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Biomedical subjects

Elliot L Chaikof

Publications and source records attributed to Elliot L Chaikof.

At least 37 records · Page 2Linked to original sources
PubMed2005

Catalytic efficiency of a thrombomodulin-functionalized membrane-mimetic film in a flow model.

The protein C anticoagulant pathway generates an "on demand" physiologic anticoagulant response, which is initiated when thrombin binds to thrombomodulin (TM), a transmembrane protein constitutively expressed by endothelial cells. A stable, protein C activating membrane-mimetic film was produced on a polyelectrolyte multilayer (PEM) by in situ photopolymerization of a phospholipid assembly containing TM. The monoacrylated phospholipid monomer was initially synthesized and prepared as unilamellar vesicles with varying molar concentrations of TM. Membrane-mimetic films were constructed on planar substrates with defined surface concentrations of catalytically active TM. 125I-labeled radiolabeling demonstrated little change in TM surface concentration over periods of up to 4 weeks. We utilized a parallel plate flow system to investigate the effects of simulated arterial (500 s(-1)) and venous (50 s(-1)) shear rates and TM surface concentration (0-1400 fmol cm(-2)) on the rate and extent of activation of protein C. The rate of production of activated protein C increased with shear rate and TM surface content. However, in agreement with an analysis of reaction kinetics and mass transfer, experimental results demonstrate that reaction rates become saturated at TM surface densities greater than or equal to 800 fmol cm(-2). We believe that the design of membrane-mimetic films that have the capacity to activate the protein C pathway will provide a useful strategy for generating "actively" antithrombogenic surfaces.

Animals↗
PubMed2005

Analysis of photoinitiated polymerization in a membrane mimetic film using infrared spectroscopy and near-IR Raman microscopy.

A method has been developed to investigate the extent of polymer cross-linking that results following in situ photopolymerization of an acrylate-functionalized phospholipid assembly adsorbed onto a stabilized, membrane-mimetic film produced from a polyelectrolyte multilayer (PEM) on polytetrafluoroethylene (PTFE) grafts. The acrylate phospholipid monomer was synthesized, prepared as a unilamellar vesicle, and fused onto closed-packed acyl chains that make up the PEM membrane-mimetic barrier on the PTFE graft. Both broad band white light and 514.5 nm laser radiation were used as excitation sources for photoinitiation; eosin Y was used as the photoinitiator. The use of 514.5 nm excitation reduced the time for maximum polymerization of the acrylate lipid from 60 min to 240 s. Infrared spectroscopy was successfully used to analyze the extent of photopolymerization in simplified model acrylate lipid systems; however, this method could not be used to analyze acrylate polymerization in heterogeneous, multicomponent PEM membrane-mimetic barriers on PTFE grafts. A near-infrared Raman microscopy method based on the ratio of the integrated areas of the CC and CN vibrations was shown to provide equivalent information to the IR method for analysis of the extent of polymerization efficiency in acrylate lipids. In addition, it proved feasible to extend this near-IR Raman method to the in situ analysis of the extent of polymerization in a stabilized acrylate lipid membrane on a PEM film in a PTFE vascular graft. This work describes a new approach for generating and analyzing the robustness of a membrane-mimetic coating on biomaterial surfaces, and may improve our ability to predict the long-term stability of polymeric membrane-mimetic films on implantable medical devices.

Electrolytes↗
PubMed2005

Toward an easy access to dendrimer-like poly(ethylene oxide)s.

Dendrimer-like poly(ethylene oxide)s (PEOs) were synthesized by an iterative divergent approach combining anionic polymerization of ethylene oxide from multi-hydroxylated precursors and branching reactions of PEO chain ends. Partial deprotonation of the hydroxyls (< 30%) and use of dimethyl sulfoxide as solvent proved crucial for a "controlled/living" polymerization of ethylene oxide at room temperature. These sequences of reactions allowed us to prepare a dendrimer-like PEO up to the eighth generation with a molar mass of 900 000 g mol(-1) and 384 external hydroxyl functions. All samples from generation 1 to 8 were characterized by 1H NMR spectroscopy, light scattering, and viscometry. The evolution of the intrinsic viscosity versus the generation number of these dendrimer-like PEO is similar to that of regular dendrimers.

