RESUMEN
Ovarian carcinoma is the fifth common cause of cancer death in women, despite advanced therapeutic approaches. αvß3 integrin, a plasma membrane receptor, binds thyroid hormones (L-thyroxine, T4; 3,5,3'-triiodo-L-thyronine, T3) and is overexpressed in ovarian cancer. We have demonstrated selective binding of fluorescently labeled hormones to αvß3-positive ovarian cancer cells but not to integrin-negative cells. Physiologically relevant T3 (1 nM) and T4 (100 nM) concentrations in OVCAR-3 (high αvß3) and A2780 (low αvß3) cells promoted αv and ß3 transcription in association with basal integrin levels. This transcription was effectively blocked by RGD (Arg-Gly-Asp) peptide and neutralizing αvß3 antibodies, excluding T3-induced ß3 messenger RNA, suggesting subspecialization of T3 and T4 binding to the integrin receptor pocket. We have provided support for extracellular regulated kinase (ERK)-mediated transcriptional regulation of the αv monomer by T3 and of ß3 monomer by both hormones and documented a rapid (30-120 min) and dose-dependent (0.1-1000 nM) ERK activation. OVCAR-3 cells and αvß3-deficient HEK293 cells treated with αvß3 blockers confirmed the requirement for an intact thyroid hormone-integrin interaction in ERK activation. In addition, novel data indicated that T4, but not T3, controls integrin's outside-in signaling by phosphorylating tyrosine 759 in the ß3 subunit. Both hormones induced cell proliferation (cell counts), survival (Annexin-PI), viability (WST-1) and significantly reduced the expression of genes that inhibit cell cycle (p21, p16), promote mitochondrial apoptosis (Nix, PUMA) and tumor suppression (GDF-15, IGFBP-6), particularly in cells with high integrin expression. At last, we have confirmed that hypothyroid environment attenuated ovarian cancer growth using a novel experimental platform that exploited paired euthyroid and severe hypothyroid serum samples from human subjects. To conclude, our data define a critical role for thyroid hormones as potent αvß3-ligands, driving ovarian cancer cell proliferation and suggest that disruption of this axis may present a novel treatment strategy in this aggressive disease.
Asunto(s)
Integrina alfaVbeta3/fisiología , Sistema de Señalización de MAP Quinasas/fisiología , Proteínas de Neoplasias/fisiología , Neoplasias Hormono-Dependientes/metabolismo , Neoplasias Ováricas/metabolismo , Tiroxina/fisiología , Triyodotironina/fisiología , Anticuerpos Neutralizantes/farmacología , División Celular/efectos de los fármacos , Línea Celular Tumoral , Medios de Cultivo/farmacología , Activación Enzimática , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Hipotiroidismo/sangre , Integrina alfaV/genética , Integrina alfaV/metabolismo , Integrina alfaVbeta3/biosíntesis , Integrina alfaVbeta3/genética , Integrina alfaVbeta3/inmunología , Integrina beta3/genética , Integrina beta3/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Neoplasias Hormono-Dependientes/genética , Neoplasias Hormono-Dependientes/patología , Oligopéptidos/farmacología , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Fosforilación , Procesamiento Proteico-Postraduccional , ARN Mensajero/biosíntesis , ARN Neoplásico/biosíntesis , Tiroxina/sangre , Tiroxina/farmacología , Transcripción Genética/efectos de los fármacos , Transcripción Genética/fisiología , Triyodotironina/sangre , Triyodotironina/farmacologíaRESUMEN
The involvement of spleen macrophages in the early stages of scrapie pathogenesis was studied by applying the 'macrophage-suicide technique' to scrapie-infected mice. This method comprises critically the intravenous administration to mice of dichloromethylene disphosphonate encapsulated into liposomes. Depletion of spleen macrophages before scrapie infection induced an increased amount of scrapie inoculum in the spleen, consequently leading to accelerated scrapie agent replication in the early phase of pathogenesis, as followed by PrPres accumulation, a specific hallmark of scrapie. The same effect was observed when spleen macrophages were depleted just before the beginning of scrapie agent replication. These findings suggest that macrophages may partly control scrapie infection in peripheral tissues by sequestration of the scrapie inoculum and may thus impair early scrapie agent replication in the spleen. In addition to macrophages, most follicular dendritic cells and B lymphocytes, which are thought to support scrapie agent replication, were also transiently depleted by dichloromethylene disphosphonate administration. This suggests that a compensatory mechanism is sufficient to ensure the persistence of infection in these early stages of pathogenesis.
