Tripartite motif-containing 55 identified as functional candidate for spontaneous cardiac hypertrophy in the rat locus cardiac mass 22

BACKGROUND: Left ventricular (LV) hypertrophy is a risk factor for cardiovascular death, but the genetic factors determining LV size and predisposition to hypertrophy are not well understood. We have previously linked the quantitative trait locus cardiac mass 22 (Cm22) on chromosome 2 with cardiac hypertrophy independent of blood pressure in the spontaneously hypertensive rat. From an original cross of spontaneously hypertensive rat with F344 rats, we derived a normotensive polygenic model of spontaneous cardiac hypertrophy, the hypertrophic heart rat (HHR) and its control strain, the normal heart rat (NHR).

METHODS AND RESULTS: To identify the genes and molecular mechanisms underlying spontaneous LV hypertrophy we sequenced the HHR genome with special focus on quantitative trait locus Cm22. For correlative analyses of function, we measured global RNA transcripts in LV of neonatal HHR and NHR and 198 neonatal rats of an HHR × NHR F2 crossbred population. Only one gene within locus Cm22 was differentially expressed in the parental generation: tripartite motif-containing 55 (Trim55), with mRNA downregulation in HHR (P < 0.05) and reduced protein expression. Trim55 mRNA levels were negatively correlated with LV mass in the F2 cross (r = -0.16, P = 0.025). In exon nine of Trim55 in HHR, we found one missense mutation that functionally alters protein structure. This mutation was strongly associated with Trim55 mRNA expression in F2 rats (F = 10.35, P < 0.0001). Similarly, in humans, we found reduced Trim55 expression in hearts of subjects with idiopathic dilated cardiomyopathy.

CONCLUSION: Our study suggests that the Trim55 gene, located in Cm22, is a novel candidate gene for polygenic LV hypertrophy independent of blood pressure.

Social determinants of health in the setting of hypertrophic cardiomyopathy.

Social determinants of health play an important role in explaining poor health outcomes across many chronic disease states. The impact of the social gradient in the setting of an inherited heart disease, hypertrophic cardiomyopathy (HCM), has not been investigated. This study sought to profile the socioeconomic status of patients attending a specialized multidisciplinary clinic and to determine the impact on clinical factors, psychosocial wellbeing and adherence to medical advice.

Intrinsic resistance of female hearts to an ischemic insult is abrogated in primary cardiac hypertrophy

Important sex differences in cardiovascular disease outcomes exist, including conditions of hypertrophic cardiomyopathy and cardiac ischemia. Studies of sex differences in the extent to which load-independent (primary) hypertrophy modulates the response to ischemia-reperfusion (I/R) damage have not been characterized. We have previously described a model of primary genetic cardiac hypertrophy, the hypertrophic heart rat (HHR). In this study the sex differences in HHR cardiac function and responses to I/R [compared to control normal heart rat (NHR)] were investigated ex vivo. The ventricular weight index was markedly increased in HHR female (7.82 ± 0.49 vs. 4.80 ± 0.10 mg/g; P < 0.05) and male (5.76 ± 0.22 vs. 4.62 ± 0.07 mg/g; P < 0.05) hearts. Female hearts of both strains exhibited a reduced basal contractility compared with strain-matched males [maximum first derivative of pressure (dP/dtmax): NHR, 4,036 ± 171 vs. 4,258 ± 152 mmHg/s; and HHR, 3,974 ± 160 vs. 4,540 ± 259 mmHg/s; P < 0.05]. HHR hearts were more susceptible to I/R (I = 25 min, and R = 30 min) injury than NHR hearts (decreased functional recovery, and increased lactate dehydrogenase efflux). Female NHR hearts exhibited a significantly greater recovery (dP/dtmax) post-I/R relative to male NHR (95.0 ± 12.2% vs. 60.5 ± 9.4%), a resistance to postischemic dysfunction not evident in female HHR (29.0 ± 5.6% vs. 25.9 ± 6.3%). Ventricular fibrillation was suppressed, and expression levels of Akt and ERK1/2 were selectively elevated in female NHR hearts. Thus the occurrence of load-independent primary cardiac hypertrophy undermines the intrinsic resistance of female hearts to I/R insult, with the observed abrogation of endogenous cardioprotective signaling pathways consistent with a potential mechanistic role in this loss of protection.

