Examining the clinical learning environment through the architectural avenue.

Medical education has traditionally focused on the learners, the educators, and the curriculum, while tending to overlook the role of the designed environment. Experience indicates, however, that processes and outcomes of medical education are sensitive to the qualities and disposition of the spaces in which it occurs. This includes the clinical education within the patient care environment, termed the clinical learning environment (CLE). Recognition of this has informed the design of some new clinical learning spaces for the past decade. Competency-based clinical education can drive design requirements that differ materially from those associated with general purpose educational or clinical spaces. In this article, we outline two conceptual frameworks: (i) materialist spatiality and (ii) actor-network theory and consider how they can guide the design of spaces to support competency-based medical education and to guide the evaluation and discussion of the educational impacts of the spaces once built. We illustrate the use of these frameworks through discussion of the educational ambitions that underpinned the design of some recent clinical educational spaces. We close with practical points for consideration by educators and designers.

Acute limb ischemia in cancer patients: should we surgically intervene?

BACKGROUND: Cancer patients have an increased risk of venous thromboembolic events. Certain chemotherapeutic agents have also been associated with the development of thrombosis. Reported cases of acute arterial ischemic episodes in cancer patients are rare. METHODS: Patients who underwent surgery for acute limb ischemia associated with malignancy in a university teaching hospital over a 10-year period were identified. Patient demographics, cancer type, chemotherapy use, site of thromboembolism, treatment and outcome were recorded. RESULTS: Four hundred nineteen patients underwent surgical intervention for acute arterial ischemia, 16 of these patients (3.8%) had associated cancer. Commonest cancer sites were the urogenital tract (n = 5) and the lungs (n = 5). Eight patients (50%) had been recently diagnosed with cancer, and four (25%) of these cancers were incidental findings after presentation with acute limb ischemia. Four patients (25%) developed acute ischemia during chemotherapy. The superficial femoral artery was the most frequent site of occlusion (50%), followed by the brachial (18%) and popliteal (12%) arteries. All patients underwent thromboembolectomy, but two (12%) patients subsequently required a bypass procedure. Six patients (37%) had limb loss, and in-patient mortality was 12%. Histology revealed that all occlusions were due to thromboembolism, with no tumor cells identified. At follow-up, 44% of patients were found to be alive after 1 year. CONCLUSION: Cancer and chemotherapy can predispose patients to acute arterial ischemia. Unlike other reports that view this finding as a preterminal event most appropriately treated by palliative measures, in this series, early diagnosis and surgical intervention enabled limb salvage and patient survival.

Osteoprotegerin is higher in peripheral arterial disease regardless of glycaemic status.

INTRODUCTION: Peripheral arterial disease (PAD) and type 2 diabetes mellitus (DM) are both associated with excessive vascular calcification and elevated levels of inflammatory markers IL-6 and hsCRP. The recently identified Osteoprotegerin(OPG)/RANKL/TRAIL pathway has been implicated in vascular calcification, but data on levels in PAD and effect of co-existent DM are lacking. MATERIALS AND METHODS: 4 groups of patients were recruited - 26 with PAD and DM, 35 with DM alone, 22 with PAD alone, and 21 healthy individuals. Serum OPG, RANKL, TRAIL, hsCRP and IL-6 were measured using commercial ELISA assays. Presence and severity of PAD was defined using ankle brachial index (ABI). RESULTS: Serum OPG (7.4±0.3 vs.5.8±0.2 pmol/l, p<0.0001), TRAIL (95.5±5.2 ng/ml vs. 76.2±4.4 ng/ml, p=0.006), hsCRP (2.6±0.3 vs. 1.8±0.3 mg/l, p=0.048), and IL-6 (4.1±0.4 vs. 2.9±0.4 pg/ml, p=0.06) were higher in patients with PAD. There was no difference in RANKL. Only OPG was significantly higher in PAD and DM (7.2±0.3 pmol/l) and PAD alone (7.7±0.4 pmol/l) compared to DM only (5.8±0.3 pmol/l) and healthy controls (5.6±0.4 pmol/l), p<0.01, but OPG was no higher in those with DM plus PAD versus those with PAD alone (p<0.3). Only OPG was associated with PAD severity, correlating negatively with ABI (r=-0.26, p=0.03), independent of age, gender, glycaemic status, hsCRP and IL-6. CONCLUSIONS: PAD is associated with higher serum OPG, regardless of the co-existence of DM. This finding, in addition to its correlation with severity of PAD, suggests that OPG may be a novel marker for the presence and severity of PAD, possibly by reflecting the degree of underlying vascular calcification.

Down syndrome: a risk factor for mycotic aneurysm?

