Expression of adhesion molecules on CD34+ cells: CD34+ L-selectin+ cells predict a rapid platelet recovery after peripheral blood stem cell transplantation

Adhesion molecules play a role in the migration of hematopoietic progenitor cells and regulation of hematopoiesis. To study whether the mobilization process is associated with changes in expression of adhesion molecules, the expression of CD31, CD44, L-selectin, sialyl Lewisx, beta 1 integrins very late antigen 4 (VLA-4) and VLA-5, and beta 2 integrins lymphocyte function-associated 1 and Mac-1 was measured on either bone marrow (BM) CD34+ cells or on peripheral blood CD34+ cells mobilized with a combination of granulocyte colony- stimulating factor (G-CSF) and chemotherapy. beta 1 integrin VLA-4 was expressed at a significantly lower concentration on peripheral blood progenitor cells than on BM CD34+ cells, procured either during steady- state hematopoiesis or at the time of leukocytapheresis. No differences in the level of expression were found for the other adhesion molecules. To obtain insight in which adhesion molecules may participate in the homing of peripheral blood stem cells (PBSCs), the number of CD34+ cells expressing these adhesion molecules present in leukocytapheresis material was quantified and correlated with hematopoietic recovery after intensive chemotherapy in 27 patients. The number of CD34+ cells in the subset defined by L-selectin expression correlated significantly better with time to platelet recovery after PBSC transplantation (r = - .86) than did the total number of CD34+ cells (r = -.55). Statistical analysis of the relationship between the number of CD34+L-selectin+ cells and platelet recovery resulted in a threshold value for rapid platelet recovery of 2.1 x 10(6) CD34+ L-selectin+ cells/kg. A rapid platelet recovery (< or = 14 days) was observed in 13 of 15 patients who received > or = 2.1 x 10(6) CD34+ L-selectin+ cells/kg (median, 11 days; range, 7 to 16 days), whereas 10 of 12 patients who received less double positive cells had a relative slow platelet recovery (median, 20 days; range, 13 to 37 days). The L-selectin+ subpopulation of CD34+ cells also correlated better with time to neutrophil recovery (r = - .70) than did the total number of reinfused CD34+ cells (r = -.51). However, this latter difference failed to reach statistical significance. This study suggests that L-selectin is involved in the homing of CD34+ cells after PBSC transplantation.     

碱性成纤维细胞生长因子复合缓释降解膜对同种异体移植神经的影响：电生理评价

目的:应用电生理检测指标评价碱性成纤维细胞生长因子复合缓释降解膜对周围神经再生的影响。方法:实验于2005-03/11在沈阳医学院奉天医院实验室完成。①实验材料:碱性成纤维细胞生长因子复合缓释降解膜:主要成分为碱性成纤维细胞生长因子、维生素C抑制剂、明胶、壳聚糖。②实验分组:大耳白兔60只,按随机数字表法分为实验组和对照组,每组30只。异体正中神经制备:每组兔分6次取正中神经,每次取5只兔的正中神经,分别切除双侧正中神经各2.5cm,用受体动物血浆浸泡20min、-196℃液氮冷存21d、室温下复温。手术方法:麻醉后暴露双侧上臂正中神经主干,在相应一致神经部位切除2.5cm,用复温后的异体正中神经缝接。实验组神经缝接处包裹碱性成纤维细胞生长因子复合缓释降解膜,对照组不包膜。③实验评估:术后8,13,26周采用Keypoint肌电诱发电位仪测定运动神经传导速度和复合肌肉动作电位波幅。采用Luzex-F图像分析仪测定移植神经近段和远段的锇酸髓鞘染色横断面标本上有髓神经纤维数量。结果:①运动神经传导速度:术后8,13,26周实验组运动神经传导速度明显快于对照组[分别为(21.62±2.81),(13.16±1.81)m/s;(40.83±3.66),(21.71±2.40)m/s;(50.41±4.84),(31.96±3.17)m/s],两组间差异有非常显著性意义(t=3.51,3.69,3.88,P<0.001)。②复合肌肉动作电位波幅:术后8,13,26周实验组复合肌肉动作电位波幅则明显高于对照组[分别为(1.47±0.16),(0.83±0.07)mV;(4.82±1.27),(2.66±0.31)mV;(14.55±4.16),(8.63±3.36)mV],两组间差异有显著性意义(t=2.34,2.48,2.66,P<0.05)。③有髓神经纤维数量:实验组术后13周神经近段和远段有髓神经纤维比例为2.5∶1,术后26周比例为1.2∶1;而对照组相应时间点有髓神经纤维比例分别为7.2∶1和2.2∶1。结论:神经传导速度和复合肌肉动作电位波幅检测结果提示碱性成纤维细胞生长因子复合缓释降解膜有促进周围神经再生的作用。     

