Polycystic echinococcosis in Pacas, Amazon region, Peru.

In the Peruvian Amazon, paca meat is consumed by humans. To determine human risk for polycystic echinococcosis, we examined wild pacas from 2 villages; 15 (11.7%) of 128 were infected with Echinococcus vogeli tapeworms. High E. vogeli prevalence among pacas indicates potential risk for humans living in E. vogeli-contaminated areas.

Pattern of health services use by immigrants from different regions of the world residing in Spain.

OBJECTIVE: To determine immigrants' frequency of use of four health services by place of origin and compare it with that of the Spanish population. METHODS: Based on the 2006 National Health Survey in Spain, we estimated the frequency of use of four health services in men and women from: Spain, Western countries, Eastern Europe, Latin America, North Africa, Sub Saharan Africa and Asia/Oceania. These results were compared with the Spanish population by calculating odds ratios adjusted for age, socioeconomic position, health status, and type of health coverage. RESULTS: Immigrant men generally use health services less frequently than Spanish nationals. The main exceptions are Latin American men, who more often use emergency services (OR 1.68, 95% CI 1.41-1.99) and Sub-Saharan men, who use specialists more frequently (OR 2.93, 1.70-5.05). Immigrant women use health services about as frequently as Spanish women. The main exceptions are North African women, who less frequently use specialists (OR 0.39, 0.22-0.71) and Sub-Saharan women who more frequently use GPs (OR 4.06, 2.21-7.44), specialists (OR 2.29, 1.06-4.95) and emergency services (OR 2.92, 1.49-5.72). CONCLUSIONS: Health services use by the immigrant population in Spain differs by gender and place of origin.

A proposal of measures for monitoring social disparities in health using AIDS and liver disease mortality before and after HAART.

BACKGROUND: To assess the more appropriate measures for monitoring health differences and evaluating the impact of interventions based on the real burden of the health problem in the population and on the best alternative for communication with policymakers and with society at large. METHODS: Disparity in mortality from acquired immunodeficiency syndrome (AIDS) and liver disease were measured in two cohorts of Spanish men: before and after the introduction of highly active antiretroviral therapy (HAART). Men were grouped into managers/professionals/technicians, clerks/service workers/manual workers and unemployed. The mortality rate difference and the mortality rate ratio in clerks/service workers/manual workers and in unemployed vs. managers/professionals/technicians were estimated. Moreover, various summary measures of absolute disparity were also calculated. RESULTS: Between the first and second period, the AIDS mortality rate difference decreased from 21.9 to 5.9 per 100,000 person-years in clerks/service workers/manual workers and from 117.2 to 59.3 in unemployed, whereas the liver mortality rate difference increased from 4.7 to 6.4 and from 37.4 to 48.9, respectively. The AIDS mortality rate ratio increased by 11% in clerks/service workers/manual workers and by 50% in unemployed, while the liver disease mortality rate ratio increased by almost 400% in both groups. The summary measures of disparity decreased in AIDS mortality and increased in liver disease, although the magnitude of the change varied from one measure to another. CONCLUSIONS: The findings in unemployed men were the most important from the public health perspective; however, they could not be adequately identified with either mortality rate ratios or summary measures of absolute disparity.

La utilización de los servicios sanitarios por la población inmigrante en España / Health services utilization by the immigrant population in Spain

Objetivo: Comparar la utilización de los servicios sanitarios por la población inmigrante y por la población autóctona. Métodos: Se ha utilizado la información proporcionada por cuatro encuestas de salud realizadas alrededor del año 2005: de Cataluña en 2006, de la ciudad de Madrid en 2005, de Canarias en 2004 y de la Comunidad Valenciana en 2005. Los servicios sanitarios investigados han sido médico general, médico especialista, servicio de urgencias, hospitalización y dos servicios preventivos: citología vaginal y mamografía. Resultados: En líneas generales, la población inmigrante utiliza con menor frecuencia que la española la mayoría de los servicios sanitarios. La consulta al médico general y la hospitalización constituyen los servicios sanitarios en que se ha encontrado una menor diferencia en su frecuentación entre ambas poblaciones, mientras que el médico especialista y los servicios preventivos constituyen los servicios sanitarios en que se ha encontrado una mayor diferencia. En la consulta al médico general y la hospitalización es donde los hallazgos son más heterogéneos, ya que algunos grupos de inmigrantes presentan una frecuencia relativamente alta en algunos ámbitos geográficos y una frecuencia relativamente baja en otros. Conclusiones: Los resultados reproducen los observados en otras investigaciones realizadas en países del entorno social y económico de España, y al igual que sucede con la evidencia disponible, no se pueden sugerir explicaciones. Las investigaciones futuras deberían probar a utilizar otros tipos de estudios y a contrastar explicaciones no sugeridas hasta ahora por la comunidad científica (AU)

