Search PubMed⌕ Search

Biomedical subjects

J Segura

Publications and source records attributed to J Segura.

At least 199 records · Page 11Linked to original sources

Applications of gas chromatography and mass spectrometry in neurochemical studies: determination of indole amine profiles at the picogram level.

Work is presented on the application of sensitive and specific analytical methods for the simultaneous assay of tryptophan and its indolic metabolites (5-hydroxytryptophan, serotonin, 5-hydroxy-indole-acetic acid, tryptamine and indoleacetic acid). Due to their small concentrations in selected areas of the central nervous system, suitable derivatives have been prepared for separation by Gas Chromatography (GC) and detection by electron capture (ECD). Carboxylic acid groups have been methylated with BCl3-methanol and phenolic and amine groups have been acylated to pentafluoropropionyl derivatives. This type of derivatives allow a detectability limit of 5 picograms (5 x 10(-12) gr) if the corresponding reaction kinetics and yields are properly optimized. Response curves are presented. Identifications have been obtained by combined GC-MS and by the use of Kovats indeces in two GC stationary phases. The GC separation of the six compounds indicated above can be performed in less than 5 minutes with quantitative reproducibility. This work opens the possibility of performing comparative studies ("screening") of various physiological and pathological conditions by detecting any changes in the profile representative of a whole metabolic pathway, such as that of the indolic compounds in this case.

Chromatography, Gas↗

Percutaneous interventions on severe coarctation of the aorta: a 21-year experience.

Different percutaneous interventions can be used to treat coarctation of the aorta. However, a great amount of information is still needed regarding the long-term course. This article reviews our experience spanning 21 years in the percutaneous treatment of aortic coarctation. Four different conditions for treatment were considered. The first condition 1 (group 1) was balloon angioplasty in neonates and infants with untractable heart failure (n = 54; mean age, 1.2 +/- 1.4 months). After balloon angioplasty, most infants sustained significant clinical improvement. However, 9 patients died in the hospital (17%). As a result, we monitored the course of the 45 survivors during a mean period of 10 +/- 6 years (range, 1-19). During this follow-up period, 17 patients needed a single additional intervention on coarctation (8 underwent surgery and 9 were treated percutaneously). After this second treatment, 11 patients needed one or more further interventions. The actuarial survival probability was 83% at 19 years, with 43% of patients remaining surgery free and 23% reintervention free. The second condition (group 2) was balloon angioplasty in children and adults with coarctation of the aorta before the stenting era (n = 28; mean age, 13 +/- 8 years). After treatment, serial hemodynamic and angiographic studies were performed. The long-term relief was higher in patients with a discrete type of coarctation. The rate of late aneurysm formation was 6%. The third condition (group 3) was stent palliation in infants and children younger than the age of 6 years (n = 17; mean age, 2.1 +/- 1.7 years). The stent was implanted for nondilatable stenoses, as a nondefinitive procedure. Stent palliation provides complete initial relief in hypoplastic coarctations or life-threatening conditions. However, further stent expansion is required to ensure adequate stent diameter in the growing aortic wall. In addition, late intrastent proliferation may occur in small stent diameters (18%) and aneurysm formation in hypoplastic coarctations (18%). Both late complications can be managed percutaneously. The fourth condition (group 4) was stent repair of severe aortic coarctation in adults, adolescents, and children older than the age of 6 years (n = 73; mean age, 20 +/- 12 years). Significant relief was observed after treatment, which persisted at follow-up. One patient died at treatment (1.3%). After a mean follow-up of 5 +/- 3 years, all 72 patients remained symptom free and no restenosis or late aneurysm were detected.

Adolescent↗

[Influence of burnout on pharmaceutical expediture among primary care physicians].