Down syndrome, or trisomy 21, has a characteristic constellation of clinical findings, including various congenital heart defects. We report a case of an adult male with Down syndrome who presented with a 3-week history of lower limb pain and swelling, attributed to cellulitis. Clinical and angiographic evaluation identified a below-knee mycotic pseudoaneurysm secondary to infective endocarditis. Surgical aneurysmal repair and revascularization were performed. Various management options are outlined in this report.

Preparing for an institutional self review using the WFME standards - an international medical school case study.

BACKGROUND: Curriculum reform poses significant challenges for medical schools across the globe. This paper describes the reforms that took place at the medical school of the Royal College of Surgeons in Ireland (RCSI) between 2005 and 2008 and the institutional self review process that accompanied these reforms. RESULTS: Although fully accredited with the Irish Medical Council the RCSI sought additional detailed review of all aspects of its undergraduate medical program. Five medical educationalists were invited to visit the College in 2005 and again in 2008 to act as 'critical friends' and guide the self review using the World Federation for Medical Education (WFME) standards which had recently been adopted in Ireland. CONCLUSION: The process of institutional self review (as opposed to more high stakes accreditation) can bring about significant reform, especially when supported by a panel of 'critical friends' working alongside faculty to help guide and support sustained curriculum reform. The WFME standards continue to provide a useful framework to consider all medical education activities within a medical school engaged in continuous renewal. Adequate preparation for such reviews is critical to the success of such an undertaking and should be supported by a comprehensive communication strategy and project plan.

N-acetylcysteine protects striated muscle in a model of compartment syndrome.

BACKGROUND: To avoid ischemic necrosis, compartment syndrome is a surgical emergency treated with decompression once identified. A potentially lethal, oxidant-driven reperfusion injury occurs after decompression. N-acetylcysteine is an antioxidant with the potential to attenuate the reperfusion injury. QUESTIONS/PURPOSES: We asked whether N-acetylcysteine could preserve striated muscle contractility and modify neutrophil infiltration and activation after simulated compartment syndrome release. MATERIALS AND METHODS: Fifty-seven rats were randomized to control, simulated compartment syndrome, and simulated compartment syndrome plus N-acetylcysteine groups. We isolated the rodent cremaster muscle on its neurovascular pedicle and placed it in a pressure chamber. Chamber pressure was elevated above critical closing pressure for 3 hours to simulate compartment syndrome. Experiments were concluded at three times: 1 hour, 24 hours, and 7 days after decompression of compartment syndrome. We assessed twitch and tetanic contractile function and tissue myeloperoxidase activity. Ten additional rats were randomized to control and N-acetylcysteine administration after which neutrophil respiratory burst activity was assessed. RESULTS: The simulated compartment syndrome decreased muscle contractility and increased muscle tissue myeloperoxidase activity compared with controls. Treatment with N-acetylcysteine preserved twitch and tetanic contractility. N-acetylcysteine did not alter neutrophil infiltration (myeloperoxidase activity) acutely but did reduce infiltration at 24 hours, even when given after decompression. N-acetylcysteine reduced neutrophil respiratory burst activity. CONCLUSION: N-acetylcysteine administration before or after simulated compartment syndrome preserved striated muscle contractility, apparently by attenuating neutrophil activation and the resultant oxidant injury. CLINICAL RELEVANCE: Our data suggest a potential role for N-acetylcysteine in the attenuation of muscle injury after release of compartment syndrome and possibly in the prophylaxis of compartment syndrome.

Attenuation of lipopolysaccharide-mediated left ventricular dysfunction by glutamine preconditioning.

OBJECTIVE: Myocardial dysfunction is often seen during the inflammatory response to major surgery at 4 to 6h postoperatively. The aim of this study was to investigate the effect of glutamine pretreatment, as a means of preconditioning, on lipopolysaccharide-induced myocardial dysfunction. METHODS: C57BL/6 mice were randomized into four groups: Control; lipopolysaccharide; glutamine plus lipopolysaccharide; and Quercetin, an inhibitor of heat shock protein synthesis plus glutamine and lipopolysaccharide. Left ventricular function was assessed at 6h following lipopolysaccharide (LPS) insult by invasive hemodynamics. Heat shock protein (HSP)72 in heart tissue was determined by Western immunoblot at 12h after glutamine administration. RESULTS: Administration of lipopolysaccharide resulted in significant decrease in left ventricular end systolic pressure (LVESP) (69.1 +/- 2.52 mm Hg versus 106.3 +/- 3.36 mm Hg in controls), reduced dP/dtmax (4704.1 +/- 425.31 mm Hg/s versus 9389.8 +/- 999.4 mm Hg/s in controls), and the increase in left ventricular end diastolic pressure (LVEDP) (5.10 +/- 0.28 mm Hg versus 2.16 +/- 0.27 mm Hg in controls) (P < 0.05). Peritoneal injection of 25 g/kg of glutamine 12 h prior to lipopolysaccharide exposure induced HSP72 expression in heart tissues and attenuated lipopolysaccharide-induced left ventricular dysfunction: LVESP 85.94 +/- 3.8 mm Hg (P < 0.05), dP/dtmax 8331 +/- 425 mm Hg (P < 0.05), LVEDP 2.32 +/- 0.23 mm Hg (P < 0.01). Quercetin partially attenuated glutamine induced HSP72 expression and blocked the protective response of glutamine. CONCLUSION: These data demonstrate that cardioprotection with glutamine is associated with induction of HSP72 and may be an approach to activating the preconditioning response in the heart in clinical practise.

