Vasomotor responses of coronary stenoses to acetylcholine and their relation to serum lipid levels in stable angina pectoris

The effects of acetylcholine administration on coronary stenoses in relation to serum lipids level were evaluated in 18 patients (15 men, 3 women) with coronary artery disease and stable angina. Intracoronary acetylcholine was infused in concentrations 10⁻⁷, 10^−6, 10⁻⁵ M, followed by intracoronary bolus administration of isosorbide dinitrate. Computerized angiography was used to assess the changes in the diameter of stenoses and of proximal and distal segments. During acetylcholine infusion, at concentrations between 10⁻⁷ to 10 ⁻⁵M, there was a significant (p <0.01) dose-dependent constriction of proximal and distal segments and of stenoses reversed by isosorbide dinitrate. There was no correlation between the serum total cholesterol level and the responses of proximal and distal segments to acetylcholine or nitrate. A correlation (p <0.05) was found between the serum total cholesterol level and the response of stenoses to acetylcholine, but there was no correlation with the response to isosorbide dinitrate. In conclusion, in patients with stable angina current serum total cholesterol level correlates with the vasomotor response of coronary stenoses to intracoronary acetylcholine. These findings are consistent with a direct effect of cholesterol, increasing basal coronary vasomotor tone and increasing the stimulated vasoconstrictor response of stenoses.     

Performance-based or self-report measures of physical function: which should be used in clinical trials of hip fracture patients?

Latham NK, Mehta V, Nguyen AM, Jette AM, Olarsch S, Papanicolaou D, Chandler J. Performance-based or self-report measures of physical function: which should be used in clinical trials of hip fracture patients?

Objectives

To assess the validity, sensitivity to change, and responsiveness of 3 self-report and 4 performance-based measures of physical function: activity measure for postacute care (AM-PAC) Physical Mobility and Personal Care scales, the Medical Outcomes Study 36-Item Short Form Health Survey Physical Function scale (SF-36 PF), the Physical Functional Performance test (PFP-10), the Short Physical Performance Battery (SPPB), a 4-meter gait speed, and the six-minute walk test (6MWT).

Design

A prospective observational study of patients after a hip fracture. Assessments were performed at baseline and 12 weeks postenrollment.

Setting

Inpatient and outpatient rehabilitation facilities in Norway, the United Kingdom, Sweden, Israel, Germany, the United States, Denmark, and Spain.

Participants

A sample of study participants (N=108) who had a hip fracture.

Interventions

Not applicable.

Main Outcome Measures

Assessments of validity (known-groups, concurrent, construct, and predictive), sensitivity to change (effect size, standardized response mean [SRM], SE of measure, minimal detectable change (MDC), and responsiveness (optimal operating cut-points and area under the curve) between baseline and 12-week follow-up.

Results

All physical function measures achieved comparably acceptable levels of validity. Odds ratios in predicting patient Global Assessment of Improvement at 12 weeks were as follows: AM-PAC Physical Mobility scale, 5.3; AM-PAC Personal Care scale, 3.6; SF-36 PF, 4.3; SPPB, 2.0; PFP-10, 2.5; gait speed, 1.9; and 6MWT, 2.4. Effect sizes and SRM exceeded 1 SD for all 7 measures. Percent of patients who exceeded the MDC₉₀ at week 12 were as follows: AM-PAC Physical Mobility scale, 90%; AM-PAC Personal Care scale, 74%; SF-36 PF, 66%; SPPB, 36%; PFP-10, 75%; gait speed, 69%; and 6MWT, 75%. When evaluating responsiveness using the area under receiver operating curves for each measure, all measures had acceptable responsiveness, and no pattern emerged of superior responsiveness depending on the type of measure used.

Conclusions

Findings reveal that the validity, sensitivity, and responsiveness of self-report measures of physical function are comparable to performance-based measures in a sample of patients followed after fracturing a hip. From a psychometric perspective, either type of functional measure would be suitable for use in clinical trials where improvement in function is an endpoint of interest. The selection of the most appropriate type of functional measure as the primary endpoint for a clinical trial will depend on other factors, such as the measure's feasibility or the strength of the association between the hypothesized mechanism of action of the study intervention and a functional outcome measure.     

ConfidenHT™ System for Diagnostic Mapping of Renal Nerves

Purpose of Review

To summarize the evidence regarding the distribution of renal nerves and their patterns of anatomic variations in animal and human settings. Moreover, the methodology and results of studies regarding renal nerve stimulation (RNS) in both preclinical and clinical models are presented.

Recent Findings

There are differences regarding the number and the size of renal fibers, as well as their distance from the lumen in the diverse parts of the main renal arteries and the branches. In both animals and humans, RNS is safe and results in an increase of blood pressure (BP) while the effect on heart rate varies. In this context, the ConfidenHT? system constitutes an integrated solution for effective RNS in humans.

Summary

Due to the diversity of renal nerve anatomy in humans, arterial areas for more effective renal denervation cannot be homogenously defined. The concept of mapping of renal nerves can improve completeness of renal denervation therapies by means of integrated RNS solutions such as the ConfidenHT? system.

