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61.
A 62-year-old woman was referred for evaluation of hypoxemia. Despite a resting SaO(2) of 89%, she was otherwise asymptomatic. The arterial blood gas on room air demonstrated a pO(2) of 58 mm Hg. Two shunt studies confirmed a shunt fraction of 25%. Echocardiogram with agitated saline demonstrated bubbles in the left atrium. Nuclear perfusion study revealed no uptake over the kidneys or brain. Computed tomography of the chest and cardiac magnetic resonance imaging confirmed the presence of a large shunt (azygous continuation of the inferior vena cava [ACIVC] with anomalous hepatic vein drainage). A large shunt fraction dictates either significant cardiac septal defect or an extracardiac shunt. The finding of ACIVC should prompt consideration of other vascular or cardiac abnormalities. The true incidence of isolated ACIVC is not known, as limited ACIVC may remain asymptomatic. However, the spectrum of vascular, cardiac and somatic abnormalities that may accompany ACIVC is quite varied. 相似文献
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P Yan D Frankhouser M Murphy HH Tam B Rodriguez J Curfman M Trimarchi S Geyer YZ Wu SP Whitman K Metzeler A Walker R Klisovic S Jacob MR Grever JC Byrd CD Bloomfield R Garzon W Blum MA Caligiuri R Bundschuh G Marcucci 《Blood》2012,120(12):2466-2474
The outcome of older (≥ 60 years) acute myeloid leukemia (AML) patients is poor, and novel treatments are needed. In a phase 2 trial for older AML patients, low-dose (20 mg/m(2) per day for 10 days) decitabine, a DNA hypomethylating azanucleoside, produced 47% complete response rate with an excellent toxicity profile. To assess the genome-wide activity of decitabine, we profiled pretreatment and post treatment (day 25/course 1) methylomes of marrow samples from patients (n = 16) participating in the trial using deep-sequencing analysis of methylated DNA captured by methyl-binding protein (MBD2). Decitabine significantly reduced global methylation compared with pretreatment baseline (P = .001). Percent marrow blasts did not correlate with global methylation levels, suggesting that hypomethylation was related to the activity of decitabine rather than to a mere decrease in leukemia burden. Hypomethylation occurred predominantly in CpG islands and CpG island-associated regions (P ranged from .03 to .04) A significant concentration (P < .001) of the hypomehtylated CpG islands was found in chromosome subtelomeric regions, suggesting a differential activity of decitabine in distinct chromosome regions. Hypermethylation occurred much less frequently than hypomethylation and was associated with low CpG content regions. Decitabine-related methylation changes were concordant with those previously reported in distinct genes. In summary, our study supports the feasibility of methylome analyses as a pharmacodynamic endpoint for hypomethylating therapies. 相似文献
64.
Targeted therapy with imatinib and other selective tyrosine kinase inhibitors has transformed the treatment of chronic myeloid leukemia. Unlike chronic myeloid leukemia, chronic lymphocytic leukemia (CLL) lacks a common genetic aberration amenable to therapeutic targeting. However, our understanding of normal B-cell versus CLL biology points to differences in properties of B-cell receptor (BCR) signaling that may be amenable to selective therapeutic targeting. The applica-tion of mouse models has further expanded this understanding and provides information about targets in the BCR signaling pathway that may have other important functions in cell development or long-term health. In addition, overexpression or knockout of selected targets offers the potential to validate targets genetically using new mouse models of CLL. The initial success of BCR-targeted therapies has promoted much excitement in the field of CLL. At the present time, GS-1101, which reversibly inhibits PI3Kδ, and ibrutinib (PCI-32765), an irreversible inhibitor of Bruton tyrosine kinase, have generated the most promising early results in clinical trials including predominately refractory CLL where durable disease control has been observed. This review provides a summary of BCR signaling, tools for studying this pathway relevant to drug development in CLL, and early progress made with therapeutics targeting BCR-related kinases. 相似文献
65.
