This nanoscale liposomal formulation (NLF) contains the pentapeptide mimic 1,4-Bis (9-O dihydroquinidinyl) phthalazine/hydroquinidine 1,4-phathalazinediyl diether (C61) as the first and only selective inhibitor of the substrate binding P-site of SYK. The C61 NLF exhibited a very favorable pharmacokinetic and safety profile in mice, induced apoptosis in primary B-precursor ALL blast cells taken directly from patients as well as in vivo clonogenic ALL xenograft cells, destroyed the in vivo clonogenic fraction of ALL blast cells, and, at nontoxic dose levels, exhibited potent in vivo antileukemic activity against patient-derived ALL cells in xenograft models of aggressive B-precursor ALL. Our findings establish SYK as an attractive molecular target for therapy of B-precursor ALL. Further development of the C61 NLF may provide the foundation for therapeutic innovation against therapy-refractory B-precursor ALL. PMID:23568490

Parvovirus B19 infection as a cause of acute myositis in an adult.

PubMed

Cakirca, Mustafa; Karatoprak, Cumali; Ugurlu, Serdal; Zorlu, Mehmet; Kıskaç, Muharrem; Çetin, Güven

2015-01-01

Parvovirus B19 infection is often asymptomatic, but clinical expressions may include transient aplastic crisis, erythema infectiosum, non-immune hydrops fetalis, and chronic red cell aplasia. This virus has also been associated with rheumatoid arthritis and other autoimmune connective tissue diseases; however, we could not identify any acute adult myositis case developed after a Parvovirus B19 infection in the literature. For this reason, we would like to present a rare case of acute myositis developed after Parvovirus B19 infection. In patients presenting with symptoms of fever, rash on the legs and myositis, viral infections such as Parvovirus B19 should be kept in mind. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

Community-acquired acute kidney injury in adults in Africa.

PubMed

Adu, Dwomoa; Okyere, Perditer; Boima, Vincent; Matekole, Michael; Osafo, Charlotte

We review recent published data on demographics, causes, diagnoses, treatment, and outcome of acute kidney injury (AKI) in Africa. A review of the incidence, etiology, diagnoses, and treatment of AKI in adults in Africa from studies published between the years 2000 and 2015. The incidence of AKI in hospitalized patients in Africa ranges from 0.3 to 1.9% in adults. Between 70 and 90% of cases of AKI are community acquired. Most patients with AKI are young with a weighted mean age of 41.3 standard deviation (SD) 9.3 years, and a male to female ratio of 1.2 : 1.0. Medical causes account for between 65 and 80% of causes of AKI. This is followed by obstetric causes in 5 - 27% of cases and surgical causes in 2 - 24% of cases. In the reported studies, between 17 and 94% of patients who needed dialysis received this. The mortality of AKI in adults in Africa ranged from 11.5 to 43.5%. Most reported cases of AKI in Africa originate in the community. The low incidence of hospital-acquired AKI is likely to be due to under ascertainment. Most patients with AKI in Africa are young and have a single precipitating cause. Prominent among these are infection, pregnancy complications and nephrotoxins. Early treatment can improve clinical outcomes.

Management of acute lymphoblastic leukemia in young adults.

PubMed

Muffly, Lori S; Reizine, Natalie; Stock, Wendy

2018-02-01

Substantial interest in acute lymphoblastic leukemia (ALL) in young adults (YAs) and investigations focused on this patient population have resulted in therapeutic advancements that are changing the management paradigm and improving outcomes. The pediatric ALL approach is feasible and effective when administered by medical oncologists. Advanced diagnostics and minimal residual disease measurements aid in prognostication and have resulted in shifting recommendations regarding allogeneic hematopoietic cell transplant in first remission. Blinatumomab, inotuzumab, and chimeric antigen receptor T-cell therapies are transforming the treatment of relapsed/refractory ALL. This comprehensive review of the current management of ALL in YAs summarizes recent scientific developments and clinical trial findings related to ALL biology, frontline management approaches, novel therapies, and supportive care specific to this patient population. Finally, a practical guide to modern YA management for practicing clinicians is provided.

Bioelectrical Impedance Measurement for Predicting Treatment Outcome in Patients With Newly Diagnosed Acute Leukemia

ClinicalTrials.gov

2018-04-26

Acute Undifferentiated Leukemia; 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); Mast Cell Leukemia; Myeloid/NK-cell Acute Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

Lenalidomide and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

ClinicalTrials.gov

2018-06-18

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); Recurrent Adult Acute Myeloid Leukemia

Absence of Genomic Ikaros/IKZF1 Deletions in Pediatric B-Precursor Acute Lymphoblastic Leukemia

PubMed Central

Qazi, Sanjive; Ma, Hong; Uckun, Fatih M

2013-01-01

Here we report the results of gene expression analyses using multiple probesets aimed at determining the incidence of Ikaros/IKZF1 deletions in pediatric B-precursor acute lymphoblastic leukemia (BPL). Primary leukemia cells from 122 Philadelphia chromosome (Ph)+ BPL patients and 237 Ph− BPL patients as well as normal hematopoietic cells from 74 normal non-leukemic bone marrow specimens were organized according to expression levels of IKZF1 transcripts utilizing two-way hierarchical clustering technique to identify specimens with low IKZF1 expression for the 10 probesets interrogating Exons 1 through 4 and Exon 8. Our analysis demonstrated no changes in expression that would be expected from homozygous or heterozygous deletions of IKZF1 in primary leukemic cells. Similar results were obtained in gene expression analysis of primary leukemic cells from 20 Ph+ positive and 155 Ph− BPL patients in a validation dataset. Taken together, our gene expression analyses in 534 pediatric BPL cases, including 142 cases with Ph+ BPL, contradict previous reports that were based on SNP array data and suggested that Ph+ pediatric BPL is characterized by a high frequency of homozygous or heterozygous IKZF1 deletions. Further, exon-specific genomic PCR analysis of primary leukemia cells from 21 high-risk pediatric BPL patients and 11 standard-risk pediatric BPL patients, and 8 patients with infant BPL did not show any evidence for homozygous IKZF1 locus deletions. Nor was there any evidence for homozygous or heterozygous intragenic IKZF1 deletions. PMID:24478816

Idarubicin, Cytarabine, and Pravastatin Sodium in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

ClinicalTrials.gov

2017-10-16

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); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Refractory Anemia With Excess Blasts; Untreated Adult Acute Myeloid Leukemia

Acute pancreatitis in children and adolescents

PubMed Central

Suzuki, Mitsuyoshi; Sai, Jin Kan; Shimizu, Toshiaki

2014-01-01

In this Topic Highlight, the causes, diagnosis, and treatment of acute pancreatitis in children are discussed. Acute pancreatitis should be considered during the differential diagnosis of abdominal pain in children and requires prompt treatment because it may become life-threatening. The etiology, clinical manifestations, and course of acute pancreatitis in children are often different than in adults. Therefore, the specific features of acute pancreatitis in children must be considered. The etiology of acute pancreatitis in children is often drugs, infections, trauma, or anatomic abnormalities. Diagnosis is based on clinical symptoms (such as abdominal pain and vomiting), serum pancreatic enzyme levels, and imaging studies. Several scoring systems have been proposed for the assessment of severity, which is useful for selecting treatments and predicting prognosis. The basic pathogenesis of acute pancreatitis does not greatly differ between adults and children, and the treatments for adults and children are similar. In large part, our understanding of the pathology, optimal treatment, assessment of severity, and outcome of acute pancreatitis in children is taken from the adult literature. However, we often find that the common management of adult pancreatitis is difficult to apply to children. With advances in diagnostic techniques and treatment methods, severe acute pancreatitis in children is becoming better understood and more controllable. PMID:25400985

Clofarabine in Adult Patients With Advanced Solid Tumors

ClinicalTrials.gov

2014-02-04

Solid Tumors; Leukemia, Lymphocytic, Acute, Pediatric; Leukemia, Lymphocytic, Acute, Adult; Leukemia, Myelocytic, Acute, Pediatric; Leukemia, Myelocytic, Acute, Adult; Myelodysplastic Syndromes, Adult

Risk-Based Classification System of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

ClinicalTrials.gov

2018-02-22

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

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

Acute and Fractionated Exposure to High-LET 56Fe HZE-Particle Radiation Both Result in Similar Long-Term Deficits in Adult Hippocampal Neurogenesis

PubMed Central

Rivera, Phillip D.; Shih, Hung-Ying; LeBlanc, Junie A.; Cole, Mara G.; Amaral, Wellington Z.; Mukherjee, Shibani; Zhang, Shichuan; Lucero, Melanie J.; DeCarolis, Nathan A.; Chen, Benjamin P. C.; Eisch, Amelia J.

2014-01-01

Astronauts on multi-year interplanetary missions will be exposed to a low, chronic dose of high-energy, high-charge particles. Studies in rodents show acute, nonfractionated exposure to these particles causes brain changes such as fewer adult-generated hippocampal neurons and stem cells that may be detrimental to cognition and mood regulation and thus compromise mission success. However, the influence of a low, chronic dose of these particles on neurogenesis and stem cells is unknown. To examine the influence of galactic cosmic radiation on neurogenesis, adult-generated stem and progenitor cells in Nestin-CreERT2/R26R-YFP transgenic mice were inducibly labeled to allow fate tracking. Mice were then sham exposed or given one acute 100 cGy 56Fe-particle exposure or five fractionated 20 cGy 56Fe-particle exposures. Adult-generated hippocampal neurons and stem cells were quantified 24 h or 3 months later. Both acute and fractionated exposure decreased the amount of proliferating cells and immature neurons relative to sham exposure. Unexpectedly, neither acute nor fractionated exposure decreased the number of adult neural stem cells relative to sham expsoure. Our findings show that single and fractionated exposures of 56Fe-particle irradiation are similarly detrimental to adult-generated neurons. Implications for future missions and ground-based studies in space radiation are discussed. PMID:24320054

Phase I Combination of Midostaurin, Bortezomib, and Chemo in Relapsed/Refractory Acute Myeloid Leukemia

ClinicalTrials.gov

2016-07-04

Acute Myeloid Leukemia; Acute Myeloid Leukemia With Multilineage Dysplasia Following; Myelodysplastic Syndrome; 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); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

Reinduction therapy for adult acute leukemia with adriamycin, vincristine, and prednisone: a Southwest Oncology Group study.

PubMed

Elias, L; Shaw, M T; Raab, S O

1979-08-01

In an attempt to improve remissions and survivals in previously treated patients with adult acute leukemia, we gave Adriamycin, vincristine, and prednisone for induction therapy, followed by 6-mercaptopurine and methotrexate for maintenance therapy to patients attaining complete remission (CR). The study group consisted of 18 patients with acute myeloblastic leukemia (AML), ten with acute lymphoblastic leukemia, and one with acute undifferentiated leukemia. Only one patient had previously received Adriamycin. Overall, there were ten CRs and two partial remissions. The five CRs and one partial remission in patients with AML occurred among those with one prior induction attempt; none of the eight AML patients with more than one prior induction attempt responded. The actuarial median duration of CR was 15 weeks and was similar for AML and acute lymphoblastic leukemia patients. Responders had a longer median survival (30 weeks) than nonresponders (9 weeks). Thus, although a reasonable number of responses in previously treated patients were obtained with this program, improvements in maintenance therapy are clearly needed.

Idarubicin, Cytarabine, and Tipifarnib in Treating Patients With Newly Diagnosed Myelodysplastic Syndromes or Acute Myeloid Leukemia

ClinicalTrials.gov

2014-05-09

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); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

[Antipsychotic Treatment of the Adult Patient in the Acute Phase of Schizophrenia].

PubMed

Bohórquez Peñaranda, Adriana; Gómez Restrepo, Carlos; García Valencia, Jenny; Jaramillo González, Luis Eduardo; de la Hoz, Ana María; Arenas, Álvaro; Tamayo Martínez, Nathalie

2014-01-01

To determine the efficacy and safety of different antipsychotic drugs in the management of patients diagnosed with schizophrenia in the acute phase. To formulate evidence-based recommendations on the antipsychotic (AP) drug management strategies for the treatment of the adult diagnosed with schizophrenia in the acute phase. Clinical practice guidelines were prepared, using the guidelines of the Methodology Guide of the Ministry of Health and Social Protection, in order to identify, synthesise, and evaluate the evidence and formulate recommendations as regards the management and follow-up of adult patients diagnosed with schizophrenia. The evidence of the NICE 82 guideline was adopted and updated, which answered the question on the management of the acute phase of adults with a diagnosis of schizophrenia. The evidence and its level were presented to the Guideline Development Group (GDG) in order to formulate recommendations following the methodology proposed by the GRADE approach. Clozapine, olanzapine, risperidone, ziprasidone, amisulpride, paliperidone, haloperidol, quetiapine, and aripiprazole were more effective than placebo for the majority of psychotic symptoms and the abandonment of treatment, but asenapine was not. Paliperidone, risperidone, quetiapine, clozapine, and olanzapine showed significant increases in weight compared to placebo. Haloperidol, risperidone, ziprasidone, and paliperidone had a higher risk of extrapyramidal symptoms than placebo. There was a significant risk of sedation or drowsiness with, risperidone, haloperidol, ziprasidone, quetiapine, olanzapine, and clozapine in the comparisons with placebo. Of the results of the comparisons between AP, it was shown that clozapine and paliperidone had a clinically significant effect compared to haloperidol and quetiapine, respectively. Olanzapine and risperidone had a lower risk of abandoning the treatment in general, and due to adverse reactions in two comparisons of each one, haloperidol was the

CD19/CD22 Chimeric Antigen Receptor T Cells and Chemotherapy in Treating Children or Young Adults With Recurrent or Refractory CD19 Positive B Acute Lymphoblastic Leukemia

ClinicalTrials.gov

2017-11-20

B Acute Lymphoblastic Leukemia; CD19 Positive; Minimal Residual Disease; Philadelphia Chromosome Positive; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Refractory Acute Lymphoblastic Leukemia

Lead decreases cell survival, proliferation, and neuronal differentiation of primary cultured adult neural precursor cells through activation of the JNK and p38 MAP kinases.

PubMed

Engstrom, Anna; Wang, Hao; Xia, Zhengui

2015-08-01

Adult hippocampal neurogenesis is the process whereby adult neural precursor cells (aNPCs) in the subgranular zone (SGZ) of the dentate gyrus (DG) generate adult-born, functional neurons in the hippocampus. This process is modulated by various extracellular and intracellular stimuli, and the adult-born neurons have been implicated in hippocampus-dependent learning and memory. However, studies on how neurotoxic agents affect this process and the underlying mechanisms are limited. The goal of this study was to determine whether lead, a heavy metal, directly impairs critical processes in adult neurogenesis and to characterize the underlying signaling pathways using primary cultured SGZ-aNPCs isolated from adult mice. We report here that lead significantly increases apoptosis and inhibits proliferation in SGZ-aNPCs. In addition, lead significantly impairs spontaneous neuronal differentiation and maturation. Furthermore, we found that activation of the c-Jun NH2-terminal kinase (JNK) and p38 mitogen activated protein (MAP) kinase signaling pathways are important for lead cytotoxicity. Our data suggest that lead can directly act on adult neural stem cells and impair critical processes in adult hippocampal neurogenesis, which may contribute to its neurotoxicity and adverse effects on cognition in adults. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

ClinicalTrials.gov

2018-04-20

Acute Lymphoblastic Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult B Acute Lymphoblastic Leukemia; Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;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

Outcome for children and young people with Early T-cell precursor acute lymphoblastic leukaemia treated on a contemporary protocol, UKALL 2003.

PubMed

Patrick, Katharine; Wade, Rachel; Goulden, Nick; Mitchell, Chris; Moorman, Anthony V; Rowntree, Clare; Jenkinson, Sarah; Hough, Rachael; Vora, Ajay

2014-08-01

We investigated the outcome for children and young people with Early T-precursor acute lymphoblastic leukaemia (ETP-ALL), a recently described poor prognosis sub-group of T-ALL, treated on a contemporary protocol, UKALL 2003. After a median follow-up of 4 years and 10 months, the ETP sub-group, representing 16% of T-ALL patients, had non-significantly inferior 5-year event-free survival (76·7% vs. 84·6%, P = 0·2) and overall survival (82·4% vs. 90·9%, P = 0·1), and a higher relapse rate (18·6% vs. 9·6%, P = 0·1) compared to typical T-ALL. ETP-ALL has an intermediate risk outcome, which does not warrant experimental treatment or first remission allogeneic transplant for the group universally. © 2014 John Wiley & Sons Ltd.

Np95/Uhrf1 regulates tumor suppressor gene expression of neural stem/precursor cells, contributing to neurogenesis in the adult mouse brain.

PubMed

Murao, Naoya; Matsubara, Shuzo; Matsuda, Taito; Noguchi, Hirofumi; Mutoh, Tetsuji; Mutoh, Masahiro; Koseki, Haruhiko; Namihira, Masakazu; Nakashima, Kinichi

2018-05-31

Adult neurogenesis is a process of generating new neurons from neural stem/precursor cells (NS/PCs) in restricted adult brain regions throughout life. It is now generally known that adult neurogenesis in the hippocampal dentate gyrus (DG) and subventricular zone participates in various higher brain functions, such as learning and memory formation, olfactory discrimination and repair after brain injury. However, the mechanisms underlying adult neurogenesis remain to be fully understood. Here, we show that Nuclear protein 95 KDa (Np95, also known as UHRF1 or ICBP90), which is an essential protein for maintaining DNA methylation during cell division, is involved in multiple processes of adult neurogenesis. Specific ablation of Np95 in adult NS/PCs (aNS/PCs) led to a decrease in their proliferation and an impairment of neuronal differentiation and to suppression of neuronal maturation associated with the impairment of dendritic formation in the hippocampal DG. We also found that deficiency of Np95 in NS/PCs increased the expression of tumor suppressor genes p16 and p53, and confirmed that expression of these genes in NS/PCs recapitulates the phenotype of Np95-deficient NS/PCs. Taken together, our findings suggest that Np95 plays an essential role in proliferation and differentiation of aNS/PCs through the regulation of tumor suppressor gene expression in adult neurogenesis. Copyright © 2018 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.

