Jordi Camí

Mapa bibliométrico de España 1994-2002: biomedicina y ciencias de la salud☆

Fundamento y objetivo: Se presenta una actualizacion para el periodo 1994-2002 del mapa bibliometrico de biomedicina en Espana, tras las publicaciones en Medicina Clinica de los periodos 1986-1989 y 1990-1993. Material y metodo: Los resultados se circunscriben al subconjunto de documentos citables clasificados tematicamente en 70 disciplinas segun el Journal Citation Reports (JCR) de 1996. El analisis bibliometrico se ha basado en indicadores simples (documentos y citas) y compuestos (como colaboracion internacional o tanto por ciento de documentos no citados). Resultados: Espana se situa en la decimoprimera posicion mundial y en septima posicion dentro de sus homologos europeos. La produccion espanola supone el 2,4% del total de documentos biomedicos del mundo, aunque solamente el 1,8% de citas recibidas. Cerca de la mitad de todos los documentos van con firma del sector sanitario. El 24,8% de los documentos se firma en colaboracion internacional, proporcion que acumula el 45,5% de todas las citas. La Comunidad Autonoma de Cataluna destaca por su perfil de investigacion clinica; la de Madrid, por su alta densidad de centros del CSIC, y la de Andalucia y la Valenciana, por los documentos procedentes del sector universitario. Conclusiones: Aunque el crecimiento en publicaciones es sostenido, la media de citas recibidas por documento aun no alcanza la media internacional. A pesar de que la internacionalizacion de las publicaciones ha superado la media mundial, sigue por debajo de la mayoria de paises europeos. El analisis de perfiles territoriales y de centros refleja una estructura del sistema cientifico biomedico espanol similar a la de los analisis precedentes, aunque con mejores resultados.

Quantification of 3,4-methylenedioxymetamphetamine and its metabolites in plasma and urine by gas chromatography with nitrogen-phosphorus detection.

A gas chromatographic method with nitrogen-phosphorus detection involving a solid-liquid extraction phase was developed and validated for the simultaneous quantification of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) in plasma. A modification of this method was validated for the analysis of MDMA, MDA, 4-hydroxy-3-methoxymethamphetamine (HMMA) and, 4-hydroxy-3-methoxyamphetamine (HMA) in urine. Under the analytical conditions described, the limits of detection in plasma and urine were less than 1.6 microg/l and 47 microg/l, respectively, for all the compounds studied. Good linearity was observed in the concentration range evaluated in plasma (5-400 microg/l) and urine (100-2000 microg/l) for all compounds tested. The recoveries obtained from plasma were 85.1% and 91.6% for MDMA and MDA, respectively. Urine recoveries were higher than 90% for MDMA and MDA, 74% for HMMA, and 64% for HMA. Methods have been successfully used in the assessment of plasma and urine concentrations of MDMA and its main metabolites in samples from clinical studies in healthy volunteers.

MDMA (ecstasy) pharmacokinetics in a CYP2D6 poor metaboliser and in nine CYP2D6 extensive metabolisers.

(CYP)isoform 2D6 [2]. HHMA is further metabolised to 4-hydroxy, 3-methoxymethamphetamine (HMMA) bycatechol- O-methyltransferase (COMT). HMMA in-duces vasopressin secretion to a higher extent thanMDMA and has been postulated to contribute to hyp-onatraemia observed in some MDMA acute intoxica-tions [4]. The CYP2D6 gene is highly polymorphic andmany variations affect the expression or activity of theenzyme. Approximately 7–10% of European Caucasianspresent a metabolic deficiency and are termed poormetabolisers (PM) [12]. Evidence that individuals pos-sessingacompromiseinCYP2D6activitywouldbemoresusceptible to acute toxic effects of MDMA has beenlacking. A previous metabolic bioactivation of MDMA,regulated partially by this enzyme, is needed to elicitneurotoxic effects in the central nervous system. It ispostulated that the chemical species involved inserotonergic neurotoxicity are catechol thiol conjugatemetabolites of the drug (HHMA) [8]. The functionalpolymorphisms in CYP2D6 could influence the devel-opment of MDMA neurotoxicity. During a trial de-signed to study the pharmacology of two consecutivedoses of MDMA [3], one subject was found to possessthe CYP2D6*4/*4 genotype and was classified as a PM.The objective of this paper was to compare the results ofthis subject with those of nine others previously pub-lished. Furthermore, the paper includes pharmacokineticdata on MDMA metabolites not previously published.

