RESUMEN
Activity of dalbavancin against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE) in biofilm was investigated and the microbicidal biofilm concentrations (MBC) were determined. Biofilms obtained from ten MRSA and ten MRSE bloodstream isolates, collected from patients in the General Hospital of Vienna between 2012 and 2015, were incubated with dalbavancin in trypticase soy broth (TSB) in serial dilution from 0.0625 mg/l to 256 mg/l using a microtiter plate biofilm model. The plates were incubated for 24 h at 37 ° C and 50% humidity. Biofilms were fixed with 2.5% glutaraldehyde and stained with crystal violet. Subsequently the optical density (OD620) was used to measure the MBC, defined as the concentration of dalbavancin leading to a 50% reduction of biofilm. MBC for MRSA was 1 mg/l-4 mg/l (minimal inhibitory concentrations (MIC) 0.0312 mg/l-0.064 mg/l). MBC for MRSE was 2 mg/l-16 mg/l (MIC 0.023 mg/l-0.0625 mg/l). Dalbavancin successfully reduced MRSA and MRSE in biofilms, and therefore provides a promising option for the treatment of biofilm-associated infections.
Asunto(s)
Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Resistencia a la Meticilina , Staphylococcus aureus/efectos de los fármacos , Staphylococcus epidermidis/efectos de los fármacos , Teicoplanina/análogos & derivados , Austria , Bacteriemia/microbiología , Colorimetría , Violeta de Genciana/análisis , Hospitales Generales , Humanos , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Coloración y Etiquetado , Staphylococcus aureus/fisiología , Staphylococcus epidermidis/fisiología , Teicoplanina/farmacologíaRESUMEN
BACKGROUND: Active surveillance is an increasingly accepted approach for managing patients with germ-cell tumors (GCTs) after an orchiectomy. Here we investigate a time-to-relapse stratification scheme for clinical stage 1 (CS1) nonseminoma GCT (NSGCT) patients according to factors associated with relapse and identify a group of patients with a lower frequency and longer time-to-relapse who may require an alternative surveillance strategy. PATIENTS AND METHODS: We analyzed 266 CS1 GCT patients from the IRB-approved DFCI GCT database that exclusively underwent surveillance following orchiectomy from 1997 to 2013. We stratified NSGCT patients according to predominance of embryonal carcinoma (EmbP) and lymphovascular invasion (LVI), using a 0, 1, and 2 scoring system. Cox regression and conditional risk analysis were used to compare each NSGCT group to patients in the seminomatous germ-cell tumor (SGCT) category. Median time-to-relapse values were then calculated among those patients who underwent relapse. Relapse-free survival curves were generated using the Kaplan-Meier method. RESULTS: Fifty (37%) NSGCT and 20 (15%) SGCT patients relapsed. The median time-to-relapse was 11.5 versus 6.3 months for the SGCT and NSGCT groups, respectively. For NSGCT patients, relapse rates were higher and median time-to-relapse faster with increasing number of risk factors (RFs). Relapse rates (%) and median time-to-relapse (months) were 25%/8.5 months, 41%/6.8 months and 78%/3.8 months for RF0, RF1 and RF2, respectively. We found a statistically significant difference between SGCT and patients with one or two RFs (P < 0.001) but not between SGCT and NSGCT RF0 (P = 0.108). CONCLUSION: NSGCT patients grouped by a risk score system based on EmbP and LVI yielded three groups with distinct relapse patterns -and patients with neither EmbP nor LVI appear to behave similar to SGCT.
