RESUMEN
Monocyte-derived conventional dendritic cells (ConvDCs) loaded with melanoma antigens showed modest responses in clinical trials. Efficacy studies were hampered by difficulties in ConvDC manufacturing and low potency. Overcoming these issues, we demonstrated higher potency of lentiviral vector (LV)-programmed DCs. Monocytes were directly induced to self-differentiate into DCs (SmartDC-TRP2) upon transduction with a tricistronic LV encoding for cytokines (granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4)) and a melanoma antigen (tyrosinase-related protein 2 (TRP2)). Here, SmartDC-TRP2 generated with monocytes from five advanced melanoma patients were tested in autologous DC:T cell stimulation assays, validating the activation of functional TRP2-specific cytotoxic T lymphocytes (CTLs) for all patients. We described methods compliant to good manufacturing practices (GMP) to produce LV and SmartDC-TRP2. Feasibility of monocyte transduction in a bag system and cryopreservation following a 24-h standard operating procedure were achieved. After thawing, 50% of the initial monocyte input was recovered and SmartDC-TRP2 self-differentiated in vitro, showing uniform expression of DC markers, detectable LV copies and a polyclonal LV integration pattern not biased to oncogenic loci. GMP-grade SmartDC-TRP2 expanded TRP2-specific autologous CTLs in vitro. These results demonstrated a simpler GMP-compliant method of manufacturing an effective individualized DC vaccine. Such DC vaccine, when in combination with checkpoint inhibition therapies, might provide higher specificity against melanoma.
Asunto(s)
Vacunas contra el Cáncer/uso terapéutico , Células Dendríticas/inmunología , Lentivirus/metabolismo , Melanoma/terapia , Proteínas de la Membrana/metabolismo , Fragmentos de Péptidos/metabolismo , Vacunas contra el Cáncer/genética , Vacunas contra el Cáncer/inmunología , Vectores Genéticos , Células HEK293 , Humanos , Inmunoterapia/métodos , Lentivirus/genética , Melanoma/inmunología , Linfocitos T Citotóxicos/inmunologíaRESUMEN
BACKGROUND: Data on treatment satisfaction in European men and women with chronic constipation are limited. AIM: To assess satisfaction with current treatment among European men and women with chronic constipation. METHODS: An internet-based survey was conducted in 2009 in 10 European countries: Austria, Germany, France, Ireland, Italy, Spain, Switzerland, the UK, Belgium and the Netherlands. Participants had self-reported chronic constipation (<3 bowel movements/week and ≥1 symptoms for ≥6 months of: pain during defecation; lumpy/hard faeces; and feeling of incomplete evacuation). Demographic data and disease history were collected. For participants using laxatives, drug name/class, satisfaction with treatment and interest in other treatments were collected. RESULTS: Of the 1941 participants screened, 1355 had chronic constipation and met the inclusion criteria (chronic constipation population). The majority of the chronic constipation population who disclosed their sex (n = 811) were women (82%). Sixty-eight per cent of respondents (n = 855/1255) reported using laxatives, with the proportion of laxative users differing between subsets. Twenty-eight per cent (n = 225/793) were (very) satisfied with their treatment, whereas 44% (n = 345/793) were neutral and 28% (n = 223/793) (very) dissatisfied. There was no relationship between type of laxative and degree of (dis)satisfaction. Interest in other treatments was high with 83% (n = 686/827) of respondents 'absolutely' or 'probably' interested. Respondents dissatisfied with their treatment were more likely to be interested in other treatments. CONCLUSIONS: Laxative-use is common for chronic constipation. In this large survey, 28% of participants were dissatisfied with their treatment, with the majority interested in other treatments.
