Assessment of competency during orotracheal intubation in medical simulation.

BACKGROUND: Clinicians performing orotracheal intubation need to be competent to perform this technical skill safely. It is recognized that aggressive force applied during direct laryngoscopy may damage the oropharyngeal soft tissue; however, force is seldom considered in assessment of competency. The objective of this study was to explore the force applied during orotracheal intubation as a method of further discriminating between levels of competence. We sought evidence of construct validity in the form of discriminant, criterion, and concurrent validity. We hypothesized that the force generated during simulated intubation could serve to discriminate skill level among clinicians. METHODS: A convenience sample of 35 health-care professionals filled a self-reported questionnaire and were then divided into the following three groups: Group 1, experts (n=16); Group 2, intermediates (n=7); and Group 3, novices (n=12). They then intubated a part-task trainer (Laerdal Airway Management Trainer) after reviewing a procedural video and engaging in one practice session. Intubations were recorded. Outcome measures were as follows: (i) force applied to the epiglottis, calculated (in newtons) using two superimposed pressure-sensitive films (Prescale; Fujifilm, Madison, WI, USA) on the laryngoscope blade; (ii) number of attempts required to achieve successful intubation; (iii) time to intubation; and (iv) hand position. RESULTS: Of the four outcome measures, only force applied during orotracheal intubation was able to discriminate between groups. All data are reported as the mean (sd). There was a significant difference in force between groups during orotracheal intubation [one-way anova; experts, 102 (25) N; intermediates, 134 (28) N; and novices, 153 (43) N], with a significant difference (P<0.05) noted between novice and experts on post hoc analysis. CONCLUSIONS: Force exerted during intubation provides meaningful information when attempting to discriminate intubation skill level. Force demonstrated criterion validity and could be used as a measure of competency during training.

Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophrenia.

Autism spectrum disorder (ASD) and schizophrenia (SCZ) are two common neurodevelopmental syndromes that result from the combined effects of environmental and genetic factors. We set out to test the hypothesis that rare variants in many different genes, including de novo variants, could predispose to these conditions in a fraction of cases. In addition, for both disorders, males are either more significantly or more severely affected than females, which may be explained in part by X-linked genetic factors. Therefore, we directly sequenced 111 X-linked synaptic genes in individuals with ASD (n = 142; 122 males and 20 females) or SCZ (n = 143; 95 males and 48 females). We identified >200 non-synonymous variants, with an excess of rare damaging variants, which suggest the presence of disease-causing mutations. Truncating mutations in genes encoding the calcium-related protein IL1RAPL1 (already described in Piton et al. Hum Mol Genet 2008) and the monoamine degradation enzyme monoamine oxidase B were found in ASD and SCZ, respectively. Moreover, several promising non-synonymous rare variants were identified in genes encoding proteins involved in regulation of neurite outgrowth and other various synaptic functions (MECP2, TM4SF2/TSPAN7, PPP1R3F, PSMD10, MCF2, SLITRK2, GPRASP2, and OPHN1).

Postnatal bone marrow stromal cells elicit a potent VEGF-dependent neoangiogenic response in vivo.

Bone marrow stromal cells (MSCs) are pluripotent cells capable of differentiation into several tissue types. This present study was performed to determine their functional neoangiogenic potential in vivo. Whole bone marrow was harvested from C57Bl/6 mice, and the adherent cellular fraction was culture expanded for 14 doublings. These MSCs were resuspended in Matrigel and their angiogenic effect assessed in isogenic recipients. At 2 weeks postimplantation, the mean vascular density in Matrigel plugs containing 2 x 10(6) MSCs/ml was 41+/-5.0 blood vessels (BVs)/mm(2) compared to 0.5+/-0.7 for empty Matrigel (P<0.001). In comparison, Matrigel plugs containing either recombinant murine VEGF 165 at 50 ng/ml or bovine bFGF at 1000 ng/ml generated 21+/-5 and 11+/-2.0 BV/mm(2), respectively. Arteriogenesis was observed only in the MSC-containing implants. With the use of LacZ retroviral labeling of ex vivo expanded MSCs, we show that approximately 10% of LacZ(+)MSCs differentiated into CD31(+) and VEGF(+) endothelial cells. More than 99% of the neoangiogenic phenomena arose from recruitment of host-derived LacZ(null) vascular structures. Neutralizing anti-VEGF antibodies inhibited the MSC-initiated angiogenic response in vivo by 85% (P<0.001). In conclusion, MSCs have the ability to effectively recruit and participate in angiogenesis and arteriogenesis de novo and VEGF plays a central role in the observed host-derived angiogenic response. We propose that ex vivo expanded autologous MSCs may serve as cell therapy to promote therapeutic angiogenesis.

