Emotional stress as a trigger of myasthenic crisis and concomitant takotsubo cardiomyopathy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Myasthenia gravis is a neuromuscular junction post-synaptic autoimmune disorder. Myasthenic crisis is characterized by respiratory failure requiring mechanical ventilation. Takotsubo cardiomyopathy is a rare clinical syndrome defined as a profound but reversible left ventricular dysfunction in the absence of coronary artery disease.</p> <p>Case presentation</p> <p>We report a unique case of a 60-year-old Hispanic woman with myasthenia gravis who developed takotsubo cardiomyopathy and concomitant myasthenic crisis that appear to have been triggered by a stressful life event. On admission, she presented with severe mid-sternal chest pain and shortness of breath shortly after a personally significant stressful life event. A pertinent neurological examination showed bilateral facial weakness and right ptosis. The left ventriculogram showed apical ballooning with hyperdynamic proximal segments with sparing of the apex. Her troponin I level was elevated, while cardiac catheterization revealed no significant coronary artery disease. The findings were consistent with takotsubo cardiomyopathy. Shortly after cardiac catheterization, she developed bilateral ophthalmoparesis and significant bulbar and respiratory muscle weakness. Forced vital capacity values were persistently less than 1 L. The patient developed respiratory failure and required endotracheal intubation. After plasmapheresis and corticosteroid treatment, her clinical course improved with successful extubation. A normal left ventricle chamber size and a normal ejection fraction were noted by an echocardiogram repeated 10 months later.</p> <p>Conclusion</p> <p>This is the first reported case of the simultaneous triggering of both takotsubo cardiomyopathy and myasthenic crisis by the physiologic consequences of a state of severe emotional stress. We hypothesize that the mechanism underlying the rare association of takotsubo cardiomyopathy with myasthenic crisis involves excessive endogenous glucocorticoid release, a high-catecholamine state, or a combination of both. We advocate careful cardiac monitoring of myasthenia gravis patients during acute emotional or physical stress, as there is potential risk of developing takotsubo cardiomyopathy.</p

Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches

Only vulnerable adults show change in chronic low-grade inflammation after contemplative mental training: evidence from a randomized clinical trial.

Growing evidence suggests that chronic low-grade inflammation can be reduced through mindfulness-based mental training interventions. However, these results are inconsistent and based on patient populations with heterogeneous conditions. Similar research in healthy adults is lacking. Moreover, common intervention protocols involve varying combinations of different contemplative practices, such that it remains unclear which types of training most effectively influence biomarkers of inflammation. The present study investigated the effect of three distinct 3-month training modules cultivating a) interoception and present-moment focus (Presence), b) socio-affective skills (Affect), or c) socio-cognitive skills (Perspective) on the inflammatory biomarkers interleukin-6 (IL-6) and high sensitive C-reactive protein (hs-CRP) in 298 healthy adults. We observed no group-level effect of training on either biomarker, but trend-level interactions of training type and participant sex. In additionally exploring the influence of participants' baseline inflammation, a selective training effect emerged: Following the Presence module, participants with relatively higher inflammatory load showed stronger reduction in IL-6 on average, and in hs-CRP if they were male. Mindfulness- and attention-based mental practice thus appears most effective when targeting chronic low-grade inflammation in healthy adults, particularly in men. Overall, our data point to a floor effect in the reduction of inflammatory markers through contemplative mental training, suggesting that mental training may be less effective in improving basal biological health outcomes in healthy, low-stressed adults than in vulnerable populations

Psychoneuroimmunology: application to ocular diseases

Psychoneuroimmunology (PNI) is a relatively new discipline within the field of neuroscience which researches the relationship between emotional states, the central and peripheral nervous systems, and the endocrine and immune systems. Negative psychological states, such as stress, anxiety, and depression, may alter immune system regulation and modulation of peripheral cytokines. A plethora of PNI studies have shown that increased psychological stress and depression are associated with an alteration of immune functioning and worsened health outcomes for many conditions. To date, application of PNI methodology has not been reported for ocular diseases. This article provides an historical perspective on the origins of the rift between the emotional and spiritual from physical aspects of disease. A review of how stress is mediated through sympathetic adrenomedullary and hypothalamic pituitary axis activation with shifts in immunity is provided. The literature which supports spirituality in healing is presented. Finally, ocular diseases which would be most amenable to a PNI approach are discussed

A mixed methods pilot study with a cluster randomized control trial to evaluate the impact of a leadership intervention on guideline implementation in home care nursing