Asunto(s)
Estreñimiento/tratamiento farmacológico , Defecación/efectos de los fármacos , Laxativos/uso terapéutico , Satisfacción del Paciente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Estreñimiento/psicología , Europa (Continente) , Femenino , Encuestas Epidemiológicas , Humanos , Internet , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenAsunto(s)
Anafilaxia/diagnóstico , Basófilos/fisiología , Hipersensibilidad a los Alimentos/diagnóstico , Sesamum/efectos adversos , Anafilaxia/etiología , Reacciones Falso Negativas , Hipersensibilidad a los Alimentos/etiología , Humanos , Inmunoglobulina E/sangre , Masculino , Persona de Mediana Edad , Sesamum/inmunología , Pruebas CutáneasRESUMEN
Agents used in medical tumor therapies can cause peculiar cutaneous side effects. In particular the newly developed targeted therapies are associated with specific cutaneous side effects, such as a papulopustular exanthems associated with EGFR inhibitors and epithelial skin cancers associated with inhibitors of mutated BRAF. In this review the clinical pictures as well as pathogenetic and therapeutic aspects of the hand-foot-syndrome, papulopustular exanthems, epithelial skin cancers, paronychia and changes of hair and nails as side effects of medical tumor therapies are summarized. Knowledge of these side effects is important to avoid interruption or termination of the tumor therapy, in particular since some of the cutaneous reactions have been shown to correlate with the therapeutic benefit of the tumor therapy.
Asunto(s)
Antineoplásicos/efectos adversos , Erupciones por Medicamentos/etiología , Erupciones por Medicamentos/prevención & control , Terapia Molecular Dirigida/efectos adversos , Erupciones por Medicamentos/diagnóstico , HumanosRESUMEN
BACKGROUND: The combination of sorafenib, a multikinase inhibitor, and pegylated interferon-α2b (Peg-IFN-α2b) could potentially lead to an improved antitumoral response. Previously, combinations of interferon and sorafenib have been used in renal cell cancer. PATIENTS AND METHODS: Patients with stage IV metastatic melanoma and no previous systemic therapies apart from adjuvant immunotherapy received Peg-IFN-α2b 3 µg/kg once per week, and sorafenib 400-mg b.i.d. for a minimum of 8 weeks. The primary study end point was disease control rate (DCR). RESULTS: Between February 2008 and February 2009, 55 patients were enrolled with a median age of 64 years (20-85). At 8 weeks, 2 patients (3.6%) had a partial response (PR) and 14 patients a stable disease (25.5%), for a DCR of 29.1% in the intention-to-treat (ITT) population. The median progression-free survival in the ITT population was 2.47 months (95% confidence interval 1.22-3.72 months). The toxicity of sorafenib and Peg-IFN-α2b combination was characterized by mainly hematological side-effects, including one treatment-related bleeding complication with a fatal outcome. Other grade 3/4 toxic effects were fatigue and flu-like symptoms. CONCLUSION: The combination of sorafenib and Peg-IFN-α2b showed modest clinical activity and some serious side-effects including fatal bleeding complications.
Asunto(s)
Antineoplásicos/uso terapéutico , Antivirales/uso terapéutico , Bencenosulfonatos/uso terapéutico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Melanoma/tratamiento farmacológico , Polietilenglicoles/uso terapéutico , Piridinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica , Femenino , Estudios de Seguimiento , Neoplasias de Cabeza y Cuello/patología , Humanos , Interferón alfa-2 , Masculino , Dosis Máxima Tolerada , Melanoma/secundario , Persona de Mediana Edad , Estadificación de Neoplasias , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Estudios Prospectivos , Proteínas Recombinantes , Sorafenib , Tasa de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
Raw milk samples collected from tanker trucks are routinely screened for beta-lactam antibiotic drug residues using rapid screening tests. If drug residues are detected, the milk may be shipped on ice blocks to a laboratory for further analysis. A study was conducted to determine the stability of ampicillin in raw milk stored at +4 degrees C in order to predict if shipping the milk would result in the degradation of ampicillin residues. Milk samples were spiked with 20 ppb ampicillin, stored at +4 degrees C and -70 degrees C for 1-6 days, and then analysed by HPLC with fluorescence detection. No loss of ampicillin residues was found in milk stored at +4 degrees C for 1-6 days.