Endovascular repair of para-anastomotic aortoiliac aneurysms.

The purpose of this study is to evaluate the use of endovascular stent grafts in the treatment of para-anastomotic aneurysms (PAAs) as an alternative to high-risk open surgical repair. We identified all patients with previous open aortic aneurysm repair who underwent infrarenal endovascular aneurysm repair (EVAR) at our institution from June 1998 to April 2007. Patient demographics, previous surgery, and operative complications were recorded. One hundred forty-eight patients underwent EVAR during the study period and 11 patients had previous aortic surgery. Of these 11 redo patients, the mean age was 62 years at initial surgery and 71 years at EVAR. All patients were male. Initial open repair was for rupture in five (45%) patients. The average time between initial and subsequent reintervention was 9 years. All patients were ASA Grade III or IV. Fifty-five percent of the PAAs involved the iliac arteries, 36% the abdominal aorta, and 9% were aortoiliac. Ten patients had endovascular stent-grafts inserted electively, and one patient presented with a contained leak. Aorto-uni-iliac stent-grafts were deployed in seven patients, and bifurcated stent-grafts in four patients. A 100% successful deployment rate was achieved. Perioperative mortality was not seen and one patient needed surgical reintervention to correct an endoleak. Endovascular repair of PAAs is safe and feasible. It is a suitable alternative and has probably now become the treatment of choice in the management of PAAs.

Should incidental asymptomatic angiographic stenoses and occlusions be treated in patients with peripheral arterial disease?

PURPOSE: The clinical importance of angiographically detected asymptomatic lower-limb stenoses and occlusions is unknown. This study aims to (i) assess the clinical outcome of asymptomatic lesions in the lower limb, (ii) identify predictors of clinical deterioration, and (iii) determine which asymptomatic lower-limb lesions should be treated at presentation. MATERIALS AND METHODS: All 918 patients undergoing peripheral angiography with or without angioplasty over a period of 7.5 years (January 1999 through June 2006) at a single institution were retrospectively evaluated. One hundred twenty-two patients (54% men; mean age, 70.3 years; age range, 41-91 y) with angiographic stenoses (> or =50%) or occlusions on the asymptomatic leg were included. The composite endpoint of interest was major adverse clinical outcome (MACO) of the asymptomatic limb at clinical follow-up, which was defined as the development of intermittent claudication (IC), critical limb ischemia (CLI), or need for subsequent endovascular or surgical revascularization. Actuarial freedom from MACO was assessed with Kaplan-Meier curves and multivariable Cox proportional-hazards regression. RESULTS: During a 4.2-year mean follow-up in 122 patients with significant concomitant asymptomatic disease, 32.8% of patients developed symptoms (13.9% with IC, 18.9% with CLI); 42.5% of these cases required revascularization. Cox regression revealed two independent predictors of MACO on the asymptomatic side: contralateral below-knee amputation (BKA; hazard ratio, 2.93; 95% CI, 1.21-7.10; P = .01) and statin treatment (hazard ratio, 3.56; 95% CI, 1.56-8.13; P = .003). CONCLUSIONS: Asymptomatic peripheral angiographic stenoses and occlusions become symptomatic in one third of patients, necessitating treatment in 13.9% overall. Previous contralateral BKA and statin use were independent predictors of adverse outcome in this population. Close clinical follow-up and appropriate risk factor modification are recommended.

Screening for abdominal aortic aneurysms in cardiovascular patients.

BACKGROUND: The objective of the study was to determine the incidence of Abdominal Aortic Aneurysms (AAA) in a population of symptomatic cardiac patients. A retrospective cohort study of investigations was done at the cardiology clinic, Beaumont Hospital, Dublin. MATERIALS AND METHODS: There were 415 men and women recruited by referral to the cardiology clinic. All participants underwent routine ultrasound screening for AAA, and full assessment of all cardiac risk factors. Data were analyzed and correlated with age, sex, and diagnosis. RESULTS: Ultrasonographic diagnosis of aneurysm was based on an anteroposterior diameter of 3 cm or more. Of the 415 patients screened, 47 aneurysms were detected. Total incidence of AAA was 9.9% (male 14.1%, female 3.95%). All aneurysms were detected in patients over 60 years, detection rate 11.7% (male 16.3%, female 3.9%). The incidence of AAA was significantly higher in those who were subsequently proven to have cardiovascular disease, 13.8% (male 18%, female 5.15%). CONCLUSION: Screening the general population for those at risk of AAA is an ongoing debate. This study supports the concept of screening a higher risk population of patients over 60 years with cardiovascular disease.