A neovascularized organoid derived from retrovirally engineered bone marrow stroma leads to prolonged in vivo systemic delivery of erythropoietin in nonmyeloablated, immunocompetent mice.

Marrow stromal cells (MSCs) are postnatal progenitor cells that can be easily cultured ex vivo to large amounts. This feature is attractive for cell therapy applications where genetically engineered MSCs could serve as an autologous cellular vehicle for the delivery of therapeutic proteins. The usefulness of MSCs in transgenic cell therapy will rely upon their potential to engraft in nonmyeloablated, immunocompetent recipients. Further, the ability to deliver MSCs subcutaneously - as opposed to intravenous or intraperitoneal infusions - would enhance safety by providing an easily accessible, and retrievable, artificial subcutaneous implant in a clinical setting. To test this hypothesis, MSCs were retrovirally engineered to secrete mouse erythropoietin (Epo) and their effect was ascertained in nonmyeloablated syngeneic mice. Epo-secreting MSCs when administered as 'free' cells by subcutaneous or intraperitoneal injection, at the same cell dose, led to a significant - yet temporary - hematocrit increase to over 70% for 55+/-13 days. In contrast, in mice implanted subcutaneously with Matrigel trade mark -embedded MSCs, the hematocrit persisted at levels >80% for over 110 days in four of six mice (P<0.05 logrank). Moreover, Epo-secreting MSCs mixed in Matrigel elicited and directly participated in blood vessel formation de novo reflecting their mesenchymal plasticity. MSCs embedded in human-compatible bovine collagen matrix also led to a hematocrit >70% for 75+/-8.9 days. In conclusion, matrix-embedded MSCs will spontaneously form a neovascularized organoid that supports the release of a soluble plasma protein directly into the bloodstream for a sustained pharmacological effect in nonmyeloablated recipients.

Exploring the scientific basis of surgery: transmyocardial revascularization.

Transmyocardial revascularization (TMR) is a new surgical procedure aimed at increasing blood flow to the ischemic myocardium. It has been used for treatment of patients with end-stage coronary artery disease who are not candidates for conventional measures such as medication, percutaneous transluminal coronary angioplasty, and coronary artery bypass grafting. TMR involves creating transmural channels in the myocardium using lasers, in areas shown to be ischemic during preoperative testing. This procedure has shown promising results in clinical trials, but the mechanism of its efficacy remains largely unknown. TMR was originally developed as a means of supplying blood to the ventricular myocardium, directly through channels made in the wall of the ventricle. This was in an attempt to recreate the situation that exists in the reptilian heart, in which the myocardium is perfused directly from the ventricular chamber through a rich network of sinusoids that bathe the myocardial cells. However, the existence of a significant sinusoidal network in the human heart is doubtful. Whether the myocardium can be perfused directly via the TMR channels is controversial; it is becoming clear that other mechanisms such as angiogenesis are also at work. This review will use TMR as an example to illustrate how surgical practice and thinking can be based on theories that have little or no sound experimental evidence to support them. The importance of elucidating the valid scientific basis of surgical procedures in this modern era of evidence-based medicine will be emphasized.

Perioperative mortality after pneumonectomy: analysis of risk factors and review of the literature.

OBJECTIVE: To determine risk factors for perioperative death associated with pneumonectomy. DESIGN: A retrospective case-control study in which a perioperative death group was compared with a survivor group, and a review of the English literature on the subject. SETTING: The Montreal General Hospital, a tertiary-care teaching institution. PATIENTS AND INTERVENTION: Ninety-two consecutive patients who underwent pneumonectomy between April 1989 and 1994. MAIN OUTCOME MEASURES: The effects of age, sex, smoking history, tumour size, type and stage, pulmonary function, cardiovascular risks, comorbidity, preoperative blood values and volume of fluids administered perioperatively. Values from the literature were reported for comparison. RESULTS: The perioperative death rate was 10.9%. Selection bias and in-hospital values reported in the literature have underestimated the death rate, with actual rates ranging from 7% to 11%. Age (odds ratio 2.48, p = 0.04), the presence of 1 or more comorbid diseases (odds ratio 7.92, p = 0.05) and amount of fluids given in the first 12 hours postoperatively (odds ratio 2.21, p = 0.06) were found to be significant risk factors for death. Multivariate logistic regression demonstrated that the volume of fluids given remains an independent risk factor whereas age and comorbid disease are dependent variables. CONCLUSIONS: The results were consistent with previously reported death rates and risk factors. Patient age and concomitant disease are not modifiable risk factors, but perioperative fluid administration and other means to prevent postpneumonectomy pulmonary edema may reduce the perioperative death rate.

