Lateral geniculate artery pseudoaneurysm after arthroscopic medial meniscectomy.

Vascular complications after arthroscopy are rare and generally present as transient paresthesia most likely due to nervous injury or vasospasm. Rare cases of genicular artery injuries can occur and generally involve the medial genicular artery due to proximity to the right arthroscopic knee hook. This case, however, represents a rare lateral inferior genicular artery injury resulting in a symptomatic pseudoaneurysm. In addition, during the workup, the best visualization of the pseudoaneurysm was possible using duplex ultrasound. The diagnostic information seen on ultrasound was paramount and superseded the findings from conventional angiography and computed tomography angiography, both of which were nonspecific. In brief, this case not only highlights a rare surgical complication but also emphasizes the importance of duplex ultrasound compared with angiography and computed tomography in the workup of pseudoaneurysms.

An early, reversible cholesterolgenic etiology of diet-induced insulin resistance.

OBJECTIVE: A buildup of skeletal muscle plasma membrane (PM) cholesterol content in mice occurs within 1 week of a Western-style high-fat diet and causes insulin resistance. The mechanism driving this cholesterol accumulation and insulin resistance is not known. Promising cell data implicate that the hexosamine biosynthesis pathway (HBP) triggers a cholesterolgenic response via increasing the transcriptional activity of Sp1. In this study we aimed to determine whether increased HBP/Sp1 activity represented a preventable cause of insulin resistance. METHODS: C57BL/6NJ mice were fed either a low-fat (LF, 10% kcal) or high-fat (HF, 45% kcal) diet for 1 week. During this 1-week diet the mice were treated daily with either saline or mithramycin-A (MTM), a specific Sp1/DNA-binding inhibitor. A series of metabolic and tissue analyses were then performed on these mice, as well as on mice with targeted skeletal muscle overexpression of the rate-limiting HBP enzyme glutamine-fructose-6-phosphate-amidotransferase (GFAT) that were maintained on a regular chow diet. RESULTS: Saline-treated mice fed this HF diet for 1 week did not have an increase in adiposity, lean mass, or body mass while displaying early insulin resistance. Consistent with an HBP/Sp1 cholesterolgenic response, Sp1 displayed increased O-GlcNAcylation and binding to the HMGCR promoter that increased HMGCR expression in skeletal muscle from saline-treated HF-fed mice. Skeletal muscle from these saline-treated HF-fed mice also showed a resultant elevation of PM cholesterol with an accompanying loss of cortical filamentous actin (F-actin) that is essential for insulin-stimulated glucose transport. Treating these mice daily with MTM during the 1-week HF diet fully prevented the diet-induced Sp1 cholesterolgenic response, loss of cortical F-actin, and development of insulin resistance. Similarly, increases in HMGCR expression and cholesterol were measured in muscle from GFAT transgenic mice compared to age- and weight-match wildtype littermate control mice. In the GFAT Tg mice we found that these increases were alleviated by MTM. CONCLUSIONS: These data identify increased HBP/Sp1 activity as an early mechanism of diet-induced insulin resistance. Therapies targeting this mechanism may decelerate T2D development.

Epigenetic basis of diabetic vasculopathy.

Type 2 diabetes mellitus (T2DM) causes peripheral vascular disease because of which several blood-borne factors, including vital nutrients fail to reach the affected tissue. Tissue epigenome is sensitive to chronic hyperglycemia and is known to cause pathogenesis of micro- and macrovascular complications. These vascular complications of T2DM may perpetuate the onset of organ dysfunction. The burden of diabetes is primarily because of a wide range of complications of which nonhealing diabetic ulcers represent a major component. Thus, it is imperative that current research help recognize more effective methods for the diagnosis and management of early vascular injuries. This review addresses the significance of epigenetic processes such as DNA methylation and histone modifications in the evolution of macrovascular and microvascular complications of T2DM.

Laser Capture Microdissection in the Spatial Analysis of Epigenetic Modifications in Skin: A Comprehensive Review.

