Promporn Suksaranjit

Metabolic phenotype and adipose and liver features in a high-fat Western diet-induced mouse model of obesity-linked NAFLD

nonalcoholic fatty liver disease (NAFLD), an obesity and insulin resistance associated clinical condition - ranges from simple steatosis to nonalcoholic steatohepatitis. To model the human condition, a high-fat Western diet that includes liquid sugar consumption has been used in mice. Even though liver pathophysiology has been well characterized in the model, little is known about the metabolic phenotype (e.g., energy expenditure, activity, or food intake). Furthermore, whether the consumption of liquid sugar exacerbates the development of glucose intolerance, insulin resistance, and adipose tissue dysfunction in the model is currently in question. In our study, a high-fat Western diet (HFWD) with liquid sugar [fructose and sucrose (F/S)] induced acute hyperphagia above that observed in HFWD-fed mice, yet without changes in energy expenditure. Liquid sugar (F/S) exacerbated HFWD-induced glucose intolerance and insulin resistance and impaired the storage capacity of epididymal white adipose tissue (eWAT). Hepatic TG, plasma alanine aminotransferase, and normalized liver weight were significantly increased only in HFWD+F/S-fed mice. HFWD+F/S also resulted in increased hepatic fibrosis and elevated collagen 1a2, collagen 3a1, and TGFβ gene expression. Furthermore, HWFD+F/S-fed mice developed more profound eWAT inflammation characterized by adipocyte hypertrophy, macrophage infiltration, a dramatic increase in crown-like structures, and upregulated proinflammatory gene expression. An early hypoxia response in the eWAT led to reduced vascularization and increased fibrosis gene expression in the HFWD+F/S-fed mice. Our results demonstrate that sugary water consumption induces acute hyperphagia, limits adipose tissue expansion, and exacerbates glucose intolerance and insulin resistance, which are associated with NAFLD progression.

Vitamin D deficiency and cardiovascular disease

We read with interest the article by Guessous et al. [1]. The author described an excellent study on vitamin D levels and associated factors. The author mentioned the association between vitamin D and cardiovascular disease, which we found fascinating, and we would like to emphasise the topic. Cardiovascular disease (CVD) is the leading cause of death in the United States. There is an increasing interest in using vitamin D levels as a novel marker for CVD [2], because epidemiological data have shown a strong correlation between the risk of CVD and vitamin D deficiency. A cross-sectional analysis of the NHANES database showed a higher prevalence of CVD among individuals with low levels of 25-hydroxy [25(OH)] vitamin D [3]. The mechanism leading to the increased cardiovascular risk is not clearly understood; however, patients with vitamin D deficiency were found to have upregulation of the renin angiotensin aldosterone system (RAAS). The relationship between vitamin D deficiency and upregulation of the RAAS was also found in a large epidemiological study of 3,000 patients [4]. A recent meta-analysis involving 19 prospective studies (6,123 CVD cases) also showed increased CVD risk in patients with serum 25(OH)-vitamin D levels of 20–60 nmol/L [5]. Though multiple lines of evidence suggest a link between low vitamin D levels and increased risk of CVD, multiple interventional trials have failed to reveal any significant benefit of vitamin D supplementation [6–7]. There is also no benefit of vitamin D supplementation in improvement of diastolic function and regression of left ventricular hypertrophy [8]. Further studies are needed to establish the effect of vitamin D supplementation on CVD risk. Correspondence: Wisit Cheungpasitporn, MD, Department of Medicine, Bassett Medical Center, USA-Cooperstown, New York 13326, wisit.cheungpasitporn[at]bassett.org

Autosomal Dominant Alport Syndrome Presenting as Proteinuria at Marine Corps Physical Fitness Test: A Case Report and Review

