Adrenergic Receptor Genotype but Not Perioperative Bisoprolol Therapy May Determine Cardiovascular Outcome in At-risk Patients Undergoing Surgery with Spinal Block: The Swiss Beta Blocker in Spinal Anesthesia (BBSA) Study: A Double-blinded, Placebo-controlled, Multicenter Trial with 1-Year Follow-up

Background: Neuraxial blockade is used as primary anesthetic technique in one third of surgical procedures. The authors tested whether bisoprolol would protect patients at risk for cardiovascular complications undergoing surgery with spinal block.

Methods: The authors performed a double-blinded, placebo-controlled, multicenter trial to compare the effect of bisoprolol with that of placebo on 1-yr composite outcome including cardiovascular mortality, nonfatal myocardial infarction, unstable angina, congestive heart failure, and cerebrovascular insult. Bisoprolol was given orally before and after surgery for a maximum of 10 days. Adrenergic receptor polymorphisms and safety outcome measures of bisoprolol therapy were also determined.

Results: A total of 224 patients were enrolled. Spinal block could not be established in 5 patients. One hundred ten patients were assigned to the bisoprolol group, and 109 patients were assigned to the placebo group. The mean duration of treatment was 4.9 days in the bisoprolol group and 5.1 days in the placebo group. Bisoprolol therapy reduced mean heart rate by 10 beats/min. The primary outcome was identical between treatment groups and occurred in 25 patients (22.7%) in the bisoprolol group and 24 patients (22.0%) in the placebo group during the 1-yr follow-up (hazard ratio, 0.97; 95% confidence interval, 0.55-1.69; P = 0.90). However, carriers of at least one Gly allele of the [beta]1-adrenergic receptor polymorphism Arg389Gly showed a higher number of adverse events than Arg homozygous (32.4% vs. 18.7%; hazard ratio, 1.87; 95% confidence interval, 1.04-3.35; P = 0.04).     

Value of Doppler ultrasound for the diagnosis of renal artery stenosis in children

To evaluate the reliability of Doppler ultrasonography (US) in identifying children with renal artery stenosis (RAS) among those with hypertension, we compared Doppler US results in 22 hypertensive children (mean age 8.9±4.3 years), with (13 cases) and without RAS at angiography, and in 33 normotensive children (mean age 8.8±4.7 years). We observed 2 false-negatives and 2 false-positives with Doppler US. Of the 2 false-negative diagnoses, 1 had RAS on an accessory renal artery located behind a normal upper polar artery and the other was observed in a patient with bilateral multiple stenosis of the very distal segments of renal arteries. The 2 false-positive diagnoses were due to sinuous left renal artery and to technical reasons, respectively. In another patient, Doppler US showed a tight RAS, while arteriography was normal. RAS was subsequently confirmed by a second arteriography. Peak systolic velocity values of Doppler US were significantly higher in patients with proven angiographic RAS (3.44±0.66 m/s) than in hypertensive patients with normal renal arteries at angiography (0.99±0.35 m/s, P <0.0001) and normotensive healthy children (1.04±0.23 m/s, P <0.0001). With the use of multiple views, and the experience acquired with practice, false-negatives or false-positives due to the geometry of the renal artery can be avoided. Nevertheless, very distal stenosis can be missed by Doppler US. Received October 30, 1995; received in revised form April 16, 1996; accepted May 14, 1996     

Risk factors for placental abruption in a socio-economically disadvantaged region.

OBJECTIVE: This study was undertaken in order to determine the risk factors for pregnancies complicated by placental abruption in a socio-economically disadvantaged region in metropolitan Adelaide. METHODS: This was a retrospective case-control study including all singleton pregnancies resulting in placental abruption between 2001 and 2005. RESULTS: The overall incidence of placental abruption was 1.0%; the overall perinatal mortality among the births with abruption was 13%. Univariate analyses showed the following significant risk factors for placental abruption: preterm pre-labor rupture of the membranes (PRE-PROM; odds ratio (OR) 4.79, 95% confidence interval (CI) 1.52-15.08), non-compliance with antenatal care (OR 2.93, 95% CI 1.06-8.90), severe intrauterine growth restriction (IUGR), and elevated homocysteine levels (OR 45.55, 95% CI 7.05-458.93). Severe IUGR was significantly more common in the abruption group compared with the control group (p = 0.032). In the multivariate analysis, PRE-PROM remained a significant independent risk factor for placental abruption. Marijuana use, domestic violence, and mental health problems were more common (borderline significance) in the abruption group. Smoking and preeclampsia were not found to be associated with placental abruption in this study. CONCLUSIONS: In this high-risk population, PRE-PROM and elevated homocysteine levels appear to represent the major risk factors for placental abruption.     

在免眼中进行经瞳孔阈值下温热疗法的组织学效应和蛋白表达

目的：研究阈值下经瞳孔温热疗法（TTT）对视网膜组织学的效应。方法：对正常视网膜色素的兔眼进行TTT，通过1个810nm激光二极管产生直径为1．2mm能量为50mW的光斑，持续时间为15、30和60秒。4周后进行荧光血管造影并摘除眼球，通过电子显微镜和免疫组化染色来检查。     

Cancer-testis genes are coordinately expressed and are markers of poor outcome in non-small cell lung cancer.

