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J Segura

Publications and source records attributed to J Segura.

At least 19 recordsLinked to original sources
PubMed2006

Effect of physical fitness and endurance exercise on indirect biomarkers of recombinant erythropoietin misuse.

Erythropoietin (EPO) and soluble transferrin receptor (sTfR) in serum have been proposed as indirect biomarkers for the detection of recombinant human EPO (rhEPO) misuse in sport. The purpose of the present study was to investigate the influence of different levels of physical fitness, sport, different training workload during the sport season, and endurance exercise in the concentrations of these serum biomarkers for their application into mathematical models to indirectly detect rhEPO misuse. Serum EPO and sTfR concentrations were measured in 96 elite athletes of various sports along the sport season, in 21 recreational athletes at baseline (non exercising) conditions and in 129 other recreational athletes before and after long-distance races (10 and 21 km). In elite athletes, hemoglobin concentrations and percentage of reticulocytes were also measured, and indirect detection models applied. In recreational athletes, for EPO and sTfR, significant differences were only observed after the 21-km race. In baseline conditions, no differences were observed between recreational and elite athletes for EPO and sTfR. In elite athletes, individual EPO and sTfR concentrations slightly changed over the sport season, with coefficients of variation (CV) of 26.1 % and 9.0 %, respectively. Hemoglobin and reticulocytes were influenced by sport, but their individual variation over the sport season was not physiologically relevant (CV of 3.7 % and 21.3 %, respectively). When applying mathematical models for detection of rhEPO administration, only one elite athlete obtained an individual model score above the established thresholds. Physical fitness, sport and different training workload during the sport season had no substantial effect on serum EPO and sTfR concentrations, except in recreational athletes after a 21-km race. Variations observed in mathematical models to detect EPO administration were mainly due to fluctuation in hemoglobin concentrations, commonly observed in elite athletes.

Adult↗
PubMed2006

Stability studies of amphetamine and ephedrine derivatives in urine.

Knowledge of the stability of drugs in biological specimens is a critical consideration for the interpretation of analytical results. Identification of proper storage conditions has been a matter of concern for most toxicology laboratories (both clinical and forensic), and the stability of drugs of abuse has been extensively studied. This concern should be extended to other areas of analytical chemistry like antidoping control. In this work, the stability of ephedrine derivatives (ephedrine, norephedrine, methylephedrine, pseudoephedrine, and norpseudoephedrine), and amphetamine derivatives (amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxymethamphetamine (MDMA)) in urine has been studied. Spiked urine samples were prepared for stability testing. Urine samples were quantified by GC/NPD or GC/MS. The homogeneity of each batch of sample was verified before starting the stability study. The stability of analytes was evaluated in sterilized and non-sterilized urine samples at different storage conditions. For long-term stability testing, analyte concentration in urine stored at 4 degrees C and -20 degrees C was determined at different time intervals for 24 months for sterile urine samples, and for 6 months for non-sterile samples. For short-term stability testing, analyte concentration was evaluated in liquid urine stored at 37 degrees C for 7 days. The effect of repeated freezing (at -20 degrees C) and thawing (at room temperature) was also studied in sterile urine for up to three cycles. No significant loss of the analytes under study was observed at any of the investigated conditions. These results show the feasibility of preparing reference materials containing ephedrine and amphetamine derivatives to be used for quality control purposes.

Amphetamine↗
PubMed2006

Effect of physical fitness and endurance exercise on indirect biomarkers of recombinant growth hormone misuse: insulin-like growth factor I and procollagen type III peptide.

Serum insulin-like growth factor-I (IGF-I) and procollagen type III peptide (P-III-P) have been proposed as indirect biomarkers of rhGH misuse in sports. The purpose of the present study was to investigate concentrations of these biomarkers in athletes at different levels of physical fitness and endurance exercise. Serum total IGF-I and P-III-P were measured in 96 elite athletes of various sports along the training season; in 21 recreational athletes at baseline non-exercising conditions and in another 129 recreational athletes before and after long-distance races (10 and 21 km). No differences were evidenced for IGF-I concentrations, but statistically higher values of serum P-III-P were found in elite athletes compared to recreational ones. Among elite athletes, the specific sport did not affect serum IGF-I. However, P-III-P was statistically higher in the sport performed by the youngest athletes (rhythmic gymnastics), even after correction of the logarithm of the concentration by the reciprocal of age. Over the training season, the within-athlete variabilities of IGF-I and P-III-P in elite athletes were low (22.8 % and 21.7 %, respectively). Recreational athletes taking part in a 21 km competition race showed a significant increase in serum values of IGF-I and P-III-P immediately after the event. Exercise workload and age had a significant effect on serum concentration of P-III-P, while age alone affected IGF-I serum concentrations. Therefore, athlete's reference concentration ranges for doping detection should include subjects from as many different ages and sports as possible.

