Accuracy of the Unipolar Electrogram for Identification of the Site of Origin of Ventricular Activation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73873/1/j.1540-8167.1997.tb00619.x.pd

Neoadjuvant chemotherapy in the setting of locally advanced olfactory neuroblastoma with intracranial extension

Olfactory neuroblastoma (esthesioneuroblastoma) is a rare malignant tumor of neuroectodermal origin. With only about 1,000 cases reported, there are no clear guidelines regarding management of this disease. Intracranial extension and orbital involvement have been shown to be independent risk factors associated with poorer outcomes. We hereby report a case of a 46-year old male presented with an 8-month history of progressive nasal obstruction and intermittent right-sided epistaxis associated with anosmia and increased pressure sensation in and around the right eye. Further evaluation revealed a large enhancing heterogeneous cystic and solid mass in the right nasal cavity measuring 5.0×5.3×4.6 cm with extension superiorly into the anterior cranial fossa and frontal lobes, ethmoid and sphenoid sinuses. A biopsy of this mass confirmed high grade olfactory neuroblastoma. Because of the intra-cranial extension, a decision was made to start neoadjuvant chemotherapy with cisplatin and etoposide. The patient had very good response to this treatment on a repeat imaging study and went on to have resection of this mass. Post-operatively, he received radiation therapy to the tumor bed and 2 more cycles of chemotherapy. He has been followed now for more than 8 months with no evidence of disease recurrence

The heart in sporadic inclusion body myositis: a study in 51 patients

The purpose of this study was to explore the prevalence and nature of cardiac abnormalities in sporadic inclusion body myositis (sIBM). Fifty-one sIBM patients were cross-sectionally studied using history-taking, physical examination, measurements of serum creatine kinase activity, the MB fraction (CK-MB), cardiac troponin T (cTnT) and I (cTnI), a 12-lead electrocardiogram (ECG) and 2-dimensional echocardiography. Present cardiac history was abnormal in 12 (24%) out of 51 patients, 12 (24%) patients had abnormalities on ECG, mostly aspecific, and in 12 (24%) patients the echocardiograph showed abnormalities. Elevated CK-MB was present in 42 (82%) patients and 40 (78%) had an elevated cTnT in the absence of acute cardiac pathology. In contrast, in one patient (2%) cTnI was elevated. There was no apparent association between elevated biomarkers, ECG or echocardiographic abnormalities. The prevalence of cardiac abnormalities in sIBM does not seem to be higher than would be expected in these elderly patients. Elevated CK-MB and cTnT levels are common, in contrast to cTnI, but do not reflect cardiac pathology

Manifold Modeling of the Beating Heart Motion

Modeling the heart motion has important applications for diagnosis and intervention. We present a new method for modeling the deformation of the myocardium in the cardiac cycle. Our approach is based on manifold learning to build a representation of shape variation across time. We experiment with various manifold types to identify the best manifold method, and with real patient data extracted from cine MRIs. We obtain a representation, common to all subjects, that can discriminate cardiac cycle phases and heart function types

Interaction between polymorphisms of the Human Leukocyte Antigen and HPV-16 Variants on the risk of invasive cervical cancer

<p>Abstract</p> <p>Background</p> <p>Persistent infection with oncogenic types of human papillomavirus (HPV) is the major risk factor for invasive cervical cancer (ICC), and non-European variants of HPV-16 are associated with an increased risk of persistence and ICC. HLA class II polymorphisms are also associated with genetic susceptibility to ICC. Our aim is to verify if these associations are influenced by HPV-16 variability.</p> <p>Methods</p> <p>We characterized HPV-16 variants by PCR in 107 ICC cases, which were typed for <it>HLA-DQA1</it>, <it>DRB1 </it>and <it>DQB1 </it>genes and compared to 257 controls. We measured the magnitude of associations by logistic regression analysis.</p> <p>Results</p> <p>European (E), Asian-American (AA) and African (Af) variants were identified. Here we show that inverse association between <it>DQB1*05 </it>(adjusted odds ratio [OR] = 0.66; 95% confidence interval [CI]: 0.39–1.12]) and HPV-16 positive ICC in our previous report was mostly attributable to AA variant carriers (OR = 0.27; 95%CI: 0.10–0.75). We observed similar proportions of <it>HLA DRB1*1302 </it>carriers in E-P positive cases and controls, but interestingly, this allele was not found in AA cases (p = 0.03, Fisher exact test). A positive association with <it>DRB1*15 </it>was observed in both groups of women harboring either E (OR = 2.99; 95% CI: 1.13–7.86) or AA variants (OR = 2.34; 95% CI: 1.00–5.46). There was an inverse association between <it>DRB1*04 </it>and ICC among women with HPV-16 carrying the 350T [83L] single nucleotide polymorphism in the <it>E6 </it>gene (OR = 0.27; 95% CI: 0.08–0.96). An inverse association between <it>DQB1*05 </it>and cases carrying 350G (83V) variants was also found (OR = 0.37; 95% CI: 0.15–0.89).</p> <p>Conclusion</p> <p>Our results suggest that the association between HLA polymorphism and risk of ICC might be influenced by the distribution of HPV-16 variants.</p