A Comprehensive Comparison of the Efficacy and Tolerability of Racecadotril with Other Treatments of Acute Diarrhea in Adults

PubMed Central

Fischbach, Wolfgang; Andresen, Viola; Eberlin, Marion; Mueck, Tobias; Layer, Peter

2016-01-01

Racecadotril is a guideline-recommended treatment to alleviate symptoms of acute diarrhea. A systematic review of randomized studies was performed comparing efficacy and safety of treatment with racecadotril to that with placebo or active treatments in adults. In five double-blind studies, racecadotril and placebo had comparable tolerability, but racecadotril was more effective. This was consistent across multiple efficacy parameters including duration of diarrhea, number of diarrheic stools, abdominal pain, and meteorism; it was also consistent across countries in Africa, Asia, and Europe. In six randomized studies in outpatients comparing racecadotril to loperamide, resolution of symptoms occurred with similar speed and efficacy; however, racecadotril treatment was associated with less rebound constipation and less abdominal discomfort. The seventh comparative study performed in geriatric nursing home residents reported a superior efficacy of racecadotril. In direct comparison with Saccharomyces boulardii treatment, racecadotril exhibited similar tolerability but was more efficacious. One study compared racecadotril to octreotide in patients with acute diarrhea requiring hospitalization, rehydration, and antibiotic treatment; in this cohort, octreotide was more efficacious than racecadotril. In conclusion, in adults with acute diarrhea, racecadotril is more efficacious than placebo or S. boulardii, similarly efficacious as loperamide and, in patients with moderate to severe disease as add-on to antibiotics, less than octreotide. The tolerability of racecadotril is similar to that of placebo or S. boulardii and better than that of loperamide, particularly with regard to risk of rebound constipation. Taken together, these data demonstrate that racecadotril is a suitable treatment to alleviate symptoms of acute diarrhea in adults. PMID:27790616

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

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

ClinicalTrials.gov

2018-05-21

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

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

ClinicalTrials.gov

2017-06-27

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 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

Proton pump inhibitors and functional decline in older adults discharged from acute care hospitals.

PubMed

Corsonello, Andrea; Maggio, Marcello; Fusco, Sergio; Adamo, Bakhita; Amantea, Diana; Pedone, Claudio; Garasto, Sabrina; Ceda, Gian Paolo; Corica, Francesco; Lattanzio, Fabrizia; Antonelli Incalzi, Raffaele

2014-06-01

To investigate the relationship between use of proton pump inhibitors (PPIs) and incident dependency in older adults discharged from acute care hospitals. Prospective observational study. Eleven geriatric and internal medicine acute care wards located throughout Italy. Individuals (mean age 79.2 ± 5.5) who were not completely dependent at the time of discharge from participating wards (N = 401). The outcome of interest was the loss of at least one basic activity of daily living (ADL) from discharge to the end of follow-up (12 months). The relationship between PPI use and functional decline was investigated using logistic regression analysis before and after propensity score matching. Use of PPIs was significantly associated with functional decline before (odds ratio (OR) = 1.75, 95% confidence interval (CI) = 1.17-2.60) and after propensity score matching (OR = 2.44; 95% CI = 1.36-4.41). Other predictors of functional decline were hypoalbuminemia (OR = 3.10, 95% CI = 1.36-7.10 before matching, OR = 2.81, 95% CI = 1.09-7.77 after matching) and cognitive impairment (OR = 4.08, 95% CI = 1.63-10.2 before matching, OR = 6.35, 95% CI = 1.70-24.0 after matching). Use of PPIs is associated with functional decline during 12 months of follow-up in older adults discharged from acute care hospitals. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

Clofarabine, Cytarabine, and G-CSF in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

ClinicalTrials.gov

2018-02-08

Acute Myeloid Leukemia; 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 Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia

The role of Hepatitis E virus infection in Adult Americans with Acute Liver Failure

PubMed Central

Fontana, Robert John; Engle, Ronald E.; Scaglione, Steven; Araya, Victor; Shaikh, Obaid; Tillman, Holly; Attar, Nahid; Purcell, Robert H.; Lee, William M.

2016-01-01

Acute hepatitis E virus (HEV) infection is a leading cause of acute liver failure (ALF) in many developing countries yet rarely identified in Western countries. Since antibody testing for HEV infection is not routinely obtained, we hypothesized that HEV-related ALF might be present and unrecognized in North American ALF patients. Serum samples of 681 adults enrolled in the US ALF Study Group were tested for anti-HEV IgM and anti-HEV IgG levels. Subjects with a detectable anti-HEV IgM also underwent testing for HEV-RNA. Mean patient age was 41.8 years, 32.9% male, and ALF etiologies included acetaminophen hepatotoxicity (29%), indeterminate ALF (23%), idiosyncratic DILI (22%), acute HBV infection (12%), autoimmune hepatitis (12%) and pregnancy related ALF (2%). Three men ages 36, 39, and 70 demonstrated repeatedly detectable anti-HEV IgM but all were HEV RNA negative and had other putative diagnoses. The latter two subjects died within 3 and 11 days of enrollment while the 36 year old underwent emergency liver transplantation on study day 2. At admission, 294 (43.4%) of the ALF patients were anti-HEV IgG positive with the seroprevalence being highest in those from the Midwest (50%) and lowest in those from the Southeast (28%). Anti-HEV IgG + subjects were significantly older, less likely to have APAP overdose, and had a lower overall 3 week survival compared to anti-HEV IgG − subjects (63% vs 70%, p= 0.018). CONCLUSIONS Acute HEV infection is very rare in adult Americans with ALF (i.e., 0.4%) and could not be implicated in any indeterminate, autoimmune, or pregnancy-related ALF cases. Prior exposure to HEV with detectable anti-HEV IgG was significantly more common in the ALF patients compared to the general US population. PMID:27215797

Recurrent acute pancreatitis secondary to a duodenal duplication cyst in an adult. A case report and literature review

PubMed Central

Salemis, Nikolaos S; Liatsos, Christos; Kolios, Michail; Gourgiotis, Stavros

2009-01-01

Duodenal duplication cysts are rare congenital abnormalities that are most commonly diagnosed in infancy and childhood. However, in rare cases, the lesion can remain asymptomatic until adulthood. An extremely rare case of a previously healthy adult patient with recurrent acute pancreatitis, who was diagnosed with a duodenal duplication cyst is presented. At laparotomy, a duplication cyst measuring 4.8 cm × 4 cm × 4 cm was found adjacent to the ampulla of Vater. A partial cyst excision and marsupialization into the duodenal lumen was performed. The patient is healthy and asymptomatic four years after surgery. The present case illustrates the necessity of considering a duodenal duplication cyst in the differential diagnosis of recurrent acute pancreatitis in previously healthy adults. PMID:19893770

Recurrent acute pancreatitis secondary to a duodenal duplication cyst in an adult. A case report and literature review.

PubMed

Salemis, Nikolaos S; Liatsos, Christos; Kolios, Michail; Gourgiotis, Stavros

2009-11-01

Duodenal duplication cysts are rare congenital abnormalities that are most commonly diagnosed in infancy and childhood. However, in rare cases, the lesion can remain asymptomatic until adulthood. An extremely rare case of a previously healthy adult patient with recurrent acute pancreatitis, who was diagnosed with a duodenal duplication cyst is presented. At laparotomy, a duplication cyst measuring 4.8 cm x 4 cm x 4 cm was found adjacent to the ampulla of Vater. A partial cyst excision and marsupialization into the duodenal lumen was performed. The patient is healthy and asymptomatic four years after surgery. The present case illustrates the necessity of considering a duodenal duplication cyst in the differential diagnosis of recurrent acute pancreatitis in previously healthy adults.

Modern Immunotherapy of Adult B-Lineage Acute Lymphoblastic Leukemia with Monoclonal Antibodies and Chimeric Antigen Receptor Modified T Cells

PubMed Central

Maino, Elena; Scattolin, Anna Maria; Viero, Piera; Sancetta, Rosaria; Pascarella, Anna; Vespignani, Michele; Bassan, Renato

2015-01-01

The introduction of newer cytotoxic monoclonal antibodies and chimeric antigen receptor modified T cells is opening a new age in the management of B-lineage adult acute lymphoblastic leukemia. This therapeutic change must be very positively acknowledged because of the limits of intensive chemotherapy programs and allogeneic stem cell transplantation. In fact, with these traditional therapeutic tools the cure can be achieved in only 40–50% of the patients. The failure rates are particularly high in the elderly, in patients with post-induction persistence of minimal residual disease and especially in refractory/relapsed disease. The place of the novel immunotherapeutics in improving the outcome of adult patients with B-lineage acute lymphoblastic leukemia is reviewed. PMID:25574360

HLA-DR-, CD33+, CD56+, CD16- myeloid/natural killer cell acute leukemia: a previously unrecognized form of acute leukemia potentially misdiagnosed as French-American-British acute myeloid leukemia-M3.

PubMed

Scott, A A; Head, D R; Kopecky, K J; Appelbaum, F R; Theil, K S; Grever, M R; Chen, I M; Whittaker, M H; Griffith, B B; Licht, J D

1994-07-01

We have identified and characterized a previously unrecognized form of acute leukemia that shares features of both myeloid and natural killer (NK) cells. From a consecutive series of 350 cases of adult de novo acute myeloid leukemia (AML), we identified 20 cases (6%) with a unique immunophenotype: CD33+, CD56+, CD11a+, CD13lo, CD15lo, CD34+/-, HLA-DR-, CD16-. Multicolor flow cytometric assays confirmed the coexpression of myeloid (CD33, CD13, CD15) and NK cell-associated (CD56) antigens in each case, whereas reverse transcription polymerase chain reaction (RT-PCR) assays confirmed the identity of CD56 (neural cell adhesion molecule) in leukemic blasts. Although two cases expressed CD4, no case expressed CD2, CD3, or CD8 and no case showed clonal rearrangement of genes encoding the T-cell receptor (TCR beta, gamma, delta). Leukemic blasts in the majority of cases shared unique morphologic features (deeply invaginated nuclear membranes, scant cytoplasm with fine azurophilic granularity, and finely granular Sudan black B and myeloperoxidase cytochemical reactivity) that were remarkably similar to those of acute promyelocytic leukemia (APL); particularly the microgranular variant (FAB AML-M3v). However, all 20 cases lacked the t(15;17) and 17 cases tested lacked the promyelocytic/retinoic acid receptor alpha (RAR alpha) fusion transcript in RT-PCR assays; 12 cases had 46,XX or 46,XY karyotypes, whereas 2 cases had abnormalities of chromosome 17q: 1 with del(17)(q25) and the other with t(11;17)(q23;q21) and the promyelocytic leukemia zinc finger/RAR alpha fusion transcript. All cases tested (6/20), including the case with t(11;17), failed to differentiate in vitro in response to all-trans retinoic acid (ATRA), suggesting that these cases may account for some APLs that have not shown a clinical response to ATRA. Four of 6 cases tested showed functional NK cell-mediated cytotoxicity, suggesting a relationship between these unique CD33+, CD56+, CD16- acute leukemias and

Supplementation with tocotrienol-rich fraction alters the plasma levels of Apolipoprotein A-I precursor, Apolipoprotein E precursor, and C-reactive protein precursor from young and old individuals.

PubMed

Heng, Eng Chee; Karsani, Saiful Anuar; Abdul Rahman, Mariati; Abdul Hamid, Noor Aini; Hamid, Zalina; Wan Ngah, Wan Zurinah

2013-10-01

Tocotrienol possess beneficial effects not exhibited by tocopherol. In vitro studies using animal models have suggested that these effects are caused via modulation of gene and protein expression. However, human supplementation studies using tocotrienol-rich isomers are limited. This study aims to identify plasma proteins that changed in expression following tocotrienol-rich fraction (TRF) supplementation within two different age groups. Subjects were divided into two age groups-32 ± 2 (young) and 52 ± 2 (old) years old. Four subjects from each group were assigned with TRF (78% tocotrienol and 22% tocopherol, 150 mg/day) or placebo capsules for 6 months. Fasting plasma were obtained at 0, 3, and 6 months. Plasma tocopherol and tocotrienol levels were determined. Plasma proteome was resolved by 2DE, and differentially expressed proteins identified by MS. The expressions of three proteins were validated by Western blotting. Six months of TRF supplementation significantly increased plasma levels of tocopherols and tocotrienols. Proteins identified as being differentially expressed were related to cholesterol homeostasis, acute-phase response, protease inhibitor, and immune response. The expressions of Apolipoprotein A-I precursor, Apolipoprotein E precursor, and C-reactive protein precursor were validated. The old groups showed more proteins changing in expression. TRF appears to not only affect plasma levels of tocopherols and tocotrienols, but also the levels of plasma proteins. The identity of these proteins may provide insights into how TRF exerts its beneficial effects. They may also be potentially developed into biomarkers for the study of the effects and effectiveness of TRF supplementation.

L-arginine levels are diminished in adult acute vaso-occlusive sickle cell crisis in the emergency department.

PubMed

Lopez, Bernard L; Kreshak, Allyson A; Morris, Claudia R; Davis-Moon, Linda; Ballas, Samir K; Ma, Xin-Liang

2003-02-01

Paediatric studies have demonstrated that l-arginine (l-arg), the precursor to nitric oxide, is diminished in vaso-occlusive crisis (VOC). This study aimed to determine whether l-arginine levels are altered in adult VOC in the emergency department. Plasma l-arg and nitric oxide metabolite (NOx) levels were obtained in adult VOC patients presenting to the emergency department. Fifty patients had significantly low plasma l-arg (29.78 micromol/l +/- 11.21, P < 0.05 vs steady-state control = 41.16 micromol/l +/- 5.04) and significantly low plasma NOx (12.33 micromol/l +/- 10.28, P < 0.05 vs steady-state control = 25.2 +/- 2.6 micro mol/l). Neither l-arg nor NOx levels could predict VOC clinical course.

Negative regulation of TLX by IL-1β correlates with an inhibition of adult hippocampal neural precursor cell proliferation.

PubMed

Ryan, Sinead M; O'Keeffe, Gerard W; O'Connor, Caitriona; Keeshan, Karen; Nolan, Yvonne M

2013-10-01

Adult hippocampal neurogenesis is modulated by a number of intrinsic and extrinsic factors including local signalling molecules, exercise, aging and inflammation. Inflammation is also a major contributor to several hippocampal-associated disorders. Interleukin-1beta (IL-1β) is the most predominant pro-inflammatory cytokine in the brain, and an increase in its concentration is known to decrease the proliferation of both embryonic and adult hippocampal neural precursor cells (NPCs). Recent research has focused on the role of nuclear receptors as intrinsic regulators of neurogenesis, and it is now established that the orphan nuclear receptor TLX is crucial in maintaining the NPC pool in neurogenic brain regions. To better understand the involvement of TLX in IL-1β-mediated effects on hippocampal NPC proliferation, we examined hippocampal NPC proliferation and TLX expression in response to IL-1β treatment in an adult rat hippocampal neurosphere culture system. We demonstrate that IL-1β reduced the proliferation of hippocampal NPCs and TLX expression in a dose and time-dependent manner and that co-treatment with IL-1β receptor antagonist or IL-1 receptor siRNA prevented these effects. We also report a dose-dependent effect of IL-1β on the composition of cell phenotypes in the culture and on expression of TLX in these cells. This study thus provides evidence of an involvement of TLX in IL-1β-induced changes in adult hippocampal neurogenesis, and offers mechanistic insight into disorders in which neuroinflammation and alterations in neurogenesis are characteristic features. Copyright © 2013 Elsevier Inc. All rights reserved.

PS-341 in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia in Blast Phase, or Myelodysplastic Syndrome

ClinicalTrials.gov

2013-01-22

Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; 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

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

ClinicalTrials.gov

2017-11-13

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 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

Microglia modulate hippocampal neural precursor activity in response to exercise and aging.

PubMed

Vukovic, Jana; Colditz, Michael J; Blackmore, Daniel G; Ruitenberg, Marc J; Bartlett, Perry F

2012-05-09

Exercise has been shown to positively augment adult hippocampal neurogenesis; however, the cellular and molecular pathways mediating this effect remain largely unknown. Previous studies have suggested that microglia may have the ability to differentially instruct neurogenesis in the adult brain. Here, we used transgenic Csf1r-GFP mice to investigate whether hippocampal microglia directly influence the activation of neural precursor cells. Our results revealed that an exercise-induced increase in neural precursor cell activity was mediated via endogenous microglia and abolished when these cells were selectively removed from hippocampal cultures. Conversely, microglia from the hippocampi of animals that had exercised were able to activate latent neural precursor cells when added to neurosphere preparations from sedentary mice. We also investigated the role of CX(3)CL1, a chemokine that is known to provide a more neuroprotective microglial phenotype. Intraparenchymal infusion of a blocking antibody against the CX(3)CL1 receptor, CX(3)CR1, but not control IgG, dramatically reduced the neurosphere formation frequency in mice that had exercised. While an increase in soluble CX(3)CL1 was observed following running, reduced levels of this chemokine were found in the aged brain. Lower levels of CX(3)CL1 with advancing age correlated with the natural decline in neural precursor cell activity, a state that could be partially alleviated through removal of microglia. These findings provide the first direct evidence that endogenous microglia can exert a dual and opposing influence on neural precursor cell activity within the hippocampus, and that signaling through the CX(3)CL1-CX(3)CR1 axis critically contributes toward this process.

Combination Chemotherapy and Dasatinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

ClinicalTrials.gov

2018-05-24

Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Core Binding Factor Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Pediatric acute respiratory distress syndrome: definition, incidence, and epidemiology: proceedings from the Pediatric Acute Lung Injury Consensus Conference.