Asunto(s)
Carcinoma Embrionario/patología , Ganglios Linfáticos/patología , Recurrencia Local de Neoplasia/patología , Neoplasias de Células Germinales y Embrionarias/patología , Medición de Riesgo , Seminoma/patología , Neoplasias Testiculares/patología , Adolescente , Adulto , Anciano , Carcinoma Embrionario/mortalidad , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia/mortalidad , Estadificación de Neoplasias , Neoplasias de Células Germinales y Embrionarias/mortalidad , Vigilancia de la Población , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Seminoma/mortalidad , Tasa de Supervivencia , Neoplasias Testiculares/mortalidad , Adulto JovenRESUMEN
Kinesio taping has also been used for athletes with Medial Elbow Epicondylar Tendinopathy (MET) as an additional treatment method. The purpose of this study was to determine the clinical effectiveness of Kinesio tape on maximal grip strength and absolute and related force sense in athletes with MET when applied to the medial forearm. 27 male athletes who voluntarily participated in this study were divided into a healthy group (n=17) and a MET group (n=10). All subjects were assessed for the maximal grip strength and grip force sense (absolute and related force sense) under 3 taping conditions: 1) without taping; 2) with placebo Kinesio taping; and 3) with Kinesio taping. No significant interaction was found between groups and taping condition in maximal grip force and related force sense error, except for absolute force sense error (p=0.04). Both groups with absolute force sense measurements had significantly decreased errors in the placebo Kinesio taping and Kinesio taping conditions. Both taping may enhance discrimination of magnitude of grip force control (absolute force sense) in both groups when applied to the forearm. However, Kinesio taping did not change maximal grip strength in either group. The effects of Kinesio taping on other muscle functions remain to be studied.
Asunto(s)
Traumatismos en Atletas/terapia , Cinta Atlética , Lesiones de Codo , Tendinopatía/terapia , Adolescente , Traumatismos del Brazo/terapia , Atletas , Traumatismos en Atletas/fisiopatología , Estudios de Casos y Controles , Humanos , Masculino , Método Simple Ciego , Tendinopatía/fisiopatología , Resultado del Tratamiento , Adulto JovenRESUMEN
1. Two novel HLA-A2.1 specific H5N1 nucleoprotein epitopes(NP373-381 AMDSNTLEL and NP458-466 FQGRGVFEL) capable of activating cytotoxic T-cells in vitro were identified. 2. When the H5N1 nucleoprotein epitopes (NP373-381AMDSNTLEL and NP458-466FQGRGVFEL) were used with the single chain trimer system, they elicited effective cytotoxic T-cell responses against the corresponding nucleoprotein peptide-loaded cells in an HHD transgenic mouse model.
Asunto(s)
Linfocitos T CD8-positivos/metabolismo , Subtipo H5N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/farmacología , Gripe Humana/inmunología , Nucleoproteínas/inmunología , Animales , Células Cultivadas , Citotoxicidad Inmunológica , Epítopos de Linfocito T , Humanos , Interferón gamma/metabolismo , Ratones , Infecciones por Orthomyxoviridae/inmunologíaRESUMEN
BACKGROUND AND PURPOSE: Damage to the blood brain barrier (BBB) may lead to haemorrhagic transformation after ischaemic stroke. The purpose of this study was to evaluate the effect of patient characteristics and stroke severity on admission BBB permeability (BBBP) values measured with perfusion-CT (PCT) in acute ischaemic stroke patients. METHODS: We retrospectively identified 65 patients with proven ischaemic stroke admitted within 12 hours after symptom onset. Patients' charts were reviewed for demographic variables and vascular risk factors. The Patlak's model was applied to calculate BBBP values from the PCT data in the infarct core, penumbra and non-ischaemic tissue in the contralateral hemisphere. Mean BBBP values and their 95% confidence intervals (CI) were calculated in the different tissue types. Effects of demographic variables and risk factors on BBBP were analyzed using a multivariate, generalized estimating equations (GEE) model. RESULTS: BBBP values in the infarct core (mean [95%CI]: 2.48 [2.16-2.85]) and penumbra (2.48 [2.21-2.79]) were significantly higher than in non-ischaemic tissue (2.12 [1.88-2.39]). Multivariate analysis demonstrated that collateral filling has effect on BBBP. Less elevated BBBP values were associated with more than 50% collateral filling. CONCLUSIONS: BBBP values are increased in ischaemic brain tissue on the admission PCT scan of acute ischaemic stroke patients. Less abnormally elevated BBBP values were observed in patients with more than 50% collateral filling, possibly explaining why there is a relationship between more collateral filling and a lower incidence of haemorrhagic transformation.
