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Biomedical subjects

E Fry

Publications and source records attributed to E Fry.

At least 19 recordsLinked to original sources
PubMed2001

Dalteparin in combination with abciximab during percutaneous coronary intervention.

BACKGROUND: Despite proved efficacy for either dalteparin or platelet glycoprotein IIb/IIIa blockade in improving clinical outcomes of patients with non-ST-segment elevation acute coronary syndromes, algorithms guiding concomitant therapy with these agents have not been devised. The purpose of this study was to assess anticoagulant effect and clinical safety for several dose regimens of dalteparin administered in combination with abciximab during percutaneous coronary intervention (PCI). METHODS AND RESULTS: Patients undergoing PCI with standard dose abciximab received dalteparin as follows: 120 IU/kg subcutaneously (SQ) to a maximum of 10,000 U if < or =8 hours before PCI (n = 3); for PCI 8-12 hours after the SQ dose, an additional 40 IU/kg intravenously (IV) was administered (n = 1); for PCI >12 hours after SQ dalteparin or with no prior dalteparin therapy, random allocation to 40 (n = 27) or 60 (n = 28) IU/kg IV during PCI was performed. Those patients who received 60 IU/kg of dalteparin IV had a lower incidence of procedural thrombosis (0% vs 11.1%, P <.01), more consistent antithrombotic effect (anti-factor Xa activity) and a similar incidence of major bleeding (3.7% vs 2.6%) compared with patients who received 40 IU/kg of intravenous dalteparin. CONCLUSIONS: Dalteparin 60 IU/kg IV appears to be safe and effective when administered in conjunction with abciximab for percutaneous coronary intervention.

Abciximab↗
PubMed2001

Enoxaparin and abciximab adjunctive pharmacotherapy during percutaneous coronary intervention.

Randomized controlled trials of patients with non-ST segment elevation acute coronary syndromes have established the superiority of enoxaparin (versus unfractionated heparin) for reducing adverse ischemic outcomes. Furthermore, adjunctive abciximab therapy during percutaneous coronary intervention (PCI) is associated with improved clinical outcomes. Since algorithms for integrating these pharmacotherapies have not been determined, patients undergoing elective PCI were enrolled into 2 distinct and separate studies conducted by the National Investigators Collaborating on Enoxaparin (NICE) study groups (NICE 1 and NICE 4 studies). Patients in NICE 1 were administered enoxaparin 1.0 mg/kg intravenously (without abciximab) and those enrolled in NICE 4 were administered a reduced dose (0.75 mg/kg) of enoxaparin in combination with standard-dose abciximab intravenously during PCI. Bleeding events and ischemic outcomes assessed in-hospital and at 30-days post-PCI were infrequent with either pharmacologic regimen. In the dose regimens studied, enoxaparin with or without abciximab appears to provide safe and effective anticoagulation during PCI. The combination of reduced-dose enoxaparin and abciximab was associated with a low incidence of adverse outcomes (bleeding or ischemic events). Additional studies may be required to establish the relative safety and efficacy of this new adjunctive pharmacologic strategy when compared with the combination of low-dose, weight-adjusted unfractionated heparin and abciximab.

Abciximab↗
PubMed2000

Immune response to blood transfusion invery-low-birthweight infants.

BACKGROUND: Allogeneic blood transfusion is common in the treatment of neonatal anemia of prematurity or anemia due to multiple phlebotomies. The immune response of neonates to passenger leukocytes from allogeneic red cells was investigated. STUDY DESIGN AND METHODS: Fourteen infants (4 male, 10 female) prospectively were randomly assigned to receive either white cell-reduced (Group 1) or non-white-cell reduced (Group 2) irradiated blood. Blood samples were taken before and at various time intervals after transfusion (Days 1, 5-7,and 10-14). Cord blood from 11 healthy term infants was used for comparison. The following surface markers were used to assess immune modulation by flow cytometry: CD45RA/CD45RO, CD4/CD8, CD25/CD28, CD3/DR, CD14/B7, and CD3/CD56+CD16. Donor cell microchimerism was studied using semi-quantitative polymerase chain reaction Y-chromosome detection in female infants who received male donor blood. Donor and recipient HLA class II typing was performed with polymerase chain reaction with sequence specific primers. RESULTS: The lymphocyte counts in both groups were significantly increased after transfusion, and there was a significant increase in lymphocytes expressing CD45RA, CD3-/CD16+CD56, CD80, and CD3-/DR on Day 14. The premature infants' pretransfusion natural killer cell population (CD3-/CD16+CD56) was significantly lower than that of term infants, but it reached a similar level by Days 10-14. CD8 subpopulations were increased but not CD4+ cells. Two female infants (of 6) had circulating Y chromosomes 1 day after transfusion, and most of the infants effectively cleared the donor cells within 24 hours of transfusion. Two Group 2 infants who by chance received presumably HLA-haploidentical donor blood developed necrotizing enterocolitis. CONCLUSION: Blood transfusion alters immune cell antigen expression in premature neonates and may initially be immunostimulatory and later immunosuppressive.