Indices of insulin sensitivity and secretion from a standard liquid meal test in subjects with type 2 diabetes, impaired or normal fasting glucose

<p>Abstract</p> <p>Background</p> <p>To provide an initial evaluation of insulin sensitivity and secretion indices derived from a standard liquid meal tolerance test protocol in subjects with normal (NFG), impaired fasting glucose (IFG) or type 2 diabetes mellitus.</p> <p>Methods</p> <p>Areas under the curve (AUC) for glucose, insulin and C-peptide from pre-meal to 120 min after consumption of a liquid meal were calculated, as were homeostasis model assessments of insulin resistance (HOMA2-IR) and the Matsuda index of insulin sensitivity.</p> <p>Results</p> <p>Subjects with NFG (n = 19), IFG (n = 19), and diabetes (n = 35) had mean ± SEM HOMA2-IR values of 1.0 ± 0.1, 1.6 ± 0.2 and 2.5 ± 0.3 and Matsuda insulin sensitivity index values of 15.6 ± 2.0, 8.8 ± 1.2 and 6.0 ± 0.6, respectively. The log-transformed values for these variables were highly correlated overall and within each fasting glucose category (r = -0.91 to -0.94, all p < 0.001). Values for the product of the insulin/glucose AUC ratio and the Matsuda index, an indicator of the ability of the pancreas to match insulin secretion to the degree of insulin resistance, were 995.6 ± 80.7 (NFG), 684.0 ± 57.3 (IFG) and 188.3 ± 16.1 (diabetes) and discriminated significantly between fasting glucose categories (p < 0.001 for each comparison).</p> <p>Conclusion</p> <p>These results provide initial evidence to support the usefulness of a standard liquid meal tolerance test for evaluation of insulin secretion and sensitivity in clinical and population studies.</p

Acute Effects of Sex Steroid Hormones on Susceptibility to Cardiac Arrhythmias: A Simulation Study

Acute effects of sex steroid hormones likely contribute to the observation that post-pubescent males have shorter QT intervals than females. However, the specific role for hormones in modulating cardiac electrophysiological parameters and arrhythmia vulnerability is unclear. Here we use a computational modeling approach to incorporate experimentally measured effects of physiological concentrations of testosterone, estrogen and progesterone on cardiac ion channel targets. We then study the hormone effects on ventricular cell and tissue dynamics comprised of Faber-Rudy computational models. The “female” model predicts changes in action potential duration (APD) at different stages of the menstrual cycle that are consistent with clinically observed QT interval fluctuations. The “male” model predicts shortening of APD and QT interval at physiological testosterone concentrations. The model suggests increased susceptibility to drug-induced arrhythmia when estradiol levels are high, while testosterone and progesterone are apparently protective. Simulations predict the effects of sex steroid hormones on clinically observed QT intervals and reveal mechanisms of estrogen-mediated susceptibility to prolongation of QT interval. The simulations also indicate that acute effects of estrogen are not alone sufficient to cause arrhythmia triggers and explain the increased risk of females to Torsades de Pointes. Our results suggest that acute effects of sex steroid hormones on cardiac ion channels are sufficient to account for some aspects of gender specific susceptibility to long-QT linked arrhythmias

ICAR: endoscopic skull‐base surgery

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A population-based phenome-wide association study of cardiac and aortic structure and function

Differences in cardiac and aortic structure and function are associated with cardiovascular diseases and a wide range of other types of disease. Here we analyzed cardiovascular magnetic resonance images from a population-based study, the UK Biobank, using an automated machine-learning-based analysis pipeline. We report a comprehensive range of structural and functional phenotypes for the heart and aorta across 26,893 participants, and explore how these phenotypes vary according to sex, age and major cardiovascular risk factors. We extended this analysis with a phenome-wide association study, in which we tested for correlations of a wide range of non-imaging phenotypes of the participants with imaging phenotypes. We further explored the associations of imaging phenotypes with early-life factors, mental health and cognitive function using both observational analysis and Mendelian randomization. Our study illustrates how population-based cardiac and aortic imaging phenotypes can be used to better define cardiovascular disease risks as well as heart–brain health interactions, highlighting new opportunities for studying disease mechanisms and developing image-based biomarkers