Magnetic Resonance Spectroscopy↗
PubMed2005

Dendrimer-like PEO glycopolymers exhibit anti-inflammatory properties.

A new class of high molecular weight polysulfated PEO dendrimer-like glycopolymer has been synthesized by a combination of arm-first and core-first methodologies followed by trichloroacetimidate glycosidation as a facile bioconjugation strategy. An L-selectin antagonist was identified that exhibits 103-fold greater activity than other multivalent sLex glycopolymers and 20-50 times greater potency than other linear heparinoids. A significant reduction in inflammatory cell recruitment was observed in vivo.

Animals↗
PubMed2005

Design and synthesis of asymmetric acyclic phospholipid bolaamphiphiles.

[structure: see text] A synthetic route was devised for the generation of asymmetric lipid bolaamphiphiles through the sequential esterification of an alkyldioic acid, bearing distinct terminal protecting groups, with propanylamine and lyso-phosphatidylcholine headgroups. Bolaamphiphile self-assembly was investigated in solvent mixes of varying polarity by nuclear magnetic resonance (NMR) and Fourier transform-infrared (FT-IR) spectroscopy, as well as in water by cryo-high-resolution scanning electron microscopy (cryo-HRSEM). We anticipate that asymmetric lipid bolaamphiphiles will provide facile building blocks for engineering a variety of unique membrane-mimetic structures.

Magnetic Resonance Spectroscopy↗
PubMed2005

Photomediated crosslinking of C6-cinnamate derivatized type I collagen.

Synthesis and characterization of cinnamated Type I collagen and its related mechanical properties after photomediated crosslinking were investigated in detail. Using an EDC/NHS conjugation method, collagen was chemically modified to incorporate a photosensitive cinnamate moiety. The cinnamated collagen was fully characterized by 1H NMR, UV-vis, and circular dichroism (CD) spectroscopy, as well as by rheological and mechanical analyses. Cinnamated collagens with varying degrees of derivatization retained collagen triple helical structure. The rheological spectra of collagen solutions demonstrate that the storage modulus decreases with increasing cinnamate content, owing to a decrease in physical crosslinking. The kinetics of the crosslinking process in both hydrated gels and dry films were monitored by UV-vis spectroscopy and confirmed that crosslinking was complete within 60 min of irradiation. The uniaxial stress-strain behavior of crosslinked collagen films, including Young's modulus and ultimate tensile strength, was comparable to values reported for glutaraldehyde-crosslinked monomeric collagen films. These data demonstrate that derivatization of collagen with photosensitive cinnamate moieties provides a facile route for solid-state crosslinking, thereby improving the mechanical properties of collagen and enhancing the potential applicability of collagen-based materials in tissue engineering and drug delivery.

Biocompatible Materials↗
PubMed2005

Viscoelastic and mechanical behavior of recombinant protein elastomers.

Recombinant DNA synthesis was employed to produce elastin-mimetic protein triblock copolymers containing chemically distinct midblocks. These materials displayed a broad range of mechanical and viscoelastic responses ranging from plastic to elastic when examined as hydrated gels and films. These properties could be related in a predictable fashion to polymer block size and structure. While these materials could be easily processed into films and gels, electrospinning proved a feasible strategy for creating protein fibers. All told, the range of properties exhibited by this new class of protein triblock copolymer in combination with their easy processability suggests potential utility in a variety of soft prosthetic and tissue engineering applications.

Biocompatible Materials↗
PubMed2005

Secondary conversion of the Gore Excluder to operative abdominal aortic aneurysm repair.

