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Biomedical subjects

J Segura

Publications and source records attributed to J Segura.

At least 91 records · Page 5Linked to original sources
PubMed1999

Quantitative aspects of drugs of abuse in urine samples: intercollaborative studies conducted in the European Union.

A description of a quantification performance by laboratories taking part in two intercollaborative studies (surveys 1 and 2) carried out in 1993 (n = 195) and 1994 (n = 228), respectively, on urine drug testing in the European Union is presented. The performance of laboratories that quantified at least one substance (33.8% and 34.6% out of the total laboratories in surveys 1 and 2, respectively) is reported as a function of the analytic technique applied for quantification, the number of parameters investigated, the precision and accuracy of results obtained, and the influence of availability of reference material, including deuterated drug-standard analogue solutions provided in survey 2. Quantification of different drugs of abuse was mainly carried out by gas chromatography coupled to mass spectrometry (63.1% of analyses in survey 1 vs. 68.6% in survey 2). It should be noted about the data obtained that the results for quantification were not particularly satisfactory in terms of precision and accuracy (CV mean = 62.8 in survey 1 and 50.4 in survey 2 and error % mean = 12.7 in survey 1 and 18.6 in survey 2). The provision of reference materials increased the number of substances quantified (45.3% in survey 1 vs. 51.8% in survey 2) and improved the performance (CV mean of matching laboratories when quantifying matching substances: 50.1% in survey 1 vs. 35.5% in survey 2). The impact of a "learning factor" (the opportunity to be challenged a second time and to correct past errors) and the influence of the provision of deuterated analogues in survey 2 was investigated in a population of repeater laboratories that quantified both in surveys 1 and 2 (55 vs. 63 laboratories, respectively). According to the European experience reported, it may be observed that laboratories able to afford quantitative analyses provided better overall analytic performance. This is probably because quantification implies some validation of the analytic procedure. Participation in interlaboratory comparison programs also aimed at assessing the performance of quantitative analyses should be considered a quality asset for laboratories involved in drug testing.

Data Collection↗
PubMed1999

Cardiovascular and neuroendocrine effects and pharmacokinetics of 3, 4-methylenedioxymethamphetamine in humans.

The cardiovascular and neuroendocrine effects and pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") were assessed in a double-blind, randomized, crossover, and controlled (placebo and amphetamine) clinical trial. Eight men with experience in the recreational use of MDMA participated in four 10-h experimental sessions with a 1-week washout period. Single oral doses of 125 mg and 75 mg of MDMA, 40 mg of amphetamine, and placebo were given. Both MDMA doses significantly increased blood pressure (increases of 40 mm Hg in systolic blood pressure), heart rate (increases of 30 beats/min), and pupillary diameter (mydriasis) as compared with placebo. Oral temperature did not show significant changes in any drug-active condition. Plasma cortisol levels showed a statistically significant increase after MDMA administration. Prolactin levels only increased after high dose of MDMA. Cmax values for 125-mg and 75-mg MDMA doses were 236.4 and 130.9 ng/ml, and Tmax was observed at 2.4 and 1.8 h, respectively. Elimination half-life was 8.6 h and 7.7 h for high and low MDMA doses, respectively. Amphetamine half-life was 15 h. Between 8 and 9% of the doses of MDMA appeared in plasma in the form of 3,4-methylenedioxyamphetamine. The important cardiovascular effects observed after MDMA administration in laboratory conditions at rest (increases of 40 mm Hg in systolic blood pressure and 30 beats/min in pulse rate) could be relevant in terms of toxicity in real-life conditions (e.g., crowded places and physical activity).

3,4-Methylenedioxyamphetamine↗
PubMed1998

Derivatization procedures for gas chromatographic-mass spectrometric determination of xenobiotics in biological samples, with special attention to drugs of abuse and doping agents.