Objective: To compare health services utilization between the immigrant and indigenous populations in Spain. Methods: We used information provided by the following four health surveys carried out around 2005: Catalonia 2005; city of Madrid 2005, Canary Islands 2004 and the Autonomous Community of Valencia 2005. The health services studied were general practice, specialist services, emergency services, hospitalization, and two preventive services: pap smear test and mammography. Results: In general, most health services were less frequently used by the immigrant population than by the Spanish population. The health services showing the least differences between the two populations were general practice and hospitalization, while the greatest differences were found in the use of specialist and preventive services. The most heterogeneous results were found in general practice and hospitalization, since some immigrant groups showed a relatively high frequency of use in some geographical areas and a relatively low frequency in other areas. Conclusion: The results of the present study reproduce those found in other studies carried out in countries with similar social and economic characteristics to Spain. Like previous results, the present results are difficult to explain. Future research should aim to use other study designs and to test hypotheses not put forward by the scientific community to date (AU)

[Health services utilization by the immigrant population in Spain]. / La utilización de los servicios sanitarios por la población inmigrante en España.

OBJECTIVE: To compare health services utilization between the immigrant and indigenous populations in Spain. METHODS: We used information provided by the following four health surveys carried out around 2005: Catalonia 2005; city of Madrid 2005, Canary Islands 2004 and the Autonomous Community of Valencia 2005. The health services studied were general practice, specialist services, emergency services, hospitalization, and two preventive services: pap smear test and mammography. RESULTS: In general, most health services were less frequently used by the immigrant population than by the Spanish population. The health services showing the least differences between the two populations were general practice and hospitalization, while the greatest differences were found in the use of specialist and preventive services. The most heterogeneous results were found in general practice and hospitalization, since some immigrant groups showed a relatively high frequency of use in some geographical areas and a relatively low frequency in other areas. CONCLUSION: The results of the present study reproduce those found in other studies carried out in countries with similar social and economic characteristics to Spain. Like previous results, the present results are difficult to explain. Future research should aim to use other study designs and to test hypotheses not put forward by the scientific community to date.

Major reduction in AIDS-mortality inequalities after HAART: the importance of absolute differences in evaluating interventions.

This study estimates the magnitude of inequalities in AIDS mortality in the period when highly active antiretroviral therapy (HAART) was introduced and after its widespread dissemination in the Region of Madrid, Spain. Two population cohorts were constructed by linking records from 1996 and 2001 population censuses with mortality registry records after initial and full implementation of HAART, respectively. Absolute and relative differences in AIDS mortality in people aged 20-49 years were estimated in each population cohort according to neighbourhood and individual socioeconomic position. The absolute difference in mortality between neighbourhoods with highest and lowest socioeconomic position (unemployment rate, per capita income) declined from about 30/100,000 person-years in the 1996 population cohort to 8/100,000 person-years in the 2001 population cohort. The absolute difference in mortality between individuals with the highest and lowest socioeconomic position fell from about 60/100,000 person-years in the first cohort to about 20/100,000 in the second. Relative differences in mortality by neighbourhood socioeconomic position and by individual education level also decreased in the 2001 cohort with respect to the 1996 cohort. Although relative differences by individual occupation increased, there was no evidence of a significant change. These findings show major reduction in absolute socioeconomic differences in AIDS mortality after HAART and indicate that the use of relative differences alone may be inadequate to fully evaluate the results of health interventions.

[Role of antiretroviral therapy in the reduction of the association between low educational level and AIDS-related mortality]. / Papel del tratamiento antirretroviral en la reducción de la asociación entre nivel educativo bajo y mortalidad por sida.

BACKGROUND AND OBJECTIVE: AIDS-related mortality has been classically associated with lowest socioeconomic groups. In Spain, the highly active antiretroviral therapy (HAART) is delivered without cost; therefore this treatment it should have reduced the great social inequalities in AIDS-mortality seen before the HAART era. This study aims to assess the absolute and relative socioeconomic differences in AIDS-mortality in the Region of Madrid after the introduction of HAART. PATIENTS AND METHOD: Two twenty-months cohorts were created, in 1996 and 2001, which correspond to an early and late HAART-era respectively. Absolute and relative differences in the AIDS-mortality rates were calculated for both periods using generalized linear models. RESULTS: Absolute differences between the lowest and highest education level AIDS-related deaths decreased around 70% in the 2001 cohort. Those with lowest education level achieved the highest reduction rate, hence relative differences descended as well. CONCLUSIONS: HAART has had an essential role in decreasing social inequalities in AIDS-mortality.

