Optimal interpretation of the supine exercise electrocardiogram in patients with right bundle branch block

A detailed analysis of the exercise ECG was performed in 82 patients with right bundle branch block who underwent supine exercise equilibrium radionuclide angiography. The sensitivity and specificity of each individual electrocardiographic lead for the detection of a positive radionuclide angiogram was determined. Leads V5 and V6 had a sensitivity of 58 percent and a specificity of 89 percent. The limb leads and lead V4 had a lower sensitivity, but an equivalent specificity. Leads V1 and V3 each had a clearly lower specificity that ranged from 56 to 67 percent. Receiver operating characteristic curve analysis demonstrated that the optimal interpretation of the exercise ECG included the limb leads and V4 to V6, but not V1 to V3. The results of coronary angiography in the subset of 16 patients who underwent this procedure confirmed these findings.     

Association between coronary heart disease risk factors and physical fitness in healthy adult women

We examined associations between physical fitness and risk factors for coronary heart disease in healthy women ages 18-65 years. Physical fitness was objectively determined by the duration of a maximal treadmill exercise test. Six physical fitness categories (very poor to superior), specific within 10-year age increments, were established. Mean risk factor levels varied across categories, but so did potential confounders such as age and weight. Multiple linear regression modeling was used to control for the effects of age, weight and year of exam on coronary risk factors. After adjustment, physical fitness was independently associated with triglycerides (p less than 0.001), high-density lipoprotein cholesterol (HDL-C) (p less than or equal to 0.001), total cholesterol/HDL-C ratio (p less than or equal to 0.001), blood pressure (p less than or equal to 0.001) and cigarette smoking (p less than or equal to 0.001).     

Angiographic visualization of a right gastroepiploic artery-left circumflex coronary artery graft

A 41-year-old man who underwent coronary artery bypass grafting using a gastroepiploic artery graft to the left circumflex coronary artery is reported. Subselective angiography of the right gastroepiploic artery using a steerable guidewire and coaxial catheter system is described.     

Primary angioplasty in myocardial infarction: assessment of improved myocardial perfusion with technetium-99m isonitrile.

Technetium-99m-hexakis-2-methoxy-2-isobutyl-isonitrile (technetium-99m isonitrile) is a new radiopharmaceutical compound that reflects myocardial perfusion. Its kinetics, especially its lack of redistribution after intravenous administration, permits the assessment of changes in myocardial perfusion without delay of therapy. Tomographic images at rest were obtained immediately and 6 to 10 days later in 17 consecutive patients undergoing successful primary angioplasty during their first transmural myocardial infarction. Thirteen patients had anterior infarction. The initial (acute) defect size before angioplasty of 48 +/- 17% of the left ventricle decreased significantly (p less than 0.0001) to 29 +/- 19% on the late scans. There was no correlation between the time to therapy and the reduction in defect size. Twelve of the 17 patients, including 7 of the 11 patients treated after 4 h, demonstrated a definite reduction in the initial defect size. Eight patients with angiographically proved persistent coronary occlusion underwent a similar imaging sequence. The initial defect size in this group remained unchanged on the late scans (24 +/- 16% versus 26 +/- 18%, p = NS). Primary angioplasty is an effective approach toward salvaging myocardium; comparison with thrombolytic drug therapy must await the results of controlled clinical trials.     

Identification of BRaf-Sparing Amino-Thienopyrimidines with Potent IRE1α Inhibitory Activity

Amino-quinazoline BRaf kinase inhibitor 2 was identified from a library screen as a modest inhibitor of the unfolded protein response (UPR) regulating potential anticancer target IRE1α. A combination of crystallographic and conformational considerations were used to guide structure-based attenuation of BRaf activity and optimization of IRE1α potency. Quinazoline 6-position modifications were found to provide up to 100-fold improvement in IRE1α cellular potency but were ineffective at reducing BRaf activity. A salt bridge contact with Glu651 in IRE1α was then targeted to build in selectivity over BRaf which instead possesses a histidine in this position (His539). Torsional angle analysis revealed that the quinazoline hinge binder core was ill-suited to accommodate the required conformation to effectively reach Glu651, prompting a change to the thienopyrimidine hinge binder. Resulting analogues such as 25 demonstrated good IRE1α cellular potency and imparted more than 1000-fold decrease in BRaf activity.     

Development and Psychometric Properties of a New Questionnaire to Assess Mental Health and Concerning Behaviors in Children and Young People with Autism Spectrum Disorder (ASD): The Assessment of Concerning Behavior (ACB) Scale

Journal of Autism and Developmental Disorders - Although 70% of autistic children and young people meet criteria for co-occurring psychiatric conditions, there are few screening measures...     

Effect of stool size and consistency on defecation.

