The impact of heat waves on daily mortality in districts in Madrid: The effect of sociodemographic factors.

Although there is significant scientific evidence on the impact of heat waves, there are few studies that analyze the effects of sociodemographic factors on the impact of heat waves below the municipal level. The objective of this study was to analyze the role of income level, percent of the population over age 65, existence of air conditioning units and hectares (Ha) of green zones in districts in Madrid, in the impact of heat on daily mortality between January 1, 2010 and December 31, 2013. Seventeen districts were analyzed, and Generalized Linear (GLM) Poisson Regression Models were used to calculate relative risks (RR) and attributable risks (RA) for the impact of heat waves on mortality due to natural causes (CIEX:A00-R99). The pattern of risks obtained was analyzed using GLM univariates and multivariates of the binomial family (link logit), introducing the socioeconomic and demographic variables mentioned above. The results indicate that heat wave had an impact in only three of the districts analyzed. In the univariate models, all of the variables were statistically significant, but Ha of green zones lost significance in the multivariate model. Income level, existence of air conditioning units, and percent of the population over age 65 in the district remained as variables that modulate the impact of heat wave on daily mortality in the municipality of Madrid. Income level was the key variable that explained this behavior. The results obtained in this study show that there are factors at levels below the municipal level (district level) that should be considered as focus areas for health policy in order to decrease the impact of heat and promote the process of adaptation to heat in the context of climate change.

PGC-related gene variants and elite endurance athletic status in a Chinese cohort: a functional study.

This study aims to examine the association between proliferator-activated receptor γ (PGC)-gene family-related single nucleotide polymorphisms (SNPs) and elite endurance runners' status in a Chinese cohort, and to gain insights into the functionality of a subset of SNPs. Genotype distributions of 133 SNPs in PPARGC1A, PPARGC1B, PPRC1, TFAM, TFB1M, TFB2M, NRF1, GABPA, GABPB1, ERRα, and SIRT1 genes were compared between 235 elite Chinese (Han) endurance runners (127 women) and 504 healthy non-athletic controls (237 women). Luciferase gene reporter activity was determined in 20 SNPs. After adjusting for multiple comparisons (in which threshold P-value was set at 0.00041), no significant differences were found in allele/genotype frequencies between athletes and controls (when both sexes were analyzed either together or separately). The lowest P-value was found in PPARGC1A rs4697425 (P = 0.001 for the comparison of allele frequencies between elite female endurance runners and their gender-matched controls). However, no association (all P > 0.05) was observed for this SNP in a replication cohort from Poland (194 endurance athletes and 190 controls). Using functional genomics tool, the following SNPs were found to have functional significance: PPARGC1A rs6821591, rs12650562, rs12374310, rs4697425, rs13113110, and rs4452416; PPARGC1B rs251466 and rs17110586; and PPRC1 rs17114388 (all P < 0.001). This study found no significant association between PGC-related SNPs and elite endurance athlete status in the Chinese population, despite some SNPs showing potential functional significance and the strong biological rationale to hypothesize that this gene pathway is a candidate to influence endurance exercise capacity.

Group or individual housing does not reduce socio-sexual and reproductive responses in anestrous goats during the first contact with the photo-stimulated buck.

Herein, we examined the effect of the type of housing (individual vs group housing) of anestrus female goats on plasma cortisol concentrations and socio-sexual behaviors during first contact with photo-stimulated male goats and determined the impact on sexual and reproductive responses after 15 d of contact with photo-stimulated males. Therefore, after weaning, 10 females each were individually and group-housed, respectively. Ten bucks were rendered sexually active by exposure to artificially long days (16 h of light and 8 h of darkness per day) for 2.5 mo. During the naturally increasing photoperiod, 15-mo-old females were exposed and maintained with males. On day 0, during the first contact with males, individually- and group-housed females exhibited similar plasma cortisol concentrations (22.6 vs 27.4 ng/mL, respectively). Likewise, socio-sexual behaviors did not differ between examined groups on day 0. Moreover, the interval from first contact with males to the first estrus, short and normal ovulatory cycles, ovulation, fertility, and prolificacy rates were similar between differently housed females. Furthermore, mounting attempts did not differ between males in contact with either female group. In conclusion, individually- and group-housed anestrus females displayed elevated and similar plasma cortisol concentrations during first contact with photo-stimulated males and similar socio-sexual behaviors and reproductive responses when exposed to photo-stimulated males.

Future care for long-term cancer survivors: towards a new model.