Papel del tratamiento antirretroviral en la reducción de la asociación entre nivel educativo bajo y mortalidad por sida / Role of antiretroviral therapy in the reduction of the association between low educational level and AIDS-related mortality

Fundamento y objetivo: La mortalidad por sida ha estado clásicamente asociada a los niveles socioeconómicos bajos. Dicha población ha podido acceder al tratamiento antirretroviral de gran actividad (TARGA) gracias a su dispensación gratuita, lo que debería de haber repercutido en una disminución de las diferencias socioeconómicas absolutas existentes. Este estudio ha evaluado la magnitud de las diferencias socioeconómicas en la mortalidad por sida, al inicio y tras la completa implementación del TARGA, en residentes en la Comunidad de Madrid. Pacientes y método: Se crearon 2 cohortes poblacionales con 20 meses de seguimiento en 1996 y en 2001, cuya mortalidad corresponde con los períodos de introducción y de plena incorporación del TARGA, respectivamente. Se calcularon las diferencias absolutas y relativas de las tasas de mortalidad según el nivel de estudios mediante modelos lineales generalizados. Resultados: La diferencia absoluta entre las tasas de mortalidad por sida en la población con mayor y menor nivel de estudios se redujo alrededor de un 70% en la cohorte de 2001 con respecto a la de 1996. El mayor porcentaje de reducción se observó en los pacientes con menor nivel de estudios y, como consecuencia, las diferencias relativas también disminuyeron. Conclusiones: El TARGA puede haber tenido un papel esencial en el descenso de las diferencias socioeconómicas en la mortalidad por sida

Background and objective: AIDS-related mortality has been classically associated with lowest socioeconomic groups. In Spain, the highly active antiretroviral therapy (HAART) is delivered without cost; therefore this treatment it should have reduced the great social inequalities in AIDS-mortality seen before the HAART era. This study aims to assess the absolute and relative socioeconomic differences in AIDS-mortality in the Region of Madrid after the introduction of HAART. Patients and method: Two twenty-months cohorts were created, in 1996 and 2001, which correspond to an early and late HAART-era respectively. Absolute and relative differences in the AIDS-mortality rates were calculated for both periods using generalized linear models. Results: Absolute differences between the lowest and highest education level AIDS-related deaths decreased around 70% in the 2001 cohort. Those with lowest education level achieved the highest reduction rate, hence relative differences descended as well. Conclusions: HAART has had an essential role in decreasing social inequalities in AIDS-mortality

Efficacy of selective 5-HT6 receptor ligands determined by monitoring 5-HT6 receptor-mediated cAMP signaling pathways.

1. Two novel selective 5-HT6 receptor ligands E-6801 (6-chloro-N-(3-(2-(dimethylamino)ethyl)-1H-indol-5-yl)imidazo[2,1-b]thiazole-5-sulfonamide) and E-6837 (5-chloro-N-(3-(2-(dimethylamino)ethyl)-1H-indol-5-yl)naphthalene-2-sulfonamide) were investigated and compared to the putative 5-HT6 receptor antagonists SB-271046 (5-chloro-N-(4-methoxy-3-(piperazin-1-yl)phenyl)-3-methylbenzo[b]thiophene-2-sulfonamide) and Ro 04-06790 (N-(2,6-bis(methylamino)pyrimidin-4-yl)-4-aminobenzenesulfonamide) using a cAMP-mediated pathway. 2. Forskolin stimulation, to increase the magnitude of agonist cAMP responses, and site-directed mutagenesis of the 5-HT6 receptor, in order to yield constitutively active receptor, were applied. 3. 5-HT (E(max), % over basal: 200), E-6801 (120) and E-6837 (23) induced cAMP formation at the rat 5-HT6 receptor. In the copresence of forskolin, cAMP responses were more potent and enhanced to 294 (5-HT, % over forskolin), 250 (E-6801) and 207 (E-6837), respectively. 5-HT-mediated cAMP formation was dose-dependently blocked by SB-271046 (pA(2): 8.76+/-0.22) and Ro 04-6790 (pA(2): 7.89+/-0.10) and not affected by the copresence of forskolin. Both E-6801 and E-6837 yielded partial antagonism of the 5-HT response in the absence of forskolin, whereas antagonism was either completely absent (E-6801) or attenuated (E-6837) in the copresence of forskolin. Intrinsic activity of these 5-HT6 receptor ligands at a constitutively active human S267K 5-HT6 receptor in Cos-7 cells indicated similar efficacy (E(max), % over basal) for 5-HT (97), E-6801 (91) and E-6837 (100), while Ro 04-6790 (-33) and SB-271046 (-39) were equi-efficacious inverse agonists. 4. The use of either forskolin or a constitutively active S267K 5-HT6 receptor enhances the resolution for monitoring the efficacy of 5-HT6 receptor ligands. E-6801 and E-6837 are potent partial agonists at the 5-HT6 receptor. Ro 04-6790 and SB-271046 appear to act as inverse agonists/antagonists.