Asunto(s)
Ampicilina/análisis , Conservación de Alimentos/métodos , Leche/química , Penicilinas/análisis , Refrigeración , Animales , Cromatografía Líquida de Alta Presión , Estabilidad de Medicamentos , Contaminación de Alimentos/análisis , Congelación , TransportesAsunto(s)
Certificación/legislación & jurisprudencia , Gastroenterología/legislación & jurisprudencia , Programas Nacionales de Salud/legislación & jurisprudencia , Gestión de la Calidad Total/legislación & jurisprudencia , Curriculum , Gastroenterología/educación , Alemania , Humanos , Guías de Práctica Clínica como Asunto , Consejos de Especialidades/legislación & jurisprudenciaRESUMEN
Sample extracts of apples, peas, green beans, oranges, raspberries, clementines, carrots, and wheat obtained using the Food and Drug Administration (acetone extraction) and Canadian Pest Management Regulatory Agency (acetonitrile extraction) multiresidue methods for pesticides were subjected to clean-up using different solid-phase extraction (SPE) cartridges in an attempt to reduce or eliminate the matrix enhancement effect. The matrix enhancement effect is related to the blocking of active sites on the injector liner by matrix components, thereby increasing signal in the presence of matrix versus standards in solvent in which the pesticides themselves interact with the active sites. Graphitized carbon black (GCB) was often used in combination with various anion-exchange SPE cartridges. The extracts were then spiked with organophosphorus insecticides. These process standards were then compared to standards in acetone of the same concentration using gas chromatography with flame photometric detection or ion trap mass spectrometric detection. Sample matrix enhancement varied from little to no effect for some pesticides (e.g. chlorpyrifos, malathion) to >200% in the case of certain susceptible pesticides. The GCB removed color components but showed little effect in reducing matrix enhancement by itself. The anion-exchange cartridges in combination with GCB or not, substantially reduced the matrix enhancement effect but did not eliminate it.
Asunto(s)
Cromatografía de Gases/métodos , Análisis de los Alimentos , Residuos de Plaguicidas/análisis , Acetona , Acetonitrilos , Grano Comestible/química , Frutas/química , Residuos de Plaguicidas/química , Control de Calidad , Sensibilidad y Especificidad , Estados Unidos , United States Food and Drug Administration , Verduras/químicaRESUMEN
A multiresidue solid-phase extraction (SPE) method for the isolation and subsequent gas chromatographic determination of organochlorine and organophosphorus pesticide residues in low-moisture, nonfatty products is described. Residues are extracted from samples with an acetonitrile/water mixture. Cleanup of the extract is performed using graphitized carbon black and anion exchange SPE columns, and analysis is performed by gas chromatography with Hall electrolytic conductivity and flame photometric detection. Recovery data was obtained by fortifying corn, oats and wheat with pesticides. The average recoveries were 79-123% for eight organochlorine and 51-122% for 28 organophosphorus pesticide residues. The limit of quantitation for chlorpyriphos was 0.05 ppm using the Hall electrolytic conductivity detector and < 0.005 ppm using the flame photometric detector.
Asunto(s)
Monitoreo del Ambiente , Contaminantes Ambientales/análisis , Hidrocarburos Clorados , Insecticidas/análisis , Compuestos Organofosforados , Residuos de Plaguicidas/análisis , Alimentación Animal/análisis , Animales , Cromatografía de Gases , Grano Comestible/química , Monitoreo del Ambiente/métodos , Contaminantes Ambientales/aislamiento & purificación , Humanos , Insecticidas/aislamiento & purificación , Residuos de Plaguicidas/aislamiento & purificaciónRESUMEN
A multiresidue solid phase extraction (SPE) method for the isolation and subsequent gas chromatographic determination of nonpolar organochlorine and polar organophosphorus pesticide residues in eggs is described. The method uses an acetonitrile extraction followed by an SPE cleanup using graphitized carbon black and aminopropyl SPE columns. Organophosphorus pesticides are determined by gas chromatography with flame photometric detection. After further cleanup of the extract using Florisil SPE columns, organochlorine pesticides are determined by gas chromatography with electron capture detection. Studies were performed using eggs containing both fortified and incurred pesticide residues. The average recoveries were 86-108% for 8 fortified organochlorine pesticide residues and 61-149% for 28 fortified organophosphorus pesticide residues.
