RESUMEN

There are limited data examining whether outcomes of methicillin-resistant Staphylococcus aureus (MRSA) healthcare-associated infections (HAIs) are worse when caused by community-associated (CA) strains compared to HA strains. We reviewed all patients' charts at our institution from 1999 to 2009 that had MRSA first isolated only after 72 h of hospitalization (n=724). Of these, 384 patients had a MRSA-HAI according to CDC criteria. Treatment failure was similar in those infected with a phenotypically CA-MRSA strain compared to a phenotypically HA-MRSA strain (23% vs. 15%, P=0.10) as was 30-day mortality (16% vs. 19%, P=0.57). Independent risk factors associated with (P<0.05) treatment failure were higher Charlson Comorbidity Index, higher APACHE II score, and no anti-MRSA treatment. These factors were also associated with 30-day mortality, as were female gender, older age, MRSA bloodstream infection, MRSA pneumonia, and HIV. Our findings suggest that clinical and host factors, not MRSA strain type, predict treatment failure and death in hospitalized patients with MRSA-HAIs.

Asunto(s)

Infecciones Comunitarias Adquiridas/epidemiología , Infección Hospitalaria/epidemiología , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Infecciones Estafilocócicas/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , California/epidemiología , Infecciones Comunitarias Adquiridas/microbiología , Infección Hospitalaria/microbiología , Femenino , Genotipo , Indicadores de Salud , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina/clasificación , Staphylococcus aureus Resistente a Meticilina/genética , Persona de Mediana Edad , Estudios Retrospectivos , Infecciones Estafilocócicas/microbiología , Resultado del Tratamiento

RESUMEN

We fabricated an radio frequency (RF) carbon nanotube field effect transistor (CNTFET) whose electrode shapes were standard RF designed ground-signal-ground (GSG)-type pads. The S-parameters measured from our RF CNTFET in the frequency range up to 6 GHz were fitted with an RF equivalent circuit, and the extracted gate capacitance was shown to be the capacitance value of the series combination of the electrostatic capacitance and the quantum capacitance. The effect of the channel resistance and the kinetic inductance was also discussed.

RESUMEN

We have obtained the continuous radio frequency spectrum of water molecule relaxation using carbon nanotubes (CNT) as a high-speed nanoprobe. Three sets of characteristic time scales are clearly identified. Two sets are attributed to the electric-field-driven polarization of water molecules bound to CNTs and the collective relaxation of water layers in the vicinity of CNTs, respectively. The third set is appreciable only in air, and can be related to triplet oxygen relaxation.

Asunto(s)

Técnicas de Sonda Molecular , Nanotubos de Carbono/química , Nanotubos de Carbono/ultraestructura , Agua/química , Ensayo de Materiales , Tamaño de la Partícula , Ondas de Radio , Electricidad Estática

RESUMEN

We demonstrate a hybrid process for fabricating one-dimensional wire devices. The process is a combination of an alignment procedure using dielectrophoresis and subsequent contact metal formation utilizing electrochemical deposition with non-toxic organic-based Au electrolytes. Several devices have been successfully made from GaN nanowires or multi-walled carbon nanotubes (MWCNTs) using our hybrid technique. We demonstrate that rapid thermal annealing improves the ohmic characteristics by five orders of magnitude in the case of the GaN devices and ∼300% in the case of the MWCNT devices. One of the reasons for this improvement is enhanced gold wetting due to the reduction of grain size at the annealing temperature.