Transvaginal and transabdominal sonography: prospective comparison

Transvaginal (TV) and transabdominal (TA) sonography were compared in a prospective study. A total of 230 examinations (126 pelvic, 104 pregnancy) were performed on 215 patients, ranging in age from 14 to 80 years. The improved anatomic detail on TV scans yielded new information in 138 (60%) examinations and better visualization of pelvic structures in 51 (22%) examinations. There was no important difference in diagnostic information provided by the two imaging modalities in 36 (16%) cases, and TV images were worse in five (2%). The clinical diagnosis was altered on the basis of TV sonographic findings in 54 (24%) cases and confirmed with certainty in 166 (72%). Diagnostic problems posed by TA scanning were not resolved by TV scanning in ten (4%) instances. Statistical analysis indicated that TV scanning was significantly better than TA scanning in the visualization of gestational sac contents (P less than .005), detection of fetal heart motion (P less than .001), and evaluation of the endometrial canal in the retroverted or retroflexed uterus (P less than .001). TV scanning was significantly better than TA scanning in visualization of the ovaries in patients with uterine leiomyomas (P less than .005) but not significantly better in peri- and postmenopausal patients (P greater than .05).     

Evaluation of BRCA1 and BRCA2 mutations and risk-prediction models in a typical Asian country (Malaysia) with a relatively low incidence of breast cancer

Introduction

The cost of genetic testing and the limited knowledge about the BRCA1 and BRCA2 genes in different ethnic groups has limited its availability in medium- and low-resource countries, including Malaysia. In addition, the applicability of many risk-assessment tools, such as the Manchester Scoring System and BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) which were developed based on mutation rates observed primarily in Caucasian populations using data from multiplex families, and in populations where the rate of breast cancer is higher, has not been widely tested in Asia or in Asians living elsewhere. Here, we report the results of genetic testing for mutations in the BRCA1 or BRCA2 genes in a series of families with breast cancer in the multi-ethnic population (Malay, Chinese and Indian) of Malaysia.

Method

A total of 187 breast cancer patients with either early-onset breast cancer (at age ≤ 40 years) or a personal and/or family history of breast or ovarian cancer were comprehensively tested by full sequencing of both BRCA1 and BRCA2. Two algorithms to predict the presence of mutations, the Manchester Scoring System and BOADICEA, were evaluated.

Results

Twenty-seven deleterious mutations were detected (14 in BRCA1 and 13 in BRCA2), only one of which was found in two unrelated individuals (BRCA2 490 delCT). In addition, 47 variants of uncertain clinical significance were identified (16 in BRCA1 and 31 in BRCA2). Notably, many mutations are novel (13 of the 30 BRCA1 mutations and 24 of the 44 BRCA2). We report that while there were an equal proportion of BRCA1 and BRCA2 mutations in the Chinese population in our study, there were significantly more BRCA2 mutations among the Malays. In addition, we show that the predictive power of the BOADICEA risk-prediction model and the Manchester Scoring System was significantly better for BRCA1 than BRCA2, but that the overall sensitivity, specificity and positive-predictive value was lower in this population than has been previously reported in Caucasian populations.

Conclusion

Our study underscores the need for larger collaborative studies among non-Caucasian populations to validate the role of genetic testing and the use of risk-prediction models in ensuring that the other populations in the world may also benefit from the genomics and genetics era.     

Trauma resuscitation and the damage control approach

Trauma is a leading cause of morbidity and mortality worldwide. Developments in trauma care, from point of wounding to rehabilitation, have often been led and driven by military medical experiences in recent conflicts. Trauma mechanisms are manifold, affecting an omnifarious patient population indiscriminately, and potentially resulting in significant multisystem dysfunction or damage, sometimes permanently. The horizontal approach to trauma resuscitation, whereby a patient is assessed and treated by multiple specialists to prioritize management of life-threatening issues swiftly and concurrently, was exploited to good effect by clinicians at Camp Bastion in Afghanistan. This tactic is just one element of the dynamic and synchronous teamwork that this complex and challenging area of clinical practice demands. Similarly, the damage control approach deploys medical and surgical treatment strategies in parallel, balancing therapies in pursuit of physiological equipoise, aiming to reduce mortality and accepting the risk of morbidity. Damage control therapy embodies bold, yet nuanced, clinical care.     

Lack of transmission of neutrophil and platelet antibodies by intravenous immunoglobulin in bone marrow transplant patients

BACKGROUND: Several studies have demonstrated that the administration of intravenous immunoglobulin (IVIG) may be followed by the transient appearance of positive red cell antibody screens, positive direct antiglobulin tests, and, occasionally, frank hemolysis. However, little information is available regarding the possibility that IVIG could transmit neutrophil and/or platelet antibodies. STUDY DESIGN AND METHODS: Serum samples were obtained both immediately before and immediately after the administration of 12 separate lots of commercially available IVIG to bone marrow transplant patients. RESULTS: None of the patients were shown by standard granulocyte immunofluorescence testing to have acquired neutrophil antibodies. Four of the 12 postinfusion sera were positive for platelet antibodies in standard platelet suspension immunofluorescence testing, but in all four instances the corresponding preinfusion serum was positive as well. CONCLUSION: The risk of acquiring neutrophil and/or platelet antibodies after the administration of commercially available IVIG appears to be low.