Effects of systemic and regional taurine on skeletal muscle function following ischaemia-reperfusion injury.

INTRODUCTION: Tissues subjected to prolonged ischaemia are paradoxically further damaged when their perfusion is restored. The mechanisms underlying this ischaemia-reperfusion injury are complex, but oxidative attack is a central feature. Among the therapeutic agents used to attenuate ischaemia-reperfusion injury, endogenous agents such as taurine which form part of the native defence mechanism against oxidative damage are of particular interest. METHODS: Using a model of hindlimb ischaemia-reperfusion injury in the rat, taurine solution was administered either into the operated hindlimb, into the systemic circulation, or both. Contraction strengths of gastrocnemius biopsies from the operated and contralateral (control) hindlimbs of each animal were measured. RESULTS: Fast twitch strength was impaired significantly by ischaemia-reperfusion injury, and taurine injected into the operated limb conferred partial protection. A similar trend was observed for tetany, but protection by taurine was not statistically significant for tetanic contraction strength. CONCLUSION: Preservation of fast twitch strength following ischaemia-reperfusion injury by administration of taurine before ischaemia has clinical potential. However, delivery to the affected tissues during ischaemia presents technical difficulties.

Clinically applicable thermal preconditioning attenuates leukocyte-endothelial interactions.

BACKGROUND: We have previously demonstrated that clinically applicable thermal preconditioning induces heat shock protein 72 (HSP72) and protects against a subsequent ischemia-reperfusion (I/R) injury in an animal model. A core component of I/R injuries is the interaction between activated leukocytes and endothelial cells. We hypothesized that the effects of clinically applicable thermal preconditioning are mediated through attenuation of this leukocyte-endothelial (L-E) interaction. STUDY DESIGN: Twenty-one male Sprague Dawley rats were divided into control, I/R, and preconditioning plus I/R groups. Preconditioning was done under general anesthesia and the animals' temperature raised by 1 degrees C for 15 minutes in a water bath. This was repeated once a day for 5 successive days. I/R injury was caused by occlusion of the superior mesenteric artery for 10 minutes followed by 1 hour of reperfusion. L-E interactions were analyzed using intravital microscopy of a mesenteric vessel in vivo. L-E interactions were determined using leukocyte velocity (which decreases as cells interact), and number of adherent and migrated leukocytes. HSP72 was assessed by Western blot. RESULTS: Ischemia-reperfusion caused a decrease in leukocyte rolling velocity at all timepoints (p < 0.05 versus controls). Preconditioning attenuated the effects of I/R, and leukocyte rolling velocity was significantly improved versus I/R (p < 0.05) to levels similar to those in controls. Similarly, the number of adherent and migrating leukocytes increased significantly (p < 0.05) after I/R versus control at all time points, and preconditioning attenuated these to control levels, (p < 0.05 versus I/R) at both the 30- and 60-minute postischemia time points. Upregulation of HSP72 was demonstrated on Western blot. CONCLUSIONS: These results demonstrate that the benefit of clinically applicable thermal preconditioning is at least partially because of an immunomodulatory role in attenuating leukocyte-endothelial interactions associated with an increased expression of HSP 72.

Taurolidine attenuates the hemodynamic and respiratory changes associated with endotoxemia.

The purpose of this study was to determine if prereatment with taurolidine, a known anti-endotoxin agent, would attenuate the hemodynamic and respiratory responses associated with endotoxin induced lung injury in a large animal model in a randomized controlled study under license from the Department of Health. All animals underwent a general anesthetic. Vascular catheters were placed in the femoral artery and in the femoral vein. A Swan-Ganz Catheter was inserted for measurement of pulmonary artery pressure. Animals were randomized into three groups: Control, with measurements taken at baseline and half hourly up to 90 min; Endotoxin, receiving 5microg/Kg E. coli endotoxin intravenously after baseline measurements; and Endotoxin + Taurolidine, receiving 5g of taurolidine via intraperitoneal infusion 1 h before endotoxin administration. Main outcome measures were mean systemic arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), arterial oxygen tension (pO2), serum endotoxin concentration, and pulmonary myeloperoxidase. Endotoxin induced a significant lung injury characterized by an increase in pulmonary artery pressure, hypoxia, and systemic hypotension. Pretreatment with intraperitoneal taurolidine significantly attenuated these hemodynamic and respiratory changes. Serum endotoxin concentration was also significantly reduced as was lung myeloperoxidase. The data suggest that taurolidine may have a therapeutic role in preventing the lung injury seen in endotoxemia.