Biomedical subjects

Michael P Savage

Publications and source records attributed to Michael P Savage.

5 recordsLinked to original sources

PubMed2007

Facilitated stent delivery using applied topical lubrication.

OBJECTIVES: The goal of this study was to assess the utility of topical lubrication to aid stent delivery in challenging anatomy and its effects on long-term clinical outcome. BACKGROUND: Failed stent delivery is encountered in up to 5% of percutaneous coronary interventions (PCI). METHODS: The effectiveness of topically applied lubrication to facilitate stent delivery after failed stent placement was evaluated in 20 (2.5%) out of 813 consecutive patients undergoing PCI. Initial attempts at stent delivery failed despite balloon predilatation and use of moderate-to-stiff guidewires in all patients. The lubricious solution used was Rotaglide, a phospholipid emulsion originally designed to reduce catheter friction during rotational atherectomy. Following unsuccessful delivery, stents were removed from the guiding catheters, topically saturated with Rotaglide, and deployment immediately reattempted. Procedural efficacy and long-term clinical outcomes were assessed. RESULTS: The study population included 20 patients aged 69 +/- 10 years, all of whom had complex lesions (ACC/AHA Class B(2) or C). Rotaglide lubricated stents were successfully deployed at the target lesions in 17 of the 20 patients (85%). Patients were followed 19.5 +/- 3.2 months after their index procedure. There were no periprocedural complications or subacute stent thromboses. Of the 14 patients with drug-eluting stents, none had clinical restenosis or target vessel revascularization. Target lesion revascularization secondary to restenosis was required in 1 of 3 patients treated with bare-metal stents. CONCLUSIONS: Topical lubrication is a simple and effective aid for stent delivery in complex lesions. Rotaglide appears safe and biocompatible with drug-eluting stents.

Aged↗

PubMed2006

Efficacy of intracoronary nicardipine in the treatment of no-reflow during percutaneous coronary intervention.

OBJECTIVES: The goal of this study was to evaluate the safety and efficacy of nicardipine in reversing no-reflow during percutaneous coronary intervention (PCI). BACKGROUND: No-reflow is a common complication of PCI in patients with acute coronary syndromes or venous bypass graft disease. Although nicardipine has an attractive pharmacological profile and has been used clinically to treat no-reflow, there is a paucity of published data regarding its effectiveness in this setting. METHODS: We conducted a retrospective analysis of 72 consecutive patients who received intracoronary nicardipine to reverse no-reflow during coronary intervention. Qualitative TIMI flow grade and quantitative TIMI frame count methods were used to assess the efficacy of nicardipine. RESULTS: A mean of 460 +/- 360 mcg of intracoronary nicardipine was used. No-reflow was successfully reversed with complete restoration of TIMI 3 flow in 71 of 72 patients (98.6%). TIMI flow grade improved from 1.65 +/- 0.53 prior to nicardipine to 2.97 +/- 0.24 after treatment (P < 0.001). TIMI frame count decreased from 57 +/- 40 at the time of no-reflow to 15 +/- 12 after nicardipine administration (P < 0.001). Nicardipine therapy was well tolerated without adverse hemodynamic or chronotropic effects. CONCLUSIONS: In this largest series to date, intracoronary nicardipine was demonstrated to be a safe and highly effective pharmacological agent to reverse no-reflow during PCI.

Adult↗

PubMed2002

Charcot-Leyden crystal protein (galectin-10) is not a dual function galectin with lysophospholipase activity but binds a lysophospholipase inhibitor in a novel structural fashion.