PubMed

Khemani, Robinder G; Smith, Lincoln S; Zimmerman, Jerry J; Erickson, Simon

2015-06-01

Although there are similarities in the pathophysiology of acute respiratory distress syndrome in adults and children, pediatric-specific practice patterns, comorbidities, and differences in outcome necessitate a pediatric-specific definition. We sought to create such a definition. A subgroup of pediatric acute respiratory distress syndrome investigators who drafted a pediatric-specific definition of acute respiratory distress syndrome based on consensus opinion and supported by detailed literature review tested elements of the definition with patient data from previously published investigations. International PICUs. Children enrolled in published investigations of pediatric acute respiratory distress syndrome. None. Several aspects of the proposed pediatric acute respiratory distress syndrome definition align with the Berlin Definition of acute respiratory distress syndrome in adults: timing of acute respiratory distress syndrome after a known risk factor, the potential for acute respiratory distress syndrome to coexist with left ventricular dysfunction, and the importance of identifying a group of patients at risk to develop acute respiratory distress syndrome. There are insufficient data to support any specific age for "adult" acute respiratory distress syndrome compared with "pediatric" acute respiratory distress syndrome. However, children with perinatal-related respiratory failure should be excluded from the definition of pediatric acute respiratory distress syndrome. Larger departures from the Berlin Definition surround 1) simplification of chest imaging criteria to eliminate bilateral infiltrates; 2) use of pulse oximetry-based criteria when PaO2 is unavailable; 3) inclusion of oxygenation index and oxygen saturation index instead of PaO2/FIO2 ratio with a minimum positive end-expiratory pressure level for invasively ventilated patients; 4) and specific inclusion of children with preexisting chronic lung disease or cyanotic congenital heart disease. This

Insurance and Quality of Care for Adults with Acute Asthma

PubMed Central

Ferris, Timothy G; Blumenthal, David; Woodruff, Prescott G; Clark, Sunday; Camargo, Carlos A

2002-01-01

OBJECTIVE The relationship between health care insurance and quality of medical care remains incompletely studied. We sought to determine whether type of patient insurance is related to quality of care and subsequent outcomes for patients who arrive in the emergency department (ED) for acute asthma. DESIGN Using prospectively collected data from the Multicenter Airway Research Collaboration, we compared measures of quality of pre-ED care, acute severity, and short-term outcomes across 4 insurance categories: managed care, indemnity, Medicaid, and uninsured. SETTING AND PARTICIPANTS Emergency departments at 57 academic medical centers enrolled 1,019 adults with acute asthma. RESULTS Patients with managed care ranked first and uninsured patients ranked last on all 7 unadjusted quality measures. After controlling for covariates, uninsured patients had significantly lower quality of care than indemnity patients for 5 of 7 measures and had lower initial peak expiratory flow rates than indemnity insured patients. Patients with managed care insurance were more likely than indemnity-insured patients to identify a primary care physician and report using inhaled steroids in the month prior to arrival in the ED. Patients with Medicaid insurance were more likely than indemnity-insured patients to use the ED as their usual source of care for problems with asthma. We found no differences in patient outcomes among the insurance categories we studied. CONCLUSIONS Uninsured patients had consistently poorer quality of care and than insured patients. Despite differences in indicators of quality of care between types of insurance, we found no differences in short-term patient outcomes by type of insurance. PMID:12472926

The Effects of Acute Dopamine Precursor Depletion on the Reinforcing Value of Exercise in Anorexia Nervosa.

PubMed

O'Hara, Caitlin B; Keyes, Alexandra; Renwick, Bethany; Leyton, Marco; Campbell, Iain C; Schmidt, Ulrike

2016-01-01

This study investigated whether dopaminergic systems are involved in the motivation to engage in behaviours associated with anorexia nervosa (AN), specifically, the drive to exercise. Women recovered from AN (AN REC, n = 17) and healthy controls (HC, n = 15) were recruited. The acute phenylalanine/tyrosine depletion (APTD) method was used to transiently decrease dopamine synthesis and transmission. The effect of dopamine precursor depletion on drive to exercise was measured using a progressive ratio (PR) exercise breakpoint task. Both groups worked for the opportunity to exercise, and, at baseline, PR breakpoint scores were higher in AN REC than HC. Compared to values on the experimental control session, APTD did not decrease PR breakpoint scores in AN REC, but significantly decreased scores in HC. These data show that women recovered from AN are more motivated to exercise than HC, although in both groups, activity is more reinforcing than inactivity. Importantly, decreasing dopamine does not reduce the motivation to exercise in people recovered from AN, but in contrast, does so in HC. It is proposed that in AN, drive to exercise develops into a behaviour that is largely independent of dopamine mediated reward processes and becomes dependent on cortico-striatal neurocircuitry that regulates automated, habit- or compulsive-like behaviours. These data strengthen the case for the involvement of reward, learning, habit, and dopaminergic systems in the aetiology of AN.

The Effects of Acute Dopamine Precursor Depletion on the Reinforcing Value of Exercise in Anorexia Nervosa

PubMed Central

O’Hara, Caitlin B.; Keyes, Alexandra; Renwick, Bethany; Leyton, Marco; Campbell, Iain C.; Schmidt, Ulrike

2016-01-01

This study investigated whether dopaminergic systems are involved in the motivation to engage in behaviours associated with anorexia nervosa (AN), specifically, the drive to exercise. Women recovered from AN (AN REC, n = 17) and healthy controls (HC, n = 15) were recruited. The acute phenylalanine/tyrosine depletion (APTD) method was used to transiently decrease dopamine synthesis and transmission. The effect of dopamine precursor depletion on drive to exercise was measured using a progressive ratio (PR) exercise breakpoint task. Both groups worked for the opportunity to exercise, and, at baseline, PR breakpoint scores were higher in AN REC than HC. Compared to values on the experimental control session, APTD did not decrease PR breakpoint scores in AN REC, but significantly decreased scores in HC. These data show that women recovered from AN are more motivated to exercise than HC, although in both groups, activity is more reinforcing than inactivity. Importantly, decreasing dopamine does not reduce the motivation to exercise in people recovered from AN, but in contrast, does so in HC. It is proposed that in AN, drive to exercise develops into a behaviour that is largely independent of dopamine mediated reward processes and becomes dependent on cortico-striatal neurocircuitry that regulates automated, habit- or compulsive-like behaviours. These data strengthen the case for the involvement of reward, learning, habit, and dopaminergic systems in the aetiology of AN. PMID:26808920

Standardizing communication from acute care providers to primary care providers on critically ill adults.

PubMed

Ellis, Kerri A; Connolly, Ann; Hosseinnezhad, Alireza; Lilly, Craig M

2015-11-01

To increase the frequency of communication of patient information between acute and primary care providers. A secondary objective was to determine whether higher rates of communication were associated with lower rates of hospital readmission 30 days after discharge. A validated instrument was used for telephone surveys before and after an intervention designed to increase the frequency of communication among acute care and primary care providers. The communication intervention was implemented in 3 adult intensive care units from 2 campuses of an academic medical center. The frequency of communication among acute care and primary care providers, the perceived usefulness of the intervention, and its association with 30-day readmission rates were assessed for 202 adult intensive care episodes before and 100 episodes after a communication intervention. The frequency of documented communication increased significantly (5/202 or 2% before to 72/100 or 72% after the intervention; P < .001) and the communication was considered useful by every participating primary care provider. Rates of rehospitalization at 30 days were lower for the intervention group than the preintervention group, but the difference was not statistically significant (41/202 or 23% vs 16/88 or 18% of discharged patients; P = .45; power 0.112 at P = .05). The frequency of communication episodes that provide value can be increased through standardized processes. The key aspects of this effective intervention were setting the expectation that communication should occur, documenting when communication has occurred, and reviewing that documentation during multiprofessional rounds. ©2015 American Association of Critical-Care Nurses.

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

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

ClinicalTrials.gov

2017-07-03

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

Understanding the reconstitution of the B-cell compartment in bone marrow and blood after treatment for B-cell precursor acute lymphoblastic leukaemia.

PubMed

Theunissen, Prisca M J; van den Branden, Anouk; Van Der Sluijs-Gelling, Alita; De Haas, Valerie; Beishuizen, Auke; van Dongen, Jacques J M; Van Der Velden, Vincent H J

2017-07-01

A better understanding of the reconstitution of the B-cell compartment during and after treatment in B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) will help to assess the immunological status and needs of post-treatment BCP-ALL patients. Using 8-colour flow cytometry and proliferation-assays, we studied the composition and proliferation of both the B-cell precursor (BCP) population in the bone marrow (BM) and mature B-cell population in peripheral blood (PB) during and after BCP-ALL therapy. We found a normal BCP differentiation pattern and a delayed formation of classical CD38 dim -naive mature B-cells, natural effector B-cells and memory B-cells in patients after chemotherapy. This B-cell differentiation/maturation pattern was strikingly similar to that during initial B-cell development in healthy infants. Tissue-resident plasma cells appeared to be partly protected from chemotherapy. Also, we found that the fast recovery of naive mature B-cell numbers after chemotherapy was the result of increased de novo BCP generation, rather than enhanced B-cell proliferation in BM or PB. These results indicate that post-treatment BCP-ALL patients will eventually re-establish a B-cell compartment with a composition and B-cell receptor repertoire similar to that in healthy children. Additionally, the formation of a new memory B-cell compartment suggests that revaccination might be beneficial after BCP-ALL therapy. © 2017 John Wiley & Sons Ltd.

Acute fluoxetine modulates emotional processing in young adult volunteers.

PubMed

Capitão, L P; Murphy, S E; Browning, M; Cowen, P J; Harmer, C J

2015-08-01

Fluoxetine is generally regarded as the first-line pharmacological treatment for young people, as it is believed to show a more favourable benefit:risk ratio than other antidepressants. However, the mechanisms through which fluoxetine influences symptoms in youth have been little investigated. This study examined whether acute administration of fluoxetine in a sample of young healthy adults altered the processing of affective information, including positive, sad and anger cues. A total of 35 male and female volunteers aged between 18 and 21 years old were randomized to receive a single 20 mg dose of fluoxetine or placebo. At 6 h after administration, participants completed a facial expression recognition task, an emotion-potentiated startle task, an attentional dot-probe task and the Rapid Serial Visual Presentation. Subjective ratings of mood, anxiety and side effects were also taken pre- and post-fluoxetine/placebo administration. Relative to placebo-treated participants, participants receiving fluoxetine were less accurate at identifying anger and sadness and did not show the emotion-potentiated startle effect. There were no overall significant effects of fluoxetine on subjective ratings of mood. Fluoxetine can modulate emotional processing after a single dose in young adults. This pattern of effects suggests a potential cognitive mechanism for the greater benefit:risk ratio of fluoxetine in adolescent patients.

CPI-613, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

ClinicalTrials.gov

2017-07-31

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); Recurrent Adult Acute Myeloid Leukemia

Detailed immunophenotyping of B-cell precursors in regenerating bone marrow of acute lymphoblastic leukaemia patients: implications for minimal residual disease detection.

PubMed

Theunissen, Prisca M J; Sedek, Lukasz; De Haas, Valerie; Szczepanski, Tomasz; Van Der Sluijs, Alita; Mejstrikova, Ester; Nováková, Michaela; Kalina, Tomas; Lecrevisse, Quentin; Orfao, Alberto; Lankester, Arjan C; van Dongen, Jacques J M; Van Der Velden, Vincent H J

2017-07-01

Flow cytometric detection of minimal residual disease (MRD) in children with B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) requires immunophenotypic discrimination between residual leukaemic cells and B-cell precursors (BCPs) which regenerate during therapy intervals. In this study, EuroFlow-based 8-colour flow cytometry and innovative analysis tools were used to first characterize the immunophenotypic maturation of normal BCPs in bone marrow (BM) from healthy children, resulting in a continuous multiparametric pathway including transition stages. This pathway was subsequently used as a reference to characterize the immunophenotypic maturation of regenerating BCPs in BM from children treated for BCP-ALL. We identified pre-B-I cells that expressed low or dim CD34 levels, in contrast to the classical CD34 high pre-B-I cell immunophenotype. These CD34 -dim pre-B-I cells were relatively abundant in regenerating BM (11-85% within pre-B-I subset), while hardly present in healthy control BM (9-13% within pre-B-I subset; P = 0·0037). Furthermore, we showed that some of the BCP-ALL diagnosis immunophenotypes (23%) overlapped with CD34 -dim pre-B-I cells. Our results indicate that newly identified CD34 -dim pre-B-I cells can be mistaken for residual BCP-ALL cells, potentially resulting in false-positive MRD outcomes. Therefore, regenerating BM, in which CD34 -dim pre-B-I cells are relatively abundant, should be used as reference frame in flow cytometric MRD measurements. © 2017 John Wiley & Sons Ltd.

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

Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group.

PubMed

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

2010-04-01

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. 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. 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%). 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.

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

Blood-brain barrier permeability is increased after acute adult stroke but not neonatal stroke in the rat

PubMed Central

Lopez, David Fernandez; Faustino, Joel; Daneman, Richard; Zhou, Lu; Lee, Sarah; Derugin, Nikita; Wendland, Michael F.; Vexler, Zinaida S

2012-01-01

The immaturity of the CNS at birth greatly affects injury after stroke but the contribution of the blood-brain barrier (BBB) to the differential response to stroke in adults and neonates is poorly understood. We asked if the structure and function of the BBB is disrupted differently in neonatal and adult rats by transient middle cerebral artery occlusion. In adult rats, albumin leakage into injured regions was markedly increased during 2–24 h reperfusion but leakage remained low in the neonates. Functional assays employing intravascular tracers in the neonates showed that BBB permeability to both large (70-kDa dextran) and small (3-kDa dextran, Gd-DTPA) tracers remained largely undisturbed 24h after reperfusion. The profoundly different functional integrity of the BBB was associated with the largely nonoverlapping patterns of regulated genes in endothelial cells purified from injured and uninjured adult and neonatal brain at 24h (endothelial transcriptome, 31,042 total probe sets). Within significantly regulated 1,266 probe sets in injured adults and 361 probe sets in neonates, changes in the gene expression of the basal lamina components, adhesion molecules, the tight junction protein occludin, and MMP-9 were among the key differences. The protein expression of collagen-IV, laminin, claudin-5, occludin and ZO-1 was also better preserved in neonatal rats. Neutrophil infiltration remained low in acutely injured neonates but neutralization of CINC-1 in the systemic circulation enhanced neutrophil infiltration, BBB permeability and injury. The markedly more integrant BBB in neonatal brain than in adult brain after acute stroke may have major implications for the treatment of neonatal stroke. PMID:22787045

Cognitive assessment of older adults at the acute care interface: the informant history.

PubMed

Dyer, Adam H; Nabeel, Shamis; Briggs, Robert; O'Neill, Desmond; Kennelly, Sean P

2016-05-01

An informant history is critical in the complete cognitive assessments of older adults, but has never been formally assessed. A convenience sample of older adults aged ≥70 years were assessed using cognitive screeners for delirium (confusion assessment method-intensive care unit) and dementia (standardised Mini Mental State Examination and AD8) in a tertiary referral emergency department (ED). A total of 220/270 (81.5%) adults were included in the study (mean age 78.8±6.16; 49.1% male). Informant histories, obtained in almost two-thirds (61.1%, 66/108) of patients where desired, revealed a cognitive pattern suggestive of previously undiagnosed dementia in 39.4% (26/66). Most informants were relatives/friends (93.9%, 62/66) and were rated very good/excellent in contribution to care (96.9%, 64/66) and ability to provide useful information (93.9%, 62/66). The acute environment was also rated suitable to brief informant interviewing (mean duration <6 min) in terms of privacy (8.4±1.6/10) and accessibility (8.5±1.47/10). Following a review of the attending ED physician's notes, an informant history (either obtained/desired/refused) was only documented in 5.6% of cases. The informant history represents a much underused tool in the cognitive assessment of older adults presenting to the ED. The main barrier to informant interviewing in the ED environment appears to be informant availability. Where available, the informant history is easy to extract and provides invaluable information to the assessing physician. The acute care environment is suitable to brief informant interviews using readily available frameworks (AD8). However, the informant history is rarely obtained in this context, and further emphasis on undergraduate and postgraduate medical curricula is warranted. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Adaptation to a long term (4 weeks) arginine- and precursor (glutamate, proline and aspartate)-free diet.

PubMed

Tharakan, John F; Yu, Yong M; Zurakowski, David; Roth, Rachel M; Young, Vernon R; Castillo, Leticia

2008-08-01

It is not known whether arginine homeostasis is negatively affected by a "long term" dietary restriction of arginine and its major precursors in healthy adults. To assess the effects of a 4-week arginine- and precursor-free dietary intake on the regulatory mechanisms of arginine homeostasis in healthy subjects. Ten healthy adults received a complete amino acid diet for 1 week (control diet) and following a break period, six subjects received a 4-week arginine, proline, glutamate and aspartate-free diet (APF diet). The other four subjects continued for 4 weeks with the complete diet. On days 4 and 7 of the first week and days 25 and 28 of the 4-week period, the subjects received 24-h infusions of arginine, citrulline, leucine and urea tracers. During the 4-week APF, plasma arginine fluxes for the fed state, were significantly reduced. There were no significant differences for citrulline, leucine or urea fluxes. Arginine de novo synthesis was not affected by the APF intake. However, arginine oxidation was significantly decreased. In healthy adults, homeostasis of arginine under a long term arginine- and precursor-free intake is achieved by decreasing catabolic rates, while de novo arginine synthesis is maintained.

T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial.