Asunto(s)
Huevos/análisis , Insecticidas/aislamiento & purificación , Compuestos Organofosforados/aislamiento & purificación , Residuos de Plaguicidas/aislamiento & purificación , Animales , Pollos , Cromatografía de Gases/métodos , Femenino , Insecticidas/análisis , Compuestos Organofosforados/análisis , Residuos de Plaguicidas/análisisRESUMEN
Abamectin, doramectin, ivermectin, and moxidectin are macrocyclic lactones derived from soil dwelling actinomycetes, and are very effective against nematode, insect, and arthropod infestations. These compounds, known as endectocides, have been approved for use in beef cattle in the United States; however, they are currently not approved for use in dairy cattle. Abamectin, doramectin, ivermectin, and moxidectin residues were isolated from milk by a series of liquid-liquid extraction steps, derivatized with trifluoroacetic anhydride, and determined by liquid chromatography with fluorescence detection. Recovery studies were performed in 2 laboratories. Recoveries of > 80% (1-30 ng/mL) were achieved for all 4 compounds.
Asunto(s)
Cromatografía Liquida/métodos , Ivermectina/análogos & derivados , Ivermectina/análisis , Leche/química , Animales , Antibacterianos/análisis , Antiparasitarios/análisis , Bovinos , Residuos de Medicamentos/análisis , Insecticidas/análisis , Macrólidos , Sensibilidad y Especificidad , Espectrometría de FluorescenciaRESUMEN
Raw milk samples collected from bulk milk tankers may be screened for the presence of tetracycline antibiotics using rapid screening tests. If tetracycline residues are detected, the milk may be shipped to a laboratory for high-pressure liquid chromatography (HPLC) analysis. Because the milk may be shipped on ice blocks, it is important to know whether tetracycline residues are stable at that temperature and for how long. Control raw milk samples fortified with 50 ppb each chlortetracycline, demeclocycline, methacycline hydrochloride, minocycline, oxytetracycline, and tetracycline were incubated at 4 degrees C or 25 degrees C, then analyzed using a metal chelate affinity chromatography extraction and HPLC. No loss of tetracycline was observed after 48 h of storage at 4 degrees C or 24 h at 25 degrees C. Losses ranging from 4 to 13% and 0 to 18% were noted after 72 h at 4 degrees C and 48 h at 25 degrees C, respectively.
Asunto(s)
Antibacterianos/análisis , Residuos de Medicamentos/análisis , Manipulación de Alimentos , Leche/química , Animales , Antibacterianos/química , Cromatografía Líquida de Alta Presión , Residuos de Medicamentos/química , Estabilidad de Medicamentos , Estándares de Referencia , Temperatura , TetraciclinasRESUMEN
A rapid, multiresidue, solid phase extraction (SPE) technique for the isolation and gas chromatographic determination of organochlorine and moderately polar organophosphorus pesticide residues in milk is described. Milk is sonicated with an acetonitrile-acetone-methanol mixture and centrifuged. The supernatant is subjected to a cleanup using both C18 and graphitized carbon black SPE columns. The pesticide residues are determined by gas chromatography with electron capture and flame photometric detection. The method required minimal volumes of solvent and resulted in the production of minimal volumes of hazardous waste.
Asunto(s)
Monitoreo del Ambiente , Hidrocarburos Clorados , Insecticidas/análisis , Leche/química , Compuestos Organofosforados , Animales , Carbono/análisis , Cromatografía de Gases , Contaminación de Alimentos , Dióxido de Silicio/análisis , Solubilidad , Factores de TiempoRESUMEN
An efficient extraction and sensitive gas chromatographic method is described for the determination of the anthelminthic drug levamisole in milk. Levamisole was extracted from alkaline milk with ethyl acetate. Clean-up of the extract was by a series of liquid-liquid extraction steps. Levamisole residues in the extract were determined by gas chromatography with a nitrogen-phosphorus detector. This method was satisfactory for determining levamisole residues in milk as low as 0.5 ng/g. Mean recoveries of 0.5-10.0 ng/g fortified milk samples ranged from 84.5 to 95.2%. Five replicate analyses performed on a milk containing incurred levamisole residues yielded a mean of 3.34 ng/g levamisole with a CV of 3.0%.