RESUMEN

We have investigated the frequencies of HLA-B*44 alleles and their haplotypic associations with HLA-A, -C, and -DRB1 loci in 450 healthy unrelated Koreans, including 213 parents from 107 families. All 79 samples (17.6%) typed as B44 by serology were analyzed for B*44 alleles using polymerase chain reaction (PCR) single-strand conformation polymorphism (SSCP) method. A total of three different B*44 alleles were detected: B*44031 (allele frequency 4.7%), B*44032 (3.1%), and B*4402 (1.3%). Three characteristic haplotypes revealing strong linkage disequilibrium were A*3303-Cw*1403-B*44031-DRB1*1302 (3.6%), A*3303-Cw*07-B*44032-DRB1*0701 (2.8%), and A*3201-Cw*05-B*4402-DRB1*0405 (0.4%). In addition, a strong association was observed for B*4402 with A*0301. The B*4403-bearing haplotypes of Koreans appear to be relatively common in Asian populations, whereas the B*4402-bearing haplotypes share some similarity to those of Caucasians. HLA-B44 alleles demonstrate a limited allelic diversity and comprise distinctive extended haplotypes in the Korean population. It is suggested that the frequencies of B44 subtype mismatches among ABDRB1-matched unrelated donor-recipient pairs would be low in this population.

Asunto(s)

Alelos , Frecuencia de los Genes/inmunología , Antígenos HLA-B/genética , Haplotipos/inmunología , Pueblo Asiatico/genética , Antígeno HLA-B44 , Antígenos HLA-C/genética , Antígenos HLA-DQ/genética , Cadenas beta de HLA-DQ , Antígenos HLA-DR/genética , Cadenas HLA-DRB1 , Prueba de Histocompatibilidad/estadística & datos numéricos , Humanos , Corea (Geográfico) , Funciones de Verosimilitud , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple

Asunto(s)

Linfocitos B/inmunología , Trasplante de Riñón , Trastornos Linfoproliferativos/diagnóstico , Nefritis Intersticial/virología , Infecciones por Polyomavirus/diagnóstico , Poliomavirus , Complicaciones Posoperatorias , Adulto , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Trasplante de Riñón/inmunología , Trasplante de Riñón/patología , Trastornos Linfoproliferativos/inmunología , Imagen por Resonancia Magnética , Masculino , Nefritis Intersticial/complicaciones , Nefritis Intersticial/patología , Infecciones por Polyomavirus/complicaciones , Infecciones por Polyomavirus/patología

RESUMEN

Coronary perforation is an uncommon but potentially life-threatening complication of percutaneous coronary intervention. The use of both atheroablative technologies for coronary intervention and adjunctive platelet glycoprotein blockade pharmacology may increase the incidence of or risk for life-threatening bleeding complications following the occurrence of coronary artery perforation. The interventional database for 6,214 percutaneous coronary interventions performed between January 1995 and June 1999 was analyzed. Hospital charts and cine angiograms for all patients identified in the database as having had coronary perforation were reviewed. Coronary perforation complicated 0.58% of all procedures and was more commonly observed in patients with a history of congestive heart failure and following use of atheroablative interventional technologies (2.8%). There was no association of abciximab therapy with either the incidence of or classification for coronary perforation. Adverse clinical outcomes (death, emergency surgical exploration) were related to the angiographic classification of perforation and were more frequently observed in patients who experienced a class 3 coronary perforation. These data suggest that specific clinical and procedural demographic factors are associated with the occurrence and severity of angiographic coronary perforation. An angiographic perforation class-specific algorithm for treatment of coronary perforation is proposed.

Asunto(s)

Algoritmos , Angioplastia Coronaria con Balón/instrumentación , Angioplastia por Láser/instrumentación , Anticuerpos Monoclonales/efectos adversos , Aterectomía Coronaria/instrumentación , Enfermedad Coronaria/terapia , Vasos Coronarios/lesiones , Lesiones Cardíacas/terapia , Hemorragia/inducido químicamente , Fragmentos Fab de Inmunoglobulinas/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Stents , Abciximab , Anciano , Anticuerpos Monoclonales/administración & dosificación , Cineangiografía , Angiografía Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Femenino , Lesiones Cardíacas/diagnóstico por imagen , Hemorragia/diagnóstico por imagen , Hemorragia/terapia , Humanos , Fragmentos Fab de Inmunoglobulinas/administración & dosificación , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/administración & dosificación , Estudios Retrospectivos , Factores de Riesgo