The development of low cost MS detectors in recent years has promoted an important increase in the applicability of GC-MS system to analyze for the presence of foreign substances in the human body. Drugs and toxic agents are in vivo metabolized in such a way that more polar compounds are usually formed. Derivatization of these metabolites is often an unavoidable requirement for gas chromatographic analysis. Application of derivatization methods in recent years has been relevant, especially for silylation, acylation, alkylation and the formation of cyclic or diastereomeric derivatives. Given the relevance of drug of abuse testing in modern toxicology, main derivatization procedures for opiates, cocaine, cannabis, amphetamines, benzodiazepines and LSD have been reviewed. Papers describing the analyses of drugs of abuse in matrixes other than blood, such as hair or sweat, have received special attention. Advances in derivatization for sports drug testing have been particularly relevant for anabolic steroids, diuretics and corticosteroids. Among the several methodologies applied, the formation of trimethylsilyl, perfluoroacyl or methylated derivatives have proved to be both versatile and extensively used. Further advances in derivatization for GC-MS applications in clinical and forensic toxicology will depend on the one hand on the degree of further use of GC-MS for routine applications and, on the other hand, on the alternative progress made for developments in LC-MS or CE-MS. Last but not least, the appearance of comprehensive libraries in which reference spectra for different derivatives of many drugs and their metabolites are collected will have an important impact on the expansion of derivatization in GC-MS for toxicological applications.

Body Fluids↗
PubMed1998

Cocaine metabolism in humans after use of alcohol. Clinical and research implications.

The simultaneous administration of cocaine and alcohol implies a pharmacological interaction at pharmacodynamic and pharmacokinetic levels. The latter involves an alteration of cocaine kinetics and metabolism, as well as the biosynthesis of newly active metabolites, such as cocaethylene. Cocaethylene is metabolized along the same pathways as cocaine. Its detection in biological samples indicates the combined consumption of cocaine and alcohol. From epidemiological and toxicological data, it has been suggested that the combination of alcohol and cocaine produces an increased toxicity in addition to behavioral changes. There has been some debate regarding the contribution of cocaethylene to this rise of toxicity. Its pharmacological and toxicological profile is very similar to cocaine. During the interaction of both substances, the rise in cocaine plasma concentrations can explain many of cardiovascular and behavioral effects observed. The contribution of cocaethylene to the interaction is probably minor; its effects are likely additive to those of cocaine. Perhaps its longer elimination half-life can help in understanding long-lasting effects of the alcohol-cocaine combination.

Alcohol Drinking↗
PubMed1998

Fibrinogen and fibrinolysis in blood and in the arterial wall: its role in advanced atherosclerotic disease.

High plasma fibrinogen appears to be an important risk factor for the development of atherosclerosis. The aim of our study was to measure fibrinogen and fibrin degradation products (D-dimer), interleukin-6 tissue plasminogen activator, plasminogen activator inhibitor-1 and urokinase-type plasminogen activator in the plasma and arterial walls of 45 patients who had arterial surgery between April 1993 and November 1995. The arterial specimens were also examined by immunohistochemists for these same factors. The serum fibrinogen and fibrin degradation products were high in all patients, and fibrinolysis was depressed. Few leukocytes were seen in the arterial walls, which had poor fibrinolytic activity. Plasminogen-activator inhibitor activity in the wall was also reduced in the affected arterial walls. The abdominal aorta appeared to have the highest levels of fibrinogen and this may be related to its ability to form aneurysms. Fibrinogen may play an important role in the progression of atherosclerotic disease.

Aorta, Abdominal↗
PubMed1998

Analytical approaches of European Union laboratories to drugs of abuse analysis.

We report a survey on urine drug testing within a total of 269 laboratories of the European Union. Clinical laboratories predominated over forensic laboratories (59.5% vs 28.5%). Screening without identification/quantification was the common approach used by clinical laboratories, whereas screening with identification/quantification was the approach used by almost all forensic laboratories. Screening was primarily performed by immunoassay in both types of laboratories. Gas chromatography coupled to mass spectrometry was the main analytical method used for specific identification/quantification of drugs, but other methods (including immunoassays) were also used. Cutoff values applied varied by laboratory type, country, and method used. A high percentage of laboratories did not use or report cutoff values. Overall, countries of the European Union vary significantly in regards to drugs tested, analytical approach, and screening and identification cutoff values. It is recommended to clearly state the analytical method and the cutoff values used when reporting results for drugs of abuse testing.

