应用非甾体抗炎药对高血压合并冠状动脉疾病患者的有害作用

慢性疼痛综合征患者常应用非甾体抗炎药( non-steroidal anti-inflammatory drugs,NSAID).许多这类患者有潜在的高血压和冠状动脉疾病.临床试验和系统性分析显示,选择性环氧化酶2抑制剂增加心肌梗死的风险[J].该发现可能导致更普遍地应用非选择性NSAID作为治疗慢性疼痛综合征的替代手...     

High-molecular-weight kininogen is exclusively membrane bound on endothelial cells to influence activation of vascular endothelium

An important biologic function of high-molecular-weight kininogen (HK) is to deliver bradykinin (BK) to its cellular receptors. Internalization and degradation of HK may provide a mechanism by which endothelial cells modulate the production of BK and control its activities. Therefore, we investigated the binding and subsequent distribution of biotinylated-HK (biotin-HK) associated with human umbilical vein endothelial cells (HUVEC). HUVEC bound 3 to 4 times more HK and with greater avidity at 1 to 3 hours at 37 degrees C than at 4 degrees C (Bmax = 1.0 +/- 0.02 x 10(7) molecules/cell, kd = 7 +/- 3 nmol/L v Bmax = 2.6 +/- 0.2 x 10(6) molecules/cell, kd = 46 +/- 8 nmol/L). However, there was no evidence that the difference was caused by internalization of HK at the higher temperature. First, the same amount of biotin-HK was associated with nonpermeabilized and permeabilized HUVEC using buffers containing 20 to 50 mumol/L zinc ion in the absence or presence of 2 mmol/L calcium ion. Second, binding of biotin-HK to HUVEC was approximately 92% reversible at 1 hour when the cells were maintained at both 37 degrees C and 4 degrees C. Third, neither chloroquine nor primaquine altered the amount of biotin-HK bound to HUVEC. Fourth, biotin-HK bound to HUVEC was almost completely removed by pronase. Fifth, the nonpermeable dye, crystal violet, almost completely quenched the fluorescence signal emitted by HUVEC-associated fluorescein isothiocyanate (FITC) HK. Finally, the localization of HUVEC-bound FITC-HK was restricted to the membrane as shown by laser scanning confocal microscopy. The expression of HK binding sites had an absolute requirement for metabolic energy, but was not dependent on new protein synthesis. Membrane-bound HK contributed to the anticoagulant nature of endothelial cells by blocking human alpha-thrombin binding and its resultant induction of prostacyclin formation. These studies indicate that HK is not internalized by HUVEC, but remains primarily on cell surfaces to be accessible for BK liberation and to modulate the binding and actions of alpha-thrombin.     

Comparison of angiography,CT arteriography and MR imaging in assessment of liver metastases treated by percutaneous transcatheter intraarterial chemotherapy

Abstract: The purpose of this study was to compare results of digital subtraction angiography (DSA), computed tomographic arteriography (CTA), and magnetic resonance imaging (MRI) in the assessment of patients with liver metastases subjected to percutaneous transcatheter intra-arterial chemotherapy. Forty-four patients with liver metastases treated by cyclic percutaneous transcatheter intra-arterial chemotherapy were examined before each cycle by an imaging protocol consisting of DSA and CTA. MRI was added to this protocol in 18 patients. DSA and CTA equally detected thrombosis of the catheter or arteries distal to the catheter tip in 16 examinations. DSA detected arterial reflux in 15 examinations, while CTA detected only one case of reflux. CTA was superior to DSA in demonstrating perfusion abnormalities and superior to MRI in detecting metastases. CT was the only method that demonstrated intratu-moral calcification. In conclusion, in patients with liver metastases subjected to percutaneous transcatheter intra-arterial chemotherapy, DSA is the best method for detection of arterial reflux, whereas CTA is the best method for detection of metastases and demonstration of perfusion abnormalities.     

Acute myeloid leukemia with T-cell receptor gamma gene rearrangement occurring in a patient with chronic lymphocytic leukemia: a case report

The association of chronic lymphocytic leukemia (CLL) and acute leukemia, either lymphoid or myeloid is a rare event. Our review of the medical literature revealed only 6 cases of CLL transformation to acute myeloid leukemia (AML) (M0, M1 and M2) with no other associated malignancy. We report a similar case but with occurrence of AML-M4 associated with normal cytogenetic analysis and molecular testing but with positive T-cell receptor gamma gene rearrangement rather than the usual Vbeta rearrangement.     

Relation of atrial electromechanical delay to P‐wave dispersion on surface ECG using vector velocity imaging in patients with hypertrophic cardiomyopathy

ObjectivesHeterogeneity of structural and electrophysiologic properties of atrial myocardium is common characteristic in hypertrophic cardiomyopathy (HCM). We assessed the dispersion of atrial refractoriness on surface ECG using P‐wave dispersion (PWD) and its relation to atrial electromechanical functions using vector velocity imaging (VVI) in HCM population.MethodsSeventy‐nine HCM patients (mean age: 43.7 ± 13 years, 67% male) were compared with 25 healthy individuals as control. P‐wave durations, P_max and P_min, P‐wave dispersion (PWD), and P terminal force (PTF) were measured from 12‐lead ECG. LA segmental delay (TTP‐d) and dispersion (TTP‐SD) of electromechanical activation were derived from atrial strain rate curves.ResultsHCM patients had longer PR interval, PW duration, higher PWD, PTF, QT_c compared to control (p < .001). HCM patients were classified according to presence of PWD into two groups, group I with PWD > 46 ms (n = 25) and group II PWD ≤ 46 ms (n = 54). Group I showed higher prevalence of female gender, higher PTF, QTc interval, left ventricular outflow tract (LVOT) obstruction, p < .01, LVOT gradient (p < .001), LV mass index (p < .01), E/E'' (p < .01), and severe mitral regurgitation (p < .001). Moreover, PWD was associated with increased atrial electromechanical delay (TTP‐d) and LA mechanical dyssynchrony (TTP‐SD), p < .001. LA segmental delay and dispersion of electromechanical activation were distinctly higher among HCM patient.ConclusionPWD is simple ECG criterion, and it is associated with more severe HCM phenotype and LA electromechanical delay while PTF is linked only to atrial remodeling.     

