RESUMEN
Objetivo. Estudiar la concordancia de la clasificación radiográfica de Eaton-Littler para el diagnóstico de la artrosis de la articulación trapeciometacarpiana (ATM). La hipótesis nula consideró que la concordancia era debida al azar, y la alternativa que la concordancia no era debida al azar. Material y método. Se estudiaron las radiografías de 46 pacientes con síntomas y signos clínicos de artrosis de la ATM. Se clasificaron independientemente por 5 facultativos: tres expertos en extremidad superior, uno en radiodiagnóstico y un residente en COT de cuarto año. Se estudió la concordancia de las observaciones mediante el índice kappa global. Discusión. El diagnóstico de la artrosis de la ATM se basa fundamentalmente en la clínica, siendo la radiografía un método complementario de confirmación. La clasificación de Eaton-Littler propone 4 estadios evolutivos de la enfermedad, con una implicación terapéutica. Conclusiones. La concordancia de la clasificación radiográfica de Eaton-Littler es moderada (AU)
Objective. To study the concordance of the radiographic classification of Eaton-Littler for the diagnosis of basal thumb joint osteoarthritis (BTJO). The null hypothesis was that the concordance was due to chance and the alternative was that the concordance was not due to chance. Material and method. We have observed the x-rays of 46 patients with symptoms and clinical signs of BTJO. They were independently classified by five physicians: three experts in upper extremity, one in radiology and a fourth year resident of Orthopedics. We studied the concordance in the observations through the global Kappa. Discussion. The diagnosis of BTJO is based primarily on clinical exploration, radiology is a complementary method of confirmation. The classification of Eaton-Littler proposes 4 stages of the disease, with a therapeutic involvement. Conclusions. The concordance of the radiographic classification of Eaton-Littler is moderate (AU)
Asunto(s)
Humanos , Masculino , Femenino , Osteoartritis/clasificación , Osteoartritis/diagnóstico , Extremidad Superior/lesiones , Extremidad Superior , Metacarpo/lesiones , Metacarpo , Huesos del Metacarpo , Mano , 28599RESUMEN
OBJECTIVE: To study the concordance of the radiographic classification of Eaton-Littler for the diagnosis of basal thumb joint osteoarthritis (BTJO). The null hypothesis was that the concordance was due to chance and the alternative was that the concordance was not due to chance. MATERIAL AND METHOD: We have observed the x-rays of 46 patients with symptoms and clinical signs of BTJO. They were independently classified by five physicians: three experts in upper extremity, one in radiology and a fourth year resident of Orthopedics. We studied the concordance in the observations through the global Kappa. DISCUSSION: The diagnosis of BTJO is based primarily on clinical exploration, radiology is a complementary method of confirmation. The classification of Eaton-Littler proposes 4 stages of the disease, with a therapeutic involvement. CONCLUSIONS: The concordance of the radiographic classification of Eaton-Littler is moderate.
Asunto(s)
Articulaciones Carpometacarpianas/diagnóstico por imagen , Osteoartritis/clasificación , Osteoartritis/diagnóstico por imagen , Hueso Trapecio , Femenino , Humanos , Masculino , Variaciones Dependientes del Observador , RadiografíaRESUMEN
Fundamento. Las recomendaciones al paciente (RP) son una de las partes fundamentales del informe de alta hospitalaria. El objetivo del estudio fue conocer la frecuencia de RP en los informes de distintas especialidades y la proporción de ellas consideradas de fácil comprensión. Material y método. Estudio observacional transversal. Ámbito: hospital general de agudos. Se revisó una muestra de informes de alta con análisis de la frecuencia y tipos de RP según su contenido y claridad. Resultados. Se analizaron 840 informes y 2.097 RP con un promedio de 2,5 RP por informe. Las RP más habituales se referían al seguimiento del paciente (46% del total), seguidas de las recomendaciones específicas para los días inmediatos al alta (37%), solo el 16% se referían a estilos de vida. Los informes de especialidades quirúrgicas contenían 3,2 RP por alta, frente a 2,3 de las especialidades médicas. Un 90,3% de las RP se consideraron de comprensión clara para un paciente medio. Conclusiones. Los informes de alta analizados contenían pocas RP, en especial las referidas a estilos de vida. Una proporción apreciable de las RP no estaban expresadas con suficiente claridad(AU)