RESUMEN

We have investigated the frequencies of HLA-B*07 alleles and their haplotypic associations with HLA-A, -C and -DRB1 loci in 489 healthy unrelated Koreans, including 214 parents from 107 families. All of the 45 samples (9.2%) typed as B7 by serology were analyzed for B*07 alleles using polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) method. Two different B*07 alleles were detected: B*0702 (allele frequency 0.041) and B*0705 (0.005). Two characteristic haplotypes showing strong linkage disequilibrium in Koreans were A*2402-Cw*07-B*0702-DRB1*0101 (haplotype frequency 0.028) and A*2901-B*0705-DRB1*0803 (0.005). The characteristic haplotype A*2901-B*0705-DRB1*0803, found in 100% (5/5) of B*0705-positive individuals, has not been previously described in other ethnic groups. HLA-B7 alleles comprise distinctive extended haplotypes in the Korean population. The probability of HLA-B7 allele mismatches among ABDR-matched unrelated donor-recipient pairs is expected to be low in Koreans.

Asunto(s)

Alelos , Pueblo Asiatico/genética , Frecuencia de los Genes/genética , Antígenos HLA-B/genética , Haplotipos/genética , Antígeno HLA-B7 , Humanos , Corea (Geográfico)

RESUMEN

BACKGROUND: Mutations of PKD1 are thought to account for approximately 85% of all mutations in autosomal dominant polycystic kidney disease (ADPKD). The search for PKD1 mutations has been hindered by both its large size and complicated genomic structure. To date, few mutations that affect the replicated segment of PKD1 have been described, and virtually all have been reported in Caucasian patients. METHODS: In the present study, we have used a long-range polymerase chain reaction (PCR)-based strategy previously developed by our laboratory to analyze exons in the replicated region of PKD1 in a population of 41 unrelated Thai and 6 unrelated Korean families with ADPKD. We have amplified approximately 3.5 and approximately 5 kb PKD1 gene-specific fragments (5'MR and 5'LR) containing exons 13 to 15 and 15 to 21 and performed single-stand conformation analysis (SSCA) on nested PCR products. RESULTS: Nine novel pathogenic mutations were detected, including six nonsense and three frameshift mutations. One of the deletions was shown to be a de novo mutation. Four potentially pathogenic variants, including one 3 bp insertion and three missense mutations, were also discovered. Two of the nonconservative amino acid substitutions were predicted to disrupt the three-dimensional structure of the PKD repeats. In addition, six polymorphisms, including two missense and four silent nucleotide substitutions, were identified. Approximately 25% of both the pathogenic and normal variants were found to be present in at least one of the homologous loci. CONCLUSION: To our knowledge, this is the first report of mutation analysis of the replicated region of PKD1 in a non-Caucasian population. The methods used in this study are widely applicable and can be used to characterize PKD1 in a number of ethnic groups using DNA samples prepared using standard techniques. Our data suggest that gene conversion may play a significant role in producing variability of the PKD1 sequence in this population. The identification of additional mutations will help guide the study of polycystin-1 and better help us to understand the pathophysiology of this common disease.

Asunto(s)

Codón sin Sentido , Etnicidad/genética , Mutación del Sistema de Lectura , Riñón Poliquístico Autosómico Dominante/genética , Proteínas/genética , Secuencia de Aminoácidos , Exones , Salud de la Familia , Femenino , Humanos , Intrones , Corea (Geográfico) , Masculino , Datos de Secuencia Molecular , Linaje , Polimorfismo Conformacional Retorcido-Simple , Estructura Terciaria de Proteína , Proteínas/química , Mapeo Restrictivo , Canales Catiónicos TRPP , Tailandia