OBJECTIVE: To determine the influence of various factors related to primary care physicians and their level of burnout on pharmaceutical expenditure per policy-holder (PEP-H). METHOD: We performed a cross-sectional study of 220 primary care physicians in the province of Barcelona in 2000. A structured and validated questionnaire was administered through direct interview. The questionnaire was divided into two parts: general sociodemographic and professional data, and the Maslach Burnout Inventory (MBI). At the same time, data on primary care physicians' pharmaceutical expenditure was collected from their corresponding health districts. RESULTS: The mean pharmaceutical expenditure was 264,627.22 euros (95% CI, 252,669.82-276,584.63) and the PEP-H was 152,36 euros (95% CI, 145,73-158,99). The variables associated with greater PEP-H were older age of the primary care physician, greater number of years of service in primary care, permanent work contract, primary care physicians who worked in several centers at the same time, primary care physicians who did not work in accredited teaching centers, urban centers, and high levels of emotional exhaustion in the MBI. CONCLUSIONS: Primary care physicians are subject to various degrees of stress in their daily work. Accumulation of these psychological stressors provokes emotional exhaustion, which complicates decision making when writing prescriptions and tends to lead to a vicious circle. Thus, primary care physicians with a high level of burnout could, on a variety of occasions, compensate for this lack of psychological resources by less efficient management of pharmaceutical expenditure when prescribing.

Burnout, Professional↗

Microalbuminuria.

The capacity of microalbuminuria to predict an increased cardiovascular and renal risk is well established in diabetic patients, as well as in essential hypertensive patients and in general population. Detection of microalbuminuria could then be relevant to select specific therapeutic strategies for reducing or preventing cardiovascular events in patients with essential hypertension. Microalbuminuria is detectable in almost 40% of the population with established hypertension, particularly in those patients not controlled satisfactorily with medical therapy. Albuminuria may represent a marker of renal damage and cardiovascular risk in essential hypertension. Microalbuminuria seems to represent a simple and reproducible method to better define cardiovascular risk profile in the hypertensive patient and to stratify the prognosis in relation to renal and cardiovascular risk. ACE-inhibitors and more recently angiotensin II receptor antagonists seem to exhibit a more market capacity to reduce microalbuminuria in patients with essential hypertension or diabetes mellitus. Determination of this parameter in daily clinical practice could facilitate the stratification of risk as well as the choice of therapy in essential hypertensive patients.

Albuminuria↗

Comprehensive screening procedure for detection of stimulants, narcotics, adrenergic drugs, and their metabolites in human urine.

An analytical procedure for the detection of stimulants, narcotics, beta-blockers, beta-agonists, and many of their metabolites in urine using a solid-phase extraction procedure and gas chromatography-mass spectrometry (GC-MS) is described. These substances have been specifically banned by the Medical Commission of the International Olympic Committee (IOC) in order to prevent their abuse in sports. Urine samples are submitted to an enzymatic hydrolysis (beta-glucuronidase arylsulfatase) and extracted by means of Bond-Elut Certify columns. The residues are then selectively derivatized with N-methyl-N-trimethylsilyl-trifluoroacetamide (MSTFA), which enables the formation of trimethylsilyl derivatives of hydroxyl, acidic, and phenolic groups, and N-methyl-bis-trifluoroacetamide (MBTFA), which enables the formation of trifluoroacetamide derivatives of primary and secondary amines. A GC-MS system working in scan mode is sensitive and specific enough to detect and identify approximately 100 compounds and metabolites in urine for at least 24 h after the administration of doses typically encountered in therapeutics. Detection in selected ion monitoring mode is needed for the determination of beta-agonist agents. The method was successfully used in doping control of urine samples during the 25th Olympic Games, July 1992, in Barcelona, Spain.

Adrenergic Agents↗

Cross-reactivity of stimulants found in sports drug testing by two fluorescence polarization immunoassays.