OBJECTIVE: Reports continue to document the occurrence of major adverse events after endovascular aortic aneurysm repair. Although many of these problems can be successfully managed through endovascular salvage, operative conversion with explantation of the endoprosthesis remains necessary in some patients. We report herein a review of all patients initially enrolled in multicenter US clinical trials of the Excluder endograft who underwent secondary conversion to open surgical repair. METHODS: Clinical data and relevant medical records of patients enrolled in phase I and II multicenter US clinical trials of the Excluder endograft were retrospectively reviewed for adverse events and further narrowed to those patients who underwent secondary operative conversion. Hospital records, operative and anesthesia reports, and all imaging studies were analyzed at initial implantation and at the time of subsequent open surgical repair. RESULTS: Late open conversion was performed in 16 (2.7%) of the 594 patients enrolled in the Excluder clinical trials. Presumed endotension accounted for 8 of 16 of secondary conversions. In two of these patients, however, an endoleak was identified at the time of open surgical repair. Of the remaining eight patients, two underwent conversion for device infection, five for persistent endoleak, and one for aneurysm rupture. The overall 30-day mortality was 6.25% (1/16), with one death occurring in a patient with a ruptured aneurysm. Of patients who underwent conversion because of endotension, the maximal abdominal aortic aneurysm diameter (mean +/- SD) at the time of initial implantation and subsequent graft removal was 61 +/- 11 mm and 70 +/- 10 mm, respectively. The mean time to open conversion for treatment of endotension was 37 +/- 12 months (range, 20-50 months; median, 42 months). Freedom from conversion was 98.6% and 96.7% at 24 and 48 months, respectively. CONCLUSIONS: Endotension in the absence of a demonstrable endoleak has been a major indication for late surgical conversion in patients treated with the Excluder endograft. Given the potential presence of an undetected endoleak and the possible effects of progressive sac enlargement on long-term device stability, continued close surveillance of patients with assumed endotension is required. Should changes in device design eliminate endotension, a further reduction in the already low incidence of late open conversion of the Excluder endograft can be anticipated.

Age Factors↗
PubMed2005

Abdominal aortic aneurysm (AAA): cost-effectiveness of screening, surveillance of intermediate-sized AAA, and management of symptomatic AAA.

Physicians must make decisions about screening patients for abdominal aortic aneurysms (AAAs), monitoring or referring for surgery patients with AAAs of various sizes, and assessing patients with symptoms that may be related to AAAs. This review article analyzes the evidence for each scenario. The effectiveness and cost-effectiveness of screening for AAA is based on results from four randomized controlled trials. A cost-effectiveness analysis using a Markov model showed that ultrasound screening of white men beginning at age 65 is both effective and cost-effective in preventing AAA-related death. Such screening would have a small but real impact over a 20-year period in these men. For patients with a known AAA-which is often detected incidentally-the evidence clearly suggests periodic ultrasound surveillance for those with small AAAs (3.0-3.9 cm in diameter) and elective surgical repair for those with large AAAs (>or=5.5 cm). Two recent randomized controlled trials have shown that early surgical repair confers no survival benefit compared with periodic surveillance for patients with intermediate-sized AAAs (4.0-5.5 cm in diameter), so those patients can also be monitored. Some centers choose to increase the frequency of monitoring to every 3 to 6 months when the AAA reaches 5.0 cm. Factors to consider in assessing symptomatic patients include the high risk of life-threatening conditions, the potential increased risk of death or poor outcome with delay in diagnosis, the limitations of ultrasound in identifying whether symptoms are due to known or suspected AAA, and the timely availability of computed tomography or other imaging tests. If available, computed tomography is preferred in patients with recent or severe symptoms, since it is better at detecting retroperitoneal hemorrhage and other complications and in providing preoperative definition of the anatomy.

Journal Article↗
PubMed2004

Design and synthesis of dimeric heparinoid mimetics.

Synthetic oligosaccharide constructs exhibiting tailored and well-defined heparan sulfate (HS) like sequences offer the potential to modulate dynamic HS-dependent biomolecular recognition processes. We report an efficient strategy for the generation of HS-like fragments [GlcA-beta-(1,4)-GlcNAc] and related dimerized (gemini) disaccharides (4a and 4b) via n-pentenyl glycoside formation. When a convergent synthetic approach was utilized, construction of target molecules was achieved through a combination of chemoselective protection/deprotection protocols, imidate and n-pentenyl glycosylations, and functional group manipulations followed by ozonolysis and reductive amination. For example, glycosylation of a 2-azido glycoside (25) with a trichloroacetimidate glucuronic acid donor (13), using a catalytic amount of TMSOTf, furnished heparin-like disaccharides (28a and 28b) that were equipped with an n-pentenyl tether at the anomeric end. In turn, heparinoid-like gemini disaccharides (4a and 4b) were produced by selective transformation of the olefinic unit in the n-pentenyl glycoside to the four-carbon aldehyde followed by reductive amination with ethylenediamine. The described synthetic approach provides access to structural variants of small heparinoid oligomers as versatile building blocks for generating novel HS mimetic pharmacotherapeutics, diagnostic reagents, and biomaterials.