Abstract Background Foot ulcers are a significant problem for people with diabetes. Comprehensive assessments of risk factors associated with diabetic foot ulcer are recommended in clinical guidelines to decrease complications such as prolonged healing, gangrene and amputations, and to promote effective management. However, the translation of clinical guidelines into nursing practice remains fragmented and inconsistent, and a recent homecare chart audit showed less than half the recommended risk factors for diabetic foot ulcers were assessed, and peripheral neuropathy (the most significant predictor of complications) was not assessed at all. Strong leadership is consistently described as significant to successfully transfer guidelines into practice. Limited research exists however regarding which leadership behaviours facilitate and support implementation in nursing. The purpose of this pilot study is to evaluate the impact of a leadership intervention in community nursing on implementing recommendations from a clinical guideline on the nursing assessment and management of diabetic foot ulcers. Methods Two phase mixed methods design is proposed (ISRCTN 12345678). Phase I: Descriptive qualitative to understand barriers to implementing the guideline recommendations, and to inform the intervention. Phase II: Matched pair cluster randomized controlled trial (n = 4 centers) will evaluate differences in outcomes between two implementation strategies. Primary outcome: Nursing assessments of client risk factors, a composite score of 8 items based on Diabetes/Foot Ulcer guideline recommendations. Intervention: In addition to the organization's 'usual' implementation strategy, a 12 week leadership strategy will be offered to managerial and clinical leaders consisting of: a) printed materials, b) one day interactive workshop to develop a leadership action plan tailored to barriers to support implementation; c) three post-workshop teleconferences. Discussion This study will provide vital information on which leadership strategies are well received to facilitate and support guideline implementation. The anticipated outcomes will provide information to assist with effective management of foot ulcers for people with diabetes. By tracking clinical outcomes associated with guideline implementation, health care administrators will be better informed to influence organizational and policy decision-making to support evidence-based quality care. Findings will be useful to inform the design of future multi-centered trials on various clinical topics to enhance knowledge translation for positive outcomes. Trial Registration Current Control Trials ISRCTN0691089

Purinergic signalling and immune cells

This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells

Internalised Values and Fairness Perception: Ethics in Knowledge Management

This chapter argues for ethical consideration in knowledge management (KM). It explores the effect that internalised values and fairness perception have on individuals’ participation in KM practices. Knowledge is power, and organisations seek to manage knowledge through KM practices. For knowledge to be processed, individual employees—the source of all knowledge—need to be willing to participate in KM practices. As knowledge is power and a key constituent part of knowledge is ethics, individuals’ internalised values and fairness perception affect knowledge-processing. Where an organisation claims ownership over knowledge, an individual may perceive being treated unfairly, which may obstruct knowledge-processing. Through adopting ethical KM practices, individual needs are respected, enabling knowledge-processing. Implications point towards an ethical agenda in KM theory and practice

A model for homeopathic remedy effects: low dose nanoparticles, allostatic cross-adaptation, and time-dependent sensitization in a complex adaptive system

BACKGROUND: This paper proposes a novel model for homeopathic remedy action on living systems. Research indicates that homeopathic remedies (a) contain measurable source and silica nanoparticles heterogeneously dispersed in colloidal solution; (b) act by modulating biological function of the allostatic stress response network (c) evoke biphasic actions on living systems via organism-dependent adaptive and endogenously amplified effects; (d) improve systemic resilience. DISCUSSION: The proposed active components of homeopathic remedies are nanoparticles of source substance in water-based colloidal solution, not bulk-form drugs. Nanoparticles have unique biological and physico-chemical properties, including increased catalytic reactivity, protein and DNA adsorption, bioavailability, dose-sparing, electromagnetic, and quantum effects different from bulk-form materials. Trituration and/or liquid succussions during classical remedy preparation create “top-down” nanostructures. Plants can biosynthesize remedy-templated silica nanostructures. Nanoparticles stimulate hormesis, a beneficial low-dose adaptive response. Homeopathic remedies prescribed in low doses spaced intermittently over time act as biological signals that stimulate the organism’s allostatic biological stress response network, evoking nonlinear modulatory, self-organizing change. Potential mechanisms include time-dependent sensitization (TDS), a type of adaptive plasticity/metaplasticity involving progressive amplification of host responses, which reverse direction and oscillate at physiological limits. To mobilize hormesis and TDS, the remedy must be appraised as a salient, but low level, novel threat, stressor, or homeostatic disruption for the whole organism. Silica nanoparticles adsorb remedy source and amplify effects. Properly-timed remedy dosing elicits disease-primed compensatory reversal in direction of maladaptive dynamics of the allostatic network, thus promoting resilience and recovery from disease. SUMMARY: Homeopathic remedies are proposed as source nanoparticles that mobilize hormesis and time-dependent sensitization via non-pharmacological effects on specific biological adaptive and amplification mechanisms. The nanoparticle nature of remedies would distinguish them from conventional bulk drugs in structure, morphology, and functional properties. Outcomes would depend upon the ability of the organism to respond to the remedy as a novel stressor or heterotypic biological threat, initiating reversals of cumulative, cross-adapted biological maladaptations underlying disease in the allostatic stress response network. Systemic resilience would improve. This model provides a foundation for theory-driven research on the role of nanomaterials in living systems, mechanisms of homeopathic remedy actions and translational uses in nanomedicine