Asunto(s)
Barrera Hematoencefálica , Isquemia Encefálica/diagnóstico por imagen , Angiografía Cerebral/métodos , Accidente Cerebrovascular/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Medios de Contraste , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Interpretación de Imagen Radiográfica Asistida por Computador , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To determine the optimal spatial coverage for CT-imaging of carotid atherosclerosis, allowing the most accurate prediction of the associated risk of ischemic stroke. METHODS: In a cross-sectional study, we retrospectively identified 136 consecutive patients admitted to our emergency department with suspected stroke who underwent a CT-angiogram (CTA) of the cervical and intracranial carotid arteries. CTA studies of the carotid arteries were processed using a custom, CT-based automated computer classifier algorithm that quantitatively assesses a battery of carotid CT features. We used this algorithm to individually analyze different lengths of the common and internal carotid arteries for carotid wall features previously shown to be significantly associated with the risk of stroke. Acute stroke patients were categorized into "acute carotid stroke patients" and "non-acute carotid stroke patients" independently of carotid wall CT features. Univariate and multivariate analyses were used to compare the different spatial coverages in terms of their ability to distinguish between the carotid stroke patients and the noncarotid stroke patients using a receiver-operating characteristic curve (ROC) approach. RESULTS: The carotid wall volume was excellent at distinguishing between carotid stroke patients and noncarotid stroke patients, especially for coverages 20mm or less. The number and location of lipid clusters had a good discrimination power, mainly for coverages 15mm or greater. Measurement of minimal fibrous cap thickness was most associated with carotid stroke when assessed using intermediate coverages. Typically, a 20mm coverage on each side of the carotid bifurcation offered the optimal compromise between the individual carotid features. CONCLUSION: We recommend assessment of 20mm of each side of the carotid bifurcation to best characterize carotid atherosclerotic disease and the associated risk of ischemic stroke.
Asunto(s)
Isquemia Encefálica/diagnóstico , Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Angiografía Cerebral/métodos , Accidente Cerebrovascular/diagnóstico , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/diagnóstico por imagen , Estudios Transversales , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Riesgo , Accidente Cerebrovascular/diagnóstico por imagen , Adulto JovenRESUMEN
Glucosamine has been widely used to treat osteoporosis in clinic and it shows an effect on hexosamine biosynthetic pathway in glucose-induced insulin resistance. However, glucosamine and chronic hyperglycemia is not correlative. Thus, we used C (2)C (12) cell line to carry out the uptake assay of 2-[14C]-deoxy-d-glucose and [3H]-glucosamine. Glucosamine inhibited the in vitro glucose uptake in a concentration-dependent manner. The glucose transporter GLUT4 prepared for [3H]-glucosamine uptake showed a concentration-dependent competition between glucose and glucosamine uptake. The effects of glucosamine on glucose tolerance and homeostasis model assessment (HOMA) were also determined in normal Wistar and fructose-fed rats. Both plasma glucose levels and/or HOMA index were not changed in normal rats treated with glucosamine as compared with the saline-treated control. However, we found that glucosamine exhibited an effect on the expression of farnesoid X receptor in liver to exacerbate the values of HOMA and accelerate the development of insulin resistance in fructose-fed rats. Thus, glucosamine should be applied with caution in type-2 diabetic patients.
Asunto(s)
Fructosa/metabolismo , Glucosamina/metabolismo , Resistencia a la Insulina , Animales , Línea Celular , Expresión Génica , Glucosa/metabolismo , Transportador de Glucosa de Tipo 4/genética , Transportador de Glucosa de Tipo 4/metabolismo , Masculino , Ratones , Ratas , Ratas Wistar , Receptores Citoplasmáticos y Nucleares/genética , Receptores Citoplasmáticos y Nucleares/metabolismoRESUMEN
Stonefish envenomation is a common marine sting. Although stonefish injuries are commonly sustained during maritime activities, this local delicacy can also be considered a regional occupational hazard for chefs. The availability and consumption of stonefish in local restaurants has increased the risk of acute carpal tunnel syndrome after a stonefish injury. This case report describes acute carpal tunnel syndrome following stonefish envenomation. An excellent recovery was achieved after surgical decompression of the carpal tunnel syndrome. Standard management of stonefish injuries should therefore take into account the possibility that this orthopaedic emergency may complicate the injury.
