Analgesic efficacy of zoledronic acid and its effect on functional status of prostate cancer patients with metastasis

Objectives: A multi-centered observational study evaluated the efficacy of zoledronic acid for improving pain and mobility, and preventing skeletal-related events (SRE) (fracture, spinal compression, pain-relieving radiotherapy), in patients with prostate cancer and bone metastasis. Materials and Methods: Males (n = 218) with prostate cancer and bone metastasis undergoing oncologic therapy received zoledronic acid (4 mg iv/month) for 6 months. Parameters evaluated were: 1) pain and movement after 2 consecutive doses; 2) quality of life; 3) SRE incidence and time-to-appearance. Medication tolerance and treatment satisfaction were assessed using a questionnaire. Results: A total of 170 that matched all the inclusion criteria (78%) out of 218 were evaluable for efficacy. There was a measurable statistically significant reduction in pain at rest and on movement as well as an improvement in the quality of life compared with baseline. Best results were obtained with early treatment. Overall incidence of bone events was 11.2%. Of the 212 patients (97.2%) evaluable for safety, 16% suffered adverse events and 66% expressed satisfaction with the treatment Discussion: Zoledronic acid is effective for reducing pain, improving mobility, and increasing the quality of life in patients with prostate cancer with bone metastasis. Its easy administration and good tolerability make zoledronic acid one of the principal therapeutic tools in the management of patients with pain associated with bone metastasis from prostate cancer.

A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p≤5×10−7). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10−8) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2×10−8) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5×10−8; rs1229984-ADH1B, p = 7×10−9; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

Functional Variants in NOS1 and NOS2A Are Not Associated with Progressive Hearing Loss in Ménière's Disease in a European Caucasian Population

Hearing loss in Meniere's disease (MD) is associated with loss of spiral ganglion neurons and hair cells. In a guinea pig model of endolymphatic hydrops, nitric oxide synthases (NOS) and oxidative stress mediate loss of spiral ganglion neurons. To test the hypothesis that functional variants of NOS1 and NOS2A are associated with MD, wed genotyped three functional variants of NOS1 (rs41279104,rs2682826, and a cytosine-adenosine microsatellite repeat in exon 1f) and the CCTTT repeat in the promoter of NOS2A gene (rs3833912) in two independent MD sets(273 patients in total) and 550 controls. A third cohort of American patients was genotyped as replication cohort for the CCTTT repeat. Neither allele nor genotype frequencies of rs41279104 and rs2682826 were associated with MD, although longer alleles of the cytosine-adenosine microsatellite repeat were marginally significant (corrected p = 0.05) in the Mediterranean cohort but not in a second Galicia cohort. Shorter numbers of the CCTTT repeat in NOS2A were significantly more frequent in Galicia controls (OR = 0.37 [CI, 0.18-0.76], corrected p =0.04), but this finding could not be replicated in Mediterranean or American case-control populations. Meta-analysis did not support an association between CCTTT repeats and risk for MD. Severe hearing loss (>75 dB) was also not associated with any functional variants studied. Functional variants of NOS1 and and NOS2A do not confer susceptibility for MD.

Analysis of TNFAIP3, a feedback inhibitor of nuclear factor-κB and the neighbor intergenic 6q23 region in rheumatoid arthritis susceptibility

INTRODUCTION Genome-wide association studies of rheumatoid arthritis (RA) have identified an association of the disease with a 6q23 region devoid of genes. TNFAIP3, an RA candidate gene, flanks this region, and polymorphisms in both the TNFAIP3 gene and the intergenic region are associated with systemic lupus erythematosus. We hypothesized that there is a similar association with RA, including polymorphisms in TNFAIP3 and the intergenic region. METHODS To test this hypothesis, we selected tag-single nucleotide polymorphisms (SNPs) in both loci. They were analyzed in 1,651 patients with RA and 1,619 control individuals of Spanish ancestry. RESULTS Weak evidence of association was found both in the 6q23 intergenic region and in the TNFAIP3 locus. The rs582757 SNP and a common haplotype in the TNFAIP3 locus exhibited association with RA. In the intergenic region, two SNPs were associated, namely rs609438 and rs13207033. The latter was only associated in patients with anti-citrullinated peptide antibodies. Overall, statistical association was best explained by the interdependent contribution of SNPs from the two loci TNFAIP3 and the 6q23 intergenic region. CONCLUSIONS Our data are consistent with the hypothesis that several RA genetic factors exist in the 6q23 region, including polymorphisms in the TNFAIP3 gene, like that previously described for systemic lupus erythematosus.