Background. Recommendations for patients (RP) are one of the key parts of the hospital discharge report (HDR). The objective was to study the frequency of RP in the HDR of different specialties and the proportion of them considered to be easy to understand. Material and method. Observational and cross-sectional study. Setting. General acute care hospital. Interventions. Review of a sample of HDR, analysis of the frequency and types of PR based on their content and clarity. Results. A total of 840 HDR and 2,097 PR were analysed with an average of 2.5 RP per report. The most common RP referred to the patient follow-up (46% of total), followed by specific recommendations for the days immediately following discharge (37%), with only 16% related to lifestyle. Reports by surgical specialties contained 3.2 RP compared to 2.3 in medical specialties. The large majority (90.3%) of the RP were considered clear to understand for a standard patient. Conclusions. The HDR analysed contained few RP, in particular those related to lifestyles. A substantial proportion of the RP were not expressed with enough clarity(AU)
Asunto(s)
Humanos , Masculino , Femenino , Alta del Paciente/estadística & datos numéricos , Alta del Paciente/normas , Alta del Paciente/tendencias , Atención al Paciente/métodos , Educación del Paciente como Asunto/organización & administración , Auditoría Médica/organización & administración , Auditoría Médica , Barreras de Comunicación , Estudios Transversales/métodos , Estudios Transversales/tendencias , Estudios Transversales , Relaciones Médico-Paciente , Manejo de Atención al Paciente/métodos , Auditoría Médica/métodos , Auditoría Médica/estadística & datos numéricos , Auditoría Médica/tendenciasRESUMEN
BACKGROUND: Recommendations for patients (RP) are one of the key parts of the hospital discharge report (HDR). The objective was to study the frequency of RP in the HDR of different specialties and the proportion of them considered to be easy to understand. MATERIAL AND METHOD: Observational and cross-sectional study. SETTING: General acute care hospital. INTERVENTIONS: Review of a sample of HDR, analysis of the frequency and types of PR based on their content and clarity. RESULTS: A total of 840 HDR and 2,097 PR were analysed with an average of 2.5 RP per report. The most common RP referred to the patient follow-up (46% of total), followed by specific recommendations for the days immediately following discharge (37%), with only 16% related to lifestyle. Reports by surgical specialties contained 3.2 RP compared to 2.3 in medical specialties. The large majority (90.3%) of the RP were considered clear to understand for a standard patient. CONCLUSIONS: The HDR analysed contained few RP, in particular those related to lifestyles. A substantial proportion of the RP were not expressed with enough clarity.
Asunto(s)
Cuidados Posteriores , Alta del Paciente , Educación del Paciente como Asunto , Barreras de Comunicación , Comprensión , Consejo , Estudios Transversales , Conducta Alimentaria , Hospitales Generales , Humanos , Lenguaje , Estilo de Vida , Medicina , Muestreo , EspañaRESUMEN
The data provided by clinical trials are often expressed in terms of survival. The analysis of survival comprises a series of statistical analytical techniques in which the measurements analysed represent the time elapsed between a given exposure and the outcome of a certain event. Despite the name of these techniques, the outcome in question does not necessarily have to be either survival or death, and may be healing versus no healing, relief versus pain, complication versus no complication, relapse versus no relapse, etc.The present article describes the analysis of survival from both a descriptive perspective, based on the KaplanMeier estimation method, and in terms of bivariate comparisons using the log-rank statistic. Likewise, a description is provided of the Cox regression models for the study of risk factors or covariables associated to the probability of survival. These models are defined in both simple and multiple forms, and a description is provided of how they are calculated and how the postulates for application are checked accompanied by illustrating examples with the shareware application R(AU)
Asunto(s)
Humanos , Análisis de Regresión , Análisis de Supervivencia , Modelos de Riesgos Proporcionales , Ensayos Clínicos como AsuntoRESUMEN
The data provided by clinical trials are often expressed in terms of survival. The analysis of survival comprises a series of statistical analytical techniques in which the measurements analysed represent the time elapsed between a given exposure and the outcome of a certain event. Despite the name of these techniques, the outcome in question does not necessarily have to be either survival or death, and may be healing versus no healing, relief versus pain, complication versus no complication, relapse versus no relapse, etc. The present article describes the analysis of survival from both a descriptive perspective, based on the Kaplan-Meier estimation method, and in terms of bivariate comparisons using the log-rank statistic. Likewise, a description is provided of the Cox regression models for the study of risk factors or covariables associated to the probability of survival. These models are defined in both simple and multiple forms, and a description is provided of how they are calculated and how the postulates for application are checked - accompanied by illustrating examples with the shareware application R.
