Vascular endothelial growth factor-eluting, polymer-coated, coronary stents: an in vitro and in vivo evaluation

INTRODUCTION: Percutaneous intervention (PCI) is complicated by restenosis, stent thrombosis and delayed endothelial recovery at the PCI site. One approach to reduce these complications is to deliver potent agents directly to the PCI site. This local drug delivery can be achieved by absorbing drugs into a polymer coating applied to the stent itself. Vascular Endothelial Growth Factor (VEGF) has been shown to accelerate the recovery of endothelium over a stent, reducing intimal hyperplasia and thrombosis. It has not previously been delivered bound onto the stent itself. VEGF-eluting stents were tested in vitro and in a rabbit model.ORIGINAL HYPOTHESIS: Polymer coated stents may absorb and gradually release Vascular Endothelial Growth Factor. This released VEGF may reduce the stent complications of thrombosis and neointimal hyperplasia, primarily by accelerating the recovery of denuded endothelium. This was tested in vitro and in an animal model.METHODS: Studies were performed to determine optimum stent loading with VEGF, which was radiolabelled. Loaded stents were perfused and the drug release kinetics measured. VEGF's potential to stimulate growth was assessed in endothelial cell culture. The VEGF-eluting stents were placed in rabbit iliac arteries and their effects on flow through the artery and acute platelet deposition were determined. Other animals were used to show longer-term effects on endothelial recovery and stent thrombosis (at 7 days) and intimal hyperplasia (at 28 days).RESULTS: 21,7pg of VEGF was absorbed. This was released with a bi-exponential release curve with 20% remaining at 9 days. In arterial tissue, 11% of the VEGF was detectable in the tissue at 24hr. VEGF-eluting stents stimulated endothelial cell growth by 11% over 5 days, with effects that were sustained beyond the initial rapid VEGF release. The animal studies showed a trend (p=0.07) towards reduced platelet deposition early after PCI, with reduced thrombus formation at 7 days (Omg in VEGF stents vs. 12.5mg in controls). No benefit of VEGF stents was seen on the re-endothelialisation process or on intimal hyperplasia.CONCLUSIONS: VEGF can be delivered by polymer-coated stents. Prolonged drug release to the injured vessel wall can be shown. However, VEGF did not fulfil the potential suggested by previous work and by the cell culture experiments when tested in vivo. It did appear to reduce thrombus formation and so may have potential benefits in clinical practice as a stent-based therapy

Use of the Bipedicled Scalp Flap for Forehead Reconstruction

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74824/1/j.1524-4725.1984.tb01210.x.pd

Master of Science

thesisWater column, sediment and pore water samples were collected from multiple locations of the Great Salt Lake (GSL), Utah to examine the spatial and temporal distribution of total mercury (THg) and methyl mercury (MeHg) concentrations and MeHg production potentials (MPPs). Sampling locations included multiple transects in the south arm of the GSL, adjacent freshwater influenced bays, and multiple impounded and sheet flow freshwater wetland sites during the period of summer 2009-summer 2012. Select water column and sediment subsamples were spiked with inorganic mercury (I204Hg) and methyl mercury (Me204Hg) to examine net production of methyl mercury (Me204Hg ) and net loss of Me201Hg. First order methylation (kmeth) and demethylation (kdemeth) rate constants were determined from changes in isotope dilution corrected concentrations and/or changes in isotope ratios as a function of time. Tin reducible inorganic Hg (Hg(II)R) was used as a proxy for bioavailable Hg(II) in GSL samples. MeHg production potentials (MPPs) were calculated as the time integrated product of kmeth and Hg(II)R to compare methylation in deep brine layer (DBL) versus underlying sediment slurry (SSL) samples of the GSL. A large range of methylation rate constants (1.4E-6 to 1.1E-3 hr-1) was observed across the region, whereas demethylation was only significant in the DBL. Positive correlation of kmeth to organic matter content was observed in sediment of the freshwater influenced bays and impounded wetlands, while this trend was not observed in DBL and SSL of the GSL. These results further indicate that sediment organic matter, as well as other factors (e.g., organic matter lability and sulfide concentrations) contribute to production of MeHg. Spatially, higher MeHg concentrations in the GSL and sheet flow freshwater wetlands present the possibility of ‘hot spots' for MeHg introduction into the food web. Greater and temporally constant MPPs in SSL relative to DBL may explain the persistence of high MeHg concentrations in the DBL

