Test–retest repeatability of [18F]Flortaucipir PET in Alzheimer’s disease and cognitively normal individuals

The aim of this study was to investigate the test–retest (TRT) repeatability of various parametric quantification methods for [¹⁸F]Flortaucipir positron emission tomography (PET). We included eight subjects with dementia or mild cognitive impairment due to Alzheimer’s disease and six cognitively normal subjects. All underwent two 130-min dynamic [¹⁸F]Flortaucipir PET scans within 3 ± 1 weeks. Data were analyzed using reference region models receptor parametric mapping (RPM), simplified reference tissue method 2 (SRTM2) and reference logan (RLogan), as well as standardized uptake value ratios (SUVr, time intervals 40–60, 80–100 and 110–130 min post-injection) with cerebellar gray matter as reference region. We obtained distribution volume ratio or SUVr, first for all brain regions and then in three tau-specific regions-of-interest (ROIs). TRT repeatability (%) was defined as |retest–test|/(average (test + retest)) × 100. For all methods and across ROIs, TRT repeatability ranged from (median (IQR)) 0.84% (0.68–2.15) to 6.84% (2.99–11.50). TRT repeatability was good for all reference methods used, although semi-quantitative models (i.e. SUVr) performed marginally worse than quantitative models, for instance TRT repeatability of RPM: 1.98% (0.78–3.58) vs. SUVr_80–100: 3.05% (1.28–5.52), p < 0.001. Furthermore, for SUVr_80–100 and SUVr_110–130, with higher average SUVr, more variation was observed. In conclusion, while TRT repeatability was good for all models used, quantitative methods performed slightly better than semi-quantitative methods.     

Simultaneous measurement of beta-amyloid(1-42), total tau, and phosphorylated tau (Thr181) in cerebrospinal fluid by the xMAP technology

BACKGROUND: To simultaneously study several biomarkers for Alzheimer disease (AD), we used the xMAP technology to develop and evaluate a multiparametric bead-based assay for quantification of beta-amyloid((1-42)) [Abeta((1-42))], total tau (T-TAU), and hyperphosphorylated tau [P-TAU((181P))] in cerebrospinal fluid (CSF). METHODS: We compared the new multianalyte assay format with established ELISA techniques for the same proteins. We then performed a clinical study using CSF samples from patients with AD or mild cognitive impairment with progression to AD, healthy controls, and patients with other neurologic disorders. RESULTS: The INNO-BIA AlzBio3 selectively and specifically measured Abeta((1-42)), T-TAU, and P-TAU((181P)) in the CSF. The new assay format had intra- and interassay CVs <10% for all analytes, even at low concentrations. The measurement range of the new assay was 3 to 4 logs compared with 1 to 2 logs for ELISAs. By plotting the mean of the values obtained in ELISA and the xMAP technology against the difference, we found that a correction factor could be used to convert xMAP results to ELISA values. The clinical study demonstrated that the new multiparametric assay could accurately distinguish patients with AD from patients with other neurologic disorders or control patients, with the diagnostic accuracy reaching recommended consensus criteria for specificity and sensitivity. CONCLUSION: The new multiparametric method may be able to replace the corresponding ELISA methods.     