Adolescent↗
PubMed2006

Stability studies of testosterone and epitestosterone glucuronides in urine.

The stability of testosterone glucuronide (TG), epitestosterone glucuronide (EG) and the T/E ratio in urine has been studied. Samples were analyzed by gas chromatography coupled to mass spectrometry (GC/MS). Urine samples were submitted to a solid-liquid cleanup followed by extraction of unconjugated testosterone (T) and epitestosterone (E) with tert-butyl methyl ether (free fraction). The remaining aqueous phase was hydrolyzed with beta-glucuronidase and extracted at alkaline pH with n-pentane. Analytes were analyzed by GC/MS as their enol-trimethylsilyl (TMS) derivatives. The urine for stability testing was obtained from an excretion study after the administration of T to healthy volunteers. The homogeneity of the sample was verified before starting the stability study. The stability of TG and EG was evaluated at different storage conditions. For long-term stability testing, analyte concentration in urine stored at 4 degrees C and -20 degrees C was determined at different time intervals for 22 months. For short-term stability testing, analyte concentration was evaluated in urine stored at 37 degrees C for 3 and 7 days. The effect of repeated freezing (at -20 degrees C) and thawing (at room temperature) was studied for up to three cycles. Data obtained in this work demonstrated the stability of TG, EG and the T/E ratio in sterilized urine samples stored at 4 and -20 degrees C for 22 months and after going through repeated freeze/thaw cycles. Decreases in concentration were observed after 7 days of storage at 37 degrees C due to the partial cleavage of the glucuronide conjugates; however, the T/E ratio was not affected. These results show the feasibility of preparing reference materials containing TG and EG to be used for quality control purposes.

Doping in Sports↗
PubMed2006

[Tansitional vesical cell carcinoma metastatizing to the sphenoid sinus].

Secundary tumors of the paranasal sinus are very uncommon with only one hundred cases reported in the literature up to 2001. The commonest site of the primary tumor is the kidney. The maxillary sinus is most often involved. The Sphenoid sinus is the rarest site. We report a rare case of metastasis to the sphenoid sinces from a transitional cell bladder tumor in a 69-year-old man who died after treatment with chemotherapy and we also review the liteature.

Aged↗
PubMed2005

Relationship between pharmacokinetic parameters of cyclosporin and the incidence of acute rejection after heart transplantation.

Despite two decades of use, there are limited data on the best way to monitor Cyclosporine (CsA) for heart transplantation. The aim of our study was to determine the relationships between pharmacokinetic parameters and clinical outcomes after heart transplantation and to evaluate the range of CsA trough levels provided the most effective protection against graft rejection. We retrospectively analyzed the clinical outcomes of all adult patients who received a heart transplant between January 1998 and February 2005. All had routine monitoring of CsA trough levels and scheduled endomyocardial biopsies. Rejection was defined as grade > or =3, based on International Society for Heart and Lung Transplantation (ISHLT) criteria. Follow-up period was 1 year. All patients were on CsA, corticosteroids, and azathioprine/mycophenolate mofetil with or without antilymphocyte induction (eight patients with basiliximab). Data were analyzed by unpaired Student t-test, Cox regression model, and ROC curve. Among 70 patients (60 men and 10 women) who entered the study, 34 (48.6%) had at least one acute rejection episode of grade > or =3 during the first posttransplant year. Mean CsA trough level (C(0)) measured at first week posttransplant was significantly lower in the rejection than the no-rejection group (125.17 +/- 56.9 ng/mL versus 169.33 +/- 48.27 ng/mL, P = .001). C(0) was the strongest predictor of acute graft rejection (P = .000, HR = .985.) The risk decreased by 1.5% for each unit increase of the C(0) value. ROC analysis showed that C(0) of 150 ng/mL provided the optimal cutoff. Patients with mean C(0) >150 ng/mL over the first week had less incidence of acute rejection than patients with levels <150 ng/mL (30.3% versus 64.9%) (P = .009, Cochran-Mantel-Haenszel test). In conclusion, our data suggest that in heart transplant patients it may be crucial to target early trough levels above 150 ng/mL during the first days postsurgery to avoid rejection.

