Dyssynchrony of segment shortening in the anterior wall of the feline left ventricle.

Non-uniformity of regional contraction may be both spatial and temporal. This study was undertaken to deal with the temporal aspects of shortening and to quantify non-uniformity with regard to timing. Nine cats were anaesthetized and artificially ventilated. Two pairs of ultrasonic crystals were situated in the anterior midwall of the left ventricle to measure regional shortening. One pair, longitudinal segment, was oriented to align with midwall fibres. The other pair, transverse segment, was placed perpendicular to the first one. Registrations in control state, during caval occlusion, and during aortic constriction were carried out with and without isoprenaline infusion. Cyclic events were analysed in terms of phase angle, 0-2 pi representing one heart cycle. Transverse segments showed marked shift of duration of shortening, from 1.19 pi +/- 0.06 pi (mean +/- SEM) in the control state to 0.40 pi +/- 0.14 pi during caval occlusion with isoprenaline infusion. Duration of shortening of longitudinal segments showed less prominent shift with mean values between 1.38 pi and 1.11 pi. Regional uniformity of timing, expressed as synchronization index, varied markedly with interventions (P less than 0.0005). Dyssynchrony was most prominent during caval occlusion with mean values less than 0.6. A simple model of force generation for the two segments visualizes that segment shortening of the transverse segment is of shorter duration than the longitudinal segment and a common mechanism for temporal and spatial non-uniformity within a region could be elaborated. This study quantifies both the time course of shortening and temporal non-uniformity of two cross-oriented segments within the same myocardial region.     

Use of isolated immature-stage B cells to understand negative selection and tolerance induction at the molecular level

Encounter with antigen by newly developing antigen receptor-positive B cells leads to negative selection. This process positions the B cell antigen receptor (BCR) in a central role for initiating the process of negative selection and suggests developmental regulation of its signaling. The observation that immature B cells are more susceptible to negative selection than are mature B cells has been demonstrated in a number of in vitro and in vivo model systems and support the idea of developmental regulation of BCR-initiated responses. Since identical antigen receptors are expressed on immature and mature B cells, the critical fate-determining distinction between these developmental stages must lie downstream of the receptor-ligand interaction itself, in the form of different BCR-linked signaling processes or with different secondary events occurring subsequent to BCR cross-linking. To address the first possibility, our laboratory and others have sought to define the differences in BCR-mediated signal transduction in immature and mature B lymphocytes. In this review article we will discuss current in vitro systems to study this question in primary, nontransformed murine B lymphocytes. In addition, we will discuss our previously published work in order to illustrate how these model systems have been useful in beginning to unravel the molecular basis for immune B cell negative selection and tolerance.     

Does alpha 1-adrenergic blockade influence regional blood flow regulation in hearts with coronary artery occlusion?

The effects of selective alpha 1-adrenergic blockade with doxazosin on regional myocardial tissue blood flow was studied in anaesthetized cats with acute coronary artery occlusion. Reflex tachycardia was prevented by selective beta 1-adrenergic blockade with atenolol and coronary perfusion pressure was kept constant by partial stenosis of the descending aorta. Administration of atenolol reduced cardiac mechanical work-load by its negative inotropic and chronotropic effects, and reduced myocardial tissue blood flow in normally perfused myocardium. This reduction was most pronounced in the endocardial half-layer of the myocardium adjacent to the ischaemic region. Administration of doxazosin in this situation clearly reduced peak systolic and coronary perfusion pressure. But when coronary perfusion pressure was raised to pre-administration values, measurements of regional blood flow revealed no changes either in ischaemic or non-ischaemic myocardium. Also, there was no sign of redistribution of blood flow between endocardial and epicardial tissue in any area. This study, therefore, indicates that alpha 1-adrenoceptors play a minor role in the regulation of coronary blood flow in normal myocardium as well as ischaemic myocardium.     