60Coγ射线局部辐射后小鼠非辐射区域骨髓巨核细胞的变化

目的:临床局部辐射条件下会造成非辐射区域组织及细胞功能损害,最为突出的是对造血功能的影响。实验建立60Coγ射线左半身辐射动物模型,观察局部电离辐射对其非辐射区域骨髓巨核细胞的影响。方法:实验于2003-10/2005-03在解放军第三军医大学辐照中心和全军复合伤研究所完成。①实验动物:6～8周龄SPF级雄性昆明小鼠180只,随机数字表法分为正常对照组、全身辐射组、左半身辐射组、全身屏蔽辐射组,45只/组。②实验方法:全身辐射组小鼠固定于辐射架内;左半身辐射组小鼠麻醉后固定体位,用铅砖屏蔽右半身;全身屏蔽辐射组小鼠麻醉固定体位,用铅砖屏蔽全身。以60Coγ射线一次性辐射,剂量率68.46cGy/min。正常对照组不作任何干预。③实验评估:辐射后不同时相检测小鼠血清丙二醛含量及超氧化物歧化酶活性变化,计数外周血血小板,检测骨髓巨核祖细胞集落形成单位,观察骨髓组织病理改变及CD41a、CD61的表达。结果:全身辐射组第8天死亡2只,第9天死亡4只,其余各组无脱失。①外周血血小板计数:辐射后第2,7天,左半身辐射组外周血血小板数量显著低于正常对照组(P<0.01),但高于全身辐射组(P<0.01)。②血清丙二醛含量及超氧化物歧化酶活性变化:辐射后第2,9天,左半身辐射组血清丙二醛含量显著高于正常对照组(P<0.01),低于全身辐射组(P<0.01);血清超氧化物歧化酶活性显著低于正常对照组(P<0.01),高于全身辐射组(P<0.01)。③骨髓巨核祖细胞集落形成单位的变化:与正常对照组比较,辐射后6h左半身辐射组非辐射侧的巨核祖细胞集落形成单位显著降低(P<0.01),高于全身辐射组及左半身辐射组(P<0.01)。④骨髓组织病理改变:正常对照组有核细胞比例较高,分布均匀,并见多量散在分布的细胞龛;辐射2d后,左半身辐射组非辐射侧骨髓有核细胞较正常对照组减少,但好于全身辐射组、左半身辐射组。⑤骨髓CD41a及CD61表达的变化:辐射后2d与正常对照组比较,左半身辐射组非辐射侧骨髓CD41a及CD61阳性细胞数和相对荧光强度均显著降低(P<0.01),但高于全身辐射组、左半身辐射组(P<0.01)。结论:局部电离辐射作用后,可导致小鼠非辐射区域骨髓巨核细胞增殖能力降低,血小板减少,产生功能障碍。氧自由基激活可能参与了该损伤过程。     

Serotonin and superior mesenteric artery resistance index

OBJECTIVE: Serotonin is a vasoactive neuroendocrine substance and serotonergic drugs are promising agents for the treatment of functional gastrointestinal disorders. The effect of serotonin on superior mesenteric blood flow in humans is unknown. The aim of this study was to examine the effect of exogenous serotonin on superior mesenteric artery blood flow, as estimated by the resistance index with Doppler ultrasound, in healthy human volunteers. MATERIAL AND METHODS: Six fasting healthy adult volunteers of both genders were studied. Transabdominal Doppler ultrasound was used to evaluate the effects of either a standard meal or intravenous infusion of serotonin (2.5-20 nmol kg-1 min-1) on the superior mesenteric artery resistance index, platelet-depleted plasma levels of serotonin, blood pressure, heart rate and electrocardiogram. RESULTS: All subjects had the same patterns of response to meal and serotonin stimulation. Meal stimulation decreased the mean resistance index from 0.84+/-0.04 to 0.72+/-0.02 (p = 0.0004) and increased platelet-depleted-plasma levels of serotonin from 50+/-36 to 61+/-46 nmol L-1 (p = 0.04). Serotonin stimulation increased the mean resistance index from 0.82+/-0.04 to 0.88+/-0.03 (p = 0.006) and mean platelet-depleted-plasma levels of serotonin from 44+/-24 to 83+/-37 nmol L-1 (p = 0.03). Most subjects reported minor short-lived adverse effects. Electrocardiogram results were unchanged during all examinations. CONCLUSIONS: We conclude that intravenous infusion of serotonin increases the resistance index of the superior mesenteric artery (increases downstream resistance) in healthy adult volunteers.     

Cold saline infusion and ice packs alone are effective in inducing and maintaining therapeutic hypothermia after cardiac arrest

Aim of the study

Hypothermia treatment with cold intravenous infusion and ice packs after cardiac arrest has been described and used in clinical practice. We hypothesised that with this method a target temperature of 32-34 °C could be achieved and maintained during treatment and that rewarming could be controlled.

Materials and methods

Thirty-eight patients treated with hypothermia after cardiac arrest were included in this prospective observational study. The patients were cooled with 4 °C intravenous saline infusion combined with ice packs applied in the groins, axillae, and along the neck. Hypothermia treatment was maintained for 26 h after cardiac arrest. It was estimated that passive rewarming would occur over a period of 8 h. Body temperature was monitored continuously and recorded every 15 min up to 44 h after cardiac arrest.

Results

All patients reached the target temperature interval of 32-34 °C within 279 ± 185 min from cardiac arrest and 216 ± 177 min from induction of cooling. In nine patients the temperature dropped to below 32 °C during a period of 15 min up to 2.5 h, with the lowest (nadir) temperature of 31.3 °C in one of the patients. The target temperature was maintained by periodically applying ice packs on the patients. Passive rewarming started 26 h after cardiac arrest and continued for 8 ± 3 h. Rebound hyperthermia (>38 °C) occurred in eight patients 44 h after cardiac arrest.

Conclusions

Intravenous cold saline infusion combined with ice packs is effective in inducing and maintaining therapeutic hypothermia, with good temperature control even during rewarming.