Asunto(s)
Síndrome del Túnel Carpiano/inducido químicamente , Venenos de los Peces/efectos adversos , Peces Venenosos , Exposición Profesional , Animales , Antivenenos/uso terapéutico , Síndrome del Túnel Carpiano/cirugía , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Profesionales , Procedimientos Ortopédicos , RestaurantesRESUMEN
1. A recombinant adenovirus encoding SARS coronavirus(SARS-CoV) nucleocapsid protein (rAd-N) was constructed. 2. The ability of the rAd-N to induce anti-SARS-CoV N antibody production and cellular immune responses was evaluated in an HLA-A2.1/Kb transgenic mouse model.
Asunto(s)
Antígeno HLA-A2/genética , Proteínas de la Nucleocápside/inmunología , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/inmunología , Vacunas Virales/inmunología , Adenoviridae/genética , Animales , Formación de Anticuerpos , Proteínas de la Nucleocápside de Coronavirus , Femenino , Vectores Genéticos , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Transgénicos , Proteínas de la Nucleocápside/genética , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genéticaRESUMEN
BACKGROUND AND PURPOSE: The goal of this study was to determine blood-brain barrier permeability (BBBP) values extracted from perfusion-CT (PCT) using the Patlak model and possible variations related to age, gender, race, vascular risk factors and their treatment and anatomy in non-stroke patients. MATERIALS AND METHODS: We retrospectively identified 96 non-stroke patients who underwent a PCT study using a prolonged acquisition time up to 3 minutes. Patients' charts were reviewed for demographic data, vascular risk factors and their treatment. The Patlak model was applied to calculate BBBP values in regions of interest drawn within the basal ganglia and the gray and white matter of the different cerebral lobes. Differences in BBBP values were analyzed using a multivariate analysis considering clinical variables and anatomy. RESULTS: Mean absolute BBBP values were 1.2 ml 100 g(-1) min(-1) and relative BBBP/CBF values were 3.5%. Statistical differences between gray and white matter were not clinically relevant. BBBP values were influenced by age, history of diabetes and/or hypertension and aspirin intake. CONCLUSION: This study reports ranges of BBBP values in non-stroke patients calculated from delayed phase PCT data using the Patlak model. These ranges will be useful to detect abnormal BBBP values when assessing patients with cerebral infarction for the risk of hemorrhagic transformation.
Asunto(s)
Barrera Hematoencefálica/fisiología , Permeabilidad Capilar/fisiología , Angiografía Cerebral/métodos , Tomografía Computarizada por Rayos X/métodos , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Interpretación de Imagen Radiográfica Asistida por Computador , Valores de Referencia , Estudios Retrospectivos , Factores de Riesgo , Factores SexualesRESUMEN
1. A novel HLA-A2.1-specific SARS coronavirus (SARS-CoV) nucleocapsid (N) protein epitope (N220-N228 LALLLLDRL) able to activate cytotoxic T cells in vitro has been identified. 2. When used with a single-chain-trimer system, the SARS-CoV N protein epitope (N220-N228 LALLLLDRL) can stimulate a cytotoxic T-cell response against N-protein expressing cells in the HLA-A2.1K(b) transgenic mouse model.