PURPOSE: The increase in the prevalence "long-term cancer survivor" (LCS) patients is expected to increase the cost of LCS care. The aim of this study was to obtain information that would allow to optimise the current model of health management in Spain to adapt it to one of efficient LCS patient care. METHODS: This qualitative study was carried out using Delphi methodology. An advisory committee defined the criteria for participation, select the panel of experts, prepare the questionnaire, interpret the results and draft the final report. RESULTS: 232 people took part in the study (48 oncologists). Absolute consensus was reached in three of the proposed sections: oncological epidemiology, training of health professionals and ICT functions. CONCLUSION: The role of primary care in the clinical management of LCS patients needs to be upgraded, coordination with the oncologist and hospital care is essential. The funding model needs to be adapted to determine the funding conditions for new drugs and technologies.

The effect of cold waves on daily mortality in districts in Madrid considering sociodemographic variables.

While there is much research that focuses on the association between cold waves and their impacts on daily mortality at the city level, few analyze the impact related to social context and demographic variables at levels lower than the municipal. The objective of this study was to determine the role of the percentage of people over age 65, income level and percentage of homes without heating in the analysis of the impact of cold waves on daily mortality between January 1, 2010 and December 31, 2013 in different districts of the municipality of Madrid. We calculated Relative Risks (RR) and Attributable Risks (RA) for each of 17 districts to determine correlations between the effect of cold waves and daily mortality due to natural causes (CIEX: A00-R99) using Generalized Linear Models (GLM) of the Poisson family (link log). The pattern of risks obtained by district was analyzed using binomial family models (link logit), considering socioeconomic and demographic variables. In terms of results, an impact of cold on mortality was detected in 9 of the 17 districts analyzed. The analysis of risk patterns revealed that the probability of detecting an impact in a district increases in a statistically significant way (p-value <0.05) with a higher percentage of homes without heating systems and a higher percentage of population over age 65. The results obtained identify the factors that should be considered in public health policies that target the district level to reduce the impact of cold waves.

Direct determination of verapamil in urine and serum samples by micellar liquid chromatography and fluorescence detection.

Verapamil, a calcium channel antagonist, is one of the most commonly prescribed drugs in the treatment of hypertension. In this work, it was determined in serum and urine samples by a sensitive and precise chromatographic procedure without any pre-treatment step in a C18 column using a micellar mobile phase of 0.15M sodium dodecyl sulfate and 5% pentanol at pH 7. Fluorescence detection set at 230 nm (excitation) and 312 nm (emission) was used. Verapamil is eluted at 12.5 min with no interference by the protein band or endogenous compounds. Linearities (r > 0.998), as well as intra- and inter-day precision, were studied in the validation of the method. LODs were also calculated to be 11.0, 18.5 and 20.2 ng/mL in micellar solution, serum and urine, respectively. Recoveries in the biological matrices were in the 97-99% range. Drug excretion in urine was studied in a volunteer receiving treatment for hypertension, and verapamil, as an unchanged drug, was separated from other metabolites. The procedure developed can be useful in the field of toxicology and clinical analysis.

Micellar liquid chromatographic determination of five antianginals in pharmaceuticals.

A procedure was developed for the determination of five antianginals (diltiazem, nadolol, nifedipine, propranolol and verapamil), using hybrid micellar mobile phases of sodium dodecyl sulphate (SDS) and pentanol, a C18 column and UV detection. All possible combinations of antianginals were resolved and determined using a mobile phase of 0.05 M SDS-5% pentanol with an analysis time of 9 min. Repeatabilities and intermediate precision were evaluated at four different drug concentrations in the 2-20 microg/ml (n=5) range. Limits of detection were in the range 0.028 microg/ml for diltiazem and 0.130 microg/ml for verapamil. The range of the limit of quantitation was from 0.092 to 0.431 microg/ml for the same compounds. Antianginal drugs were studied in pharmaceuticals with no interference from related compounds. The results of the analyses of pharmaceuticals formulations were in agreement with the declared compositions.

Assessment of resting energy expenditure in pediatric mitochondrial diseases with indirect calorimetry.

