Citations

BACKGROUND AND OBJECTIVE: Simulation-based medical education (SBME) is used to teach residents. However, few studies have evaluated its clinical impact. The goal of this study was to evaluate the impact of an SBME session on pediatric interns’ clinical procedural success. METHODS: This randomized trial was conducted at 10 academic medical centers. Interns were surveyed on infant lumbar puncture (ILP) and child intravenous line placement (CIV) knowledge and watched audiovisual expert modeling of both procedures. Participants were randomized to SBME mastery learning for ILP or CIV and for 6 succeeding months reported clinical performance for both procedures. ILP success was defined as obtaining a sample on the first attempt with <1000 red blood cells per high-power field or fluid described as clear. CIV success was defined as placement of a functioning catheter on the first try. Each group served as the control group for the procedure for which they did not receive the intervention. RESULTS: Two-hundred interns participated (104 in the ILP group and 96 in the CIV group). Together, they reported 409 procedures. ILP success rates were 34% (31 of 91) for interns who received ILP mastery learning and 34% (25 of 73) for controls (difference: 0.2% [95% confidence interval: –0.1 to 0.1]). The CIV success rate was 54% (62 of 115) for interns who received CIV mastery learning compared with 50% (58 of 115) for controls (difference: 3% [95% confidence interval: –10 to 17]). CONCLUSIONS: Participation in a single SBME mastery learning session was insufficient to affect pediatric interns’ subsequent procedural success.

ICD in Cardiac AmyloidosisBackgroundCardiac amyloidosis (CA) is associated with increased risk of sudden cardiac arrest. Although ICD therapy improves survival in patients with cardiomyopathy due to other etiologies, the benefit of ICD therapy in patients with CA is unclear in large part due to limited data on the precise mechanism of sudden cardiac arrest and selection of patients with cardiac amyloidosis for ICD therapy.ObjectiveThe objective was to determine the benefit of ICD therapy in cardiac amyloidosis.MethodsWe reviewed all ICD implant indications, procedures, and therapies, of CA patients evaluated at Mayo Clinic between 2000 and 2009.ResultsA total of 53 patients with CA (33 AL, 10 senile, 9 familial, and 1 AA) who underwent ICD implantation were included. Indication for ICD implantation was for primary prevention of sudden cardiac arrest in 41 (77%) patients and secondary prevention in 12 (23%) patients. The rate of appropriate ICD shocks was 32% in the first year and was observed almost exclusively in AL amyloidosis patients, occurring in 15 patients (12 AL amyloidosis, 2 senile, 1 AA). Appropriate ICD shocks were more frequent in patients with prior sudden cardiac arrest or sustained ventricular arrhythmias (secondary prevention indication), and less frequent in patients who presented with decreased ejection fraction or syncope.ConclusionsA high rate of appropriate ICD shocks was observed especially in patients with AL‐type amyloidosis. However, appropriate ICD therapy did not translate into overall survival benefit, suggesting that selection of patients with CA who might be candidates for ICD is imprecise.

Abstract The mammalian target of rapamycin (mTOR) consists of two distinct complexes, mTORC1 and mTORC2. mTOR plays a pivotal role in Hepatocellular Carcinoma (HCC). Previous studies indicated that inhibition of mTORC1 only moderately enhanced histone deacetylase inhibitors (HDACis)-mediated anti-tumor activity. This limited effect may be attributable to the increase of AKT activation through S6K1-IRS1-PI3K negative feedback loop triggered by selective mTORC1 inhibition. While as AKT is the downstream effector of mTORC2, we hypothesize that dual targeting of mTORC1/C2 would be more efficient in suppressing AKT and in enhancing anti-tumor activity of HDACi. In this study, the interactions between mTOR kinase inhibitors (mTORKis) and HDACis were examined in vitro using established HCC cell lines and in vivo using patient-derived HCC tumor xenografts on SCID mice. Our results demonstrate that inhibition of both mTORC1/2 not only effectively blocked mTORC1 signaling, but also abrogated negative-feedback activation of AKT caused by mTORC1 inhibition. Furthermore, inactivation of mTORC1/C2 by mTORKis substantially enhanced HDACi-induced anti-tumor activity. Either dysfunction of mTORC2 by knockdown of Rictor (a component of mTORC2), or diminution of AKT1 significantly lowered the threshold of HDACi-induced apoptosis. Lastly, in vivo study indicated that the combination of AZD8055 and Vorinostat yielded much greater tumor-growth inhibition compared to either agent alone in primary HCC xenografts without obvious adverse effects. Conclusion: Dual mTORC1/2 inhibition is more efficient than selective mTORC1 inhibition in enhancing anti-tumor activity of HDACi due to abrogation of negative-feedback activation of AKT induced by selective mTORC1 inhibition. Our findings suggest that combining regimen of mTORKi and HDACi may be an effective therapeutic strategy for HCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5363. doi:10.1158/1538-7445.AM2011-5363

A group of 26 patients who had peripheral occlusive arterial disease of the lower extremity were studied before and after chemical or surgical unilateral lumbar sympathectomy. The temperatures of the gastrocnemius muscle and of the skin of the sural area were determined simultaneously preoperatively and postoperatively. Only patients who had undergone successful unilateral lumbar sympathetic denervation based on the postoperative area of anhidrosis were included. The data were obtained under basal conditions among the 26 patients, and the persons studied were divided into two groups. Group 1 was composed of 17 patients (65 per cent) who had a definite parallel increase of 1.2 C. in the temperature of the gastrocnemius muscle and the skin after unilateral sympathectomy. In group 2 (nine patients or 35 per cent) the temperature of the gastrocnemius muscle and the skin of the sural area was unchanged after unilateral sympathectomy. Since none of these patients were suitable for surgical bypass arterial-grafting procedures and all were in the older age group, not too much could be expected from the standpoint of an increase in temperature. However, when the temperature of the skin after operation increased, the temperature of the gastrocnemius muscle also increased.