Clinical Laboratory Techniques↗
PubMed1998

Hemangiopericytoma ischiorectal. Report of a case.

Hemangiopericytoma (HP) is a rare tumoral neoplasm of the soft tissues. Here, we report a case of HP that appeared in a young woman in a very uncommon location (perianal). Initially it was considered as a perianal abscess: arteriography, CT-scan and, eventually, histological studies, confirmed the diagnosis of HP. The tumoral mass was first embolized and thereafter was resected through a double approach (abdominal and perineal). One and a half years after surgery, the patient remains asymptomatic.

Adult↗
PubMed1997

In-laboratory removal of femoral sheath following protamine administration in patients having intracoronary stent implantation.

Two hundred twenty-eight patients with successful coronary stent implantation were randomized either to protamine administration and femoral sheath removal (group I, n = 117) or no heparin neutralization and delayed sheath removal (group II, n = 111). The hospital stay after treatment was shorter in patients receiving protamine; therefore, protamine use for neutralizing circulating heparin may be safely administered immediately after stent implantation.

Anticoagulants↗
PubMed1997

Angiographic predictors of neointimal thickening after successful coronary wall healing following percutaneous revascularization.

This study was undertaken to characterize, by intracoronary ultrasound technique, the neointimal thickening at follow-up of treated coronary segments after successful arterial wall repair and to compare the findings with serial angiographic studies. We selected for study 81 patients with single-vessel coronary disease successfully treated by percutaneous revascularization who were angiographically and ultrasonically reevaluated at a mean follow-up time of 22 +/- 21 months; 23 had been treated by balloon angioplasty, 27 by directional atherectomy, and 31 by elective Palmaz-Schatz stent implantation. The late maximal neointimal thickness varied between 0.1 and 1.5 mm (mean 0.65 +/- 0.31 mm), and the neointimal area ranged between 0.97 and 14.9 mm2 (mean 5.19 +/- 3.14 mm2). The neointimal repair was thinner in patients who obtained a better acute angiographic result immediately after treatment and in stented (3.4 +/- 1.8 mm2) versus dilated (7.8 +/- 4.1 mm2) or resected (5 +/- 1.6 mm2, p < 0.001) segments. On the contrary, the repaired neointimal layer was thicker in those patients who angiographically exhibited less late luminal loss or even expansion and in those evaluated after a longer time since treatment. The acute gain and the time influence resulted in independent predictors of the degree of neointimal thickness. These findings suggest that two reparative mechanisms of the coronary wall may operate in close relation.

Angioplasty, Balloon, Coronary↗
PubMed1997

Electrospray mass spectrometry of testosterone esters: potential for use in doping control.

The study described involves an attempt to identify 17 beta-fatty acid esters of testosterone in blood plasma following administration of such agents. These drugs are therapeutic but are increasingly misused by athletes in an attempt to improve sports performance. The mass spectral properties of testosterone esters under electrospray ionization are described. These esters (testosterone acetate, propionate, isocaproate, benzoate, enanthate, cypionate, phenylpropionate, decanoate, and undecanoate) essentially give only a protonated molecular ion (MH+) under "optimum sensitivity" mass spectrometric conditions but could be induced to fragment in the source or collision cell of a triple quadrupole mass spectrometer. The underivatized steroid esters were analyzed by direct infusion because development of solvent systems compatible with high-performance liquid chromatography (HPLC) was not achieved for these nonpolar compounds. HPLC/MS (mass spectrometry) was possible when the steroids were converted to polar, water soluble, Girard hydrazones, and almost all were separated by microbore C4 HPLC using a water, acetonitrile, TFA gradient. The mass spectra under optimal ionization conditions essentially comprised only a molecular ion (M+), but source fragmentation gave major ions at M - 59 and M - 87 for all compounds. The molecular ion and these fragment ions were monitored in a selected-ion-recording (SIR) method developed for detecting the steroids in plasma. Using this methodology, testosterone enanthate and undecanoate could be detected after intramuscular injection or oral administration of the drugs. Further development of the technique could form the basis of a protocol for confirming the misuse of testosterone in sport, especially if sensitivity could be improved.