BACKGROUND & AIMS: Mitochondrial diseases (MD) are the most frequent inborn errors of metabolism. In affected tissues, MD can alter cellular oxygen consumption rate leading to potential decreases in whole-body resting energy expenditure (REE), but data on pediatric children are absent. We determined, using indirect calorimetry (IC), whole-body oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory quotient (RQ) and REE in pediatric patients with MD and healthy controls. Another goal was to assess the accuracy of available predictive equations for REE estimation in this patient population. METHODS: IC data were obtained under fasting and resting conditions in 20 MD patients and 27 age and gender-matched healthy peers. We determined the agreement between REE measured with IC and REE estimated with Schofield weight and FAO/WHO/UNU equations. RESULTS: Mean values of VO2, VCO2 (mL·min-1·kg-1) or RQ did not differ significantly between patients and controls (P = 0.085, P = 0.055 and P = 0.626 respectively). Accordingly, no significant differences (P = 0.086) were found for REE (kcal·day-1 kg-1) either. On the other hand, although we found no significant differences between IC-measured REE and Schofield or FAO/WHO/UNU-estimated REE, Bland-Altman analysis revealed wide limits of agreement and there were some important individual differences between IC and equation-derived REE. CONCLUSIONS: VO2, VCO2, RQ and REE are not significantly altered in pediatric patients with MD compared with healthy controls. The energy demands of pediatric patients with MD should be determined based on IC data in order to provide the best possible personalized nutritional management for these children.

Rapid determination of acetaminophen in physiological fluids by liquid chromatography using SDS mobile phase and ED detection.

Acetaminophen is determined in serum and urine samples by a rapid, sensitive, and precise chromatographic method without any pretreatment step in a C18 column using a pure micellar mobile phase of 0.02M sodium dodecyl sulfate at pH 7. Acetaminophen is eluted in less than 5 min with no interference of the protein band. The use of electrochemical and UV detection is compared. Linearities (r > 0.999), as well as intra- and interday precision, are studied in the validation of the method. Limits of detection (LOD) are also calculated to be 0.56, 0.83, and 0.74 ng/mL in micellar solution, serum, and urine using electrochemical detection. The developed micellar liquid chromatographic method is useful for the quantitation of acetaminophen in serum and urine. Recoveries in the biological matrices are in the 98-107% range and results are compared with those obtained using a reference method. Drug excretion (in urine) and serum distribution are studied in several healthy volunteers, and no interference from metabolites is found. The developed procedure can be applied in routine analyses, toxicology, and therapeutic monitoring.

Progression of natural immunity during one-year treatment of residual disease in neuroblastoma patients with high doses of interleukin-2 after autologous bone marrow transplantation.

The aim of this work was to monitor the functional and phenotypic variations of natural killer (NK) cells in seven children with stage IV neuroblastoma (NB) treated with recurrent 5-day cycles of interleukin-2 (IL-2) at a dose of 18 x 10(6) IU/m2/d by continuous intravenous infusion. All patients who entered the study had no detectable disease after hematologic recovery from intensive chemotherapy and autologous bone marrow transplantation (ABMT). To evaluate the effect of this treatment on tumor relapse, IL-2 immunotherapy was adjusted to maintain levels of NK activity above those of age-matched controls (threshold of 40 lytic units [LU]/10(9) mononuclear cells) during a 1-year period since hematologic recovery of ABMT. The levels of NK and endogenous lymphokine-activated killer (eLAK) cell cytotoxic activities, as well as phenotype-differentiated lymphocyte counts, were determined from patients' freshly isolated peripheral blood mononuclear cells (MNC). Data were analyzed at different points between each cycle of IL-2, and before and 36 hours after each infusion. NK and eLAK activities significantly increased in response to IL-2. Both cytotoxic parameters correlated with the serum levels of the soluble IL-2 receptor (sIL-2R). IL-2 increased the amounts of NK and T cell subsets but not of B cells. The effects of IL-2 were time-dependent. Early cycles of IL-2 preferentially increased cell numbers, especially of cells bearing a CD3-/CD16-/CD56+bright and CD8+dim phenotype. Conversely, late courses promoted higher cytotoxic effects but with a smaller increase in NK and T cell counts; the main NK subset became CD16+, and CD8+dim cells remained a minor subset. It is worthy to note that the patient who relapsed after completing immunotherapy showed only a slight increase of the NK subset in response to IL-2. These results show the feasibility of sustaining an increased NK activity during 1 year after ABMT in children with advanced neuroblastoma and suggest the occurrence of changes in the functional and phenotypic characteristics of the NK cells generated throughout the 1-year treatment.

Micellar liquid chromatography determination of B vitamins with direct injection and ultraviolet absorbance detection.