Asunto(s)
Antinematodos/análisis , Contaminación de Alimentos/análisis , Levamisol/análisis , Leche/química , Animales , Cromatografía de Gases/métodos , Residuos de Medicamentos , HumanosRESUMEN
The widespread use of antibiotics in dairy cattle management may result in the presence of antibiotic residues in milk. While rapid screening tests are commonly used to detect the presence of antibiotics in milk, more accurate chromatographic methods are required by government regulatory agencies to identify and confirm the identity and quantity of antibiotic present. This paper review recent developments in the chromatographic determination of antibiotic residues in milk.
Asunto(s)
Antibacterianos/análisis , Cromatografía , Leche/química , Animales , Residuos de MedicamentosRESUMEN
Florisil solid-phase extraction cartridges were evaluated for cleanup of organochlorine pesticide residues in food extracts. Elution patterns and recoveries were determined for 24 organochlorine pesticides. A range of elution solvents was evaluated. A 2% ethyl ether-petroleum ether eluant optimized overall recoveries while minimizing interferences from coextractants.
Asunto(s)
Análisis de los Alimentos , Hidrocarburos Clorados , Insecticidas/aislamiento & purificación , Silicatos de Magnesio/química , Residuos de Plaguicidas/aislamiento & purificación , Animales , Braquiuros , Cromatografía de Gases , Contaminación de Alimentos , Guías como Asunto , Insecticidas/análisis , Leche/química , Residuos de Plaguicidas/análisis , Estándares de Referencia , Mariscos , Estados Unidos , United States Food and Drug AdministrationRESUMEN
A rapid, multiresidue solid-phase extraction (SPE) technique for determination of organochlorine pesticide and polychlorinated biphenyl (PCB) residues in nonfatty fish was modified for use with fatty fish. In the modified procedures, samples are extracted with acetonitrile, and the extract is cleaned up with both C18 and Florisil SPE columns. Residues are determined by gas chromatography with electron capture detection. The original method was modified for use with fatty fish by reducing the amount of tissue extracted and by using an improved Florisil SPE cleanup. Recovery data are presented for 24 fortified organochlorine pesticide residues (0.12 ppm) and 3 fortified PCB residues (0.80 ppm) from flounder, bluefish, and shad samples, which contained 0.8, 5.4, and 22.6% fat, respectively. For the 3 types of fish, recoveries of 23 of 24 fortified organochlorine pesticide residues ranged from 55 to 129%, and recoveries of 3 fortified PCB residues ranged from 55 to 104%. There were no significant differences in recovery based on fish species and/or fat content for the majority of residues studied. This SPE method and the official AOAC method yielded comparable results for fish containing incurred organochlorine residues.
Asunto(s)
Peces/metabolismo , Insecticidas/análisis , Residuos de Plaguicidas/análisis , Bifenilos Policlorados/análisis , Animales , Cromatografía de Gases , Contaminación de Alimentos , Insecticidas/metabolismo , Silicatos de Magnesio/química , Bifenilos Policlorados/metabolismo , Estándares de Referencia , Estadística como AsuntoRESUMEN
Six U.S. Food and Drug Administration laboratories participated in an Interlaboratory trial of a solid-phase extraction cleanup method for determination of pesticides in nonfatty seafood products. The participants analyzed control and fortified (about 0.050 ppm lindane, heptachlor epoxide, p,p'-DDE, and endrin) croaker and flounder samples and a sea trout sample containing incurred p,p'-DDE residues. Mean recoveries of the fortified residues from the fish ranged from 89.1 to 107.8%. The within-laboratory coefficients of variation (CVs) ranged from 4.2 to 8.5%, and the among-laboratory CVs ranged from 10.9 to 26.5%. The 6 laboratories reported a mean value of 0.040 ppm p,p'-DDE in a fish sample which contained incurred residues. The same value (0.040 ppm) was obtained by using official methodology. The within-laboratory CVs ranged from 3.5 to 18.3%, and the among-laboratory CV was 17.3%.