Home care: a safe and attractive alternative to inpatient administration of intensive chemotherapies.

OBJECTIVE: The objective of this study was to evaluate feasibility, safety, perception, and costs of home care for the administration of intensive chemotherapies. METHODS: Patients receiving sequential chemotherapy in an inpatient setting, living within 30 km of the hospital, and having a relative to care for them were offered home care treatment. Chemotherapy was administered by a portable, programmable pump via an implantable catheter. The main endpoints were safety, patient's quality of life [Functional Living Index-Cancer (FLIC)], satisfaction of patients and relatives, and costs. RESULTS: Two hundred days of home care were analysed, representing a total of 46 treatment cycles of intensive chemotherapy in 17 patients. Two cycles were complicated by technical problems that required hospitalisation for a total of 5 days. Three major medical complications (heart failure, angina pectoris, and major allergic reaction) could be managed at home. Grades 1 and 2 nausea and vomiting occurring in 36% of patients could be treated at home. FLIC scores remained constant throughout the study. All patients rated home care as very satisfactory or satisfactory. Patient benefits of home care included increased comfort and freedom. Relatives acknowledged better tolerance and less asthenia of the patient. Home care resulted in a 53% cost benefit compared to hospital treatment (420 ± 120/day vs. 896 ± 165/day). CONCLUSION: Administration of intensive chemotherapy regimens at home was feasible and safe. Quality of life was not affected; satisfaction of patients and relatives was very high. A psychosocial benefit was observed for patients and relatives. Furthermore, a cost-benefit of home care compared to hospital treatment was demonstrated.

25/9 1963 Herra Kustannusjohtaja, maisteri Martti Qvist

Kirje 25.9.1963

A Novel HLA-B18 Restricted CD8+ T Cell Epitope Is Efficiently Cross-Presented by Dendritic Cells from Soluble Tumor Antigen.

NY-ESO-1 has been a major target of many immunotherapy trials because it is expressed by various cancers and is highly immunogenic. In this study, we have identified a novel HLA-B*1801-restricted CD8(+) T cell epitope, NY-ESO-1(88-96) (LEFYLAMPF) and compared its direct- and cross-presentation to that of the reported NY-ESO-1(157-165) epitope restricted to HLA-A*0201. Although both epitopes were readily cross-presented by DCs exposed to various forms of full-length NY-ESO-1 antigen, remarkably NY-ESO-1(88-96) is much more efficiently cross-presented from the soluble form, than NY-ESO-1(157-165). On the other hand, NY-ESO-1(157-165) is efficiently presented by NY-ESO-1-expressing tumor cells and its presentation was not enhanced by IFN-γ treatment, which induced immunoproteasome as demonstrated by Western blots and functionally a decreased presentation of Melan A(26-35); whereas NY-ESO-1(88-96) was very inefficiently presented by the same tumor cell lines, except for one that expressed high level of immunoproteasome. It was only presented when the tumor cells were first IFN-γ treated, followed by infection with recombinant vaccinia virus encoding NY-ESO-1, which dramatically increased NY-ESO-1 expression. These data indicate that the presentation of NY-ESO-1(88-96) is immunoproteasome dependent. Furthermore, a survey was conducted on multiple samples collected from HLA-B18(+) melanoma patients. Surprisingly, all the detectable responses to NY-ESO-1(88-96) from patients, including those who received NY-ESO-1 ISCOMATRIX? vaccine were induced spontaneously. Taken together, these results imply that some epitopes can be inefficiently presented by tumor cells although the corresponding CD8(+) T cell responses are efficiently primed in vivo by DCs cross-presenting these epitopes. The potential implications for cancer vaccine strategies are further discussed.

Informe sobre el estado del recurso anchoveta a fines de setiembre y las perspectivas para la pesquería en la temporada octubre-diciembre 1974

Presenta información sobre el nivel actual del stock del recurso de anchoveta, las perspectivas de reclutamiento y crecimiento durante los próximos tres meses y la determinación de la magnitud de recuperación del recurso.

Población de la "concha navaja" Ensis macha (Molina, 1782) en el litoral de la Región Ancash, Perú. Inicios del Otoño 2006

El estudio se llevó a cabo del 25 de marzo al 2 de abril del 2006, entre los paralelos 9"25'5 y 10"19'5, que limitan cinco áreas litorales de las provincias Huarmey y Casma: Bernardino, Punta Gorda, Punta Huaro, Punta Cruz del Cabo y Las Zorras. Se realizaron 128 estaciones biológicas y 53 estaciones oceanográficas, distribuidas en tres estratos de profundidad, según el área; las densidades y biomasas se evaluaron con el método del área barrida. Las tallas estuvieron comprendidas de 6 a 144 mm de longitud valvar; las tallas medias variaron según la localidad; los ejemplares >110 mm tuvieron mínima representatividad (O,O a 9,1%). Los cálculos de biomasa y densidad media fueron: 3,4 t y 30,53 ind./m2 para Bernardino; 0,9 t y 2,43 ind./m2 para el área Punta Gorda - Punta Huaro; 73,3 t y 66,44 ind./m2 para Punta Cruz del Cabo y 63,8 t y 101,51 ind./ m2 para Las Zorras. No existen registros de la explotación de los bancos evaluados.

