Treatment of thalassaemia: a review of the new approaches on transfusion safety and the novel therapeutics

Lifetime red cell concentrate (RCC) transfusions still account for significant iron overload‐related morbidity and mortality despite chelation therapy in thalassaemia. The cumulative risk of transfusion‐transmitted infections is substantial for thalassaemia patients. Pathogen reduction technologies for RCC may imply a proactive approach against new/re‐emerging pathogens and may be an ultimate safeguard for transfusion safety in the developing countries. Red cell alloimmunization may become a significant clinical challenge in thalassaemia. The availability of high‐throughput molecular blood group antigen typing in the donors may allow perfect match transfusion, beyond ABO‐D and CEK antigen‐matched transfusions. Allogeneic stem cell transplantation (A‐SCT) is the only available curative therapy in thalassaemia, but carries a substantial risk of serious adverse events and mortality. Gene addition therapy for correction of the α‐globin chain imbalance overcomes the problems of donor availability and immunological complications of A‐SCT. Gene editing by either gene disruption or correction emerged as a potential alternative to gene addition therapy in beta‐thalassaemia. A new era of novel therapeutics targeting α/β imbalance, ineffective erythropoiesis or iron dysregulation is unfolding in thalassaemia management, and a number of those now have agents in preclinical and clinical development. Hydroxyurea (HU) may improve globin chain imbalance and be beneficial for reducing or omitting transfusion requirement. Ruxolitinib has allowed steady decrease in spleen volume that may serve for avoiding splenectomy in beta‐thalassaemia. Luspatercept may restore normal erythroid differentiation and improve anaemia. Hepcidin mimetics or TMPRSS6 inhibitors may modulate ineffective erythropoiesis by iron restriction and improve anaemia and organ iron loading.     

~99m锝-葡聚糖淋巴系统显像剂研制及其初步临床应用

作者采用沉淀法对药用葡聚糖进行分级纯化,通过家兔实验筛选出合乎淋巴系统定向要求分子量(105000)的葡聚糖,并制成一步标记法的亚锡葡聚糖药盒,4℃贮存8个月,标记率大于95％。~(99)m锝-葡聚糖的体内外稳定性均佳。家兔研究表明:(1)淋巴结内聚集量最高,其他非靶器(除肝脏、肾脏外)均处于极低水平;(2)显像速度快、图像清晰,既显示淋巴结又显示淋巴管;(3)注射部位清除速度快,6.5h清除95％。安全试验表明:~(99)m锝-葡聚糖是一种毒性极低、非常安全的药物。临床试用100余例,均获满意图像,检查全过程1h内完成,检查结果与诊断基本相符,故~(99)m锝-葡聚糖是目前临床上比较理想的淋巴系统显像剂,可进一步推广应用。     

ANALYSIS OF BURIED BUMPER SYNDROME AFTER PERCUTANEOUS ENDOSCOPIC GASTROSTOMY DUE TO USE OF A BUTTON‐TYPE KIT

Background: Buried bumper syndrome (BBS) is a rare complication of percutaneous endoscopic gastrostomy (PEG). Along with the widespread use of the button‐type kit, BBS is encountered frequently. Methods: In the present study, we examined causes and treatments for BBS among 1400 patients who had undergone PEG. Results: The causes of BBS after PEG were classified into two categories: early causes consisted of wound infection, inappropriate size of kit and severe lordosis, while late causes were inappropriate exchange of kit, rough management or weight gain. The treatments for BBS could be determined by the degree of wound infection, fistula and burial of the bumper. Conclusion: We prepared a flowchart for replacement, by which BBS can be managed safely and quickly without surgical or endoscopic intervention.     

Bleeding from foveolar hyperplasia developing on a gastrointestinal stromal tumor of the stomach

A 52‐year‐old Japanese woman who presented with gastrointestinal (GI) bleeding underwent a proximal gastrectomy for a gastrointestinal stromal tumor (GIST) with a foveolar hyperplasia at the apex of the tumor, 4.5 cm in size, located in the upper body of the stomach. Although GIST are often asymptomatic and are found only incidentally, clinical symptoms such as bleeding, abdominal pain, or obstruction, occasionally lead to a premorbid diagnosis. When submucosal tumors present GI bleeding, the source of the bleeding usually is an ulceration of the mucosa over the tumor. However, in the present study, it was thought that the bleeding originated from the region of foveolar hyperplasia.     

