上颈椎三维有限元模型的建立

目的:建立上颈椎三维有限元模型,以期应用于临床相关的生物力学实验研究中。方法:实验于2005-05/2006-01在南方医科大学解剖及生物力学实验室完成。选取2例自愿参与实验的健康青年男性,均经医院伦理委员会批准,且受试者知情同意。复习病史并行X射线平片检查排除枕颈部疾患。通过对正常人的CT薄层扫描获得原始DICOM图像数据,采用CAD数据处理技术进行计算机三维重建,改良建立的模型导入ANSYS9.0软件进行计算机模拟仿真生物力学研究。结果:所建模型外观清晰逼真,几何相似性好。所建的上颈椎有限元模型能够通过验证,与体外生物力学实验结果基本吻合,可进一步行各种上颈椎有限元力学分析。结论:为临床对枕颈交界区有限元三维模型的建立提供了一种便捷而精确的方法,对计算机分析及研究该模型局部结构在各种受力情况下的生物力学表现创造条件。     

彩色多普勒超声对肾移植患者围手术期及术后3个月相关指标动态评估的意义

目的:通过观察围手术期及术后3个月肾移植患者肾形态结构和相关血流的彩色多普勒超声指标变化,分析彩色多普勒超声对肾移植术后并发症的早期评估作用。方法:选择2005-04/2006-04在南方医院超声诊断科就诊的同种异体肾移植患者152例,患者均知情同意。应用彩色多普勒超声对肾移植患者进行术前评价和术后监测,重点观察肾移植术后3d、术后7d、术后1个月及术后3个月内移植肾形态结构及血流动力学各项参数,及时发现术后并发症。先用二维超声观察移植肾的形态,测量长径、宽径、厚径,并测量肾皮质厚度和锥体大小。随后应用彩色多普勒血流显像观察移植肾髂动脉、吻合口处肾动脉、肾门处肾动脉、段动脉的血流充盈情况,接着用高频探头检测大叶间动脉和小叶间动脉的血管树结构。最后用脉冲式多普勒采集频谱,测量收缩期峰值血流速度、舒张末期血流速度、阻力指数和搏动指数等。结果:152例肾移植患者全部进入结果分析,无脱落。术后彩色多普勒超声及时发现手术并发症64例,占肾移植患者的42.11%,部分受检者同时合并两项或多项并发症。①急性排斥反应23例,发病率15.14%,移植肾各级动脉阻力指数均大于0.75,其中大于0.85的患者共12例。②吻合口处肾动脉狭窄14例,发病率9.22%,收缩期峰值流速明显增高,均收缩期峰值流速>180cm/s,其中收缩期峰值流速>300cm/s的患者5例,占35.71%,14例病例中合并急性排斥者6例,占42.86%。③肾盂积水25例,发病率16.45%,移植肾大小为(208.52±42.43)cm3;肾周积液20例,发病率13.16%。结论:应用彩色多普勒超声动态观察肾移植术前、术后肾内血流灌注情况,以各项血流指标进行临床评估,有助于及早发现术后并发症,对于提高肾移植术的成功率和患者的生存率具有重要意义。     

CD44 mediates hyaluronan binding by human myeloid KG1A and KG1 cells

Hyaluronan-binding function of the CD44 molecule has not been so far detected in myeloid cells. To study pure populations of primitive myeloid cells, we investigated the hyaluronan-binding function of the CD44 molecule from three myeloid cell lines: KG1a, KG1, and HL60. Both KG1a and KG1 cells express the CD34 antigen characteristic of the hematopoietic stem cells and HL60 cells do not; accordingly, KG1a and KG1 cells are generally considered as the most primitive and HL60 cells as the most mature of these cell lines. Measurement of cell adhesion to hyaluronan-coated surfaces (using 51Cr-labeled cells) and of aggregate formation in hyaluronan-containing solutions, showed that 45% of KG1 cells and 22% to 24% of KG1a spontaneously bind to hyaluronan, whereas HL60 cells do not either spontaneously or after treatment with a phorbol ester. Hyaluronan binding by KG1a and KG1 cells is mediated by CD44, because it is specifically abolished by monoclonal antibodies (MoAbs) to this molecule. The binding might require phosphorylation by protein kinase C and perhaps also by protein kinase A, because it is prevented by staurosporine, which inhibits these enzymes. 12-O- tetradecanoylphorbol-13-acetate (TPA) which activates protein kinase C, rises to 80% the proportion of KG1 and KG1a cells that bind hyaluronan; this activation is dependent on protein synthesis, for it is abrogated by cyclophosphamide, a protein synthesis inhibitor. Binding of TPA- treated cells to hyaluronan is only partly inhibited by MoAb to CD44: this suggests that TPA may induce synthesis of a hyaluronan-binding protein distinct from CD44. Considering the abundance of hyaluronan in human bone marrow, these results suggest that CD44 may be involved in mediating precursor-stroma interaction.     

