Biomedical subjects

Elliot L Chaikof

Publications and source records attributed to Elliot L Chaikof.

67 records · Page 4Linked to original sources

PubMed2002

Endoluminal versus open treatment of descending thoracic aortic aneurysms.

PURPOSE: This report describes the authors' initial experience with the Excluder thoracic endoprosthesis (W. L. Gore and Associates, Inc, Flagstaff, Ariz) and the thoracic Talent endoprosthesis (Medtronic AVE, Sunrise, Fla) and their safety and efficacy in the primary endovascular repair of descending thoracic aortic aneurysms (TAAs). In addition, comparison with a historic nonrandomized cohort of patients that had undergone open repair of descending TAAs is reported. PATIENTS AND METHODS: Repair of TAA (mean diameter, 68 +/- 22 mm) was attempted in 19 patients with the Excluder (n = 14) and the Talent (n = 5) endoprostheses between March 1999 and January 2000. This group was compared with a historic nonrandomized cohort of 10 patients that had undergone open repair of anatomically similar descending TAA (mean diameter, 74 +/- 22 mm) between January 1996 and January 1998. The mean age in the endovascular group was 70.6 +/- 5.3 years versus 70.1 +/- 4.5 years in the historic open group. All the procedures were performed in a standard operating room with angiographic capabilities. In the historic open group, each standard tube graft repair of descending TAA was performed by one of three staff surgeons. RESULTS: Endograft deployment was successful in 18 patients (95%). The procedure was aborted in one patient (Excluder) because of small iliac arteries and access difficulty. The average operative time was 155 +/- 62 minutes, with a mean blood loss of 325 +/- 353 mL (versus 256 +/- 102 minutes and 1205 +/- 1493 mL, respectively, in the open group). Eight patients needed the planned use of more than one component for enhanced sealing or additional length in the endovascular group. No type I endoleaks were identified on the intraoperative completion angiography. One perioperative mortality occurred in the endovascular group and the open group. In the endovascular group, other complications included retroperitoneal hematoma and external iliac artery dissection (n = 1), lymphocele (n = 1), and common femoral artery pseudoaneurysm (n = 1). In the open group, other complications included ischemic colitis (n = 1), severe renal insufficiency (n = 2), wound infection (n = 1), and stroke (n = 1). In the endovascular group, the length of stay was 6.2 +/- 3.3 days (range, 1 to 13 days), with only nine patients needing intensive care, whereas in the open group, the length of stay was 16.3 +/- 6.7 days, with all patients needing intensive care. Endoleaks, graft migrations, or ruptures were not seen on the 1-month, 6-month, and 12-month follow-up computed tomographic scans in the endovascular group. On the average, aneurysm size decreased from 68 +/- 22 mm to 58 +/- 13 mm, to 51 +/- 14 mm, and to 49 +/- 12 mm at 1, 6, and 12 months after endovascular repair, respectively. No spinal cord ischemia was seen in either group. CONCLUSION: The endoluminal repair was effective in exclusion of descending TAAs from the systemic circulation in this selected group of patients. In this short-term follow-up, compared with the nonrandomized historic cohort of open descending TAA repair, the endovascular group had significantly shorter operating times and hospital and intensive care unit stays and lower operative blood loss. Further follow-up and continued assessment of the long-term durability of these devices in elective and emergency circumstances are warranted.

Aged↗

PubMed2002

Conservatism and new technology: the impact on abdominal aortic aneurysm repair.

