Direct cardiac effects of coronary site-directed thiopental and its enantiomers: a comparison to propofol in conscious sheep

BACKGROUND: Previous evidence from laboratory animal studies indicates that R-thiopental has a greater margin of safety than either the more potent S-thiopental or the clinically used rac-thiopental. Although thiopental can cause cardiovascular depression from direct myocardial effects as well as indirect central nervous system and peripheral effects, no studies have yet determined whether its myocardial effects are enantioselective. A lesser direct effect would provide further evidence supporting R-thiopental as a preferred single enantiomer replacement for rac-thiopental. METHODS: The direct myocardial effects of the thiopental enantiomers were compared to those of rac-thiopental and propofol, using a crossover design with small incremental doses infused over 3 min, on separate days, into the left coronary arteries of conscious sheep. Hemodynamic and electrocardiographic measurements were acquired, and serial blood samples were collected during the studies for drug analyses. RESULTS: All three forms of thiopental and propofol produced significant hemodynamic effects consisting of dose-related and rapid-onset decreases in left ventricular dP/dtmax and stroke volume, and increases in left coronary blood flow and heart rate. Cardiac output, mean arterial blood pressure, and central venous pressure remained unaltered. The effects did not differ significantly among rac-thiopental, enantiopure R- or S-thiopental, or propofol. Arterial blood drug concentrations were consistently less than those associated with systemic effects. CONCLUSIONS: Although previous evidence indicates that R-thiopental could make a suitable single-enantiomer replacement for rac-thiopental, the current study did not find a significant difference in direct cardiac effects among the thiopental enantiomers, racemate, or propofol.     

Interactions between endothelin and nitric oxide in the regulation of vascular tone in obesity and diabetes

Endothelial dysfunction reflects an imbalance of vasodilators and vasoconstrictors. Endogenous endothelin activity seems to be increased in human obesity and type 2 diabetes, and cellular studies suggest that this factor may itself reduce bioavailable nitric oxide (NO). We studied 20 lean, 20 obese, and 14 type 2 diabetic individuals under three protocols, measuring leg vascular responses to intra-arterial infusions of NG-monomethyl-l-arginine (l-NMMA; an inhibitor of NO synthase) alone or in combination with BQ123 (an antagonist of type A endothelin receptors) or phentolamine (used as a control vasodilator). NO synthase inhibition alone (study 1) produced an approximately 40% increase in leg vascular resistance (LVR) in all three participant groups, which was not statistically different across groups (increase in LVR: lean, 135 +/- 28; obese, 140 +/- 32; type 2 diabetic, 184 +/- 51 units; NS). By design, BQ123 at the infused rate of 3 micromol/min produced equivalent approximately 35% reductions in LVR across groups. The subsequent addition of l-NMMA produced a greater increase in LVR among obese participants than lean or type 2 diabetic participants (study 2: lean, 182 +/- 48; obese, 311 +/- 66; type 2 diabetic, 186 +/- 40; P = 0.07). Compared with study 1, the effect of l-NMMA was magnified by BQ123 in obese participants but not in lean or type 2 diabetic participants (P = 0.005, study 1 vs. 2; P = 0.03 for group effect). Phentolamine (75 mg/min) produced vasodilation in obese participants comparable to that seen with BQ123 but failed to augment the L-NMMA response. Endothelin antagonism unmasks or augments NO synthesis capacity in obese but not type 2 diabetic participants. This suggests that impaired NO bioavailability as a result of endogenous endothelin may contribute to endothelial dysfunction in obesity, in addition to direct vasoconstrictor effects of endothelin. In contrast, endothelin antagonism alone is insufficient to restore impaired NO bioavailability in diabetes.     

Impact of fluid balance on incidence of atrial fibrillation after cardiothoracic surgery

Excessive fluid administration after cardiothoracic surgery has been proposed as a cause of postoperative atrial fibrillation. In this study, we observed that fluid balance and volume administered on postoperative day 2 was greater in patients who developed postoperative AF than in those who did not. We also found that net fluid balance on postoperative day 2 was an independent predictor of postoperative AF among patients not receiving prophylactic therapy.     

Development and preliminary validation of the Meta-cognitions Questionnaire-Adolescent Version

This study describes the development of the Meta-cognitions Questionnaire for Adolescents (MCQ-A). The adult version of this questionnaire has been widely used, and the meta-cognitive theory of emotional disorders has become influential in the adult literature. This study sought to examine the prevalence and emotional correlates of meta-cognition in adolescents. The MCQ-A was administered to 177 schoolchildren aged 13 through 17 years, together with measures of emotional well-being. Factor analysis suggested a five-factor solution similar to that reported for the adult version. Internal consistency of the scale was high. Scores ranged from low to high across the age range, suggesting that meta-cognitive beliefs are well-established by adolescence. Scores on the MCQ-A were highly correlated with a number of measures of emotional symptoms. The MCQ-A is a reliable and valid instrument for measuring meta-cognitive beliefs in adolescents. Young people aged between 13 and 17 years report a range of types and levels of meta-cognitive beliefs and these are positively associated with emotional symptoms.     