Guía de servicios de sanidad ambiental

Publicado en la página web de la Consejería de Salud y Bienestar Social: www.juntadeandalucia.es/salud (Consejería de Salud y Bienestar Social / Ciudadanía / Nuestra Salud / Medio ambiente y Salud)

Human Exposure to Endocrine-Disrupting Chemicals and Prenatal Risk Factors for Cryptorchidism and Hypospadias: A Nested Case-Control Study

BACKGROUND. Exposure to xenoestrogens during pregnancy may disturb the development and function of male sexual organs. OBJECTIVE. In this study we aimed to determine whether the combined effect of environmental estrogens measured as total effective xenoestrogen burden (TEXB) is a risk factor for male urogenital malformations. METHODS. In a case-control study, nested in a mother-child cohort (n = 702) established at Granada University Hospital, we compared 50 newborns with diagnosis of cryptorchidism and/or hypospadias with 114 boys without malformations matched by gestational age, date of birth, and parity. Controls did not differ from the total cohort in confounding variables. TEXB and levels of 16 organochlorine pesticides were measured in placenta tissues. Characteristics of parents, pregnancy, and birth were gathered by questionnaire. We used conditional and unconditional regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS. TEXB from organohalogenated compounds was detectable in 72% and 54% of case and control placentas, respectively. Compared with controls, cases had an OR for detectable versus non-detectable TEXB of 2.82 (95% CI, 1.10-7.24). More pesticides were detected in cases than in controls (9.34 +/- 3.19 vs. 6.97 +/- 3.93). ORs for cases with detectable levels of pesticides, after adjusting for potential confounders in the conditional regression analysis, were o,p'-DDT (OR = 2.25; 95% CI, 1.03-4.89), p,p'-DDT (OR = 2.63; 95% CI, 1.21-5.72), lindane (OR = 3.38; 95% CI, 1.36-8.38), mirex (OR = 2.85; 95% CI, 1.22-6.66), and endosulfan alpha (OR = 2.19; 95% CI, 0.99-4.82). Engagement of mothers in agriculture (OR = 3.47; 95% CI, 1.33-9.03), fathers' occupational exposure to xenoestrogens (OR = 2.98; 95% CI, 1.11-8.01), and history of previous stillbirths (OR = 4.20; 95% CI, 1.11-16.66) were also associated with risk of malformations. CONCLUSIONS We found an increased risk for male urogenital malformations related to the combined effect of environmental estrogens in placenta.

Different profiles of immune reconstitution in children and adults with HIV-infection after highly active antiretroviral therapy.

BACKGROUND Recent advances in characterizing the immune recovery of HIV-1-infected people have highlighted the importance of the thymus for peripheral T-cell diversity and function. The aim of this study was to investigate differences in immune reconstitution profiles after highly active antiretroviral therapy (HAART) between HIV-children and adults. METHODS HIV patients were grouped according to their previous clinical and immunological status: 9 HIV-Reconstituting-adults (HIV-Rec-adults) and 10 HIV-Reconstituting-children (HIV-Rec-children) on HAART with viral load (VL) or=500 cells/microL at least during 6 months before the study and CD4+

Serum phospholipid fatty acid profile and dietary intake in an adult Mediterranean population with cystic fibrosis.

