Increasing the value of student audits.

This short article provides simple tips on how to increase the educational value of student audits, whilst at the same time ensuring that the audits are of real value to the practice.

Impact of aerobic fitness on cerebral blood flow and cerebral vascular responsiveness to CO2 in young and older men.

We sought to test the hypothesis that brain blood flow and cerebral vascular responsiveness to carbon dioxide (CVRCO2 ) are greater in aerobically trained young and old individuals compared to their untrained counterparts. In 11 young trained {[23 (20-26) years] [mean (95% confidence interval)]}, 10 young untrained [25 (22-28) years], 8 older trained [65 (61-69) years], and 9 older untrained [67 (64-71) years] healthy individuals, Doppler ultrasound of the internal carotid (ICA) and vertebral (VA) artery blood flow were determined, along with middle cerebral artery mean flow velocity (MCA Vmean ). Bilateral ICA blood flow was higher in trained individuals when compared to untrained (≈31%, P < 0.05), but was not influenced by age. VA blood flow was not affected by age or cardiorespiratory fitness. MCA Vmean was reduced with age [59.5 (55.0-64.1) cm/s young vs 43.6 (38.4-48.9) cm/s old, P < 0.05] with no significant effect of training observed. MCA CVRCO2 were not significantly affected by either age or training status, while ICA CVRCO2 tended to be elevated in the old trained group. These findings indicate that endurance training enhances bilateral ICA but not VA blood flow in both young and older individuals.

Contrasting biofunctionalization strategies for the enhanced endothelialization of biodegradable vascular grafts.

Surface modification of biodegradable vascular grafts is an important strategy to improve the in situ endothelialization of tissue engineered vascular grafts (TEVGs) and prevent major complications associated with current synthetic grafts. Important strategies for improving endothelialization include increasing endothelial cell mobilization and increased endothelial cell capture through biofunctionalization of TEVGs. The objective of this study was to assess two biofunctionalization strategies for improving endothelialization of biodegradable polyester vascular grafts. These techniques consisted of cross-linking heparin to graft surfaces to immobilize vascular endothelial growth factor (VEGF) or antibodies against CD34 (anti-CD34Ab). To this end, heparin, VEGF, and anti-CD34Ab attachment and quantification assays confirmed the efficacy of the modification strategy. Cell attachment and proliferation on these groups were compared to unmodified grafts in vitro and in vivo. To assess in vivo graft functionality, the grafts were implanted as inferior vena cava interpositional conduits in mice. Modified vascular grafts displayed increased endothelial cell attachment and activity in vivo, according to microscopy techniques, histological results, and eNOS expression. Inner lumen diameter of the modified grafts was also better maintained than controls. Overall, while both functionalized grafts outperformed the unmodified control, grafts modified with anti-CD34Ab appeared to yield the most improved results compared to VEGF-loaded grafts.

Relationship between aerobic endurance training and dynamic cerebral blood flow regulation in humans.

The incidence of orthostatic intolerance is elevated in endurance-trained individuals. We sought to test the hypothesis that aerobic endurance training is associated with an attenuated control of the cerebral vasculature. Endurance trained (ET, n = 13) and age-matched untrained (UT, n = 11) individuals (peak O2 consumption, mean ± SEM; 63 ± 1 vs 42 ± 1 mL/min/kg, P < 0.05) were examined while supine and seated upright. Dynamic cerebral autoregulation (CA) was assessed by calculation of the rate of regulation (RoR) from the arterial blood pressure (ABP) and middle cerebral artery (MCA) mean blood velocity (V mean ) responses to a bilateral thigh cuff release, which evoked a transient hypotension. Cerebral oxygenation (oxyhemoglobin; HbO2 ) was determined with near-infrared spectroscopy. When seated upright, cuff release evoked a greater decrease in ABP (P < 0.001), MCA V mean (P = 0.096) and HbO2 (P < 0.001) in ET compared with UT. However, RoR was similar in ET and UT individuals while seated upright (to 0.193 ± 0.039 vs 0.129 ± 0.029/s, P > 0.05), and there was no significant difference in the relative change in RoR from the supine to upright positions (ΔRoR: -65 ± 7 and -69 ± 7%, for ET and UT, respectively). These findings suggest that aerobic endurance training is not associated with an attenuation in dynamic CA.

Epizootic neoplasia of the lateral line system of lake trout (Salvelinus namaycush) in New York's Finger Lakes.

