Ticlopidine-associated aplastic anemia

 Serious hematologic complications associated with ticlopidine have been reported, including aplastic anemia. We report here an additional case of fatal aplastic anemia due to ticlopidine. A 66-year-old male patient developed fever and pancytopenia 2 months after ticlopidine was started. Despite the administration of granulocyte colony-stimulating factor (G-CSF) and broad-spectrum antibiotics, as well as aggressive red cell and platelet transfusions, the patient died 16 days after admission due to septic shock. Eighteen other cases of ticlopidine-induced aplastic anemia published in the English literature are also reviewed and presented here. Eight of the total 19 patients (including the one reported here) have died, mostly due to infection. Of the seven who received supportive treatment only, four had spontaneous recovery. Nine cases were treated with G-CSF or granulocyte-macrophage colony-stimulating factor (GM-CSF), and response was observed in only four of them. Several other cases were treated with high-dose corticosteroids or androgens; however, it was not possible to evaluate the efficacy of these treatments because of the limited number of cases. In the absence of satisfactory treatment for ticlopidine-induced aplastic anemia at present, it may be reasonable to try antilymphocyte globulin or cyclosporine. Also, great efforts should be made in the prevention and management of infection accompanying this disease. Received: 2 November 1997 / Accepted: 12 January 1998     

抗-CD47单克隆抗体对输血前检测试验的干扰及处理措施——附1例报告

目的探讨抗-CD47单克隆抗体对输血前检测试验的干扰及处理措施。方法收集1名接受抗-CD47单克隆抗体治疗的骨髓增生异常综合征受试者标本,进行ABO和Rh血型抗原鉴定,直接抗球蛋白试验,不规则抗体筛选和抗体鉴定试验,交叉配血试验;收集多人份O型献血者血小板制备成压积血小板,与受试者血浆进行吸收试验;收集Rh抗原分型分别为CCDee、ccDEE和ccdee的O型红细胞各1人份,分别与受试者血浆进行吸收试验;使用缺乏IgG4的抗球蛋白试剂Gamma-clone进行抗体筛选与交叉配血试验,使用Immucor Capture-R固相凝集试剂盒进行不规则抗体筛选试验。结果受试者直接抗球蛋白为阳性,游离抗体筛选和鉴定试验在所有介质中均为阳性(3+~4+);血浆与红细胞多次吸收后,抗体筛选和抗体鉴定为阴性;与多次血小板吸收后,抗体筛选和抗体鉴定仍为阳性;使用Gamma-clone抗球试剂进行不规则抗体筛选和配血试验,结果均为阴性;Immucor Capture-R固相凝集试剂盒进行不规则抗体筛选试验,结果为阴性。结论抗-CD47单克隆抗体可干扰输血前检测及交叉配血,使用缺乏检测IgG4的抗球蛋白试剂Gamma-clone和Immucor capture-R固相凝集法可较好去除抗-CD47干扰。     

Resting-state beta and gamma activity in Internet addiction

Internet addiction is the inability to control one's use of the Internet and is related to impulsivity. Although a few studies have examined neurophysiological activity as individuals with Internet addiction engage in cognitive processing, no information on spontaneous EEG activity in the eyes-closed resting-state is available. We investigated resting-state EEG activities in beta and gamma bands and examined their relationships with impulsivity among individuals with Internet addiction and healthy controls. Twenty-one drug-naïve patients with Internet addiction (age: 23.33 ± 3.50 years) and 20 age-, sex-, and IQ-matched healthy controls (age: 22.40 ± 2.33 years) were enrolled in this study. Severity of Internet addiction was identified by the total score on Young's Internet Addiction Test. Impulsivity was measured with the Barratt Impulsiveness Scale-11 and a stop-signal task. Resting-state EEG during eyes closed was recorded, and the absolute/relative power of beta and gamma bands was analyzed. The Internet addiction group showed high impulsivity and impaired inhibitory control. The generalized estimating equation showed that the Internet-addiction group showed lower absolute power on the beta band than did the control group (estimate = − 3.370, p < 0.01). On the other hand, the Internet-addiction group showed higher absolute power on the gamma band than did the control group (estimate = 0.434, p < 0.01). These EEG activities were significantly associated with the severity of Internet addiction as well as with the extent of impulsivity. The present study suggests that resting-state fast-wave brain activity is related to the impulsivity characterizing Internet addiction. These differences may be neurobiological markers for the pathophysiology of Internet addiction.     

