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E L Chaikof

Publications and source records attributed to E L Chaikof.

At least 37 records · Page 2Linked to original sources
PubMed1999

Cytomimetic biomaterials. 3. Preparation and transport studies of an alginate/amphiphilic copolymer/polymerized phospholipid film.

The significance of molecular design methodologies based upon membrane-mimetic systems lies in the ability to engineer robust materials of varying geometry with a high degree of reproducibility and molecular control over surface order and chemistry. However, non-covalently associated assemblies, in and of themselves, are often insufficiently robust for many applications. We have previously reported the in situ polymerization of a single phospholipid monolayer on a self-assembled film of octadecyltrichrolosilane (OTS) on glass, as well as the polymerization of phospholipids on an amphiphilic, dialkyl-containing terpolymer bound to a gold-coated silicon wafer. We now report the polymerization of a phospholipid monolayer assembly onto an alkylated hydrogel substrate with significant alteration in both surface chemistry and mass transport properties at the hydrogel-water interface. A general platform is thereby created for enhancing the control of either the local delivery of specific macromolecules or the immunoisolation barrier for many cell based therapies.

Alginates↗
PubMed1999

Anatomic changes after endovascular grafting for aneurysmal disease.

Long-term follow-up of controlled clinical trials of endovascular grafting for aortic aneurysms will provide data on the safety and efficacy of this new treatment to reduce morbidity and mortality compared with standard treatment. It will be several years before this information will be available, and careful analysis of surrogate markers for clinical success has value for predicting long-term outcome. One essential surrogate marker is aortic aneurysm diameter, which has traditionally been the most important variable in calculating rupture risk, and multiple studies have shown that aneurysms shrink after complete endovascular exclusion. Furthermore, measurements of aortic neck size and aortic length has shown interesting patterns that may affect the durability of endovascular repair and, thus, may suggest potential strategies for the design of future devices.

Aorta↗
PubMed1998

Concomitant aortic and renal artery reconstruction in patients on an intensive antihypertensive medical regimen: long-term outcome.

A beneficial effect in blood pressure control is presumed for patients on an intensive preoperative antihypertensive regimen who undergo empiric renal revascularization. Nonetheless, a noticeable decline in surgical cure rates for hypertension has been recently observed in patients with generalized atherosclerosis. The outcome of patients on multiple preoperative antihypertensive agents who underwent combined aortic and renal artery reconstruction was reviewed. The study population comprised 43 patients who underwent concomitant renal artery and aortic reconstruction for atherosclerotic disease between 1983 and 1995 and who were taking two or more antihypertensive medications and had a serum creatinine of less than or equal to 1.7 mg/dL. Operative management included an aortic reconstruction with either unilateral (n = 22) or bilateral (n = 19) aortorenal bypass or renal endarterectomy (n = 2). Operative mortality was 4.7% (2 of 43). The estimated 5-yr probability of survival was 83% (95% C.I. 0.70, 0.99). Late follow-up data on blood pressure control were available for review in 32 patients at a median follow-up of 37 months. Hypertension was cured in 1 (3%) and improved in an additional 15 (47%) patients. The numbers of antihypertensive medications taken preoperatively (mean = 2.7) declined at late follow-up (mean = 1.6). Notably, the largest reduction was observed with beta blockers (p = 0.006), central sympatholytics (p = 0.041), and angiotensin converting enzyme (ACE) inhibitors (p = 0.052). The number of preoperative antihypertensive medications was not significantly related to survival or to blood pressure improvement. However, uncontrolled preoperative hypertension despite antihypertensive therapy was associated with a favorable blood pressure response to operation (p < 0.001). Patients on an intensive antihypertensive regimen can safely undergo concomitant renal artery and aortic reconstruction for the empiric management of hypertension. Poorly controlled preoperative hypertension in the presence of multiple antihypertensive agents is a favorable marker for improved postoperative blood pressure control.

Aged↗
PubMed1998

The synthesis of neoglycophospholipid conjugates via reductive amination of omega-oxoalkylglycosides and phosphatidylethanolamines.

Phospholipid conjugates of mono- and disaccharides tethered with an n-decanyl spacer were efficiently synthesized via an improved reductive amination of deprotected omega-oxodecanyl beta-glycosides and phosphatidylethanolamines with or without alkenyl groups. The omega-oxodecanyl beta-glycosides were prepared by stereoselective glycosidation of glycosyl halides with 1, 10-decanediol followed by pyridinium dichromate oxidation. The acetyl groups of the omega-oxodecanyl beta-glycosides were removed with sodium methoxide prior to their conjugation with phosphatidylethanolamines.

