Arterial compliance adds to conventional risk factors for prediction of angiographic coronary artery disease

Background

Arterial compliance is related to left ventricular hypertrophy and risk for cardiovascular disease events; however, its association with coronary artery stenosis remains uncertain. We sought to assess the relation between lower extremity arterial compliance and presence of angiographically defined coronary artery disease.

Methods

Lower extremity arterial compliance was measured with the use of a noninvasive air plethysmography technique in 376 subjects undergoing routine diagnostic coronary angiography.

Results

Measures of calf arterial compliance were significantly associated with the presence of one or more stenoses ≥50% compared with no stenoses, even after adjustment for age, sex, smoking, diabetes, hypertension, hypercholesterolemia, and obesity (P = .03). Measures of thigh arterial compliance were also lower in subjects with disease, although this association did not reach statistical significance (P = .07). Receiver operator curves illustrate the incremental predictive ability of calf arterial compliance over and above age, sex, and conventional risk factors.

Conclusions

Lower extremity arterial compliance is associated with presence of significant coronary stenoses in a cardiac catheterization laboratory referral population. This observation lends support for additional efforts to determine the utility of vascular stiffness measures in both clinical and pre-clinical populations to guide treatment and prevention efforts.     

The life cycle of the steroidogenic acute regulatory (StAR) protein: from transcription through proteolysis

The Steroidogenic Acute Regulatory (StAR) protein is a mitochondrial protein required for the transport of cholesterol substrate to the P450scc enzyme located in the inner mitochondrial membranes of steroid producing cells. This study suggests that the acute regulation of the rodent StAR gene in the ovary is mediated by two factors, C/EBPbeta and GATA-4. Once translated, the StAR precursor protein is either imported into the mitochondria, or it is rapidly degraded in the cytosol. We predicted that in order to perpetuate StAR activity cycles, imported StAR should turn over rapidly to avoid a potentially harmful accumulation of the protein in sub-mitochondrial compartments. Pulse-chase experiments in metabolically labeled cells showed that: (a) the turnover rate of mature mitochondrial StAR protein (30 kDa) is much faster (t(1/2) = 4-5 h) than that of other mitochondrial proteins; (b) dissipation of the inner membrane potential (-delta psi) by carbonyl cyanide m-chlorophenylhydrazone (mCCCP) accelerates the mitochondrial degradation of StAR; (c) unexpectedly, the mitochondrial degradation of StAR is inhibited by MG132 and lactacystin, but not by epoxomicin. Furthermore, StAR degradation becomes inhibitor-resistant two hours after import. Therefore, these studies suggest a bi-phasic route of StAR turnover in the mitochondria. Shortly after import, StAR is degraded by inhibitor-sensitive protease(s) (phase I), whereas at later times, StAR turnover proceeds to completion through an MG132-resistant proteolytic activity (phase II). Collectively, this study defines StAR as a unique protein that can authentically be used to probe multiple proteolytic activities in mammalian mitochondria.     

Ischemia-reperfusion model in rat spinal cord: cell viability and apoptosis signaling study

This work aimed at determining the ideal ischemia time in an in vitro ischemia-reperfusion model of spinal cord injury. Rat spinal cord slices were prepared and then exposed or not to oxygen deprivation and low glucose (ODLG) for 30, 45, 60, 75 and 90 minutes. Cell viability was assessed by triphenyltetrazolium (TTC), lactate dehydrogenase (LDH) release, and fluorochrome dyes specific for cell dead (ethidium homodimer) using the apotome system. Glutamate release was enzymatically measured by a fluorescent method. Gene expression of apoptotic factors was assessed by real time RT-PCR. Whereas spinal cord slices exposed to ODLG exhibited mild increase in fluorescence for 30 minutes after the insult, the 45, 60, 75 and 90 minutes caused a 2-fold increase. ODLG exposure for 45, 60, 75 or 90 minutes, glutamate and LDH release were significantly elevated. nNOS mRNA expression was overexpressed for 45 minutes and moderately increased for 60 minutes in ODLG groups. Bax/bcl-xl ratio, caspase 9 and caspase 3 mRNA expressions were significantly increased for 45 minutes of ODLG, but not for 30, 60, 75 and 90 minutes. Results showed that cell viability reduction in the spinal cord was dependent on ischemic time, resulting in glutamate and LDH release. ODLG for 45 minutes was adequate for gene expression evaluation of proteins and proteases involved in apoptosis pathways.     

Actionable Nuggets: Knowledge translation tool for the needs of patients with spinal cord injury

Objective

To present the results of a pilot study of an innovative methodology for translating best evidence about spinal cord injury (SCI) for family practice.

Design

Review of Canadian and international peer-reviewed literature to develop SCI Actionable Nuggets, and a mixed qualitative-quantitative evaluation to determine Nuggets’ effect on physician knowledge of and attitudes toward patients with SCI, as well as practice accessibility.

Setting

Ontario, Newfoundland, and Australia.

Participants

Forty-nine primary care physicians.

Methods

Twenty Actionable Nuggets (pertaining to key health issues associated with long-term SCI) were developed. Nugget postcards were mailed weekly for 20 weeks to participating physicians. Prior knowledge of SCI was self-rated by participants; they also completed an online posttest to assess the information they gained from the Nugget postcards. Participants’ opinions about practice accessibility and accommodations for patients with SCI, as well as the acceptability and usefulness of Nuggets, were assessed in interviews.