Anemia, Neonatal↗
PubMed2000

Combination enoxaparin and abciximab therapy during percutaneous coronary intervention: "NICE guys finish first".

Data from randomized clinical trials support the administration of both enoxaparin and platelet glycoprotein IIb/IIIa blockade to patients who present with non-ST segment evaluation acute coronary syndromes. Enoxaparin does not activate platelets, has a more predictable dose response that facilitates weight-adjusted dosing and may have enhanced antithrombotic (increased anti-Xa activity) and safety (reduced anti-IIa activity) properties when compared with unfractionated heparin. Abciximab administration during percutaneous coronary intervention reduces the incidence of ischemic adverse outcomes and may improve survival in long-term follow-up. The preliminary experience with combining abciximab and intravenous enoxaparin during percutaneous coronary intervention in the NICE-4 Trial demonstrates a low incidence of minor/major bleeding (TIMI definition) and transfusion and infrequent major cardiac events to 30 days follow-up. Future algorithms to facilitate the transition of patients from the clinical service who have received subcutaneous administration of enoxaparin to the cardiac catheterization laboratory prior to percutaneous coronary intervention are forthcoming and will provide seamless integration of "optimal" adjunctive pharmacology through the course of hospitalization for patients with non-ST elevation acute coronary syndromes.

Abciximab↗
PubMed2000

Combination Enoxaparin and Abciximab During Percutaneous Coronary Intervention: A New Standard of Care?

Evidence from randomized trials supports the administration of platelet glycoprotein (GP) IIb/IIIa blockade both to patients undergoing percutaneous coronary intervention (PCI) and those presenting with non-ST elevation acute coronary syndromes (ACSs). Similarly, the low molecular weight heparin (LMWH), enoxaparin, has demonstrated superior efficacy when compared with unfractionated heparin (UFH) in the treatment of patients with non-ST elevation ACS. Algorithms for seamless integration of pharmacotherpy through the course of hospitalization for patients who present with ACS and who require PCI will likely combine therapy with enoxaparin and platelet GP IIb/IIIa blockade (abciximab). Our preliminary experience with combination enoxaparin and abciximab as adjunctive pharmacotherapy for PCI suggests that this strategy is safe and effective and may offer advantages over a conventional strategy, which employs UFH.

Journal Article↗
PubMed1999

The crystal structure of coxsackievirus A9: new insights into the uncoating mechanisms of enteroviruses.

BACKGROUND: Coxsackievirus A9 (CAV9), a human pathogen causing symptoms ranging from common colds to fatal infections of the central nervous system, is an icosahedral single-stranded RNA virus that belongs to the genus Enterovirus of the family Picornaviridae. One of the four capsid proteins, VP1, includes the arginine-glycine-aspartate (RGD) motif within its C-terminal extension. This region binds to integrin alpha v beta 3, the only receptor for CAV9 to be conclusively identified to date. RESULTS: The crystal structure of CAV9 in complex with the antiviral compound WIN 51711 has been solved to 2.9 A resolution. The structures of the four capsid proteins, VP1 to VP4, resemble those of other picornaviruses. The antiviral compound is bound in the VP1 hydrophobic pocket, and it is possible that the pocket entrance contains a second WIN 51711 molecule. Continuous electron density for the VP1 N terminus provides a complete picture of the structure close to the fivefold axis. The VP1 C-terminal portion is on the outer surface of the virus and becomes disordered five-residues N-terminal to the RGD motif. CONCLUSIONS: The RGD motif is exposed and flexible in common with other known integrin ligands. Although CAV9 resembles coxsackie B viruses (CBVs), several substitutions in the areas implicated in CBV receptor attachment suggest it may recognise a different receptor. The structure along the fivefold axis provides new information on the uncoating mechanism of enteroviruses. CAV9 might bind a larger natural pocket factor than other picornaviruses, an observation of particular relevance to the design of new antiviral compounds.

