可乐定硬膜外腔预注的镇静效应及其对脑电双频谱指数的影响

目的观察可乐定硬膜外腔预注对左旋布比卡因硬膜外麻醉患者的镇静效应及其对脑电双频谱指数(BIS)的影响。方法45例ASAⅠ～Ⅱ级经腹全子宫切除手术患者,根据硬膜外腔预注可乐定剂量的不同,随机分为3组:C2组(n=15)2μg/kg,C4组(n=15)4μg/kg和C0组对照(n=15)。L2～3硬膜外腔穿刺置管,可乐定注射15min后以0.5%左旋布比卡因行硬膜外阻滞麻醉。结果各组麻醉效果良好,阻滞平面T6(T3～6),术中左旋布比卡因用量组间无显著差异,C0组1例需要辅助镇静药物。可乐定给药5～15min后,BIS明显降低,C4组降低比C2组更显著;警觉/镇静评分为C4组相似文献   

MHC class I chain-related molecules induced on monocytes by IFN-gamma promote NK cell activation

NKG2D receptor-ligand interaction triggers NK cell-mediated cytolysis and IFN-gamma secretion. IFN-gamma produced by NK cells has been found to promote the interaction between NK cells and monocytes; however, the underlying mechanism remains elusive. We demonstrate here that IFN-gamma exclusively induced or upregulated the expression of MHC class I chain-related (MIC) molecules, which are ligands of the NKG2D receptor, on the surface of human monocytes of the PBMC population. The IFN-gamma-induced MIC molecules on monocytes played an essential role in triggering the activation of NK cells because mAb-mediated masking of the MIC molecules and the inhibition of cell-to-cell contact using transwell inserts significantly abolished NK cell activation. Meanwhile, membrane-bound IL-15 (mIL-15) was concomitantly induced with MIC molecules on IFN-gamma-treated monocytes and played an essential role in protecting NK cells cocultured with monocytes from MIC-induced NKG2D down-modulation. Therefore, we conclude that the IFN-gamma-induced MIC molecules participated in monocyte/NK cell interaction and that this interaction also involved mIL-15.     

Left ventricular diastolic function in normotensive type-2 diabetic subjects

BACKGROUND: Most previous studies on diastolic function in diabetics are confounded by coexisting ischemic heart disease, obesity and hypertension. Therefore, there may be advantages in studying patients with diabetes mellitus in developing nations where confounding variables are less prevalent. The aim of this study was to assess the effect of type-2 diabetes mellitus on left ventricular diastolic function in normotensive subjects in Nigeria. METHODS: One-hundred-twenty-two patients with type-2 diabetes mellitus aged 35-74 years with a mean age of 55.30 +/- 8.53 years were studied. Patients with blood pressure > or =140/90 mmHg or on treatment for hypertension were excluded from the study. Ninety-one healthy volunteers aged 40-75 years with a mean age of 55.30 +/- 8.56 years were recruited as normal controls. Transthoracic echocardiography was performed in all subjects to assess their left ventricular diastolic filling pattern by analyzing mitral and pulmonary flow velocities. RESULTS: Seventy-one (58%) of the type-2 diabetic subjects had evidence of impaired relaxation, 9 (7%) had pseudonormal filling and 7 (6%) had a restrictive filling pattern. Only 29% of the diabetics had a normal filling profile compared to 58% of the normal controls (X2 = 19.4, p = 0.0002). CONCLUSIONS: The result of the study shows that Nigerian type-2 diabetics have impaired left ventricular filling compared with normal subjects independent of confounding factors such as obesity and blood pressure. Therefore, not only Caucasians, African Americans and Asians but also African diabetic subjects suffered from diastolic dysfunction.     

Development of a mobile pulse waveform analyzer for cardiovascular health monitoring

Noninvasive pulse waveforms contain rich pathophysiological information of cardiovascular system. It is hereby a tradition of interest to implement risk stratification by pulse waveform monitoring and analysis. In contrast to conventional computer- or network-based solutions, we attempt to accomplish pulse waveform monitoring and analysis within a self-contained mobile platform. It adopts a compact biosensor for pulse waveform acquisition. The collected signals are then submitted to a core board for pulse waveform processing and analysis. In addition, the core board coordinates user interaction and network communication too. Such compact pulse waveform analyzer is of great help for cardiovascular health monitoring at home. A carefully designed evaluation has been undertaken within our research group. The results confirmed its prospect in home healthcare.     

A biomechanical model for real-time simulation of PMMA injection with haptics

We have developed a computationally efficient rheological model to simulate polymethylmethacrylate (PMMA) injection into cancellous bone during percutaneous vertebroplasty. The model employs the Hagen-Poiseuille law to predict pressure drop across a delivery cannula with viscoelastic changes of curing PMMA modeled via a time and shear-rate-dependent power law. The power law was derived based on dynamic rheological testing of curing PMMA samples. In conjunction with a branching-pipe geometrical model that is reconstructed from micro-computed tomography scans of cancellous bone for estimating pressure changes during PMMA flow in bone, the method provides a fast estimation of overall injection pressure, and, hence, the reaction force during manual PMMA injection.     

Hepatitis C virus RNA elimination and development of resistance in replicon cells treated with BMS-790052

BMS-790052, a first-in-class hepatitis C virus (HCV) replication complex inhibitor, targeting nonstructural protein 5A (NS5A), displays picomolar to nanomolar potency against genotypes 1 to 5. This exceptional potency translated into robust anti-HCV activity in clinical studies with HCV genotype 1-infected subjects. To date, all BMS-790052-associated resistance mutations have mapped to the N-terminal region of NS5A. To further characterize the antiviral activity of BMS-790052, HCV replicon elimination and colony formation assays were performed. Replicon was cleared from genotype 1a and 1b replicon cells in a time- and dose-dependent manner. Elimination of the genotype 1a replicon required longer treatment durations and higher concentrations of BMS-790052 than those for the genotype1b replicon. Single amino acid substitutions that conferred relatively low levels of resistance were observed at early time points and at low doses. Higher doses and longer treatment durations yielded mutations that conferred greater levels of resistance, including linked amino acid substitutions. Replicon cells that survived inhibitor treatment remained fully sensitivity to pegylated alpha interferon (pegIFN-α) and other HCV inhibitors. Moreover, genotype 1a replicon elimination was markedly enhanced when pegIFN-α and BMS-790052 were combined. Resistant variants observed in this study were very similar to those observed in a multiple ascending dose (MAD) monotherapy trial of BMS-790052, validating replicon elimination studies as a model to predict clinical resistance. Insights gained from the in vitro anti-HCV activity and resistance profiles of BMS-790052 will be used to help guide the clinical development of this novel HCV inhibitor.     

In vitro activity of BMS-790052 on hepatitis C virus genotype 4 NS5A

The antiviral profile of BMS-790052, a potent hepatitis C virus (HCV) replication complex inhibitor targeting nonstructural protein NS5A, is well characterized for HCV genotype-1. Here, we report that BMS-790052 inhibits hybrid replicons containing HCV genotype-4 NS5A genes with 50% effective concentrations (EC(50)s) ranging from 7 to 13 pM. NS5A residue 30 was an important site for BMS-790052-selected resistance in the hybrid replicons. Our results support the potential of BMS-790052 as a valuable component of combination therapy for HCV genotype-4 chronic infection.