PURPOSE: Cancer-testis genes mapping to the X chromosome have common expression patterns and show similar responses to modulators of epigenetic mechanisms. We asked whether cancer-testis gene expression occurred coordinately, and whether it correlated with variables of disease and clinical outcome of non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Tumors from 523 NSCLC patients undergoing surgery were evaluated for the expression of nine cancer-testis genes (NY-ESO-1, LAGE-1, MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A10, CT7/MAGE-C1, SSX2, and SSX4) by semiquantitative PCR. Clinical data available for 447 patients were used to correlate cancer-testis expression to variables of disease and clinical outcome. RESULTS: At least one cancer-testis gene was expressed by 90% of squamous carcinoma, 62% of bronchioloalveolar cancer, and 67% of adenocarcinoma samples. Statistically significant coexpression was observed for 34 of the 36 possible cancer-testis combinations. Cancer-testis gene expression, either cumulatively or individually, showed significant associations with male sex, smoking history, advanced tumor, nodal and pathologic stages, pleural invasion, and the absence of ground glass opacity. Cox regression analysis revealed the expression of NY-ESO-1 and MAGE-A3 as markers of poor prognosis, independent of confounding variables for adenocarcinoma of the lung. CONCLUSIONS: Cancer-testis genes are coordinately expressed in NSCLC, and their expression is associated with advanced disease and poor outcome.     

Pharmacokinetics,biocompatibility and bioavailability of a controlled release monoclonal antibody formulation

The sustained and localized delivery of monoclonal antibodies has become highly relevant, because of the increasing number of investigated local delivery applications in recent years. As the local delivery of antibodies is associated with high technological hurdles, very few successful approaches have been reported in the literature so far. Alginate-based delivery systems were previously described as promising sustained release formulations for monoclonal antibodies (mAbs). In order to further investigate their applicability, a single-dose animal study was conducted to compare the biocompatibility, the pharmacokinetics and the bioavailability of a human monoclonal antibody liquid formulation with two alginate-based sustained delivery systems after subcutaneous administration in rats. 28 days after injection, the depot systems were still found in the subcutis of the animals. A calcium cross-linked alginate formulation, which was injected as a hydrogel, was present as multiple compartments separated by subcutaneous tissue. An in situ forming alginate formulation was recovered as a single compact and cohesive structure. It can be assumed that the multiple compartments of the hydrogel formulation led to almost identical pharmacokinetic profiles for all tested animals, whereas the compact nature of the in situ forming system resulted in large interindividual variations in pharmacokinetics. As compared to the liquid formulation the hydrogel formulations led to lower mAb serum levels, and the in situ forming system to a shift in the time to reach the maximum mAb serum concentration (T_max) from 2 to 4 days. Importantly, it was shown that after 28 days only marginal amounts of residual mAb were present in the alginate matrix and in the tissue at the injection site indicating nearly complete release. In line with this finding, systemic drug bioavailability was not affected by using the controlled release systems. This study successfully demonstrates the suitability and underlines the potential of polyanionic systems for local and controlled mAb delivery.     

Effects of short-term supplementation with bovine lactoferrin and/or immunoglobulins on body mass and metabolic measures: a randomised controlled trial

Given the role of the intestinal microbiota in obesity and related disease, strategies to modulate the composition of the intestinal microbiota may augment traditional weight-management approaches. Here, we examined the safety and tolerability of 28 days of supplementation with bovine whey-derived lactoferrin and immunoglobulin supplements in a cross-sectional cohort of free-living adults. Participants (n?=?20 each group) received enteric-coated whey-derived bovine lactoferrin (200?mg), immunoglobulin (200?mg or 800?mg), combination lactoferrin/immunoglobuiln supplements (200?mg/200?mg, 200?mg/800?mg) or placebo in a double-blind design. Supplement use was generally well tolerated and routine haematology, and clinical chemistry measures were largely unchanged following supplementation. Measures of body composition remained stable and indices of glycaemic control and blood lipids revealed fluctuations of?<5% but were not significantly different between groups. Overall, short-term lactoferrin/immunoglobulin supplementation was well tolerated in this cohort; use of these types of supplements to enhance other weight management strategies should be investigated over extended periods.     

Efficient and non-toxic gene transfer to cardiomyocytes using novel generation amplicon vectors derived from HSV-1

OBJECTIVE: The feasibility of gene transfer to myocardial tissue using viral vectors was investigated over the last few years. In this study we report gene transfer using a recently described improved of Herpes simplex virus (HSV-1)-derived amplicon vectors and demonstrate that these vectors are a powerful and potentially very interesting tool for gene transfer into neonatal primary as well as in adult cardiac myocytes. METHODS AND RESULTS: Non-pathogenic HSV-1 amplicon vectors simultaneously expressing GFP and LacZ were constructed using a novel helper system that yields essentially helper-free vector particles. These vectors were used to infect either cultured primary neonatal rat cardiomyocytes or adult cardiac tissue. Transgenic expression was quantified using a FACS (GFP) or X-gal staining (LacZ). Infection of primary cardiomyocytes showed efficient transduction even at very low multiplicity of infection (MOI), and expression increased with the infectious dose. By investigating release of lactate dehydrogenase (LDH) or spontaneous beating of the cells, we failed to detect cytotoxic effects in cardiomyocytes infected at high MOI. Thin slices of adult cardiac tissue placed in medium containing vectors also showed very good levels of transduction, without any evidence of toxic effects. CONCLUSIONS: Helper-free amplicon vectors very efficiently transduce genes into cardiomyocytes. Our results indicate similar or better transduction efficiencies than those reported using other vector systems. Furthermore, the very high transgenic capacity of amplicon vectors (up to 150 kbp) makes these vectors a unique and very suitable system to transduce large genomic sequences into cardiomyocytes.