Carbohydrate Sequence↗
PubMed1998

Continued expansion of aortic necks after endovascular repair of abdominal aortic aneurysms. EVT Investigators. EndoVascular Technologies, Inc.

BACKGROUND: Longitudinal studies have revealed that the aortic segment proximal to an infrarenal abdominal aortic aneurysm (AAA) is at risk for continued enlargement after a standard aneurysm repair. Similarly, preliminary reports have shown expansion of one or both aortic necks after endovascular repair. Although some investigators have suggested that this may be a transient effect, continued dilatation at the endograft attachment site could effect the overall device stability. METHODS: As part of a multi-institutional trial of endovascular grafting for the treatment of AAA, 59 patients were successfully implanted with straight endografts between February 1993 and January 1995. A morphometric analysis of aortic neck size was undertaken with serial review of computed tomography scans available through April 1997. The neck sizes at both graft attachment sites were measured, with investigators blinded to patient identity and date of scan. Changes in minor diameter were defined, annual interval expansion rates were calculated, and the data were correlated with endoleak, device migration, aneurysm size change, endograft diameter, attachment system fractures, and initial preimplant neck size. RESULTS: Significant aortic neck enlargement, particularly at the level of the distal neck, was observed for at least 24 months after AAA repair. The annual interval dilation rates of the proximal aortic neck were 0.7 +/- 2.1 mm/year (P = .023) and 0.9 +/- 1.9 (P = .008) mm/year during the first and second years, respectively. Enlargement of the distal neck during the observation period was more marked, with corresponding annual expansion rates of 1.7 +/- 2.9 mm/year (P < .001) and 1.9 +/- 2.5 (P < .001) mm/year. In 5 patients (14%), the minor diameter of the distal neck was at least 6 mm larger than the preimplant diameter of the graft. Migration of the distal attachment system was observed in 3 of these 5 patients. Expansion rates did not have a statistically significant correlation with initial neck size, endograft dimensions, aneurysm size change, presence of endoleak, or attachment system fracture. CONCLUSIONS: Aortic neck enlargement was observed for at least 2 years after endovascular grafting. Close patient follow-up remains mandatory in lieu of the potential risk of late failure as a result of continued aortic expansion. The relative contribution of device design to this phenomenon will need to be defined.

Aged↗
PubMed1997

Characterization of single-cell migration using a computer-aided fluorescence time-lapse videomicroscopy system.

Single-cell assays of cell migration, while yielding dynamic measurements of cell position and morphology, are predominantly limited by the time required for data collection and analysis. Computer-aided fluorescence time-lapse videomicroscopy (CAFTiV) was developed in order to facilitate the tracking and rapid examination of large numbers of motile cells. The system combines time-lapse videomicroscopy with epifluorescence capability, which allows full automation of image capture, sorting, and analysis due to the low background in the fluorescence images. Utilizing the CAFTiV system, data analysis time was reduced from over 125 h to less than 1 labor minute. In addition, fluorescence imaging permits cell tracking in small-volume chambers (<100 microL), which is useful should the addition of expensive reagents be required. It is anticipated that the ability to characterize both biochemical and biophysical properties responsible for cell movement will be enhanced by this methodology.

Cell Movement↗
PubMed1997

Endothelial cells exhibit differential chemokinetic and mitogenic responsiveness to alpha-thrombin.

Rapid regeneration of the endothelium is a critical component of vascular wall repair because limitations of this process enhance early thrombotic and vasospastic complications, as well as late sequelae of recurrent lesion formation. We have postulated that direct activation of the thrombin receptor initiates both mitogenic and chemokinetic endothelial behavior which facilitates intimal repair. To characterize the role of the thrombin receptor in human endothelial cell (EC) proliferation and migration, we investigated the effects of both alpha-thrombin (0.5-10 U/ml) and its receptor-activating peptide (TRAP; 1-100 microM). Responses of human aortic (HAEC) and umbilical vein (HUVEC) were characterized using [3H]thymidine and 61Cr microcarrier bead assays of proliferation and migration, respectively. Expression of motility-related genes was evaluated using a ribonuclease protection assay. Thrombin exerts both of its chemokinetic and mitogenic effects differentially in human endothelial cells. Following 2 or 4 days in culture, HUVEC proliferation increased two- to threefold after exposure to thrombin, primarily in the low concentration range (P < 0.05). However, HACE proliferation was inhibited up to 50% after a 4-day incubation period (P < 0.005). These mitogenic effects, including the inhibition of aortic endothelial cell proliferation, were reproduced, in part, by thrombin receptor activation with TRAP. In contrast, thrombin stimulates migratory responses in HAEC, but not HUVEC. However, this behavior was not reproduced by TRAP. It is noteworthy that urokinase-plasminogen activator (u-PA) expression was much more strongly expressed in migrating HAEC than in the HUVEC population. Moreover, when stimulated with thrombin, u-PA gene expression was significantly augmented in HAEC. It has been speculated that an effective human thrombin receptor (HTR) antagonist may reduce the proliferation of vascular smooth muscle cells and the development of a restenotic lesion following arterial wall injury. Our data suggest that such an inhibitor will likely also accelerate intimal regeneration through a dominant effect on limiting the HTR inhibitory effect on endothelial proliferation.