Asunto(s)
Macrófagos/inmunología , Scrapie/inmunología , Bazo/inmunología , Analgésicos no Narcóticos/farmacología , Animales , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Ácido Clodrónico/farmacología , Macrófagos/efectos de los fármacos , Ratones , Priones/metabolismo , Scrapie/virología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunologíaRESUMEN
In 1990 there was a sudden increase in the incidence of colonization and infection due to Acinetobacter baumannii (AB) in our intensive care units (ICUs). The isolates were multiply resistant to beta-lactam and aminoglycoside antibiotics, but remained susceptible to imipenem, amikacin, and ampicillin-sulbactam. We examined the frequency of infection and colonization with AB and the effects of increased imipenem and amikacin therapy on Pseudomonas aeruginosa. We also used disease-matched controls to determine the clinical and financial impacts of treating colonization. All patients with at least one AB isolate from January-December 1992 were identified retrospectively and classified as infected or colonized based on published Centers for Disease Control criteria; the control group was selected from a computerized medical records data base matching primary diagnostic codes (102 patients both groups). The 102 patients yielded 140 isolates, 124 resistant AB and 16 sensitive AB. Thirty three patients were infected, 69 colonized. Mortality correlated with APACHE II scores. Patients acquired the organism approximately 2 weeks after admission; they had a mean ICU stay of 27.35 days, compared with 5.53 days for controls. Patients with positive AB cultures required significantly more use of ventilators than those with negative AB cultures. They also had significantly longer hospital stay, more bed transfers, greater duration and number of antibiotics, and higher hospital and pharmacy charges. Unnecessary treatment for colonization with either imipenem or amikacin resulted in a substantial decrease of P. aeruginosa susceptibility to each agent. The financial impact of treating colonization was significant and is a potential area for cost avoidance. Our results emphasize the need to extubate and move patients to non-ICU beds as soon as possible to decrease the risk of nosocomial infection. It also highlights the need to avoid treating colonization, thus avoiding unnecessary antibiotic therapy.
Asunto(s)
Infecciones por Acinetobacter/epidemiología , Infección Hospitalaria/microbiología , Acinetobacter/aislamiento & purificación , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/economía , Infecciones por Acinetobacter/mortalidad , Adulto , Aminoglicósidos , Antibacterianos/economía , Antibacterianos/uso terapéutico , Estudios de Casos y Controles , Farmacorresistencia Microbiana/fisiología , Resistencia a Múltiples Medicamentos/fisiología , Femenino , Hospitales Universitarios , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa , Factores de Riesgo , Factores de TiempoRESUMEN
The retention of urokinase activity after frozen storage was studied. Urokinase powder was reconstituted aseptically in sterile water for injection or preservative-free 0.9% sodium chloride injection to a final concentration of 5000 IU/mL. Samples were stored in 5-mL plastic syringes at -20 or -70 degrees C for up to six months. Samples containing urokinase 25,000 IU/mL were similarly prepared by using sodium chloride injection as the diluent and were stored frozen at the same temperatures for up to 93 days. Urokinase activity was measured with a chromogenic assay at each test interval. Samples were also cultured after thawing to evaluate their potential to support microbial growth. The activity of urokinase at either concentration did not change appreciably during the study period. The method of thawing-at room temperature or in a refrigerator-had no effect on urokinase activity. No microbial growth was observed. Urokinase 5000 IU/mL did not show any changes in activity when reconstituted with sterile water for injection or 0.9% sodium chloride injection and frozen for up to six months. Urokinase 25,000 IU/mL in sodium chloride injection was also stable after 93 days of frozen storage.