This article documents an epizootic of inflammation and neoplasia selectively affecting the lateral line system of lake trout (Salvelinus namaycush) in 4 Finger Lakes in New York from 1985 to 1994. We studied more than 100 cases of this disease. Tumors occurred in 8% (5/64) of mature and 21% (3/14) of immature lake trout in the most severely affected lake. Lesions consisted of 1 or more neoplasm(s) in association with lymphocytic inflammation, multifocal erosions, and ulcerations of the epidermis along the lateral line. Lesions progressed from inflammatory to neoplastic, with 2-year-old lake trout showing locally extensive, intense lymphocytic infiltrates; 2- to 3-year-old fish having multiple, variably sized white masses up to 3 mm in diameter; and fish over 5 years old exhibiting 1 or more white, cerebriform masses greater than 1 cm in diameter. Histologic diagnoses of the tumors were predominantly spindle cell sarcomas or benign or malignant peripheral nerve sheath neoplasms, with fewer epitheliomas and carcinomas. Prevalence estimates did not vary significantly between sexes or season. The cause of this epizootic remains unclear. Tumor transmission trials, virus isolation procedures, and ultrastructural study of lesions failed to reveal evidence of a viral etiology. The Finger Lakes in which the disease occurred did not receive substantially more chemical pollution than unaffected lakes in the same chain during the epizootic, making an environmental carcinogen an unlikely primary cause of the epizootic. A hereditary component, however, may have contributed to this syndrome since only fish of the Seneca Lake strain were affected.

Broad responses and attitudes to having music in surgery (the BRAHMS study) - a South African perspective.

BACKGROUND: Music is played in operating theatres (OTs) throughout the world, though controversy around its use exists. While some clinicians may find background music favourable to the theatre mood and a way to augment surgical performance, there is concern raised over its distracting and noise-creating properties. METHODS: In this prospective observational study, between August and December 2021, 110 surgeons and registrars in South Africa responded to a survey investigating the way they use music, and their perceptions and attitudes towards its effect on the OT environment. RESULTS: In this cohort, 66% were male, 29% were consultants and the most common age range was 30-39 years old. Eighty per cent of respondents reported that music was played at least "sometimes", with 74% reporting that they enjoyed it. Easy Listening was the most played and preferred genre followed by Top 40/Billboard hits. Overwhelmingly, respondents reported that background music in the OT improved temperament, focus, mood, and performance, though over a quarter felt it worsened communication. Thirty-one per cent of respondents reported that the choice of music depended on the type of operation, and 70% would turn music down or off during crises. Those who enjoyed music in their spare time were significantly more likely to enjoy music in the OT and perceive it positively. CONCLUSION: This study provides a window into the surgeons' use of and attitudes to intraoperative music in South Africa. While overall, music is viewed positively by this cohort, some concerns remain regarding communication and distractedness. Further interventional and qualitative studies would be useful.

3D-Printed Biodegradable Polymeric Vascular Grafts.

Congenital heart defect interventions may benefit from the fabrication of patient-specific vascular grafts because of the wide array of anatomies present in children with cardiovascular defects. 3D printing is used to establish a platform for the production of custom vascular grafts, which are biodegradable, mechanically compatible with vascular tissues, and support neotissue formation and growth.

Intracardiac ultrasound determination of left ventricular volumes: in vitro and in vivo validation.

OBJECTIVES: This study was designed to assess the feasibility of calculating left ventricular volumes using intracardiac ultrasound. BACKGROUND: Previous studies have validated transthoracic echocardiographic determinations of left ventricular volumes and have indicated the superiority of Simpson rule reconstruction algorithms. The feasibility of imaging the left ventricle with intracardiac ultrasound has also been demonstrated. METHODS: The determination of left ventricular volumes with Simpson rule reconstruction of intracardiac ultrasound images was evaluated in two phases. In vitro validation was performed in 29 animal hearts preserved in either a nondistended or distended state. Latex cast volumes were the reference standard. In vivo studies used 14 pigs, and compared intracardiac ultrasound volumes and ejection fraction with single-plane contrast angiographic values. A 12.5-MHz device was used to record short-axis images at 0.5-cm intervals. These were used to reconstruct the ventricle as a stack of cylindric elements using all imaged levels as well as sections recorded every 1 and 2 cm and at a single midventricular level. RESULTS: In the in vitro hearts, when all recorded sections were used, there was excellent agreement between intracardiac ultrasound and latex cast volumes (intracardiac ultrasound volume = 0.89 latex cast volume + 2.22, r = 0.95; intracardiac ultrasound volume = 0.97 latex cast volume + 0.91, r = 0.99) for nondistended and distended hearts, respectively. In vivo, there was again close correspondence between ultrasound and angiographic volumes (intracardiac ultrasound volume = 1.04 angiographic volume - 3.6, r = 0.91). The relation between intracardiac ultrasound and angiographic ejection fraction was fair (intracardiac ultrasound ejection fraction = 1.00 angiographic ejection fraction + 6.85, r = 0.69). Excellent correlations for the volumes were maintained as the number of cross sections was reduced to those recorded every 1 and 2 cm (r = 0.87 to 0.99). With a single midventricular site more variable but generally good correlations were obtained (r = 0.77 to 0.99). CONCLUSIONS: The application of Simpson rule reconstruction to short-axis images of the left ventricle obtained with intracardiac ultrasound provides accurate determination of left ventricular volumes in animal hearts. This technique may prove useful in the analysis of left ventricular structure and function.

