Búsqueda de la atención médica y determinates de la utilización de servicio de salud / Determinants of health services utilization and search for medical care

There are four different conceptual approaches to assess the factors that explain, condition and determine the use of health services. This article discusses the epidemiological, psychosocial, sociological and economical models. The stages and determinants of the health service use process are described and a cross study is made with each of the four models, using a contingency matrix. A holistic analysis is proposed, as a starting point, for the search of a model that will allow the identification of factors that determine the use of health services. This analysis should be used as a conceptual framework for future work on health services utilization

Tendencias en la generación y reproducción del conocimiento sobre evaluación económica y salud / Trends on generation and reproduction of knowledge about economic evaluation and health

This paper identifies the trends and recent progress in the generation and reproduction of knowledge on health economic evaluation. Analysis is organized along nine public health action fields, namely: health determinants and predictors, economic value of health, healthcare demand, healthcare supply, microeconomic evaluation of healthcare, healthcare market balance, evaluation of policy instruments, general evaluation of the health system, and healthcare planning, regulation and supervision. Each action field is defined to place the reader in the proper setting and level of analysis. In addition, thematic research topics developed in each action field are proposed and discussed. The generation and reproduction of knowledge on the different action fields was based on the review of the bibliographic databases MEDLINE and LILACS for the 1992-2000 period. Results lead to the conclusion that development and application of economic evaluation of healthcare has been uneven across different countries and that there is a growing increase of applications starting in 1994, the year of initiation of healthcare reform in Latin America

Role of nerve growth factor in experimental autoimmune encephalomyelitis.

The expression of neural regulatory molecules by immune cells that infiltrate the nervous system upon injury may be a mechanism for cross-regulation between the nervous system and the immune system. Several lines of evidence implicate nerve growth factor (NGF) signaling through its receptors (TrkA and p75(NGFR)) as a potential source of communication between the two systems. We observed changes in NGF mRNA expression and protein secretion by T lymphocytes polarized toward the Th2 phenotype. The presence of NGF did not affect T cell proliferation or cytokine production in vitro. Mice treated with NGF by i. p. injection following induction of experimental autoimmune encephalomyelitis, an inflammatory, demyelinating disease of the central nervous system, showed a delayed onset of disease and lower clinical scores during the course of disease. These data suggest a role for NGF signaling in the regulation of the immune response, possibly by enhancing sympathetic innervation of lymphoid tissues.

The enhanced antigen-specific production of cytokines induced by pertussis toxin is due to clonal expansion of T cells and not to altered effector functions of long-term memory cells.

Pertussis toxin (PT) has been shown to act as an adjuvant that enhances the production of both Th1 and Th2 cytokines to coinjected protein antigens. It has remained unresolved, however, how PT affects the clonal sizes, long-term effector functions, and Th1/Th2/Th0 differentiation of the T cell responses induced. We have studied the effects of PT on the development of the CD4(+) T cell response to a prototypic antigen, hen eggwhite lysozyme (HEL). HEL injection with incomplete Freund's adjuvant (IFA) resulted in an IFN-gamma(-)/IL-5(+) Th2 recall response. In comparison, co-administration of PT with HEL:IFA enhanced the frequencies of IL-5-producing T cells up to eightfold, and induced the differentiation of high frequencies of IFN-gamma-producing CD4(+) T cells. The results showed that the IFN-gamma and IL-5 produced, originated from clonally expanded Th1 and Th2, but not Th0 cells, and that the effector functions of long-term memory cells were unaffected. Adoptive transfer experiments suggested that PT mediated these effects via activation of APC, not by acting on the T cells directly. The effects of PT on the developing T cell response required the presence of the holotoxin (A- and B-subunit); the individual subunits did not show adjuvant effects. The data suggest that PT enhanced cytokine production by promoting differentiation and vigorous clonal expansion of Th1 and Th2 cells via activation of APC.

The role of costimulation in autoimmune demyelination.