The last decade has represented a time of fundamental change in the treatment of abdominal aortic aneurysms (AAAs). Potentially, vascular surgeons will either acquire catheter-based skills or relinquish the care for many patients with infrarenal AAA. We investigated AAA referral patterns and method of AAA repair after the establishment of an endovascular AAA program at our institution. We conducted a retrospective review of elective AAA repairs after the initiation of an endovascular AAA program in April 1994. Six vascular surgeons performed all procedures with a clear distinction between the surgeons (n=3) who performed traditional AAA repair only and those (n=3) who managed AAAs by means of either endovascular or traditional treatment. From April 1994 through December 2000, 740 elective AAA repairs were performed. During this time the mean number of AAA repairs has been 106/year ranging from 75 to 155/year. More notable however is the steady increase in the percentage of endovascular AAA repairs from 6 per cent of all AAA repairs in 1994 to 61 per cent in 2000. During this time traditional surgeons have experienced a plateau in total AAA repairs performed per year with their number of open repairs decreasing by 36 per cent. At the same time endovascular surgeons have seen a progressive rise in total AAA cases including an increase of 200 per cent in open repairs and of 1367 per cent in endovascular repairs. Our vascular surgeons who repair AAA utilizing both endovascular and open techniques have experienced an increase in aneurysm referrals since the advent of an endovascular AAA program. Those who have not adopted endovascular skills have seen a decline in their aneurysm practice. The larger question about whether or not to embrace new technology before the availability of long-term follow-up remains unanswered.

Aortic Aneurysm, Abdominal↗

PubMedDate not supplied

Glycosaminoglycan-mimetic biomaterials. 3. Glycopolymers prepared from alkene-derivatized mono- and disaccharide-based glycomonomers.

Mono- and disaccharide-containing glycopolymers were synthesized by two different free-radical processes, and their ability to act as heparan sulfate glycomimetics in promoting the binding of Fibroblast Growth Factor-2 (FGF-2) to its receptor (FGFR-1) was evaluated using an in vitro cell-based assay. Cyanoxyl (*OC triple bond N)-mediated polymerization of acrylamide with alkene-derivatized mono- and disaccharides including sulfated or nonsulfated N-acetyl-D-glucosamine is described. The results of this approach are compared to those obtained via the classical ammonium peroxodisulfate (APS)/N,N,N',N'-tetramethylethylenediamine (TMEDA) initiating system and confirm the capacity of cyanoxyl-mediated polymerization to generate a variety of glycopolymers with high saccharide contents and low polydispersity indexes. In vitro assays demonstrate that specific glycopolymers can potentiate FGF-2/FGFR-1 binding interactions.

Alkenes↗

PubMedDate not supplied

A glycopolymer chaperone for fibroblast growth factor-2.

Mono- and disaccharide-containing glycopolymers were synthesized by cyanoxyl-mediated polymerization of acrylamide with acrylate-derivatized mono- and disaccharides. We demonstrate that a glycopolymer bearing pendant, fully sulfated lactose units effectively replaces heparin and heparan sulfate as a molecular chaperone for fibroblast growth factor-2 (FGF-2). Specifically, a compound was identified that protects FGF-2 from proteolytic, acid, and heat-induced degradation, while selectively promoting growth factor and receptor dimerization. Significantly, the capacity of this heparin-mimic to promote an FGF-2 specific proliferative cell response was confirmed and suggests potential applications for this compound and related derivatives in areas related to therapeutic angiogenesis.

Acids↗

PubMedDate not supplied

C-terminal site-specific PEGylation of a truncated thrombomodulin mutant with retention of full bioactivity.

Addition of poly(ethylene glycol) to bioactive proteins (PEGylation) improves their plasma half-life, enhances stability against proteolytic cleavage, and may also decrease protein immunogenicity. Characteristically, PEGylation usually involves a reaction to available lysine amino groups, some of which may be within or near a bioactive site. Thus, most protocols are nonspecific and result in a loss of protein activity. We report herein a strategy for site-specific PEGylation of a thrombomodulin (TM) derivative at the C terminus. A truncated TM mutant consisting of epidermal growth factor (EGF)-like domains 4-6 was expressed in Escherichia coli with a C-terminal azido-methionine. The TM mutant was site-specifically conjugated to a methyl-PEG-triarylphosphine compound via the Staudinger reaction. Enzymatic activity of the TM construct before and after PEGylation was unchanged, which confirms the utility of this site-specific PEGylation scheme.

Binding Sites↗

PubMedDate not supplied

Facile synthesis of chain-end functionalized glycopolymers for site-specific bioconjugation.