Carbohydrate Sequence↗
PubMed2004

Oxidized linoleic acid regulates expression and shedding of syndecan-4.

Syndecan-4, a heparan sulfate proteoglycan that is widely expressed in the vascular wall and as a cell surface receptor, modulates events relevant to acute tissue repair, including cell migration and proliferation, cell-substrate interactions, and matrix remodeling. While syndecan-4 expression is regulated in response to acute vascular wall injury, its regulation under chronic proatherogenic conditions such as those characterized by prolonged exposure to oxidized lipids has not been defined. In this investigation, arterial smooth muscle cells were treated with 13-hydroperoxy-9,11-octadecadienoic acid (HPODE) and 13-hydroperoxy-10,12-octadecadienoic acid, oxidized products of linoleic acid, which is the major oxidizable fatty acid in LDL. Both oxidized fatty acids induced a dose-dependent, rapid upregulation of syndecan-4 mRNA expression that was not attenuated by cycloheximide. This response was inhibited by pretreatment with N-acetylcysteine, catalase, or MEK1/2 inhibitors, but not by curcumin or lactacystin, known inhibitors of NF-kappaB. These data suggest that oxidized linoleic acid induces syndecan-4 mRNA expression through the initial generation of intracellular hydrogen peroxide with subsequent activation of the extracellular signal-regulated kinase signaling pathway via MEK1/2. Notably, the HPODE-induced enhancement of syndecan-4 mRNA was accompanied by accelerated shedding of syndecan-4. In principle, alterations in both the cell surface expression and shedding of syndecan-4 may augment a variety of proatherogenic events that occur in response to oxidized lipids.

Animals↗
PubMed2004

Endovascular abdominal aortic aneurysm repair in the octogenarian.

The aim of this study was to analyze patient outcomes following endovascular repair of infrarenal abdominal aortic aneurysms (EAR) among patients 80 years of age or older. In this study, reporting standards of the Ad Hoc Committee for Standardized Reporting Practices for Endovascular Aortic Aneurysm Repair of the Society of Vascular Surgery/American Association for Vascular Surgery (SVS/AAVS) were followed. Between August 8, 1996 and February 12, 2001 EAR was performed in 31 patients (29 male and 2 female) with an average age of 83 +/- 3 years and an average maximum aneurysm diameter of 59 +/- 7 mm. Overall technical success was 90% (28/31) with a single acute conversion and a 6% (2/32) incidence of major morbidity. There were no in-hospital deaths, but two patients (6%) died within 30 days of intervention. Four endoleaks, two type I and two type II, were observed within the first 30 days after endograft implantation and three new type II endoleaks were noted after implant periods that exceeded 1 month. Average follow-up was 16 months, with a single aneurysm-related death that occurred after late conversion to open repair, 2 years following initial endovascular treatment. Kaplan-Meier analysis revealed 3-, 12-, and 24-month estimated survivals of 93% (+/-5), 75% (+/-8), and 68% (+/-10), respectively. Clinical success rates were 90% (+/-5), 90% (+/-5), and 72% (+/-17) at 12, 24, and 36 months, respectively. We conclude that, in the octogenarian with mild to moderate medical comorbidities, endovascular aneurysm repair provides an alternative to open AAA repair with low operative morbidity and good clinical success rates. Elevated SVS/AAVS medical comorbidity scores were not associated with increased operative mortality rates, but they did show a trend toward decreased mid-term survival. Careful consideration of life expectancy and the probability of rupture, as with traditional AAA repair, should dictate necessity for intervention.

Aged↗
PubMed2004

Repair of mycotic aortic pseudoaneurysm with a stent graft using transesophageal echocardiography.

A 54-year-old man who underwent uneventful orthotopic heart transplantation 1 year previously had low-grade fever and dyspnea. Imaging studies revealed an ascending aortic pseudoaneurysm (AAP), which was repaired with a 5-mm polyester patch, with circulatory arrest and cardiopulmonary bypass. Intraoperative cultures of the AAP grew methicillin-resistant Staphylococcus aureus, and the pseudoaneurysm recurred after 6 weeks despite intravenously administered antibiotic therapy. A 28.5-mm x 3.3-cm Gore Excluder aortic cuff was deployed in the ascending aorta through a left axillary artery cutdown with use of combined transesophageal echocardiography and fluoroscopy. In addition, controlled hypotension and asystole were established with administration of adenosine to facilitate precise device deployment. Postoperative imaging with transesophageal echocardiography and magnetic resonance angiography revealed complete resolution of the AAP, and the patient had done well at 7-month follow-up. Treatment of a mycotic aortic pseudoaneurysm with an endoprosthesis in a patient without other treatment alternatives can be performed safely, with acceptable short-term results.