Amino Acid Sequence↗
PubMed1997

Role of fibronectin and sulfated proteoglycans in endothelial cell migration on a cultured smooth muscle layer.

Endothelial cell (EC) migration is essential for the healing of denudation injuries to the vessel wall. This event occurs in vivo in a pericellular environment and should be regulated in part by juxtacrine and paracrine interactions with underlying smooth muscle cells (SMCs). To investigate the EC migration behavior over SMCs under direct cell-cell contact conditions, we have utilized human umbilical vein endothelial cells (HUVECs) grown to confluence on microcarrier beads and radiolabeled with chromium-51. The EC carrying beads were spread over a confluent human aortic SMC monolayer and cocultured for 48 hr, allowing the EC to migrate from beads onto the underlying SMC monolayer in the presence of sodium chlorate, cycloheximide (CHM), or anti-fibronectin monoclonal antibody (anti-FN mAb). The level of EC migration was quantified by counting the amount of radioactivity on the SMC layer after the removal of the beads. The presence of a SMC layer enhanced EC migration more than threefold (P < 0.05). Furthermore, EC migration was inhibited from 30 to 80% (P < 0.05) by sodium chlorate, CHM, and anti-FN mAb in a dose-dependent fashion. This model has shown that smooth muscle cells augment endothelial motility. Both fibronectin and sulfated proteoglycans released by ECs and SMCs likely play an important role in the regulation of EC migration behavior over SMCs. The method described of using radiolabeled ECs on microcarrier beads should prove to be a useful tool in the study of cell migration in a heterotypic cellular environment.

Antibodies↗
PubMed1996

Lipopeptide conjugates: biomolecular building blocks for receptor activating membrane-mimetic structures.

A simple method for the derivatization of phospholipid subunits with short peptide sequences is presented. Amphiphilic conjugates of distearoylphosphatidylethanolamine (DSPE) and the minimal human thrombin-receptor peptide agonist SFLLRN were synthesized via coupling of the bromoacetyl derivative of DSPE (PEBr) with a thiol-terminated decapeptide of SFLLRN. Bromoderivatization of DSPE was performed by condensation of bromoacetic acid and DSPE, with an overall yield of 40%. Coupling of PEBr and the unprotected thiol-terminated decapeptide was performed in chloroform/methanol/water in the presence of triethylamine and afforded 25.5% of the lipopeptide. The compound was characterized by TLC, 1H-NMR (600 MHz) and mass spectrometry. Lipopeptide bioactivity was confirmed by a platelet aggregation assay. The EC50 of the all-L amino acid lipopeptide was 38 +/- 3 microM. The all-D conjugate was inactive. Model receptor-activating systems, including well-ordered assemblies of amphiphilic phospholipid-peptide conjugates, represent the first step in the construction of bioactive surfaces for tissue engineering based on a membrane-mimetic approach.

Bromine Compounds↗
PubMed1996

Carotid endarterectomy in patients with contralateral carotid occlusion: review of a 10-year experience.

A total of 116 carotid endarterectomies were performed in patients with a totally occluded opposite internal carotid artery over a 10-year period from 1983 until 1992. The average age of patients was 66.4 years; 75% were men and 25% were women. The average degree of stenosis on the operated side was 76.7%. Twenty-one patients (18.1%) had had a documented previous stroke referrable to the side of the occlusion; 22 had a neurologic deficit attributable to the occluded vessel at the time of preoperative evaluation. Indications for surgery included transient ischemic attacks in 35 (30.2%), ipsilateral stroke in 10 (8.6%), amaurosis fugax in 11 (9.5%), and high-grade asymptomatic stenosis in 60 (51.7%). Forty-eight percent of the procedures were performed using local anesthesia, with intraluminal shunts inserted in all except one patient. The combined 30-day mortality and stroke morbidity in this population was 4.3%, which is comparable with a combined stroke and death rate of 4.0% among 956 patients without contralateral carotid occlusion undergoing endarterectomy during this period. This experience suggests that endarterectomy can be performed safely in the patient with internal carotid occlusion and is an important mechanism for the prevention of stroke.