Preventing Macrovascular Disease in Patients with Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (DM) is associated with an increased risk for both micro-and macrovascular complications, and cardiovascular diseases (CVD) are the most common causes of death in these patients, accounting for almost 70% of the deaths. Given the high prevalence of the condition and the expected global increase in the prevalence of type 2 DM, a case is made for prevention of these serious complications in order to reduce the individual morbidity and the economic burden on society. In this review we present the knowledge of how macrovascular disease in patients with type 2 DM may be prevented, and suggest possible strategies for doing so. A thorough search of the published literature was conducted and we first present relevant epidemiological studies demonstrating the impact of important risk factors for CVD in DM, such as dyslipidemia, hyperglycemia, hypertension, smoking, familial premature coronary heart disease and some non-classical risk factors such as hyperinsulinemia, insulin resistance, endothelial dysfunction and inflammation. Secondly, we review the results from published randomized controlled clinical trials and meta-analysis of these, evaluate the findings and suggest strategies for preventing CVD in patients with type 2 DM using non-pharmacological and pharmacological approaches. Present knowledge indicates that most patients with type 2 DM either have manifest CVD or have a high risk for future cardiovascular events, men with DM have a 2- to 4-fold; and women with DM a 3- to 5-fold increased risk for cardiovascular death compared with non-diabetic individuals. Care of patients with type 2 DM should include yearly risk assessment by the use of published risk equations or risk charts. On the background of this assessment, an individual risk reducing strategy should be tailored to each patient’s need, including the treatment of hyperglycemia, hypertension and dyslipidemia together with the use of aspirin (acetylsalicylic acid) and ACE inhibitors. Such measures can reduce the risk of cardiovascular events in patients with type 2 DM.     

Caries decline before fluoride toothpaste was available: earlier and greater decline in the rural north than in southwestern Norway

The purpose of this study was to evaluate factors related to caries in 6–17-year-olds in 2 groups of Norwegian counties between 1966 and 1983. The average number of surfaces filled and permanent teeth extracted due to caries declined in the 4 northern counties from 1967. An increase was recorded in the 7 southwestern counties until 1971, then a decline. In the 1960s significantly more surfaces were filled and teeth extracted in the north compared to the southwest. Based on intra-county comparisons, the decline in surfaces treated was greater in the north between 1967 and 1983; 5.4 ± 0.4 vs 3.7 ± 0.7, P < 0.01. The averages were 1.9 surfaces treated in the north and the southwest in 1983. Higher infant mortality, lower percentage of people with completed senior secondary education, and more inhabitants per doctor and per dentist in the north indicate a less favorable situation than in the southwest. School-based fluoride programs had been implemented in both groups from the mid-1960s and around 60% participated when fluoride toothpaste became freely marketed in 1971. More fluoride programs and more fluoride tablets were available to children in the north; this may indicate a preventive attitude among dentists. The decline of caries started at different times in different parts of Norway. In the rural north with the most unfavorable situation, the decline was greater and started years before fluoride toothpaste came on to the market. The early decline may partly be ascribed to the school-based fluoride programs, the continued decline to several factors.     