The ability of subjects to expel from the rectum objects simulating stools of different characteristics was assessed in paired studies carried out in a total of 58 normal subjects and 25 young women with severe constipation. Our results showed that a lower percentage of normal subjects and a lower percentage of constipated patients were able to pass a 1.8 cm incompressible sphere compared with a 50 ml deformable balloon, although constipated patients found it more difficult than normal subjects to expel both types of simulated stool. It was also more difficult for normal subjects to pass a soft compressible silicon rubber simulated stool than a stool made up of a similar volume of incompressible 1 cm wooden spheres contained in a cylindrical latex envelope, but both objects were much easier to pass than the same number of 1 cm spheres placed loose within the rectum. When normal subjects were instructed to expel single incompressible spheres of different sizes placed in the rectal ampulla, the intrarectal pressure and the time needed to pass these objects varied inversely with their diameter. These results suggest that more effort is required to expel stools from the rectum if they are small and hard than if they are large and soft.     

Left ventricular systolic response to exercise in patients with systemic hypertension without left ventricular hypertrophy

Supine exercise radionuclide angiography was performed in 367 men to assess left ventricular (LV) systolic response to exercise; 58 had systemic hypertension without LV hypertrophy on a resting electrocardiogram and 309 were normotensive. All patients met the following criteria defining a low pretest likelihood of coronary artery disease: age less than 50 years; normal electrocardiographic response to exercise; absence of typical or atypical chest pain; and exercise heart rate greater than 120 beats/min. Patients taking beta-receptor blockers were excluded. There were no significant differences between hypertensive and normotensive groups in peak exercise heart rate, workload or exercise duration. However, hypertensive patients had significantly higher peak exercise systolic blood pressures and peak exercise rate-pressure products. There were no differences between patients with and without hypertension in resting ejection fraction, peak exercise ejection fraction (hypertensive patients 0.71 +/- 0.01, normotensive patients 0.70 +/- 0.05) or change in ejection fraction at peak exercise (hypertensive patients 0.07 +/- 0.01, normotensive patients 0.07 +/- 0.04). Diastolic and systolic ventricular volumes tended to be smaller in the hypertensive patients, but the difference was not statistically significant. The change in systolic volume with exercise was similar in the 2 groups (hypertensive -10 +/- 3 ml/m2, normotensive -10 +/- 1 ml/m2). In the absence of electrocardiographic evidence of LV hypertrophy, systemic hypertension does not influence LV systolic response to exercise.     

Laboratory-based Japanese encephalitis surveillance in Nepal and the implications for a national immunization strategy

We report on two years of Japanese encephalitis (JE) surveillance in Nepal and the implications for a national immunization strategy. From May 2004 to April 2006, 4,652 patients with encephalitis were evaluated. A serum or cerebrospinal fluid specimen was collected from 3198 (69%) patients of which 1,035 (32%) were positive by Japanese encephalitis IgM ELISA. Most cases (N = 951, 92%) were from the 24 Terai districts (i.e., southern plains, 12.3 million persons) with the majority (N = 616, 65%) from four western Terai districts (population = 1.8 million). The case fatality ratio was 14.7% and 6.3% and the proportion of cases under 15 years old was 52% and 62% in the four western and 20 non-western Terai districts, respectively. Japanese encephalitis immunization targeting residents one year of age and older in the western districts and one through 14 years old in the non-western Terai districts may have reduced Japanese encephalitis cases by 84% and deaths by 92%, nationally.     

Maximal exercise test as a predictor of risk for mortality from coronary heart disease in asymptomatic men

Exercise testing in asymptomatic persons has been criticized for failing to accurately predict those at risk for coronary heart disease (CHD). Previous studies on asymptomatic subjects, however, may not have been large enough or long enough to provide reliable outcome measures. This study examines the ability of a maximal exercise test to predict death from CHD and death from any cause in a population of asymptomatic men. This is a prospective longitudinal study performed between 1970 and 1989, with an average follow-up of 8.4 years. The subjects are 25,927 healthy men, 20 to 82 years of age at baseline (mean 42.9 years) who were free of cardiovascular disease and who were evaluated in a preventive medicine clinic. The main outcome measures are CHD mortality and all-cause mortality. During follow-up there were 612 deaths from all causes and 158 deaths from CHD. The sensitivity of an abnormal exercise test to predict coronary death was 61%. The age-adjusted relative risk of an abnormal exercise test for CHD death was 21 (6.9 to 63.3) in those with no risk factors, 27 (10.7 to 68.8) in those with 1 risk factor, 54 (21.5 to 133.7) in those with 2 risk factors, and 80 (30.0 to 212. 5) in those with >/=3 factors. A maximal exercise test performed in asymptomatic men free of cardiovascular disease does appear to be a worthwhile tool in predicting future risk of CHD death. An abnormal exercise test is a more powerful predictor of risk in those with than without conventional risk factors.