     

Detection of Multivessel Disease Post Myocardial Infarction Using an Exercise‐Induced QRS Score

Objective: The aim of this study was to investigate the ability of Athens QRS score values to detect stenoses in other coronary arteries than the obstructed ones (which caused the myocardial infarction [MI]) in patients with a history of MI. Methods: We studied 125 patients (93 males and 32 females, mean age 54 ± 7 years [range 45–68 years]) with a history of MI (46 patients with anterior MI, 54 patients with inferior MI, 25 patients with lateral MI). All patients underwent treadmill exercise testing and coronary arteriography. Results: Athens QRS score values were inversely related to the extent of CAD: ?0.5 ± 0.3 mm for patients with 1‐VD (obstructed vessel), ?3.4 ± 2.2 mm for patients with 2‐VD (obstructed vessel and stenosis in another vessel), and ?5 ± 1.8 mm for patients with 3‐VD (obstructed vessel and stenoses in two more vessels). The ROC curves for the detection of multivessel disease showed that the area under the curve for QRS score values < ?3 mm is significantly higher than the curve for ST‐segment depression ≥1 mm (0.948 vs 0.792, P < 0.001). Conclusions: Values of the Athens QRS score less than ?3 may distinguish single‐ from multivessel coronary artery disease in patients with a history of MI.     

Levosimendan: beyond its simple inotropic effect in heart failure

Classic inotropic agents provide short-term haemodynamic improvement in patients with heart failure, but their use has been associated with poor prognosis. A new category of inotropic agents, the Ca(2+) sensitizers, may provide an alternative longer lasting solution. Levosimendan is a relatively new Ca(2+) sensitizer which offers haemodynamic and symptomatic improvement by combining a positive inotropic action via Ca(2+) sensitization and a vasodilatory effect via adenosine triphosphate(ATP)-sensitive K(+) (K(ATP)), Ca(2+)-activated K(+) (K(Ca)(2+)) and voltage-dependent K(+) (K(V)) channels activation. Levosimendan also seems to induce a prolonged haemodynamic improvement in patients with heart failure as a result of the long half-life of its active metabolite, OR-1896. Furthermore, there is also evidence that levosimendan may have additional antiinflammatory and antiapoptotic properties, affecting important pathways in the pathophysiology of heart failure. Despite the initial reports for a clear benefit of levosimendan on short- and long-term mortality in patients with severe heart failure, the results from the recent clinical trials are rather disappointing, and it is still unclear whether it is superior to dobutamine in affecting survival of patients with severe heart failure. In conclusion, levosimendan is a promising agent for the treatment of decompensated heart failure. As further to its positive inotropic effect, it affects multiple pathways with key roles in the pathophysiology of heart failure. The results of the ongoing trials examining the effect of levosimendan on mortality in patients with heart failure will hopefully resolve the controversy as to whether levosimendan is superior to classic inotropic agents for the treatment of severe heart failure.     

CD8- DCs induce IL-12-independent Th1 differentiation through Delta 4 Notch-like ligand in response to bacterial LPS

Toll-like receptor (TLR) ligation is believed to skew T cell responses toward T helper (Th)1 differentiation by inducing interleukin (IL)-12 secretion by CD8(+) dendritic cells (DCs). However, TLR-dependent Th1 responses occur in the absence of IL-12. To determine how DCs induce Th1 differentiation in the absence of IL-12, we examined the response of IL-12-deficient DCs to bacterial lipopolysaccharide (LPS). We find that LPS activates MyD88-dependent Delta 4 Notch-like ligand expression by CD8(-) DCs, and that these cells direct Th1 differentiation by an IL-12-independent and Notch-dependent mechanism in vitro and in vivo. Thus, activation of the two DC subsets by TLR4 leads to Th1 responses by two distinct MyD88-dependent pathways.     

Effects of blood loss and fluid volume replacement on serum and tissue gentamicin concentrations during colorectal surgery