Aneurysm, False↗
PubMed2003

Impact of an endovascular program on the operative experience of abdominal aortic aneurysm in vascular fellowship and general surgery residency.

BACKGROUND: This study was performed to determine the impact of an endovascular program (EVP) on open and endovascular abdominal aortic aneurysm (AAA) operations in a residency training institution. METHODS: Over an 8-year period ending in September 2001, hospital records of all patients undergoing open or endovascular AAA repair were retrospectively reviewed. Data were analyzed to determine the changing patterns of case volume, type of operative repair, and complexity of open repair with regards to the training of both general surgical chief residents and vascular fellows. RESULTS: A total of 849 AAA operations were performed during the study period. The initiation of the EVP in 1997 resulted in a steady increase in the total annual AAA cases (P < 0.05), due in part to an increase in endovascular AAA operations despite a decrease in the annual open AAA volume. EVP had a positive impact on the overall operative experience of vascular fellows owing to the large increase in their endovascular AAA experience (annual mean pre-EVP 3 +/- 0.8 versus post-EVP 47 +/- 9.6, P < 0.01). A significant reduction occurred in the vascular fellows' open AAA experience (annual mean pre-EVP 40 +/- 12.7 versus post-EVP 19 +/- 9.4, P < 0.05). EVP did not affect the endovascular AAA experience of general surgery chief residents (annual mean pre-EVP 1 +/- 0.8 versus post-EVP 3 +/- 1.5, not significant). A significant reduction occurred in chief residents' open AAA experience (annual mean pre-EVP 39 +/- 9.7 versus post-EVP 18 +/- 7.4, P < 0.05). EVP did not affect the operative experience of complex open AAA operations in either vascular fellows or general surgery residents. CONCLUSIONS: An endovascular program has a positive impact on the aortic aneurysm practice in an academic institution, as evidenced by the significant increase in annual endovascular AAA cases despite a decrease in open AAA operations. Although vascular fellows continued to maintain sufficient experience in both open and endovascular AAA operations, general surgery chief residents suffered a significant decrease in their open AAA experience. Further evaluation of the residency system is warranted to better optimize the training paradigm of both vascular fellowship and general surgery residency.

Aortic Aneurysm, Abdominal↗
PubMed2003

The LifeSite Hemodialysis Access System in patients with limited access.

OBJECTIVE: The LifeSite Hemodialysis Access System was recently introduced as a completely subcutaneous device with reported advantages of improved patient comfort and reduced catheter-related infection. The performance of the LifeSite catheter at a single, tertiary-care university medical center was reviewed. METHODS: We retrospectively reviewed all patients who underwent placement of the LifeSite catheter between February 2001 and March 2002. Kaplan-Meier analysis was used to determine the probability of patient survival, freedom from catheter-related infection, and freedom from device failure necessitating catheter removal. RESULTS: Thirty-six patients who had previously received dialysis for an average of 6.1 years underwent placement of 37 LifeSite catheters. Most patients (95%) were referred for LifeSite placement because they had exhausted all available arteriovenous fistula and graft sites. Mean follow-up was 6.8 months, with a patient survival rate of 81% at 8 months. Primary and secondary patency rates were 62% and 87% at 8 months, respectively. Two patients died from infectious device-related complications. Twelve of 17 patients (71%) with device-related infection did not manifest any signs or symptoms at the valve site. There were 2.4 catheter-related infections and 2.6 device failures requiring removal per 1000 patient-catheter days. Freedom from infection and device removal at 8 months was 46% and 49%, respectively. CONCLUSIONS: The LifeSite demonstrated acceptable patency, infection, and device failure rates; however, in patients with limited access, unrecognized infection and death may occur. The LifeSite should not be used as a substitute for a more permanent form of hemodialysis access.

Bacterial Infections↗