The relative importance of the usual diet in serum phospholipids in subjects with cystic fibrosis (CF) has been poorly studied. To compare the fatty acid profile in serum phospholipids from adult CF subjects with that of healthy subjects, and determine the role of the normal diet in this profile, we studied thirty-seven adult CF subjects with stable pulmonary disease and thirty-seven healthy controls matched for age, sex and nutritional status. A dietary questionnaire was obtained, anthropometric data were recorded, and the fatty acid profile measured by GLC. Compared with the controls, the percentages of myristic, palmitoleic and stearic acids and total MUFA were significantly higher in the CF group, and DHA, linoleic acid, total PUFA and n-6 fatty acids were significantly lower in the CF group. The CF subjects with worse pulmonary function and with pancreatic insufficiency had significantly lower levels of linoleic and n-6 fatty acids. The total energy intake was significantly higher in the CF subjects, although the energy distribution in the CF subjects and the controls was not different for the carbohydrates, lipids and proteins. No differences were detected in fat intake for MUFA (51 (SD 4) v. 52 (SD 4) %) or saturated fatty acids (33.5 (SD 5) v. 31.2 (SD 3.8) %), but the PUFA were slightly lower in the CF subjects (15.4 (SD 4.5) v. 17.4 (SD 4.2) %; P=0.02). The usual dietary intake of fatty acids by adult CF subjects does not appear to explain the difference in the fatty acid profile compared with controls. This suggests an abnormal fatty acid metabolism in CF subjects.

Kallikrein genes are associated with lupus and glomerular basement membrane-specific antibody-induced nephritis in mice and humans.

Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody-induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that maybe responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody-induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family,which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody-induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms,some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody-induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody-induced nephritis and lupus.

El futuro de la sanidad ambiental en Andalucía: oportunidades de mejora.

In the present article is presented a portrait of the situation of the environmental health in the administration of Andalusian Goverment; are analyzed implanted management formulations and we believe a reflection space on the professional exercise and the course begun with the organizational process in the Andalusian public health. The public health system has not undergone reconstruction from the process of transferences from the State towards the autonomous Communities. We identified the extrapolation of the model clinicalassistance management to the public health structures without delving what is sufficient in their organization and objectives. Setting of business process management (BMP) has got worse the administrative bureaucracy and the teamwork has not been preceded of alliances and agreements that generate feeling of ownership the same organization to avoid professional conflicts. We bet on strengthening the paper of the environmental health technicians as referring in the identification of this performances within public health system. For this propose we need the implication of all the professionals in the reform of the organization and management of the health public, to evolve in the professional exercise creating a regulated academic specialty and to define the competences maps in their different capabilites areas.

Plan Andaluz de Atención Integrada a Pacientes con Enfermedades Crónicas

Vigencia del plan 2012-2016. Publicado en la página web de la Consejería de Salud y Bienestar Social: www.juntadeandalucia.es/salud (Consejería de Salud y Bienestar Social / Ciudadanía / Quiénes somos / Planes y Estrategias)

Proceso de inspección

En la port.: Secretaría General de Salud Pública y Participación

Prospective phase II trial of extended treatment with rituximab in patients with B-cell post-transplant lymphoproliferative disease.

BACKGROUND AND OBJECTIVES The elective treatment of patients with post-transplant lymphoproliferative disorders is controversial. The purpose of this trial was to evaluate the efficacy of treatment with extended doses of rituximab adapted to the response in patients with post-transplant lymphoproliferative disorders after solid organ transplantation. DESIGN AND METHODS This was a prospective, multicenter, phase II trial. Patients were treated with reduction of immunosuppression and four weekly infusions of rituximab. Those patients who did not achieve complete remission (CR) received a second course of four rituximab infusions. The primary end-point of the study was the CR rate. RESULTS Thirty-eight patients were assesable. One episode of grade 4 neutropenia was the only severe adverse event observed. After the first course of rituximab, 13 (34.2%) patients achieved CR, 8 patients did not respond, and 17 patients achieved partial remission. Among those 17 patients, 12 could be treated with a second course of rituximab, and 10 (83.3%) achieved CR, yielding an intention-to-treat CR rate of 60.5%. Eight patients excluded from the trial because of absence of CR were treated with rituximab combined with chemotherapy, and six (75%) achieved CR. Event-free survival was 42% and overall survival was 47% at 27.5 months. Fourteen patients died, ten of progression of their post-transplant lymphoproliferative disorder. INTERPRETATION AND CONCLUSIONS These results confirm that extended treatment with rituximab can obtain a high rate of CR in patients with post-transplant lymphoproliferative disorders after solid organ transplantation without increasing toxicity, and should be recommended as initial therapy for these patients.