A review of clozapine safety

Clozapine is a distinctive antipsychotic agent, having a unique clinical profile and an idiosyncratic safety profile. More so than with other agents, the weighting of its adverse event profile is critical, in order to counterbalance its clear clinical advantages. The safety issues with clozapine are in a number of areas, some of which are considered medical emergencies and potentially life-threatening. These include haematological (neutropenia and agranulocytosis), CNS (seizures), cardiovascular (myocarditis and cardiomyopathy), metabolic (diabetes), gastrointestinal and neuromuscular. Understanding the safety profile of clozapine allows an informed use of the agent that can maximise its clear clinical benefit and minimise the known risks.

Visual impairment and eye care among Alaska native people

Purpose: To estimate the prevalence of visual impairment, eye disease and eye care in the Alaska Native (AN) population, by demographic and socioeconomic factors.

Methods: Population-based cross-sectional study of 3,793 AN adults aged 18–94 years enrolled in the Education and Research Towards Health (EARTH) Study from March 2004–March 2006. Data on self-reported visual impairment, cataract, glaucoma, diabetic eye disease and previous dilated eye examinations were collected using audio computer-assisted self-administered questionnaires.

Results: The unadjusted prevalence of self-reported visual impairment was 8.7% (95% confidence interval (CI): 7.9–9.7), cataract 5.9% (95% CI: 5.2–6.7), glaucoma 2.5% (95% CI: 2.0–3.0) and diabetic eye disease 1.3% (95% CI: 0.9–1.7). In all cases, age-sex adjusted prevalence estimates for the AN population were greater than available estimates for the general U.S. population. Prevalence of visual impairment and each eye disease increased with age (P < 0.01). Additional factors associated with visual impairment were education and annual household income. Overall, 70.0% (95% CI: 68.5–71.6) of participants reported a dilated eye examination within the previous two years. Dilated eye examination within the previous two years was associated with increasing age (P < 0.001). However, men and participants with lower formal education were less likely to report recent dilated eye examination. Among those with diabetes, only 67.7% (95% CI: 60.8–74.1) reported a dilated eye examination within the recommended previous one year.

Conclusions: Self-reported visual impairment, cataract, glaucoma and diabetic eye disease are prevalent in the AN population. These data may be useful in healthcare planning and education programs.

Psychosocial risk factors for coronary heart disease: a consensus statement from the National Heart Foundation of Australia

In 2003, the National Heart Foundation of Australia published a position statement on psychosocial risk factors and coronary heart disease (CHD). This consensus statement provides an updated review of the literature on psychosocial stressors, including chronic stressors (in particular, work stress), acute individual stressors and acute population stressors, to guide health professionals based on current evidence. It complements a separate updated statement on depression and CHD.

Perceived chronic job strain and shift work are associated with a small absolute increased risk of developing CHD, but there is limited evidence regarding their effect on the prognosis of CHD. Evidence regarding a relationship between CHD and job (in)security, job satisfaction, working hours, effort-reward imbalance and job loss is inconclusive.

Expert consensus is that workplace programs aimed at weight loss, exercise and other standard cardiovascular risk factors may have positive outcomes for these risk factors, but no evidence is available regarding the effect of such programs on the development of CHD.

Social isolation after myocardial infarction (MI) is associated with an adverse prognosis. Expert consensus is that although measures to reduce social isolation are likely to produce positive psychosocial effects, it is unclear whether this would also improve CHD outcomes. Acute emotional stress may trigger MI or takotsubo ("stress") cardiomyopathy, but the absolute increase in transient risk from an individual stressor is low. Psychosocial stressors have an impact on CHD, but clinical significance and prevention require further study.

Awareness of the potential for increased cardiovascular risk among populations exposed to natural disasters and other conditions of extreme stress may be useful for emergency services response planning. Wider public access to defibrillators should be available where large populations gather, such as sporting venues and airports, and as part of the response to natural and other disasters.

Effect of exercise training on left ventricular remodeling in diabetic patients with diastolic dysfunction: rationale and design

This study will examine the effects of combined aerobic and resistance training on left ventricular remodeling in diabetic patients with diastolic dysfunction. This is the first randomized controlled trial to look for effects of combined strength training and aerobic exercise on myocardial function as well as other clinical, functional, or psychological parameters in diabetic patients with isolated diastolic dysfunction, and will provide important insights into the potential management strategies for heart failure with preserved ejection fraction.