Asunto(s)
Modelos de Riesgos Proporcionales , Ensayos Clínicos como Asunto , Humanos , Estimación de Kaplan-Meier , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
In the health sciences it is quite common to carry out studies designed to determine the influence of one or more variables upon a given response variable. When this response variable is numerical, simple or multiple regression techniques are used, depending on the case. If the response variable is a qualitative variable (dichotomic or polychotomic), as for example the presence or absence of a disease, linear regression methodology is not applicable, and simple or multinomial logistic regression is used, as applicable.
Asunto(s)
Diseño de Investigaciones Epidemiológicas , Modelos Logísticos , Dinámicas no Lineales , Animales , Factores de Confusión Epidemiológicos , Humanos , Funciones de Verosimilitud , Dinámica Poblacional , Factores de Riesgo , Programas InformáticosRESUMEN
In biomedical research it is common to find problems in which we wish to relate a response variable to one or more variables capable of describing the behaviour of the former variable by means of mathematical models. Regression techniques are used to this effect, in which an equation is determined relating the two variables. While such equations can have different forms, linear equations are the most widely used form and are easy to interpret. The present article describes simple and multiple linear regression models, how they are calculated, and how their applicability assumptions are checked. Illustrative examples are provided, based on the use of the freely accessible R program (AU)
Asunto(s)
Modelos Lineales , Análisis de RegresiónRESUMEN
In biomedical research it is common to find problems in which we wish to relate a response variable to one or more variables capable of describing the behaviour of the former variable by means of mathematical models. Regression techniques are used to this effect, in which an equation is determined relating the two variables. While such equations can have different forms, linear equations are the most widely used form and are easy to interpret. The present article describes simple and multiple linear regression models, how they are calculated, and how their applicability assumptions are checked. Illustrative examples are provided, based on the use of the freely accessible R program.
Asunto(s)
Investigación Biomédica/métodos , Modelos Lineales , Modelos Estadísticos , Análisis MultivarianteRESUMEN
Lipopolyamines are a class of polycationic amphiphilic compounds that have been shown to bind with high affinity to polyanionic macromolecules, including both DNA and bacterial lipopoly-saccharide (LPS). One of these compounds, termed DOSPER (1,3-di-oleoyloxy-2-(6-carboxyl-spermyl)- propylamide), is non-cytotoxic and has been shown to inhibit LPS-mediated cytokine release and lethality in endotoxin challenge models. In the study reported here, the activity of DOSPER was tested in neutropenic rats with invasive Gram-negative bacteremia caused by Pseudomonas aeruginosa. DOSPER alone was ineffective (0/8) at influencing mortality, but provided a significant survival advantage if administered in combination with a bactericidal antibiotic, ceftazidime (10/12; P<0.05). Ceftazidime alone was partially protective (6/12) while the control group had no survivors (0/8). DOSPER administration markedly reduced circulating endotoxin levels (P<0.01) and interleukin-6 levels (P<0.05) but had no significant effect on bacteremia and bacterial concentrations of P. aeruginosa in liver or spleen tissue. Lipopolyamines may be potentially valuable as a therapeutic adjunct in treatment of Gram-negative bacterial sepsis.