A micellar reversed-phase liquid chromatographic procedure was developed for the control of five water-soluble vitamins, B (nicotinamide), B1 (thiamine), B2 (riboflavin), B6 (pyridoxine and pyridoxamine), in multivitamin pharmaceutical formulations (capsules, pills and syrups). Optimization procedure includes studies about the composition of the mobile phase (sodium dodecyl sulphate and the modifiers propanol, butanol or pentanol), flow-rate and temperature. Chromatographic analysis of all vitamins was carried out using a single mobile phase of 0.1 M SDS-4% (v/v) pentanol at pH 3, in a C18 column in isocratic mode, and UV-detection at 270, 290 and 325 nm. The flow-rates selected were 1.0 ml/min in the interval 0 to 6 min, and 2.0 ml/min until the end of the chromatogram and temperature was 45 degrees C. In the micellar liquid chromatographic system, the samples were injected without pretreatment, and the analysis time was below 12 min. Repeatabilities and intermediate precision were achieved according to ICH, and were below 5%. When the method is applied to real samples, the amount found with respect to the declared compositions were within the 91-105% range. These results were similar to those obtained with a conventional 60:40 (v/v) methanol-water mixture for some of the vitamins, but with the advantage of use a single mobile phase for the analyses of the five vitamins, with direct injection of the samples and reduced toxicity, flammability, environmental impact and cost of the micellar-pentanol solutions.

Interleukin-2 in neuroblastoma: clinical perspectives based on biological studies.

Stage IV neuroblastoma (NB) is a disease with a poor prognosis. Chemotherapeutical intensification and hematological rescue with autologous bone marrow transplantation (ABMT) achieve some complete remissions (CR), but most patients relapse during the first year. Immunotherapy could be an alternative in this situation of high risk of relapse due to residual disease and ABMT-related immunodepression. Ten stage IV NB patients in CR or very good partial remission have been treated with recurrent 5-day cycles of high doses of Interleukin-2 (IL2) after ABMT throughout one year (usually 5-6 cycles). Natural killer (NK) and lymphokine-activated killer (LAK) cytotoxic activities, as well as phenotype and number of circulating NK cells were determined, before and after each course of IL2 treatment. The effects promoted by IL2 varied during treatment: early cycles of IL2 induced a great extent of cell expansion, mainly on CD3-/CD16-/CD56+bright and CD8+dim cell phenotypes; conversely, late courses of IL2 promoted higher NK cytotoxic activity but a lesser increase on circulating NK cells. The induction of LAK activity did not significantly differ from early and late IL2 treatments. Clinical results are still inconclusive due to the small number of patients. The median follow-up of patients treated with IL2 is 24 months and the disease free survival (DFS) probability is 0.80 +/- 0.12 vs 0.16 +/- 0.15 from a historical control with identical treatment, but in the absence of IL2 treatment (p < 0.005). IL2 treatment-related toxicity was mild and no interruption of the treatment was required. Extremely accurate hydric control was carried out to avoid, as much as possible, the consequences of vascular leak syndrome, one of the most important toxic effects of IL2 treatment. The results presented here suggest an evolution of NK activity during IL2 treatment after ABMT, which should be taken into account for the designing of new immunotherapeutical protocols and opens a promising perspective in treatment of stage IV neuroblastoma.

Micellar liquid chromatography determination of some biogenic amines with electrochemical detection.

A simple and reliable liquid chromatographic procedure is successfully applied to the simultaneous determination of the biogenic amines, dopamine, serotonin, their metabolites (homovalinic acid (HVA) and hydroxyindoleacetic acid (HIAA)) as well as tyramine in serum samples. After an optimization procedure using a C18 column, the mobile phase selected was 0.15 M sodium dodecyl sulfate buffered at pH 3, in which the serum samples were directly injected and the analysis time for the five substances was less than 12 min. The use of electrochemical (ED) and ultraviolet (UV) detection was compared. The limits of detection of the biogenic amines studied were drastically improved using ED detection. Repeatability and intermediate precision were tested at three different concentrations and the relative standard deviations were below 1.5% for most assays. Finally, the method was successfully applied to the determination of biogenic amines in serum samples.

[Cardiac rhabdomyosarcoma. Its echographic diagnosis]. / Rabdomiosarcoma cardíaco. Diagnóstico ecocardiográfico.

We report a case of cardiac rhabdomyosarcoma whose initial clinical features were fever and palpitations due to documented ventricular tachycardia. Sequential two-dimensional echocardiographic studies pointed out the presumed diagnosis, showing intracavitary masses at multiple sites appearing within a short period of time. The postmortem examination confirmed the diagnosis of rhabdomyosarcoma.

[Primary care physicians' and patients' degree of satisfaction with a new respiratory medicine health care program]. / Grado de satisfacción de médicos y pacientes en atención primaria con un nuevo esquema asistencial neumológico.

