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Swigris J.J.,Autoimmune Lung Center and Interstitial Lung Disease Program | Brown K.K.,Autoimmune Lung Center and Interstitial Lung Disease Program | Flaherty K.R.,500 dical Center Drive
Current Rheumatology Reviews | Year: 2010

The idiopathic interstitial pneumonias (IIP) are seven fibro-inflammatory interstitial lung diseases of unknown cause, grouped together because of potentially similar clinical features. Each of the seven has a distinct histologic pattern; however, these patterns are not specific to the IIP, and they provide a framework for defining interstitial lung disease (ILD) of known-cause, including ILD associated with underlying connective tissue disease (CTD). With the exception of respiratory bronchiolitis, the histologic patterns corresponding with the other six IIP can be found in association with CTD. Considering all CTD together, the pattern of non-specific interstitial pneumonia is most common. High-resolution computed tomography (HRCT) can hint at the histologic pattern, track changes over time, and assess response to therapy. The goal of this article is to review histologic patterns and HRCT findings of the IIP as they relate to CTD-associated ILD. © 2010 Bentham Science Publishers Ltd. Source

Crosby E.C.,University of Michigan | Crosby E.C.,Northwestern University | Crosby E.C.,500 dical Center Drive | Abernethy M.,University of Michigan | And 9 more authors.
Obstetrics and Gynecology | Year: 2014

OBJECTIVE: Complications from transvaginal mesh placed for prolapse often require operative management. The aim of this study is to describe the outcomes of vaginal mesh removal. METHODS: A retrospective review of all patients having surgery by the urogynecology group in the department of obstetrics and gynecology at our institution for a complication of transvaginal mesh placed for prolapse was performed. Demographics, presenting symptoms, surgical procedures, and postoperative symptoms were abstracted. Comparative statistics were performed using the χ2 or Fisher's exact test with significance at P<.05. RESULTS: Between January 2008 and April 2012, 90 patients had surgery for complications related to vaginal mesh and 84 had follow-up data. The most common presenting signs and symptoms were: mesh exposure, 62% (n556); pain, 64% (n558); and dyspareunia, 48% (n543). During operative management, mesh erosion was encountered unexpectedly in a second area of the vagina in 5% (n54), in the bladder in 1% (n51), and in the bowel in 2% (n52). After vaginal mesh removal, 51% (n543) had resolution of all presenting symptoms. Mesh exposure was treated successfully in 95% of patients, whereas pain was only successfully treated in 51% of patients. CONCLUSION: Removal of vaginal mesh is helpful in relieving symptoms of presentation. Patients can be reassured that exposed mesh can almost always be successfully managed surgically, but pain and dyspareunia are only resolved completely in half of patients. © 2013 by The American College of Obstetricians and Gynecologists. Source

Goonewardena S.N.,University of Michigan | Goonewardena S.N.,500 dical Center Drive | Prevette L.E.,University of Michigan | Desai A.A.,University of Chicago
Current Atherosclerosis Reports | Year: 2010

Metabolites reflect the dynamic processes underlying cellular homeostasis. Recent advances in analytical chemistry and molecular biology have set the stage for metabolite profiling to help us understand complex molecular processes and physiology. Metabolomics is the comparative analysis of metabolite flux and how it relates to biological phenotypes. As an intermediate phenotype, metabolite signatures capture a unique aspect of cellular dynamics that is not typically interrogated, providing a distinct perspective on cellular homeostasis. To date, there have been only a few metabolomics studies investigating cardiovascular diseases. In this review, we explore the principles of metabolomics and how it can provide further insight into the mechanisms of cardiovascular physiology and ultimately lead to improved diagnostic and therapeutic options for patients with cardiovascular disease. © Springer Science+Business Media, LLC 2010. Source

Tumbarello J.A.,University of Michigan | Tumbarello J.A.,500 dical Center Drive | Hsu Y.,University of Michigan | Lewicky-Gaupp C.,University of Michigan | And 2 more authors.
International Urogynecology Journal and Pelvic Floor Dysfunction | Year: 2010

Introduction and hypothesis: This study seeks to quantify differences in anterior vaginal wall prolapse during sequential Valsalva attempts on dynamic magnetic resonance imaging (MRI). Methods: Subjects were taken from an on-going case-control study evaluating anterior vaginal wall prolapse. Women with a prolapse whose leading edge extended ≥1 cm beyond the hymenal ring were included (n=40). All subjects performed three maximal Valsalva efforts while mid-sagittal dynamic MRI scans were obtained. Bladder descent between the first, second, and third maximal Valsalva efforts were compared. Results: Forty percent of women had a greater than 2-cm increase in prolapse size from their first to third Valsalva attempt. Ninety-five percent of women extended their prolapse further with a third Valsalva. Conclusions: As is true during clinical examination, several attempts may be required to have maximal anterior compartment prolapse present during dynamic MRI of the pelvic floor. © The International Urogynecological Association 2010. Source

Pasca di Magliano M.,500 dical Center Drive
BMC cancer | Year: 2014

BACKGROUND: Pancreatic cancer is one of the deadliest human malignancies, with few therapeutic options. Re-activation of embryonic signaling pathways is commonly in human pancreatic cancer and provided rationale to explore inhibition of these pathways therapeutically. Notch signaling is important during pancreatic development, and it is re-activated in pancreatic cancer. The functional role of Notch signaling during pancreatic carcinogenesis has been previously characterized using both genetic and drug-based approaches. However, contrasting findings were reported based on the study design. In fact, Notch signaling has been proposed to act as tumor-promoter or tumor-suppressor. Given the availability of Notch inhibitors in the clinic, understanding how this signaling pathway contributes to pancreatic carcinogenesis has important therapeutic implications. Here, we interrogated the role of Notch signaling specifically in the epithelial compartment of the pancreas, in the context of a genetically engineered mouse model of pancreatic cancer.METHODS: To inhibit Notch signaling in the pancreas epithelium, we crossed a mouse model of pancreatic cancer based on pancreas-specific expression of mutant Kras with a transgenic mouse that conditionally expresses a dominant negative form of the Mastermind-like 1 gene. MAML is an essential co-activator of the canonical Notch signaling-mediated transcription. DNMAML encodes a truncated MAML protein that represses all canonical Notch mediated transcription in a cell autonomous manner, independent of which Notch receptor is activated. As a result, in mice co-expressing mutant Kras and DNMAML, Notch signaling is inhibited specifically in the epithelium upon Cre-mediated recombination. We explored the effect of epithelial-specific DNMAML expression on Kras-driven carcinogenesis both during normal aging and following the induction of acute pancreatitis.RESULTS: We find that DNMAML expression efficiently inhibits epithelial Notch signaling and delays PanIN formation. However, over time, loss of Notch inhibition allows PanIN formation and progression.CONCLUSIONS: Epithelial-specific Notch signaling is important for PanIN initiation. Our findings indicate that PanIN formation can only occur upon loss of epithelial Notch inhibition, thus supporting an essential role of this signaling pathway during pancreatic carcinogenesis. Source

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