Vascular calcification is not associated with increased ambulatory central aortic systolic pressure in prevalent dialysis patients

Vascular calcification (VC) is a novel vascular risk factor strongly associated with mortality in dialysis patients.1,2 Although various explanations exist for this association, one mechanism is through alterations in pulse-wave velocity (PWV). Vascular calcification is associated with increased aortic PWV,3 which in turn is associated with raised central aortic systolic pressure (CASP) and reduced coronary perfusion.4,5 As a result, brachial pressure may significantly under- or over-estimate central pressure.6Not surprisingly therefore, central blood pressure parameters have been shown to predict hard cardiovascular endpoints (including mortality) better than concomitant brachial measurements.7-10 Whether vascular calcification is directly linked to central pressures is, however, unknown since there are many determinants of aortic stiffening other than calcification. Furthermore, a primarily damaged and stiff aorta may be the target for secondary deposition of calcium.11CASP can be calculated using applanation tonometry-derived peripheral pulse waveforms and associated software.12 This avoids the obvious disadvantages of invasive central pressure determination. The major disadvantage of standard techniques, however, is the one-dimensional static measurement that is obtained, with no information on ambulatory values or nocturnal dipping status.Loss of normal nocturnal systolic blood pressure dipping is prevalent in chronic kidney disease (CKD) and likely contributes to cardiovascular disease.13 Dipping, which can only be assessed using ambulatory monitoring techniques, correlates better with left ventricular mass index (LVMI) in end-stage renal disease than office-based blood pressure measurement.14,15There have been calls for the routine use of ambulatory blood pressure monitoring (ABPM) in clinical studies of CKD13,16 and indeed, for investigations into the utility of ambulatory CASP in clinical practice.17,18 Combining both ambulatory and central pressure measurements is an attractive strategy, but until recently has not been technically possible.A non-invasive wrist watch-like device, BPro with A-Pulse CASP software (HealthStats, Singapore) was recently approved by the US Food and Drug Administration (FDA: K072593) for the measurement of CASP as well as ambulatory blood pressure. It is a small, wrist watch-like, cuffless monitor which obtains radial pressure waveforms by applanation tonometry. BPro has the ability to measure ambulatory CASP and although not yet commercially available, the manufacturer is able to convert data into ambulatory CASP using the same software.As part of a recently published study on vascular calcification,19 we sought to prospectively evaluate whether the presence of vascular calcification had any relationship with ambulatory CASP in our young CKD-5D cohort using the BPro® radial pulse-wave acquisition device. We also sought to determine the utility of inter-dialytic office brachial and central blood pressure measurements in predicting ambulatory parameters.     

Can local administration of tranexamic acid during total knee arthroplasty reduce blood loss and transfusion requirements in the absence of surgical drains?

Blood transfusions are frequently required following total knee arthroplasty. Tranexamic acid (TXA) inhibits fibrinolysis and has been shown to reduce blood loss and transfusion requirements when delivered intravenously. Topical and intra-articular applications directly target bleeding sites whilst limiting systemic uptake and theoretically reduce the risk of thromboembolic complications. However, in the absence of surgical drains, which increase post-operative blood loss, the efficacy of these techniques for reducing transfusion requirements is unclear. Our aim was to determine if locally administered tranexamic acid during total knee arthroplasty could reduce both blood loss and transfusion requirements in the absence of surgical drains. A retrospective review of 248 patients treated with primary unilateral cemented total knee arthroplasty was performed. Patients treated after January 2011 received topical and intra-articular tranexamic acid at the end of the procedure (n = 136). A second group of consecutive patients treated before this period acted as historical controls (n = 112). Patient groups were equivalent in terms of age, gender and ASA grade. There was a significant reduction in mean blood loss of 246 ml between the groups (p < 0.01). In addition, the requirement for post-operative allogenic blood transfusion was significantly reduced from 15.5 to 5.4 % after introduction of the tranexamic acid regimen (p = 0.02). This is the largest patient cohort reviewed to measure the efficacy of locally administered tranexamic acid during total knee arthroplasty and demonstrates that this is an effective technique for reducing both blood loss and transfusion requirements in the absence of surgical drains.     