RESUMEN

BACKGROUND: Placebo-controlled randomized trials of platelet glycoprotein (GP) IIb/IIIa blockade during percutaneous coronary intervention have demonstrated efficacy of these agents for reducing the risk of periprocedural ischemic events. However, cost-effectiveness of this adjunctive pharmacotherapy has been scrutinized. Extrapolation of cost-efficacy observations from clinical trials to "real world" interventional practice is problematic. METHODS: Consecutive percutaneous coronary interventions (n = 1472) performed by Ohio Heart Health Center operators at The Christ Hospital, Cincinnati, Ohio, in 1997 were analyzed for procedural and long-term (6-month) outcomes and charges. Observations on cost and efficacy (survival) were adjusted for nonrandomized abciximab allocation by means of "propensity scoring" methods. RESULTS: Abciximab therapy was associated with a survival advantage to 6 months after percutaneous coronary intervention. The average reduction in mortality rate at 6 months was 3.4% (unadjusted) and 4.9% when adjusted for nonrandomization. The average charge increment to 6 months was $1512 (unadjusted) and $950 when adjusted for nonrandomization. Patients deriving the greatest reduction in mortality rates also had a reduction in total cardiovascular charges to 6 months. Distinguishing demographics of this population included multivessel coronary intervention, coronary stent deployment, intervention within 1 week of myocardial infarction, and lower left ventricular ejection fraction. The average cost per life-year gained in this study was $2875 for all patients (unadjusted) and $1243 when adjusted for nonrandomization. CONCLUSIONS: Abciximab provides a cost-effective survival advantage in high-volume interventional practice that compares favorably with currently accepted standards. Clinical and procedural demographics associated with increased cost-effectiveness included multivessel coronary intervention, stent deployment, recent (<1 week) myocardial infarction, and impaired left ventricular function.

Asunto(s)

Angioplastia Coronaria con Balón/mortalidad , Anticuerpos Monoclonales/economía , Enfermedad Coronaria/economía , Fragmentos Fab de Inmunoglobulinas/economía , Inhibidores de Agregación Plaquetaria/economía , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Abciximab , Anticuerpos Monoclonales/uso terapéutico , Enfermedad Coronaria/mortalidad , Enfermedad Coronaria/terapia , Análisis Costo-Beneficio , Femenino , Humanos , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Masculino , Persona de Mediana Edad , Ohio/epidemiología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pronóstico , Tasa de Supervivencia/tendencias

RESUMEN

We investigated the mechanism of mitomycin C (MMC)-induced apoptosis in SNU-16 human gastric adenocarcinoma cells. Caspase-8 and caspase-3 were activated in MMC-treated cells whereas caspase-1 was not activated, and cytochrome c was released from mitochondrial membrane to cytosol suggesting that caspase-9 was activated during the MMC-induced apoptotic process. Protein kinase C (PKC) delta was cleaved to its characteristic 40 kDa fragment in a caspase-3-dependent manner; on the other hand PKC zeta was cleaved to approximately 40 kDa independently of caspase-3 in the drug-induced apoptosis of the cells. Incubation with z-DEVD-fmk and benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk) almost completely abrogated MMC-induced DNA fragmentation, indicating that activation of these caspases was crucially involved in MMC-induced apoptosis. Activation of caspase-8 in response to Fas triggering by recruitment of caspase-8 to the Fas has also been found, however, MMC did not induce FasL and Fas expression, as evidenced by reverse transcriptase-polymerase chain reaction and Western blotting. Taken together, these findings indicate that MMC-induced apoptosis in SNU-16 cells was mediated by caspase-8, caspase-9, and caspase-3 activation independently of FasL/Fas interactions.