Prevalence of cardiovascular and metabolic events in patients prescribed clozapine: a retrospective observational, clinical cohort study

BACKGROUND: The efficacy of clozapine for the treatment of schizophrenia has been demonstrated. However, a range of adverse events have been associated with its use. To date, there remains a paucity of data regarding the prevalence of clozapine-induced cardiovascular (CV) and parameters associated with the development of metabolic syndrome, alongside associated risk factors for their development. METHODS: An observational, clinical cohort study design of 355 clozapine patients who were enrolled in the Barwon Health Clozapine Program at Geelong Hospital, Victoria, Australia, between 2008-12. Medical records were accessed retrospectively. Multivariate logistic regression was used to determine associations with adverse event(s). RESULTS: Older age of commencement with clozapine was consistently associated with increased risk of CV abnormalities, with the exception of tachycardia where older age was protective (Odds Ratio [OR]: 0.97; 95% Confidence Intervals [CI]: 0.95, 0.99). Males had significantly greater odds of most metabolic disturbances with the exception of being obese (BMI: ≥30 OR: 0.45; 95% CIs: 0.24, 0.85). Older age of commencement was a significantly associated variable with High- Density Lipoprotein-cholesterol (OR: 1.03; 95% CIs: 1.01, 1.07) and fasting glucose (OR:1.04; 95% CIs: 1.02, 1.07). An increase in BMI was consistently and significantly associated with all metabolic events. CONCLUSION: Male patients who are obese at any point during treatment and older at treatment commencement may be the most vulnerable to adverse CV and metabolic events. While future studies using a matched case-control design may be required to verify these findings, we recommend that treating clinicians consider these risks when assessing patient suitability to clozapine therapy.

Pan & zoom

PAN & ZOOM take the effects inscribe in the global language of cinema and turn them into performative and participatory image-making apparatuses. Jondi Keane & Kaya Barry’s installation invites visitors to collaborate in the construction of the images in order to re-explore relations between media technologies and embodied experience. The result is an expanded, amplified and dilated experience of the performative power of image-making and image-viewing. .. PAN activates an accumulating collection of moving panoramic images – provided by Kaya Barry and PSi Fluid States participants from around the world – that one may interactively inhabit. The visitor manipulates relationships between an image projector mounted upon a dolly-track and a ‘trackpad’ that scrolls the projected panorama. The live event of constructing-perceiving panoramic tracking shots open up in ways that expand sensory experience beyond usual peripheries. ZOOM co-opts the ‘dolly-zoom’ effect in cinema, wherein the camera zooms in while moving backwards, or zooms out while moving forwards, resulting in the image expanding to amplify an intense moment of realisation. Keane pulls apart the double movement of the camera effect by himself performing the pulling back and forth of a moving wall as backdrop. Moments of realisation are created between visitors who take up camera operation and as an improvising actor’s role, to accompany Keane’s durational wall moving. An updating collection of short videos were made over the exhibition period shown on one of the installation screen

Cardiovascular alterations and management

This chapter reviews the support of cardiovascular function in the face of
many compromises to the system. It focuses on two of the most prevalent and fatal diseases affecting the heart: coronary heart disease and heart failure. These diseases are also a common comorbidity in elderly patients admitted to critical care units. The first section on coronary heart disease reviews the pathophysiological concepts of myocardial ischaemia and associated complications, with detailed consideration of the clinical implications, assessment and associated management. Heart failure is discussed in terms of the body’s compensatory mechanisms and the clinical sequelae and associated clinical features of heart failure. Nursing and medical management is outlined including the management of acute exacerbations of heart failure. Finally, other cardiovascular disorders commonly managed in critical care units are reviewed, ranging from other forms of heart failure to hypertensive emergencies and aortic aneurysms. The case study presented at the end of the chapter highlights the key aspects of the management of coronary heart disease and heart failure in patients admitted to critical care units.

Vasodilatory effects of homologous adrenomedullin 2 and adrenomedullin 5 on isolated blood vessels of two species of eel

In mammals, adrenomedullin (AM) is a potent vasodilator through signalling pathways that involve the endothelium. In teleost fishes, a family of five AMs are present (AM1/4, AM2/3 and AM5) with four homologous AMs (AM1, AM2/3 and AM5) recently cloned from the Japanese eel, Anguilla japonica. Both AM2 and AM5 have been shown to be strong in vivo vasodepressors in eel, but the mechanism of action of homologous AMs on isolated blood vessels has not been examined in teleost fish. In this study, both eel AM2 and AM5 caused a marked vasodilation of the dorsal aorta. However, only AM5 consistently dilated the small gonadal artery in contrast to AM2 that had no effect in most preparations. Neither AM2 nor AM5 had any effect when applied to the first afferent branchial artery; in contrast, eel ANP always caused a large vasodilation of the branchial artery. In the dorsal aorta, indomethacin significantly reduced the AM2 vasodilation, but had no effect on the AM5 vasodilation. In contrast, removal of the endothelium significantly enhanced the AM5 vasodilation only. In the gonadal artery, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ) significantly reduced the AM5 vasodilation suggesting a role for soluble guanylyl cyclase in the dilation, but l-NNA and removal of the endothelium had no effect. The results of this study indicate that AM2 and AM5 have distinct vasodilatory effects that may be due to the peptides signalling via different receptors to regulate vascular tone in eel.