SM Jaglowski AS Ruppert NA Heerema A Bingman JM Flynn MR Grever JA Jones P Elder SM Devine JC Byrd LA Andritsos 《British journal of haematology》2012,159(1):82-87
Complex karyotype (CK) on metaphase cytogenetics discriminates poor outcome in chronic lymphocytic leukaemia (CLL) patients undergoing salvage treatment; we hypothesized that it might provide prognostic information for patients undergoing allogeneic stem cell transplant. Fifty‐one CLL patients were analysed following transplant; 18‐month overall survival (OS), event‐free survival (EFS) and cumulative incidence of progression estimates were 35%, 14% and 63%, respectively, in patients with CK (n = 19) versus 83%, 68% and 29% in patients without (n = 32) (P ≤ 0·0001, P ≤ 0·0001, and P = 0·02). In patients with high‐risk interphase cytogenetics, CK remained predictive of worse OS (P = 0·02) and EFS (P = 0·009). These findings support further evaluation of metaphase karyotype in transplant risk assessment. 相似文献
66.
Michelle M. Jacobs Jacinta Murray Desiree A. Byrd Yasmin L. Hurd Susan Morgello 《Journal of neurovirology》2013,19(5):495-504
It has been postulated that drugs of abuse act synergistically with HIV, leading to increased neurotoxicity and neurocognitive impairment. The CNS impacts of HIV and drug use converge on the mesocorticolimbic dopamine (DA) system, which contains two main receptor subtypes: dopamine receptors 1 (DRD1) and 2 (DRD2). DRD1 and DRD2 have been linked to substance dependence; whether they predict HIV-associated neurocognitive disorder (HAND) is unclear. Using an advanced-stage HIV+ population, we sought to determine if drug dependence impacts the contribution of DA receptor polymorphisms on neurocognition. We observed that both DRD1 and DRD2 polymorphisms were associated with opiate and cocaine dependence (P?<?0.05) in Caucasian subjects, but not African-American individuals. Using linear regression analysis, we examined the polymorphisms for associations with neuropsychological performance in global and cognitive domain T-scores (Motor, Processing Speed, Verbal Fluency, Learning, Memory, Executive Functioning, Working Memory) while controlling for opiate and cocaine dependency. In the Motor domain, we observed an association for two DRD2 polymorphisms (P?<?0.05) in Caucasian subjects. The effects differed for substance dependence groups as the direction of the correlations with DRD2 were opposite to what was seen in subjects without these dependencies. In African-American subjects, associations were observed in nearly every domain, and again, the direction of the correlation differed between substance-dependent and substance-independent groups. We conclude that studies to examine genetic risk for HAND must carefully account for substance dependence patterns when assaying dopaminergic systems, as the neurobiological substrates of cognition in HIV populations may vary with tonic alterations secondary to chronic substance exposures. 相似文献
67.
Geoffrey A. Coalson Courtney T. Byrd Shanley B. Treleaven Lillian Dang 《Clinical linguistics & phonetics》2013,27(3):256-278
Non-word repetition is weaker for adults who stutter (AWS) compared to adults who do not stutter (AWNS) as phonological demands increase. However, non-word stimuli used in previous studies varied by length, but did not vary with regard to segmental or metrical complexity. The purpose of the present study was to examine the unique influence of these two distinct types of complexity on non-word repetition in AWS and AWNS via administration of the Test of Phonological Structure (TOPhS). Twenty-four adults (12 AWNS, 12 AWS) repeated 96 non-words within a soundproof booth immediately after auditory presentation. All 96 non-word targets included on the TOPhS were one to four syllables in length and ranked based on segmental complexity (simple, moderate and complex) and metrical complexity (simple, moderate and complex). No main effect of metrical complexity was detected between groups, and no differences in accuracy were observed for non-words with simple or moderate segmental complexity. However, AWS were significantly more likely to produce a phonemic error when repeating words with complex segmental structure than AWNS, irrespective of metrical complexity. Segmental complexity may contribute to the differences in phonological working memory in AWS when controlling for metrical complexity and length. 相似文献
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