Asunto(s)
Epítopos de Linfocito T/inmunología , Proteínas de la Nucleocápside/inmunología , Síndrome Respiratorio Agudo Grave/prevención & control , Síndrome Respiratorio Agudo Grave/terapia , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/inmunología , Vacunas Virales/farmacología , Animales , Proteínas de la Nucleocápside de Coronavirus , ADN Viral/inmunología , ADN Viral/metabolismo , Modelos Animales de Enfermedad , Antígenos HLA-A/inmunología , Antígeno HLA-A2/inmunología , Humanos , Ratones , Ratones Transgénicos , Probabilidad , Distribución Aleatoria , Sensibilidad y Especificidad , Síndrome Respiratorio Agudo Grave/inmunología , Linfocitos T Citotóxicos/inmunología , Vacunas de ADN/inmunología , Vacunas Virales/inmunologíaRESUMEN
We have previously shown that the yeast PRP19 protein is associated with the spliceosome during the splicing reaction by immunoprecipitation studies with anti-PRP19 antibody. We have extended such studies by using extracts depleted of specific splicing factors to investigate the step of the spliceosome assembly process that PRP19 is involved in. PRP19 was not associated with the splicing complexes formed in U2- or U6-depleted extracts but was associated with the splicing complex formed in heat-inactivated prp2 extracts. This finding indicates that PRP19 becomes associated with the splicing complexes after or concomitant with binding of the U6 small nuclear ribonucleoprotein particle (snRNP) to the precursor RNA and before formation of the functional spliceosome. We further analyzed whether PRP19 is an integral component of snRNPs. We have constructed a strain in which an epitope of nine amino acid residues recognized by a well-characterized monoclonal antibody, 12CA5, is linked to the carboxyl terminus of the wild-type PRP19 protein. Immunoprecipitation of the splicing extracts with anti-PRP19 antibody or precipitation of the extracts prepared from the epitope-tagged strain with the 12CA5 antibody did not precipitate significant amounts of snRNAs. Addition of micrococcal nuclease-treated extracts to the PRP19-depleted extract restored its splicing activity. These results indicate that PRP19 is not tightly associated with any of the snRNAs required for the splicing reaction. No non-snRNP protein factor has been demonstrated to participate in either step of the spliceosome assembly pathway that PRP19 might be involved in. Thus, PRP19 represents a novel splicing factor.
Asunto(s)
Proteínas Fúngicas/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Empalme del ARN , Ribonucleoproteína Nuclear Pequeña U2/metabolismo , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Empalmosomas/metabolismo , Anticuerpos Monoclonales , Secuencia de Bases , ARN Helicasas DEAD-box , Epítopos , Proteínas Fúngicas/inmunología , Datos de Secuencia Molecular , Precursores del ARN/metabolismo , Factores de Empalme de ARN , ARN Nuclear Pequeño/metabolismo , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/metabolismo , Ribonucleoproteína Nuclear Pequeña U4-U6/metabolismoRESUMEN
We have isolated the gene of a splicing factor, PRP19, by complementation of the temperature-sensitive growth defect of the prp19 mutant of Saccharomyces cerevisiae. The gene encodes a protein of 502 amino acid residues of molecular weight 56,500, with no homology to sequences in the data base. Unlike other PRP proteins or mammalian splicing factors, the sequence of PRP19 has no discernible motif. Immunoprecipitation studies showed that PRP19 is associated with the spliceosome during the splicing reaction. Although the exact function of PRP19 remains unknown, PRP19 appears to be distinct from the other PRP proteins or other spliceosomal components.
Asunto(s)
Proteínas Fúngicas/genética , Genes Fúngicos/genética , Empalme del ARN/genética , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Empalmosomas/química , Secuencia de Aminoácidos , Secuencia de Bases , Mapeo Cromosómico , Codón , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Factores de Empalme de ARN , Análisis de Secuencia de ADN , Transcripción Genética , Transformación GenéticaRESUMEN
The yeast protein Prp19p is essential for pre-mRNA splicing and is associated with the spliceosome concurrently with or just after dissociation of U4 small nuclear RNA. In splicing extracts, Prp19p is associated with several other proteins in a large protein complex of unknown function, but at least one of these proteins is also essential for splicing (W.-Y. Tarn, C.-H. Hsu, K.-T. Huang, H.-R. Chen, H.-Y. Kao, K.-R. Lee, and S.-C. Cheng, EMBO J. 13:2421-2431, 1994). To identify proteins in the Prp19p-associated complex, we have isolated trans-acting mutations that exacerbate the phenotypes of conditional alleles of prp19, using the ade2-ade3 sectoring system. A novel splicing factor, Snt309p, was identified through such a screen. Although the SNT309 gene was not essential for growth of Saccharomyces cerevisiae under normal conditions, yeast cells containing a null allele of the SNT309 gene were temperature sensitive and accumulated pre-mRNA at the nonpermissive temperature. Far-Western blot analysis revealed direct interaction between Prp19p and Snt309p. Snt309p was shown to be a component of the Prp19p-associated complex by Western blot analysis. Immunoprecipitation studies demonstrated that Snt309p was also a spliceosomal component and associated with the spliceosome in the same manner as Prp19p during spliceosome assembly. These results suggest that the functions of Prp19p and Snt309p in splicing may require coordinate action of these two proteins.
