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A clinically meaningful fetal hemoglobin threshold for children with sickle cell anemia during hydroxyurea therapy 下载免费PDF全文
Jeremie H. Estepp Matthew P. Smeltzer Guolian Kang Chen Li Winfred C. Wang Christina Abrams Banu Aygun Russell E. Ware Kerri Nottage Jane S. Hankins 《American journal of hematology》2017,92(12):1333-1339
Hydroxyurea has proven clinical benefits and is recommended to be offered to all children with sickle cell anemia (SCA), but the optimal dosing regimen remains controversial. Induction of red blood cell fetal hemoglobin (HbF) by hydroxyurea appears to be dose‐dependent. However, it is unknown whether maximizing HbF% improves clinical outcomes. HUSTLE (NCT00305175) is a prospective observational study with a primary goal of describing the long‐term clinical effects of hydroxyurea escalated to maximal tolerated dose (MTD) in children with SCA. In 230 children, providing 610 patient‐years of follow up, the mean attained HbF% at MTD was >20% for up to 4 years of follow‐up. When HbF% values were ≤20%, children had twice the odds of hospitalization for any reason (P < .0001), including vaso‐occlusive pain (P < .01) and acute chest syndrome (ACS) (P < .01), and more than four times the odds of admission for fever (P < .001). Thirty day readmission rates were not affected by HbF%. Neutropenia (ANC <1000 × 106/L) was rare (2.3% of all laboratory monitoring), transient, and benign. Therefore, attaining HbF >20% was associated with fewer hospitalizations without significant toxicity. These data support the use of hydroxyurea in children, and suggest that the preferred dosing strategy is one that targets a HbF endpoint >20%. 相似文献
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Odabasoglu F Yildirim OS Aygun H Halici Z Halici M Erdogan F Cadirci E Cakir A Okumus Z Aksakal B Aslan A Unal D Bayir Y 《European journal of pharmacology》2012,674(2-3):171-178
Usnea longissima Ach., a lichen species, is a traditional herbal medicine with anti-detrimental effects. We evaluated the in vivo effects of a major constituent of U. longissima, diffractaic acid, and the main fatty component of the Mediterranean diet, olive oil, against apoptosis, including various caspase activations and oxidative injury in surrounding tissues after titanium implantation in rabbit femurs. Furthermore, we evaluated the underlying molecular mechanisms. In this study, this lichen metabolite and olive oil activated caspase-dependent cell death with apoptotic morphology, which is distinctly different from necrosis. Both orally and locally administered olive oil and diffractaic acid exerted pro-apoptotic induction in tissues surrounding the implants in titanium-implanted rabbits through the activation of initiator caspases (Cas-2, -8 and -9) and executioner caspase (Cas-3). In addition, they displayed strong myeloperoxidase and inducible nitric oxide synthase activities, providing an alleviating effect. Furthermore, administrations of diffractaic acid and olive oil attenuated the Ti-alloy implantation, and decreased superoxide dismutase activity and total glutathione level in peri-implant tissues. These results demonstrate that diffractaic acid and olive oil are involved in the induction of apoptotic cell death both through caspase-dependent cell death and as an antioxidant. Thus, the data suggest that both diffractaic acid and olive oil could be developed as effective proapoptotic agents in various disorders treatments. 相似文献
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Apollonsky N Shende A Ouansafi I Brody J Atlas M Aygun B 《Journal of pediatric hematology/oncology》2008,30(11):860-864
Transient myeloproliferative disorder (TMD) in newborns with Down syndrome (DS) has been well described. We report 4 newborns, 2 with DS and 2 without DS, who developed TMD. One newborn with DS developed multiorgan failure and died despite treatment with low-dose cytarabine. In 3 newborns, the TMD resolved spontaneously. Two of these patients, 1 with and 1 without DS developed leukemia on subsequent follow-up and were treated successfully. We reviewed the clinical and laboratory data on 14 non-DS infants with TMD reported in the literature. According to limited data, these patients are more likely to develop leukemia than DS patients, however their outcome is better. 相似文献
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Left ventricular non‐compaction is a rare form of cardiomyopathy believed to be the result of intrauterine arrest of compaction of the endomyocardial morphogenesis, leading to persistence of the embryonic myocardium. Clinical manifestations are highly variable, ranging from no symptoms to a progressive deterioration in cardiac function that results in congestive heart failure, systemic thromboemboli, arrhythmias, and sudden cardiac death. Presented here is the case of a 4‐year‐old child with a history of aborted sudden cardiac death. Following resuscitation, he was admitted to the intensive care unit with neurologic sequelae that regressed later on. Transthoracic echocardiography and magnetic resonance imaging showed numerous prominent trabeculations and deep intertrabecular recesses at the apical and anterolateral region of the left ventricle. Electrophysiologic study showed polymorphic ventricular tachycardia. An implantable cardioverter–defibrillator (ICD) was implanted following clinical recovery. Five months after implantation, appropriate ICD shock due to ventricular fibrillation was documented. 相似文献
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Arzu Ozturk Nafi Aygun Seth A. Smith Brian Caffo Peter A. Calabresi Daniel S. Reich 《Neuroradiology》2013,55(4):431-439
Introduction
In multiple sclerosis (MS), spinal cord imaging can help in diagnosis and follow-up evaluation. However, spinal cord magnetic resonance imaging (MRI) is technically challenging, and image quality, particularly in the axial plane, is typically poor compared to brain MRI. Because gradient-recalled echo (GRE) images might offer improved contrast resolution within the spinal cord at high magnetic field strength, both without and with a magnetization transfer prepulse, we compared them to T2-weighted fast-spin-echo (T2-FSE) images for the detection of MS lesions in the cervical cord at 3T.Methods
On a clinical 3T MRI scanner, we studied 62 MS cases and 19 healthy volunteers. Axial 3D GRE sequences were performed without and with off-resonance radiofrequency irradiation. To mimic clinical practice, all images were evaluated in conjunction with linked images from a sagittal short tau inversion recovery scan, which is considered the gold standard for lesion detection in MS. Two experienced observers recorded image quality, location and size of focal lesions, atrophy, swelling, and diffuse signal abnormality independently at first and then in consensus.Results
The number and volume of lesions detected with high confidence was more than three times as high on both GRE sequences compared to T2-FSE (p?<?0.0001). Approximately 5 % of GRE scans were affected by artifacts that interfered with image interpretation, not significantly different from T2W-FSE.Conclusions
Axial 3D GRE sequences are useful for MS lesion detection when compared to 2D T2-FSE sequences in the cervical spinal cord at 3T and should be considered when examining intramedullary spinal cord lesions. 相似文献50.