A series of derivatized arylamine initiators were used to generate chain-end functionalized glycopolymers by cyanoxyl-mediated free-radical polymerization. Significant features of this strategy include the capacity to produce polymers of low polydispersity (PDI < 1.5) under aqueous conditions using unprotected monomers bearing a wide range of functional groups. In addition, the presence of a phenyl ring simplifies calculation of polymer saccharide content and molar mass by (1)H NMR. It is particularly noteworthy, however, that derivatized arylamine initiators in conjunction with the presence of a terminal cyanate group provide a convenient approach for synthesizing polymers with a variety of distinct functional groups at alpha and omega chain ends. In the process, the capacity to label glycopolymers or otherwise conjugate them to proteins or other molecules is greatly enhanced.

Binding Sites↗

PubMedDate not supplied

Carbohydrate and protein immobilization onto solid surfaces by sequential Diels-Alder and azide-alkyne cycloadditions.

We demonstrate the applicability of sequential Diels-Alder and azide-alkyne [3 + 2] cycloaddition reactions (click chemistry) for the immobilization of carbohydrates and proteins onto a solid surface. An alpha,omega-poly(ethylene glycol) (PEG) linker carrying alkyne and cyclodiene terminal groups was synthesized and immobilized onto an N-(epsilon-maleimidocaproyl) (EMC)-functionalized glass slide via an aqueous Diels-Alder reaction. In the process, an alkyne-terminated PEGylated surface was provided for the conjugation of azide-containing biomolecules via click chemistry, which proceeded to completion at low temperature and in aqueous solvent. As anticipated, alkyne, azide, cyclodiene, and EMC are independently stable and do not react with common organic reagents nor functional groups in biomolecules. Given an appropriate PEG linker, sequential Diels-Alder and azide-alkyne [3 + 2] cycloaddition reactions provide an effective strategy for the immobilization of a wide range of functionally complex substances onto solid surfaces.

Alkynes↗

PubMedDate not supplied

Glycosaminoglycan mimetic biomaterials. 4. Synthesis of sulfated lactose-based glycopolymers that exhibit anticoagulant activity.

Cyanoxyl persistent radicals can be used as chain-growth moderators of the statistical copolymerization of a variety of monomers. We report herein the preparation of fully sulfated lactose-based glycopolymers by cyanoxyl (.OC[triple bond]N)-mediated free-radical polymerization of acrylamide derivatized glycomonomers in good yield (60-80%) and low polydispersity (1.1 < M(w)/M(n) < 1.6). Prolongation of the activated partial thromboplastin time (aPTT) was observed, and structure-activity relationships were defined. Specifically, the anticoagulant effect varied in response to both polymer molecular weight and the density of pendant sulfated lactose units. Nonetheless, measured thrombin times were only modestly prolonged suggesting that the observed anticoagulant effect is not primarily related to direct thrombin inhibition.

Acrylic Resins↗

PubMedDate not supplied

Photo-cross-linking of type I collagen gels in the presence of smooth muscle cells: mechanical properties, cell viability, and function.

The effectiveness of photomediated cross-linking of type I collagen gels in the presence of rat aortic smooth muscle cells (RASMC) as a method to enhance gel mechanical properties while retaining native collagen triple helical structure and maintaining high cell viability was investigated. Collagen was chemically modified to incorporate an acrylate moiety. Collagen methacrylamide was cast into gels in the presence of a photoinitiator along with RASMC. The gels were cross-linked using visible light irradiation. Neither acrylate modification nor the cross-linking reaction altered collagen triple helical content. The cross-linking reaction, however, moved the denaturation temperature beyond the physiologic range. A twelve-fold increase in shear modulus was observed after cross-linking. Cell viability in the range of 70% (n = 4, p > 0.05) was observed in the photo-cross-linked gels. Moreover the cells were able to contract the cross-linked gel in a manner commensurate with that observed for natural type I collagen. Methacrylate-mediated photo-cross-linking is a facile route to improve mechanical properties of collagen gels in the presence of cells while maintaining high cell viability. This enhances the potential for type I collagen gels to be used as scaffolds for tissue engineering.

Acrylamides↗

PubMedDate not supplied

Synthesis and characterization of glycopolymer-polypeptide triblock copolymers.