Adolescent↗
PubMed2005

Ofuji papuloerythroderma evolving to cutaneous T-cell lymphoma.

Ofuji papuloerythroderma is an uncommon entity of unknown aetiology, characterized by a pruritic eruption of widespread, red-brown, flat papules that leads to spare skin folds. A number of cases have been described associated with tumour pathology, mainly cutaneous T-cell lymphomas. We report a new case of Ofuji papuloerythroderma evolving to cutaneous T-cell lymphoma in an 85-year-old woman who had been previously diagnosed with papuloerythroderma 7 years previously.

Aged↗
PubMed2005

Influence of chronic kidney disease development and renin-angiotensin system inhibition on cardiovascular prognosis.

Recently published guidelines recognize the relevance of the development of chronic kidney disease in the stratification of risk of the hypertensive patient. Adequate assessment of renal function, including estimation of glomerular filtration rate, is mandatory in order to ensure an adequate evaluation of global cardiovascular risk in the hypertensive patient. The presence of subtle elevations of serum creatinine concentrations is a potent predictor of a poor cardiovascular prognosis. Clustering of associated risk factors seems to justify the elevated cardiovascular risk observed in patients with essential hypertension and mild renal function derangement. Chronic kidney disease is associated with a significant increase in cardiovascular risk attributable to the simultaneous existence of other risk factors related to the metabolic syndrome. The inhibition of the effects of angiotensin II is necessary to ensure the best degree of renal protection. It has demonstrated to improve the long-term renal outcome of patients with nephrosclerosis and to reduce the appearance of cardiovascular complications in high risk patients The high prevalence of chronic kidney disease in the general and in the hypertensive populations forces the recognition of its relevance and the need for an integrative therapeutic approach to protect simultaneously renal and cardiovascular systems.

Angiotensin II↗
PubMed2005

Correlations of smoothness index and trough-to-peak ratio with left ventricular mass index changes induced by lercanidipine in hypertensive patients. A pilot trial.

AIM: The aim of this study was to determine the correlation of changes in left ventricular mass, with changes in office blood pressure (BP) and in 24-h ambulatory (ABP), with the trough-to-peak (T/P) ratio and with the smoothness index (SI), as induced by antihypertensive treatment with lercanidipine. METHODS: This was done through an observational, prospective, open, non-comparative, single centre, pilot study in patients naïve to antihypertensive therapy. All patients were treated with lercanidipine 10-20 mg/day plus hydrochlorothiazide 12.5-25 mg/day if treated BP exceeded an arbitrarily defined safety level (>160/100 mmHg) after 1 month on monotherapy. ABP monitoring was repeated after 1 month and after 6 months. Two-dimensional mode echocardiography was performed twice, at the beginning and end of the study. Seventeen patients were included in the final analysis (aged 45.8 +/- 10.7 years, 35% women). RESULTS: Treatment-induced changes in left ventricular mass index (LVMI) were not found to correlate neither with changes in office BP, with changes in ABP values, nor with T/P. However, a significant correlation was found between LVMI changes and SI at 6 months (r=0.50, P=0.039). CONCLUSION: The results of this study suggest that the SI has a higher predictive value, compared to other BP-derived parameters, for treatment-induced LVMI changes, in hypertensive patients treated with lercanidipine.

Adult↗
PubMed2004

Evaluation of immunoassays for the measurement of soluble transferrin receptor as an indirect biomarker of recombinant human erythropoietin misuse in sport.

