Molecular genetics of sudden cardiac death in small animals - A review

Sudden cardiac death in small animals is uncommon but often occurs due to cardiac conduction defects or myocardial diseases. Primary cardiac conduction defects are mainly caused by mutations in genes involved in impulse conduction processes (e.g., gapjunction genes and transcription factors) or repolarisation processes (e.g., ion-channel genes), whereas primary cardiomyopathies are mainly caused by defective force generation or force transmission due to gene mutations in either sarcomeric or cytoskeleton proteins. Although over 50 genes have been identified in humans directly or indirectly related to sudden cardiac death, no genetic aetiologies have been identified in small animals. Sudden cardiac deaths have been also reported in German Shepherds and Boxers. A better understanding of molecular genetic aetiologies for sudden cardiac death will be required for future study toward unveiling actiology in sudden cardiac death in small animals. (c) 2005 Elsevier Ltd. All rights reserved.

The effect of provocation in the form of mild erotica on attitude to the ad and corporate image: Differences between cause-related and product-based advertising

Provocative advertising is characterized by a deliberate attempt to gain attention through shock. This research investigates the reactions of individuals to a provocative appeal for a cause as opposed to a provocative advertisement for a standard consumer product, using mild erotica as the element of provocative imagery. An experiment using 391 adult subjects was conducted, and two analyses were performed. The first examined the effect of stimulus type (mildly erotic/nonerotic) by product category (cause appeal/consumer product) on attitude to the ad. The second examined the effect of stimulus type (mildly erotic/nonerotic) by cause (AIDS [acquired immunodeficiency syndrome]/SIDS [sudden infant death syndrome]) on corporate image. Both analyses also included gender as a third independent variable. The results suggest that people prefer mildly erotic ads generally, that an organization using mild erotica in appeals for a cause will be viewed more favorably where the erotica is congruent with the cause, and that women may be more responsive to mild erotica in cause appeals than are men.

Metformin and serious adverse effects

Metformin, a biguanide derivative, has been used in the treatment of type 2 diabetes for nearly 50 years. It acts as an insulin-sensitising agent, lowering fasting plasma insulin concentrations by inducing greater peripheral uptake of glucose, as well as decreasing hepatic glucose output. In 1998, the United Kingdom Prospective Diabetes Study reported that, in overweight patients with type 2 diabetes, treatment with metformin compared with diet alone resulted in statistically significant absolute risk reductions (ARRs) in all-cause mortality (ARR, 7%), diabetes-related deaths (ARR, 5%), any diabetes-related endpoint (ARR, 10%), and macrovascular disease (myocardial infarction, sudden death, angina, stroke, peripheral vascular disease).1 This was achieved without hypoglycaemia or weight gain. As a result, metformin is now regarded as the oral hypoglycaemic agent of choice in the treatment of overweight people with type 2 diabetes.

CHARMed - the effects of candesartan in heart failure

The Candesartan in Heart failure: Assessment of Reduction in Mortality and mortality (CHARM) programme has already shown that candesartan is an effective alternative to angiotensin-converting enzyme (ACE) inhibitors (CHARM-Alternative), that additional benefits can be achieved by adding candesartan to ACE inhibitors (CHARM-Added), and that in patients with a preserved cardiac output there are reduced hospital admissions (CHARM-Preserved). Further recent analysis of the CHARM programme has shown that of the cardiovascular deaths, the benefit of candesartan was due to a reduction in sudden death and progressive heart failure, and that these reductions were observed in the -Alternative and -Added but not -Preserved components. Combination of the CHAR M-Alternative and -Added trials confirmed this reduction of cardiovascular deaths, and also demonstrated that candesartan reduced hospital admissions. There were also improvements in the New York Heart Association functional class of heart failure in the -Alternative and -Added, but not -Preserved, components of CHARM. The benefits of candesartan in heart failure are maintained in the presence of an ACE inhibitor and P-blocker. So far, all of the findings with candesartan in the CHARM programme have been favourable/CHARMed, although the beneficial effects in patients with a preserved cardiac output are limited.

Is exercise good for you?

Physical activity can significantly reduce the risk of cardiovascular disease, diabetes, some forms of cancer, osteoporosis, obesity, falls and fractures, and some mental health problems. While the benefits of physical activity are clear, there is a slightly increased risk of sudden death while exercising (compared with while sedentary), especially in untrained people undertaking unaccustomed vigorous activity. Routine exercise testing yields a significant number of false-positive results, and has not been shown to prevent exercise-related acute cardiac events. There is no convincing evidence that exercise is itself associated with osteoarthritis, but significant joint injury which occurs during sport is associated with an increased risk of subsequent development of osteoarthritis.

Simulation of Brugada syndrome using cellular and three-dimensional whole-heart modeling approaches

Brugada syndrome (BS) is a genetic disease identified by an abnormal electrocardiogram ( ECG) ( mainly abnormal ECGs associated with right bundle branch block and ST-elevation in right precordial leads). BS can lead to increased risk of sudden cardiac death. Experimental studies on human ventricular myocardium with BS have been limited due to difficulties in obtaining data. Thus, the use of computer simulation is an important alternative. Most previous BS simulations were based on animal heart cell models. However, due to species differences, the use of human heart cell models, especially a model with three-dimensional whole-heart anatomical structure, is needed. In this study, we developed a model of the human ventricular action potential (AP) based on refining the ten Tusscher et al (2004 Am. J. Physiol. Heart Circ. Physiol. 286 H1573 - 89) model to incorporate newly available experimental data of some major ionic currents of human ventricular myocytes. These modified channels include the L-type calcium current (ICaL), fast sodium current (I-Na), transient outward potassium current (I-to), rapidly and slowly delayed rectifier potassium currents (I-Kr and I-Ks) and inward rectifier potassium current (I-Ki). Transmural heterogeneity of APs for epicardial, endocardial and mid-myocardial (M) cells was simulated by varying the maximum conductance of IKs and Ito. The modified AP models were then used to simulate the effects of BS on cellular AP and body surface potentials using a three-dimensional dynamic heart - torso model. Our main findings are as follows. (1) BS has little effect on the AP of endocardial or mid-myocardial cells, but has a large impact on the AP of epicardial cells. (2) A likely region of BS with abnormal cell AP is near the right ventricular outflow track, and the resulting ST-segment elevation is located in the median precordium area. These simulation results are consistent with experimental findings reported in the literature. The model can reproduce a variety of electrophysiological behaviors and provides a good basis for understanding the genesis of abnormal ECG under the condition of BS disease.

Medicalizing meaning: demoralization syndrome and the desire to die

Objective: To critically analyse the proposed new psychiatric condition, demoralization syndrome, and the implications drawn by its proponents for the clinical-ethical status of requests by terminally ill patients for assistance to die. Method: The diagnostic features of demoralization syndrome, a proposed new psychiatric disorder, recognizable particularly in palliative care settings, are summarized. The consequences of proposed therapeutic interventions are described, one of which is relief of the desperation which motivates some demoralized patients to consider ending their lives and to seek assistance in dying. The connections between the proposed condition and the desire to die are analysed in the context of the continuing tensions surrounding the ontological status and sociopolitical implications of psychiatric categories and the pervasive medicalization of modern life. Results: The analysis suggests that by medicalizing existential cognitions at the end of life, the proposed diagnostic category also normalizes a particular moral view concerning assistance in dying. Conclusions: While further research into the issues described in this provisional syndrome may benefit some patients, the categorization of demoralization as a medical diagnosis is a questionable extension of psychiatry's influence, which could serve particular social, political and cultural views concerning the end of life.