Asunto(s)
Fibrinolíticos/química , Hemorragias Intracraneales/tratamiento farmacológico , Activador de Plasminógeno de Tipo Uroquinasa/química , Ventrículos Cerebrales , Estabilidad de Enzimas , Congelación , Humanos , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo , Activador de Plasminógeno de Tipo Uroquinasa/uso terapéuticoRESUMEN
Using a mouse model, we examine drug targeting towards bone marrow. One cytotoxic (doxorubicin) and one stimulating (rhG-CSF), bound to polyalkylcyanoacrylate nanoparticles, were studied. Histological studies, using a fluorescence microscope, showed rapid capture of nanoparticles by bone marrow macrophages and granulocytes as soon as 15 minutes after injection into the blood stream. Doxorubicin nanoparticles, administered at a dose of 11 mg/kg were more toxic than free doxorubicin on all blood and marrow cell lines. Moreover, the choice of the nature of the polymer had an influence on toxicity: doxorubicin polyisohexylcyanoacrylate nanoparticles were more toxic than polyisobutylcyanoacrylate particles. Quantification of doxorubicin in bone marrow has confirmed these results. The bone marrow concentrations observed demonstrated that there was a high level of targeting towards the bone marrow that would be very interesting to use for a stimulating drug. Nevertheless, rhG-CSF nanoparticles did not show better efficacy than free rhG-CSF.
Asunto(s)
Células de la Médula Ósea/citología , Cianoacrilatos , Doxorrubicina/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Granulocitos/efectos de los fármacos , Células Madre Hematopoyéticas/efectos de los fármacos , Macrófagos/efectos de los fármacos , Animales , Células de la Médula Ósea/efectos de los fármacos , Doxorrubicina/toxicidad , Portadores de Fármacos , Factor Estimulante de Colonias de Granulocitos/farmacología , Granulocitos/citología , Células Madre Hematopoyéticas/citología , Humanos , Macrófagos/citología , Ratones , Proteínas RecombinantesRESUMEN
After intravenous injection, the main part of nanoparticles trapped by the spleen are concentrated in the marginal zone. The first step of this capture is the adhesion of the particles to the marginal zone macrophages. As classical techniques of cell suspension preparation did not allow to isolate without damage these actively capturing cells, tightly bound to a well-developed reticular meshwork, we designed a tissue slice incubation method, in order to study in vitro the interaction of nanoparticles with these particular macrophages, in conditions close to in vivo. In a serum supplemented medium, this in vitro model was able to give similar uptake profile than after intravenous injection of nanoparticles thus proving its validity. Surprisingly, no significant decrease of nanoparticles capture was observed when the medium was depleted from complement, immunoglobulins or proteins affine for heparin, while substitution of serum by purified albumin allowed a near optimal uptake. Addition of competitive ligands for lectin-like receptors did not show any clear inhibition of spleen capture. On the other hand, the scavenger receptor blocking agents, such as maleylated albumin or polyinosinic acid, induced a strong reduction of the spleen nanoparticles uptake. Thus, this paper proposes an in vitro binding assay as a reliable method to investigate the spleen capture of a large variety of nanoparticulate drug carriers. It is also a useful methodology to highlight the interactions between spleen cells and nanoparticles. The data obtained suggest that capture of nanoparticles depends on a multifactorial and complex phenomenon involving for a part albumin and the scavenger receptor.