Chromatography, High Pressure Liquid↗
PubMed1997

Antiproteinuric effect of angiotensin-converting enzyme inhibition and C5b-9 urinary excretion in membranous glomerulonephritis.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors have an antiproteinuric effect in membranous glomerulonephritis (MGN). However, no studies have investigated whether this antiproteinuric effect is influenced by urinary C5b-9 excretion, a marker of immunological activity in this disease. METHODS: Eleven patients with biopsy-proven MGN were treated with captopril for 8 weeks. The evolution of several clinical and biochemical parameters, including 24-h urinary protein excretion was evaluated every 4 weeks. Urinary C5b-9 excretion was measured at the onset and at the end of captopril treatment. RESULTS: Patients with MGN had significantly higher C5b-9 excretions than a group of 14 healthy controls (89 +/- 23 vs 3.7 +/- 1.4 ng/mg UCr; P < 0.001). A significant correlation was found between urinary C5b-9 and the magnitude of proteinuria, both at the onset and at the end of treatment. After 8 weeks of captopril treatment, proteinuria had decreased from 8 +/- 1.8 to 5.2 +/- 1.3 g/day (P < 0.05). Four weeks after captopril discontinuation, proteinuria rose to 7.3 +/- 1.7 g/day (P < 0.05). A marked variability in the antiproteinuric response was observed, ranging from 0 to 85% with respect to baseline values. No correlation between decrease in proteinuria and baseline urinary C5b-9 levels was observed. Several patients with elevated urinary C5b-9 levels had captopril-induced decrease in proteinuria. CONCLUSIONS: ACE inhibition induces an antiproteinuric effect in patients with MGN. The urinary C5b-9 excretion does not predict the magnitude of this response.

Adult↗
PubMed1997

[Primary stent treatment in the acute phase of myocardial infaction].

INTRODUCTION: Although direct balloon angioplasty has emerged as an alternative to thrombolytic therapy in patients with acute myocardial infarction, reocclusion and restenosis rates are limiting factors. We postulated that these limitations could be partly overcome by primary stenting of the responsible lesion. MATERIAL AND METHODS: Since January/94 we have studied 59 patients with acute myocardial infarction who were treated in the early phase (3.1 +/- 2 hours since the onset of symptoms) by elective Palmaz-Schatz stent implantation. No adjunctive thrombolytic therapy was associated. Two patients were in cardiogenic shock and were treated under percutaneous cardiopulmonary support. At cardiac catheterization a left ventriculography and coronary angiograms were obtained. Then, mechanical recanalization of the responsible lesion was performed. If the angiographic anatomy was considered suitable, a stent was implanted at the lesion. RESULTS: The infarct related artery was the left anterior descending in 29 patients, the circumflex in 14 and the right coronary artery in 16. At baseline conditions, 40 patients had a totally occluded artery and 19 showed a TIMI-grande 1 antegrade flow. One patient had an early clinical recurrence 4 days later, which required an additional divided Palmaz-Schatz stent at the distal portion of the lesion, in order to seal a residual dissection. All remaining patients had a favourable clinical course without major complications. Immediately after treatment the minimal lumen diameter was 3.2 +/- 0.4 mm and no residual stenosis was detectable at the treated segment. Six-month angiographic reevaluation was performed in all 29 (49%) eligible patients. Restenosis (> 50% stenosis) was detected in 6 out of the 29 evaluated patients (21%). CONCLUSIONS: Primary stent implantation in selected patients with an evolving myocardial infarction provides good initial and 6-month results.

Acute Disease↗
PubMed1996

Detection of diuretic agents in doping control.

Since the inclusion of diuretics in the list of banned substances in sports in 1988, a large number of screening and confirmation procedures to detect the presence of these substances in urine samples have been developed. In this paper, a review of the analytical methodology described to analyze diuretics is presented. The paper has been focused on the needs of doping control and mainly screening procedures including sample preparation and liquid or gas chromatographic separation have been considered. More relevant papers using capillary zone electrophoresis have been also considered. Mass spectrometry is mandatory in doping control for confirmation purposes, and finally, mass spectrometric techniques described for diuretics have been reviewed.

Chromatography, Gas↗