Adult↗
PubMed1996

Empirical reconstruction of the renal artery: long-term outcome.

PURPOSE: Unequivocal indications for renal artery reconstruction remain the presence of significant underlying renal insufficiency or severe hypertension. Thus surgical intervention for renal artery stenosis in the absence of this clinical picture may well be considered empirical and, as a consequence, treatment recommendations are ill-defined. Our experience with reconstruction of the minimally symptomatic or asymptomatic renal artery lesion in association with primary aortic repair over a 10-year period was reviewed. METHODS: Thirty-two patients who had atherosclerotic renal artery stenosis > or = 70% underwent prophylactic renal revascularization between 1982 and 1992. The patients' median age was 63 years (range, 44 to 79 years); 23 (72%) were men and nine (28%) were women. All had preoperative serum creatinine levels < or = 1.7 mg/dl (1.29 +/- 0.24 mg/dl) and were receiving either no antihypertensive medication (22%) or only a single agent (78%). Aortoiliac occlusive disease was present in 38% of this population, and aortic aneurysmal disease either alone or in combination with occlusive disease was found in 62%. RESULTS: Operative management included unilateral renal artery repair in 21 patients (66%) and bilateral renal revascularization in the remaining 11 (34%). The median decrease in postoperative serum creatinine level (> or = 7 days after operation) was 0.81 +/- 0.05% (mean postoperative serum creatinine level 1.27 +/- 0.07 mg/dl). The 30-day operative mortality rate was 3.1% (1 of 32). Late follow-up was available for 96% of patients (30 of 31; median, 64 months). Kaplan-Meier life table analysis revealed a 5-year probability of survival of 90.2% (95% confidence interval, 0.802 to 1.00). Stability of renal function was assessed by modeling the change in serum creatinine level over time with the intraclass correlation model. A serum creatinine level (mg/dl) = 1.3348 + 0.0011 x time (months) demonstrated minimal deterioration of excretory function during the observation period. Furthermore, the blood pressure of the majority of patients (75%) remained normal either with a single agent or without medication. Recurrent stenosis in one patient required treatment by percutaneous transluminal angioplasty. CONCLUSIONS: Adjunctive repair of the renal artery may be an appropriate option in selected patients who undergo simultaneous aortic surgery, even in the absence of severe hypertension or renal insufficiency. Surgical intervention can be accomplished with acceptable perioperative morbidity rates, and stability of renal function is sustainable in the majority of patients.

Adult↗
PubMed1995

Growth-related responses in arterial smooth muscle cells are arrested by thrombin receptor antisense sequences.

The capacity of antisense sequences to the thrombin receptor to selectively inhibit thrombin receptor expression and limit mitogenic responses in vascular wall cells was investigated in vitro. Eight phosphorothioate oligodeoxynucleotides based on the sequences of the rat thrombin receptor (including sense, antisense, scrambled, and missense controls) were synthesized, characterized, and purified by high performance liquid chromatography. The antisense oligodeoxynucleotide (ODN 4) inhibitory effect was sequence-specific and both time-and concentration-dependent. A reduction in serum or alpha-thrombin-induced smooth muscle cell (SMC) proliferation was noted as early as 3 days at 30 microM (82%; 6.17 +/- 1.01 versus 34.08 +/- 3.89 x 10(4) cells/well; p < 0.05) and at a dose as low as 15 microM after 4 days in culture (19%; p < 0.05). Nonspecific effects were enhanced after prolonged exposure of SMC to the antisense oligodeoxynucleotide (> or = 6 days). A reduction of inositol phosphate generation greater than 50% (p < 0.05) was detected after exposure of SMC to antisense but not to sense or scrambled nucleotide sequences. This was observed after stimulation with both thrombin and SFFLRN (thrombin receptor peptide agonist). Northern blot analysis and enzyme-linked immunosorbent assays revealed 50 and 22% decreases, respectively, in thrombin receptor mRNA and protein (cell surface) levels in antisense oligonucleotide-treated (72 h) SMC as compared to untreated cells, suggesting that thrombin receptor down-regulation occurred at the pretranslational level. Thus, thrombin receptor-specific antisense sequences inhibit growth-related effects both of serum and thrombin on smooth muscle cells, potentially providing a new strategy for selective inhibition of receptor-mediated arterial injury responses.