A 19-year-old Caucasian male presented to Nephrology Clinic for evaluation of proteinuria. He denied any hearing or vision impairment. The patient reported significant family history for kidney problem in his father, paternal uncle, paternal aunts and his half brother who shared the same father. Physical examination revealed a blood pressure of 136/60 mmHg with no peripheral edema. Laboratory evaluation disclosed a serum creatinine of 0.7 mg/dl, 24-hour urine protein of 2.4 g and serum albumin of 3.7 g/dl. Urinalysis demonstrated dysmorphic red blood cells. A renal biopsy revealed the diagnosis of Alport syndrome. From his paternal family history, the disease was transmitted by autosomal dominant inheritance. The diagnosis of autosomal dominant Alport syndrome was made. He was prescribed lisinopril 5 mg per day. Referrals with Ophthalmology and Audiology were performed with showed no evidences of extrarenal involvement. At follow-up, 3 months later, patient continued to do well with serum creatinine of 0.7 mg/dl and urine protein-to-creatinine ratio of 1.75. Alport syndrome is most commonly transmitted in an X-linked manner (80% of cases). Autosomal dominant transmission is rare and only accounts for 5% of affected patients. Extrarenal manifestations include hearing loss and ocular defects. Although the presence of these defects should prompt a search for Alport syndrome, patients with autosomal dominant Alport syndrome may present without these manifestations.

Hypercalcemia in Human Immunodeficiency Virus-Related Lymphoma and Valacyclovir Toxicity

To the Editor: We thank Shrayyef et al for their article entitled “Hypercalcemia in Two Patients with Sarcoidosis and Mycobacterium avium intracellulare Not Mediated by Elevated Vitamin D Metabolites,”1 which was published in the October issue of The American Journal of the Medical Sciences (Vol. 342, 4, pp 336–340). The authors wrote very excellent review on granulomatous diseases induced by hypercalcemia without elevated active vitamin D level. We found an interesting association between human immunodeficiency virus (HIV) infection, valacyclovir and hypercalcemia in the first case study. Hypercalcemiarelated granulomatous diseases and non-Hodgkin lymphomas are not uncommon in HIV-infected patients especially in patients with low CD4 counts, high HIV viral loads and a prior diagnosis of AIDS.2 In addition, Li et al3 recently reported a case of severe hypercalcemia due to valacyclovir toxicity. The dose of valacyclovir should be renally adjusted for kidney function, and physicians should be aware of the possibility of valacyclovir-induced hypercalcemia as in the first case presentation.

Interstudy repeatability of self-gated quantitative myocardial perfusion MRI.

To evaluate the interstudy repeatability of multislice quantitative cardiovascular magnetic resonance myocardial blood flow (MBF), myocardial perfusion reserve (MPR), and extracellular volume (ECV). A unique saturation recovery self‐gated acquisition was used for the perfusion scans.

Unveiling the hidden eagle: acute parotitis-induced eagle syndrome.

Context: A cervicofacial pain and foreign body sensation in pharynx associated with styloid process elongation is called Eagle syndrome. Typically, this syndrome is provoked by tonsillectomy or trauma. We report the first case of acute parotitis-induced Eagle syndrome. Case Report: A 65-year-old woman presented with right facial pain. CT scan of neck revealed asymmetric enhancement of the right parotid gland compatible with acute parotitis. All inflammation was resolved with antibiotics. However, the patient complained of pain in right mandibular region out of proportion to inflammation. Review CT found to have an asymmetrically long right styloid process measures. The diagnosis of acute parotitis-induced Eagle syndrome was established. Conclusion: Physicians should have a high index of suspicion for Eagle syndrome in patients with atypical neck pain and elongated styloid process since another significant manifestation of Eagle syndrome is carotid artery compression leading to recurrent syncope or stroke.

A rare combination of giant right coronary artery aneurysm

Context: Giant coronary artery aneurysm (CAA) in adults is a rare clinical entity with an estimated incidence of 0.02%. CAA is commonly found in the right coronary artery with significant number of cases associated with fistula formation. Case Report: We describe a rare case of an 87 year-old man with large CAA with fistulous drainage into the right ventricle (RV) along with RV free wall vegetation as a cause of chronic weakness and lethargy. Conclusion: Giant CAA with fistulous drainage to the RV could present in the form of infective endocarditis. Early detection and surgical treatment would provide a significant benefit to these patients.