Asunto(s)
Ceftazidima/uso terapéutico , Cefalosporinas/uso terapéutico , Ácidos Grasos Monoinsaturados/uso terapéutico , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Sepsis/tratamiento farmacológico , Animales , Bacteriemia , Ceftazidima/administración & dosificación , Cefalosporinas/administración & dosificación , Modelos Animales de Enfermedad , Quimioterapia Combinada , Ácidos Grasos Monoinsaturados/administración & dosificación , Neutropenia/tratamiento farmacológico , Ratas , Análisis de SupervivenciaRESUMEN
P-selectin is a major component in the early interaction between platelets, endothelial cells, and inflammatory cells in the initial phases of the innate immune response. The major ligand for P-selectin is P-selectin glycoprotein ligand-1 (PSGL-1) and this ligand is expressed on the surface of monocyte, lymphocyte, and neutrophil membranes. A truncated form of recombinant human P-selectin glycoprotein ligand-1 has been covalently linked to immunoglobulin G (rPSGL-Ig) and this fusion peptide functions as a competitive inhibitor of PSGL-1. As an inhibitor of neutrophil-endothelial cell adherence, rPSGL-Ig is in early clinical development for the treatment of ischemia reperfusion injury. To determine the potential for deleterious effects from inhibition in P-selectin-mediated neutrophil attachment in the presence of bacterial infection, the effects of therapeutic doses of rPSGL-Ig were tested in three standard laboratory sepsis models. The experimental models included: the murine systemic Listeria monocytogenes infection model, the Pseudomonas aeruginosa bacteremia model in neutropenic rats, and the cecal ligation and puncture (CLP)-induced peritonitis model in rats. Recombinant human PSGL-Ig had no adverse effects on mortality or immune clearance in systemic bacterial infection in any of the three infection models. The PSGL-1 inhibitor did significantly decrease local neutrophil infiltration and bacterial clearance in the peritoneum following CLP, but this did not increase the systemic levels of proinflammatory cytokines, the quantitative levels of bacteremia, or the overall mortality rate following CLP. The results indicate that rPSGL-Ig did not exacerbate infection in these experimental sepsis models.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Quimiotaxis de Leucocito/efectos de los fármacos , Inmunoconjugados/uso terapéutico , Glicoproteínas de Membrana/antagonistas & inhibidores , Glicoproteínas de Membrana/uso terapéutico , Animales , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/toxicidad , Bacteriemia/sangre , Bacteriemia/tratamiento farmacológico , Bacteriemia/inmunología , Bacteriemia/microbiología , Infecciones Bacterianas/inmunología , Ciego/lesiones , Adhesión Celular/efectos de los fármacos , Citocinas/sangre , Depresión Química , Evaluación Preclínica de Medicamentos , Femenino , Genes de Inmunoglobulinas , Humanos , Inmunoconjugados/farmacología , Inmunoconjugados/toxicidad , Fragmentos Fc de Inmunoglobulinas , Inmunoglobulina G/genética , Perforación Intestinal/complicaciones , Listeriosis/tratamiento farmacológico , Listeriosis/inmunología , Glicoproteínas de Membrana/farmacología , Glicoproteínas de Membrana/toxicidad , Ratones , Ratones Endogámicos C57BL , Neutropenia/inducido químicamente , Neutropenia/complicaciones , Neutrófilos/efectos de los fármacos , Neutrófilos/fisiología , Selectina-P/fisiología , Peritonitis/tratamiento farmacológico , Peritonitis/inmunología , Infecciones por Pseudomonas/sangre , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/inmunología , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes de Fusión/farmacología , Proteínas Recombinantes de Fusión/uso terapéutico , Proteínas Recombinantes de Fusión/toxicidad , Seguridad , Organismos Libres de Patógenos EspecíficosRESUMEN
The passive infusion of antibodies elicited in rabbits with a detoxified J5 lipopolysaccharide (LPS)/group B meningococcal outer membrane protein complex vaccine protected neutropenic rats from heterologous lethal gram-negative bacterial infection. In this study, active immunization was studied in neutropenic rats infected with Pseudomonas aeruginosa, in the presence or absence of ceftazidime therapy, and with Klebsiella pneumoniae. This vaccine elicited a > 200-fold increase in anti-J5 LPS antibody, which remained elevated throughout the duration of cyclophosphamide-induced neutropenia and for < or = 3 months. There was improved survival among immunized versus control animals: 48% (13/28) versus 7% (2/29) in Pseudomonas-challenged rats; 61% (11/18) versus 0% (0/10) in Pseudomonas- and ceftazidime-treated rats; and 64% (9/14) versus 13% (2/15) in Klebsiella-challenged rats (P < 0.01 for each comparison). Immunized animals had lower levels of bacteria in organs and lower levels of circulating endotoxin at the onset of fever. In conclusion, active immunization with an anti-endotoxin vaccine improved survival after infection with > or = 2 heterologous, clinically relevant bacterial species in immunocompromised animals. Active immunization with this vaccine merits further investigation.