Low pressure radiofrequency balloon angioplasty: evaluation in porcine peripheral arteries.

OBJECTIVES: The purpose of this study was to evaluate the efficacy of radiofrequency-powered thermal balloon angioplasty in an in vivo porcine model. BACKGROUND: Various modes of thermal energy used adjunctively during balloon angioplasty have demonstrated the potential to enhance the results of acute lumen dilation. METHODS: In normal pigs, 75 peripheral arteries were dilated with a newly designed, radiofrequency-powered, thermal angioplasty balloon. All inflations were performed at 2-atm pressure for 85 s. Dilations were performed either with (hot) or without (cold) the application of heat. Lumen dimensions and vessel morphology were assessed with intravascular ultrasonography. At the end of each study, dilated arterial segments were harvested for histologic examination. RESULTS: Single cold balloon inflations resulted in a 12.7% increase in arterial cross-sectional area whereas single hot inflations resulted in a 22.9% increase (p < 0.03). Similarly, when multiple cold inflations were compared with multiple hot inflations, two, three and four sequential hot inflations resulted in a significantly greater increase in cross-sectional area than an equivalent number of cold inflations (p < 0.03). Histologic examination demonstrated a temperature-dependent effect on the depth of medial necrosis and extent of arterial wall thinning (p < 0.001) as well as evidence for uniform alteration of elastic tissue fibers at temperatures of > or = 60 degrees C (p < 0.03). CONCLUSIONS: Low pressure radiofrequency thermal balloon angioplasty results in a greater increase in cross-sectional area in porcine peripheral arteries than does nonheated conventional balloon angioplasty. The pathologic basis for this enhanced dilation may be a temperature-dependent effect on medial necrosis, thinning of the arterial wall or alteration of vascular elastic fibers, alone or in combination.

Intracardiac echocardiography in humans using a small-sized (6F), low frequency (12.5 MHz) ultrasound catheter. Methods, imaging planes and clinical experience.

OBJECTIVES: This study was designed to determine the clinical utility and feasibility of using 12.5-MHz ultrasound catheters for intracardiac echocardiography. BACKGROUND: Intracardiac echocardiography is a potentially useful technique of cardiac imaging and monitoring in certain settings. The feasibility of intracardiac echocardiography using 20-MHz ultrasound catheters in patients has been demonstrated. High resolution images of normal cardiac structures as well as cardiac abnormalities have been obtained. However, imaging has been limited by the shallow depth of field inherent in high frequency ultrasound imaging. METHODS: Intracardiac echocardiography with 12.5-MHz catheters was performed in eight mongrel dogs and 92 patients. Catheters were introduced percutaneously in 80 patients studied in the catheterization laboratory and directly into the heart in 12 patients in the operating room. Right heart imaging was performed in 68 patients and arterial and left heart imaging in 35 patients. RESULTS: When these catheters were introduced into the venous system, the right atrium, tricuspid valve, right ventricle, pulmonary valve and pulmonary artery were visualized. Pericardial effusion, intracardiac masses and atrial septal defects were correctly identified. The left ventricle, left atrium, mitral valve, aortic valve, aorta and coronary arteries could be imaged from the arterial circulation. Diseases identified included valvular aortic stenosis, subvalvular aortic stenosis and Kawasaki disease. Average imaging time was 10 min. No complications occurred as a result of intracardiac echocardiography. CONCLUSIONS: Intracardiac echocardiography with 12.5-MHz ultrasound catheters is safe and feasible; it also provides anatomic and physiologic information. This feasibility study provides a foundation for wider clinical use of intracardic echocardiography.

Monitoring changes in thioredoxin and over-oxidised peroxiredoxin in response to exercise in humans.