Benefit of open lung biopsy in patients with respiratory failure.

OBJECTIVE: To determine the benefit of open lung biopsy (OLB) in patients with respiratory failure in whom medical therapy is unsuccessful. DESIGN: A retrospective case series. SETTING: A tertiary care centre. PATIENTS: Thirty-one patients (20 men, 11 women, mean age 55 years) without the human immunodeficiency virus or AIDS who were suffering from respiratory failure. INTERVENTION: OLB through a limited anterior thoracotomy. MAIN OUTCOME MEASURES: Diagnosis, change in therapy, timing of OLB, immune status, survival. RESULTS: A specific diagnosis was made in 68% of patients, and nonspecific pulmonary fibrosis was found in 32%. Eighteen patients (59%) had a change in therapy: 11 had new therapy and 7 had medical therapy withdrawn because of irreversible disease. There was a significant (p = 0.012) improvement in survival in those who had OLB early compared with those who had OLB later in the course of the disease (70% versus 14%). There was a significant (p = 0.026) difference in the proportion of specific diagnoses made among those who had OLB early compared with those who had it later (100% versus 52%). A significant (p = 0.18) improvement in survival was noted in those who had new therapy instituted as a result of early OLB compared with late OLB (86% versus 25%). Patients not immunocompromised before OLB had a significantly (p = 0.02) better survival rate than those who were immunocompromised. CONCLUSIONS: The duration of respiratory failure before OLB and the immune status were associated with improved survival in patients with respiratory failure and unsuccessful medical therapy. This was not directly attributable to changes in therapy after OLB. However, five survived as a direct result of therapy instituted after OLB and seven were spared needless therapy when irreversible disease was found. Overall survival may not be altered by OLB, but individual clinical benefit may be seen in nearly 40% of patients.

Chronic benign retinal pigment epithelial detachment: a subtype of central serous choroidopathy.

Between October 1983 and December 1991, 14 patients (mean age 48.1 [range 38 to 68] years) presented with single, clear, cystic-appearing juxtafoveal lesions beneath the retina, with discrete borders measuring approximately 2 mm in diameter. All patients had vision of 6/7.5 or better, which did not deteriorate over a follow-up period of 3 to 91 (mean 18.1) months. Angiographically, the lesions showed relative homogeneous hyperfluorescence with very discrete margins, the angiographic appearance of serous retinal pigment epithelial detachment. We describe the clinical and angiographic appearance on presentation and in follow-up and discuss the probable relationship of these lesions to central serous choroidopathy.

Antibacterial activity, antibiotic retention, and infection resistance of a rifampin-impregnated gelatin-sealed Dacron graft.

PURPOSE: A gelatin-sealed porous Dacron graft impregnated with rifampin was evaluated in a two-part study of its use in preventing prosthetic infection. METHODS: The graft was impregnated by soaking it for 15 minutes in rifampin (1 mg/ml). In part 1 its antibacterial activity and rifampin retention over time were determined. Infrarenal aortic replacement was performed in pigs, and the rifampin concentration of the graft, serum, and perigraft space was assayed up to 96 hours after surgery. In part 2, infection resistance was tested in pigs in which the retroperitoneum was contaminated with Staphylococcus aureus after graft replacement. The postoperative infection rate was compared in three groups: pigs given gelatin-sealed grafts without rifampin (controls), pigs receiving nonimpregnated grafts and intravenous rifampin (15 mg/kg) for 3 days after surgery, and those given the rifampin grafts. RESULTS: Rifampin was present in the grafts for up to 72 hours after surgery and in the perigraft fluid for 24 hours but was never detected in the serum. The grafts had inhibitory activity in vitro against S. aureus and the biofilm phase of Staphylococcus epidermidis for up to 3 days and against Escherichia coli for 2 days. Pigs given intravenous rifampin had a significantly lower infection rate than had control pigs (7/12 vs 13/13; p = 0.02); those receiving the rifampin graft had a lower rate (2/13) than had either the control pigs (p < 0.001) or those given intravenous rifampin (p < 0.04). CONCLUSIONS: This simple method of graft impregnation resulted in antibiotic retention for 3 days and appeared to be superior to intravenous antibiotic administration in preventing perioperative graft infection.

A persistent hindlimb ischemia model in the rabbit.