Experimental allergic encephalomyelitis (EAE) is a T cell-mediated, autoimmune disorder characterized by central nervous system (CNS) inflammation and demyelination, features reminiscent of the human disease, multiple sclerosis (MS). In addition to the signal the encephalitogenic T cell receives through the T cell receptor (TCR), a second signal, termed costimulation, is required for complete T cell activation. The B7 family of cell surface molecules expressed on antigen presenting cells (APC) is capable of providing this second signal to T cells via two receptors, CD28 and CTLA-4. Our studies have shown that costimulation provided by B7 molecules to its ligand CD28 is important in the initiation of the autoimmune response in EAE. Further, it appears the costimulation provided by B7-1 is important in disease development, while B7-2 may play an important regulatory role. We and others later showed that B7/CTLA-4 interaction plays a critical role in down-regulating the immune response. Previous work has shown that activated T cells and T cells of a memory phenotype are less dependent on costimulation than naive T cells. T cells reactive with myelin components that are involved in the pathogenesis of EAE and possibly MS would be expected to have been activated as part of the disease process. Building upon our prior work in the EAE model, we have tested the hypothesis that myelin-reactive T cells, which are relevant to the pathogenesis of CNS inflammatory demyelination, can be distinguished from naive myelin-reactive T cells by a lack of dependence upon costimulation for activation and that the costimulatory requirements of these myelin-reactive T cells change during the course of disease. Our studies in the EAE model have also addressed the mechanisms of extrathymic (peripheral) T cell tolerance following intravenous (i.v. ) administration of high dose antigen. It is believed that TCR signaling in the absence of costimulation is a vital component of peripheral tolerance mechanisms. However, recent evidence suggests that peripheral tolerance of antigen-specific T cells induced in vivo may require CTLA-4 engagement of the tolerized T cells. We have begun to examine the molecular mechanisms of tolerance induction following intravenous and intraperitoneal administration of myelin antigens in the EAE model and test the hypothesis that tolerance induction is dependent on the B7:CD28/CTLA-4 pathway. The results from our studies will enhance our understanding of the role that myelin-reactive T cells may play in the pathogenesis of MS. We have determined that MBP-reactive T cells in MS patients are less dependent upon CD28 costimulation than in normal controls, suggesting that these T cells were previously primed in vivo. Characterization of these CD28-independent myelin-specific T cells will have broad implications for a variety of immunologically based therapies in diseases such as MS.

Developmentally regulated gene expression of Th2 cytokines in the brain.

Given the critical role of cytokines in the regulation of an inflammatory response, we investigated whether certain cytokines are expressed in the brains of normal mice during maturation that could contribute to the immune-privileged nature of the CNS or potentially influence an immune-mediated illness such as experimental allergic encephalomyelitis. The gene expression of IFN gamma (Th1 cytokine) and IL-4 (Th2 cytokine) was analyzed in the brain of several strains of mice. IFN gamma was not detectable. However, IL-4 was present in the brains of neonatal mice, but not adult mice. Resident CNS cells are believed to be the source of the IL-4, because mice deficient in T cells (SCID and RAG2-/-) expressed the IL-4 gene in the CNS. Further analysis indicated that the gene expression of the Th2 cytokine transcription factor, GATA-3, correlated with IL-4 and IL-10 expression in the brain. Since GATA-3-deficient mice have an abnormal CNS, brain-derived Th2 cytokines may play an important role in CNS development, as well as potentially contribute to the immune-privileged nature of the brain.

The role of CTLA-4 in tolerance induction and T cell differentiation in experimental autoimmune encephalomyelitis: i.p. antigen administration.

Recent evidence suggests that co-stimulation provided by B7 molecules through CTLA-4 is important in establishing peripheral tolerance. In the present study, we examined the kinetics of tolerance induction and T cell differentiation following i.p. administration of myelin basic protein (MBP) Ac1-11 in mice transgenic for a TCR V(beta)8.2 gene derived from an encephalitogenic T cell clone specific for MBP Ac1-11. Examination of the lymph node cell response after antigen administration demonstrated a dependence on CTLA-4 for i.p. tolerance induction. Examination of splenocyte responses suggested that i.p. antigen administration induced a T(h)2 response, which was potentiated by anti-CTLA-4 administration. Interestingly, i.p. tolerance was able to inhibit the induction of experimental autoimmune encephalomyelitis and anti-CTLA-4 administration did not alter this phenotype, suggesting that CTLA-4 blockade did not block tolerance induction. Thus, T cell differentiation and the dependence on CTLA-4 for tolerance induction following i.p. antigen administration differs between lymph node and spleen in a model of organ-specific autoimmunity.

