Biomedical subjects

Michael O Montgomery

Publications and source records attributed to Michael O Montgomery.

3 recordsLinked to original sources

PubMed2006

Intra-arterial reteplase and intravenous abciximab in patients with acute ischemic stroke: an open-label, dose-ranging, phase I study.

OBJECTIVE: New approaches are focusing on using a combination of medication that lyse fibrin and prevent aggregation of platelets to achieve higher rates of recanalization and improved clinical outcomes. METHODS: A prospective, nonrandomized, open-label trial evaluated the safety of an escalating dose of reteplase in conjunction with intravenous abciximab (platelet glycoprotein IIb/IIIa inhibitor) in patients with acute ischemic stroke (3-6 h after symptom onset). The primary endpoint was symptomatic intracerebral hemorrhage at 24 to 72 hours, and secondary endpoints were partial or complete recanalization (> or = one grade improvement), early neurological improvement (decrease in National Institutes of Health Stroke Scale > or = 4 at 24 h), and favorable outcome at 1 month (defined by modified Rankin scale < or = 2). RESULTS: A total of 20 patients (mean age, 65 yr; 13 men) were recruited. Five patients were recruited in each of the escalating tiers of intra-arterial reteplase (0.5, 1, 1.5, and 2 units). Intravenous abciximab (0.25 mg/kg bolus followed by 0.125 mug/kg/min) was successfully administered in 18 out of 20 patients. The safety stopping rule was not activated in any of the tiers. One symptomatic intracerebral hemorrhage was observed in one of the 20 patients (in the 1-unit tier). Partial or complete recanalization was observed in 13 of the 20 patients. Thirteen patients demonstrated early neurological improvement, and favorable outcome at 1 month was observed in six patients. CONCLUSION: In this study, a combination of intra-arterial reteplase and intravenous abciximab was safely administered to patients with ischemic stroke presenting between 3 and 6 hours after symptom onset.

Abciximab↗

PubMed2004

Expression and function of periostin-isoforms in bone.

Periostin was originally identified in MC3T3-E1 osteoblast-like cells. We have identified an isoform of periostin referred to as periostin-like-factor (PLF). It is homologous to other proteins such as fasciclin I (fas I), MPB70, betaIG-H3, and Algal-CAMs. All of these proteins are implicated in regulating cell adhesion. PLF and the other isoforms of periostin differ in their C-terminal sequences. PLF and periostin differ in two specific regions, between 673 and 699 amino acids (aa) and 785-812 aa. Periostin isoforms are expressed in vivo and in vitro during the stages of osteoblast differentiation and maturation. Their mRNAs are present in pre-osteoblast cells as detected by in situ hybridization, and the proteins are between 86 and 93 kD in size as determined by Western blot analysis. Antisense oligonucleotides and antibodies directed against the isoforms of periostin were used to block the activity of these proteins. In both cases, the levels of osteoblast-specific-differentiation markers were markedly reduced suggesting a role for these proteins in osteoblast differentiation.

Amino Acid Sequence↗

PubMed2004

Clot lysis in a primate model of peripheral arterial occlusive disease with use of systemic or intraarterial reteplase: addition of abciximab results in improved vessel reperfusion.

PURPOSE: This study was designed to compare the ability of reteplase (a fibrinolytic agent) alone or in combination with abciximab (a monoclonal antibody antagonist of platelet glycoprotein IIb/IIIa) to achieve and sustain vessel patency in an acute model of peripheral arterial occlusive disease in cynomolgus monkeys. MATERIALS AND METHODS: Total arterial occlusion was induced in the femoral arteries of 32 cynomolgus monkeys (eight groups of four) by endothelial injury and injection of thrombin-treated autologous blood. Reteplase was administered by intravenous bolus dose or by intraarterial infusion at the site of the clot. Abciximab was administered as a single weight-adjusted intravenous bolus dose. Platelet activity was measured by ex vivo platelet aggregation before and after abciximab treatment. Different groups of animals received sequential partial doses of reteplase with or without increasing doses of abciximab until either the weight-adjusted human dose equivalent of reteplase was reached or vessel recanalization was achieved. RESULTS: Animals receiving reteplase-only regimens demonstrated variability in the times required for reperfusion and the permanence of the effect. The coadministration of abciximab at doses of the antibody that achieved near or full inhibition of platelet function generally decreased the time to reperfusion and resulted in more consistent and sustained vessel patency. In the case of systemic intravenous reteplase, the coadministration of abciximab resulted in effective reperfusion of thrombosed vessels at decreased doses of the lytic agent. CONCLUSIONS: Reteplase administered systemically or at the site of thrombotic occlusion restored blood flow for periods of varying duration in monkeys with acute femoral artery thrombosis. The coadministration of systemic intravenous abciximab to intravenous or intraarterial reteplase allowed the use of lower doses of fibrinolytic agent with more accelerated and sustained reperfusion.

Abciximab↗