A phase 1B trial of humanized monoclonal antibody M195 (anti-CD33) in myeloid leukemia: specific targeting without immunogenicity

This trial studied the biodistribution, pharmacology, toxicity, immunogenicity, and biologic characteristics of a trace-labeled, anti- CD33, humanized monoclonal antibody M195 (Hu-M195) in patients with relapsed and refractory myeloid leukemia. Hu-M195 is a computer- modeled, "complementarity-determining region-grafted," IgG1, humanized version of M195. M195 is a murine monoclonal antibody that reacts with CD33, a 67-kD glycoprotein expressed on early myeloid progenitor cells and myeloid leukemia (acute myelogenous leukemia and chronic myelogenous leukemia) cells, but not normal stem cells. 131I-murine- M195 has already shown significant ability to cytoreduce patients with relapsed or refractory myeloid leukemias. Hu-M195 has higher avidity than the original mouse monoclonal antibody and, unlike murine M195, has the capability to mediate antibody-dependent cellular cytotoxicity against leukemia targets. Thirteen patients with relapsed or refractory myelogenous leukemia were treated with Hu-M195 at 4 levels of 0.5, 1.0, 3.0, and 10.0 mg/m2 in a phase I trial. Patients received a total of 6 doses per patient over 18 days. Two patients were retreated for a total of 12 doses. The first dose of Hu-M195 was trace-labeled with 131I to allow detailed pharmacokinetic and biodistribution studies by serial sampling of blood, radioimmunoassays of cells, and whole-body gamma- camera imaging. Cumulative total doses of up to 216 mg of Hu-M195 were administered safely. Reversible fever and rigors were observed after infusion at the highest dose levels. The entire bone marrow was specifically and clearly imaged within hours after infusion, with optimal biodistribution occurring at the 3 mg/m2 level. Adsorption of Hu-M195 onto targets in vivo was demonstrated by flow cytometry; near saturation of available sites occurred at the 3 mg/m2 dose level. Plasma and whole body half lives were 38 and 51 hours, respectively, which may reflect continual replenishment of target sites on new leukemia cells. 131I-Hu-M195 was rapidly internalized into the target cells in vivo within 1 hour. Human antihuman antibody responses were not observed. In conclusion, Hu-M195 can be administered safely in multiple doses, without significant toxicity or any evidence of immunogenicity, and can localize rapidly and efficiently to the bone marrow in patients with myeloid leukemias. Additional phase II trials with this agent alone or in combination with cytokines or isotopes are warranted at the optimal biologic dose.     

Bone marrow stromal cell blockade of human leukemic cell differentiation

Bone marrow (BM) stromal cell inhibition of leukemic cell differentiation was studied in cellular coculture experiments. In coculture, a significant percentage of cells from the human myeloid leukemic cell lines HL-60, PLB-985, and K562 adhere to fibroblastic KM- 102 BM stromal cells. A sensitive two-color immunofluorescence assay was developed to monitor stromal cellular effects upon leukemic cell differentiation. After chemical induction with 1 alpha,25- dihydroxyvitamin D3, strongly adherent HL-60 and PLB-985 cells were inhibited from differentiating into more mature monocytic cells, as measured by the monocytic surface marker CD14. In contrast, loosely adherent and nonadherent HL-60 and PLB-985 leukemic cells in the same cocultures, as well as both adherent and nonadherent K562 cells induced with phorbol ester, were not blocked in their capacity to differentiate. Scanning electron microscopy and intercellular dye transfer experiments correlated intimate stromal cell/leukemic cell interaction and intercellular communication with the blockade of leukemic cell differentiation. These studies indicate that there is significant variability among leukemic lines with respect to the nature of their adhesion to stromal cells. Moreover, the data implicate gap- junction formation as a potentially significant event in stromal cell- mediated leukemic cell regulation.     