Asunto(s)
Proteínas Sanguíneas/metabolismo , Proteínas de la Membrana , Receptores de Lipoproteína , Bazo/citología , Bazo/metabolismo , Animales , Adhesión Celular , Medios de Cultivo , Macrófagos/fisiología , Ratones , Técnicas de Cultivo de Órganos , Tamaño de la Partícula , Poliestirenos , Receptores Inmunológicos/metabolismo , Receptores Depuradores , Receptores Depuradores de Clase B , Albúmina Sérica Bovina/metabolismoRESUMEN
PURPOSE: To investigate the influence of animal species and nanoparticle surface characteristics on the intrasplenic distribution of polystyrene nanoparticles. METHODS: Two types of fluorescent polystyrene nanoparticles (Estapor and Fluoresbrite), plain or coated, were used in mice and rats. First, a fluorimetric method was developed for nanoparticle tissue quantification. Then, intrasplenic distribution of plain or coated nanoparticles was studied using histological examination and image analysis. Finally, the role of direct interactions between nanoparticles and spleen capturing cells was assessed by in vitro binding assays, using incubation of thick spleen slices with polystyrene nanoparticles. RESULTS: The two types of polystyrene nanoparticles showed different levels of trapping: Fluoresbrite nanoparticles were more efficiently trapped by the spleen than Estapor nanoparticles, both in mice and rats. In mice, most of the injected nanoparticles were localized in the marginal zone of the spleen, involving a special population of capturing cells, while in rats, the predominant capture occured in the red pulp. In mice, coated nanoparticles were localized both in the marginal zone and in the red pulp, whereas the coating did not seem to change the intrasplenic distribution of the nanoparticles in rats. CONCLUSIONS: These complementary approaches showed different uptake pathways of nanoparticles, according to their surface characteristics and the rodent species used.
Asunto(s)
Bazo/metabolismo , Animales , Etilenodiaminas/farmacología , Fluorometría , Ratones , Microquímica , Tamaño de la Partícula , Poloxámero/farmacología , Polietilenglicoles/farmacología , Ratas , Solubilidad , Especificidad de la Especie , Propiedades de Superficie , Tensoactivos/farmacología , Agua/químicaRESUMEN
The human recombinant granulocyte colony-stimulating factor (rhG-CSF) is largely used in the treatment of neutropenia occurring during chemotherapy. After injection, this glycoprotein distributes through the whole body. Thus, to obtain high and durable bone marrow concentrations, targeting with polyalkylcyanoacrylate nanoparticles was considered. Two methods of preparation were investigated: anionic polymerization and precipitation of the preformed polymer. By anionic polymerization, it was possible to associate more than 66% of rhG-CSF with nanoparticles (polyisobutyl- or polyisohexylcyanoacrylate nanoparticles) when the glycoprotein was added at the end of the polymerization process. It has been shown that the rhG-CSF was mainly adsorbed on the surface of the nanoparticles and most of the colony stimulating activity was conserved. Using precipitation of performed polyisohexylcyanoacrylate, 90% of rhG-CSF was associated with nanoparticles, the protein being mainly adsorbed onto the nanoparticle surface. In this case, a decrease of the colony stimulating activity was however observed. Whatever the method used, the in vitro release of rhG-CSF from the polyisohexylcyanoacrylate nanoparticles, was progressive during 8 h in seric conditions. Nevertheless, using mice as an animal model, it has been shown that the short-term effects of intravenously injected rhG-CSF were not increased by its association with polyisohexylcyanoacrylate nanoparticles.
Asunto(s)
Cianoacrilatos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Animales , Portadores de Fármacos , Femenino , Humanos , Ratones , Proteínas RecombinantesRESUMEN
A 41-year-old man being treated for severe esophageal reflux disease developed red, exfoliative scaling on his back, trunk, and legs after taking omeprazole 20 mg twice/day for 3 months. He also had redness and extreme sloughing of the skin on his hands. Even after he discontinued omeprazole and after several courses of topical and systemic steroids, symptoms continued to occur 18 months after treatment, mostly localized to the hands. Exfoliative dermatitis is associated with many drugs, but omeprazole has been implicated only once before in the literature.