INTRODUCTION: Peroxiredoxin (PRDX) and thioredoxin (TRX) are antioxidant proteins that control cellular signalling and redox balance, although their response to exercise is unknown. This study aimed to assess key aspects of the PRDX-TRX redox cycle in response to three different modes of exercise. METHODS: Healthy males (n = 10, mean ± SD: 22 ± 3 yrs) undertook three exercise trials on separate days: two steady-state cycling trials at moderate (60% [Formula: see text]O2MAX; 27 min, MOD) and high (80% [Formula: see text]O2MAX; 20 min, HIGH) intensities, and a low-volume high-intensity interval training trial (10 × 1 min 90% [Formula: see text]O2MAX, LV-HIIT). Peripheral blood mononuclear cells were assessed for TRX-1 and over-oxidised PRDX (isoforms I-IV) protein expression before, during, and 30 min following exercise (post + 30). The activities of TRX reductase (TRX-R) and the nuclear factor kappa B (NF-κB) p65 subunit were also assessed. RESULTS: TRX-1 increased during exercise in all trials (MOD, + 84.5%; HIGH, + 64.1%; LV-HIIT, + 205.7%; p < 05), whereas over-oxidised PRDX increased during HIGH only (MOD, - 28.7%; HIGH, + 202.9%; LV-HIIT, - 22.7%; p < .05). TRX-R and NF-κB p65 activity increased during exercise in all trials, with the greatest response in TRX-R activity seen in HIGH (p < 0.05). DISCUSSION: All trials stimulated a transient increase in TRX-1 protein expression during exercise. Only HIGH induced a transient over-oxidation of PRDX, alongside the greatest change in TRX-R activity. Future studies are needed to clarify the significance of heightened peroxide exposure during continuous high-intensity exercise and the mechanisms of PRDX-regulatory control.

Drug-induced left ventricular failure in patients with pulmonary disease. Endomyocardial biopsy demonstration of catecholamine myocarditis.

Three patients with severe chronic lung disease had left ventricular failure develop with marked impairment of cardiac function. Ejection fractions by radioactive blood pool ventriculography were 0.17, 0.24, and 0.20. Right ventricular endomyocardial biopsy specimens showed interstitial hemorrhage and foci of interstitial polymorphonuclear leukocytes, strongly suggestive of catecholamine myocarditis. These patients had used beta-adrenergic agonist inhalants and methylxanthines. One of them clearly abused the inhalant and had elevated levels of urinary catecholamines. Progressive deterioration of pulmonary and cardiac function occurred in two patients, with death within three months of the initial myocardial biopsy. Concomitant use of beta-adrenergic agonists and methylxanthines may cause myocarditis with left ventricular failure in susceptible patients.

Toxicity, efficacy, and clearance of intravitreally injected of cefazolin.

The intravitreal injection of cefazolin sodium was evaluated with respect to its potential toxicity, efficacy, and clearance in the treatment of bacterial endophthalmitis in the rabbit model. Toxicity evaluation included indirect ophthalmoscopy, scotopic electroretinogram, and light microscopy of histopathologic specimens. Rabbits given doses up to and including 2.25 mg of cefazolin sodium showed no evidence of toxic reaction by these criteria after two weeks of observation. When injected within 24 hours of inoculation, 2.25 mg of cefazolin sodium sterilized five of six rabbit eyes infected with Staphylococcus aureus. Following intravitreal injection of 2.25 mg of cefazolin sodium, vitreous concentrations in excess of the minimum inhibitory concentration for S aureus were maintained for five days. A 2.25-mg dose of cefazolin sodium appears to be nontoxic, effective, and biologically active against susceptible organisms during a prolonged period, when injected into the vitreous cavity of the pigmented rabbit in vivo.

Factors determining hydrogel permeability.

Developing hydrogel membranes and coatings of appropriate permeability characteristics is key to the success of a number bioartificial organ technologies. Key principles relevant to the design and application of hydrogels for such applications were reviewed. The first key point is that permeability is a function of both transport and thermodynamic properties, the diffusion coefficient and partition coefficient, respectively, and that these parameters can be evaluated separately. Although the aspect of partitioning often emphasized is size exclusion, this review points out that many other relevant interactions come into play, especially hydrophobic and electrostatic interactions, and that these phenomena can dominate size exclusion. Similarly, while the diffusion coefficient also is strongly dependent upon size, other interactions can also cause diffusivity to deviate from theories which consider only solute size and gel swelling. For example, the heterogeneity of hydrogel networks can result in permeabilities that fail to decline as much as might be anticipated if networks were uniform.

Aroclors 1254 and 1260 reduce dopamine concentrations in rat striatal slices.