Soluble transferrin receptor (sTfR) has been proposed as an indirect biomarker of the misuse of recombinant human erythropoietin in sport. An extended validation of four commercially available immunoassays for its measurement in serum is presented. Two ELISA techniques (ELISA1: Orion Diagnostica; ELISA2: R&D Systems), an immunoturbidimetric technique (Turbid: Roche Diagnostics), and a nephelometric technique (Nephel: Dade Behring) were investigated. Intra-laboratory precision better than 3% and correct accuracies were obtained for the Turbid and Nephel techniques using autoanalysers. Slightly worse precision (but always better than 11%) and correct accuracies were also obtained in almost all cases for the two ELISA techniques. Inter-laboratory results showed higher concordances for the ELISA procedures (intraclass correlation coefficients of 0.848 for ELISA1 and 0.973 for ELISA2 which was clearly better). Inter-technique correlations were good for the four techniques with lower dispersions found for the techniques using autoanalysers, i.e. Turbid and Nephel. While Turbid and ELISA1 results (expressed in mg/l) were comparable, results obtained with Nephel were approximately 2.7 times lower. The relationship between those three techniques was maintained when compared with ELISA2, which uses different units (nmol/l). We conclude that ELISA2 and Nephel in our hands were the most suitable techniques in terms of sensitivity, precision and accuracy, and adequacy of the calibration curve for the measurement of sTfR in real serum samples. Discrepancies observed in the results obtained with the different sTfR techniques showed that different reference standards were used and harmonization is recommended in order to obtain comparable results.

Biomarkers↗
PubMed2004

Reference materials for analytical toxicology including doping control: freeze-dried urine samples.

The feasibility of freeze-dried urine samples containing doping agents to be used in intercomparison exercises and/or as reference materials has been evaluated. Freeze-dried urine samples containing caffeine, ephedrine derivatives (ephedrine, methylephedrine, norephedrine, pseudoephedrine and norpseudoephedrine), amphetamine derivatives (amphetamine, metamphetamine, 3,4-methylenedioxyamphetamine and 3,4-methylenedioxymethamphetamine) and testosterone and epitestosterone glucuronides have been evaluated. For preparation of the samples, blank urines previously subjected to filtration for clarification were fortified with standard solutions of the corresponding compounds and filtered under sterile conditions. Some aliquots of the sterile liquid samples were used for homogeneity testing, others were stored at -80 degree C for reference purposes, and the rest were subjected to lyophilisation. Freeze-dried urine samples were stored at 4-8 degree C and their stability was assessed for a period up to 18 months. Results obtained showed minimal differences (lower than 5%) between lyophilised and non-lyophilised aliquots (stored at -80 degree C) at all time periods except for amphetamine (up to 18%) and norpseudoephedrine (up to 10%). Nevertheless, such differences remained constant over the entire period of study, indicating that the loss of analytes was due to the initial lyophilisation process. The loss of analytes in freeze-dried samples was due to their volatility. Furthermore, an increase in pH by 1 unit was observed following reconstitution of samples prepared from drug-free urine of commercial origin.

Amphetamine↗
PubMed2004

Recombinant erythropoietin and analogues: a challenge for doping control.

Erythropoietin (EPO) increases the number of circulating erythrocytes and thus muscle oxygenation. The availability of the recombinant protein (rEPO) has increased the risk of its illegal use in sports, its detection being a difficult challenge. Five different hematopoietic parameters were initially chosen as indirect markers of rEPO abuse: concentration of serum EPO, concentration of serum-soluble transferrin receptors (sTFr), hematocrit, percentage of reticulocytes, and percentage of macrocytes. New models considering only hemoglobin, serum EPO concentration, and percentage of reticulocytes are simpler and seem to be more sensitive when low doses of rEPO are used. A more direct method of urine analysis (isoelectrofocusing, double blotting, and chemiluminescent detection) based on the charge differences between rEPO and endogenous EPO, related to their carbohydrate composition, provides proof of rEPO use. Furthermore, this approach permits the detection of darbepoetin, a direct analogue of EPO also known as NESP ("new erythropoiesis stimulating protein"). Recently a protein conjugate, "synthetic erythropoiesis protein" (SEP), containing precision-length, monodisperse, negatively charged polymers instead of oligosaccharides has been synthesized. Finally, EPO-mimetics are molecules capable of acting as EPO in dimerizing the EPO receptor. Two kinds of EPO-mimetics have been described: peptides and nonpeptides. The enhancement of oxygen availability to muscles by rEPO, analogues, and mimetics constitutes one of the main challenges to doping control. Major steps have already been developed for detection ofrEPO and some analogues. In the near future, the transfection to an athlete's body of genes that code for erythropoietin might be an emerging doping issue, and sports authorities have incorporated "gene doping" among the prohibited practices.

Biomarkers↗
PubMed2004

Chronic kidney disease and global cardiovascular risk in essential hypertension.