Asunto(s)
Proteínas Fúngicas/metabolismo , Empalme del ARN , Ribonucleoproteína Nuclear Pequeña U4-U6/metabolismo , Proteínas de Saccharomyces cerevisiae , Empalmosomas/metabolismo , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , ADN de Hongos , Proteínas Fúngicas/genética , Genes Letales , Genes Sintéticos , Datos de Secuencia Molecular , Mutagénesis , Fenotipo , Unión Proteica , Factores de Empalme de ARN , ARN Mensajero/metabolismo , Saccharomyces cerevisiae , TemperaturaRESUMEN
In Saccharomyces cerevisiae, positioning of the mitotic spindle depends on the interaction of cytoplasmic microtubules with the cell cortex. In this process, cortical Kar9p in the bud acts as a link between the actin and microtubule cytoskeletons. To identify Kar9p-interacting proteins, a two-hybrid screen was conducted with the use of full-length Kar9p as bait, and three genes were identified: BIM1, STU2, and KAR9 itself. STU2 encodes a component of the spindle pole body. Bim1p is the yeast homologue of the human microtubule-binding protein EB1, which is a binding partner to the adenomatous polyposis coli protein involved in colon cancer. Eighty-nine amino acids within the third quarter of Bim1p was sufficient to confer interaction with Kar9p. The two-hybrid interactions were confirmed with the use of coimmunoprecipitation experiments. Genetic analysis placed Bim1p in the Kar9p pathway for nuclear migration. Bim1p was not required for Kar9p's cortical or spindle pole body localization. However, deletion of BIM1 eliminated Kar9p localization along cytoplasmic microtubules. Furthermore, in the bim1 mutants, the cytoplasmic microtubules no longer intersected the cortical dot of Green Fluorescent Protein-Kar9p. These experiments demonstrate that the interaction of cytoplasmic microtubules with the Kar9p cortical attachment site requires the microtubule-binding protein Bim1p.
Asunto(s)
Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Microtúbulos/genética , Proteínas de Microtúbulos/metabolismo , Microtúbulos/fisiología , Proteínas Nucleares/metabolismo , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/fisiología , Secuencia de Aminoácidos , Animales , Sitios de Unión , Proteínas de Ciclo Celular/química , Citoplasma/fisiología , Citoplasma/ultraestructura , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Genes Fúngicos , Genotipo , Humanos , Proteínas de Microtúbulos/química , Proteínas Asociadas a Microtúbulos/química , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Microtúbulos/ultraestructura , Datos de Secuencia Molecular , Proteínas Nucleares/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/ultraestructura , Alineación de Secuencia , Homología de Secuencia de AminoácidoRESUMEN
Young and old human red blood cells contain about the same amount of alpha-tocopherol, a compound which has previously been shown to be the major lipid-soluble, chain-breaking antioxidant present in such cells. Since red blood cells lose up to ca. 20% of lipid material from their membrane as they age, the alpha-tocopherol/membrane-lipid ratio actually rises with age rather than declining as might have been expected on the basis of the free radical theory of aging. The alpha-tocopherol/arachidonic acid moiety ratios increase in the order: young red blood cells less than old red blood cells less than plasma, which argues against the suggested membrane stabilizing effect of alpha-tocopherol/arachidonic acid moiety complexes.
