Sweet's syndrome as a dermatological manifestation of underlying coronary artery disease

SummaryWe report an unusual case of a 50-year-old female with no significant past medical history who reported with a sudden eruption of painful erythematous papules accompanied by fever. Clinical and pathological findings were consistent with acute febrile neutrophilic dermatosis (or Sweet's syndrome). Two weeks later, she complained of chest pain and was diagnosed with non-ST elevation myocardial infarction. Coronary angiogram demonstrated stenosis of right coronary artery and left Circumflex artery. Subsequent workup to identify underlying malignant or autoimmune disorders was negative. She refused to undergo percutaneous coronary intervention and was treated conservatively with steroids, resulting in dramatic resolution of skin lesions. Six months later, the patient was readmitted with similar complaints including fever, generalized rash, and chest pain. Electrocardiography demonstrated old infero-lateral wall infarction. Cardiac enzymes were not elevated. Repeat workup failed to identify underlying systemic disorder except coronary artery disease (CAD). She recovered following administration of steroids and continued to receive medical therapy for CAD. This case demonstrates an unusual association between Sweet's syndrome and CAD in an adult female. Sweet's syndrome is considered to be a reactive phenomenon of underlying systemic disorders. Therefore, patients presenting with Sweet's syndrome should be evaluated for CAD, especially in the absence of underlying malignant or autoimmune disorders

Mitochondrial Cardiomyopathy: Pathophysiology, Diagnosis, and Management

Mitochondrial disease is a heterogeneous group of multisystemic diseases that develop consequent to mutations in nuclear or mitochondrial DNA. The prevalence of inherited mitochondrial disease has been estimated to be greater than 1 in 5,000 births; however, the diagnosis and treatment of this disease are not taught in most adult-cardiology curricula. Because mitochondrial diseases often occur as a syndrome with resultant multiorgan dysfunction, they might not immediately appear to be specific to the cardiovascular system. Mitochondrial cardiomyopathy can be described as a myocardial condition characterized by abnormal heart-muscle structure, function, or both, secondary to genetic defects involving the mitochondrial respiratory chain, in the absence of concomitant coronary artery disease, hypertension, valvular disease, or congenital heart disease. The typical cardiac manifestations of mitochondrial disease—hypertrophic and dilated cardiomyopathy, arrhythmias, left ventricular myocardial noncompaction, and heart failure—can worsen acutely during a metabolic crisis. The optimal management of mitochondrial disease necessitates the involvement of a multidisciplinary team, careful evaluations of patients, and the anticipation of iatrogenic and noniatrogenic complications. In this review, we describe the complex pathophysiology of mitochondrial disease and its clinical features. We focus on current practice in the diagnosis and treatment of patients with mitochondrial cardiomyopathy, including optimal therapeutic management and long-term monitoring. We hope that this information will serve as a guide for practicing cardiologists who treat patients thus affected

Hepatopulmonary syndrome - Past to present

Hepatopulmonary syndrome (HPS) is the one of the complication of liver cirrhosis with portal hypertension, irrespective of etiology, age and sex. It has also been observed in non cirrhotic portal hypertension and in acute hepatic conditions. Presence of hypoxemia or abnormal alveolar arterial oxygen tension with intra-pulmonary vasodilation in liver cirrhosis is termed as HPS. Contrast echocardiogram is the better screening tool to demonstrate intrapulmonary shunt. Clinicians should be aware of other common chronic pulmonary and cardiac comorbid conditions, in particular COPD, tuberculosis, bronchial asthma and idiopathic pulmonary fibrosis, etc. which may coexist with HPS. There is no specific clinical finding to diagnose but digital clubbing, cyanosis, dyspnoea, platypnoea, and spider naevi are more common among cirrhosis with HPS. The presence of HPS independently worsens prognosis of cirrhosis. Even though number of mechanisms have been proposed to explain arterial hypoxemia in HPS, role of nitric oxide is the major one along with cytokines. Liver transplantation is the choice of treatment though mortality is comparatively high. There is no still effective recommended medical therapy to reverse this condition and anti cytokine/ nitric oxide inhibitors, etc are under preliminary stage

Hepatitis C virus induced miR200c down modulates FAP-1, a negative regulator of Src signaling and promotes hepatic fibrosis.