Amino Acid Sequence↗
PubMed1995

Morbidity and mortality associated with carotid endarterectomy: effect of adjunctive coronary revascularization.

The occurrence of significant carotid disease in patients requiring coronary revascularization results in the dilemma of whether simultaneous or staged operations should be performed. To determine appropriate therapy we reviewed this experience at Emory University Hospital. During a 10-year period from 1983 to 1992, 110 patients underwent carotid endarterectomy during the same hospitalization or simultaneously with coronary artery bypass; 907 patients underwent carotid endarterectomy alone during the same period. The combined 30-day postoperative stroke and death rate was 18.2% for the 110 patients undergoing concomitant procedures. When comparing morbidity and mortality rates for those having simultaneous carotid endarterectomy and coronary artery bypass with those having delayed coronary artery bypass, the latter group was found to have a 6.6% combined risk of postoperative stroke or death within 30 days, whereas those undergoing simultaneous procedures had a 26.2% rate. In the control group of 907 patients undergoing carotid endarterectomy alone during the same period, the combined 30-day mortality and stroke morbidity rate was 2.1%. Although the patient population undergoing simultaneous carotid and coronary revascularization may have more severe disease, we believe that combining the procedures during the same operative setting results in an increased perioperative stroke and death rate. Consequently only extremely high-risk patients are selected for simultaneous procedures; otherwise our experience suggests that delaying coronary artery bypass by several days will reduce overall postoperative mortality and stroke morbidity.

Cerebrovascular Disorders↗
PubMed1995

The occluded renal artery: an ongoing surgical challenge.

Nephrectomy and revascularization are currently the preferred options in the management of the chronically occluded renal artery in patients with renovascular hypertension or renal insufficiency. We review our experience with these two options including early and late functional outcome. Between December 1982 and August 1993, chronic occlusion of the main renal artery was documented in 30 patients. Patients were categorized with respect to surgical intervention: group I underwent nephrectomy (on the occluded side) plus contralateral revascularization and group II underwent revascularization of the occluded renal artery. The median age at the time of operative intervention was 63 years; 53% of the patients were women and 47% were men. Hypertension was poorly controlled (> or = 3 medications) in 19 patients, and the preoperative serum creatinine level was > 1.8 mg/dl in 24 patients (mean 2.6 +/- 1.4 mg/dl). There were 16 patients in group I and 14 patients in group II, and there were no perioperative deaths. Estimated glomerular filtration rate (> or = 7 days after operation) was either unchanged or improved in 15 of 16 patients in group I and in 13 of 14 in group II, one of whom became dialysis dependent. Follow-up data were available for 25 of 30 (83%) patients (mean 45 months; range 1 to 108 months). Excluding one early failure, 10 of 13 patients in group I and 7 of 11 in group II did not have end-stage renal disease at last follow-up. Overall, hypertension was cured or improved in 16 of 21 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Delayed rupture of aortic aneurysms following endovascular stent grafting.

BACKGROUND: Deployment of transfemoral, endovascular stent grafts for treatment of abdominal aortic aneurysms is appealing for several reasons: avoidance of abdominal incision, lack of aortic cross-clamping, potential for regional anesthesia, and shortened hospital stay. Concerns remain, however, regarding the ability of these devices to completely exclude the aneurysm and prevent aneurysm rupture and the long-term integrity of the device. The availability of endografts and the likely development of percutaneous devices have also raised the delicate issue of personnel training for patient selection, endograft implantation, and postoperative follow-up. PATIENTS AND METHODS: The cases of 2 patients are reported in which Dacron endovascular grafts, anchored proximally and distally by Palmaz stents, were deployed for treatment of infrarenal abdominal aortic aneurysms. RESULTS: In a patient with and absent distal cuff, choosing this procedure represented a clear error in patient selection. The endograft failed to reach the aortic bifurcation and the aneurysm ruptured, with the death of the patient 4 months postimplantation. In a patient with anatomy suitable for endograft placement, a perigraft leak persisted at the distal anastomosis following device placement. The aneurysm ruptured 14 days postprocedure. Although the patient survived emergent aneurysm repair, he developed acute renal failure. CONCLUSION: Careful preoperative assessment of aortic anatomy is crucial in selection of patients for transfemoral endovascular graft placement. Lack of a distal cuff of at least 1 cm precludes tube graft implantation. Patients with a perigraft leak are not protected by the endograft from aneurysm rupture. Vascular surgeons must be involved in the preoperative evaluation of these patients and are the only specialty group who can provide the prerequisite care in evaluation and management of postoperative complications.

Aged↗