We investigated the usefulness of immunological methods for presumptive detection of stimulants found in sports drug testing. The ingestion of substances that show no cross-reactivity in tests commercially available for the detection of amphetamines can produce positive results in the urine. Human metabolism contributes to the positive results of some urine samples when the parent compound does not cross-react with the antibodies of the assay. Urine samples from healthy volunteers given stimulants were tested by chromatographic methods and by two different fluorescence polarization immunoassays (FPIA) from Abbott Laboratories for the analysis of amphetamines. According to the results obtained, we classified stimulants into four groups: detectable stimulants that gave rise to amphetamine by human metabolism (group 1); detectable ephedrines and related compounds, appearing in the urine either as parent compounds or originated by metabolism (group 2); detectable stimulants that displayed actual cross-reactivity with amphetamine tests (group 3); and stimulants not detected by FPIA (group 4). Most of the true doping cases due to the ingestion of stimulants may be detected by FPIA. The specificity of the results may be increased by combining immunological assays with different antibodies.

Amphetamine↗

Survey on drugs-of-abuse testing in the European Union.

A survey on the quality of drugs-of-abuse testing in European laboratories was performed in 1993 (Part I) and 1994 (Part II). A total of 195 laboratories participated in Part I and 228 in Part II. There were 154 repeater laboratories. In each part of the survey, six urine samples were sent for analysis under routine conditions. A set of reference materials, including deuterated drug-standard solutions, was provided in Part II of the survey for optimization of analytical procedures. Screening for groups of substances was mainly performed by immunological techniques. Rates of false-positive (FP) results were 0 and 0.5%, respectively, in Parts I and II, and rates of false-negative (FN) results were 7.7% in Part I and 3.4% in Part II. Identification and quantitation of specific substances was mainly carried out by chromatographic methods, particularly gas chromatography coupled to mass spectrometry. Application of chromatographic methods showed a lack of sensitivity (14.9% and 16.7% FN in Parts I and II, respectively) and a lack of specificity (0.8% FP in Part I versus 1.1% in Part II). Repeater laboratories improved their results (17.4% FN in Part I versus 14.2% Part II). The improvement of repeater laboratories emphasizes the need of external quality control programs. The experience is being used as a basis for a recommendation on drug-testing guidelines by a group of European toxicologists.

Clinical Laboratory Techniques↗

Screening procedure for beta-adrenergic drugs in sports drug testing by immunological methods.

A systematic study of the cross-reactivities of beta-adrenergic agonists and antagonists and their metabolites with an ELISA test designed to detect terbutaline and other beta 2-agonists has been performed in order to evaluate the applicability of this immunological test as screening method in routine human sports drug testing. Concentration response curves were calculated. IC50 values from 1.7 to 21.5 ng/mL were obtained for beta 2-agonists, and values from 3.1 to 520.8 ng/mL were obtained for most of the beta-blockers. The highest cross-reactivity was mainly depending on the amino substituent of the molecules although the structure of the aromatic ring was also important. Minor changes in the aromatic ring, such as 4-hydroxylation for propranolol, did not largely influence the IC50 value. Distribution of control activities (percentage of optical density as compared with a blank sample) of urines obtained in controlled excretion studies (70 samples) and urines collected after competition in sports in which beta-blockers are recommended to be tested (147 samples) showed a very small overlapping between the subpopulations of positive and negative samples. Cutoff values of 45 or 60% control activity were proposed for routine analysis. Sensitivity and specificity values of 92.8 and 98.8%, respectively (cutoff 45%), or 98.2 and 95.0%, respectively (cutoff 60%), were obtained. Because the known prevalence of positive results of beta-blockers and beta 2-agonists in the target population was very low, the predicted percentage of presumptive positive cases that would need further confirmation by gas chromatography-mass spectrometry was also low, accounting for a 1.48 and 5.28% (for the cutoffs of 45 and 60%, respectively) of the total number of samples to be screened by the presented ELISA test. Thus, in terms of time and cost savings, the ELISA test is a powerful tool for the purpose of screening for beta-adrenergic drugs in human urine.

Adrenergic beta-Agonists↗