Asunto(s)
Proteínas de la Membrana Bacteriana Externa/inmunología , Vacunas contra Escherichia coli/administración & dosificación , Escherichia coli/inmunología , Lipopolisacáridos/inmunología , Neisseria meningitidis/inmunología , Sepsis/prevención & control , Animales , Anticuerpos Antibacterianos/sangre , Ceftazidima/uso terapéutico , Cefalosporinas/uso terapéutico , Ciclofosfamida , Modelos Animales de Enfermedad , Supervivencia sin Enfermedad , Endotoxinas/sangre , Femenino , Klebsiella pneumoniae , Neutropenia/inducido químicamente , Pseudomonas aeruginosa , Ratas , Ratas Sprague-Dawley , Sepsis/inmunología , Sepsis/microbiología , Vacunas ConjugadasRESUMEN
OBJECTIVES: To study recombinant human tissue factor pathway inhibitor (rhTFPI) in a superantigen-induced shock model and in a cecal ligation and puncture (CLP) model of peritonitis in mice. DESIGN: Prospective, randomized, experimental study. SETTING: An experimental animal research laboratory. SUBJECTS: Eighty BALB/c mice for the superantigen model, and 56 BALB/c mice for the CLP model. INTERVENTIONS: In the superantigen-induced shock model, animals received rhTFPI (350 mg/kg) subcutaneously every 12 hrs (n = 30) or saline control (n = 30) for 60 hrs after staphylococcal enterotoxin B (SEB; 10 microg iv) and a sublethal dose of E. coli 0111:B4 lipopolysaccharide (LPS; 75 microg ip). Control groups received SEB alone (n = 10) and LPS alone (n = 10). In the CLP model, rhTFPI or saline was given every 8 hrs for 48 hrs by using a 21-gauge needle (n = 9) or 23-gauge needle (n = 14) for CLP. A sham surgery control group (n = 10) was also included. MEASUREMENTS AND MAIN RESULTS: There was 0% mortality in the SEB and LPS control groups. The mortality rate was 64% in the saline control group that received both SEB and LPS (19 of 30), whereas the rhTFPI- treated animals had a mortality rate of 20% (6 of 30; p < .01). The rhTFPI-treated group had significantly lower interleukin-6 levels (61.8 +/- 41 pg/mL vs. 285 +/- 63 pg/mL; p < .05) than the control group but no differences in tumor necrosis factor-alpha or interferon-gamma levels. In the CLP experiment, rhTFPI-treated animals did not have any survival advantage over the control group after the large-bore (21-gauge) needle puncture. The rhTFPI group had significantly improved 7-day mortality rate after CLP with the small-bore needle (23-gauge; 21.4% [rhTFPI] vs. 71.4% [control], p < .01). Plasma LPS, interleukin-6, interferon-gamma, and tumor necrosis factor-alpha levels were unchanged by rhTFPI treatment, but significantly reduced LPS (p = .006) and IFNgamma (p = .001) levels were found in the peritoneal fluid. CONCLUSIONS: Tissue factor pathway inhibitor significantly improves the mortality rate in models of superantigen-induced shock and polymicrobial intra-abdominal infection, supporting its potential use in clinical trials for septic shock.
Asunto(s)
Anticoagulantes/uso terapéutico , Inhibidores del Factor Xa , Lipoproteínas/uso terapéutico , Peritonitis/tratamiento farmacológico , Choque Séptico/tratamiento farmacológico , Animales , Citocinas/sangre , Endotoxinas/sangre , Ratones , Ratones Endogámicos BALB C , Peritonitis/inmunología , Peritonitis/mortalidad , Distribución Aleatoria , Proteínas Recombinantes/uso terapéutico , Choque Séptico/inmunología , Choque Séptico/mortalidad , Staphylococcus , Estadísticas no Paramétricas , Superantígenos , Tasa de SupervivenciaRESUMEN
Severe melioidosis is a life-threatening, systemic bacterial infection caused by Burkholderia pseudomallei. A prospective, randomized treatment trial was conducted in northeast Thailand to compare ceftazidime (a penicillin-binding protein [PBP]-3-specific agent that causes release of large amounts of endotoxin in vitro) and imipenem (a PBP-2-specific agent that kills B. pseudomallei more rapidly but releases low amounts of endotoxin) in severe melioidosis over a 6-h time course after the first dose of antibiotic. Despite similar clinical, microbiological, endotoxin, and cytokine measures at study entry, ceftazidime-treated patients (n=34) had significantly greater systemic endotoxin (P<.001) than patients treated with imipenem (n=34) after the first dose of antibiotic. No overall difference in mortality was observed (35% in both groups [95% confidence interval, 20%-50%]). Differential antibiotic-induced endotoxin release is demonstrable in severe melioidosis. These differences in endotoxin release did not appear to have a significant impact on survival in this group of patients.