Screening for diabetic retinopathy using a non-mydriatic retinal camera in rural Victoria

PURPOSE: To develop a screening programme for the early detection of diabetic retinopathy using non-mydriatic retinal photography. METHODS: A community based screening service was offered to all people with known diabetes mellitus in selected townships in the LaTrobe and Goulburn Valleys in Victoria. At the local examination centre, basic sociodemographic information was collected as well as details of previous use of eye care services for the early detection of diabetic retinopathy. The examination included visual acuity (VA), glycosylated haemoglobin level and Polaroid photographs of each fundus using a Canon CR5-45NM non-mydriatic retinal camera (Canon, Tochigiken, Japan). Dilating drops were not used. Photographs were subsequently reviewed and letters were sent to all participants (with copies to their general practitioners) with recommendations for appropriate follow up. RESULTS: A total of 1177 people with diabetes attended the screening service, which is estimated to be 40% of the total population with known diabetes in the study area. The mean age was 65 years (range 20-94 years); 559 (48%) people reported not having a dilated fundus examination within the past 2 years; 345 (29%) people had never had a dilated fundus examination. Of the 2354 eyes, 2126 (90%) of the photographs were gradable. A total of 704 people (60%) had normal VA and no evidence of diabetic retinopathy, 209 people (18%) had diabetic retinopathy, 101 people (9%) had evidence of other fundus pathology, 42 people (3%) had reduced acuity (< 6/18) in one or both eyes (with no fundus pathology evident) and 121 people (10%) had ungradable photographs in one or both eyes. CONCLUSIONS: The present study demonstrates the usefulness of a screening programme with non-mydriatic retinal photography as an adjunct to current eye care services for the early detection of diabetic retinopathy.

Use of eye care services by people with diabetes: the Melbourne Visual Impairment Project

AIM: The use of eye care services by people with and without diabetes was investigated in the Melbourne Visual Impairment Project (VIP), a population based study of eye disease in a representative sample of Melbourne residents 40 years of age and older. METHODS: A comprehensive interview was employed to elicit information on history of diabetes, medication use, most recent visit to an ophthalmologist and optometrist, and basic demographic details. Presence and extent of diabetic retinopathy was determined by dilated fundus examination. RESULTS: The Melbourne VIP comprised 3271 people who ranged in age from 40 to 98 years; 46.2% of them were male. Of 3189 people who had the fundus examination and knew their diabetes status, 162 (5.1%) reported having been previously diagnosed with diabetes and, of these, 37 (22.2%) were found to have diabetic retinopathy. Seven people (4.3%) had developed diabetes before age 30. The mean duration of diabetes was 9.2 years. People with diabetes were significantly more likely to have visited an ophthalmologist ever or in the past 2 years than people without diabetes. However, 31.8% of people with diabetes had never visited an ophthalmologist. The proportion of people who had never seen an ophthalmologist was 47.1% for people without diabetes, 34.2% for people with diabetes but without diabetic retinopathy, and 25% for people with diabetic retinopathy. Sixty one per cent of people with diabetic retinopathy had seen an ophthalmologist in the past year and a further 3% within the past 2 years. People with diabetes were not significantly more likely to have visited an optometrist than people without diabetes (p = 0.51). Overall, 37.7% of people with diabetes and 32.9% of people without diabetes had visited an optometrist within the past year (chi 2 = 2.25, 1 df, p = 0.13). Information concerning retinal examinations was available for 135 individuals (83.3% of people with diabetes). Only 74 (54.8%) could recall ever having a dilated fundus examination; 10 (14%) by an optometrist, 62 (86%) by an ophthalmologist, and five (7%) by a general practitioner. Of those 68 people who had seen an ophthalmologist in the past 2 years, 48 (71%) reported a dilated fundus examination during that time. This compares with 28 (43%) reported dilated fundus examinations in the 65 people who had seen an optometrist in the past 2 years. This finding is statistically significant (chi 2 = 10.2, 1 df, p < 0.005). CONCLUSION: These results indicate that nearly half of people with diabetes in Melbourne are not receiving adequate screening or follow up for diabetic retinopathy, despite universal health care.