Treatment of Perichondritis with a Quinolone Derivative—Norfloxacin

Auricular perichondritis is an uncommon complication following surgery of the external ear. Pseudomonas aeruginosa is the most commonly associated pathogen. Presented is a patient with auricular perichondritis successfully treated with norfloxacin, a newly available, orally administered antibiotic with antipseudomonal activity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74571/1/j.1524-4725.1988.tb03381.x.pd

Chronic Radiodermatitis with Dystrophic Calcification Treated with Mohs Surgery

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72255/1/j.1524-4725.1985.tb02983.x.pd

Treatment of Malignant Fibrous Histiocytoma and Atypical Fibrous Xanthomas with Micrographic Surgery

Fibrous tumors of the soft tissue are usually benign, but some fibrous neoplasms such as dermatofibrosarcoma protuberans (DFSP), atypical fibroxanthoma (AFX), and malignant fibrohistiocytoma (MFH) can be very destructive locally with a high recurrence rate after local excision. On occasion, they can metastasize. Previous reports have confirmed the high success rate of Mohs micrographic surgery for the treatment of DFSP, but data have been lacking on the potential benefit of this surgical approach for MFH and AFX tumors. Over the past 6 years, we have treated 17 patients with MFH (20 tumors) and 5 patients with AFX with Mohs micrographic surgery. A retrospective analysis of the surgical results is presented. To date (average 3-year follow-up), all patients contacted are tumor free with only one recurrence; no patient has developed metastatic disease. Our results to date are very encouraging; they lend support to Mohs micrographic surgery as a desired surgical approach for these diffiult-to-cure neoplasms.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73298/1/j.1524-4725.1989.tb03149.x.pd

Immunology of Injectable Collagen in Human Subjects

Associated with the use of Zyderm Collagen Implant (ZCI) for soft tissue augmentation, the rate of localized hypersensitivity reactions to the initial test injection of ZCI range from 3.0–3.5% in the literature, and subsequent reactions to treatment have reportedly ranged from 1.1–5.0%. The inflammatory symptoms to the Collagen Test Implant occur within 72 hours in 2% of those injected, indicating a preexisting sensitivity to bovine collagen in this healthy population. Most adverse treatment reactions follow the first treatment and after injection of <5 ml of collagen. Furthermore, antibodies against collagen in sera of subjects reporting localized symptoms of hypersensitivity at test or treatment sites are specific for bovine interstitial collagens and show no cross-reactivity with human collagens. Thus, immunologic reaction to ZCI results in antibovine collagen antibodies and localized inflammatory symptoms in those few subjects who experience hypersensitivity to test or treatment. Glutaraldehyde cross-linked Zyplast Implant (ZI), has demonstrated a lower incidence of hypersensitivity reactions than ZCI. In examining patients tested with ZI or treated for intradermal and subdermal indications, we have experienced only 7 hypersensitivity reactions at test sites of ZI, out of 803 tested subjects, and only 3 reactions among 498 treated patients. Therefore, ZI appears to induce a lower incidence of hypersensitivity reactions than ZCI in man.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74914/1/j.1524-4725.1988.tb04040.x.pd

Research Directions in Information Systems: Toward an Institutional Ecology

This essay identifies three characteristic problems in how the Information Systems field sets its research directions. First is the propensity of our field to create research agendas modeled after the transitory infatuations that industry has with certain popular topics in IT-related innovation. The second problem is our field\u27s inclination to develop insular sub-communities that consume resources on behalf of research programs that are of limited theoretical and practical interest. A third problem is noted from time to time by our partners in industry: We sometimes neglect topics that are of practical interest to them. This paper argues that these seemingly diverse phenomena can be brought under a common umbrella by examining how the shaping of research agendas depends on forces in our field\u27s larger institutional milieu. Specifically, we suggest that the field\u27s research directions constitute responses to institutionally constituted market forces that arise both within academia and in the larger economy and society. Furthermore, we propose that the substance of the discourse associated with any particular research stream is dictated by the workings of these forces, in ways our community has yet to fully understand. We make four proposals for reflexive inquiry that we believe will advance this understanding and ultimately help to foster research that better serves both theory and practice, while being less subject to the whims of industry fashion

Concepts of Sliding and Lifting Tissue Movement in Flap Reconstruction

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94457/1/j.1524-4725.2000.09172.x.pd

Evaluation of an erythropoietic factor obtained from blood of experimentally-induced anemic cattle using radioactive Fe⁵⁹

Call number: LD2668 .T4 1960 S8