Asunto(s)
Antibacterianos/uso terapéutico , Ceftazidima/uso terapéutico , Endotoxinas/metabolismo , Imipenem/uso terapéutico , Melioidosis/tratamiento farmacológico , Adulto , Anciano , Citocinas/sangre , Femenino , Humanos , Masculino , Melioidosis/inmunología , Melioidosis/mortalidad , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
To determine whether recombinant human (rh) interleukin (IL)-11 disrupts the clearance of microbial pathogens, mice were challenged with Listeria monocytogenes after receiving high-dose rhIL-11, anti-tumor necrosis factor (TNF) monoclonal antibody (MAb), anti-IL-11 MAb, or saline control. The LD50 was not affected by rhIL-11 but was 10-fold lower in the anti-TNF MAb group (P<.001). Plasma IL-6, IL-1beta, and TNF-alpha levels were not different between rhIL-11-treated animals and the control group; however, interferon-gamma levels were significantly reduced by IL-11 treatment (2477 vs. 0 pg/mL, P<.01). Compared with the control group, the quantitative level of L. monocytogenes in hepatic and splenic tissue was unchanged by rhIL-11 but was significantly increased by TNF or IL-11 inhibition. The results indicate that IL-11 down-regulates cytokine production but does not exacerbate systemic infection in the murine Listeria infection model.
Asunto(s)
Interleucina-11/inmunología , Listeria monocytogenes/inmunología , Listeriosis/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Recuento de Colonia Microbiana , Citocinas/biosíntesis , Femenino , Listeria monocytogenes/aislamiento & purificación , Listeriosis/microbiología , Hígado/microbiología , Ratones , Ratones Endogámicos C57BL , Proteínas Recombinantes/inmunología , Bazo/microbiología , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Plasma endotoxin and lipopolysaccharide-binding protein (LBP) levels were measured in a group of 253 patients at the onset of severe sepsis and/or septic shock. Endotoxin levels were significantly greater than control levels (n=33; mean +/- SD, 5.1+/-7.3 pg/mL) in 78.3% of patients. Median endotoxin levels in patients with sepsis were 300 pg/mL (25%-75% interquartile range, 110-726 pg/mL). LBP levels were elevated in 97% of patients compared with normal control values of 4.1+/-1.65 microgram/mL. Median LBP levels in patients with sepsis were 31.2 microgram/mL (interquartile range, 22.5-47.7 microgram/mL). Median endotoxin levels at study entry were more highly elevated (515 vs. 230 pg/mL; P<.01), and LBP levels were less highly elevated (28.0 vs. 33.2 microgram/mL; P<.05) in nonsurvivors than survivors over the 28-day study period. No correlation was found between endotoxin and LBP levels. The quantitative level of both endotoxin and LBP may have prognostic significance in patients with severe sepsis.
