Eleven AJCC stage IV melanoma patients with progressive disease after treatment with biochemotherapy were treated with autologous dendritic cells pulsed with heterologous tumor cell lysates. The vaccine used mature DCs (CD1a +++ , CD40 ++ , CD80 ++ , CD83 + , and CD86 +++ ) generated from peripheral blood monocytes in the presence of GM-CSF and IL-4. After 7 days, DCs were matured with a defined cocktail of cytokines (IL-1+IL-6+TNF-α+PGE 2 ) and simultaneously pulsed with lysates of heterologous melanoma cell lines, for 2 days. A total of 4×10 6 DCs was injected monthly under ultrasound control in an inguinal lymph node of normal appearance. The study was closed when all patients died as a consequence of tumor progression. No sign of toxicity was observed during the study. One patient experienced a partial response lasting 5 months, and two patients showed a mixed response which lasted 3 months. The median survival of the whole group was 7.3 months (range 3–14 months). This vaccination program had specific antitumoral activity in highly pretreated and large tumor burden stage IV melanoma patients and was well tolerated. The clinical responses and the median survival of the group of patients, together with the low toxicity of our DC vaccine, suggest that this approach could be applied to earlier AJCC stage IV melanoma patients.
Hoy en día, la reacción en cadena de la polimerasa (PCR) se utiliza normalmente en la rutina asistencial de la mayoría de nuestros laboratorios, pero su empleo se ha limitado, con pocas excepciones, al campo de la virología y en especial a un reducido grupo de virus con gran interés económico, para los que se dispone de ensayos comerciales bien estandarizados. Por diversas razones, la PCR convencional se ha implementado poco en el diagnóstico de otras muchas enfermedades infecciosas a pesar de aportar indudables ventajas. La PCR a tiempo real combinada con los nuevos sistemas automáticos para la purificación de ácidos nucleicos, ofrece una plataforma ideal para el desarrollo de una gran variedad de pruebas moleculares para la identificación y cuantificación de los agentes infecciosos de interés clínico. Debido a sus indudables ventajas, como la facilidad de empleo, la mayor rapidez o el menor riesgo de contaminación, la PCR a tiempo real, irá reemplazando la PCR convencional y se extenderá a un amplio abanico de aplicaciones microbiológicas. PCR based assays are currently used routinely in most microbiology laboratories. But, with few exceptions, they are restricted to the field of virology, especially to a limited number of viral targets with important economical interest for which commercially well standardized assays are available. For several reasons, it has had a poor implementation of the PCR assays into routine diagnostics for other infectious diseases despite they are advantageous. Combined with automated sample isolation of nucleic acids, real-time PCR gives an ideal platform for the development of molecular assays for a wide range of infectious agents with clinical interest. Because of its advantages, as simplicity, rapidity and minor risk of contamination, real-time PCR will go replace conventional PCR assays and its use will extend to a wide range of applications in clinical microbiology.
PCR based assays are currently used routinely in most microbiology laboratories. But, with few exceptions, they are restricted to the field of virology, especially to a limited number of viral targets with important economical interest for which commercially well standardized assays are available. For several reasons, it has had a poor implementation of the PCR assays into routine diagnostics for other infectious diseases despite they are advantageous. Combined with automated sample isolation of nucleic acids, real-time PCR gives an ideal platform for the development of molecular assays for a wide range of infectious agents with clinical interest. Because of its advantages, as simplicity, rapidity and minor risk of contamination, real-time PCR will go replace conventional PCR assays and its use will extend to a wide range of applications in clinical microbiology.
PCR based assays are currently used routinely in most microbiology laboratories. But, with few exceptions, they are restricted to the field of virology, especially to a limited number of viral targets with important economical interest for which commercially well standardized assays are available. For several reasons, it has had a poor implementation of the PCR assays into routine diagnostics for other infectious diseases despite they are advantageous. Combined with automated sample isolation of nucleic acids, real-time PCR gives an ideal platform for the development of molecular assays for a wide range of infectious agents with clinical interest. Because of its advantages, as simplicity, rapidity and minor risk of contamination, real-time PCR will go replace conventional PCR assays and its use will extend to a wide range of applications in clinical microbiology.
Unresectable metastatic melanoma has no elective treatment. Neither chemotherapy, intravenous IL‐2 nor biochemotherapy clearly improves the overall survival. Recent assays with therapeutic vaccines have been recently yielded promising results. Here, we describe the application, clinical tolerance and antitumoural activity of a heterologous polyvalent melanoma whole cell vaccine in patients with metastatic melanoma. Twenty‐eight AJCC stage III/IV melanoma patients with progressive unresectable metastatic disease were treated with our heterologous polyvalent melanoma whole cell vaccine between July 1, 1998 and July 1, 2002. All patients had already been unsuccessfully treated with high doses of IFN‐α2 and/or polychemotherapy and/or biochemotherapy and/or perfusion of extremities, or could not receive other treatments due to their age or underlying illness. Twenty‐three were assessable. The vaccine was constituted by 10 melanoma cell lines, derived from primary, lymph node and metastatic melanomas. Prior to intradermal inoculation, the cells were irradiated and mixed with BCG, and 50% were treated with DNFB. After a median follow‐up of 19 months, 26% of patients responded: 3 CR (18, 16+, and 26+ months), 2 PR (8 and 22 months) and 1 MR (36+ months). The median survival of the whole group was 20.2 months. None of the 28 patients initially included in the study presented significant toxicity. This vaccination program had specific antitumoural activity in advanced metastatic melanoma patients and was well tolerated. The clinical responses and the median survival of our group of patients, together with the low toxicity of our polyvalent vaccine, suggest that this approach could be applied to earlier metastatic melanoma patients. © 2003 Wiley‐Liss, Inc.
Abstract. This article analyses the discussion, enactment and characteristics of the Linguistic Policy Act adopted by the Catalan Parliament in 1998, from the point of view of current normative political theory. The main theoretical question is whether its provisions promoting the Catalan language are compatible with the liberal political tradition, considering its different streams. The discussion shows that the main arguments are not different from those used by scholars dealing with issues of national and cultural pluralism in Western democratic societies. Thus, the opponents of the Act tend to rely upon various individual rights‐based arguments taken from classical liberalism. Its advocates, on the other hand, accuse them of neglecting the value of cultural membership, asserted by influential authors within the liberal tradition. Ultimately, the article concludes that this law neither promotes nor allows illiberal practices.
This article examines the relevance of a theory of the multinational state for the evaluation of claims for self-determination and secession. Considerations of ‘ethnocultural justice’ imply that the recognition of the multinational character of a state – or the granting of some of the minority nations' demands – is a matter of justice. If these requirements are not met, secession could be justified. Indeed, if secession needs a just cause (as it has been argued), a failure to build a truly multinational arrangement can be a valid reason for a minority nation to secede. An approach like the one proposed would also contribute to the resolution of some of the key problems of the three main theories of secession and their appeals to nationalism, choice and remedial rights.