Main findings

With Actionable Nuggets, participants’ knowledge of the health needs of patients with SCI improved, as knowledge increased from a self-rating of fair (58%) to very good (75%) based on posttest quiz results. The mean overall score for accessibility and accommodations in physicians’ practices was 72%. Participants’ awareness of the need for screening and disease prevention among this population also increased. The usefulness and acceptability of SCI Nugget postcards were rated as excellent.

Conclusion

Actionable Nuggets are a knowledge translation tool designed to provide family physicians with concise, practical information about the most prevalent and pressing primary care needs of patients with SCI. This evidence-based resource has been shown to be an excellent fit with information consumption processes in primary care. They were updated and adapted for distribution by the Canadian Medical Association to approximately 50 000 primary care physicians in Canada, in both English and French.     

Children's Parasympathetic Reactivity to Specific Emotions Moderates Response to Intervention for Early-Onset Aggression

Following theories that individual differences in respiratory sinus arrhythmia (RSA) denote differential sensitivity to environmental influences, this study examines whether differences in RSA reactivity to specific emotional challenges predict differential response to intervention. We present data from a randomized clinical trial of a targeted intervention for early onset aggression. In collaboration with a high-risk urban school district, 207 kindergarten children (73% African American, 66% male), identified by their teachers as having high levels of aggressive and disruptive behavior, were recruited. All children received a universal social-emotional curriculum. One hundred children were randomly assigned to an additional intervention consisting of weekly peer-based social skills training. Complete RSA data were available for 139 of the children. Teacher-reported externalizing symptoms and emotion regulation in 1st grade (post intervention) were examined controlling for baseline levels. First-grade peer nominations of aggressive behavior, controlling for baseline nominations, were also examined as outcomes. No effect of resting RSA was found. However, greater reactivity to anger was associated with higher externalizing symptoms and lower emotion regulation skills in 1st grade relative to low reactive children. Lower reactivity to fear was associated with greater improvement over time, an effect that was enhanced in the targeted intervention condition. Results suggest that measures of affective reactivity may provide insight into children's capacity to benefit from different types of interventions.     

A randomized controlled trial comparing haemodynamic stability in elderly patients undergoing spinal anaesthesia at L5, S1 versus spinal anaesthesia at L3, 4 at a tertiary African hospital

Background

Spinal anaesthesia is a routinely used anaesthetic technique in elderly patients (> 60 years) undergoing operations involving the lower limbs, lower abdomen, pelvis and the perineum. Spinal anaesthesia has several advantages over general anaesthesia including stable haemodynamic variables, less blood loss, less post-operative pain, faster recovery time and less post-operative confusion. Despite these advantages, the sympathetic blockade induced by spinal anaesthesia can result in hypotension, bradycardia, dysrhythmias and cardiac arrests. Conventionally, spinal anaesthesia is performed at the level of L3,4 interspace; with a reported incidence of hypotension in the elderly ranging between 65% and 69%. A possible strategy for reducing spinal induced hypotension would be to minimize the peak block height to as low as possible for the planned procedure.

Objective

To determine the difference in haemodynamic stability between elderly patients undergoing spinal anaesthesia at L5, S1 interspace compared to those at L3, 4.

Methods

Thirty two elderly patients scheduled for lower limb or pelvic surgery under spinal anaesthesia were randomized into 2 groups (control group and intervention group) using a computer generated table of numbers.Control group; received 2.5 mls 0.5% hyperbaric bupivacaine injected intrathecally at the L3, 4 interspace and Intervention group; 2.5mls 0.5% hyperbaric bupivacaine injected intrathecally at the L5, S1 interspace

Results

The two groups had similar baseline characteristics in age, sex, body mass index and use of anti-hypertensive medications. There was 68.8% proportion of hypotension in the control group and 75% in the intervention group. The difference was not found to be statistically significant (p= 0.694). During the study period, there were 106 episodes of hypotension, out of which, 65 were in the control group and 41 in the intervention group (p=0.004).. Linear regression analysis of the decrease in mean arterial pressures (MAP) showed a higher decrease in MAP in the control group (p 0.018). There were more crystalloids used in the control group (1006mls ± 374) than in the intervention group (606mls ±211) with a p< 0.0001. There was no difference in the amounts of vasopressors used between the two groups (p=0.288). There was no difference in the change in heart rates, conversion to general anaesthesia, use of supplementary intravenous fentanyl and the peak maximum block level achieved. The time to peak maximum sensory block level was 9.06min and 13.07min in the control group and intervention groups, respectively (p<0.0001).

Conclusion

Among this population, there was no difference in the proportion of those with hypotension between the elderly patients who received their spinal anaesthesia at L3,4 and those who received spinal anaesthesia at L5,S1. The intervention group had better outcomes with significantly less episodes of hypotension. It took a longer time to achieve a maximum peak sensory block in the intervention group. Performing spinal anaesthesia at the level of L5,S1 was found to provide an adequate sensory block for a wide range of pelvic, perineal and lower limb surgeries.