Asunto(s)

Adenocarcinoma/prevención & control , Antibióticos Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Caspasas/metabolismo , Mitomicina/farmacología , Neoplasias Gástricas/prevención & control , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Clorometilcetonas de Aminoácidos/farmacología , Caspasa 3 , Caspasa 8 , Caspasa 9 , Inhibidores de Caspasas , Muerte Celular/efectos de los fármacos , Inhibidores de Cisteína Proteinasa/farmacología , Activación Enzimática/efectos de los fármacos , Humanos , Oligopéptidos/farmacología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Factores de Tiempo , Células Tumorales Cultivadas , Receptor fas/metabolismo

RESUMEN

Inorganic zeolites are used for many practical applications that exploit the microporosity intrinsic to their crystal structures. Organic analogues, which are assembled from modular organic building blocks linked through non-covalent interactions, are of interest for similar applications. These range from catalysis, separation and sensor technology to optoelectronics, with enantioselective separation and catalysis being especially important for the chemical and pharmaceutical industries. The modular construction of these analogues allows flexible and rational design, as both the architecture and chemical functionality of the micropores can, in principle, be precisely controlled. Porous organic solids with large voids and high framework stability have been produced, and investigations into the range of accessible pore functionalities have been initiated. For example, catalytically active organic zeolite analogues are known, as are chiral metal-organic open-framework materials. However, the latter are only available as racemic mixtures, or lack the degree of framework stability or void space that is required for practical applications. Here we report the synthesis of a homochiral metal-organic porous material that allows the enantioselective inclusion of metal complexes in its pores and catalyses a transesterification reaction in an enantioselective manner. Our synthesis strategy, which uses enantiopure metal-organic clusters as secondary building blocks, should be readily applicable to chemically modified cluster components and thus provide access to a wide range of porous organic materials suitable for enantioselective separation and catalysis.

RESUMEN

We have investigated the frequencies of HLA-A*02 alleles and their haplotypic associations with HLA-B and -DRB1 loci in 439 healthy unrelated Koreans, including 214 parents from 107 families. All of the 227 samples (51.7%) typed as A2 by serology were analyzed for A*02 alleles using polymerase chain reaction (PCR)-low ionic strength-single-strand conformation polymorphism (LIS-SSCP) method. A total of six different A*02 alleles were detected (A*02 allele frequency 29.6%): A*0201/9 (16.6%), *0203 (0.5%), *0206 (9.3%), *0207 (3.0%), and one each case of *0210 and *02 undetermined type. Two characteristic haplotypes showing the strongest linkage disequilibrium were A*0203-B38-DRB]*1502 and A*0207-B46-DRB1*0803. Besides these strong associations, significant two-locus associations (P<0.001) were observed for A*0201 with B61, DRB1*0901 and DRB1*1401, and for A*0206 with B48 and B61. HLA haplotypes carrying HLA-A2 showed a variable distribution of A*02 alleles, and all of the eight most common A2-B-DR haplotypes occurring at frequencies of > or =1% were variably associated with two different A*02 alleles. These results demonstrate that substantial heterogeneity is present in the distribution of HLA-A*02 alleles and related haplotypes in Koreans.

Asunto(s)

Alelos , Antígeno HLA-A2/genética , Frecuencia de los Genes , Antígenos HLA-B/genética , Antígenos HLA-DR/genética , Cadenas HLA-DRB1 , Haplotipos , Humanos , Corea (Geográfico)

Asunto(s)

Angioplastia Coronaria con Balón/métodos , Anticuerpos Monoclonales/uso terapéutico , Puente de Arteria Coronaria/efectos adversos , Enoxaparina/uso terapéutico , Oclusión de Injerto Vascular/terapia , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Abciximab , Anciano , Terapia Combinada , Angiografía Coronaria , Puente de Arteria Coronaria/métodos , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/cirugía , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Quimioterapia Combinada , Estudios de Seguimiento , Oclusión de Injerto Vascular/diagnóstico por imagen , Humanos , Infusiones Intravenosas , Masculino , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Grado de Desobstrucción Vascular

Asunto(s)

Enfermedad Coronaria/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Abciximab , Enfermedad Aguda , Anticuerpos Monoclonales/uso terapéutico , Enfermedad Coronaria/sangre , Quimioterapia Combinada , Electrocardiografía/efectos de los fármacos , Eptifibatida , Humanos , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Péptidos/uso terapéutico , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/metabolismo , Tirofibán , Resultado del Tratamiento , Tirosina/análogos & derivados , Tirosina/uso terapéutico