Each cell in the body contains an intricate regulation for the expression of its relevant DNA. While every cell in a multicellular organism contains identical DNA, each tissue-specific cell expresses a different set of active genes. This organizational property exists in a paradigm that is largely controlled by forces external to the DNA sequence via epigenetic regulation. DNA methylation and chromatin modifications represent some of the classical epigenetic modifications that control gene expression. Complex tissues like skin consist of heterogeneous cell types that are spatially distributed and mixed. Furthermore, each individual skin cell has a unique response to physiological and pathological cues. As such, it is difficult to classify skin tissue as homogenous across all cell types and across different environmental exposures. Therefore, it would be prudent to isolate targeted tissue elements prior to any molecular analysis to avoid a possibility of confounding the sample with unwanted cell types. Laser capture microdissection (LCM) is a powerful technique used to isolate a targeted cell group with extreme microscopic precision. LCM presents itself as a solution to tackling the problem of tissue heterogeneity in molecular analysis. This review will cover an overview of LCM technology, the principals surrounding its application, and benefits of its application to the newly defined field of epigenomics, in particular of cutaneous pathology. This presents a comprehensive review about LCM and its use in the spatial analysis of skin epigenetics. Within the realm of skin pathology, this ability to isolate tissues under specific environmental stresses, such as oxidative stress, allows a far more focused investigation.

Management of Clozapine Titration in the Setting of Cardiac Comorbidities.

Treatment-resistant schizophrenia is commonly treated by the initiation of Clozapine therapy. Clozapine (Clozaril) has a wide side effect profile with significant mortality stemming from early myocarditis or late cardiomyopathy. This risk profile is complicated in those with preexisting comorbidities. A 67-year-old male with a decade-long history of paranoid schizophrenia. His previous treatment regimen consisted of a combination of Haloperidol-Decanoate, Aripiprazole, and Olanzapine. On his most recent admission, the patient presented with an acute exacerbation of his schizophrenia with incontinence, agitation, and difficulty following commands. Due to the refractory nature of his symptoms, Clozapine therapy was initiated. During this time serial C-reactive protein (CRP) measurements increased markedly. This increase was seen in the context of worsening lower leg edema and air hunger. Clozapine taper was held, and the medical team was consulted. The consultation resulted in an echocardiogram showing signs of diastolic failure with an unknown etiology. Subsequent CT chest, however, ruled out any pericardial pathology and eliminated suspicion for clozapine-induced myocarditis. Clozapine taper was then restarted. When beginning clozapine in a patient with underlying cardiac risk factors, it is paramount to take into consideration the patient's baseline cardiopulmonary function. This report outlines the necessity of a baseline echocardiogram for patients with severe cardiac comorbidities. This in turn may have prevented a four-day delay of clozapine titration. Earlier and more frequent CRP measurements titration would have also guided clinical assessment as well. Furthermore, this case stresses the larger implications of investigating medical comorbidities among patients presenting on a psychiatric unit.

Beneficial Effects of Amnion-Chorion Stem Cell Grafting in the Long Term Management of Nonuremic Calciphylaxis Wounds.

Calciphylaxis is a poorly understood disease with high morbidity and mortality. The current primary literature on treatment is lacking; however, disease management often involves a multifaceted approach with a primary focus on consistent wound care. This report describes a case outlining the long-term management of nonuremic calciphylaxis wounds in a patient with severe malnutrition with the use of human amniotic membrane grafts, aggressive surgical debridement, nutritional therapy, and advanced wound healing techniques. A 38-year-old African American female with a history of non-uremic calciphylaxis presented from a transitional facility with numerous non-healing wounds in the setting of severe malnutrition secondary to bariatric surgery. Biweekly wound debridement was initiated utilizing an amniotic stem cell skin graft, dry applicable absorbent dressing, high-frequency ultrasonic ablation, and wound vacuum-assisted closure (VAC) over the course of approximately nine months. Nutritional supplementation was given in the form of jejunostomy tube feed due to a gastric bypass and a perforated viscus. At the current date, the patient demonstrates significant improvement in pain and wound healing. The patient is also able to ambulate with care and has begun steps towards independent management of wounds. Future goals of care include independent bedside wound management, placement of allograft, and discharge to a long-term care facility. Most patients with refractory pain, widespread necrotic wounds, and dangerous comorbidities will inevitably be referred to palliative care. This case creates a framework for the long term management of medically complex patients with nonuremic calciphylaxis using human amniotic membrane stem cell grafts and appropriate advanced wound care techniques.