血液胆碱酯酶活力测定方法的进一步研究Ⅰ．红细胞／全血胆碱酯酶活力比例及红细胞计数校正酶活力值的研究

应用硫代乙酰胆碱－联硫代双硝基苯甲酸（ＡＳＣｈ－ＤＴＮＢ）比色测定法，测定了４０名健康者及５名贫血者血样的全血胆碱酯酶（ｂｌ－ＣｈＥ）活力值、红细胞胆碱酯酶（ｅ－ＣｈＥ）活力值及血浆胆碱酯酶（ｐ－ＣｈＥ）活力值，探讨它们之间的比例关系并用红细胞计数值（ＲＢＣ）校正酶活力。结果表明：ｅ－ＣｈＥ与ｂ１－ＣｈＥ之间关系密切（ｒ＝０．９４８，Ｐ＜０．００１），ｅ－ＣｈＥ稳定地占ｂｌ－ＣｈＥ的８４．９７％，在质和量两方面验证了以ｂｌ－ＣｈＥ值表示ｅ－ＣｈＥ值的可靠性和可信程度，血液胆碱酯酶（ｂ１ＣｈＥ）活力主要取决于ｅ－ＣｈＥ活力，ＲＢＣ值的离散对ｅ－ＣｈＥ值有极大影响，故用ＲＢＣ值校正ｅ－ＣｈＥ活力，这样可缩小人群测定值的变异度，得到较难确的群体均值；消除男女之间测定值的差异，建立更合理和通用的临界参比值，极大地方便了使用，使血液胆碱酯酶（ＣＨＥ）活力测定法在防治有机磷农药中毒中的应用，更为敏感和特异。     

三种检测梅毒螺旋体血清学方法评估

目的 寻求一种敏感度和特异性高的方法用于输血前和临床诊断检查梅毒螺旋体抗原血清学试验。方法 应用TPPA、ELISA、TRUST等三种梅毒螺旋体血清学检测方法，对25例各期梅毒血清标本进行检测，对其敏感性及特异性进行比较。结果 25例梅毒血清标本，ELISA法和TPPA法检测阳性率为100％，TRUST法为93％；经稀释法检测，ELISA法较TPPA法敏感。对815例临床标本检测，ELISA方法与TPPA法的检出符合率为100％。结论 ELISA法操作简单，结果判断可标准化，特异性强，敏感性高；既可用于过筛试验，又可用于筛检阳性样本的确认。     

Determination of Red Blood Cell Velocity by Video Shuttering and Image Analysis

A novel modification of conventional video imaging techniques has been developed to determine the velocity of red blood cells (RBCs), which offers compatibility with existing video-based methods for determining blood oxygenation and hemoglobin concentration. Traditional frame-by-frame analysis of video recordings limits the maximum velocity that can be measured for individual cells in vivo to about 2 mm/s. We have extended this range to about 20 mm/s, by electronic shuttering of an intensified charge-coupled device camera to produce multiple images of a single RBC in the same video frame. RBCs were labeled with fluorescein isothiocyanate and the labeled cells (FRBCs) were used as probes to determine RBC velocities in microvessels of the hamster retractor muscle. Velocity was computed as the product of the distance between centroids of two consecutive image positions of a FRBC and the shuttering frequency of the camera intensifier. In vitro calibrations of the system using FRBC and Sephadex beads coated onto a rotating disk yielded an average coefficient of variation of about 6%. Flow conservation studies at bifurcations indicated that the maximum diameter of microvessels below which all the FRBCs in the lumen could be detected was 50 m. The technique was used to estimate mean-FRBC velocity distributions in vessels with diameters ranging from 8 to 50 m. The mean-FRBC velocity profiles were found to be blunter than would be expected for Poiseuille flow. Single FRBCs tracked along an unbranched arteriole exhibited significant temporal variations in velocity. © 1999 Biomedical Engineering Society. PAC99: 8719Tt, 8717Jj, 4279Pw, 8780Tq, 8719Ff, 4230Va, 0705Pj