RESUMEN

We describe the first reported case in Korea of a woman with a D--/ D-- phenotype, a high-titer anti-Hr0, and the successful delivery of her newborn. The mother had a history of spontaneous abortion and artificial termination. In her third pregnancy, a live infant was delivered, but died of severe hemolytic disease of the newborn due to anti- Hr0 in spite of intensive medical intervention. In her fourth pregnancy, at 22 weeks gestation, the titer of anti- Hr0 was 1024, fetal cells were direct antiglobulin test positive and the blood type was group O, D+ (CDe). We performed plasma exchanges in the mother; however, the titer of antibody rebounded to its initial level after the third plasma exchange. At 26 weeks gestation, cord blood Hb decreased to 7.1 g/dL and three intrauterine transfusions were performed using the mother's washed red blood cells (RBCs). At 34 weeks gestation, a live baby was delivered by cesarean section. The infant was hydropic with hyperbilirubinemia and severe anemia. However, after two exchange transfusions using the washed RBCs of the mother's sister, who was also D--/D--, laboratory and clinical findings returned to normal.

RESUMEN

We evaluated the differential effect of platelet count in platelet-rich plasma (PRP) on the level of ex vivo inhibition of platelet aggregation provided by abciximab, eptifibatide, and tirofiban as part of a randomized, comparative trial of these agents on platelet function in patients with unstable angina pectoris undergoing percutaneous coronary intervention. Platelet count <350 K/microL in PRP reduced measured platelet inhibition by abciximab, but not eptifibatide nor tirofiban. This observation suggests the need for standardized, uniform platelet counts in PRP during future comparisons of the degree of platelet inhibition by these agents.

Asunto(s)

Angina Inestable/sangre , Angina Inestable/tratamiento farmacológico , Anticuerpos Monoclonales/farmacología , Fragmentos Fab de Inmunoglobulinas/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Abciximab , Factores de Confusión Epidemiológicos , Eptifibatida , Femenino , Humanos , Masculino , Péptidos/farmacología , Agregación Plaquetaria/efectos de los fármacos , Recuento de Plaquetas , Pruebas de Función Plaquetaria , Tirofibán , Tirosina/análogos & derivados , Tirosina/farmacología

RESUMEN

A reliable method for high-resolution HLA-DQB1 typing using a combination of PCR- restriction fragment length polymorphism (RFLP) and PCR-single strand conformation polymorphism (SSCP) analysis is described. The second exon of the DQB1 gene was subjected to PCR using generic primers and digested with two restriction enzymes, MspA1I and HaeIII, and the DQB1 alleles were divided into seven groups. According to the RFLP patterns, appropriate group specific primers for DQ5, 6 and DQ2, 3, 4 groups were used to selectively amplify the alleles and the SSCP technique was used to distinguish the individual alleles. A total of 88 quality control samples of various ethnic groups distributed in the International Cell Exchange and HLA DNA Exchange programs and the ASHI/CAP Proficiency Tests were investigated by the PCR-RFLP/SSCP method. The concordance between our typing results and the consensus results of the surveys were 100%, and a total of 14 DQB1 alleles in 49 homozygous and heterozygous combinations were all correctly identified by the method described. This method is accurate, economical and relatively easy to interpret and well suited for routine clinical and research uses.

Asunto(s)

Antígenos HLA-DQ/clasificación , Prueba de Histocompatibilidad/métodos , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo Conformacional Retorcido-Simple , Antígenos HLA-DQ/genética , Cadenas beta de HLA-DQ , Humanos , Reacción en Cadena de la Polimerasa/métodos

