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.     

Cardiotoxicity with modern local anaesthetics: is there a safer choice?

The recognition that long-acting local anaesthetics, particularly bupivacaine the de facto standard long-acting local anaesthetic, were disproportionately more cardiotoxic than their shorter-acting counterparts stimulated the development of the bupivacaine congeners, ropivacaine and levobupivacaine. These agents, like all local anaesthetics, can produce cardiotoxic sequelae by direct and indirect mechanisms that derive from their mode of local anaesthetic actions, i.e. inhibition of voltage-gated ion channels. While all local anaesthetics can cause direct negative inotropic effects, ropivacaine and levobupivacaine are less cardiotoxic than bupivacaine judging by the larger doses tolerated in laboratory animal preparations before the onset of serious cardiotoxicity (particularly electro-mechanical dissociation or malignant ventricular arrhythmias). Additionally, they are less toxic to the CNS than bupivacaine judging by the larger doses tolerated before the onset of seizures. This may be clinically important because CNS effects may be involved in the production of serious cardiotoxicity. Preclinical studies in humans are a 'blunt instrument' in their ability to distinguish significant differences between these drugs because of the relatively small doses that can be used. Nevertheless, available evidence from human studies corroborates the preclinical laboratory animal studies. Because clinically significant differences between these drugs are more quantitative than qualitative, i.e. toleration of a larger dose before manifestation of toxicity, we have concluded that these newer agents have a lower risk of causing serious cardiotoxicity than bupivacaine. Thus, compared with bupivacaine, the newer agents may be seen as 'safer', but they must not be regarded as 'safe'.     

Direct cardiac effects of intracoronary bupivacaine, levobupivacaine and ropivacaine in the sheep

1. The racemic local anaesthetic agent bupivacaine is widely used clinically for its long duration of action. Levobupivacaine and ropivacaine are bupivacaine enantiopure congeners, developed to improve upon the clinical safety of bupivacaine, especially the risk of fatal arrhythmogenesis. 2. In previous preclinical studies of the safety of these drugs with intravenous administration in conscious ewes over a wide dose range, we found that central nervous system (CNS) excito-toxicity reversed the cardiac depressant effects when doses approached the convulsant threshold and thus precluded accurate comparison of their cardiovascular system (CVS) effects. 3. To study CVS effects over a wide range of doses with minimal CNS and other influences, brief (3 min) infusions of bupivacaine, levobupivacaine or ropivacaine were administered into the left main coronary arteries of previously instrumented conscious ewes (approximately 50 Kg body weight). After dose-ranging studies, the drugs were compared in a randomized, blinded, parallel group design. Equimolar doses were increased from 8 micromol (approximately 2.5 mg) in 8 micromol increments, to either a fatal outcome or a 40 micromol (approximately 12.5 mg) maximum. 4. All three drugs produced tachycardia, decreased myocardial contractility and stroke volume and widening of electrocardiographic QRS complexes. Thirteen of 19 animals died of ventricular fibrillation: four of six with bupivacaine (mean+/-s.e.mean actual fatal dose: 21.8+/-6.4 micromol), five of seven with levobupivacaine (22.9+/-3.5 micromol), four of six with ropivacaine (22.9+/-5.9 micromol). No significant differences in survival or in fatal doses between these drugs were found. 5. The findings suggest that ropivacaine, levobupivacaine and bupivacaine have similar intrinsic ability to cause direct fatal cardiac toxicity when administered by left intracoronary arterial infusion in conscious sheep and do not explain the differences between the drugs found with intravenous dosage.     

Antibody targeting studies in a transgenic murine model of spontaneous colorectal tumors

Monoclonal antibodies (mAbs) have been used to treat malignancies in humans with varying degrees of success. Progress has been hindered by the lack of suitable animal models, which would ideally consist of immunocompetent animals that are tolerant to tumor-associated antigens. Suitable models would allow the study and optimization of anti-tumor immunotherapy. We describe a murine model for the study of immunotherapy in colorectal cancers. Carcinoembryonic antigen (CEA) is a cell-surface glycoprotein that is expressed on normal human intestinal epithelium and that is overexpressed in intestinal tumors. Mice that are transgenic for the human CEA gene (CEA.Tg) were crossed with multiple intestinal neoplasia (MIN) mice. MIN mice carry a germline APC mutation and are prone to the development of intestinal adenomas. The offspring from the MIN x CEA.Tg cross developed intestinal adenomas that were shown by immunohistochemistry to overexpress CEA. Pharmacokinetic studies by using (125)I-labeled anti-CEA mAb PR1A3 showed rapid localization of antibody to tissues expressing CEA, especially the gastrointestinal tract. Macroscopic and microscopic radioautographic analysis of the gastrointestinal tracts from MIN/CEA.Tg mice indicated that PR1A3 targeted and was retained in tumors at levels higher than in areas of normal gut. These results demonstrate the utility of the MIN/CEA.Tg mouse as a model for the study of anti-CEA immunotherapy and, furthermore, demonstrate the efficiency of tumor localization by PR1A3.     

Hyperinsulinemia in polycystic ovary syndrome correlates with increased cardiovascular risk independent of obesity

OBJECTIVE: To assess the role of insulin resistance, independent of obesity, in determining cardiovascular risk among women with the polycystic ovarian syndrome (PCOS). DESIGN: Cross-sectional study examining the relationships between hyperinsulinemia, composite cardiovascular risk scores, and prevalence of individual risk factors among lean and obese women with PCOS and healthy controls. SETTING: University-based tertiary care outpatient endocrinology clinic. PATIENT(S): 57 women with clinically defined PCOS and 45 unselected healthy age-matched controls. INTERVENTION(S): Clinical and anthropomorphic measurements and laboratory determinations of insulin and lipid levels. MAIN OUTCOME MEASURE(S): Fasting serum insulin and a cardiovascular risk score. RESULTS: Hyperinsulinemic women with PCOS carried more cardiovascular risk than their normoinsulinemic counterparts, who in turn had more risk than the control women (P=.004 by analysis of covariance). In addition to the lipid changes expected with insulin resistance (high triglyceride and low HDL cholesterol levels), there was an excess of LDL cholesterol among the women with PCOS (P=.006 by analysis of covariance). Across the range of body mass index, women with PCOS had greater insulin resistance than controls, suggesting that PCOS itself and body mass index both contribute to the observed insulin resistance. CONCLUSIONS: Our data support the hypothesis that insulin resistance in PCOS is a determinant of overall cardiovascular risk independent of obesity. The mechanism of this relationship remains uncertain and is the subject of ongoing research.