Asunto(s)
Antiulcerosos/efectos adversos , Dermatitis Exfoliativa/inducido químicamente , Omeprazol/efectos adversos , Adulto , Antiulcerosos/uso terapéutico , Reflujo Gastroesofágico/tratamiento farmacológico , Humanos , Masculino , Omeprazol/uso terapéutico , Piel/efectos de los fármacos , Piel/patologíaRESUMEN
Apparent diffusion coefficients (ADC) of protons contributing to the functional signal can be determined from diffusion weighted functional magnetic resonance imaging (MRI) studies. An earlier study indicated that ADCs calculated from the functional signal of an activated primary sensorimotor cortex are large, and consistent with a CSF or intravascular contribution to the functional signal. We have added inversion recovery pulses to isotropic diffusion weighted imaging to null CSF protons selectively within the imaging slice, or to null the outer volume blood flowing into the imaging slice. With the use of gradient recalled diffusion weighted echo-planar imaging at low gradient b factors, and without the use of inversion pulses, the ADCs x 10(3) in mm2/s (+/- SD) from the functional signal were 6.81 +/- 1.19. These ADCs were significantly higher than resting primary sensorimotor cortex ADCs of 2.26 +/- 1.49, measured at the same b factors. When CSF nulling was applied, the functional signal ADCs remained high. Application of inflow nulling decreased the functional signal to such a small value, that ADCs estimated from these functional signals were not assessed. The results are consistent with an intravascular contribution to the functional signal and to its large ADC.
Asunto(s)
Encéfalo/fisiología , Líquido Cefalorraquídeo/fisiología , Circulación Cerebrovascular/fisiología , Adulto , Encéfalo/anatomía & histología , Encéfalo/irrigación sanguínea , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Corteza Motora/anatomía & histología , Corteza Motora/irrigación sanguínea , Corteza Motora/fisiologíaRESUMEN
PURPOSE: To identify more accurately in the spleen, the areas and the cells where nanoparticulate carriers were taken up from the blood flow, a series of complementary approaches were used. METHODS: First, in and ex vivo examination of the whole spleen led to a global view of all the trapping areas. Then, histological studies on frozen sections of the same organ allowed for a more precise localization of these areas and image analysis gave an evaluation of tissue distribution of the nanoparticles. Finally, immunological and enzymological characteristics of the capturing cells were determined in situ, using monoclonal antibodies (F4/80 and anti-sialoadhesin) and cytochemical reactions (esterases and acid phosphatase). Furthermore incubation of spleen slices with different nanoparticles was used so as to know if the capture was due to a high capturing capacity of these cells or to a high blood flow in their vicinity. RESULTS: It was shown that more than 90% of the splenic capture was localized in the marginal zone of the follicles. The capturing cells form a special population of macrophages inserted in a reticular meshwork, showing low esterase and acid phosphatase activities, giving faint or no reaction with F4/80 or anti-sialoadhesin antibodies. The circulating nanoparticles were quickly trapped with rather low specificity by these cells. CONCLUSIONS: Combination of coherent approaches allowed for the tracking of capturing cells from in vivo observations to their in situ identification on immunological and enzymological criteria.
Asunto(s)
Portadores de Fármacos/farmacocinética , Bazo/metabolismo , Animales , Femenino , Inmunohistoquímica , Ratones , Tamaño de la Partícula , Distribución TisularRESUMEN
A prospective program to convert patients from parenteral to oral antibiotics was evaluated over 12 months to determine its pharmacoeconomic impact on antibiotic acquisition and length of hospital stay. Physicians of patients meeting predetermined clinical criteria for mild and moderate infections were contacted to discuss potential oral alternative therapy. Clinical end points and economic data were followed in 242 patients (200 converted and 42 not converted but meeting criteria). No significant differences were noted between the groups with regard to demographic data, infection diagnosis, clinical outcome, or adverse effects. The average number of days of therapy for patients converted was 1.53 days shorter than that of patients who were not converted to oral therapy (p < 0.003). Cost savings for drug acquisition and length of stay were $15,149.24 and $161,071.88, respectively. The intervention program appeared to provide a cost-effective conversion from parenteral to oral antimicrobial administration without compromising patient care. It is anticipated that expansion of the program to include additional antibiotics will result in even greater cost savings for the institution.