PubMed

Lee, Daniel W; Kochenderfer, James N; Stetler-Stevenson, Maryalice; Cui, Yongzhi K; Delbrook, Cindy; Feldman, Steven A; Fry, Terry J; Orentas, Rimas; Sabatino, Marianna; Shah, Nirali N; Steinberg, Seth M; Stroncek, Dave; Tschernia, Nick; Yuan, Constance; Zhang, Hua; Zhang, Ling; Rosenberg, Steven A; Wayne, Alan S; Mackall, Crystal L

2015-02-07

(6) CD19-CAR T cells per kg. All toxicities were fully reversible, with the most severe being grade 4 cytokine release syndrome that occurred in three (14%) of 21 patients (95% CI 3·0-36·3). The most common non-haematological grade 3 adverse events were fever (nine [43%] of 21 patients), hypokalaemia (nine [43%] of 21 patients), fever and neutropenia (eight [38%] of 21 patients), and cytokine release syndrome (three [14%) of 21 patients). CD19-CAR T cell therapy is feasible, safe, and mediates potent anti-leukaemic activity in children and young adults with chemotherapy-resistant B-precursor acute lymphoblastic leukaemia. All toxicities were reversible and prolonged B-cell aplasia did not occur. National Institutes of Health Intramural funds and St Baldrick's Foundation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adoption of pediatric-inspired acute lymphoblastic leukemia regimens by adult oncologists treating adolescents and young adults: A population-based study.

PubMed

Muffly, Lori; Lichtensztajn, Daphne; Shiraz, Parveen; Abrahão, Renata; McNeer, Jennifer; Stock, Wendy; Keegan, Theresa; Gomez, Scarlett Lin

2017-01-01

Studies have demonstrated superior outcomes for adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) who are treated using pediatric versus adult therapeutic regimens. To the best of our knowledge, whether adult oncologists in the United States have adopted this approach to ALL in AYA patients is currently unknown. The objective of the current study was to provide a population-based description of ALL treatment patterns in AYA individuals over the past decade. Data regarding AYA patients aged 15 to 39 years and diagnosed with ALL between 2004 and 2014 while living in the Greater Bay Area were obtained from the Greater Bay Area Cancer Registry (GBACR). Treating facilities were designated as pediatric or adult centers; induction treatment regimens were abstracted from registry text data fields. Of 304 patients diagnosed in the GBACR catchment region, complete treatment data were available for 229 (75%). The location of care was identified for 296 patients (97%) treated at 31 unique centers. Approximately 70% of AYA patients received induction therapy at an adult treatment center. All AYA patients who were treated at pediatric centers received pediatric ALL regimens. Among AYA patients treated by adult oncologists with complete treatment data, none received a pediatric regimen before 2008. Between 2008 and 2012, while the US Adult Intergroup C10403 pediatric-inspired ALL protocol was open to accrual, 31% of AYA patients treated by adult oncologists received pediatric regimens. This rate fell to 21% from 2013 through 2014. Adult facilities treating ≥ 2 AYA patients with ALL per year captured in the GBACR were more likely to administer pediatric regimens than lower volume centers (P = .03). As of 2014, only a minority of AYA patients with ALL received pediatric ALL regimens at adult cancer centers. Cancer 2017;122-130. © 2016 American Cancer Society. © 2016 American Cancer Society.

Refractory acute leukaemia in adults treated with sequential colaspase and high-dose methotrexate.

PubMed

Yap, B S; McCredie, K B; Benjamin, R S; Bodey, G P; Freireich, E J

1978-09-16

Thirty-nine adults with acute leukaemia who had relapsed when receiving extensive chemotherapy were treated with a combination of methotrexate and colaspase (L-asparaginase) given sequentially. Patients initially received 50-80 mg/m(2) methotrexate, followed three hours later by intravenous colaspase, 40 000 IU/m(2). Seven days later intravenous methotrexate, 120 mg/m(2) was given. Each dose of methotrexate was followed 24 hours later by colaspase, and the two-day course of treatment was repeated every 7-14 days. The methotrexate dose was increased to tolerance by increments of 40 mg/m(2) with each course, while the colaspase dose remained constant unless abnormal liver function developed, when it was reduced by half.Overall, 18 out of 39 patients achieved complete remission (46%). Of these, 13 out of 21 (62%) had acute lymphoblastic leukaemia, three out of seven (43%) acute undifferentiated leukaemia, and two out of 11 (18%) acute myeloblastic leukaemia. The median duration of complete remission was 20 weeks and the median duration of survival in complete responders was 45 weeks. The median number of courses needed to achieve complete remission was three. The maximum tolerated dose of methotrexate was 400 mg/m(2) (median 200 mg/m(2)). Major side effects were due to colaspase. Methotrexate in doses of up to 400 mg/m(2) caused minimal myelosuppression and stomatitis, which suggested that colaspase given sequentially provides relative protection from methotrexate toxicity without the need for folinic acid (citrovorum factor) rescue.The combination of sequential colaspase and methotrexate is highly effective in reinducing remission in patients with acute lymphoblastic leukaemia or acute undifferentiated leukaemia. The regimen is easy to administer and relatively non-toxic, so it is suitable for use in outpatients, either alone or combined with other agents.

Co-occurrence of biphenotypic acute leukaemia, glucose 6-phosphate dehydrogenase deficiency and haemoglobin E trait in a single child.

PubMed

Mallick, Debkrishna; Thapa, Rajoo; Biswas, Biswajit

2016-02-01

Acute leukaemias occur as the result of clonal expansion subsequent to transformation and arrest at a normal differentiation stage of haematopoietic precursors, which commit to a single lineage, such as myeloid or B-lymphoid or T-lymphoid cells. Biphenotypic acute leukaemia (BAL) constitutes a biologically different group of leukaemia arising from a precursor stem cell and co-expressing more than one lineage specific marker. The present report describes a child with unusual co-occurrence of biphenotypic (B-precursor cell and Myeloid) acute leukaemia, haemoglobin E trait and glucose 6-phosphate dehydrogenase (G6-PD) deficiency. To the best of our knowledge, this constellation of haematological conditions in a single child has never been described before. 2016 BMJ Publishing Group Ltd.

Acute hypoglycemia impairs executive cognitive function in adults with and without type 1 diabetes.

PubMed

Graveling, Alex J; Deary, Ian J; Frier, Brian M

2013-10-01

Acute hypoglycemia impairs cognitive function in several domains. Executive cognitive function governs organization of thoughts, prioritization of tasks, and time management. This study examined the effect of acute hypoglycemia on executive function in adults with and without diabetes. Thirty-two adults with and without type 1 diabetes with no vascular complications or impaired awareness of hypoglycemia were studied. Two hyperinsulinemic glucose clamps were performed at least 2 weeks apart in a single-blind, counterbalanced order, maintaining blood glucose at 4.5 mmol/L (euglycemia) or 2.5 mmol/L (hypoglycemia). Executive functions were assessed with a validated test suite (Delis-Kaplan Executive Function). A general linear model (repeated-measures ANOVA) was used. Glycemic condition (euglycemia or hypoglycemia) was the within-participant factor. Between-participant factors were order of session (euglycemia-hypoglycemia or hypoglycemia-euglycemia), test battery used, and diabetes status (with or without diabetes). Compared with euglycemia, executive functions (with one exception) were significantly impaired during hypoglycemia; lower test scores were recorded with more time required for completion. Large Cohen d values (>0.8) suggest that hypoglycemia induces decrements in aspects of executive function with large effect sizes. In some tests, the performance of participants with diabetes was more impaired than those without diabetes. Executive cognitive function, which is necessary to carry out many everyday activities, is impaired during hypoglycemia in adults with and without type 1 diabetes. This important aspect of cognition has not received previous systematic study with respect to hypoglycemia. The effect size is large in terms of both accuracy and speed.

Management of acute pancreatitis in children.

PubMed

Abu-El-Haija, Maisam; Lin, Tom K; Nathan, Jaimie D

2017-10-01

Pediatric acute pancreatitis has been on the rise in the last decades, with an incidence close to adult pancreatitis. In the majority of cases acute pancreatitis resolves spontaneously, but in a subset of children the disease progresses to severe acute pancreatitis with attendant morbidity and mortality. Pediatric acute pancreatitis in this era is recognized as a separate entity from adult acute pancreatitis given that the causes and disease outcomes are different. There are slow but important advances made in understanding the best management for acute pancreatitis in children from medical, interventional, and surgical aspects. Supportive care with fluids, pain medications, and nutrition remain the mainstay for acute pancreatitis management. For complicated or severe pancreatitis, specialized interventions may be required with endoscopic or drainage procedures. Surgery has an important but limited role in pediatric acute pancreatitis.

Differentiation of vascular smooth muscle cells from local precursors during embryonic and adult arteriogenesis requires Notch signaling

PubMed Central

Chang, Linda; Noseda, Michela; Higginson, Michelle; Ly, Michelle; Patenaude, Alexandre; Fuller, Megan; Kyle, Alastair H.; Minchinton, Andrew I.; Puri, Mira C.; Dumont, Daniel J.; Karsan, Aly

2012-01-01

Vascular smooth muscle cells (VSMC) have been suggested to arise from various developmental sources during embryogenesis, depending on the vascular bed. However, evidence also points to a common subpopulation of vascular progenitor cells predisposed to VSMC fate in the embryo. In the present study, we use binary transgenic reporter mice to identify a Tie1+CD31dimvascular endothelial (VE)-cadherin−CD45− precursor that gives rise to VSMC in vivo in all vascular beds examined. This precursor does not represent a mature endothelial cell, because a VE-cadherin promoter-driven reporter shows no expression in VSMC during murine development. Blockade of Notch signaling in the Tie1+ precursor cell, but not the VE-cadherin+ endothelial cell, decreases VSMC investment of developing arteries, leading to localized hemorrhage in the embryo at the time of vascular maturation. However, Notch signaling is not required in the Tie1+ precursor after establishment of a stable artery. Thus, Notch activity is required in the differentiation of a Tie1+ local precursor to VSMC in a spatiotemporal fashion across all vascular beds. PMID:22509029

[Acute kidney injury-emergency or coincidence?].

PubMed

Öttl, Tobias

2013-02-27

An unifying definition of acute kidney injury as a precursor of acute renal failure has been published in march last year. Its remarkable mortality makes an early diagnosis an important goal. New biomarkers will be an important step to reach this goal in the near future. Depending on the underlying cause, therapeutic actions should be realized as soon as possible to diminish in-hospital mortality and chronic nephropathy. Intensive care units often are the first to test for new active substances.

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

211^At-BC8-B10 Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

ClinicalTrials.gov

2018-02-21

Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; CD45-Positive Neoplastic Cells Present; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome With Excess Blasts; Recurrent Adult Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia

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

Skeletal Muscle Acute and Chronic Metabolic Response to Essential Amino Acid Supplementation in Hypertriglyceridemic Older Adults

PubMed Central

Marquis, Bryce J; Hurren, Nicholas M; Carvalho, Eugenia; Kim, Il-Young; Schutzler, Scott; Azhar, Gohar; Wolfe, Robert R; Børsheim, Elisabet

2017-01-01

Abstract Background: Supplementation with essential amino acids (EAAs) + arginine is a promising nutritional approach to decrease plasma triglyceride (TG) concentrations, which are an independent risk factor for ischemic heart disease. Objective: The objective of this study was to examine the effects of 8 wk of EAA supplementation on skeletal muscle basal metabolite concentrations and changes in metabolic response to acute EAA intake, with an emphasis on mitochondrial metabolism, in adults with elevated TGs to better understand the mechanisms of lowering plasma TGs. Methods: Older adults with elevated plasma TG concentrations were given 22 g EAAs to ingest acutely before and after an 8-wk EAA supplementation period. Skeletal muscle biopsy samples were collected before and after acute EAA intake, both pre- and postsupplementation (4 biopsy samples), and targeted metabolomic analyses of organic acids and acylcarnitines were conducted on the specimens. Results: Acute EAA intake resulted in increased skeletal muscle acylcarnitine concentrations associated with oxidative catabolism of the supplement components, with the largest increases found in acylcarnitines of branched-chain amino acid oxidative catabolism, including isovaleryl-carnitine (2200%) and 2-methylbutyryl-carnitine (2400%). The chronic EAA supplementation resulted in a 19% decrease in plasma TGs along with accumulation of long-chain acylcarnitines myristoyl- (90%) and stearoyl- (120%) carnitine in skeletal muscle and increases in succinyl-carnitine (250%) and the late-stage tricarboxylic acid cycle intermediates fumarate (44%) and malate (110%). Conclusions: Supplementation with EAAs shows promise as an approach for moderate reduction in plasma TGs. Changes in skeletal muscle metabolites suggest incomplete fatty acid oxidation and increased anaplerosis, which suggests a potential bottleneck in fatty acid metabolism.

Survival analysis of adult patients with ALL in Mexico City: first report from the Acute Leukemia Workgroup (ALWG) (GTLA).

PubMed

Crespo-Solis, Erick; Espinosa-Bautista, Karla; Alvarado-Ibarra, Martha; Rozen-Fuller, Etta; Pérez-Rocha, Fernando; Nava-Gómez, Chantal; Ortiz-Zepeda, Maricela; Álvarez-Vera, José Luis; Ramos-Peñafiel, Christian Omar; Meillón-García, Luis Antonio; Rodríguez-Rodríguez, Sergio; Pomerantz-Okon, Alan; Turrubiates-Hernández, Francisco Javier; Demichelis-Gómez, Roberta

2018-06-01

Acute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by the clonal expansion of hematopoietic lymphoid progenitors. With new target therapies, the survival of adults with ALL has improved in the past few decades. Unfortunately, there are no large ALL patient series in many Latin American countries. Data from the Acute Leukemia Workgroup that includes five Mexico City referral centers were used. Survival was estimated for adult patients with ALL during 2009-2015. In total, 559 adults with ALL were included. The median age was 28 years; 67% were classified into the adolescent and young adult group. Cytogenetic information was available in 54.5% of cases. Of the 305 analyzed cases, most had a normal caryotype (70.5%) and Philadelphia-positive was present in 16.7%. The most commonly used treatment regimen was hyper-CVAD. In approximately 20% of cases, there was considerable delay in the administration of chemotherapy. Primarily refractory cases accounted for 13.1% of patients. At the time of analysis, 26.7% of cases had survived. The 3-year overall survival was 22.1%. The main cause of death was disease progression in 228 (55.6%). Clinical and public health strategies are needed to improve diagnosis, treatment and survivorship care for adult with ALL. This multicentric report represents the largest series in Mexico of adult ALL patients in which a survival analysis and risk identification were obtained. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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

Bortezomib and Combination Chemotherapy in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

ClinicalTrials.gov

2016-11-30

B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Lymphoblastic Lymphoma; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

Management of adult-onset methylmalonic acidemia with hypotonia and acute respiratory failure: A case report.

PubMed

Zhao, Zhanqi; Chu, Chan-Ching; Chang, Mei-Yun; Chang, Hao-Tai; Hsu, Yeong-Long

2018-06-01

Methylmalonic acidemia (MMA) is an autosomal recessive disease of organic acidemia. We report a 26-year-old male who presented with metabolic acidosis, acute renal failure required hemodialysis and acute respiratory failure required mechanical ventilation support. Progressive hypotonia of muscles made weaning from mechanical ventilator difficult. High level of serum methylmalonic acid and the mut genotype sequences confirmed the diagnosis of this adult-onset MMA. Two mut genotype sequences were found by analyzing all coding exons and exon-intron junctions. One genotype was well documented (Exon 6 Mutation, c. 1280G>A. p. G427D, heterozygous). The other mut genotype sequence had never been reported elsewhere (Intron 6 Novel, c. 1333-13_c. 1333-8delTTTTTC, heterozygous). Diet modification, medication, regular hemodialysis and physical rehabilitation. Weaning strategy adjusted with help of electrical impedance tomography. The muscle power of the patient gradually recovered. Extubation of the patient was successful and he was discharged without oxygen required. This case gives us the lesson that MMA can be newly diagnosed in adult patient. A new mut genotype sequence was discovered. The use of electrical impedance tomography to select a suitable method for inspiratory muscle training was possible and useful.

Symptom-Adapted Physical Activity Intervention in Minimizing Physical Function Decline in Older Patients With Acute Myeloid Leukemia Undergoing Chemotherapy

ClinicalTrials.gov

2018-05-24

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); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

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

ClinicalTrials.gov

2018-05-24

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

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

ClinicalTrials.gov

2017-12-07

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

Dedifferentiated Schwann Cell Precursors Secreting Paracrine Factors Are Required for Regeneration of the Mammalian Digit Tip.

PubMed

Johnston, Adam P W; Yuzwa, Scott A; Carr, Matthew J; Mahmud, Neemat; Storer, Mekayla A; Krause, Matthew P; Jones, Karen; Paul, Smitha; Kaplan, David R; Miller, Freda D

2016-10-06

Adult mammals have lost multi-tissue regenerative capacity, except for the distal digit, which is able to regenerate via mechanisms that remain largely unknown. Here, we show that, after adult mouse distal digit removal, nerve-associated Schwann cell precursors (SCPs) dedifferentiate and secrete growth factors that promote expansion of the blastema and digit regeneration. When SCPs were dysregulated or ablated, mesenchymal precursor proliferation in the blastema was decreased and nail and bone regeneration were impaired. Transplantation of exogenous SCPs rescued these regeneration defects. We found that SCPs secrete factors that promote self-renewal of mesenchymal precursors, and we used transcriptomic and proteomic analysis to define candidate factors. Two of these, oncostatin M (OSM) and platelet-derived growth factor AA (PDGF-AA), are made by SCPs in the regenerating digit and rescued the deficits in regeneration caused by loss of SCPs. As all peripheral tissues contain nerves, these results could have broad implications for mammalian tissue repair and regeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

Kawasaki syndrome in an adult: endomyocardial histology and ventricular function during acute and recovery phases of illness.