Synthesis of new benzoxazinone derivatives as neuropeptide Y5 antagonists for the treatment of obesity.

Screening of our internal chemical collection against the neuropeptide Y5 (NPY Y5) receptor allowed the identification of a benzoxazine derivative 5f as a hit that showed moderate affinity (IC(50) = 300 nM). With the aim of improving the in vitro potency, a series of 2-benzoxazinone derivatives have been synthesized and tested for NPY Y5 activity. Most of the compounds were found to be potent and selective NPY Y5 antagonists having nanomolar binding affinities for the NPY Y5 receptor and showing functional antagonism in the forskolin-induced cyclic AMP test. Prelimminary studies in order to understand the structure-activity relationship were undertaken. Selected compounds were further evaluated for in vivo efficacy, affording the lead compound 2-[4-(8-methyl-2-oxo-4H-benzo[d][1,3]oxazin-1-yl)piperidin-1-yl]-N-(9-oxo-9H-fluoren-3-yl)acetamide 5p, which displayed in vivo activity reducing food intake in rodents.

Medicinal chemistry driven approaches toward novel and selective serotonin 5-HT6 receptor ligands.

Based on a medicinal chemistry guided hypothetical pharmacophore model, novel series of indolyl sulfonamides have been designed and prepared as selective and high-affinity serotonin 5-HT(6) receptor ligands. Furthermore, based on a screening approach of a discovery library, a series of benzoxazinepiperidinyl sulfonamides were identified as selective 5-HT(6) ligands. Many of the compounds described in this paper possess excellent affinities, displaying pK(i) values greater than 8 (some even >9) and high selectivities against a wide range (>50) of other CNS relevant receptors. First, structure-affinity relationships of these ligands are discussed. In terms of functionality, high-affinity antagonists, as well as agonists and even partial agonists, were prepared. Compounds 19c and 19g represent the highest-affinity 5-HT(6) agonists ever reported in the literature. These valuable tool compounds should allow for the detailed study of the role of the 5-HT(6) receptor in relevant animal models of disorders such as cognition deficits, depression, anxiety, or obesity.

The ABO blood group genotype and factor VIII levels as independent risk factors for venous thromboembolism.

Factor VIII (FVIII), von Willebrand factor (vWF) and the ABO blood groups have been associated with thrombosis. The ABO locus has functional effects on vWF and FVIII levels and is genetically correlated with FVIII, vWF and thrombosis. We carried out a case-control study to assess the role of FVIII, vWF and ABO types on thrombotic risk. We analyzed 250 patients with venous thrombosis and 250 unrelated controls. FVIII, vWF and other factors related to thrombophilia were measured, ABO groups were analyzed by genotyping. FVIII and vWF were higher in non-O individuals. Group O was more frequent in the controls (44.3% v 23.3%; difference 21.1%; 95% CI: 13.0-29.3%) and Group A in patients (59.2% v. 41.5%; difference 17.7%, 95% CI: 9.1-26.4%). Individuals carrying the A1 allele had a higher risk of thrombosis (OR 2.6; 95% CI, 1.8-3.8). The risk attributed to vWF disappeared after adjusting for the ABO group. Patients with FVIII above the 90th percentile had a high thrombotic risk (adjusted OR 3.7; 95% CI, 2.1-6.5), and a high risk of recurrence (OR 2.3; 95% CI: 1.3-4.1). In conclusion, high FVIII levels and non-O blood groups, likely those with the A1 allele, are independent risk factors for venous thromboembolism and should be considered in evaluating of thrombophilia.

Complexity of the genetic contribution to factor VII deficiency in two Spanish families: clinical and biological implications.