Asunto(s)
Proteínas de Fase Aguda , Bacteriemia/sangre , Proteínas Portadoras/sangre , Endotoxinas/sangre , Fungemia/sangre , Lipopolisacáridos/sangre , Glicoproteínas de Membrana , Choque Séptico/sangre , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is widely used to promote granulocyte recovery from a variety of pathologic states. Recombinant human interleukin-11 (rhIL-11) has recently become available clinically as a platelet restorative agent after myelosuppressive chemotherapy. Preclinical data has shown that rhIL-11 limits mucosal injury after chemotherapy and attenuates the proinflammatory cytokine response. The potential efficacy of combination therapy with recombinant human forms of rhIL-11 and rhG-CSF was studied in a neutropenic rat model of Pseudomonas aeruginosa sepsis. At the onset of neutropenia, animals were randomly assigned to receive either rhG-CSF at a dose of 200 micrograms/kg subcutaneously every 24 hours for 7 days; rhIL-11 at 200 micrograms/kg subcutaneously every 24 hours for 7 days; the combination of both rhG-CSF and rhIL-11; or saline control. Animals were orally colonized with Pseudomonas aeruginosa 12.4.4 and then given a myelosuppressive dose of cyclophosphamide. rhG-CSF resulted in a slight increase in absolute neutrophil counts (ANC), but did not provide a survival advantage (0 of 12, 0% survival) compared with the placebo group (1 of 12, 8% survival). rhIL-11 was partially protective (4 of 10, 40% survival); the combination of rhG-CSF and rhIL-11 resulted in a survival rate of 80% (16 of 20; P <.001). rhIL-11 alone or in combination with rhG-CSF resulted in preservation of gastrointestinal mucosal integrity (P <.001), lower circulating endotoxin levels (P <.01), and reduced quantitative levels of P. aeruginosa in quantitative organ cultures. These results indicate that the combination of rhIL-11 and rhG-CSF is additive as a treatment strategy in the prevention and treatment of experimental Gram-negative sepsis in immunocompromised animals. This combination may prove to be efficacious in the prevention of severe sepsis in neutropenic patients.
Asunto(s)
Bacteriemia/terapia , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Interleucina-11/uso terapéutico , Infecciones por Pseudomonas/terapia , Animales , Bacteriemia/patología , Ciclofosfamida/farmacología , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Inmunosupresores/farmacología , Inflamación , Inyecciones Subcutáneas , Interleucina-11/administración & dosificación , Mucosa Intestinal/patología , Intestino Delgado/patología , Neutropenia/complicaciones , Infecciones por Pseudomonas/patología , Pseudomonas aeruginosa , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéutico , SobrevidaRESUMEN
The therapeutic potential of recombinant human interleukin-11 (rhIL-11) was tested in a neutropenic rat model that mimics the clinical consequences of myelosuppressive chemotherapy complicated by Pseudomonas aeruginosa sepsis. rhIL-11-treated animals (150 micrograms/kg intravenously every 24 h for 3 days) had reduced endotoxin levels (P < .05) and less pulmonary edema fluid (P < .001) and were protected (P < .01) against thinning and necrosis of the intestinal mucosa compared with the control group. The survival rate in rhIL-11-treated animals was 40% (19/47), whereas it was 0 (0 of 19) in the control group (P < .01). The addition of ciprofloxacin (10 mg/kg every 12 h) resulted in a survival rate of 9 (60%) of 15, while the combination of rhIL-11 and ciprofloxacin resulted in 100% survival (15/15; P < .05). These results indicate that rhIL-11 supports mucous membrane integrity of the alimentary tract and decreases the systemic inflammatory response to experimental gram-negative infection in immunocompromised animals.
Asunto(s)
Huésped Inmunocomprometido , Interleucina-11/uso terapéutico , Infecciones por Pseudomonas/tratamiento farmacológico , Sepsis/tratamiento farmacológico , Animales , Antiinfecciosos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacteriemia/mortalidad , Ciprofloxacina/uso terapéutico , Modelos Animales de Enfermedad , Quimioterapia Combinada , Humanos , Neutropenia , Infecciones por Pseudomonas/mortalidad , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes/uso terapéuticoRESUMEN
Using an actual infection model of Pseudomonas aeruginosa sepsis in neutropenic rats, the potential utility of a combination anticytokine approach for the treatment of sepsis was tested. A dimeric tumor necrosis factor binding protein (TNF-BP) consisting of two soluble recombinant human TNF type 1 receptors linked with polyethylene glycol was used with recombinant human interleukin-1 receptor antagonist (IL-1ra). Despite having levels of bacteremia and endotoxemia similar to the control group (survivors, 0/18), 30% of IL-1ra-treated animals survived (P < .05); 31% of TNF-BP-treated animals survived (P < .01). Unexpectedly, the combination of IL-1ra plus TNF-BP proved to be uniformly fatal (survivors, 0/20). Endotoxin (P < .0001) and bacteremia (P < .01) levels were >10-fold higher than levels in animals treated with IL-1ra alone, TNF-BP alone, or placebo. Disseminated microabscesses in major organs were found in animals treated with combination immunotherapy. Combination anticytokine therapy may exacerbate systemic infection and worsen outcome in experimental sepsis.