PubMed

Marcella, J J; Ursell, P C; Goldberger, M; Lovejoy, W; Fenoglio, J J; Weiss, M B

1983-08-01

Kawasaki syndrome, an acute systemic inflammatory illness of unknown origin usually affecting children, may develop into a serious illness complicated by coronary artery aneurysms or myocarditis. This report describes an adult with Kawasaki syndrome studied by right ventricular endomyocardial biopsy and cardiac catheterization during the acute and recovery phases of illness. The initial biopsy specimen showed acute myocarditis and was associated with hemodynamic evidence of biventricular dysfunction, a severely depressed left ventricular ejection fraction and global hypokinesia. With time, there was spontaneous and rapid resolution of the inflammatory cell infiltrate with concurrent return to normal myocardial function. Right ventricular endomyocardial biopsy studies early in the course of the cardiac disease associated with Kawasaki syndrome may correlate with ventricular function and may be useful for monitoring immunosuppressive therapy in patients with this syndrome.

Results of a prospective multicentre myeloablative double-unit cord blood transplantation trial in adult patients with acute leukaemia and myelodysplasia.

PubMed

Barker, Juliet N; Fei, Mingwei; Karanes, Chatchada; Horwitz, Mitchell; Devine, Steven; Kindwall-Keller, Tamila L; Holter, Jennifer; Adams, Alexia; Logan, Brent; Navarro, Willis H; Riches, Marcie

2015-02-01

Double-unit cord blood (CB) grafts may improve engraftment and relapse risk in adults with haematological malignancies. We performed a prospective high-dose myeloablative double-unit CB transplantation (CBT) trial in adults with high-risk acute leukaemia or myelodysplasia (MDS) between 2007 and 2011. The primary aim was to establish the 1-year overall survival in a multi-centre setting. Fifty-six patients (31 acute myeloid leukaemia, 19 acute lymphoblastic leukaemia, 4 other acute leukaemias, 2 myelodysplastic syndrome [MDS]) were transplanted at 10 centres. The median infused total nucleated cell doses were 2·62 (larger unit) and 2·02 (smaller unit) x 10(7) /kg. The cumulative incidence of day 100 neutrophil engraftment was 89% (95% confidence interval [CI]: 80-96). Day 180 grade II-IV acute graft-versus-host disease (GVHD) incidence was 64% (95%CI: 51-76) and 36% (95%CI: 24-49) of patients had chronic GVHD by 3-years. At 3-years post-transplant, the transplant-related mortality (TRM) was 39% (95%CI: 26-52), and the 3-year relapse incidence was 11% (95%CI: 4-21). With a median 37-month (range 23-71) follow-up of survivors, the 3-year disease-free survival was 50% (95%CI: 37-63). Double-unit CBT is a viable alternative therapy for high-risk acute leukaemia/ MDS in patients lacking a matched unrelated donor. This is especially important for minority patients. The relapse incidence was low but strategies to ameliorate TRM are needed. © 2014 John Wiley & Sons Ltd.

Monitoring gap junctional communication in astrocytes from acute adult mouse brain slices using the gap-FRAP technique.

PubMed

Yi, Chenju; Teillon, Jérémy; Koulakoff, Annette; Berry, Hugues; Giaume, Christian

2018-06-01

Intercellular communication through gap junction channels plays a key role in cellular homeostasis and in synchronizing physiological functions, a feature that is modified in number of pathological situations. In the brain, astrocytes are the cell population that expresses the highest amount of gap junction proteins, named connexins. Several techniques have been used to assess the level of gap junctional communication in astrocytes, but so far they remain very difficult to apply in adult brain tissue. Here, using specific loading of astrocytes with sulforhodamine 101, we adapted the gap-FRAP (Fluorescence Recovery After Photobleaching) to acute hippocampal slices from 9 month-old adult mice. We show that gap junctional communication monitored in astrocytes with this technique was inhibited either by pharmacological treatment with a gap junctional blocker or in mice lacking the two main astroglial connexins, while a partial inhibition was measured when only one connexin was knocked-out. We validate this approach using a mathematical model of sulforhodamine 101 diffusion in an elementary astroglial network and a quantitative analysis of the exponential fits to the fluorescence recovery curves. Consequently, we consider that the adaptation of the gap-FRAP technique to acute brain slices from adult mice provides an easy going and valuable approach that allows overpassing this age-dependent obstacle and will facilitate the investigation of gap junctional communication in adult healthy or pathological brain. Copyright © 2018 Elsevier B.V. All rights reserved.

Outcomes of allogeneic hematopoietic cell transplantation for adolescent and young adults compared with children and older adults with acute myeloid leukemia.

PubMed

Majhail, Navneet S; Brazauskas, Ruta; Hassebroek, Anna; Bredeson, Christopher N; Hahn, Theresa; Hale, Gregory A; Horowitz, Mary M; Lazarus, Hillard M; Maziarz, Richard T; Wood, William A; Parsons, Susan K; Joffe, Steven; Rizzo, J Douglas; Lee, Stephanie J; Hayes-Lattin, Brandon M

2012-06-01

Adolescents and young adults (AYAs) with cancer have not experienced improvements in survival to the same extent as children and older adults. We compared outcomes among children (<15 years), AYAs (15-40 years) and older adults (>40 years) receiving allogeneic hematopoietic cell transplant (HCT) for acute myeloid leukemia (AML). Our cohort consisted of 900 children, 2,708 AYA, and 2,728 older adult recipients of HLA-identical sibling or unrelated donor (URD) transplantation using myeloablative or reduced-intensity/nonmyeloablative conditioning. Outcomes were assessed over three time periods (1980-1988, 1989-1997, 1998-2005) for siblings and two time periods (1989-1997, 1998-2005) for URD HCT. Analyses were stratified by donor type. Results showed overall survival for AYAs using either siblings or URD improved over time. Although children had better and older adults had worse survival compared with AYAs, improvements in survival for AYAs did not lag behind those for children and older adults. After sibling donor HCT, 5-year adjusted survival for the three time periods was 40%, 48%, and 53% for children, 35%, 41%, and 42% for AYAs, and 22%, 30%, and 34% for older adults. Among URD HCT recipients, 5-year adjusted survival for the two time periods was 38% and 37% for children, 24% and 28% for AYAs, and 19% and 23% for older adults. Improvements in survival occurred because of a reduction in risk of treatment-related mortality. The risk of relapse did not change over time. Improvements in survival among AYAs undergoing allogeneic HCT for AML have paralleled those among children and older adults. Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Cediranib Maleate in Treating Patients With Relapsed, Refractory, or Untreated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

ClinicalTrials.gov

2016-12-28

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); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

Functional electrical stimulation-facilitated proliferation and regeneration of neural precursor cells in the brains of rats with cerebral infarction

PubMed Central

Xiang, Yun; Liu, Huihua; Yan, Tiebin; Zhuang, Zhiqiang; Jin, Dongmei; Peng, Yuan

2014-01-01

Previous studies have shown that proliferation of endogenous neural precursor cells cannot alone compensate for the damage to neurons and axons. From the perspective of neural plasticity, we observed the effects of functional electrical stimulation treatment on endogenous neural precursor cell proliferation and expression of basic fibroblast growth factor and epidermal growth factor in the rat brain on the infarct side. Functional electrical stimulation was performed in rat models of acute middle cerebral artery occlusion. Simultaneously, we set up a placebo stimulation group and a sham-operated group. Immunohistochemical staining showed that, at 7 and 14 days, compared with the placebo group, the numbers of nestin (a neural precursor cell marker)-positive cells in the subgranular zone and subventricular zone were increased in the functional electrical stimulation treatment group. Western blot assays and reverse-transcription PCR showed that total protein levels and gene expression of epidermal growth factor and basic fibroblast growth factor were also upregulated on the infarct side. Prehensile traction test results showed that, at 14 days, prehension function of rats in the functional electrical stimulation group was significantly better than in the placebo group. These results suggest that functional electrical stimulation can promote endogenous neural precursor cell proliferation in the brains of acute cerebral infarction rats, enhance expression of basic fibroblast growth factor and epidermal growth factor, and improve the motor function of rats. PMID:25206808

Azacitidine With or Without Entinostat in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia

ClinicalTrials.gov

2016-12-08

Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; 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 Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

Adaptation to a long term (4 weeks) arginine- and precursor (glutamate, proline and aspartate)-free diet☆

PubMed Central

Tharakan, John F.; Yu, Yong M.; Zurakowski, David; Roth, Rachel M.; Young, Vernon R.; Castillo, Leticia

2008-01-01

Summary Background & aims It is not known whether arginine homeostasis is negatively affected by a “long term” dietary restriction of arginine and its major precursors in healthy adults. To assess the effects of a 4-week arginine- and precursor-free dietary intake on the regulatory mechanisms of arginine homeostasis in healthy subjects. Methods Ten healthy adults received a complete amino acid diet for 1 week (control diet) and following a break period, six subjects received a 4-week arginine, proline, glutamate and aspartate-free diet (APF diet). The other four subjects continued for 4 weeks with the complete diet. On days 4 and 7 of the first week and days 25 and 28 of the 4-week period, the subjects received 24-h infusions of arginine, citrulline, leucine and urea tracers. Results During the 4-week APF, plasma arginine fluxes for the fed state, were significantly reduced. There were no significant differences for citrulline, leucine or urea fluxes. Arginine de novo synthesis was not affected by the APF intake. However, arginine oxidation was significantly decreased. Conclusions In healthy adults, homeostasis of arginine under a long term arginine- and precursor-free intake is achieved by decreasing catabolic rates, while de novo arginine synthesis is maintained. PMID:18590940

[Efficacy and tolerance of fenspiride in adult patients with acute respiratory tract infections].

PubMed

Płusa, T; Nawacka, D

1998-12-01

Fenspiride is an antiinflammatory drug targeted for the respiratory tract. In our study clinical efficacy and tolerance of drug were evaluated in 392 adult patients with acute respiratory tract infections. According to clinical criteria all observed symptoms were classified as mild, moderate and severe. The most of observed patients were included into moderate symptom score. Cough and nose obturation were dominant symptoms. All noticed changes in the upper respiratory tract were decreased after fenspiride therapy in 7 days trial. In 168 observed patients systemic and in 60 local acting antibiotics were successfully applied. Excellent tolerance of fenspiride was documented in 59% and good tolerance --in 34% of patients. Observed adverse reactions were classified as mild and in 20 patients fenspiride was rejected. Authors suggest that fenspiride therapy is save and successful in patient with acute respiratory tract infection. Good results in patients with bronchitis in decreasing of bronchospasm indicate fenspiride as a good tool in bronchial infection.

Mast cells and histamine are triggering the NF-κB-mediated reactions of adult and aged perilymphatic mesenteric tissues to acute inflammation

PubMed Central

Nizamutdinova, Irina Tsoy; Dusio, Giuseppina F.; Gasheva, Olga Yu.; Skoog, Hunter; Tobin, Richard; Peddaboina, Chander; Meininger, Cynthia J.; Zawieja, David C.; Newell-Rogers, M. Karen; Gashev, Anatoliy A.

2016-01-01

This study aimed to establish mechanistic links between the aging-associated changes in the functional status of mast cells and the altered responses of mesenteric tissue and mesenteric lymphatic vessels (MLVs) to acute inflammation. We used an in vivo model of acute peritoneal inflammation induced by lipopolysaccharide treatment of adult (9-month) and aged (24-month) F-344 rats. We analyzed contractility of isolated MLVs, mast cell activation, activation of nuclear factor-κB (NF-κB) without and with stabilization of mast cells by cromolyn or blockade of all types of histamine receptors and production of 27 major pro-inflammatory cytokines in adult and aged perilymphatic mesenteric tissues and blood. We found that the reactivity of aged contracting lymphatic vessels to LPS-induced acute inflammation was abolished and that activated mast cells trigger NF-κB signaling in the mesentery through release of histamine. The aging-associated basal activation of mesenteric mast cells limits acute inflammatory NF-κB activation in aged mesentery. We conclude that proper functioning of the mast cell/histamine/NF-κB axis is necessary for reactions of the lymphatic vessels to acute inflammatory stimuli as well as for interaction and trafficking of immune cells near and within the collecting lymphatics. PMID:27875806

High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia

ClinicalTrials.gov

2018-02-28

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 Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

cGMP production of patient-specific iPSCs and photoreceptor precursor cells to treat retinal degenerative blindness

PubMed Central

Wiley, Luke A.; Burnight, Erin R.; DeLuca, Adam P.; Anfinson, Kristin R.; Cranston, Cathryn M.; Kaalberg, Emily E.; Penticoff, Jessica A.; Affatigato, Louisa M.; Mullins, Robert F.; Stone, Edwin M.; Tucker, Budd A.

2016-01-01

Immunologically-matched, induced pluripotent stem cell (iPSC)-derived photoreceptor precursor cells have the potential to restore vision to patients with retinal degenerative diseases like retinitis pigmentosa. The purpose of this study was to develop clinically-compatible methods for manufacturing photoreceptor precursor cells from adult skin in a non-profit cGMP environment. Biopsies were obtained from 35 adult patients with inherited retinal degeneration and fibroblast lines were established under ISO class 5 cGMP conditions. Patient-specific iPSCs were then generated, clonally expanded and validated. Post-mitotic photoreceptor precursor cells were generated using a stepwise cGMP-compliant 3D differentiation protocol. The recapitulation of the enhanced S-cone phenotype in retinal organoids generated from a patient with NR2E3 mutations demonstrated the fidelity of these protocols. Transplantation into immune compromised animals revealed no evidence of abnormal proliferation or tumor formation. These studies will enable clinical trials to test the safety and efficiency of patient-specific photoreceptor cell replacement in humans. PMID:27471043

8-Chloro-Adenosine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

ClinicalTrials.gov

2018-01-30

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

Sapanisertib in Treating Patients With Relapsed and/or Refractory Acute Lymphoblastic Leukemia

ClinicalTrials.gov

2018-05-23

Acute Lymphoblastic Leukemia in Remission; B Acute Lymphoblastic Leukemia; B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative; Blasts 10 Percent or More of Bone Marrow Nucleated Cells; Recurrent Adult Acute Lymphoblastic Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; T Acute Lymphoblastic Leukemia

Diagnostic performance of a biomarker panel as a negative predictor for acute appendicitis in adult ED patients with abdominal pain.

PubMed

Huckins, David S; Copeland, Karen; Self, Wesley; Vance, Cheryl; Hendry, Phyllis; Borg, Keith; Gogain, Joseph

2017-03-01

Evaluate the diagnostic accuracy of the APPY1TM biomarker panel, previously described for use in pediatric patients, for identifying adult ED patients with abdominal pain who are at low risk of acute appendicitis. This study prospectively enrolled subjects >18years of age presenting to seven U.S. emergency departments with <72hours of abdominal pain suggesting possible acute appendicitis. The APPY1 panel was performed on blood samples drawn from each patient at the time of initial evaluation and results were correlated with the final diagnosis either positive or negative for acute appendicitis. 431 patients were enrolled with 422 completing all aspects of the study. The APPY1 biomarker panel exhibited a sensitivity of 97.5% (95% CI, 91.3-99.3%), a negative predictive value of 98.4% (95% CI, 94.4-99.6%), a negative likelihood ratio of 0.07 (95% CI, 0.02-0.27), with a specificity of 36.5% (95% CI, 31.6-41.8%) for acute appendicitis. The panel correctly identified 125 of 342 (36.6%) patients who did not have appendicitis with 2 (2.5%) false negatives. The CT utilization rate in this population was 72.7% (307/422). Of 307 CT scans, 232 were done for patients who did not have appendicitis and 79 (34%) of these patients were correctly identified as negative with "low risk" biomarker panel results, representing 26% (79/307) of all CT scans performed. This biomarker panel exhibited high sensitivity and negative predictive value for acute appendicitis in this prospective adult cohort, thereby potentially reducing the dependence on CT for the evaluation of possible acute appendicitis. Copyright © 2016 Elsevier Inc. All rights reserved.

Decitabine as Maintenance Therapy After Standard Therapy in Treating Patients With Previously Untreated Acute Myeloid Leukemia

ClinicalTrials.gov

2018-05-23

Acute Myeloid Leukemia; Acute Myeloid Leukemia With Myelodysplasia-Related Changes; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; Untreated Adult Acute Myeloid Leukemia

Screening of Variations in CD22 Gene in Children with B-Precursor Acute Lymphoblastic Leukemia.

PubMed

Aslar Oner, Deniz; Akin, Dilara Fatma; Sipahi, Kadir; Mumcuoglu, Mine; Ezer, Ustun; Kürekci, A Emin; Akar, Nejat

2016-09-01

CD22 is expressed on the surface of B-cell lineage cells from the early progenitor stage of pro-B cell until terminal differentiation to mature B cells. It plays a role in signal transduction and as a regulator of B-cell receptor signaling in B-cell development. We aimed to screen exons 9-14 of the CD22 gene, which is a mutational hot spot region in B-precursor acute lymphoblastic leukemia (pre-B ALL) patients, to find possible genetic variants that could play role in the pathogenesis of pre-B ALL in Turkish children. This study included 109 Turkish children with pre-B ALL who were diagnosed at Losante Hospital for Children with Leukemia. Genomic DNA was extracted from both peripheral blood and bone marrow leukocytes. Gene amplification was performed with PCR, and all samples were screened for the variants by single strand conformation polymorphism. Samples showing band shifts were sequenced on an automated sequencer. In our patient group a total of 9 variants were identified in the CD22 gene by sequencing: a novel variant in intron 10 (T2199G); a missense variant in exon 12; 5 intronic variants between exon 12 and intron 13; a novel intronic variant (C2424T); and a synonymous in exon 13. Thirteen of 109 children (11.9%) carried the T2199G novel intronic variant located in intron 10, and 17 of 109 children (15.6%) carried the C2424T novel intronic variant. Novel variants in the CD22 gene in children with pre-B ALL in Turkey that are not present, in the Human Gene Mutation Database or NCBI SNP database, were found.

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

Laser ablation of persistent twist cells in Drosophila: muscle precursor fate is not segmentally restricted

NASA Technical Reports Server (NTRS)

Farrell, E. R.; Keshishian, H.