The effect of gamma oscillations in boosting primary motor cortex plasticity is greater in young than older adults

ObjectiveIn healthy subjects, the long-term potentiation (LTP)-like plasticity of the primary motor cortex (M1) induced by intermittent theta-burst stimulation (iTBS) can be boosted by modulating gamma (γ) oscillations through transcranial alternating current stimulation (tACS). γ-tACS also reduces short-interval intracortical inhibition (SICI). We tested whether the effects of γ-tACS differ between young (YA) and older adults (OA).MethodsTwenty YA (27.2 ± 2.7 years) and twenty OA (65.3 ± 9.5 years) underwent iTBS-γ tACS and iTBS-sham tACS in randomized sessions. In a separate session, we delivered γ-tACS alone and recorded SICI during stimulation.ResultsiTBS-sham tACS produced comparable motor evoked potential (MEP) facilitation between groups. While iTBS-γ tACS boosted MEP facilitation in both the YA and OA groups, the magnitude of its effect was significantly lower in OA. Similarly, γ-tACS-induced modulation of GABA-A-ergic neurotransmission, as tested by SICI, was reduced in OA. The effect of iTBS-γ tACS negatively correlated with the age of OA subjects.ConclusionsMechanisms underlying the effects of γ oscillations on LTP-like plasticity become less efficient in older adults. This could reflect age-related changes in neural elements of M1 resonant to γ oscillations, including GABA-A-ergic interneurons.SignificanceThe beneficial effect of γ-tACS on iTBS-induced plasticity is reduced in older adults.     

Dichotic listening deficits in amblyaudia are characterized by aberrant neural oscillations in auditory cortex

ObjectiveChildren diagnosed with auditory processing disorder (APD) show deficits in processing complex sounds that are associated with difficulties in higher-order language, learning, cognitive, and communicative functions. Amblyaudia (AMB) is a subcategory of APD characterized by abnormally large ear asymmetries in dichotic listening tasks.MethodsHere, we examined frequency-specific neural oscillations and functional connectivity via high-density electroencephalography (EEG) in children with and without AMB during passive listening of nonspeech stimuli.ResultsTime-frequency maps of these “brain rhythms” revealed stronger phase-locked beta-gamma (~35 Hz) oscillations in AMB participants within bilateral auditory cortex for sounds presented to the right ear, suggesting a hypersynchronization and imbalance of auditory neural activity. Brain-behavior correlations revealed neural asymmetries in cortical responses predicted the larger than normal right-ear advantage seen in participants with AMB. Additionally, we found weaker functional connectivity in the AMB group from right to left auditory cortex, despite their stronger neural responses overall.ConclusionOur results reveal abnormally large auditory sensory encoding and an imbalance in communication between cerebral hemispheres (ipsi- to -contralateral signaling) in AMB.SignificanceThese neurophysiological changes might lead to the functionally poorer behavioral capacity to integrate information between the two ears in children with AMB.     

ArcCheck探测螺旋断层放疗误差的敏感性

目的:针对螺旋断层放疗（HT）系统,分析ArcCheck验证患者计划通过率对治疗床运动速度误差、机架旋转周期误差、机架起始角度误差、多叶准直器叶片开启时间误差的敏感性。方法:选取9例行HT的鼻咽癌患者计划,由自编程序生成与原计划相对应的误差计划。应用点剂量及Gamma分析,计算得出上述误差的临床可检测误差值。结果:所有患者的原计划采用3%/2 mm、2%/1 mm标准时的平均Gamma通过率分别为97.49%±1.08%、73.38%±4.31%。应用3%/2 mm通过率标准时,可检测的最小误差分别为治疗床运动速度:-1.58%、1.38%（上下限阈值）,机器旋转周期:-1.68%、1.31%（上下限阈值）,机架起始角度误差:2.50°,多叶准直器叶片开启时间:1.62%。而应用2%/1 mm标准时,检测精度得到提升,可检测的最小误差分别为治疗床运动速度:-0.69%、1.27%,机器旋转周期:-0.69%、0.69%,机架起始角度误差:2.06°,多叶准直器叶片开启时间:0.52%。结论:ArcCheck与电离室测量点剂量联用与单独使用ArcCheck Gamma通过率相比并未表现出明显优势,ArcCheck可以检测出临床相关的照射误差,更为严格的Gamma通过率标准可以明显提高误差计划的检测精度。     