Hepatitis C virus (HCV) induced liver disease is the leading indication for liver transplantation (LTx). Reinfection and accelerated development of fibrosis is a universal phenomenon following LTx. The molecular events that lead to fibrosis following HCV infection still remains poorly defined. In this study, we determined microRNA (miRNA) and mRNA expression profiles in livers from chronic HCV patients and normals using microarrays. Using Genego software and pathway finder we performed an interactive analysis to identify target genes that are modulated by miRNAs. 22 miRNAs were up regulated (>2 fold) and 35 miRNAs were down regulated (>2fold) compared to controls. Liver from HCV patients demonstrated increased expression of 306 genes (>3 fold) and reduced expression of 133 genes (>3 fold). Combinatorial analysis of the networks modulated by the miRNAs identified regulation of the phospholipase C pathway (miR200c, miR20b, and miR31through cellular proto-oncogene tyrosine-protein kinase Src (cSrc)), response to growth factors and hormones (miR141, miR107 and miR200c through peroxisome proliferator-activated receptor alpha and extracellular-signal-regulated kinases, and regulation of cellular proliferation (miR20b, miR10b, and miR141 through cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1 p21). Real time PCR (RT-PCR) validation of the miRNA in HCV infected livers demonstrated a 3.3 ±0.9 fold increase in miR200c. In vitro transfection of fibroblasts with miR200c resulted in a 2.2 fold reduction in expression of tyrosine-protein phosphatase non-receptor type 13 or FAS associated phosphatase 1 (FAP-1) and 2.3 fold increase in expression of cSrc. miR200c transfection resulted in significant increases in expression of collagen and fibroblast growth factor (2.8 and 3.4 fold, p<0.05). Therefore, we propose that HCV induced increased expression of miR200c can down modulate the expression of FAP1, a critical regulator of Src and MAP kinase pathway that play an important role in the production of fibrogenic growth factors and development of fibrosis

Increased TGF-β in serum of HCV patients.

<p>We measured the levels of TGF-β in the sera of chronic HCV patients and compared them to normal subjects using a TGF-β ELISA kit. The bars represent the mean ± SD levels of TGF-β concentration. The levels of TGF-β in the sera from chronic HCV patients were significantly elevated when compared to healthy controls (450 vs. 64 µg/ml, p<0.05).</p

Biological networks modulated by the differentially expressed miRNA in chronic HCV.

<p>The biological networks modulated by differentially expressed miRNA following HCV infection was analyzed using the Genego software. Genego analysis of the networks identified: a) regulation of the phospholipase C pathway (miR200c, miR20b, and miR31 through cSrc); b) response to endogenous stimulus of growth factors and hormones (miR141, miR107 and miR200c through PPAR-α and ERK); and c) regulation of cellular proliferation (miR20b, miR10b, and miR141 through p21) as the major biological pathways that are impacted.</p

Pathways modulated in chronic HCV.

<p>RNA from liver biopsies from 8 HCV patients and normal donor livers were isolated using Trizol reagent and miRNA expression profile in the samples were analyzed using Illumina Bead array. The differentially expressed miRNA identified using Partek analysis were grouped based on the biological pathways that could be modulated.</p

Modulation of growth factor signaling cascade in chronic HCV infection.

<p>Liver biopsies were obtained from 10 HCV infected patients with inflammation but no fibrosis, 10 HCV infected patients with grade III/IV fibrosis and 10 patients with NASH. Expression levels of: a) mIR200c; b) FAP-1 and c) cSrc were analyzed by quantitative RT-PCR using pre-developed Taqman miRNA assays. The small RNA U6b was used as an endogenous control and relative miRNA quantity was calculated by the ΔΔCt method. The horizontal line represents the average and standard deviation of fold expression levels in the groups.</p

Transcriptional modulation of biological networks in chronic HCV infection.

<p>Transcriptional modulation of biological networks in chronic HCV infection.</p