Acute Stress Desensitizes Hypothalamic CRH Neurons to Norepinephrine and Physiological Stress

ABSTRACTNoradrenergic afferents to corticotropin releasing hormone (CRH) neurons of the hypothalamic paraventricular nucleus (PVN) provide a major excitatory drive to the hypothalamic-pituitary-adrenal (HPA) axis via α1 adrenoreceptor activation. The ascending noradrenergic afferents are recruited preferentially by physiological, rather than psychological, stress modalities.Glucocorticoids secreted in response to HPA activation feed back onto the hypothalamus to negatively regulate the HPA axis, providing a critical autoregulatory constraint that prevents glucocorticoid overexposure. Whether differential negative feedback mechanisms target stress modality-specific HPA activation is not known. Here, we reveal a desensitization of the α1 adrenoreceptor activation of the HPA axis following acute stress that is mediated by rapid glucocorticoid regulation of adrenoreceptor trafficking. Prior stress desensitized the HPA axis to subsequent physiological, but not psychological, stress. Our findings demonstrate rapid glucocorticoid suppression of adrenoreceptor signaling in CRH neurons that is specific to physiological stress activation, and reveal, therefore, a rapid, modality-selective glucocorticoid feedback mechanism.

Safety and Diagnostic Accuracy of Dobutamine Stress Echocardiography

Exercise and pharmacologic stress echocardiography has been used routinely in clinical practice for the past twenty to thirty years. Dobutamine stress echocardiography (DSE) is well established as a safe, feasible, and accurate modality for detection of myocardial ischemia and prognostication in patients with known or suspected coronary artery disease, particularly when they have limited exercise capacity. Serious side effects during or shortly after DSE are uncommon, with ventricular fibrillation or myocardial infarction occurring in approximately 1 of 2,000 studies. No deaths have been reported. On the basis of a total number of 2,246 patients, reported in 28 studies, the sensitivity, specificity and accuracy of the test for the detection of coronary artery disease (CAD) were 80%, 84% and 81%, respectively. Mean sensitivities for one, two and three-vessel disease were 74%, 86% and 92%, respectively. The sensitivity of detection of disease in the let circumflex coronary artery (55%) was lower, both compared with that for left anterior descending (72%) and right coronary artery disease (76%). The sensitivity of predicting multivessel disease by multiregional echocardiographic abnormalities varied widely, from 8% to 71%. In direct comparisons, DSE was superior to exercise electrocardiography and dipyridamole echocardiography and comparable to exercise echocardiography and radionuclide imaging. DSE is useful, feasible and safe exercise independent stress modality for assessing the presence, localization and extent of CAD.

Ankle Reconstruction in Charcot's Neuroarthropathy: Challenges and Solutions

ABSTRACT Ankle injuries in the presence of neuropathy have potential to cause deformity in the ankle, which can in turn cause ulcerations and infections leading to significant morbidity including loss of limb or even life. These injuries although devastating can start off innocuously and may not be immediately apparent to the patient because of lack of pain. This can lead to a late presentation. Often, the main concern is swelling, for which the patient seeks attention. And even when medical attention is sought, unless the physician is vigilant, the condition can potentially be missed or misdiagnosed as deep vein thrombosis or cellulitis. A sprain or even a fracture in the ankle is not suspected as the patient retains the ability to walk. This condition and its true nature further escapes detection if, as often is the case, a nonweight-bearing radiograph is obtained. Radiographs obtained without the weight-bearing or other stress modality may not reveal the instability at the ankle joint due to ligament damage. A thorough clinical evaluation including assessment for neuropathy and weight-bearing radiographs are necessary for diagnosis. Stable fractures and ankle sprains can be managed conservatively in a cast or boot. Unstable ankle following ligamentous disruption and/or fractures in the vicinity of the ankle needs internal or external stabilization. The stabilization in the presence of neuropathy should be stronger and the protection from weight bearing last longer and twice that used for patients with similar condition but without neuropathy. How to cite this article Panchbhavi VK. Ankle Reconstruction in Charcot's Neuroarthropathy: Challenges and Solutions. J Foot Ankle Surg (Asia-Pacific) 2016;3(2):65-70.

Ischaemic heart disease

Echocardiography with its multiple modalities plays a central role in the evaluation of patients with known or suspected coronary artery disease, starting from the differential diagnosis of the patient presenting with acute chest pain. In the patient presenting with acute myocardial infarction (raised troponins) whether it is with ST-segment elevation or without, echocardiography is the first imaging modality used in order to ascertain the presence and extent of LV dysfunction and the presence of complications. In the absence of myocardial infarction (negative troponins), echocardiography will play an important diagnostic role in identifying the presence of reversible myocardial ischaemia. Stress echocardiography in many institutions is now the preferred stress modality associated with imaging as it is cost-effective and does not use ionizing radiation. Finally, echocardiography plays a pivotal role in the assessment of myocardial viability since the presence and extent of viable myocardium may guide therapeutic strategies. It has been stressed that laboratories and individuals need to have experience and be accredited by the authorities so that the results of echocardiographic investigations will be credible.