Asunto(s)
Envejecimiento Eritrocítico , Eritrocitos/metabolismo , Vitamina E/sangre , Adulto , Ácido Araquidónico , Ácidos Araquidónicos/sangre , Separación Celular , Colesterol/sangre , Ácidos Grasos/sangre , Humanos , Persona de Mediana EdadRESUMEN
PURPOSE: To review a single institution's long-term results with doxorubicin-based preoperative chemotherapy for American Joint Committee on Cancer (AJCC) stage IIIB extremity soft tissue sarcoma (STS). PATIENTS AND METHODS: The records of all patients with AJCC stage IIIB extremity STS treated with preoperative chemotherapy between 1986 and 1990 at The University of Texas M.D. Anderson Cancer Center were reviewed to assess rates of response, local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). RESULTS: Seventy-six patients with stage IIIB disease received preoperative chemotherapy. The median sarcoma size was 10 cm. Seventy-two patients (95%) had tumors located deep to the muscular fascia. Most patients received a median of three preoperative cycles of doxorubicin and dacarbazine (ADIC), cyclophosphamide and ADIC (CyADIC), or other doxorubicin-based regimens. Radiographic response rates were as follows: complete response (CR), 9%; partial response (PR), 19%; minor response, 13%; stable disease, 30%; and progression, 30%. The overall objective major response rate (CRs plus PRs) was 27%. At a median follow-up time of 85 months, 5-year actuarial rates of LRFS, DMFS, DFS, and OS with 95% confidence intervals (CIs) were 83% (CI, 73% to 94%), 52% (CI, 41% to 66%), 46% (CI, 35% to 60%), and 59% (CI, 48% to 72%), respectively. Comparison of responding patients (CRs plus PRs) and nonresponding patients did not show any significant differences in LRFS, DMFS, DFS, or OS. CONCLUSION: Preoperative doxorubicin-based chemotherapy was associated with response, DFS, and OS rates similar to those observed in randomized postoperative chemotherapy trials. Responding patients had rates of LRFS, DMFS, DFS, and OS comparable to those of nonresponders.
Asunto(s)
Antineoplásicos/uso terapéutico , Brazo , Doxorrubicina/uso terapéutico , Pierna , Sarcoma/terapia , Neoplasias de los Tejidos Blandos/terapia , Adolescente , Adulto , Anciano , Terapia Combinada , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Cuidados Preoperatorios , Sarcoma/tratamiento farmacológico , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/cirugía , Factores de TiempoRESUMEN
PURPOSE: It has been suggested that patients with small (< 5 cm), high-grade extremity soft tissue sarcomas (STS) have an excellent overall prognosis and, consequently, may not require adjuvant therapies. PATIENTS AND METHODS: A comprehensive review of all patients with extremity STS treated at a tertiary care cancer hospital over a 9-year period (January 1984 to December 1992) was performed. Prognostic factors, treatment data, and long-term outcome were evaluated in the subset of 111 patients with American Joint Committee on Cancer stage IIB (G3/4, T1a/b) disease. RESULTS: The median tumor size was 3.0 cm (range, 0.6 to 4.9 cm), and 55 tumors (50%) were deep in location. All patients underwent surgical resection; 68 (61%) received pre- or postoperative radiotherapy, and 32 (29%) received doxorubicin-based chemotherapy. The median follow-up was 76 months. Forty patients (36%) experienced 59 recurrences. First recurrences occurred at local, regional, and distant sites in 21, five, and 14 patients, respectively. The 5-year actuarial local recurrence-free, distant recurrence-free, disease-free, and overall survival rates were 82%, 83%, 68%, and 83%, respectively. The presence of a microscopically positive surgical margin was an independent adverse prognostic factor for both local recurrence (relative risk [RR] = 3.75; 95% confidence interval [CI], 1.25 to 11.25; P =.02) and disease-free survival (RR = 2.57; 95% CI, 1.33 to 4.98; P =.005). CONCLUSION: Event-free outcome for this subset of patients with high-grade STS does not seem as favorable as previously reported by other investigators. Patients who undergo maximal surgical resection with microscopically positive margins represent a subset of T1 STS patients who warrant consideration for adjuvant therapies.