Bilateral determinations of the blood pressures were made nonsimultaneously and simultaneously by the indirect method under basal conditions on 447 patients. In this group 26.6 per cent of the paired measurements by the nonsimultaneous indirect method exhibited systolic differences of 10 mm. Hg or greater and 15 per cent exhibited diastolic differences of this magnitude, whereas only 5.3 per cent of the measurements by the simultaneous indirect method had systolic differences and only 4 per cent had diastolic differences of this degree. This indicates that bilateral determinations of blood pressure must be performed simultaneously on patients being examined for possible inequalities of blood pressure. Bilateral differences in blood pressure obtained by the simultaneous indirect and simultaneous direct methods in 14 normal subjects and 53 selected patients were compared. In the normal subjects, 3 of the 42 paired indirect measurements and none of the paired direct measurements in either the radial or brachial arteries had systolic differences of 10 mm. Hg or greater, and none of the diastolic differences were of this level. In the 53 selected patients, 10 per cent of the indirect and 6 per cent of the direct measurements of systolic blood pressure differed by 10 mm. Hg or more and 8 per cent of the paired indirect measurements of diastolic blood pressure and less than 1 per cent of the paired direct measurements differed by this amount. These differences in bilateral blood pressures were characterized by their inconstancy and lack of agreement with subsequent measurements when studied by both the indirect and direct methods, which apparently separates them from those due to altered hemodynamics from pathologic conditions of the aortic arch or its tributaries. Bilateral differences of blood pressure are of clinical importance when they are great and are reproducible by the direct as well as by the indirect methods, as illustrated by a patient encountered in this study. In addition, 1 case of extreme obesity and 1 of advanced arteriosclerosis were reported. Both patients were found to have pseudohypertension, which was detected in this study. A slight increase in the incidence of bilateral differences in indirect blood pressures was found in a group of patients whose blood pressures were measured while they were in the supine and then in the sitting position. A slight increase in the incidence of bilateral differences was found at higher levels of blood pressure by comparing the blood pressures of nonhypertensive and hypertensive patients and of hypertensive patients before and during treatment with antihypertensive drugs. Bilateral inequalities of blood pressure did not appear to be related to the age or sex of the subjects. Likewise, differences in circumferences of the arm or right or left-handedness did not appear to influence these inequalities, and there was no marked side dominance for differences found. Bilaterally simultaneous, indirect measurements of blood pressure should be carried out on patients with hypertension who will be treated with antihypertensive drugs. Bilateral direct measurements may be used to verify the existence of inequality of blood pressures detected by the indirect method and to determine the correct pressure to be followed. This is particularly important in patients being screened for pheochromocytomas, since such differences may produce false-positive results.

Today pharmacologic and chemical tests are helpful in screening a relatively large number of patients for pheochromocytoma and are a definite aid to a correct diagnosis. No one test is infallible, and knowledge concerning the drugs used or the manner in which the blood and urine are collected, or both, is necessary to avoid a false-positive or false-negative result from the tests.

When 24 normal subjects under basal conditions smoked two thirds of 2 cigarettes, there was no appreciable rise in the levels of the fasting blood sugar and the epinephrine-like substances of the systemic venous blood. However, the smoking of two thirds of 2 cigarettes significantly raised the blood pressure and pulse rate, and decreased the skin temperature of fingers and toes.

In normal subjects smoking or the injection of nicotine produces transient vascular effects on the heart and blood vessels. Apparently tobacco angina or tobacco heart is a clinical entity. Abnormal vascular responses after smoking in normal subjects may be due to hypersensitivity to nicotine, such as occurs in tobacco heart, or to the effect of nicotine on a vascular system demonstrated to be hyperreactive by the cold pressor test. Tobacco is one of the most prominent contributing factors in thromboangiitis obliterans, as thromboangiitis is rarely found in nonsmokers. The question as to whether the effects of smoking are due to sudden increased work of the heart or constriction of the coronary artery has stimulated a great amount of research. There is evidence to support both theories. The findings of abnormal ballistocardiograms before and after smoking in the offspring of hypertensive parents and after smoking in the offspring of parents with coronary heart disease are highly important. Statistically coronary artery disease seems to occur more frequently and at an earlier age in the person who smokes much than in the nonsmoker. Likewise, the mortality rate is higher among younger persons with coronary disease who are smokers than among those who are nonsmokers.

Various indirect methods of measuring blood flow in the peripheral blood vessels of man are available. Irrespective of the method used for measuring blood flow, certain fundamental factors concerned with the status of the subject or patient influence the measurement of blood flow. These factors are environmental temperature, position of the extremities and food. The present investigation indicates that a consideration of the basal metabolic rate or basal heat production is another important factor.