BACKGROUND: No ideal model for coordinating primary care and specialized respiratory medicine has been established. OBJECTIVE: To evaluate primary care physicians' and patients' degree of satisfaction with a new program for coordinating respiratory medicine and primary care. METHOD: A questionnaire survey of the level of satisfaction with a program combining consultation and direct patient care. The study was carried out at a primary care facility whose staff comprised 31 general practitioners. The respiratory medicine staff consisted of one physician and two nurses from the reference hospital. A questionnaire to determine the physicians' and patients' satisfaction with the program asked for a) overall evaluation on a scale of 0 to 10; b) evaluation on a scale naming five levels from "very bad" to "very good", and c) comparison of the new program with previous ones. RESULTS: One thousand one hundred seventy patients were seen in 12 months; 663 (57%) received a first visit, 400 (34%) received a second visit, and 107 (9%) received emergency care. The level of satisfaction was 7.8 (1.2) among physicians and 8.7 (1.5) among patients (p = 0.030); 97% of the physicians and 94% of the patients described the program as "very good" or "good". According to 100% of the physicians and 64% of the patients, the new program was better than the old one (p = 0.110). CONCLUSIONS: The coordinated care plan proposed is accepted by most physicians and patients and uses primary respiratory medicine resources more efficiently.

[Septic arthritis due to Streptococcus bovis]. / Artritis séptica por Streptococcus bovis.

A 47-year-old man presented with arthritis of the right shoulder and spondylodiscitis by Streptococcus bovis. This microorganism is a frequent cause of endocarditis and has been associated with gastrointestinal neoplasm, mainly carcinoma of the colon; however up to the present it had not been described as an causal agent of septic arthritis. The studies carried out on the patient permitted the exclusion of the existence of a digestive neoplasm and endocarditis. Despite a prolonged evolution prior to treatment with elevated doses of penicillin G and not requiring surgical drainage, the evolution was good and no destructive lesions were produced in the shoulder joint. Hematogenous infections (in this case septic arthritis) by Streptococcus bovis may present in patients without gastrointestinal diseases or endocarditis, possibly have a low damage to skeletal structures and respond adequately to conventional treatment with penicillin G.

Optimization by factorial design of a capillary zone electrophoresis method for the simultaneous separation of antihistamines.

A 3(2) full factorial design was used to optimize the experimental conditions of a capillary zone electrophoresis method aimed at achieving simultaneous separation and quantification of the antihistamines brompheniramine, chlorpheniramine, cyproheptadine, diphenhydramine, doxylamine, hydroxyzine, and loratadine according to their therapeutic group. A statistical program, SPSS, was used to calculate the mathematical model with which to obtain the response surface. Critical parameters such as pH and applied voltage were studied to evaluate their effect on resolution and on efficiency. Optimum separation conditions were phosphate buffer pH 2.0, 5kV, and 2psis(-1) at 214nm. The analysis time was below 9min and the theoretical plates were between 6000 and 63,000N. Calibration curves were prepared for the antihistamines. The limits of detection were 4-14ngmL(-1), which allow their quantification in pharmaceuticals. The RSD% of each antihistamine was fairly good. Up to seven antihistamines belonging to the antihistaminic H(1)-receptor group were separated in the same electropherogram. The proposed method was then applied to the determination of antihistamines in pharmaceutical, urine, and serum samples with recoveries in agreement with the stated contents.

Differential effect of cryopreservation on natural killer cell and lymphokine-activated killer cell activities.

The use of lymphokine-activated killer (LAK) cell therapy in delayed treatment requires the use of cryopreserved effector cells. The purpose of this study was to determine the optimal cryopreservation protocol for the maintenance of cytotoxic activity in mononuclear cells (MNCs). MNCs were cryopreserved with dimethyl sulfoxide or 1,2-propanediol before and after 3 days of culture with recombinant interleukin 2. The effects of cryopreservation on cell recovery, LAK cell and natural killer (NK) cell cytotoxic activities, and surface antigen markers were studied. Recovery of nonactivated MNCs was higher with 1,2-propanediol than with dimethyl sulfoxide (p < 0.05). Cytotoxic activities, measured with a 51Cr release assay, significantly decreased after thawing, on both activated cells (76.3%; range, 35.8-92.2%) and fresh cells (54.6%; range, 17.5-75.4%). A 6-day kinetic test was used to compare the cytotoxic activity of cryopreserved and fresh cells. The results showed different patterns for NK cells (cryopreserved cells had lower levels of activity than fresh cells) and LAK cells (cryopreserved cells had higher levels of activity than fresh cells). Phenotype changes of effector cells in culture, with and without cryopreservation, were monitored by flow cytometry using monoclonal antibodies. These results were compared with changes in the cytotoxicity of cells with and without cryopreservation. After thawing, there was a decrease in MNCs expressing CD14 and CD56. Recovery of the CD56 marker correlates with increased cytotoxic activity. Despite some loss of NK cell activity, it is concluded that MNCs may be successfully cryopreserved before their use in immunotherapeutic treatment.