Combining depth cues: effects upon accuracy and speed of performance in a depth-ordering task

Two experiments investigated how the number of available depth cues affected the speed and accuracy of depth-ordering judgements. A series of textured tiles was presented on a computer monitor, with relative depths defined by combinations of contrast, blur and interposition. Subjects were required to move a mouse pointer inside each tile in turn, starting with the tile that appeared nearest, clicking on each. Accuracy of depth-ordering was much higher than chance in all conditions, though performance using the interposition cue alone was worse than in all other conditions. The only difference in reaction time in different cue conditions was in the time elapsed before the first-click. Subjects responded substantially faster when three depth cues were present (0.84 s) than when only one depth cue was present (1.41 s). The improvement in reaction time with cue numerosity is consistent with probability summation between cues extracted by independent processes.     

Emergency management program operational responses to weapons of mass destruction: Veterans Health Administration, 2001-2004

BACKGROUND: Despite the recognition of chemical emergencies, terrorist events, and ongoing threats, little practical guidance exists for healthcare facilities. METHODS: An approach and materials developed by the Veterans Health Administration in a five-element program over the last 2 years to enhance the existing emergency management program is outlined. Nine steps to the development of a comprehensive all-hazards, emergency plan and program, with auditing and improvement tools are offered. RESULTS: Cognitive aids for clinical use are available on-line and in hard copy. A hazard assessment modeled patients as emission sources documenting the operations strategies under which level C personal protective equipment will protect healthcare workers. The development of this response program appears to support a broader, long-standing VHA approach to problem solving. This involves bringing together individual talented field staff, representing specific skills, geographic regions, and work styles; investing in face-to-face consensus development; and developing programs with extensive internal peer-review ("field-based," "bottom-up and top-down," and external reviews). CONCLUSIONS: Comprehensive and effective programs can be constructed at low cost with reasonable speed within large systems with a public mandate, leading to responsible use of public funds internally, and as models for private sector programs. It is the long-term operational cost implications, under budget constraints in health care, which often present the true challenge.     

The inhibition of calcium signaling in T lymphocytes from old mice results from enhanced activation of the mitochondrial permeability transition pore

Aging attenuates calcium signaling in T lymphocytes from old mice. Aging also attenuates the sustained elevation of cell free calcium by ionomycin, which is similar to the T cell receptor signal. In T lymphocytes from young mice, the ionomycin-induced elevation of cell free calcium was inhibited by collapsing the mitochondrial membrane potential by uncouplers and ionophores, and activation of the permeability transition. In T lymphocytes from old mice, the mitochondrial membrane potential was largely collapsed, but cyclosporin and N-methyl-val-4-cyclosporin, inhibitors of the permeability transition, restored the mitochondrial potential, as well as the ionomycin-induced elevation of cell free calcium. In addition, the generation of reactive oxygen species in the presence of mitochondrial electron transport inhibitors was relatively enhanced in T lymphocytes from old mice. The association between low rhodamine 123 fluorescence and attenuated calcium signaling in T lymphocytes from old mice is also shown to be a consequence of the collapsed mitochondrial potential. These results suggest that Ca2+ signaling is attenuated in T lymphocytes from old mice because of an enhanced activation of the permeability transition.     

Clinical evaluation of an automatic flossing device vs. manual flossing

The aim of this study was to compare the effectiveness of an automatic flossing device to manual flossing. A total of seventy adult subjects (20 males and 50 females) were stratified into two groups balanced for age, sex, modified gingival index (MGI), plaque index (PI) and bleeding sites (Eastman Bleeding Index) using screening data. One group was randomly assigned the automatic power flosser and the other group was assigned manual dental floss. The subjects were instructed to brush their teeth twice a day (in the morning and before bedtime) for 30 seconds using the provided manual toothbrush and toothpaste. They were also to use their assigned dental floss or automatic power flosser once in the morning following toothbrushing. There was no significant difference between manual flossing and automatic flossing with respect to the MGI and the BI. There was, however, a significant difference at day 15 in the PI; however, this difference was only 0.73%. There was no significant difference in the PI at day 30 between the two techniques. The statistically significant difference noted in the interproximal PI at both day 15 and day 30 was less than 2%. Since the differences in plaque scores between the groups were so small, there was no apparent impact on gingival health since both flossers resulted in similar health benefits. Since there was a marked preference for the automatic flosser, patient compliance with the automatic flossing device may be better than with manual floss. Therefore, overall gingival health may benefit from this device.