Reported Cases of Recurrent Takotsubo Cardiomyopathy with Variant Forms of Left Ventricular Dysfunction

We read with great interest the article by Aggarwal and Krantz, entitled “Migratory takotsubo cardiomyopathy in the setting of cholecystitis.” This was a very interesting case presentation regarding stress-related cardiomyopathy involving variable myocardial segments at different time points. The author mentioned that this was the first reported case. After careful review, however, we found several reports in the literature of recurrent takotsubo cardiomyopathy with variable patterns of left ventricular dysfunction. In 2007, Blessing et al reported a 70-year-old man with recurrent takotsubo cardiomyopathy demonstrating basal area akinesis initially and apical ballooning on the second episode. In 2009, Izumo et al reported a 78-year-old male with recurrent takotsubo cardiomyopathy. At the first episode, the patient was found to have apical akinesis and basal hyperkinesis while at the second episode; 2 years later, he was found to have mid-ventricular akinesis combined with normal apical wall motion. In 2011, From et al presented a clinical image of a 65-year-old female with recurrent takotsubo cardiomyopathy manifesting as typical apical ballooning at the first episode and mid-ventricular variant at

Clinical Implication of T2* Cardiac Magnetic Resonance Imaging in Cardiac Siderosis

A 55-year-old woman with a history of myelodysplastic syndrome status after multiple blood transfusions presented with a 2-week history of shortness of breath, decreased exercise tolerance, weight gain, and bilateral leg edema. Transthoracic echocardiography 1 week before revealed a left ventricular ejection fraction of 35%. With the concern for iron-overload syndrome and new-onset heart failure, the patient was admitted for further evaluation. The patient had an irregularly irregular tachycardic rhythm with normal blood pressure and pulse oximetry on room air. Pertinent physical findings included jugular venous distention, bibasilar rales, and edematous lower extremities. Laboratory results revealed an anemia, mildly elevated transaminase levels, a ferritin level of 7300 ng/mL, and a negative troponin. Electrocardiogram showed atrial fibrillation with a ventricular rate of 130 beats/min without ST-T changes. Chest x-ray showed mild cardiomegaly with minimal perihilar vascular congestion. Transthoracic echocardiogram demonstrated moderate left atrial enlargement and left ventricular global hypokinesis with an ejection fraction of 20%. Cardiovascular magnetic resonance imaging revealed a decreased signal in both the heart and the liver with a myocardial T2* of 7.2 ms (Figure 1). Magnetic resonance imaging of the abdomen showed a decreased signal on T2weighted imaging consistent with iron deposition in the liver, spleen, and pancreas. A diagnosis of iron overload syndrome with cardiac siderosis was made, and intravenous deferoxamine therapy was initiated. The hospital course was uneventful, and the patient was discharged with intravenous deferoxamine and oral deferiprone. Cardiac siderosis resulting in cardiomyopathy is a serious complication of chronic transfusion therapy. Diagnosis of this condition can be challenging. Although history and physical examination can provide clinical clues, to quantify myocardial iron deposition requires further diagnostic evaluation. Serum ferritin level and

Warfarin-related nephropathy can be mimicked by an interaction between sulfonamide derivatives and vitamin K antagonists

To the Editor: We thank Brodsky et al.1 for their excellent study on warfarin-related nephropathy (WRN). The authors analyzed data and risk factors of WRN in patients with and without chronic kidney disease. However, an interesting topic that the authors did not mention is concurrent treatment of warfarin with antimicrobial agents, especially sulfonamide derivatives. Interaction between trimethoprim/sulfamethoxazole and warfarin can mimic WRN by causing both elevation of international normalized ratio (INR) level and serum creatinine, without the mechanism of WRN. Sulfamethoxazole inhibits CYP2C9, the main enzyme responsible for metabolizing (S)-warfarin (60–70% of warfarins activity), in the liver.2 This antimicrobial agent can cause elevated INR levels with concurrent warfarin treatment. At the same time, trimethoprim is known to decrease the tubular secretion of creatinine and lead to increases in serum creatinine with intact glomerular filtration rate (GFR),3 unlike the case in WRN, which decreases GFR. Moreover, not mentioned in their paper are the large numbers of medications that can acutely increase INR in warfarin-treated patients, and therefore are risk factors for WRN.