Caracterización del Área Costera de Tumbes por organismos del fitoplancton durante 1990-1991

De un total de 80 muestras de red, se determinó un máximo de 133 especies en agosto y un mínimo de 60 durante noviembre, ambos en 1991. En todo el período de estudio los grupos que aportaron mayor número de especies fueron dinoflagelados y diatomeas; silicoflagelados, fitoflagelados y cocolitofóridos fueron muy escasos o estuvieron ausentes. Dentro de los dinoflagelados resaltaron diferentes especies del género Ceratium, entre las diatomeas lo hicieron aquellas considerados de agua cálidas y cosmopolitas, y entre los silicoflagelados lo hizo Distyocha fibula. Se analizaron 70 muestras de agua, en donde se determinó 111 diatomeas, 89 dinoflagelados, 8 cocolitofóridos, 4 silicoflagelados y 4 fitoflagelados, dando un total de 216 especies de fitoplancton. En superficie el fitoplancton total alcanzó su máximo valor en agosto con 494 963 cel/l y el mínimo en febrero con 11 400 cel/l, ambos durante 1991. A 10 m el máximo fue de 122 690 cel/l durante setiembre y el mínimo de 3 165 cel/l en octubre, ambos en 1991. Tanto en superficie como a 10 m el mayor aporte lo dieron el nanoplancton y diatomeas. Los organismos que alcanzaron mayores cantidades celulares fueron Emiliana huxleyi y monadas. Los análisis de red reportan organismos del microplancton, principalmente diatomeas y dinoflagelados, encontrándose raramente organismos del nanoplancton, mientras que en los análisis de agua, se determinan principalmente diatomeas y nanoplancton.

Observación de la velocidad de los cardúmenes de anchoveta (Engraulis ringens JENYNS) en el mar peruano

Da a conocer las observación sobre la velocidad de natación de los cardúmenes de la anchoveta peruana, para comprender los desplazamientos latitudinales y longitudinales que realizan debido a la influencia de las condiciones oceanográficas del mar peruano. Por lo que se debería continuar con el estudio de la velocidad de natación de estos cardúmenes en función a sus características como tallas y pesos.

El calamar gigante en el mar peruano. Crucero B/P Hakurei Maru Nº 8. Primavera 2010 y Verano 2011

El crucero se desarrolló en dos etapas, la primera en primavera 2010, de 4° a 11°25’S y la segunda en verano 2011, de 10°10’ a 17°23’S, entre 50 a 200 mn de la costa. La captura del recurso en la primera etapa fue 35.079,6 kg (25.669,1 kg de producción) y en la segunda 165.955,7 kg (123.229,5 kg de producción). La captura por unidad de esfuerzo por día de trabajo fluctuó de 2,9 a 4.292,6 kg/hora; 0,68 a 948,4 kg/línea; 0,07 a 99,8 kg/ línea*hora y 0,0017 a 2,4957 kg/pot*hora. La longitud del manto varió de 17 a 119 cm. Se registró hembras en estadio desovante III (51,5%), madurante II (21,6%); y machos en estadio evacuación III (85,1%) y virginales I (9,7%). Los grupos tróficos más importantes fueron: cefalópodos (% IRI= 66,4), crustáceos (% IRI= 23,7), peces (% IRI= 9,9). Las hembras presentaron: L∞ =111,233 cm LM, K=0,016, t0= 235 y los machos L∞ =99,718 cm LM, K=0,167 y t0=228,4; esta especie tiene una longevidad próxima o poco mayor a un año.

Interplay between T cell receptor binding kinetics and the level of cognate peptide presented by major histocompatibility complexes governs CD8+ T cell responsiveness.

Through a rational design approach, we generated a panel of HLA-A*0201/NY-ESO-1(157-165)-specific T cell receptors (TCR) with increasing affinities of up to 150-fold from the wild-type TCR. Using these TCR variants which extend just beyond the natural affinity range, along with an extreme supraphysiologic one having 1400-fold enhanced affinity, and a low-binding one, we sought to determine the effect of TCR binding properties along with cognate peptide concentration on CD8(+) T cell responsiveness. Major histocompatibility complexes (MHC) expressed on the surface of various antigen presenting cells were peptide-pulsed and used to stimulate human CD8(+) T cells expressing the different TCR via lentiviral transduction. At intermediate peptide concentration we measured maximum cytokine/chemokine secretion, cytotoxicity, and Ca(2+) flux for CD8(+) T cells expressing TCR within a dissociation constant (K(D)) range of ∼1-5 μM. Under these same conditions there was a gradual attenuation in activity for supraphysiologic affinity TCR with K(D) < ∼1 μM, irrespective of CD8 co-engagement and of half-life (t(1/2) = ln 2/k(off)) values. With increased peptide concentration, however, the activity levels of CD8(+) T cells expressing supraphysiologic affinity TCR were gradually restored. Together our data support the productive hit rate model of T cell activation arguing that it is not the absolute number of TCR/pMHC complexes formed at equilibrium, but rather their productive turnover, that controls levels of biological activity. Our findings have important implications for various immunotherapies under development such as adoptive cell transfer of TCR-engineered CD8(+) T cells, as well as for peptide vaccination strategies.

« Histoire sommaire du commerce et de la navigation des anciens, » par P.-D. HUET. (1669).

Ms. autographe, dédié à Colbert.