Pediatric peripheral blood progenitor cell collection: haemonetics MCS 3P versus COBE Spectra versus Fresenius AS104

BACKGROUND: An increasing number of apheresis machines are becoming available for peripheral blood progenitor cell (PBPC) collection in children. STUDY DESIGN AND METHODS: At the Children's Hospital of Florence (Italy), three apheresis machines were evaluated: MCS 3P (Haemonetics) (10 procedures in 4 patients, aged 10–12 years, weight 23.5-64 kg), Spectra, (COBE) (8 procedures in 3 patients, aged 4–17 years, weight 19–59 kg), and AS104 (Fresenius) (24 procedures in 9 patients, aged 2–16 years, weight 13.6-60 kg). For PBPC quantitative analysis, CD34 cytofluorimetry was employed. Relevant variables analyzed included efficiency of CD34+ cell extraction and enrichment, mononuclear cell purity and red cell contamination of the apheresis components, and platelet count decreases after leukapheresis. RESULTS: No significant differences in CD34+ cell-extraction abilities were found. However, the AS104 provided consistently purer leukapheresis components in terms of mononuclear cell and CD34+ cell enrichment (441 +/− 59%, vs. 240 +/− 35% and 290 +/− 42% for MCS 3P and Spectra, respectively). Postapheresis platelet counts dropped the least with the AS104. The smallest patient who underwent apheresis with MCS 3P (the only machine working on discontinuous flow and hence with greater volume shifts) weighed 23.5 kg and tolerated the procedure well, with no signs of hemodynamic instability. No significant complications were observed. CONCLUSION: All machines seem to have comparable PBPC extraction efficiency, but the AS104 seems to give the component with the greatest PBPC enrichment. This feature might be relevant for further ex vivo cell processing (CD34+ cell selection, expansion, and so on).     

Heterogeneity of breakpoints of 11q23 rearrangements in hematologic malignancies identified with fluorescence in situ hybridization

Twenty-four patients whose cells contained a variety of 11q23 rearrangements, including translocations, insertions, and an inversion, were studied using fluorescence in situ hybridization with cosmid, phage, and plasmid probes mapped to 11q22-24. In 17 patients, the breakpoints of the common 11q23 translocations involving chromosomes 4, 6, 9, and 19 as well as some uncommon translocations involving 3q23, 17q25, 10p11, and an insertion 10;11 were all located in the breakpoint cluster region of the MLL gene, regardless of age, phenotype of disease, or involvement of a third chromosome. The breakpoints in 11q23 in the other 7 patients with a t(7;11)(p15;q23), inv(11)(p11q23), t(4;11)(q23;q23), der(5)t(5;11)(q13;q23), ins(10;11)(p11;q23q24), t(11;14)(q23;q11), or t(11;18;11) (p15;q21;q23) were located either centromeric to CD3D or telomeric to THY1. Thus, although most 11q23 rearrangements, involve the same breakpoint cluster region of MLL, there is heterogeneity in the breakpoint in some of the rare rearrangements.     

Detection and viability of tumor cells in peripheral blood stem cell collections from breast cancer patients using immunocytochemical and clonogenic assay techniques [see comments]

Although peripheral blood stem cell collections (PBSC) are thought to have less tumor involvement than bone marrow (BM), the incidence of circulating tumor cells in patients with breast cancer has not been widely investigated. We prospectively investigated the incidence and viability of tumor cell involvement in PBSC and BM collections from breast cancer patients undergoing high-dose chemotherapy/hematopoietic stem cell transplantation. Paired samples of PBSC and BM from 48 patients were analyzed using an immunocytochemical technique that detects one epithelial-derived tumor cell per 5 x 10(5) mononuclear cells. Immunostained tumor cells were detected in 9.8% (13/133) PBSC specimens from 9/48 (18.7%) patients and in 62.3% (38/61) BM specimens from 32/48 (66.7%) patients, a significantly higher rate than in PBSC (P < .005). The geometric mean concentration of tumor cells in contaminated PBSC specimens was 0.8/10(5) mononuclear cells (range 0.33 to 2.0/10(5)) compared with 22.9/10(5) mononuclear cells in BM (range 1 to 3,000/10(5), P < .0001). In culture experiments, clonogenic tumor colonies grew in 21/26 immunocytochemically positive specimens. No tumor colony growth was detected in 30/32 immunocytochemically negative specimens. Immunocytochemical detection of tumor involvement in BM and PBSC correlated significantly with in vitro clonogenic growth (P < .0001). We conclude that PBSC contain fewer tumor cells than paired BM specimens from patients with advanced breast cancer and that these tumor cells appear to be capable of clonogenic growth in vitro.