探讨尿常规与血肌酐检查在诊断心源性脑梗死中的应用

目的：探讨尿常规检查在诊断心源性脑梗死疾病中应用价值,为临床提高此类患者诊断正确率提供可靠依据,保障患者生活质量与生命安全。方法指定同一名具有专业知识及丰富经验的临床检验人员对研究组心源性脑梗死患者与对照组非心源性脑梗死患者进行尿常规临床检验,检验内容包括尿液中白细胞计数、红细胞计数、尿比重、尿蛋白水平、血肌酐水平等。观察并记录两组患者尿常规检测结果,给予统计学分析,得出结论。结果研究组患者尿常规检测结果中白细胞计数（5．54±2．48）×10^9/L、红细胞计数（61．53±25．34）×10^12/L以及血肌酐水平（114．36±24．87）μmol/L均明显高于对照组非心源性脑梗死患者的（3．29±1．71）×10^9/L、（7．92±3．50）×10^12/L、（89．67±16．54）μmol/L,差异有统计学意义（P＜0．05）;研究组患者尿液中尿比重1．01±0．30以及24h尿蛋白水平（0．06±0．01）g/L与对照组患者的（1．01±0．23）、（0．05±0．01）g/L比较差异无统计学意义（P＞0．05）。结论应用尿常规检测可准确区分心源性脑梗死及非心源性脑梗死疾病,且尿常规检测具有取材方便,可快速获得结果,操作简单,价格低廉等优点,利于患者接受检验,值得临床推广应用。     

Chronic expression of P-selectin on endothelial cells stimulated by the T-cell cytokine, interleukin-3

P-selectin expressed on the surface of endothelium mediates leukocyte adhesion in vitro and rolling in vivo. Several inducers of cell-surface P-selectin expression on endothelial cells (EC) have previously been identified, all of which yield transient cell-surface expression of P- selectin lasting minutes to a few hours. We now show that a T- lymphocyte product, interleukin-3 (IL-3), stimulates the long-term endothelial cells (HUVEC). IL-3 induced cell-surface P-selectin expression in two phases. An initial peak at 10 minutes was followed by a prolonged upregulation beginning 16 hours after IL-3 addition and lasting at least 4 days. The level of P-selectin expression induced by IL-3 added for 48 hours was similar to that induced by treatment of HUVEC for 10 minutes with thrombin, and the effect of adding IL-3 for 48 hours followed by thrombin for 10 minutes was additive. Induction of cell-surface P-selectin expression by IL-3 was blocked by pretreatment of EC with a blocking monoclonal antibody against the IL-3 receptor alpha-chain. Lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF alpha) and a mutant form of IL-3 with decreased potency did not induce cell-surface P-selectin expression after 48 hours' incubation with HUVEC, suggesting that the effect was specific to IL-3. The increase in cell-surface P-selectin expression occurring after 16 hours of incubation with IL-3 was accompanied by a similar prolonged increase in the steady-state mRNA level that was not observed at 10 minutes after IL-3 addition. As T-lymphocyte infiltration is a hallmark of chronic inflammation, our observations suggest that the secretion of IL-3 by T lymphocytes may serve to maintain the inflammatory state during chronic inflammation.     

Twenty four hour variation in plasma atrial natriuretic factor during VVI and DDD pacing.

OBJECTIVE: To investigate whether plasma atrial natriuretic factor (ANF) follows a pattern of circadian variation similar to that of other hormones in patients paced under VVI and DDD pacing modes and to determine if the known effect of pacing mode on ANF secretion is maintained throughout the 24 hour period. PATIENTS AND DESIGN: 20 patients were studied. They had complete atrioventricular block and had been paced for 17 (SD 3.5) months with a dual chamber multiprogrammable pacemaker. They were divided into two groups according to the duration of pacing in either VVI or DDD mode before the measurements: group A, n = 11 (8 men, 3 women, aged 65 (7) years), each paced for 24 h under each of VVI and DDD modes in random order; group B, n = 9 (7 men, 2 women, aged 63 (8) years), each paced for 60 d under each pacing mode before the measurements. Blood samples were taken and ANF concentrations measured every 4 h over a 24 h period, starting at 09.00. Measurements were also made of plasma cortisol, which has a known circadian pattern, so that the 24 h curve could be compared with that of ANF. RESULTS: In contrast to cortisol, ANF values indicated a pulsatile pattern of secretion throughout the 24 h period, with no clear circadian variation. In group B, ANF concentrations were significantly higher during VVI than during DDD pacing throughout the 24 h period, whereas in group A this difference was statistically significant only at certain times of day. CONCLUSIONS: ANF does not show the circadian pattern of variation shown by cortisol and other hormones. Dual chamber pacing contributes to an improvement not only in cardiac haemodynamics but also in the neuroendocrine system, especially in the long term.     