1999-01-01

In Drosophila the precursors of the adult musculature arise during embryogenesis. These precursor cells have been termed Persistent Twist Cells (PTCs), as they continue to express the transcription factor Twist after that gene ceases expression elsewhere in the mesoderm. In the larval abdomen, the PTCs are associated with peripheral nerves in stereotypic ventral, dorsal, and lateral clusters, which give rise, respectively, to the ventral, dorsal, and lateral muscle fiber groups of the adult. We tested the developmental potential of the PTCs by using a microbeam laser to ablate specific clusters in larvae. We found that the ablation of a single segmental PTC cluster does not usually result in the deletion of the corresponding adult fibers of that segment. Instead, normal or near normal numbers of adult fibers can form after the ablation. Examination of pupae following ablation showed that migrating PTCs from adjacent segments are able to invade the affected segment, replenishing the ablated cells. However, the ablation of homologous PTCs in multiple segments does result in the deletion of the corresponding adult muscle fibers. These data indicate that the PTCs in an abdominal segment can contribute to the formation of muscle fibers in adjacent abdominal segments, and thus are not inherently restricted to the formation of muscle fibers within their segment of origin.

Explanatory variables for adult patients' self-reported recovery after acute lateral ankle sprain.

PubMed

van Rijn, Rogier M; Willemsen, Sten P; Verhagen, Arianne P; Koes, Bart W; Bierma-Zeinstra, Sita M A

2011-01-01

Longitudinal research on musculoskeletal disorders often makes use of a single measure of recovery, despite the large variation in reported recovery that exists. Patients with an acute ankle sprain often experience no pain or functional disability following treatment, yet report not being fully recovered, or vice versa. The purpose of this study was to find explanatory variables for reporting recovery by analyzing the extent to which different outcomes (eg, pain intensity) were associated with recovery and how baseline scores of different variables influence this association in adult patients after acute lateral ankle sprain. This was a cohort study based on data collected in a randomized controlled trial (RCT). This study was constructed within the framework of an RCT. One hundred two patients who incurred an acute ankle sprain were included. Recovery, pain intensity, giving way of the ankle, and Ankle Function Score (AFS) were assessed during the RCT at baseline and at 4 weeks, 8 weeks, 3 months, and 12 months postinjury. Mean differences were calculated between baseline and follow-up. Associations were calculated using linear mixed models, and the influence of baseline scores on these associations was determined using linear regression with interaction. Associations were found between recovery and the mean differences of pain during running on flat and rough surfaces (4 and 8 weeks, 3 months) and between recovery and the mean difference of giving way of the ankle during walking on a rough surface (8 weeks, 3 months). This study used data collected from an RCT. Therefore, the study was limited to the outcomes measured in that trial, and some explanatory factors easily could have been missed. This study is the first to identify explanatory variables for reporting recovery in adults after ankle sprain. Pain intensity and giving way of the ankle measured during high ankle load activities make it easier to measure and to generalize recovery in this population and

Cyclophosphamide and Busulfan Followed by Donor Stem Cell Transplant in Treating Patients With Myelofibrosis, Acute Myeloid Leukemia, or Myelodysplastic Syndrome

ClinicalTrials.gov

2017-12-01

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); Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Myelodysplastic Syndrome With Isolated Del(5q); Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Secondary Myelofibrosis; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia.

PubMed

Kantarjian, Hagop; Stein, Anthony; Gökbuget, Nicola; Fielding, Adele K; Schuh, Andre C; Ribera, Josep-Maria; Wei, Andrew; Dombret, Hervé; Foà, Robin; Bassan, Renato; Arslan, Önder; Sanz, Miguel A; Bergeron, Julie; Demirkan, Fatih; Lech-Maranda, Ewa; Rambaldi, Alessandro; Thomas, Xavier; Horst, Heinz-August; Brüggemann, Monika; Klapper, Wolfram; Wood, Brent L; Fleishman, Alex; Nagorsen, Dirk; Holland, Christopher; Zimmerman, Zachary; Topp, Max S

2017-03-02

Blinatumomab, a bispecific monoclonal antibody construct that enables CD3-positive T cells to recognize and eliminate CD19-positive acute lymphoblastic leukemia (ALL) blasts, was approved for use in patients with relapsed or refractory B-cell precursor ALL on the basis of single-group trials that showed efficacy and manageable toxic effects. In this multi-institutional phase 3 trial, we randomly assigned adults with heavily pretreated B-cell precursor ALL, in a 2:1 ratio, to receive either blinatumomab or standard-of-care chemotherapy. The primary end point was overall survival. Of the 405 patients who were randomly assigned to receive blinatumomab (271 patients) or chemotherapy (134 patients), 376 patients received at least one dose. Overall survival was significantly longer in the blinatumomab group than in the chemotherapy group. The median overall survival was 7.7 months in the blinatumomab group and 4.0 months in the chemotherapy group (hazard ratio for death with blinatumomab vs. chemotherapy, 0.71; 95% confidence interval [CI], 0.55 to 0.93; P=0.01). Remission rates within 12 weeks after treatment initiation were significantly higher in the blinatumomab group than in the chemotherapy group, both with respect to complete remission with full hematologic recovery (34% vs. 16%, P<0.001) and with respect to complete remission with full, partial, or incomplete hematologic recovery (44% vs. 25%, P<0.001). Treatment with blinatumomab resulted in a higher rate of event-free survival than that with chemotherapy (6-month estimates, 31% vs. 12%; hazard ratio for an event of relapse after achieving a complete remission with full, partial, or incomplete hematologic recovery, or death, 0.55; 95% CI, 0.43 to 0.71; P<0.001), as well as a longer median duration of remission (7.3 vs. 4.6 months). A total of 24% of the patients in each treatment group underwent allogeneic stem-cell transplantation. Adverse events of grade 3 or higher were reported in 87% of the patients in the

BMS-214662 in Treating Patients With Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myeloid Leukemia

ClinicalTrials.gov

2013-01-22

Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

When is acute persistent cough in school-age children and adults whooping cough? A prospective case series study.

PubMed

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

2013-08-01

Pertussis is a vaccine modified disease in most age groups and hence subtle in its presentation. Current diagnostic approaches require relatively invasive sampling. 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. 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. 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. 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. 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.

Evolution of Tumor Clones in Adult Acute Lymphoblastic Leukemia.

PubMed

Smirnova, S Yu; Sidorova, Yu V; Ryzhikova, N V; Sychevskaya, K A; Parovichnikova, E N; Sudarikov, A B

2016-01-01

Clonal instability of a tumor cell population in acute lymphoblastic leukemia (ALL) may complicate the monitoring of a minimal residual disease (MRD) by means of patient-specific targets identified at the disease onset. Most of the data concerning the possible instability of rearranged clonal TCR and IG genes during disease recurrence were obtained for ALL in children. The appropriate features of adult ALL, which are known to differ from those of childhood ALL in certain biological characteristics and prognosis, remain insufficiently studied. The aim of this study was to assess the stability of IG and TCR gene rearrangements in adult ALL. Rearrangements were identified according to the BIOMED-2 protocol (PCR followed by fragment analysis). Mismatch in clonal rearrangements at onset and relapse was identified in 83% of patients, indicating clonal instability during treatment. Clonal evolution and diversity of IG and TCR gene rearrangements may be one of the tumor progression mechanisms. New rearrangements may emerge due to residual VDJ-recombinase activity in tumor cells. Also, many clonal IG and TCR gene rearrangements may be present at different levels at a diagnosis, but less abundant clones may be "invisible" due to limited detection sensitivity. Later, major clones may disappear in the course of chemotherapy, while others may proliferate. Investigation of clonal evolution and heterogeneity in ALL and their impact on the treatment efficacy will contribute to the identification of new prognostic factors and the development of therapeutic approaches.

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

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. 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. 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. 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 .).

5-Fluoro-2'-Deoxycytidine and Tetrahydrouridine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

ClinicalTrials.gov

2015-06-03

Adult Acute Myeloid Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

Combined 677CC/1298AC genotypes of methylenetetrahydrofolate reductase (MTHFR ) reduce susceptibility to precursor B lymphoblastic leukemia in a Chinese population.

PubMed

Lv, Ling; Wu, Cuie; Sun, Henjuan; Zhu, Saijuan; Yang, Yongchen; Chen, Xi; Fu, Hua; Bao, Liming

2010-06-01

The methylenetetrahydrofolate reductase (MTHFR) encodes a major enzyme in folate metabolism. It has been suggested that two MTHFR polymorphisms, 677C>T and 1298A>C, influence risk of acute lymphoblastic leukemia (ALL). Most studies on relation of MTHFR polymorphisms to ALL susceptibility have been in pediatric populations because ALL is relatively rare in adults. Here, we report a case-control study of 127 Chinese patients with adult precursor B lymphoblastic leukemia (B-ALL) to examine correlation between the MTHFR polymorphisms and B-ALL susceptibility in adults. Our data show that although the prevalence of genotype 1298CC was significantly higher in the female patients than in the controls (P = 0.04), the differences in distributions of combined genotypes of 1298CC with either 677CC or 677CT between the cases and the controls were statistically insignificant. Haplotype analysis revealed no significant difference between the cases and the controls. The prevalence for joint MTHFR genotypes 677CC/1298AC was significantly lower in the female B-ALL cases than in the controls [odds ratio (OR) = 0.06, 95% CI = 0.00-0.53, P = 0.0033] and no differences among the men [OR = 0.71, 95% CI = 0.20-2.53, P = 0.55], suggesting that protective effects of combined MTHFR 677CC/1298AC genotypes on susceptibility of adult B-ALL are gender bias toward women with 677CC/1298AC women being at a 17-fold reduced odds to develop B-ALL.

Duodenal duplication cyst (DDC) communicating with the pancreatobiliary duct--a rare cause of recurrent acute pancreatitis in adults.

PubMed

Bong, Jan Jin; Spalding, Duncan

2010-01-01

Duodenal duplication cysts (DDC) are rare congenital anomalies that usually present in infancy and childhood. Acute presentation in adults is even rarer. We report a case of a 34-year-old man who presented with recurrent acute pancreatitis and was found to have a cystic lesion in the second part of his duodenum. Further investigations revealed communication between the cystic lesion and the distal common bile duct. We describe the details of the operative approach taken to resect the DDC. We describe the differential diagnoses and the criteria for diagnosing DDC. Management options for DDC are discussed along with our recommendations.

Can we incorporate geriatric assessment in the management of acute lymphoblastic leukemia in older adults?

PubMed

Loh, Kah Poh; Liesveld, Jane L; O'Dwyer, Kristen M

2018-04-05

Acute lymphoblastic leukemia (ALL) is an uncommon disease. Approximately 14% of new ALL cases occur in adults aged 60 and over, and the three-year overall survival in this population is poor at 12.8%. Older adults with ALL are heterogeneous in terms of their underlying health status, which can make treatment selection challenging given the disease rarity and limited inclusion of older patients in clinical trials. A comprehensive geriatric assessment (CGA) is a compilation of tools to assess multiple domains such as physical function and cognition, and may assist in guiding treatment selection and supportive care interventions. However, studies on the use of CGA are limited in older adults with ALL. In this review, we discuss the utility of CGA in patients with various hematologic malignancies. Using two patient cases of ALL, we also describe how CGA may be use to guide treatment and supportive care interventions. Copyright © 2018 Elsevier Inc. All rights reserved.

Health-related quality of life in adults with relapsed/refractory acute lymphoblastic leukemia treated with blinatumomab.

PubMed

Topp, Max S; Zimmerman, Zachary; Cannell, Paul; Dombret, Hervé; Maertens, Johan; Stein, Anthony; Franklin, Janet; Tran, Qui; Cong, Ze; Schuh, Andre C

2018-05-08

In the phase 3 TOWER study, blinatumomab significantly improved overall survival in adults with relapsed or refractory (R/R) Philadelphia chromosome-negative (Ph-) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) relative to standard-of-care chemotherapy. A secondary objective of this study was to assess the impact of blinatumomab on health-related quality of life (HRQL) as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). This analysis included the 342 of 405 randomized patients for whom baseline and ≥1 post-baseline result were available in any EORTC multi-item scale or single-item measure. In general, patients receiving blinatumomab (n=247) reported better posttreatment HRQL across all QLQ-C30 subscales, based on descriptive mean change from baseline, than did those receiving chemotherapy (n=95). The hazard ratios for time to a ≥10-point deterioration from baseline (TTD) in HRQL or death ranged from 0.42 to 0.81 in favor of blinatumomab, with the upper bounds of the 95% CI <1.0 across all measures, except insomnia, social functioning, and financial difficulties; sensitivity analysis of TTD in HRQL without the event of death were consistent with these findings. When treatment effect over time was tested using a restricted maximum likelihood-based mixed model for repeated measures analysis, p<0.05 was reached for blinatumomab vs chemotherapy for all subscale measures except financial difficulties. The clinically meaningful benefits in overall survival and HRQL support the clinical value of blinatumomab in patients with R/R Ph- BCP-ALL when compared with chemotherapy. Funded by Amgen (TOWER ClinicalTrials.gov number, NCT02013167). Copyright © 2018 American Society of Hematology.

Donor Peripheral Blood Stem Cell Transplant and Pretargeted Radioimmunotherapy in Treating Patients With High-Risk Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

ClinicalTrials.gov

2017-08-28

Chronic Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ringed Sideroblasts; Secondary Acute Myeloid Leukemia

Effect of Oral Prednisolone on Symptom Duration and Severity in Nonasthmatic Adults With Acute Lower Respiratory Tract Infection

PubMed Central

Little, Paul; Harnden, Anthony; Thompson, Matthew; Wang, Kay; Kendrick, Denise; Orton, Elizabeth; Brookes, Sara T.; Young, Grace J.; May, Margaret; Hollinghurst, Sandra; Carroll, Fran E.; Downing, Harriet; Timmins, David; Lafond, Natasher; El-Gohary, Magdy; Moore, Michael

2017-01-01

Importance Acute lower respiratory tract infection is common and often treated inappropriately in primary care with antibiotics. Corticosteroids are increasingly used but without sufficient evidence. Objective To assess the effects of oral corticosteroids for acute lower respiratory tract infection in adults without asthma. Design, Setting, and Participants Multicenter, placebo-controlled, randomized trial (July 2013 to final follow-up October 2014) conducted in 54 family practices in England among 401 adults with acute cough and at least 1 lower respiratory tract symptom not requiring immediate antibiotic treatment and with no history of chronic pulmonary disease or use of asthma medication in the past 5 years. Interventions Two 20-mg prednisolone tablets (n = 199) or matched placebo (n = 202) once daily for 5 days. Main Outcomes and Measures The primary outcomes were duration of moderately bad or worse cough (0 to 28 days; minimal clinically important difference, 3.79 days) and mean severity of symptoms on days 2 to 4 (scored from 0 [not affected] to 6 [as bad as it could be]; minimal clinically important difference, 1.66 units). Secondary outcomes were duration and severity of acute lower respiratory tract infection symptoms, duration of abnormal peak flow, antibiotic use, and adverse events. Results Among 401 randomized patients, 2 withdrew immediately after randomization, and 1 duplicate patient was identified. Among the 398 patients with baseline data (mean age, 47 [SD, 16.0] years; 63% women; 17% smokers; 77% phlegm; 70% shortness of breath; 47% wheezing; 46% chest pain; 42% abnormal peak flow), 334 (84%) provided cough duration and 369 (93%) symptom severity data. Median cough duration was 5 days (interquartile range [IQR], 3-8 days) in the prednisolone group and 5 days (IQR, 3-10 days) in the placebo group (adjusted hazard ratio, 1.11; 95% CI, 0.89-1.39; P = .36 at an α = .05). Mean symptom severity was 1.99 points in the prednisolone

Adolescent and adult rat cortical protein kinase A display divergent responses to acute ethanol exposure

PubMed Central

Gigante, Eduardo D.; Santerre, Jessica L.; Carter, Jenna M.; Werner, David F.

2014-01-01

Adolescent rats display reduced sensitivity to many dysphoria-related effects of alcohol (ethanol) including motor ataxia and sedative hypnosis, but the underlying neurobiological factors that contribute to these differences remain unknown. The cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) pathway, particularly the type II regulatory subunit (RII), has been implicated in ethanol-induced molecular and behavioral responses in adults. Therefore, the current study examined cerebral cortical PKA in adolescent and adult ethanol responses. With the exception of early adolescence, PKA RIIα and RIIβ subunit levels largely did not differ from adult levels in either whole cell lysate or P2 synaptosomal expression. However, following acute ethanol exposure, PKA RIIβ P2 synaptosomal expression and activity were increased in adults, but not in adolescents. Behaviorally, intracerebroventricular administration of the PKA activator Sp-cAMP and inhibitor Rp-cAMP prior to ethanol administration increased adolescent sensitivity to the sedative-hypnotic effects of ethanol compared to controls. Sp-cAMP was ineffective in adults whereas Rp-cAMP suggestively reduced loss of righting reflex (LORR) with paralleled increases in blood ethanol concentrations. Overall, these data suggest that PKA activity modulates the sedative/hypnotic effects of ethanol and may potentially play a wider role in the differential ethanol responses observed between adolescents and adults. PMID:24874150

Adult diagnosed Dandy Walker malformation presenting as an acute brainstem event--a case report and review of the literature.

PubMed

Warwick, C Tanya; Reyes, Bernardo J; Ayoob, M Rose; Subit, Michael

2008-01-01

The Dandy Walker Malformation (DWM) is an infrequent condition seen in pediatric patients. Adult presentation of DWM is extremely rare. This condition usually presents in childhood with hydrocephalus and cerebellar signs and symptoms. This case describes a woman with an undiagnosed DWM who was asymptomatic until the age of 56 when she developed the acute onset of headache, nausea, vomiting, and diplopia. Her history and physical exam were consistent with an acute brainstem infarct. MRI revealed the underlying malformation. The clinical and radiological findings are discussed as well as their implications and possible etiologies.

Blinatumomab and Combination Chemotherapy or Dasatinib, Prednisone, and Blinatumomab in Treating Older Patients With Acute Lymphoblastic Leukemia

ClinicalTrials.gov

2018-06-01

Acute Lymphoblastic Leukemia; B Acute Lymphoblastic Leukemia; B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative; Philadelphia Chromosome Positive; Recurrent Adult Acute Lymphoblastic Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

In search of adult renal stem cells.