Serkan Guneyli Meltem Tor Hur Hassoy Murat Serhat Aygun Emre Altinmakas Susamber Dik Altintas Recep Savas 《Diagnostic and interventional radiology (Ankara, Turkey)》2021,27(4):469
PURPOSEWe aimed to investigate the value of magnetic resonance imaging (MRI)-based parameters in differentiating between progressive massive fibrosis (PMF) and lung cancer.METHODSThis retrospective study included 60 male patients (mean age, 67.0±9.0 years) with a history of more than 10 years working in underground coal mines who underwent 1.5 T MRI of thorax due to a lung nodule/mass suspicious for lung cancer on computed tomography. Thirty patients had PMF, and the remaining ones had lung cancer diagnosed histopathologically. The sequences were as follows: coronal single-shot turbo spin echo (SSH-TSE), axial T1- and T2-weighted spin-echo (SE), balanced turbo field echo, T1-weighted high-resolution isotropic volume excitation, free-breathing and respiratory triggered diffusion-weighted imaging (DWI). The patients’ demographics, lesion sizes, and MRI-derived parameters were compared between the patients with PMF and lung cancer.RESULTSApparent diffusion coefficient (ADC) values of DWI and respiratory triggered DWI, signal intensities on T1-weighted SE, T2-weighted SE, and SSH-TSE imaging were found to be significantly different between the groups (p < 0.001, for all comparisons). Median ADC values of free-breathing DWI in patients with PMF and cancer were 1.25 (0.93–2.60) and 0.76 (0.53–1.00) (× 10−3 mm2/s), respectively. Most PMF lesions were predominantly iso- or hypointense on T1-weighted SE, T2-weighted SE, and SSH-TSE, while most malignant ones predominantly showed high signal intensity on these sequences.CONCLUSIONMRI study including SE imaging, specially T1-weighted SE imaging and ADC values of DWI can help to distinguish PMF from lung cancer.Pneumoconiosis, defined as the accumulation of inhaled particles is relatively common in industrial areas (1). Coal worker’s pneumoconiosis, silicosis, and asbestosis are the most common forms of pneumoconiosis (2). Progressive massive fibrosis (PMF) of the lung is defined as a combination of anthracosilicotic nodules and connective tissue, and it may be seen in the chronic stage of pneumoconiosis (1).The imaging features of PMF on chest radiography and computed tomography (CT) have been well investigated (3, 4). The main characteristic finding of PMF on CT is an irregular nodule or mass with or without calcification, located mostly in the upper and middle lung zones (5). However, it is occasionally difficult to distinguish PMF from lung cancer due to a similar appearance on these imaging modalities as well as similar clinical presentation. The differentiation is especially difficult, when PMF lesion appears as a mass or mass-like lesion and grows in size during the follow-up. Additionally, lung cancer may be seen together with underlying PMF lesion. 18F-fluoro-2-deoxy-D-glucose positron emission tomography/CT (18F-FDG PET/CT) can be used in differentiation between PMF and lung cancer but it may not be helpful in some cases (6).Magnetic resonance imaging (MRI) with high conrast resolution and additional diignostic facility tools may be helpful in terms of avoiding biopsy and its possible complications in the differentiation between PMF and lung cancer (7, 8). A low signal intensity (SI) on T2-weighted MRI and a gradual increase in SI in a dynamic MRI study are the reported, characteristic MRI findings of PMF (9, 10). However, the use of several MRI sequences has not yet been fully explored for the differentiation between PMF and lung cancer. In addition to the SI changes, assessment of quantitative MRI parameters could also be helpful in the differentiation of these entities. The purpose of this study was to investigate the value of MRI-based parameters in differentiating between PMF and lung cancer. 相似文献