BACKGROUND AND OBJECTIVES: Although many F7 DNA variants have been described to be associated with alterations in factor VII (FVII) levels, the correlation of functional levels of FVII with disease (i.e. bleeding) is highly variable indicating that other factors are likely involved in producing this phenotype. DESIGN AND METHODS: We studied two unrelated Spanish families, identified from two asymptomatic propositi with FVII:C levels lower than 1% and 3%. Family members showed a wide range of FVII:C levels. Amplification and direct DNA sequencing of the F7 (promoter, exons, 3'-UTR and a large proportion of introns) identified the genetic variants involved. RESULTS: We characterized 3 mutations in the F7 coding region (homozygous Q100R in one patient, and double heterozygosity for M298I and G331S in another patient). We also found 16 new DNA polymorphisms. The high variability of FVII levels in family members with the same mutation shows that the inheritance of FVII phenotypes is extremely complex and suggests that polymorphisms might play an important role in modulating FVII levels, and ensuring hemostatic balance under pathologic conditions. INTERPRETATION AND CONCLUSIONS: These results highlight the importance of a concerted effect of multiple genetic factors in determining FVII levels. Since there is evidence that FVII levels constitute a risk factor for coronary heart disease and considering the importance of F7 DNA polymorphisms in determining FVII levels, further analyses of these polymorphisms should yield information to aid the understanding of the quantitative variation in FVII levels and the relative genetic risk for cardiovascular disease in the general population.

A new locus on chromosome 18 that influences normal variation in activated protein C resistance phenotype and factor VIII activity and its relation to thrombosis susceptibility.

Activated protein C resistance (APCR) is the most prevalent risk factor for thrombosis, accounting for 20% to 60% of familial thrombophilia. A mutation in the F5 gene, factor V Leiden (FVL), is a major determinant of pathological APCR in some populations. However, APCR predicts risk for thrombosis independently of FVL. This suggests that other genetic factors may influence risk of thrombosis through quantitative variation in APCR. To search for these unknown loci, we conducted a genome-wide linkage screen for genes affecting normal variation in APCR in the 21 Spanish families from the Genetic Analysis of Idiopathic Thrombophilia (GAIT) project. Conditional on FVL, the strongest linkage signal for APCR was found on chromosome 18 near D18S53. Bivariate linkage analyses with a genetically correlated trait, levels of clotting factor VIII, strengthened evidence for the chromosome 18 quantitative trait locus (QTL; logarithm of the odds [LOD], 4.5; P = 3.08 x 10(-5)). However, the region on chromosome 1 that contains the F5 structural gene showed little evidence of linkage to APCR (LOD, < 1). This indicates that apart from the FVL, the F5 locus itself plays a relatively minor role in normal variation in APCR, including the HR2 haplotype polymorphisms. A second bivariate analysis of APCR with thrombosis liability suggested that this QTL also influences the risk of thrombosis (P =.0016). These results indicate that a locus on chromosome 18 pleiotropically influences normal variation in the APCR phenotype and factor VIII (FVIII) levels as well as susceptibility to thrombosis. Importantly, there are no known thrombosis-related candidate genes in this region, implying that this QTL represents a completely novel thrombosis risk factor.

Identification of a large deletion and three novel mutations in exon 13 of the factor V gene in a Spanish family with normal factor V coagulant and anticoagulant properties.

As part of the GAIT (genetic analysis of idiopathic thrombophilia) project, we analyzed polymorphisms in the factor V (FV) gene to assess their role as genetic determinants of normal phenotypic variation of hemostasis-related traits in a Spanish population. During the analysis of exon 13 polymorphisms, we detected an abnormal PCR-amplified fragment in some members of the GAIT19 family. Direct sequence analysis revealed a deletion of 108 bp in eight out of 20 individuals in this family. This deletion removes exactly 36 amino acids from the B domain of FV; thus it does not alter the reading frame of the sequence. Among the deleted amino acids there is the 4070A>G polymorphism (H1299R), which could affect the level or function of FV. In addition, in the same family we identified three novel DNA variants (L1257I, Q1317Q and T1327T) in exon 13 of the F5 gene. Despite these variants, we did not detect any differences either in the coagulant or anticoagulant traits, or in the plasma protein levels involved in the blood coagulation cascade, between the carriers compared with their non-carrier relatives. From these results, we can conclude that the mutant allele is expressed and the resultant protein is functional. Moreover, it is unlikely that the 4070A>G polymorphism, within the deletion, and the novel DNA variants alter the functional properties of the mature FV protein. Further analyses of this naturally occurring mutation and the novel DNA variants should yield useful information for the understanding of the function of the B domain of FV.

Aspectos histológicos sobre la piel

El conocimiento de la estructura y el funcionamiento de la piel normal es muy importante debido al papel protector que este órgano realiza y a otras funciones esenciales para el mantenimiento del equilibrio entre el medio externo e interno garantizando de estaforma la salud del individuo, principal objetivo de la medicina y muy especialmente de la medicina preventiva cubana