A case of misdiagnosed arterial thoracic outlet syndrome as primary Raynaud's phenomenon.

Arterial thoracic outlet syndrome (aTOS) is a rare, but potentially, limb-threatening condition that is often misdiagnosed. We present the case of a 29-year-old man who was initially managed under the presumption of primary Raynaud's phenomenon for >1 year before the correct diagnosis of aTOS, and the delay in diagnosis was complicated by substantial distal thromboembolic occlusion. Successful staged treatment included thoracic outlet decompression, subclavian artery aneurysm repair with subclavian-to-axillary bypass, anticoagulation, and an unconventional axillary-to-ulnar artery bypass. This report highlights the diagnostic challenges of aTOS and the importance of considering it in patients with Raynaud's phenomenon and vaso-occlusive symptoms.

Glycosphingolipids in Diabetes, Oxidative Stress, and Cardiovascular Disease: Prevention in Experimental Animal Models.

Diabetes contributes to about 30% morbidity and mortality world-wide and has tidal wave increases in several countries in Asia. Diabetes is a multi-factorial disease compounded by inflammation, dyslipidemia, atherosclerosis, and is sometimes accompanied with gains in body weight. Sphingolipid pathways that interplay in the enhancement of the pathology of this disease may be potential therapeutic targets. Thus, the application of advanced sphingolipidomics may help predict the progression of this disease and therapeutic outcomes in man. Pre-clinical studies using various experimental animal models of diabetes provide valuable information on the role of sphingolipid signaling networks in diabetes and the efficacy of drugs to determine the translatability of innovative discoveries to man. In this review, we discuss three major concepts regarding sphingolipids and diabetes. First, we discuss a possible involvement of a monosialodihexosylceramide (GM3) in insulin-insulin receptor interactions. Second, a potential role for ceramide (Cer) and lactosylceramide (LacCer) in apoptosis and mitochondrial dysfunction is proposed. Third, a larger role of LacCer in antioxidant status and inflammation is discussed. We also discuss how inhibitors of glycosphingolipid synthesis can ameliorate diabetes in experimental animal models.

Head and Neck Cystic Lesions: A Cytology Review of Common and Uncommon Entities.

BACKGROUND: Cystic lesions of the head and neck are a diagnostic challenge since they are seen in the clinical presentation of a wide variety of conditions. Herein, common and uncommon entities that present as cystic lesions in the head and neck are reviewed. SUMMARY: In this study, peer-reviewed articles were selected using the database PubMed, Google, Google Scholar, and Scopus. Emphasis was placed on peer-reviewed articles that discuss the cytomorphology and differential diagnosis of entities that present as cystic lesions of the head and neck. In the anterior neck, both benign and malignant neoplasms can present, including papillary thyroid carcinoma (PTC), thyroid adenomatoid nodule, parathyroid cysts, and thyroglossal cysts. In the lateral neck, branchial cleft cyst, PTC, ectopic thyroid cyst, and squamous cell carcinomas (human papilloma virus and non- human papilloma virus-related) are common. Age over 40 years raises the possibility of malignancy. In the deep neck, mostly benign cystic entities occur such as a pleomorphic adenoma, paraganglioma, schwannoma, branchial cyst, epidermal inclusion cyst, and lymphoepithelial cyst. Lesions with squamous cell features can pose diagnostic dilemmas. CONCLUSION: Cytologic examination of head and neck cysts can provide valuable information regarding the nature of the cystic lesions. Information about anatomic site and clinical history can assist with the differential diagnoses. Ancillary studies can improve the diagnosis in some cases. Each case should be evaluated very carefully since there are a wide variety of congenital conditions, infectious/inflammatory conditions, benign neoplasms, and primary and secondary malignancies presenting as a cystic mass in the head and neck.

Convergence: Lactosylceramide-Centric Signaling Pathways Induce Inflammation, Oxidative Stress, and Other Phenotypic Outcomes.

Lactosylceramide (LacCer), also known as CD17/CDw17, is a member of a large family of small molecular weight compounds known as glycosphingolipids. It plays a pivotal role in the biosynthesis of glycosphingolipids, primarily by way of serving as a precursor to the majority of its higher homolog sub-families such as gangliosides, sulfatides, fucosylated-glycosphingolipids and complex neutral glycosphingolipids-some of which confer "second-messenger" and receptor functions. LacCer is an integral component of the "lipid rafts," serving as a conduit to transduce external stimuli into multiple phenotypes, which may contribute to mortality and morbidity in man and in mouse models of human disease. LacCer is synthesized by the action of LacCer synthase (ß-1,4 galactosyltransferase), which transfers galactose from uridine diphosphate galactose (UDP-galactose) to glucosylceramide (GlcCer). The convergence of multiple physiologically relevant external stimuli/agonists-platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), stress, cigarette smoke/nicotine, tumor necrosis factor-α (TNF-α), and in particular, oxidized low-density lipoprotein (ox-LDL)-on ß-1,4 galactosyltransferase results in its phosphorylation or activation, via a "turn-key" reaction, generating LacCer. This newly synthesized LacCer activates NADPH (nicotinamide adenine dihydrogen phosphate) oxidase to generate reactive oxygen species (ROS) and a highly "oxidative stress" environment, which trigger a cascade of signaling molecules and pathways and initiate diverse phenotypes like inflammation and atherosclerosis. For instance, LacCer activates an enzyme, cytosolic phospholipase A2 (cPLA2), which cleaves arachidonic acid from phosphatidylcholine. In turn, arachidonic acid serves as a precursor to eicosanoids and prostaglandin, which transduce a cascade of reactions leading to inflammation-a major phenotype underscoring the initiation and progression of several debilitating diseases such as atherosclerosis and cancer. Our aim here is to present an updated account of studies made in the field of LacCer metabolism and signaling using multiple animal models of human disease, human tissue, and cell-based studies. These advancements have led us to propose that previously unrelated phenotypes converge in a LacCer-centric manner. This LacCer synthase/LacCer-induced "oxidative stress" environment contributes to inflammation, atherosclerosis, skin conditions, hair greying, cardiovascular disease, and diabetes due to mitochondrial dysfunction. Thus, targeting LacCer synthase may well be the answer to remedy these pathologies.