PubMed

Anglani, F; Forino, M; Del Prete, D; Tosetto, E; Torregrossa, R; D'Angelo, A

2004-01-01

The therapeutic potential of adult stem cells in the treatment of chronic degenerative diseases has becoming increasingly evident over the last few years. Significant attention is currently being paid to the development of novel treatments for acute and chronic kidney diseases too. To date, promising sources of stem cells for renal therapies include adult bone marrow stem cells and the kidney precursors present in the early embryo. Both cells have clearly demonstrated their ability to differentiate into the kidney's specialized structures. Adult renal stem cells have yet to be identified, but the papilla is where the stem cell niche is probably located. Now we need to isolate and characterize the fraction of papillary cells that constitute the putative renal stem cells. Our growing understanding of the cellular and molecular mechanisms behind kidney regeneration and repair processes - together with a knowledge of the embryonic origin of renal cells - should induce us, however, to bear in mind that in the kidney, as in other mesenchymal tissues, the need for a real stem cell compartment might be less important than the phenotypic flexibility of tubular cells. Thus, by displaying their plasticity during kidney maintenance and repair, terminally differentiated cells may well function as multipotent stem cells despite being at a later stage of maturation than adult stem cells. One of the major tasks of Regenerative Medicine will be to disclose the molecular mechanisms underlying renal tubular plasticity and to exploit its biological and therapeutic potential.

Busulfan and Etoposide Followed by Peripheral Blood Stem Cell Transplant and Low-Dose Aldesleukin in Treating Patients With Acute Myeloid Leukemia

ClinicalTrials.gov

2017-05-03

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 t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Childhood Acute Myeloid Leukemia in Remission; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia

Human herpesvirus 6 encephalitis followed by acute disseminated encephalomyelitis in an immunocompetent adult.

PubMed

Horie, Junichi; Suzuki, Keisuke; Nakamura, Toshiki; Okamura, Madoka; Iwasaki, Akio; Hirata, Koichi

2017-04-28

A 26-year-old, otherwise healthy man presented with visual abnormality followed by loss of consciousness and convulsion. The patient then developed headache and fever 14 days later. Brain MRI showed hyperintensities in the left cingulate cortex. The cerrebrospinal fluid examinations showed mononuclear pleocytosis and positive PCR results for human herpesvirus 6 (HHV-6). A diagnosis of HHV-6 encephalitis and symptomatic epilepsy was made. The patient's clinical symptoms improved promptly following acyclovir treatment. However, 3 months later the patient noticed dysesthesia in the trunk, the left upper limb and the right lower limb. Brain and spine MRI showed multiple brain white matter lesions, the middle cerebellar peduncle and cervical spinal lesions. The symptoms resolved following methylprednisolone pulse therapy only. We report an adult patient with HHV-6 encephalitis followed by acute disseminated encephalomyelitis whose initial presentation was epilepsy. HHV-6 encephalitis should be included in the differential diagnosis of encephalitis of unknown etiology in an immunocompetent adult.

Examining the association between adult attachment style and cortisol responses to acute stress

PubMed Central

Kidd, Tara; Hamer, Mark; Steptoe, Andrew

2011-01-01

Summary The quality of social relationships may contribute to variations in biological stress responses, thereby affecting health risk. The association between an important indicator of social relationships, adult attachment style, and cortisol has been relatively unexplored. The present study examined adult romantic attachment style and cortisol responses to acute laboratory stress. Salivary cortisol was measured in response to two behavioural tasks, a colour/word interference task and mirror tracing task, in 498 healthy men and women from the Heart Scan study, a subsample of the Whitehall II cohort. Participants were classified as secure, fearful, preoccupied or dismissive on the basis of responses to the Relationship Questionnaire. Cortisol output was lowest in the fearful group, followed by the preoccupied group, with both secure and dismissive groups having higher levels. The results from this study tentatively support the proposition that attachment style is a factor in determining the manifestation of HPA dysregulation. PMID:21106296

Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8 Followed by Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

ClinicalTrials.gov

2018-03-19

Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Secondary Acute Myeloid Leukemia

Re-evaluation of DNA Index as a Prognostic Factor in Children with Precursor B Cell Acute Lymphoblastic Leukemia.

PubMed

Noh, O Kyu; Park, Se Jin; Park, Hyeon Jin; Ju, HeeYoung; Han, Seung Hyon; Jung, Hyun Joo; Park, Jun Eun

2017-09-01

We aimed to investigate the prognostic value of DNA index (DI) in children with precursor B cell acute lymphoblastic lymphoma (pre-B ALL). From January 2003 to December 2014, 72 children diagnosed with pre-B ALL were analyzed. We analyzed the prognostic value of DI and its relations with other prognostic factors. The DI cut-point of 1.16 did not discriminate significantly the groups between high and low survivals (DI≥1.16 versus <1.16; 5-year OS, 90.5% vs. 82.8%, p =0.665). We explored the survivals according to the level of DI (<1.00, 1.00, 1.01-1.30, 1.31-1.60, 1.61-1.90, and >1.90), and the survival of children with a DI between 1.00-1.90 were significantly higher than that of children with DI of <1.00 or >1.90 (5-year OS, 90.6% vs. 50.0%, p <0.001). The DI of 1.16 was not a significant cut-point discriminating the risk group in children with pre-B ALL. However, the DI divided by specific ranges of values remained an independent prognostic factor. Further studies are warranted to re-evaluate the prognostic value and cut-point of DI in children treated with recent treatment protocols. © 2017 by the Association of Clinical Scientists, Inc.

Cytomegalovirus-induced colonic stricture presenting as acute intestinal obstruction in an immunocompetent adult.

PubMed

Dinesh, B V; Selvaraju, Karthikeyan; Kumar, Sampath; Thota, Sumath

2013-09-10

Cytomegalovirus (CMV) infection causes significant morbidty and mortality in immunopromised patients. Though it is usually silent in immunocompetent adults, rarely it can cause serious life-threatening complications. Gastrointestinal tract is one of the commonly involved organs, where it produces a spectrum of clinical manifestation ranging from mild non-specific abdominal pain and diarrhoea to severe infection with toxic megacolon and death. We present a 65-year-old immunocompetent male patient admitted with acute colonic obstruction secondary to CMV-induced colonic stricture, highlighting the importance of considering it as a differential diagnosis for colonic obstruction and reviewing its management.

Acute measles encephalitis in partially vaccinated adults.

PubMed

Fox, Annette; Hung, Than Manh; Wertheim, Heiman; Hoa, Le Nguyen Minh; Vincent, Angela; Lang, Bethan; Waters, Patrick; Ha, Nguyen Hong; Trung, Nguyen Vu; Farrar, Jeremy; Van Kinh, Nguyen; Horby, Peter

2013-01-01

The pathogenesis of acute measles encephalitis (AME) is poorly understood. Treatment with immune-modulators is based on theories that post-infectious autoimmune responses cause demyelination. The clinical course and immunological parameters of AME were examined during an outbreak in Vietnam. Fifteen measles IgM-positive patients with confusion or Glasgow Coma Scale (GCS) score below 13, and thirteen with uncomplicated measles were enrolled from 2008-2010. Standardized clinical exams were performed and blood collected for lymphocyte and measles- and auto-antibody analysis. The median age of AME patients was 21 years, similar to controls. Eleven reported receiving measles vaccination when aged one year. Confusion developed a median of 4 days after rash. Six patients had GCS <8 and four required mechanical ventilation. CSF showed pleocytosis (64%) and proteinorrhachia (71%) but measles virus RNA was not detected. MRI revealed bilateral lesions in the cerebellum and brain stem in some patients. Most received dexamethasone +/- IVIG within 4 days of admission but symptoms persisted for ≥3 weeks in five. The concentration of voltage gated calcium channel-complex-reactive antibodies was 900 pM in one patient, and declined to 609 pM ∼ 3 months later. Measles-reactive IgG antibody avidity was high in AME patients born after vaccine coverage exceeded 50% (∼ 25 years earlier). AME patients had low CD4 (218/µl, p = 0.029) and CD8 (200/µl, p = 0.012) T-cell counts compared to controls. Young adults presenting with AME in Vietnam reported a history of one prior measles immunization, and those aged <25 years had high measles-reactive IgG avidity indicative of prior vaccination. This suggests that one-dose measles immunization is not sufficient to prevent AME in young adults and reinforces the importance of maintaining high coverage with a two-dose measles immunization schedule. Treatment with corticosteroids and IVIG is common practice, and should be assessed in

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

A prospective registration study to determine feasibility of hematopoietic SCT in adults with acute leukemia: planning, expectations and reality.

PubMed

Labopin, M; Gorin, N-C; Polge, E; Socié, G; Gurman, G; Gluckman, E; Jindra, P; Poiré, X; Schäfer-Eckart, K; Ruutu, T; Milone, G; Arcese, W; Mohty, M; Rocha, V

2014-03-01

For adults with acute leukemia, it is important to know whether the therapeutic schemes initially planned were actually implemented. The European Group for Blood and Marrow transplantation Acute Leukemia Working Party prospectively followed 695 consecutive patients who were registered at the time of HLA typing. Of 304 patients with an available matched sibling donor (MSD), SCT was planned in 264, chemotherapy in 33 and autografting in 7. For the rest, an unrelated donor (UD) search was initiated in 198. Among these, 117 were transplanted, 114 received chemotherapy and 77 underwent autografting. Probabilities of receiving a planned treatment were 60 and 65% at 1 and 2 years, respectively. Patients scheduled to receive MSD SCT had an 82% probability, whereas those scheduled to undergo UD SCT had a 57% probability, of receiving their transplant at 1 year. The only factor associated with a lower probability of MSD SCT in first remission was delayed HLA typing (HR=0.82; P=0.03). One year after enrollment, 40% of patients did not follow their initial treatment plan. Because OS was 50% only at 3 years and only 57% of the patients without a MSD underwent SCT, this suggests room for improvement in outcomes for adults with acute leukemia.

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

2018-04-20

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; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; 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; Myelodysplastic Syndrome; 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

Unique Characteristics of Adolescent and Young Adult Acute Lymphoblastic Leukemia, Breast Cancer, and Colon Cancer

PubMed Central

Seibel, Nita L.; Blair, Donald G.; Albritton, Karen; Hayes-Lattin, Brandon

2011-01-01

Each year in the United States, nearly 70 000 individuals between the ages of 15 and 40 years are diagnosed with cancer. Although overall cancer survival rates among pediatric and older adult patients have increased in recent decades, there has been little improvement in survival of adolescent and young adult (AYA) cancer patients since 1975 when collected data became adequate to evaluate this issue. In 2006, the AYA Oncology Progress Review Group made recommendations for addressing the needs of this population that were later implemented by the LIVESTRONG Young Adult Alliance. One of their overriding questions was whether the cancers seen in AYA patients were biologically different than the same cancers in adult and/or pediatric patients. On June 9–10, 2009, the National Cancer Institute (NCI) and the Lance Armstrong Foundation (LAF) convened a workshop in Bethesda, MD, entitled “Unique Characteristics of AYA Cancers: Focus on Acute Lymphocytic Leukemia (ALL), Breast Cancer and Colon Cancer” that aimed to examine the current state of basic and translational research on these cancers and to discuss the next steps to improve their prognosis and treatment. PMID:21436065

Acute Splenic Sequestration Crisis in Adult Sickle Cell Disease: A Report of 16 Cases.

PubMed

Naymagon, Leonard; Pendurti, Gopichand; Billett, Henny H

2015-01-01

Acute splenic sequestration crisis (ASSC), characterized by rapidly progressive anemia and circulatory compromise in the setting of sudden splenic enlargement, is an uncommon entity among adult sickle cell patients. We reviewed cases of adult ASSC encountered at our institution to generate insight into the recognition, diagnosis, and treatment of the condition. Cases of adult ASSC during a 10-year period were identified retrospectively. Patient charts were reviewed for laboratory and imaging results; demographic data and clinical course were collected and reviewed. Sixteen cases of adult ASSC were identified. Most patients presented with pain crisis; only four of 16 patients presented with abdominal pain. The maximum decreases in hemoglobin (Hb) (42.0%) and platelets (62.1%) occurred at day 2.9, delaying identification and treatment. Hemodynamic instability played a large role in dictating risk stratification. Therapy consisted of transfusion (14/16) and splenectomy (5/16). No recurrences were noted in a mean follow-up time of 5.3 years but review of patients' charts demonstrated that at least one of the patients had two prior episodes. Adult ASSC may present with non specific findings and patients may not deteriorate until several days into a previously uneventful hospital course. Changes in platelet counts may be more reliable markers than changes in Hb level since red cell transfusions may interfere with assessments of the sequestration process. This case series of adult ASSC, the largest reported in the literature to date, highlights common clinical, laboratory, radiological, and pathological features of this uncommon entity and helps to guide recognition, diagnosis, and treatment.

Metabolic alkalosis contributes to acute hypercapnic respiratory failure in adult cystic fibrosis.

PubMed

Holland, Anne E; Wilson, John W; Kotsimbos, Thomas C; Naughton, Matthew T

2003-08-01

and study objectives: Patients with end-stage cystic fibrosis (CF) develop respiratory failure and hypercapnia. In contrast to COPD patients, altered electrolyte transport and malnutrition in CF patients may predispose them to metabolic alkalosis and, therefore, may contribute to hypercapnia. The aim of this study was to determine the prevalence of metabolic alkalosis in adults with hypercapnic respiratory failure in the setting of acute exacerbations of CF compared with COPD. Levels of arterial blood gases, plasma electrolytes, and serum albumin from 14 consecutive hypercapnic CF patients who had been admitted to the hospital with a respiratory exacerbation were compared with 49 consecutive hypercapnic patients with exacerbations of COPD. Hypercapnia was defined as a PaCO(2) of > or = 45 mm Hg. Despite similar PaCO(2) values, patients in the CF group were significantly more alkalotic than were those in the COPD group (mean [+/- SD] pH, 7.43 +/- 0.03 vs 7.37 +/- 0.05, respectively; p < 0.01). A mixed respiratory acidosis and metabolic alkalosis was evident in 71% of CF patients and 22% of COPD patients (p < 0.01). The mean concentrations of plasma chloride (95.1 +/- 4.9 vs 99.8 +/- 5.2 mmol/L, respectively; p < 0.01) and sodium (136.5 +/- 2.8 vs 140.4 +/- 4.5 mmol/L, respectively; p < 0.01) were significantly lower in the CF group, and the levels of serum albumin were significantly reduced (27.4 +/- 5.8 vs 33.7 +/- 4.8 mmol/L, respectively; p < 0.01). Metabolic alkalosis contributes to hypercapnic respiratory failure in adults with acute exacerbations of CF. This acid-base disturbance occurs in conjunction with reduced total body salt levels and hypoalbuminemia.

CXCR6 Expression Is Important for Retention and Circulation of ILC Precursors.

PubMed

Chea, Sylvestre; Possot, Cécilie; Perchet, Thibaut; Petit, Maxime; Cumano, Ana; Golub, Rachel

2015-01-01

Innate lymphoid cells are present at mucosal sites and represent the first immune barrier against infections, but what contributes to their circulation and homing is still unclear. Using Rag2(-/-) Cxcr6(Gfp/+) reporter mice, we assessed the expression and role of CXCR6 in the circulation of ILC precursors and their progeny. We identify CXCR6 expressing ILC precursors in the bone marrow and characterize their significant increase in CXCR6-deficient mice at steady state, indicating their partial retention in the bone marrow after CXCR6 ablation. Circulation was also impaired during embryonic life as fetal liver from CXCR6-deficient embryos displayed decreased numbers of ILC3 precursors. When injected, fetal CXCR6-deficient ILC3 precursors also fail to home and reconstitute ILC compartments in vivo. We show that adult intestinal ILC subsets have heterogeneous expression pattern of CXCR6, integrin α 4 β 7, CD62L, CD69, and CD44, with ILC1 and ILC3 being more likely tissue resident lymphocytes. Intestinal ILC subsets were unchanged in percentages and numbers in both mice. We demonstrate that the ILC frequency is maintained due to a significant increase of ILC peripheral proliferation, as well as an increased proliferation of the in situ ILC precursors to compensate their retention in the bone marrow.

CXCR6 Expression Is Important for Retention and Circulation of ILC Precursors

PubMed Central

Chea, Sylvestre; Possot, Cécilie; Perchet, Thibaut; Petit, Maxime; Cumano, Ana; Golub, Rachel

2015-01-01

Innate lymphoid cells are present at mucosal sites and represent the first immune barrier against infections, but what contributes to their circulation and homing is still unclear. Using Rag2 −/− Cxcr6 Gfp/+ reporter mice, we assessed the expression and role of CXCR6 in the circulation of ILC precursors and their progeny. We identify CXCR6 expressing ILC precursors in the bone marrow and characterize their significant increase in CXCR6-deficient mice at steady state, indicating their partial retention in the bone marrow after CXCR6 ablation. Circulation was also impaired during embryonic life as fetal liver from CXCR6-deficient embryos displayed decreased numbers of ILC3 precursors. When injected, fetal CXCR6-deficient ILC3 precursors also fail to home and reconstitute ILC compartments in vivo. We show that adult intestinal ILC subsets have heterogeneous expression pattern of CXCR6, integrin α 4 β 7, CD62L, CD69, and CD44, with ILC1 and ILC3 being more likely tissue resident lymphocytes. Intestinal ILC subsets were unchanged in percentages and numbers in both mice. We demonstrate that the ILC frequency is maintained due to a significant increase of ILC peripheral proliferation, as well as an increased proliferation of the in situ ILC precursors to compensate their retention in the bone marrow. PMID:26494947

Total Marrow and Lymphoid Irradiation and Chemotherapy Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Lymphocytic or Myelogenous Leukemia

ClinicalTrials.gov

2018-03-15

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); Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia

MR imaging of adult acute infectious encephalitis.