p53、C-erbB-2癌基因蛋白在涎腺粘液表皮样癌中的表达及其临床病理学意义

目的探讨癌基因蛋白p53、C-erbB-2（p185）过度表达与粘液表皮样癌生物学行为的关系。方法利用微波免疫组织化学方法对32例人粘液表皮样癌的癌基因蛋白p53、C-erbB-2进行检测。结果正常诞腺组织p53、C-erbB-2均为阴性反应。癌旁导管上皮细胞两者阳性率分别为10.0％及15.0％,但腺泡细胞阴性。粘波表皮样癌组织中p53、C-erbB-2阳性率分别为40.6％及46.9％。p53、C-erbB-2在粘液细胞、表皮样细胞及中间细胞内均有表达。p53、C-erbB-2的表达与粘液表皮样癌肿瘤组织学类型、分化程度及肿瘤复发等肿瘤生物学行为密切相关（P＜0.01）。结论p53、C-erbB-2可作为粘液表皮样癌的分化性标志物,用于监测病情、判断预后等。     

Endothelial cell function during atrial fibrillation and after restoration of sinus rhythm

Beat-to-beat variation in blood flow dynamics during atrial fibrillation (AF) has been associated with evidence of endothelial dysfunction. The aim of the present work is to confirm endothelial dysfunction in patients with AF and test the hypothesis that endothelial dysfunction is reversible upon restoration of normal sinus rhythm. Endothelium-dependent (flow-mediated dilation [FMD]) and endothelium-independent (nitroglycerin-mediated dilation [NMD]) vasodilator function of the brachial artery were measured using high-resolution ultrasound in 46 patients with persistent AF who were scheduled for internal electrical cardioversion and in 25 control subjects. In patients who remained in sinus rhythm after cardioversion, these measurements were repeated after 24 hours (n = 32) and 1 month (n = 19). Compared with control subjects, patients (n = 32) showed lower FMD during AF (8.1 +/- 3.6% vs 12.2 +/- 3.2%, respectively, p <0.001) and similar NMD (17.0 +/- 3.5% vs 15.9 +/- 3.1%, respectively, p = 0.21). In 19 patients who remained in sinus rhythm, FMD increased at both 24 hours (8.0 +/- 3.9% vs 10.6 +/- 4.6%, p = 0.015) and 1 month (8.0 +/- 3.9% vs 13.6 +/- 5.3%, p <0.001). In contrast, NMD was not significantly altered at 24 hours or 1 month after sinus rhythm restoration (17.1 +/- 3.9% vs 17.2 +/- 4.0% vs 16.9 +/- 4.1%). In conclusion, AF is associated with impairment in endothelial function that improves after sinus rhythm restoration.     

Temozolomide and radiotherapy in newly diagnosed glioblastoma patients: O<Superscript>6</Superscript>-methylguanine-DNA methyltransferase (MGMT) promotor methylation status and Ki-67 as biomarkers for survival and response to treatment

Objective  

This phase II study aimed at investigating the correlation between O⁶-methylguanine-DNA methyltransferase (MGMT) promoter methylation and protein expression, together with Ki-67 labeling index (LI), to response, time to progression (TTP), and overall survival (OS) in newly diagnosed glioblastoma multiforme (GBM) patients treated with temozolomide (TMZ) concomitant with and adjuvant to radiotherapy (RT).     

THE PHYSICIAN IN COURT: A VIEW FROM THE BENCH

Only lawyers and judges-and not even all of them-look forward to being in court. For the physician it is usually not an experience sought or savoured. Yet some physicians are in court more frequently than some lawyers because they are expert witnesses or because they have treated a person who is before the court in a civil or criminal case. There is also the physician who is sued and is thus a defendant. I believe it important that physicians know the basic ingredients of a civil action. I will be drawing on my experience as a trial judge for eight years and an Alberta Court of Appeal judge for five, and as a former professor in the faculties of law and medicine at the University of Alberta, to present the perspective from the bench on civil non-jury actions.