Disturbances in calcium metabolism and cardiomyocyte necrosis: the role of calcitropic hormones

A synchronized dyshomeostasis of extra- and intracellular Ca(2+), expressed as plasma ionized hypocalcemia and excessive intracellular Ca(2+) accumulation, respectively, represents a common pathophysiologic scenario that accompanies several diverse disorders. These include low-renin and salt-sensitive hypertension, primary aldosteronism and hyperparathyroidism, congestive heart failure, acute and chronic hyperadrenergic stressor states, high dietary Na(+), and low dietary Ca(2+) with hypovitaminosis D. Homeostatic responses are invoked to restore normal extracellular [Ca(2+)](o), including increased plasma levels of parathyroid hormone and 1,25(OH)(2)D(3). However, in cardiomyocytes these calcitropic hormones concurrently promote cytosolic free [Ca(2+)](i) and mitochondrial [Ca(2+)](m) overloading. The latter sets into motion organellar-based oxidative stress, in which the rate of reactive oxygen species generation overwhelms their detoxification by endogenous antioxidant defenses, including those related to intrinsically coupled increments in intracellular Zn(2+). In turn, the opening potential of the mitochondrial permeability transition pore increases, allowing for osmotic swelling and ensuing organellar degeneration. Collectively, these pathophysiologic events represent the major components to a mitochondriocentric signal-transducer-effector pathway to cardiomyocyte necrosis. From necrotic cells, there follows a spillage of intracellular contents, including troponins, and a subsequent wound healing response with reparative fibrosis or scarring. Taken together, the loss of terminally differentiated cardiomyocytes from this postmitotic organ and the ensuing replacement fibrosis each contribute to the adverse structural remodeling of myocardium and progressive nature of heart failure. In conclusion, hormone-induced ionized hypocalcemia and intracellular Ca(2+) overloading comprise a pathophysiologic cascade common to diverse disorders and that initiates a mitochondriocentric pathway to nonischemic cardiomyocyte necrosis.     

Ocular Leishmaniasis - A systematic review

The incidence of leishmaniasis is reported to be up to 1 million per year. To date, there has been no comprehensive review describing the diversity of clinical presentations of ocular leishmaniasis (OL) and its treatment. This systematic review aims to address this knowledge gap and provide a summary of the clinical presentation, natural course, and treatment options for OL. Our study identified a total of 57 published articles as describing cases of OL involving: adnexa (n = 26), orbit (n = 1), retina (n = 7), uvea (n = 18) and cornea (n = 6). Though well described and easily treated, palpebral leishmaniasis is often misdiagnosed and may lead to chronic issues if untreated. The retinal manifestations of Leishmaniasis consist of self-resolving hemorrhages secondary to thrombocytopenia. Two main uveitis etiologies have been identified: uveitis in the context of active Leishmanial infection (associated with immunosuppression) and uveitis occurring as an immune reconstitution syndrome. Corneal involvement in most geographic areas generally follows an aggressive course, most often ending in corneal perforation if left untreated. In the Americas, a chronic indolent interstitial keratitis may also occur. Topical steroids are of little use in keratitis (systemic antileishmanials being the cornerstone of treatment). However, these are essential in cases of uveitis, with or without concomitant systemic antileishmanial therapy. In conclusion, though ocular involvement in Leishmaniasis is rare, severe sight-threatening consequences follow if left untreated. Early diagnosis, enthusiastic follow-up and aggressive treatment are essential for good outcomes.     

Pulsatile Scalp Swelling

Metastasis from follicular carcinoma is usually blood-borne. Here, we present a case of skull metastasis with intracranial extension presenting as a pulsatile scalp swelling from the follicular thyroid carcinoma.     

Early use of MRI improves diagnostic accuracy in young adults with stroke

ObjectivesThe misdiagnosis of acute ischemic stroke in young adults is a significant problem since patients may have many decades of potential disability. Also, proven therapies for acute stroke may not be administered if there is an initial misdiagnosis. We assessed the hypothesis that early use of MRI, arrival by ambulance, and presentation to a Primary Stroke Center (PSC) would be associated with a reduced rate of misdiagnosis.MethodsA prospective database of young adults (ages 16–49 years) with ischemic stroke (final diagnosis provided by vascular neurologists) was reviewed. We collected information on several variables, including age, race, arrival by ambulance, whether brain MRI was performed within 48 h, and initial presentation to a PSC. Variables were tested against emergency department (ED) misdiagnosis using univariate and multivariate methods.Results77 patients with a mean age of 37.9 years were reviewed. 48.3% of patients arrived by ambulance, 53.2% had a brain MRI within 48 h, and 23.4% initially presented to a PSC. The overall rate of ED misdiagnosis was 14.5%. In multivariate testing, performance of MRI within 48 h (p = 0.023) was associated with a lower rate of misdiagnosis and age < 35 years was linked with greater likelihood of misdiagnosis (p = 0.047).ConclusionsEarly performance of MRI leads to greater accuracy of stroke diagnosis in young adults presenting to the ED. Patients less than age 35 years have a greater risk of misdiagnosis. ED physicians and neurologists should consider early use of MRI in young adults with stroke-like deficits and diagnostic uncertainty.     

Risk factors for maternal mortality in Delhi slums: a community-based case-control study

BACKGROUND: In order to develop, implement and evaluate policy for reducing maternal mortality, it is essential to study the risk factors associated with maternal deaths. AIMS: The study aims to determine the epidemiological risk factors and its related causes associated with maternal deaths in Delhi slums. MATERIALS AND METHODS: A community-based case-control study was designed, wherein snowball-sampling method was used to identify the maternal deaths (cases) in the community and circular systematic random sampling procedure was used to select the controls from the same area where a maternal death was found. STATISTICAL ANALYSIS: Data on 70 cases and 384 controls that had live births as the outcome of the pregnancy were analyzed. Logistic regression was applied to identify the risk factors. RESULTS: In the study population, most of the deliveries were conducted at home by untrained 'dais.' Cases were mostly illiterate, young, having high parity and no antenatal care taken during pregnancy (P CONCLUSIONS: The study findings suggest that women should be educated about the importance of antenatal registration and regular checkups. Untrained 'dais' should be trained to recognize the obstetric complications at an early stage and refer high-risk cases for adequate management. These preventive measures could help in reducing maternal mortality at the community level.