RESUMEN

Adjunctive platelet glycoprotein IIb/IIIa blockade during percutaneous coronary intervention (PCI) reduces platelet-mediated adverse ischemic outcomes. Although abciximab, eptifibatide, and tirofiban have received U.S. Food and Drug Administration approval for use, these agents differ in their pharmacodynamic profiles. Each of these agents has been compared in randomized trials with placebo for patients undergoing PCI, but no randomized comparative studies of these agents have been performed. We compared ex vivo platelet function by both standard light transmission aggregometry and rapid platelet function assay during and after administration of abciximab, eptifibatide, or tirofiban in approved dose regimens on a randomized basis at the time of PCI in patients with unstable angina pectoris. A reduced intensity of platelet inhibition by light transmission aggregometry was observed for tirofiban compared with either eptifibatide or abciximab. In addition, the 30-minute bolus strategy used for tirofiban was associated with delayed onset of maximal platelet inhibition relative to the initiation of bolus infusion. Whether the trends in platelet function observed in this study will be translated into differences in clinical outcomes awaits definition by larger scale randomized clinical trials comparing these platelet glycoprotein IIb/IIIa inhibitors.

Asunto(s)

Angina Inestable/terapia , Angioplastia Coronaria con Balón , Anticuerpos Monoclonales/uso terapéutico , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Péptidos/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Tirosina/análogos & derivados , Abciximab , Angina Inestable/sangre , Anticuerpos Monoclonales/administración & dosificación , Plaquetas/efectos de los fármacos , Eptifibatida , Femenino , Estudios de Seguimiento , Humanos , Fragmentos Fab de Inmunoglobulinas/administración & dosificación , Inyecciones Intravenosas , Masculino , Péptidos/administración & dosificación , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Recuento de Plaquetas , Factores de Tiempo , Tirofibán , Resultado del Tratamiento , Tirosina/administración & dosificación , Tirosina/uso terapéutico

RESUMEN

Anciximab provides potent, but variable degrees of platelet inhibition both during the duration of intravenous administration and at 12 hours following therapy. Platelet function was assessed using the PC-RPFA system in 78 patients scheduled for percutaneous coronary revascularization who were administered the standard abciximab weight-adjusted bolus and 12-hour infusion. The PC-RPFA system is a cartridge-based, semiautomated point-of-care whole-blood assay that incorporates fibrinogen-coated polystyrene beads, buffers, and a modified thrombin receptor activating peptide (Isotrap) in lyophilized form. The instrument detects the agglutination rate between the stimulated platelets and the fibrinogen-coated beads, and provides a quantitative digital display in less than 2 minutes. No differences in the level of platelet inhibition were observed in these abciximab-treated patients by diabetic status, gender, smoking, diagnosis (unstable angina, chronic stable angina, recent myocardial infarction), or abciximab treatment status (first time vs. retreatment). Nocorrelation of the PC-RPFA rate of platelet aggregation with clinical demographic factors was observed, with the exception of baseline hematocrit (r2 = 0.4556). The relationship between the PC-RPFA rate of aggregation and hematocrit reflects light absorbance by erythrocytes and is specific to the PC-RPFA system. The absolute rate of platelet aggregation (slope) reported by the PC-RPFA is correlated with percent aggregation, thus making it potentially possible to predict the level of aggregation without reference to a baseline (pretreatment) measure of platelet function. This correlation was closest for patients having <40% baseline aggregation (r2 = 0.55). Thus, PC-RPFA provides a rapid point-of-care assessment of platelet function that could allow for adjustment of abciximab dosing to achieve targeted levels of platelet inhibition. The utility of this device to optimize therapy with platelet glycoprotein IIb/IIIa inhibitors is currently being evaluated.

Asunto(s)

Anticuerpos Monoclonales/uso terapéutico , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pruebas de Función Plaquetaria/métodos , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Abciximab , Adulto , Anciano , Angioplastia Coronaria con Balón , Automatización , Comorbilidad , Femenino , Fibrinógeno/metabolismo , Humanos , Masculino , Microesferas , Persona de Mediana Edad , Fragmentos de Péptidos/metabolismo , Adhesividad Plaquetaria/efectos de los fármacos , Agregación Plaquetaria/efectos de los fármacos , Pruebas de Función Plaquetaria/instrumentación , Resultado del Tratamiento