The role of CTLA-4 in tolerance induction and ttigen administration cell differentiation in experimental autoimmune encephalomyelitis: i. v. antigen administration.

Interactions between B7 molecules on antigen-presenting cells and CTLA-4 on T cells have been shown to be important in establishing tolerance. In the present study, we examined the kinetics of tolerance induction following i.v. administration of myelin basic protein (MBP) Ac1-11 in mice transgenic for a TCR V(beta)8.2 gene derived from an encephalitogenic T cell clone specific for MBP Ac1-11. Examination of the lymph node cell (LNC) response 10 days after antigen administration demonstrated an accentuation of i.v. tolerance induction with anti-CTLA-4 blockade. Anergy was induced in splenocytes by i.v. antigen administration as shown by a decrease in MBP-specific proliferation and IL-2 production, and anti-CTLA-4 potentiated this effect. In addition, i.v. antigen plus anti-CTLA-4 and complete Freund's adjuvant was not encephalitogenic. Interestingly, i.v. tolerance (a single injection) did not inhibit experimental autoimmune encephalomyelitis (EAE) and anti-CTLA-4 administration did not alter this phenotype. These results suggest that while the majority of MBP-specific T cells are tolerized by i.v. antigen and that this process is potentiated by anti-CTLA-4 administration, a population of T cells remains that is quite efficient in mediating EAE.

Indicadores de eficiencia para la asignación de recursos en salud / Efficacy indicators for the allocation of health resources

This review proposes an analytical method for the development of efficacy indicators, that will allow the integration of diverse technical criteria in the allocation of health resources. Indicators of epidemiological, clinical, organizational and economic efficiency were the four levels of conceptual approach integrated in the analytical framework. The different elements of each level are interrelated to compose an analytical perspective that can be used to guide the mechanisms of resource allocation based on technical criteria. This perspective allows the development of new relevant public health instruments, specially designed for the allocation of resources

Increased transmitter release and aberrant synapse morphology in a Drosophila calmodulin mutant.

The ubiquitous calcium-binding protein calmodulin (CaM) has been implicated in the development and function of the nervous system in a variety of eukaryotic organisms. We have generated mutations in the single Drosophila Calmodulin (Cam) gene and examined the effects of these mutations on behavior, synaptic transmission at the larval neuromuscular junction, and structure of the larval motor nerve terminal. Flies hemizygous for Cam3c1, a mutation in the first Ca2+-binding site, exhibit behavioral, neurophysiological, and neuroanatomical abnormalities. In particular, adults exhibit defects in locomotion, coordination, and flight. Larvae exhibit increased neurotransmitter release from the motor nerve terminal at low [Ca2+] in the presence of the K+ channel-blocking drug quinidine. In addition, synaptic bouton structure at motor nerve terminals is altered. These effects are distinct from those produced by altering the activity of the CaM target enzymes CaM-activated kinase II (CaMKII) and CaM-activated adenylyl cyclase (CaMAC). Furthermore, previous in vitro studies of mutant Cam3c1 demonstrated that although its Ca2+ affinity is decreased, Cam3c1 protein can activate CaMKII, CaMAC, and CaM-activated phosphatase calcineurin in a manner similar to wild-type CaM. Thus, the Cam3c1 mutation might affect Ca2+ buffering or interfere with the activation or inhibition of a CaM target distinct from CaMKII or CaMAC.

Evaluación económica del cambio en el perfil epidemiológico: información para las reformas del sector salud / Economical assessment of the epidemiological profile change: information for health care reforms

Taking into account the information needed to implement the reform of the health sector, we present the results of an analysis of costs and financial consequences of the epidemiological change of four tracer diseases in México, 2 chronic (diabetes and hypertension) and 2 infectious diaseases (pneumonia and diarrhea). The hospital cost-case management of diabetes expected for 1998 represents the same amount of hospital and ambulatory case management of diarrheas and pneumonias for the same year. The internal competition for resource allocations that is expected, among other factors, is one of the results that permits the argument that changes in the epidemiological profile generate relevant financial consequences in the planning and implementing of structural reforms of the health systems, particularly with regards to the patterns of resource allocation for specific health programs

Factores asociados con la productividad médica / Associated factors with medical productivity