Asunto(s)
Antiinfecciosos/economía , Costos de los Medicamentos , Farmacéuticos , Administración Oral , Adulto , Anciano , Antiinfecciosos/administración & dosificación , Antiinfecciosos/uso terapéutico , Costos y Análisis de Costo , Femenino , Humanos , Inyecciones Intravenosas , Tiempo de Internación , Masculino , Michigan , Persona de Mediana EdadRESUMEN
Dissection using ultrasonic aspiration is characterized by its unique tendency to spare fibrous and vascular structures during removal of parenchymal lesions. This preliminary study was undertaken to evaluate the feasibility and efficiency of tonsillectomy using the ultrasonic aspirator. Tonsillectomy was performed on 23 patients using the ultrasonic aspirator. Pericapsular removal of the tonsil was easily accomplished with complete preservation of the tonsillar pillars and minimal peritonsillar trauma. The ability to identify significant vasculature before transection, and the constant aspiration integrated into the ultrasonic aspirator allowed excellent visualization of the operative field at all times. No postoperative complications were noted and recovery was typical for tonsillectomy patients. The ultrasonic aspirator may increase the efficiency and margin of safety of tonsillectomy.
Asunto(s)
Succión/instrumentación , Tonsilectomía/métodos , Terapia por Ultrasonido/instrumentación , Adolescente , Adulto , Niño , Preescolar , Disección , Diseño de Equipo , Estudios de Factibilidad , Femenino , Humanos , Masculino , Tonsila Palatina/cirugía , Sonicación , Succión/efectos adversos , Tonsilectomía/efectos adversos , Resultado del Tratamiento , Terapia por Ultrasonido/efectos adversos , UltrasonidoRESUMEN
We conducted a retrospective, literature-based decision analysis to compare the cost-effectiveness of conventional low-dose heparin, dalteparin, and intermittent pneumatic compression (IPC) as thromboembolic prophylaxis to a no-prophylaxis option in patients at moderate risk of developing thromboembolic complications after major elective abdominal surgery. The analysis was conducted through an institutional perspective. Probability and incidence rate data were summarized from the literature. Cost data were obtained from the Detroit Medical Center's cost accounting systems and from national diagnosis-related group estimates. Mortality and complications avoided were the main outcome measures on which cost-effectiveness was based. Overall costs associated with conventional low-dose heparin, dalteparin, intermittent pneumatic compression, and no prophylaxis were $84, $122, $102, and $112, respectively in the primary analysis, which included costs of labor. Corresponding cost-effectiveness ratios in terms of costs/complication-free patient were $86, $124, $103, and $118, respectively. Compared with no prophylaxis, incremental cost-effectiveness analysis in terms of cost/mortality avoided involved savings of $6087 and $3125 with conventional low-dose heparin and IPC, respectively, and expenses of $2857 with dalteparin. A secondary analysis excluding costs of labor showed similar results. The results of the study consistently showed conventional low-dose heparin to provide the most cost-effective thromboembolic prophylaxis of the methods considered in terms of reducing both morbidity and mortality in the patient population studied.