Recently published guidelines recognize the relevance of the finding of chronic kidney disease (CKD) in the stratification of risk of the hypertensive patient. Determination of the presence of microalbuminuria and estimation of glomerular filtration rate are mandatory in order to ensure an adequate evaluation of global cardiovascular (CV) risk in the hypertensive patient. Indices of altered renal function (e.g. microalbuminuria, increased serum creatinine concentrations, decrease in estimated creatinine clearance or overt proteinuria) are independent predictors of CV morbidity and mortality. Clustering of associated risk factors seems to justify the elevated CV morbidity and mortality observed in patients with essential hypertension and mild alterations of renal function. The increased prevalence of CKD in the general and in the hypertensive populations forces the recognition of its relevance and the need for an integrative therapeutic approach to fully protect simultaneously renal and CV systems.

Adult↗
PubMed2003

Stability studies of selected doping agents in urine: caffeine.

The stability of caffeine in urine samples has been studied. A high-performance liquid chromatography (HPLC) method for the quantification of caffeine in urine samples was validated for that purpose. The method consists of a liquid-liquid extraction at alkaline pH with chloroform-2-propanol (9:1, v/v) with a salting out effect. 7-Ethyltheophylline was used as internal standard (ISTD). Analyses were performed with an Ultrasphere ODS C18 column using water/acetonitrile (90:10, v/v) as a mobile phase at a flow rate of 1 ml/min. Ultraviolet absorption at 280 nm was monitored. Extraction recoveries for caffeine and 7-ethyltheophylline were 81.4+/-6.0 and 87.3+/-5.7%, respectively. The calibration curves were demonstrated to be linear in the working range of 6-30 microg/ml (r2>0.990). The limit of detection and the limit of quantitation were estimated as 0.7 and 2.0 microg/ml, respectively. Precisions in the range of 1.5-9.2 and 4.1-5.8% were obtained in intra- and inter-assay studies, respectively, using control samples containing 10, 14 and 26 microg/ml of caffeine. Accuracies ranging from 2.9 to 7.4% for intra-assay experiments, and from 3.9 to 5.4% in inter-assay studies were obtained. Stability of caffeine in urine samples was evaluated after long- and short-term storage at different temperature conditions. The batches of spiked urine were submitted to sterilization by filtration. No adsorption of the analyte on filters was observed. Before starting stability studies, batches of reference materials were tested for homogeneity. For long-term stability testing, caffeine concentration in freeze-dried urine stored at 4 degrees C and in liquid urine samples stored at 4, -20, -40 and -80 degrees C was determined at several time intervals for 18 months. For short-term stability testing, caffeine concentration was evaluated in liquid urine stored at 37 degrees C for 7 days. The effect of repeated freezing (at -20 degrees C) and thawing was also studied for up to three cycles. The stability of caffeine was also evaluated in non-sterile samples stored at -20 degrees C for 18 months. No significant loss of the compound was observed at any of the investigated conditions.

Caffeine↗
PubMed2003

[Job satisfaction and burnout in general practitioners].

OBJECTIVE: To describe job satisfaction in general practitioners (GP) in the province of Barcelona, and to analyse its relationship with their job burnout, and social and professional characteristics. DESIGN: Transversal observational study.Setting. Province of Barcelona, Spain. PARTICIPANTS: 603 General Practitioners had participated in ninety three primary care centers. MEASUREMENT: Through a direct interview (individual or in group) a validated questionnaire was administered in three parts: general data (social, demographic and professional), job satisfaction (Font Roja-9 dimensions) and job burnout (Maslach Burnout Inventory-3 scales). RESULTS: The job satisfaction questionnaire (score ranging from 1-5) showed a global satisfaction level of 3.02 (95%CI, 2.98%-3.05%) and we obtained a 18% non response rate. There was a positive association between overall satisfaction and the following variables: less years working in primary health, working in centres providing instruction, and willingness to receive information from the survey. Low levels of satisfaction were associated to high scores in emotional exhaustion and depersonalisation scales, and low scores in personal accomplishment scale. CONCLUSIONS: Overall satisfaction has a medium score in the Font-Roja questionnaire. Age seems to lead to a significant tendency to decrease satisfaction as practitioners grow older. Job satisfaction and job burnout present a closely linked behaviour, inversely, as satisfaction increases when job burnout presents low scores.

Adult↗