Prognostic value of the pretreatment albumin:globulin ratio combined with adult comorbidity evaluation 27 and TMN staging in patients with squamous cell carcinoma of the maxillary sinus

The albumin:globulin (A:G) ratio, adult comorbidity evaluation 27 (ACE-27), and TMN staging have been shown to be strong predictive indicators of the survival of patients with many types of tumours. We have investigated the prognostic value of pretreatment based on the A:G ratio combined with TMN staging and ACE-27 in patients with squamous cell carcinoma (SCC) of the maxillary sinus. We studied 196 patients, and the prognostic value was explored by univariate and multivariate Cox’s hazards analysis. Multivariate analyses suggested that pretreatment A:G ratio was independently associated with overall survival (hazard ratio (HR) 1.542, 95% CI 1.219 to 1.991, p = 0.002); disease-specific survival, (HR 1.499, 95% CI 1.197 to 1.842, p = 0.001); and disease-free survival (HR 1.452, 95% CI 1.207 to 1.834, p < 0.001). Additional prognostic factors shown in the survival analyses included ACE-27, pathological T stage, and pathological N stage. Pretreatment A:G ratio combined with ACE-27 and TMN staging were powerful prognostic indicators of outcome in patients with SCC of the maxillary sinus, which has potentially important ramifications for stratification of the disease in the future.     

γ刀照射三叉神经的剂量-效应关系研究

目的 探讨伽玛刀不同剂量照射大鼠三叉神经(感觉根)后对照射范围内三叉神经组织的损伤以及对周围临近脑干组织和脑桥的影响,为优化伽玛刀照射剂量提供理论依据。方法 选用成年雄性SD大鼠65只,分别以不同照射剂量(20、40、80、160 Gy)照射三叉神经,观察照射后1周、2周、4周大鼠行为学变化,取全脑组织进行HE、Nissl、MAPLC3B、53BP1、XRCC1染色观察细胞形态学和自噬以及DNA损伤和修复等变化。结果 所有剂量组照射大鼠均存活。20和40 Gy组均无行为学和病理学改变;80和160 Gy组均出现了照射部位毛发脱落;HE、Nissle、LC3B、53BP1及XRCC1染色发现,受照部位组织在80和160 Gy照射后,可见神经元细胞固缩、膨胀,神经元细胞发生自噬以及DNA损伤明显,160 Gy组DNA损伤明显加重。40 Gy照射后,神经元发生DNA损伤修复的程度较其他剂量增高。结论 伽玛刀照射三叉神经根对神经元有明显的剂量-效应关系。     

Induction of suppressive allogeneic regulatory T cells via rabbit antithymocyte polyclonal globulin during homeostatic proliferation in rat kidney transplantation

Experimental studies have shown that rabbit antithymocyte polyclonal globulin (ATG) can expand human CD4+CD25++Foxp3+ cells (Tregs). We investigated the major biological effects of a self‐manufactured rabbit polyclonal anti‐rat thymoglobulin (rATG) in vitro, as well as its effects on different peripheral T‐cell subsets. Moreover, we evaluated the allogeneic suppressive capacity of rATG‐induced Tregs in an experimental rat renal transplant model. Our results show that rATG has the capacity to induce apoptosis in T lymphocyte lymphocytes as a primary mechanism of T‐cell depletion. Our in vivo studies demonstrated a rapid but transient cellular depletion of the main T cell subsets, directly proportional to the rATG dose used, but not of the effector memory T cells, which required significantly higher rATG doses. After rATG administration, we observed a significant proliferation of Tregs in the peripheral blood of transplanted rats, leading to an increase in the Treg/T effector ratio. Importantly, rATG‐induced Tregs displayed a strong donor‐specific suppressive capacity when assessed in an antigen‐specific allogeneic co‐culture. All of these results were associated with better renal graft function in rats that received rATG. Our study shows that rATG has the biological capacity immunomodulatory to promote a regulatory alloimmune milieu during post‐transplant homeostatic proliferation.