Amino Acid Sequence↗
PubMed1998

Umbilical arterial S-nitrosothiols in stressed newborns: role in perinatal circulatory transition.

S-Nitrosothiols are potent endogenous vasodilators recently found to be in greater concentrations in fetal umbilical venous than arterial blood. We hypothesized that neonatal increases in SNOs may be involved in the normal human perinatal circulatory transition. Paired human umbilical artery and vein plasma samples were collected after birth. S-Nitrosothiol concentrations were measured as NO after photolysis--and NO3- after reduction in vanadium chloride--by chemiluminescence. Normal umbilical arterial serum SNO levels were nearly twice those of matched venous samples but were low in infants who did not transition normally to neonatal circulation. There was no difference in the concentration of NO3- between the normal and depressed infants. The parallel failure of some fetuses to switch both to a normal arteriovenous SNO relationship and a normal clinical post-partum state suggests that SNOs may be involved in the perinatal circulatory transition.

Blood Circulation↗
PubMed1997

Specific interactions between human integrin alpha v beta 3 and chimeric hepatitis B virus core particles bearing the receptor-binding epitope of foot-and-mouth disease virus.

Purified integrin alpha v beta 3 was used in solid-phase binding studies with chimeric hepatitis B cores which carry the RGD-containing loop of VP1 protein of the foot-and-mouth disease virus (FMDV). High levels of specific binding between the integrin and the particles were detected by enzyme-linked immunosorbent assays. The binding was Mn2+ cation dependent and could be competed with fibronectin, vitronectin, and the peptide GRGDSPK. Particles in which the RGD motif had been mutated to RGE failed to bind, indicating that the chimeric cores bound specifically to the ligand binding site of integrin alpha v beta 3. Electron micrographs showed several individual alpha v beta 3 molecules bound to the surface of each chimeric particle. Collectively, these data constitute firm evidence that the RGD-containing loop of FMDV is critical for binding to alpha v beta 3 and provide support for identification of alpha v beta 3 as a potential cellular receptor for FMDV.

Antigens, Viral↗
PubMed1997

Coronary artery and saphenous vein graft remodeling: a review of histologic findings after various interventional procedures--Part V.

Catheter balloon angioplasty is a well accepted form of nonsurgical treatment of acutely and chronically obstructed coronary artery vessels. It is also the centerpiece for various new intervention techniques. Their morphologic effect on the site of obstruction has been termed "remodeling." Part V of this six-part series focuses on remodeling effects of balloon angioplasty on obstructed young (< or = 1 year) and old (> 1 year) saphenous vein bypass grafts.

Angioplasty, Balloon, Coronary↗
PubMed1997

Coronary artery and saphenous vein graft remodeling: a review of histologic findings after various interventional procedures--Part VI.

Catheter balloon angioplasty is a well accepted form of nonsurgical treatment of acutely and chronically obstructed coronary artery vessels. It is also the centerpiece for various new intervention techniques. Their morphologic effects on the site of obstruction has been termed "remodeling." Part VI of this six-part series focuses on atherectomy and restenosis tissue obtained by atherectomy procedures.

Angioplasty, Balloon↗
PubMed1997

Dissecting the roles of VP0 cleavage and RNA packaging in picornavirus capsid stabilization: the structure of empty capsids of foot-and-mouth disease virus.

Empty capsids of foot-and-mouth disease virus (FMDV) type A22 Iraq 24/64, whose structure has been solved by X-ray crystallography, are unusual for picornaviruses since they contain VP2 and VP4, the cleavage products of the protein precursor VP0. Both the N terminus of VP1 and the C terminus of VP4, which pack together close to the icosahedral threefold symmetry axis where three pentamers associate, are more disordered in the empty capsid than they are in the RNA-containing virus. The ordering of these termini in the presence of RNA strengthens interactions within a single protomer and between protomers belonging to different pentamers. The disorder in the FMDV empty capsid forms a subset of that seen in the poliovirus empty capsid, which has VP0 intact. Thus, VP0 cleavage confers stability on the picornavirus capsid over and above that attributable to RNA encapsidation. In both FMDV and poliovirus empty capsids, the internal disordering uncovers a conserved histidine which has been proposed to be involved in the cleavage of VP0. A comparison of the putative active sites in FMDV and poliovirus suggests a structural explanation for the sequence specificity of the cleavage reaction.