Asunto(s)
Dalteparina/uso terapéutico , Trajes Gravitatorios/economía , Heparina/economía , Heparina/uso terapéutico , Laparotomía/economía , Complicaciones Posoperatorias/economía , Complicaciones Posoperatorias/prevención & control , Tromboembolia/economía , Tromboembolia/prevención & control , Análisis Costo-Beneficio , Dalteparina/economía , Humanos , Modelos Económicos , Estados UnidosRESUMEN
The affinity of nanoparticles for hematopoietic organs could be valuable for the targeting of certain stimulating factors to those tissues, but this affinity should also be taken into account in the toxicological evaluation of those carriers, especially when they are loaded with antimitotic compounds such as doxorubicin. However, the cells responsible for the capture of the nanoparticles and their localization in these organs is an important point to know before trying to modulate the nanoparticle's tissue distribution. Thus, we have studied, in this paper, the capture, the localization, and the retention in the bone marrow and in the spleen of biodegradable poly(isohexyl cyanoacrylate) nanoparticles as well as of nonbiodegradable polystyrene nanoparticles. The histological localization of these nanoparticles has been completed by cytological localization with a method used in cytochemistry for the evaluation of intracellular accumulation of various substances, such as iron deposits in bone marrow sideroblasts. These data indicate that, in the bone marrow, after a quick passage through the endothelium, nanoparticles were dispersed throughout in the tissue and captured by all types of phagocytizing cells. In the spleen, nanoparticles were mainly localized in large angular capturing cells in the marginal zone of the lymphoid follicles.
Asunto(s)
Médula Ósea/metabolismo , Cianoacrilatos/metabolismo , Portadores de Fármacos/metabolismo , Bazo/metabolismo , Animales , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacocinética , Masculino , Ratones , Poliestirenos/metabolismoAsunto(s)
Antiinfecciosos/uso terapéutico , Revisión de la Utilización de Medicamentos , Servicio de Farmacia en Hospital/organización & administración , Antiinfecciosos/economía , Bases de Datos Factuales , Control de Formularios y Registros , Joint Commission on Accreditation of Healthcare Organizations , Michigan , Farmacéuticos , Centros TraumatológicosRESUMEN
A cost-minimization analysis was performed to compare the direct costs of various neuromuscular blocking agents (NMBAs) in procedures of specific durations. Secondary objectives were to review the role of the NMBAs studied with respect to their place on our hospital formulary, and to develop a pharmacoeconomic methodology to be applied to other formulary decisions. Patients were stratified according to estimated length of surgical procedure; group 1 (55 patients) included surgeries estimated to take less than 2 hours, and group 2 (55 patients) included those estimated to be 2-4 hours long. Patients were then randomized to one of three intermediate-acting NMBAs: atracurium, vecuronium, or rocuronium. Anesthesia records were used to obtain all anesthetic agents administered in the operating room, and drug costs were calculated from hospital drug acquisition costs as of December 1994. Postanesthesia care unit (PACU) costs were estimated from patient charges and converted to costs using our hospital's cost-to-charge ratio. Costs that were common to all study treatments or unrelated to the use of NMBAs were excluded from the analysis. Two time-adjusted costs were calculated to determine the cost of neuromuscular blockade/hour and the total anesthesia drug costs/hour. In group 1 there were no statistical differences in NMBA cost/hour, anesthesia cost/hour, or PACU times or costs. In group 2, a significant difference was found in NMBA cost/case between atracurium ($54.23 +/- 41.26, mean +/- SD) and vecuronium ($31.95 +/- 15.33, p = 0.046). Atracurium was also significantly more costly than either vecuronium or recuronium/hour ($21.95 +/- 7.42 vs $14.39 +/- 7.02 and $16.07 +/- 8.15, respectively, p = 0.011) and anesthesia cost/hour ($28.77 +/- 7.43 vs $ 22.82 +/- 7.46 and $23.32 +/- 6.54, respectively, p = 0.03). There were no differences in PACU times or costs. Based on these results, vecuronium or rocuronium is preferred over atracurium in procedures with an estimated duration of 2-4 hours. In the patient population evaluated, there were no significant cost differences among the three NMBAs in surgeries with an estimated duration of less than 2 hours.