El presente estudio de caso muestra el análisis de los factores asociados a la productividad médica como uno de los problemas prioritarios de la organización de los sistemas de salud. La productividad quedó definida como la relación entre los resultados obtenidos y los insumos utilizados en un periodo de tiempo determinado. Para demostrar el planteamiento anterior, se tomó el marco de referencia elaborado por distintos autores en otros países, principalmente Estados Unidos y Canadá

Empresas de aparatos médicos y su vinculación con centros de desarrollo tecnológico en México / Medical equipment companies and their ties with technology development centers in Mexico

El objetivo de esta investigación fue determinar las características de las empresas productoras, distribuidoras y de servicios de aparatos médicos en México, y los factores asociados al establecimiento o no de vínculos con centros de investigación y desarrollo tecnológico. Los datos analizados provienen de un censo de dichas empresas llevado a cabo en la Ciudad de México y alrededores en 1989. Los datos fueron actualizados en 1991. Se realizaron análisis multivariados para identificar las características de las empresas que habían establecido vínculos o deseaban hacerlo y las áreas de interés de esas empresas. De 208 empresas encuestadas, solo el 23 por ciento tenían vínculos con centros de investigación. Las empresas con vínculos o interés en establecerlos tendían a invertir en investigación y a haber hecho planes de expansión. El establecimiento de vínculos se perfiló como un proceso bidireccional, con consecuencias positivas para las empresas del ramo, los centros de investigación y el sector de la salud. Se concluyó que sería conveniente dirigir programas que fomenten esos vínculos a las empresas con las características mencionadas

Empresas de aparatos médicos y su vinculación con centros de desarrollo tecnológico en México / Medical equipment companies and their ties with technology development centers in Mexico

El objetivo de esta investigación fue determinar las características de las empresas productoras, distribuidoras y de servicios de aparatos médicos en México, y los factores asociados al establecimiento o no de vínculos con centros de investigación y desarrollo tecnológico. Los datos analizados provienen de un censo de dichas empresas llevado a cabo en la Ciudad de México y alrededores en 1989. Los datos fueron actualizados en 1991. Se realizaron análisis multivariados para identificar las características de las empresas que habían establecido vínculos o deseaban hacerlo y las áreas de interés de esas empresas. De 208 empresas encuestadas, solo el 23 por ciento tenían vínculos con centros de investigación. Las empresas con vínculos o interés en establecerlos tendían a invertir en investigación y a haber hecho planes de expansión. El establecimiento de vínculos se perfiló como un proceso bidireccional, con consecuencias positivas para las empresas del ramo, los centros de investigación y el sector de la salud. Se concluyó que sería conveniente dirigir programas que fomenten esos vínculos a las empresas con las características mencionadas

Human lens enzyme alterations with age and cataract: glyceraldehyde-3-P dehydrogenase and triose phosphate isomerase.

The isoelectric point distribution of G-3-P DH and TPI from human lenses was examined as a function of age and cataract formation. Both enzymes exhibited progressive heterogeneity with age and a shift towards an acidic charge. Little qualitative differences in the pI profiles of G-3-P DH and TPI were found to distinguish mixed cataracts from age comparable normal lenses. While the most alkaline form of G-3-P DH required less HAsO4= for optimal activity, no other kinetic property, i.e. Km substrate, cofactor and inhibitors distinguished any of the charge forms of G-3-P DH. All metaor isozyme forms of TPI had the same Km substrate in the forward and reverse reaction direction. The most acidic forms of G-3-P DH and TPI were less stable to increased temperatures than their more alkaline counterparts suggesting a decreased stability.

Purification and properties of human cataractous lens glyceraldehyde-3-phosphate dehydrogenase.

Glyceraldehyde-3-phosphate dehydrogenase has been shown to occur in three different forms in the human adult cataractous lens: a membrane bound form (M) and at least two cytosolic isozymes: I1 and I2. Similar Km's for substrate, cofactor and HAsO4 were established for each form and all three forms, to differing degree, require a reduced sulfhydryl group for maximum activity. A variety of phosphonucleosides (ATP, ADP, AMP and 3' 5' cyclic AMP) as well as NADH inhibit enzyme activity. Inhibition by ATP is non-competitive whereas cyclic AMP and NADH compete for the cofactor binding site. Chloride ion stimulates and inhibits enzyme activity at low and high concentrations respectively.