Aphthovirus↗
PubMed1996

Perturbations in the surface structure of A22 Iraq foot-and-mouth disease virus accompanying coupled changes in host cell specificity and antigenicity.

BACKGROUND: Foot-and-mouth disease virus (FMDV) is an extremely infectious and antigenically diverse picornavirus of cloven-hoofed animals. Strains of the A22 subtype have been reported to change antigenically when adapted to different growth conditions. To investigate the structural basis of this phenomenon we have determined the structures of two variants of an A22 virus. RESULTS: The structures of monolayer- and suspension-cell-adapted A22 FMDV have been determined by X-ray crystallography. Picornaviruses comprise four capsid proteins, VP1-4. The major antigenic loop of the capsid protein VP1 is flexible in both variants of the A22 subtype but its overall disposition is distinct from that observed in other FMDV serotypes (O and C). A detailed structural comparison between A22 FMDV and a type O virus suggests that different conformations in a portion of the major antigenic loop of VP1 (the GH loop, which is also central to receptor attachment) result in distinct folds of the adjacent VP3 GH loop. Also, a single mutation (Glu82-->Gly) on the surface of VP2 in the suspension-cell-adapted virus appears to perturb the structure of the VP1 GH loop. CONCLUSION: The GH loop of VP1 is flexible in three serotypes of FMDV, suggesting that flexibility is important in both antigenic variability and structural communication with other regions of the virus capsid. Our results illustrate two instances of the propagation of structural perturbations across the virion surface: the change in the VP3 GH loop caused by the VP1 GH loop and the Glu82-->Gly change in VP2 which we believe perturbs the GH loop of VP1. In the latter case, the amplification of the sequence changes leads to differences, between the monolayer- and suspension-cell-adapted viruses, in host-cell interactions and antigenicity.

Antigens, Viral↗
PubMed1996

Coronary artery and saphenous vein graft remodeling: a review of histologic findings after various interventional procedures--Part I.

Catheter balloon angioplasty is a well accepted form of nonsurgical treatment of acutely and chronically obstructed coronary artery vessels. It is also the centerpiece for various new intervention techniques. Their morphologic effects on the site of obstruction has been termed "remodeling." Part I of this six-part series focuses on mechanisms of remodeling after various interventional techniques, particularly balloon angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed1996

Coronary artery and saphenous vein graft remodeling: a review of histologic findings after various interventional procedures--Part II.

Catheter balloon angioplasty is a well accepted form of nonsurgical treatment of acutely and chronically obstructed coronary artery vessels. It is also the centerpiece for various new intervention techniques. Their morphologic effects on the site of obstruction has been termed "remodeling." Part II of this six-part series focuses on morphologic causes of acute closure after remodeling and discusses findings late after successful balloon angioplasty remodeling.

Adult↗
PubMed1996

Coronary artery and saphenous vein graft remodeling: A review of histologic findings after various interventional procedures--Part III.

Catheter balloon angioplasty is a well accepted form of nonsurgical treatment of acutely and chronically obstructed coronary artery vessels. It is also the centerpiece for various new intervention techniques. Their morphologic effects on the site of obstruction has been termed "remodeling." Part III of this six-part series focuses on intimal proliferation and chronic recoil in patients undergoing previous remodeling techniques by balloon angioplasty.

Adult↗
PubMed1996

Coronary artery and saphenous vein graft remodeling: a review of histologic findings after various interventional procedures--Part IV.

Catheter balloon angioplasty is a well accepted form of nonsurgical treatment of acutely and chronically obstructed coronary artery vessels. It is also the centerpiece for various new intervention techniques. Their morphologic effects on the site of obstruction has been termed "remodeling." Part IV of this six-part series focuses on morphologic correlates of coronary angiographic patterns of remodeling after balloon angioplasty and discusses effects of angioplasty on adjacent, nondilated vessels.

Adult↗