Striatal slices from adult male Wistar-derived rats were exposed to a 1:1 mixture of Aroclor 1254:1260 at concentrations in media of 10, 20, 40, 60 or 100 ppm for 6 hr. Following exposure, slices and media were analyzed by high-performance liquid chromatography for dopamine (DA) and its metabolites. PCBs caused a significant dose-dependent decrease in slice DA content at concentrations greater than 20 ppm. Media concentrations of DA and its metabolites were significantly increased by PCB exposure greater than 60 ppm, indicating that, in addition to their suggested role in inhibiting DA synthesis, PCBs may interfere with either vesicular storage or release of DA. These data suggest that in addition to the recognized action of PCBs in inhibiting tyrosine hydroxylase, PCBs may also interfere with the vesicular monoamine transporter, and thereby suggest an additional mechanism by which DA concentrations and metabolism may be altered by PCB exposure.

The influence of age and weight status on cardiac autonomic control in healthy children: a review.

Heart rate variability (HRV) analyses can provide a non-invasive evaluation of cardiac autonomic activity. How autonomic control normally develops in childhood and how this is affected by obesity remain incompletely understood. In this review we examine the evidence that childhood age and weight status influence autonomic control of the heart as assessed using HRV. Electronic databases (Pubmed, EMBASE and Cochrane Library) were searched for studies examining HRV in healthy children from birth to 18 years who adhered to the Task Force (1996) guidelines. Twenty-four studies met our inclusion criteria. Seven examined childhood age and HRV. A reduction in 24-hour LF:HF was reported from birth to infancy (1 year), while overall HRV (SDNN) showed a marked and progressive increase. From infancy to early-to-late childhood (from 12 months to 15 years) LF:HF ratio was reported to decline further albeit at a slower rate, while RMSSD and SDNN increased. Twenty studies examined the effects of weight status and body composition on HRV. In a majority of studies, obese children exhibited reductions in RMSSD (n = 8/13), pNN50% (n = 7/9) and HF power (n = 14/18), no difference was reported for LF (n = 10/18), while LF:HF ratio was elevated (n = 10/15). HRV changes during childhood are consistent with a marked and progressive increase in cardiac parasympathetic activity relative to sympathetic activity. Obesity disrupts the normal maturation of cardiac autonomic control.

The sympathetic nervous system and blood pressure in humans: implications for hypertension.

A neurogenic component to primary hypertension (hypertension) is now well established. Along with raised vasomotor tone and increased cardiac output, the chronic activation of the sympathetic nervous system in hypertension has a diverse range of pathophysiological consequences independent of any increase in blood pressure. This review provides a perspective on the actions and interactions of angiotensin II, inflammation and vascular dysfunction/brain hypoperfusion in the pathogenesis and progression of neurogenic hypertension. The optimisation of current treatment strategies and the exciting recent developments in the therapeutic targeting of the sympathetic nervous system to control hypertension (for example, catheter-based renal denervation and carotid baroreceptor stimulation) will be outlined.

Contribution of nitric oxide to the blood pressure and arterial responses to exercise in humans.

An exaggerated blood pressure (BP) response to exercise predicts future cardiovascular risk. The mechanisms underlying exercise-induced hypertension remain unclear, although endothelial dysfunction and elevated arterial stiffness may contribute. Given the association between reductions in nitric oxide (NO) and vascular dysfunction, we sought to determine whether acute inhibition of NO synthase with N(G)-monomethyl-L-arginine (L-NMMA) would lead to exaggerated BP responses to maximal exercise and attenuate exercise-induced reductions in arterial stiffness. In 10 healthy subjects (31±5 years), BP and heart rate (HR) were measured before, during and after an incremental cycling exercise test to determine maximal oxygen consumption (VO(2)max). Trials were performed with placebo (saline) or intravenous infusion of L-NMMA on separate days in a randomized, double-blind, crossover design. Central (aortic) and peripheral (femoral) arterial stiffness were assessed using pulse wave velocity (PWV). BP was increased with L-NMMA at rest and during sub-maximal exercise, but not at maximal exercise (mean BP 117±5 vs 118±8 mm Hg, saline vs L-NMMA, P>0.05). Furthermore, L-NMMA had no influence on exercising HR or VO(2)max (P<0.05). Notably, aortic PWV was similarly increased after exercise with either saline or L-NMMA (P<0.05), whereas postexercise decreases in femoral PWV were attenuated with L-NMMA (P<0.05). Our findings suggest that NO is an important contributor to reductions in femoral artery stiffness after maximal exercise in healthy individuals. Furthermore, acute pharmacological inhibition of NO synthase causes augmented BP responses to sub-maximal exercise, but does not lead to exaggerated BP responses to maximal exercise or reduce maximal oxygen consumption.