The study of new approaches for the treatment of limb-threatening ischemia has been hampered by the lack of a suitable animal model of persistent limb ischemia. We describe the development and evaluation of an animal model of persistent hindlimb ischemia, in which ischemia was induced in the left hindlimb of 28 rabbits by ligation of the distal external iliac artery and excision of the common and superficial femoral arteries. The severity of the ischemia and its relief in each animal were evaluated every 10 days postoperatively until day 40 (all animals) or day 90 (five animals). Nine animals developed superficial tissue necrosis in the foot, but no deaths were attributable to the ischemia-inducing procedure. Angiography demonstrated minimal collateralization and sluggish filling of distal vessels up to postoperative day 90. This was accompanied by a decrease at rest in the calf blood flow ratio (p < 0.005 vs day 0), an increase in lactic acid in the femoral venous blood (left vs right side, p < 0.002) up to postoperative day 40, and a decrease in the calf blood pressure ratio (p < 0.0001 vs day 0) up to day 90. Histologic study of the gastrocnemius muscle demonstrated evidence of atrophy and fibrosis in the left hindlimb. This model can be used to evaluate direct and indirect approaches to the treatment of chronic limb ischemia.

Enhanced revascularization of the ischemic limb by angiogenic therapy.

BACKGROUND: This study tests the efficacy of an angiogenic growth factor, endothelial cell growth factor, in a rabbit model of persistent hindlimb ischemia. METHODS AND RESULTS: Ischemia was induced in the left hindlimb of 22 New Zealand White rabbits by ligation of the distal external iliac artery and complete excision of the common and superficial femoral arteries. Two groups of animals were studied: Group 1 consisted of 11 animals who for 10 days received daily intramuscular injections of 4 mg of endothelial cell growth factor beginning on postoperative day 11, and group 2 consisted of 11 animals who underwent the same surgical ischemic procedure but received only injections of saline daily for the same postoperative period. Perfusion of the ischemic left limb was compared with the normal right limb in each animal on postoperative days 10, 20, 30, and 40 using the calf blood pressure ratio, 99mTc macroaggregate radioisotopic perfusion scans, and serial angiography. Neovascularization in the left thigh at day 40 was quantified from the angiograms. Each technique documented that animals in group 1 had significantly better perfusion than animals in group 2; that is, the calf pressure ratio was higher in group 1 than in group 2 (0.56 versus 0.32 at day 20, 0.64 versus 0.44 at day 30, and 0.70 versus 0.50, P < .0001), and the calf radioisotopic perfusion ratio was also higher in group 1 than in group 2 (0.88 versus 0.74 at day 20, P < .02; 0.93 versus 0.76 at day 30, and 0.96 versus 0.79 at day 40, P < .008). Angiographic studies correlated well with these results demonstrating much earlier distal arterial reconstitution and enhanced neovascularization (23.8 versus 9.0 vessels, P < .007). CONCLUSIONS: The data clearly indicate that an angiogenic growth factor, endothelial cell growth factor, promotes revascularization in this experimental ischemic hindlimb model, raising the possibility that in the future such agents might be of value in humans.

Does the clinical evaluation of the cardiac status predict outcome in patients with abdominal aortic aneurysms?

A cost-effective method to reduce mortality rates after abdominal aortic aneurysm repair centers on selecting and investigating only those patients at risk for cardiac-related death. All 146 patients undergoing asymptomatic abdominal aortic aneurysm repair over a 5-year period (1986 to 1990) were retrospectively placed into one of the three following groups on the basis of a clinical evaluation. Group I: no history of myocardial infarction or angina, no congestive heart failure, and no ischemic changes on electrocardiogram (ECG). Group II: history of myocardial infarction or class I-II angina or ischemic changes on ECG. Group III: presence of congestive heart failure or class III-IV angina. Patients in group I had no further cardiac work-up; patients in group II with angina had left ventricular ejection fraction assessment by multiple gated acquisition (all greater than 37%) and were cleared for operation by a cardiologist; patients in group II without angina had no further cardiac work-up; patients in group III had coronary angiography and then coronary revascularization. The overall mortality rate was 4.8%, with a cardiac mortality rate of 3.4%. The mortality rate in group I (n = 64) was 1.8%, with no cardiac-related deaths; the mortality rate in group II (n = 63) was 9.5% (8% cardiac-related deaths). No deaths occurred in group III (n = 19). The difference between the cardiac mortality rates in groups I and II was significant (p = 0.02) as was the postoperative cardiac morbidity: total myocardial infarctions (p less than 0.001); congestive heart failure (p = 0.02); tachyarrhythmias (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)