Glycopolymer-polypeptide triblock copolymers of the structure, poly(l-alanine)-b-poly(2-acryloyloxyethyl-lactoside)-b-poly(l-alanine) (AGA), have been synthesized by sequential atom transfer radical polymerization (ATRP) and ring-opening polymerization (ROP). Controlled free radical polymerization of 2-O-acryloyl-oxyethoxyl-(2,3,4,6-tetra-O-acetyl-beta-d-galactopyranosyl)-(1-4)-2,3,6-tri-O-acetyl-beta-d-glucopyranoside (AEL) by ATRP with a dibromoxylene (DBX)/CuBr/bipy complex system was used to generate a central glycopolymer block. Telechelic glycopolymers with diamino end groups were obtained by end group transformation and subsequently used as macroinitiators for ROP of l-alanine N-carboxyanhydride monomers (Ala-NCA). Gel permeation chromatography (GPC) and nuclear magnetic resonance (NMR) spectroscopy analysis demonstrated that copolymer molecular weight and composition were controlled by both the molar ratios of the Ala-NCA monomer to macroinitiator and monomer conversion and exhibited a narrow distribution (Mw/Mn = 1.06-1.26). FT-IR spectroscopy of triblock copolymers revealed that the ratio of alpha-helix/beta-sheet increased with poly(l-alanine) block length. Of note, transmission electron microscopy (TEM) demonstrated that selected amphiphilic glycopolymer-polypeptide triblock copolymers self-assemble in aqueous solution to form nearly spherical aggregates of several hundreds nanometer in diameter. Significantly, the sequential application of ATRP and ROP techniques provides an effective method for producing triblock copolymers with a central glycopolymer block and flanking polypeptide blocks of defined architecture, controlled molecular weight, and low polydispersity.

Biocompatible Materials↗

PubMedDate not supplied

Alterations in physical cross-linking modulate mechanical properties of two-phase protein polymer networks.

Physically cross-linked protein-based materials possess a number of advantages over their chemically cross-linked counterparts, including ease of processing and the ability to avoid the addition or removal of chemical reagents or unreacted intermediates. The investigations reported herein sought to examine the nature of physical cross-links within two-phase elastin-mimetic protein triblock copolymer networks through an analysis of macroscopic viscoelastic properties. Given the capacity of solution processing conditions, including solvent type and temperature to modulate the microstructure of two-phase protein polymer networks, viscoelastic properties were examined under conditions in which interphase block mixing had been either accentuated or diminished during network formation. Protein networks exhibited strikingly different properties in terms of elastic modulus, hysteresis, residual deformability, and viscosity in response to interdomain mixing. Thus, two-phase protein polymer networks exhibit tunable responses that extend the range of application of these materials to a variety of tissue engineering applications.

Biocompatible Materials↗

PubMedDate not supplied

One-pot glyco-affinity precipitation purification for enhanced proteomics: the flexible alignment of solution-phase capture/release and solid-phase separation.

A one-pot affinity precipitation purification of carbohydrate-binding protein was demonstrated by designing thermally responsive glyco-polypeptide polymers, which were synthesized by selective coupling of pendant carbohydrate groups to a recombinant elastin-like triblock protein copolymer (ELP). The thermally driven inverse transition temperature of the ELP-based triblock polymer is maintained upon incorporation of carbohydrate ligands, which was confirmed by differential scanning calorimetry and (1)H NMR spectroscopy experiments. As a test system, lactose derivatized ELP was used to selectively purify a galactose-specific binding lectin through simple temperature-triggered precipitation in a high level of efficiency. Potential opportunities might be provided for enhanced proteomic, cell isolation as well as pathogen detection applications.

Amino Acid Sequence↗

PubMedDate not supplied

Unusual case of right-sided May-Thurner syndrome and review of its management.

May-Thurner syndrome is a phenomenon commonly described as an acquired stenosis of the left common iliac vein as a result of right common iliac artery compression. We report an unusual case of right-sided May-Thurner syndrome in a patient found to have a left-sided inferior vena cava. We also review the management of this patient using angioplasty, intraoperative thrombolysis, and endoluminal stent placement.

Angioplasty, Balloon↗