Charcot-Leyden crystal (CLC) protein, initially reported to possess weak lysophospholipase activity, is still considered to be the eosinophil's lysophospholipase, but it shows no sequence similarities to any known lysophospholipases. In contrast, CLC protein has moderate sequence similarity, conserved genomic organization, and near structural identity to members of the galectin superfamily, and it has been designated galectin-10. To definitively determine whether or not CLC protein is a lysophospholipase, we reassessed its enzymatic activity in peripheral blood eosinophils and an eosinophil myelocyte cell line (AML14.3D10). Antibody affinity chromatography was used to fully deplete CLC protein from eosinophil lysates. The CLC-depleted lysates retained their full lysophospholipase activity, and this activity could be blocked by sulfhydryl group-reactive inhibitors, N-ethylmaleimide and p-chloromercuribenzenesulfonate, previously reported to inhibit the eosinophil enzyme. In contrast, the affinity-purified CLC protein lacked significant lysophospholipase activity. X-ray crystallographic structures of CLC protein in complex with the inhibitors showed that p-chloromercuribenzenesulfonate bound CLC protein via disulfide bonds with Cys(29) and with Cys(57) near the carbohydrate recognition domain (CRD), whereas N-ethylmaleimide bound to the galectin-10 CRD via ring stacking interactions with Trp(72), in a manner highly analogous to mannose binding to this CRD. Antibodies to rat pancreatic lysophospholipase identified a protein in eosinophil and AML14.3D10 cell lysates, comparable in size with human pancreatic lysophospholipase, which co-purifies in small quantities with CLC protein. Ligand blotting of human and murine eosinophil lysates with CLC protein as probe showed that it binds proteins also recognized by antibodies to pancreatic lysophospholipase. Our results definitively show that CLC protein is not one of the eosinophil's lysophospholipases but that it does interact with eosinophil lysophospholipases and known inhibitors of this lipolytic activity.

Animals↗

PubMed2002

Coronary intervention in the diabetic patient: improved outcome following stent implantation compared with balloon angioplasty.

BACKGROUND: Diabetic patients undergoing coronary interventional procedures are at increased risk of restenosis and adverse clinical events. The relative impact of stents compared with balloon angioplasty on the outcome of percutaneous intervention in diabetics remains controversial. HYPOTHESIS: The goal of this study was to determine whether stent placement was superior to balloon angioplasty in reducing restenosis of diabetic patients undergoing coronary intervention. METHODS: The STRESS Trial was a prospective randomized comparison of stent placement and balloon angioplasty in the treatment of new native coronary lesions. Of 594 randomized patients. 92 (16%) were diabetic. In this substudy analysis of the STRESS Trial, the outcomes after stenting and balloon angioplasty in diabetic patients were compared. The primary endpoint was restenosis as determined by angiography at 6 months. Clinical outcomes at 1 year were assessed. RESULTS: Procedural success was achieved in 82% of diabetic patients assigned to angioplasty and in 100% assigned to stenting (p < 0.01). Compared with angioplasty, stenting resulted in a larger postprocedural lumen diameter (2.34 +/- 0.44 vs. 1.87 +/- 0.52 mm, p < 0.001) and greater acute luminal gain (1.61 +/- 0.47 vs. 1.06 +/- 0.46 mm, p < 0.001). At 6 months, stenting conferred a larger lumen (1.69 +/- 0.57 vs. 1.38 +/- 0.60 mm, p = 0.03) and greater net luminal gain (0.97 +/- 0.55 vs. 0.52 +/- 0.52 mm, p < 0.001). Restenosis occurred in 60% of the angioplasty group and in 24% of the stent group (p < 0.01). This was accompanied by a lower need for repeat target vessel revascularization after stenting (31 vs. 13%, p < 0.03). CONCLUSIONS: Compared with balloon angioplasty, stent placement in diabetic patients with focal de novo lesions resulted in superior procedural results, reduced restenosis, and improved clinical outcome with fewer repeat revascularization procedures.

Angioplasty, Balloon↗

PubMed2002

New developments in high-throughput resequencing and variation detection using high density microarrays.

We developed a high-throughput method for resequencing for single nucleotide polymorphism (SNP) discovery using high-density microarrays. Over the two-year course of this study a number of improvements in sample preparation methods, hybridization assay, array handling, and analysis method were developed and implemented. DNA from 40 unrelated individuals of three different ethnic origins was amplified, labeled, and hybridized to arrays designed with probes representing genomic, coding, and regulatory regions. Protocol improvements including the use of long PCR and semi-automation reduced labeling and fragmentation costs by 33%. Automation improvements include the development of a scanner autoloader for arrays, a faster array wash station, and a linked laboratory tracking and data management system. Validation of a smaller feature size, 20 x 24 microns, allowed the simultaneous screening of 30-kb sense and 30-kb antisense DNA on each microarray, increasing throughput to 1.4 Mb per day per two laboratory personnel. More than 15,000 SNPs were identified in 8.3 Mb of the human genome using high-density resequencing and variation detection arrays (microarrays).

Automation↗