Asunto(s)
Extremidades , Recurrencia Local de Neoplasia , Sarcoma , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Neoplasia Residual/patología , Neoplasia Residual/cirugía , Pronóstico , Estudios Retrospectivos , Sarcoma/mortalidad , Sarcoma/patología , Sarcoma/terapiaRESUMEN
BACKGROUND: Paricalcitol, a vitamin D analog, is commonly administered three times weekly to control secondary hyperparathyroidism in hemodialysis patients. Less frequent dosing would be more convenient, require less nursing time, and be an option in other dialysis modalities. No studies have examined the efficacy of once-weekly dosing of paricalcitol. METHODS: Chronic hemodialysis patients receiving a stable dose of paricalcitol three times weekly with intact PTH (iPTH) 100-500 ng/l were monitored during a two-week baseline, then were converted to a single mid-week paricalcitol dose equal to the previous cumulative weekly dose. Serum calcium and phosphorus were monitored weekly and iPTH levels determined during study Weeks 4 and 8. A single paricalcitol dose adjustment was made during study Week 5 based on iPTH to achieve a target value of 150-300 ng/l. Phosphate binders and calcium dialysate bath were kept constant during the study. RESULTS: In the 25 patients, mean iPTH was 295 +/- 107 ng/l at baseline, and not significantly different at Week 4 (307 +/- 111 ng/l) or Week 8 (285 +/- 98 ng/l). Paricalcitol dose increases mid-study were almost exclusively in patients with iPTH > 300 ng/l. Calcium, phosphorus, and calcium x phosphorus product were not significantly different on weekly therapy. (Only one patient developed a calcium > 2.55 mmol/l during the study.) CONCLUSION: Once-weekly dosing of paricalcitol is an effective option in treatment of secondary hyperparathyroidism. Less frequent dosing may better allocate nursing time and potentially benefit other patient populations with CKD and ESRD.
Asunto(s)
Ergocalciferoles/administración & dosificación , Hiperparatiroidismo Secundario/tratamiento farmacológico , Fallo Renal Crónico/terapia , Diálisis Renal/efectos adversos , Calcio/sangre , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Hiperparatiroidismo Secundario/sangre , Hiperparatiroidismo Secundario/complicaciones , Inyecciones Intravenosas , Fallo Renal Crónico/sangre , Fallo Renal Crónico/complicaciones , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Fósforo/sangre , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Evidence-based guidelines for the treatment of patients with acute myocardial infarction (AMI) have been published and disseminated by the American College of Cardiology and the American Heart Association. Few studies have examined the rates of adherence to these guidelines in eligible populations and the influence of age and gender on highly effective AMI treatments in community hospital settings. METHODS: Medical records of 2409 individuals admitted to 37 Minnesota hospitals between October 1992 and July 1993 for AMI, suspected AMI, or rule-out AMI, and meeting electrocardiographic, laboratory, and clinical criteria suggestive of AMI were reviewed to determine the proportion of eligible patients who received thrombolytic, beta-blocker, aspirin, and lidocaine hydrochloride therapy. The effects of patient age, gender, and hospital teaching status on the use of these treatments were estimated using logistic regression models. RESULTS: Eligibility for treatment ranged from 68% (n=1627) for aspirin therapy, 38% (n=906) for lidocaine therapy, and 30% (n=734) for thrombolytic therapy to 19% (n=447) for beta-blocker therapy. Seventy-two percent of patients eligible to receive a thrombolytic agent received this therapy; 53% received beta-blockers; 81% received aspirin; and 88% received lidocaine. Among patients ineligible for lidocaine therapy (n=1503), 20% received this agent. Use of study drugs was lower among eligible elderly patients, especially those older than 74 years (thrombolytic agent: odds ratio, 0.2; 95% confidence interval, 0.1 to 0.4; aspirin: odds ratio, 0.4, 95% confidence interval, 0.3 to 0.6; beta-blocker: odds ratio, 0.4; 95% confidence interval, 0.2 to 0.8). Female gender was associated with lower levels of aspirin use among eligible patients (odds ratio, 0.7; 95% confidence interval, 0.6 to 0.9); and there was a trend toward lower levels of beta-blocker and thrombolytic use among eligible women. CONCLUSIONS: Use of lifesaving therapies for eligible patients with AMI is higher than previously reported, particularly for aspirin and thrombolytic use in nonelderly patients. Lidocaine is still used inappropriately in a substantial proportion of patients with AMI. Increased adherence to AMI treatment guidelines is required for elderly patients and women.