Mycobacterium fortuitum Infection Occurring After a Punch Biopsy Procedure

Abstract: Mycobacterium fortuitum is a rapidly growing atypical mycobacterium frequently reported as a postsurgical wound complication from a major surgical procedure. We present a unique case of M. fortuitum infection occurring in a 4-year-old boy after a minor punch biopsy surgical procedure. As far as we know there has been no published case of M. fortuitum occurring after a punch biopsy procedure.     

A systematic review of the use of simulated patients and pharmacy practice research

Objective The use of simulated patients to assess current practice, or to derive outcome measures for pharmacy practice research, has received much attention in recent years. A simulated patient is an individual who is trained to visit a pharmacy to enact a scenario testing specific behaviour of the pharmacist or pharmacy staff. The aim of this study was to provide a definitive review of the use of simulated patients as a methodological tool for pharmacy practice research. Method A systematic review was undertaken to identify all pharmacy practice studies that had used simulated patient methodology. The electronic databases searched to identify relevant studies were MEDLINE, EMBASE and CINAHL. Articles fulfilling all the following criteria were considered for inclusion in the review: primary reports of trials conducted in community pharmacy and drug store settings which used simulated patients to derive outcome measures. The review was not restricted by language or by country. The review was restricted to publications from 1976 to May 2005. Key findings In total, 56 full publications were retrieved for further examination, of which 46 studies were included in the review, including: nine randomised controlled trials, three controlled trials, 30 cross‐sectional, two time‐series and two ‘other’ studies. Ten publications were excluded: seven reviews, one laboratory‐based study, one telephone survey and one study presented only as an abstract. Conclusions There has been steady growth in the use of simulated patient methodology over the past 30 years. Although simulated patients have received negative attention in the pharmaceutical media, they can be a rigorous and robust method of measuring practice if used appropriately. This review demonstrates the range of activities for which this method can be used, including the assessment of counselling and advice provision, the treatment of minor and major illness, and the assessment of the public health activities of pharmacy and drug store staff. Simulated patient methodology has been used in developing countries to a similar, if not greater extent, than the developed world, demonstrating its versatility and applicability to pharmacy practice research globally.     

Increased frequency of wild-type arylamine-N-acetyltransferase allele NAT2*4 homozygotes in Portuguese patients with colorectal cancer

Here we report that colorectal cancer patients show a markedly higher frequency (3-fold) of wild-type NAT2*4 allele homozygotes than the control population. However, a marked difference in NAT2*4/NAT2*4 genotype frequency associated with the patients gender was observed pointing to a male-specific effect of this genotype as a risk factor in colon cancer. The arylamine-N-acetyltransferase (E.C. 2.3.1.5.) NAT2, a phase II detoxification enzyme, has been implicated in procarcinogen activation, namely from food contained arylamines, cigarette smoking, as well as environmental amines of various types. NAT2 is encoded by a polymorphic gene presenting several allelic variants encoding partially inactive enzymes expressed in human liver and colon. Epidemiological studies based on phenotype determination have long indicated the importance of the NAT2 active phenotype as a susceptibility factor in colorectal cancer. In the present study we investigated the NAT2 allelic frequencies and genotype distribution in a group of 114 unrelated colorectal cancer patients, in parallel with 201 healthy Portuguese subjects. We first demonstrate that the frequency of the wild-type NAT2*4 allele in the Portuguese sample population (23.4%) does not significantly differ from the values described for other Europeans. Besides the 3-fold higher frequency of NAT2*4 homozygotes found in colorectal cancer subjects, the NAT2*4/NAT2*5A compound genotype, known to determine a faster acetylator phenotype than other heterozygotic combinations, also increased by the same order of magnitude. These two genotypes represent 32% of the patients population versus 11% of the healthy controls. Taken together, our results strongly indicate that NAT2 genotype, particularly NAT2*4 allele zygosity, constitutes an individual susceptibility trait associated with sporadic colorectal cancer development, probably due to the local dietary habits in Portugal.