Workplace Bullying and Suicidal Ideation: A 3-Wave Longitudinal Norwegian Study

Objectives. We examined whether victimization from bullying is related to an increased risk of suicidal ideation over time and whether suicidal ideation is related to subsequent bullying.Methods. In a longitudinal study (2005–2010), we used well-established single-item measures to assess victimization from bullying and suicidal ideation. We used latent Markov models to determine forward and reverse relationships between variables at 3 time points with 2 or 3 years between the measurement points among a randomized nationwide sample of 1846 employees in Norway.Results. Victimization from bullying was associated with subsequent suicidal ideation (odds ratio = 2.05; 95% confidence interval = 1.08, 3.89). Suicidal ideation at baseline was not related to subsequent victimization from workplace bullying.Conclusions. Workplace bullying may be a precursor to suicidal ideation, whereas suicidal ideation seems to have no impact on subsequent risk of being bullied. Regulations against bullying should be integrated into work-related legislation and public health policies.Suicide is a leading cause of death around the globe. Estimates show that more than 800 000 people take their own lives every year.1 In Norway (with a population of 5 165 802) there are about 530 reported suicides every year.2 In the United States, 12 suicide deaths per 100 000 people were reported in 2010, making suicide the 10th leading cause of death among Americans.3 Altogether, 1719 employees committed suicide in US workplaces between 2003 and 2010.4Although psychiatric disorders are involved in the majority of suicide attempts,5 most psychiatric patients do not commit suicide. A psychiatric disorder alone is, therefore, an insufficient condition for suicide.6 To identify other risk factors, we must look beyond the presence of a psychiatric syndrome and understand the underlying factors of suicide and suicidal ideation. Among many potential causes, exposure to workplace bullying has been proposed to be an important predictor of both suicidal ideation and actual suicide.7,8To date, bullying as an antecedent to suicide has been examined only with anecdotal evidence9,10 and cross-sectional research designs.11,12 Einarsen et al.13 established that severely bullied workers were 6 times more likely than nonbullied workers to report suicidal ideations. Sterud et al.8 found that workplace bullying was positively associated with suicidal ideation in a nationwide sample of 1022 Norwegian ambulance personnel. Bullying was more strongly associated with suicidal ideation than were gender, neuroticism, anxiety, somatic complaints, depersonalization, and job dissatisfaction.Cross-sectional research cannot provide adequate evidence for anything more than that suicidal ideation is a correlate of bullying. To understand the directional nature of the association, longitudinal research is needed. In this representative, longitudinal study, we contribute to the literature by examining whether victimization from bullying is related to increased risk of suicidal ideation over time and whether suicidal ideation is related to subsequent bullying.Workplace bullying refers to a situation in which 1 or several individuals persistently perceive themselves to be on the receiving end of negative actions from superiors or co-workers and in which the targets find it difficult to defend themselves against these actions.14,15 Following this definition, there are 3 main characteristics of workplace bullying: (1) an employee becomes the target of systematic negative and unwanted social behavior in the workplace; (2) the exposure occurs over a prolonged period, often with ever more escalating intensity and frequency in the attacks; and (3) targets feel they cannot easily escape the situation or stop the unwanted treatment. This third characteristic, the feeling of being victimized by the harassment, distinguishes bullying from other forms of mistreatment in the workplace.15 Globally, about 11% of workers perceive themselves as victims of bullying,16 and 5% of the Norwegian working population is victimized by bullying at any time.17The interpersonal theory of suicide (ITS)5 provides a theoretical foundation for how exposure to such bullying may be related to suicide. The theory posits that fundamental to suicidal ideation and behavior is that an individual has both the desire and the ability to die by suicide.18 With regard to the desire to die, displayed through suicidal ideation, the ITS asserts that when people over a prolonged period perceive themselves to be socially alienated from others and simultaneously feel that they are a burden on others, they develop a desire for death.19 As for the ability to commit suicide, displayed through suicidal behavior, the ITS proposes that people who are repeatedly exposed to painful and provocative events will lose any fear of pain, injury, and death and thereby be able to overcome the instinct of self-preservation.Because of its focus on persistent exposure to painful events and social alienation, the ITS strongly suggests that repeated and long-term exposure to negative treatment and social exclusion from one’s peers or supervisors at work constitutes a risk factor for suicidal ideation and behavior.Although previous research has assumed bullying to be an antecedent to suicidal ideation, it is possible that the established cross-sectional association reflects a relationship in which suicidal ideation is a precursor to bullying. Two different mechanisms can explain such a reverse association. First, employees with suicidal ideation may report less favorable work characteristics because their distress makes them evaluate their work environment increasingly more negatively.20 Second, employees with suicidal ideations may elicit aggressive behavior in others because their psychological state creates aversive feelings among co-workers and supervisors.21,22To provide better indications of how workplace bullying is related to suicidal ideation, we investigated direct forward and reverse associations with longitudinal data. We tested the following hypotheses:

• Hypothesis 1: Victimization from bullying is associated with an increased risk of later suicidal ideation.
• Hypothesis 2: Suicidal ideation is associated with an increased risk of later victimization from bullying.

     

Relationship between blood pressure and in vivo action of insulin in type II (non-insulin-dependent) diabetic subjects.

In nondiabetic hypertensive subjects, a relationship has been found between insulin resistance and level of blood pressure. Since type II (non-insulin-dependent) diabetic subjects are often both insulin-resistant and hypertensive, we studied the relationship between insulin resistance and blood pressure level in a group of patients with type II diabetes. Fourteen women and 19 men with diabetes for 2 to 14 (mean, 7.4) years, treated with diet alone (five subjects) or combined with hypoglycemic agents, were studied. Their average hemoglobin A1c (HbA1c) levels during the study period were 6.6% to 11.7% (mean, 8.6%), and their body mass indexes (BMI) were 20.8 to 33.1 (mean, 26.3) kg/m2. Insulin sensitivity was measured using the hyperinsulinemic, euglycemic glucose clamp technique, and an insulin-sensitivity index was calculated as the ratio of the glucose disposal rate (GDR) to the insulin concentration during clamp (GDR/I). The average of three to eight measurements of diastolic blood pressure (DBP) during the study period (9 to 24 months) in each subject was 79 to 111 (mean, 95.1) mm Hg, and DBP also showed significant correlations to BMI (r = .54) and fasting C-peptide level (r = .38). In a multiple regression model, GDR/I, antihypertensive treatment, and known duration of diabetes were significant and independent predictors of variations in blood pressure, and GDR/I could account for 35% of the observed variations in DBP. We conclude that, in accordance with what has been found in nondiabetic hypertensives, DBP correlates significantly to insulin resistance in type II diabetic subjects.