BACKGROUND: The prophylactic administration of antimicrobial agents to surgical patients has become standard practice to minimize the risk for postsurgical infection. During surgery, factors such as renal clearance, fluid administration, and blood loss contribute to drug concentrations achieved in the blood and tissues. The aminoglycoside gentamicin was chosen to investigate these factors because it is used for standard antimicrobial prophylaxis in colorectal surgery. OBJECTIVE: The aim of this study was to investigate the effects of surgical blood loss and fluid volume replacement on gentamicin concentrations in serum and in 3 tissue types (subcutaneous fat, epiploic fat, and colonic wall) in patients undergoing colorectal surgery. METHODS: This uncontrolled, open-label study was conducted at the Aretaieion Hospital (Athens, Greece) between November 2002 and March 2003. Patients selected for this study were scheduled to undergo elective colorectal surgery of ? 2-hour duration with general and epidural anesthesia and to receive gentamicin as major antimicrobial prophylaxis. Blood and tissue samples were obtained concurrently at specific times throughout each procedure. The effect of intraoperative blood loss on gentamicin concentrations and its pharmacokinetic properties was determined. RESULTS: Sixteen patients completed the study (11 men, 5 women; white race, 16 patients [100%]; mean [SD] age, 61 [3] years [range, 39-80 years]). Mean (SEM) serum gentamicin concentration was found to be insufficient; the maximum plasma drug concentration/minimum inhibitory concentration (MIC) ratio was <8:1 for pathogens commonly isolated in the surgical unit of the hospital (MIC: 1-4 microg/mL). The mean (SEM) concentration at first surgical incision was 7.83 (0.82) microg/mL and decreased to 2.60 (0.28) microg/mL at skin closure, resulting in borderline effectiveness even for susceptible gram-positive microorganisms (MIC approximately 1.0). Initially, mean (SEM) tissue gentamicin concentrations in subcutaneous fat, epiploic fat, and colonic wall were low (2.02 [0.34] microg/mL, 2.41 [0.42] microg/mL, and 1.93 [0.38] microg/mL, respectively) and decreased approximately 1.0 microg/mL ( approximately 50%) by skin closure. Statistically significant positive correlations were found between gentamicin concentrations in serum and tissues (P 相似文献   

The diagnosis of Gestational Diabetes Mellitus and its impact on In Vitro Fertilization pregnancies. A pilot study

BackgroundIn Vitro Fertilization (IVF) is increasingly becoming a necessary mode of reproduction. This high risk group is prone to Gestational Diabetes Mellitus (GDM) which further exposes these pregnancies to an increased risk of adverse outcomes. In light of the limited data in the current literature, further investigation is needed regarding the time of GDM diagnosis in IVF pregnancies as well as the outcome of IVF pregnancies complicated by GDM.MethodsIn this three center pilot cross sectional study, the data of 101 singleton IVF pregnancies complicated by GDM were analyzed. Prompt GDM diagnosis in IVF pregnancies was accomplished by self-blood glucose monitoring (SMBG) from the first antenatal visit and confirmed by an OGTT. To evaluate pregnancy outcome, maternal and fetal complications in the 101 GDM IVF group was compared to 101 IVF as well as 101 spontaneous conceptions (SC). The three groups were matched by age. The effect of demographic and glycemic parameters on the outcome of GDM IVF pregnancies was investigated.ResultsGDM diagnosis was made before the 24th week in 37.6% of the GDM IVF group. The week of delivery was earlier for the GDM IVF group (37 ± 1.7) relative to the IVF (37.9 ± 0.9, p < 0.001) and the SC group (38.1 ± 0.8, p < 0.001). GDM IVF pregnancies exhibited greater preeclampsia rates and 84.8% underwent caesarian section. No significant difference regarding LGA and SGA birth weights was found. Complications of GDM IVF pregnancies were associated with the 1-h postprandial BG (r = 0.267, p = 0.007).ConclusionGDM screening in IVF pregnancies may be considered earlier than the 24th week. IVF pregnancies affected by GDM are prone to increased maternal and fetal complications which are associated with 1-h postprandial BG.     

Functional electrical stimulation improves endothelial function and reduces peripheral immune responses in patients with chronic heart failure.

BACKGROUND: Previous studies have shown beneficial effects of functional electrical stimulation (FES) on muscle performance and exercise capacity of patients with chronic heart failure. This study evaluates the impact of FES on endothelial function and peripheral markers of immune activation in patients with moderate to severe heart failure. METHODS: Twenty-four patients with a left ventricular ejection fraction of less than 40% and New York Heart Association class II-III symptoms, undergoing optimized drug therapy, were randomly assigned (2 : 1) to a 6-week training programme of FES (n=16) or served as controls (n=8). Endothelial function was assessed by Doppler flow-mediated dilatation (FMD) of the brachial artery before and after the training programme. Peripheral pro-inflammatory/anti-inflammatory markers such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, soluble intercellular adhesion molecule (sICAM)-1, soluble vascular cell adhesion molecule (sVCAM)-1 and IL-10 were also measured before and after training. RESULTS: A significant improvement on the 6-min walk test (7.5+/-3.3%), Minnesota Living Score (18.2+/-8.6%) and FMD (38.5+/-15.1%) was observed only in the FES-treated group. FES also causes a significant reduction of TNF-alpha (-11.5+/-8.9%), sICAM-1 (-13.1+/-9.8%), and sVCAM-1 (-10.6+/-6.6%), as well as a respective increase in the ratio IL-10/TNF-alpha (37.1+/-29.4%). In the FES group, the percentage improvement in the Minnesota Living Score was significantly correlated with respective changes in circulating TNF-alpha (r=0.624, P<0.01), sVCAM-1 (r=0.665, P<0.001) and the ratio IL-10/TNF-alpha (r=-0.641, P<0.01). CONCLUSION: FES is an exercise training programme that improves endothelial function in patients with chronic heart failure, and also has anti-inflammatory effects.