PubMed

Bertrand, A; Leclercq, D; Martinez-Almoyna, L; Girard, N; Stahl, J-P; De-Broucker, T

2017-05-01

Imaging is a key tool for the diagnosis of acute encephalitis. Brain CT scan must be urgently performed to rule out a brain lesion with mass effect that would contraindicate lumbar puncture. Brain MRI is less accessible than CT scan, but can provide crucial information with patients presenting with acute encephalitis. We performed a literature review on PubMed on April 1, 2015 with the search terms "MRI" and "encephalitis". We first described the various brain MRI abnormalities associated with each pathogen of acute encephalitis (HSV, VZV, other viral agents targeting immunocompromised patients or travelers; tuberculosis, listeriosis, other less frequent bacterial agents). Then, we identified specific patterns of brain MRI abnomalies that may suggest a particular pathogen. Limbic encephalitis is highly suggestive of HSV; it also occurs less frequently in encephalitis due to HHV6, syphillis, Whipple's disease and HIV primary infection. Rhombencephalitis is suggestive of tuberculosis and listeriosis. Acute ischemic lesions can occur in patients presenting with severe bacterial encephalitis, tuberculosis, VZV encephalitis, syphilis, and fungal infections. Brain MRI plays a crucial role in the diagnosis of acute encephalitis. It detects brain signal changes that reinforce the clinical suspicion of encephalitis, especially when the causative agent is not identified by lumbar puncture; it can suggest a particular pathogen based on the pattern of brain abnormalities and it rules out important differential diagnosis (vascular, tumoral or inflammatory causes). Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Acute epiglottitis due to Serratia marcescens in an immunocompetent adult.

PubMed

Musham, Chaitanya K; Jarathi, Archana; Agarwal, Abhishek

2012-08-01

Acute epiglottitis (AE) is inflammation of the epiglottis and contiguous tissues, which carries a potential for complete airway obstruction. With routine pediatric immunization for Hemophilus influenzae serotype b, epiglottitis is now more prevalent in adults, with a shift in the causative organisms and a change in the natural history of this disease. Over the past 5 decades, Serratia marcescens has gone from being recognized as a harmless saprophyte to an important opportunistic human pathogen. It is known to be associated with outbreaks of nosocomial infections, but it is an uncommon cause of serious invasive infections in patients presenting from the community. The authors present a fatal case of AE caused by S marcescens in a previously immunocompetent 58-year-old woman, which was complicated by fasciitis, myositis and bacteremia. To the authors' knowledge, till date, only 3 cases of AE by S marcescens have been reported, all in immunocompromised patients.

Chronic Nicotine Treatment During Adolescence Attenuates the Effects of Acute Nicotine in Adult Contextual Fear Learning.

PubMed

Holliday, Erica D; Gould, Thomas J

2017-01-01

Adolescent onset of nicotine abuse is correlated with worse chances at successful abstinence in adulthood. One reason for this may be due to enduring learning deficits resulting from nicotine use during adolescence. Previous work has indicated that chronic nicotine administration beginning in late adolescence (PND38) caused learning deficits in contextual fear when tested in adulthood. The purpose of this study was to determine if chronic nicotine treatment during adolescence would alter sensitivity to nicotine's cognitive enhancing properties in adulthood. C57BL/6J mice received saline or chronic nicotine (12.6mg/kg/day) during adolescence (postnatal day 38) or adulthood (postnatal day 54) for a period of 12 days. Following a 30-day protracted abstinence, mice received either an acute injection of saline or nicotine (0.045, 0.18, and 0.36mg/kg) prior to training and testing a mouse model of contextual fear. It was found that chronic nicotine administration in adult mice did not alter sensitivity to acute nicotine following a protracted abstinence. In adolescent mice, chronic nicotine administration disrupted adult learning and decreased sensitivity to acute nicotine in adulthood as only the highest dose tested (0.36mg/kg) was able to enhance contextual fear learning. These results suggest that adolescent nicotine exposure impairs learning in adulthood, which could increase the risk for continued nicotine use in adulthood by requiring administration of higher doses of nicotine to reverse learning impairments caused by adolescent nicotine exposure. Results from this study add to the growing body of literature suggesting chronic nicotine exposure during adolescence leads to impaired learning in adulthood and demonstrates that nicotine exposure during adolescence attenuates the cognitive enhancing effects of acute nicotine in adulthood, which suggests altered cholinergic function. © The Author 2016. Published by Oxford University Press on behalf of the Society for

Zika virus-induced acute myelitis and motor deficits in adult interferon αβ/γ receptor knockout mice.

PubMed

Zukor, Katherine; Wang, Hong; Siddharthan, Venkatraman; Julander, Justin G; Morrey, John D

2018-06-01

Zika virus (ZIKV) has received widespread attention because of its effect on the developing fetus. It is becoming apparent, however, that severe neurological sequelae, such as Guillian-Barrë syndrome (GBS), myelitis, encephalitis, and seizures can occur after infection of adults. This study demonstrates that a contemporary strain of ZIKV can widely infect astrocytes and neurons in the brain and spinal cord of adult, interferon α/β receptor knockout mice (AG129 strain) and cause progressive hindlimb paralysis, as well as severe seizure-like activity during the acute phase of disease. The severity of hindlimb motor deficits correlated with increased numbers of ZIKV-infected lumbosacral spinal motor neurons and decreased numbers of spinal motor neurons. Electrophysiological compound muscle action potential (CMAP) amplitudes in response to stimulation of the lumbosacral spinal cord were reduced when obvious motor deficits were present. ZIKV immunoreactivity was high, intense, and obvious in tissue sections of the brain and spinal cord. Infection in the brain and spinal cord was also associated with astrogliosis as well as T cell and neutrophil infiltration. CMAP and histological analysis indicated that peripheral nerve and muscle functions were intact. Consequently, motor deficits in these circumstances appear to be primarily due to myelitis and possibly encephalitis as opposed to a peripheral neuropathy or a GBS-like syndrome. Thus, acute ZIKV infection of adult AG129 mice may be a useful model for ZIKV-induced myelitis, encephalitis, and seizure activity.

Impact of a Vitamin D Replacement Algorithm in Children and Young Adults With Acute Lymphoblastic Leukemia.

PubMed

Young, Jennifer; Welin, Elizabeth; Braeutigam, Carina; Gilger, Elizabeth; Lane, Adam; Salloum, Ralph

2018-05-04

Pediatric cancer patients have a high prevalence of vitamin D deficiency. Children and young adults with acute lymphoblastic leukemia are at high risk for associated poor bone outcomes due to contributing effects of chemotherapy and supportive care. Evidence-based vitamin D guidelines are lacking in this population. This is a retrospective study following the implementation of an institutional guideline for standardized monitoring and supplementing vitamin D based on 25-hydroxyvitamin D levels and patient age. Goal 25-hydroxyvitamin D level was defined as ≥30 ng/mL and levels were checked every 3 months. Over a period of 22 months, 69 patients (median age, 6.7 y) were included. At diagnosis, 42 patients (60.8%) were insufficient. Among insufficient patients at diagnosis, 83.3% became sufficient at first repeat level following supplementation. At completion of the study 95.6% of patients were sufficient. Insufficiency was more common in winter than summer at baseline (74.3% vs. 47.1%, P=0.03), though the impact of seasonality was overcome following the algorithm. Throughout the study 4 patients had supratherapeutic but nontoxic levels. Vitamin D replacement guidelines implemented in the pediatric and young adult acute lymphoblastic leukemia population markedly increased the percentage of vitamin D sufficient patients in a short period of time.

Total Marrow and Lymphoid Irradiation and Chemotherapy Before Donor Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Leukemia

ClinicalTrials.gov

2018-03-27

Adult Acute Lymphoblastic Leukemia in Complete Remission; Acute Myeloid Leukemia in Remission; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Childhood Acute Lymphoblastic Leukemia in Complete Remission

Treatment of acute decompensation of maple syrup urine disease in adult patients with a new parenteral amino-acid mixture.

PubMed

Servais, A; Arnoux, J B; Lamy, C; Hummel, A; Vittoz, N; Katerinis, I; Bazzaoui, V; Dubois, S; Broissand, C; Husson, M C; Berleur, M P; Rabier, D; Ottolenghi, C; Valayannopoulos, V; de Lonlay, P

2013-11-01

Acute decompensation of maple syrup urine disease (MSUD) is usually treated by enteral feeding with an amino-acid mixture without leucine (Leu), valine or isoleucine. However, its administration is ineffective in cases of gastric intolerance and some adult patients refuse enteral feeding via a nasogastric tube. We developed a new parenteral amino-acid mixture for patients with MSUD. Seventeen decompensation episodes in four adult patients with MSUD treated with a parenteral amino-acid mixture (group P) were compared to 18 previous episodes in the same patients treated by enteral feeding (group E). The mean Leu concentration at presentation was similar in the groups P and E (1196.9 μmol/L and 1212.2 μmol/L, respectively). The mean decrease in the Leu concentration during the first 3 days of hospitalisation was significantly higher in group P than group E (p = 0.0026); there were no side effects. The mean duration of hospitalisation was similar (4 vs. 4.5 days, p = NS). No patient in group P deteriorated whereas one patient in group E required dialysis. This new parenteral amino-acid mixture is safe and allows efficient Leu concentration decrease during acute MSUD decompensation episodes in adults. Its use avoids the need for nasogastric tube insertion.

Current practices related to family presence during acute deterioration in adult emergency department patients.

PubMed

Youngson, Megan J; Currey, Judy; Considine, Julie

2017-11-01

To explore the characteristics of and interactions between clinicians, patients and family members during management of the deteriorating adult patient in the emergency department. Previous research into family presence during resuscitation has identified many positive outcomes when families are included. However, over the last three decades the epidemiology of acute clinical deterioration has changed, with a decrease in in-hospital cardiac arrests and an increase in acute clinical deterioration. Despite the decrease in cardiac arrests, research related to family presence continues to focus on care during resuscitation rather than care during acute deterioration. Descriptive exploratory study using nonparticipatory observation. Five clinical deterioration episodes were observed within a 50-bed, urban, Australian emergency department. Field notes were taken using a semistructured tool to allow for thematic analysis. Presence, roles and engagement describe the interactions between clinicians, family members and patients while family are present during a patient's episode of deterioration. Presence was classified as no presence, physical presence and therapeutic presence. Clinicians and family members moved through primary, secondary and tertiary roles during patients' deterioration episode. Engagement was observed to be superficial or deep. There was a complex interplay between presence, roles and engagement with each influencing which form the other could take. Current practices of managing family during episodes of acute deterioration are complex and multifaceted. There is fluid interplay between presence, roles and engagement during a patient's episode of deterioration. This study will contribute to best practice, provide a strong foundation for clinician education and present opportunities for future research. © 2017 John Wiley & Sons Ltd.

Factor V Leiden 1691G/A and prothrombin gene 20210G/A polymorphisms as prothrombotic markers in adult Egyptian acute leukemia patients.

PubMed

El Sissy, Azza Hamdy; El Sissy, Maha H; Elmoamly, Shereef

2014-11-01

Factor V Leiden 1691G/A and prothrombin gene 20210G/A mutations are the most common genetic defects leading to thrombosis. This work aimed to study the FV Leiden and the prothrombin gene polymorphism in adult Egyptian patients with acute leukemia and their importance in thrombophilia screening. The study included 76 patients with acute leukemia and 100 healthy controls. Genotyping was done by real-time polymerase chain reaction technique. For factor V Leiden, the frequency of G/A mutation conferred more than 2.5-fold of increased risk of (OR 2.639 95 % CI 1.045-6.669). The frequency of factor V Leiden combined (G/A + A/A) genotypes conferred 2.83-fold of increased risk (OR 2.828, CI 1.13-7.075), The A allele conferred almost threefold increased risk (OR 2.824, 95 % CI 1.175-6.785). Despite higher frequency in patients compared to controls, there was no risk of association between prothrombin gene mutation and acute leukemia in adult Egyptians nor was there between combined genotypes of prothrombin gene mutation and factor V Leiden.

Tretinoin and Arsenic Trioxide in Treating Patients With Untreated Acute Promyelocytic Leukemia

ClinicalTrials.gov

2017-07-18

Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Childhood Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Myeloid Neoplasm

Acute myeloid leukemia (AML) - children

MedlinePlus

Acute myeloid leukemia is a cancer of the blood and bone marrow. Bone marrow is the soft tissue inside ... develops quickly. Both adults and children can get acute myeloid leukemia ( AML ). This article is about AML in children.

Decitabine and Total-Body Irradiation Followed By Donor Bone Marrow Transplant and Cyclophosphamide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

ClinicalTrials.gov

2018-02-16

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; 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; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

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

Current challenges and opportunities in treating adult patients with Philadelphia-negative acute lymphoblastic leukaemia.

PubMed

Wolach, Ofir; Amitai, Irina; DeAngelo, Daniel J

2017-12-01

Significant advances have been made in recent years in the field of Philadelphia-negative acute lymphoblastic leukaemia (ALL). New insights into the biology and genetics of ALL as well as novel clinical observations and new drugs are changing the way we diagnose, risk-stratify and treat adult patients with ALL. New genetic subtypes and alterations refine risk stratification and uncover new actionable therapeutic targets. The incorporation of more intensive, paediatric and paediatric-inspired approaches for young adults seem to have a positive impact on survival in this population. Minimal residual disease at different time points can assist in tailoring risk-adapted interventions for patients based on individual response. Finally, novel targeted approaches with monoclonal antibodies, immunotherapies and small molecules are moving through clinical development and entering the clinic. The aim of this review is to consolidate the abundance of emerging data and to review and revisit the concepts of risk-stratification, choice of induction and post-remission strategies as well as to discuss and update the approach to specific populations with ALL, such as young adult, elderly/unfit and relapsed/refractory patients with ALL. © 2017 John Wiley & Sons Ltd.

Clofarabine, Cytarabine, and Filgrastim in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia, Advanced Myelodysplastic Syndrome, and/or Advanced Myeloproliferative Neoplasm

ClinicalTrials.gov

2017-09-18

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); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Refractory Anemia With Excess Blasts; Untreated Adult Acute Myeloid Leukemia; Myeloproliferative Neoplasm With 10% Blasts or Higher

Transplantation of oligodendrocyte precursors and sonic hedgehog results in improved function and white matter sparing in the spinal cords of adult rats after contusion.

PubMed

Bambakidis, Nicholas C; Miller, Robert H

2004-01-01

A substantial cause of neurological disability in spinal cord injury is oligodendrocyte death leading to demyelination and axonal degeneration. Rescuing oligodendrocytes and preserving myelin is expected to result in significant improvement in functional outcome after spinal cord injury. Although previous investigators have used cellular transplantation of xenografted pluripotent embryonic stem cells and observed improved functional outcome, these transplants have required steroid administration and only a minority of these cells develop into oligodendrocytes. The objective of the present study was to determine whether allografts of oligodendrocyte precursors transplanted into an area of incomplete spinal cord contusion would improve behavioral and electrophysiological measures of spinal cord function. Additional treatment incorporated the use of the glycoprotein molecule Sonic hedgehog (Shh), which has been shown to play a critical role in oligodendroglial development and induce proliferation of endogenous neural precursors after spinal cord injury. Laboratory study. Moderate spinal cord contusion injury was produced in 39 adult rats at T9-T10. Ten animals died during the course of the study. Nine rats served as contusion controls (Group 1). Six rats were treated with oligodendrocyte precursor transplantation 5 days after injury (Group 2). The transplanted cells were isolated from newborn rat pups using immunopanning techniques. Another eight rats received an injection of recombinant Shh along with the oligodendrocyte precursors (Group 3), while six more rats were treated with Shh alone (Group 4). Eight additional rats received only T9 laminectomies to serve as noninjured controls (Group 0). Animals were followed for 28 days. After an initial complete hindlimb paralysis, rats of all groups receiving a contusive injury recovered substantial function within 1 week. By 28 days, rats in Groups 2 and 3 scored 4.7 and 5.8 points better on the Basso, Beattie, Bresnahan

Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma

ClinicalTrials.gov

2018-01-24

Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Ann Arbor Stage II Adult T-Cell Leukemia/Lymphoma; Ann Arbor Stage II Childhood Lymphoblastic Lymphoma; Ann Arbor Stage II Contiguous Adult Lymphoblastic Lymphoma; Ann Arbor Stage II Non-Contiguous Adult Lymphoblastic Lymphoma; Ann Arbor Stage III Adult Lymphoblastic Lymphoma; Ann Arbor Stage III Adult T-Cell Leukemia/Lymphoma; Ann Arbor Stage III Childhood Lymphoblastic Lymphoma; Ann Arbor Stage IV Adult Lymphoblastic Lymphoma; Ann Arbor Stage IV Adult T-Cell Leukemia/Lymphoma; Ann Arbor Stage IV Childhood Lymphoblastic Lymphoma; Childhood T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

Genetically Modified T-cell Immunotherapy in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia and Persistent/Recurrent Blastic Plasmacytoid Dendritic Cell Neoplasm

ClinicalTrials.gov

2018-03-02

Adult Acute Myeloid Leukemia in Remission; Acute Biphenotypic Leukemia; Early Relapse of Acute Myeloid Leukemia; Late Relapse of Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Blastic Plasmacytoid Dendritic Cell Neoplasm; Acute Myeloid Leukemia; Adult Acute Lymphoblastic Leukemia; Interleukin-3 Receptor Subunit Alpha Positive; Minimal Residual Disease; Refractory Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Decitabine, Vorinostat, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

ClinicalTrials.gov

2017-08-01

Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Low-Dose or High-Dose Conditioning Followed by Peripheral Blood Stem Cell Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia

ClinicalTrials.gov

2014-10-23

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Acute Myeloid Leukemia/Transient Myeloproliferative Disorder; 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); Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Myelodysplastic Syndrome With Isolated Del(5q); Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

Genetically engineered mouse models of human B-cell precursor leukemias.