Mapa bibliométrico de España 1996-2004: biomedicina y ciencias de la salud

BACKGROUND AND OBJECTIVE: The study presents the bibliometric analysis of the Spanish scientific output in biomedicine during 1996-2004. This is the last edition of a series of bibliometric studies aimed to characterize the Spanish scientific performance in biomedicine. MATERIAL AND METHOD: The analysis was restricted to citable documents for which simple and composite bibliometric indicators were obtained at different aggregation levels: fields, autonomous regions, institutional sectors and research centres. The documents were selected according to the Journal Citation Reports, and were assigned to affiliation centres following an integer counting scheme after an exhaustive normalization of the affiliation addresses. RESULTS: Compared to the period 1994-2002, research activity in biomedicine grew as much as Spain: 8.9% in the number of documents; 22.5% citations; 12.5% citation per document average and 27.2% international cooperation. Besides, biomedicine showed the highest citation per document average compared to other major fields. International cooperation in biomedicine (27.2%) reached the European average. The documents published in international cooperation account for the half of citations to documents in biomedicine. The number of documents and citations belonging to the clinic medicine subfield and to the health sector showed the highest growth. CONCLUSIONS: In general, these results reproduce the tendencies described in prior studies. The documents in biomedicine showed a highly asymmetric distribution among institutional sectors, autonomous regions, scientific fields and research centres. The remarkably increase in the output of clinical medicine field and in the health sector could be the consequence of important science policy actions undertaken in these areas in the last years.

Effect of quinolones on caffeine disposition

Six healthy volunteers received a single caffeine dose after pretreatment with norfloxacin, pipemidic acid, or placebo in a crossover, randomized, single‐blind clinical trial. Quinolones altered the pharmacokinetics of caffeine, with a significant increase in the AUCs and a decrease in plasma clearance. The elimination half‐life increased significantly with pipemidic acid. The apparent volume of distribution, mean renal clearance, and time to reach maximum caffeine concentrations remained unaltered. There was a decline in caffeine metabolite levels in the 24‐hour urine samples for both quinolone treatments, suggesting that pipemidic acid and, to a lesser degree, norfloxacin inhibit metabolism of the N‐demethylation pathways of caffeine. The practical consequence of this observation could be caffeine accumulation during repeated intake of coffee. In two additional healthy volunteers under a controlled multiple‐dose regimen of caffeine ingestion, administration of pipemidic acid for 2 days caused a fourfold increase in the plasma concentrations of caffeine.

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.

Abuse liability of flunitrazepam among methadone-maintained patients

Abstract Abuse liability and acute subjective and psychomotor effects of flunitrazepam were assessed in ten methadone-maintained males with history of benzodiazepine and alcohol use, who voluntarily participated in a double-blind, controlled, cross-over, randomized clinical trial. There were six experimental sessions in which a single oral dose of flunitrazepam 1, 2, and 4 mg; triazolam 0.5 and 0.75 mg; and placebo was given. Evaluations included physiological measures; psychomotor performance tasks (simple reaction time, Digit Symbol Substitution Test, balance task, Maddox-wing device); and self-administered subjective effects questionnaires [Addiction Research Center Inventory (ARCI), Profile of Mood States (POMS), a series of visual analog scales (VAS)]. All drugs but flunitrazepam 1 mg caused an impairment of psychomotor tasks. Effects were more evident with the highest doses of both drugs. Only flunitrazepam 4 mg produced a significant decrease in balance time. Triazolam 0.75 mg induced increases in sedation measured by ARCI-PCAG, depression in POMS, and VAS-drowsiness scores. Flunitrazepam 4 mg caused euphoria-related effects as measured by increases in ARCI-MBG and “high” scores in the VAS. Our findings of flunitrazepam-induced euphoria in methadone-maintained subjects together with epidemiological evidence of flunitrazepam abuse by opioid dependents, suggest that it may be included in the group of benzodiazepines with a relatively high abuse potential.

Acute Effects of Tramadol in Methadone-Maintained Volunteers

SummaryThe opioid agonist and antagonist properties of tramadol were assessed in 6 male opioid-dependent volunteers enrolled in a methadone maintenance programme. Subjects participated in 3 experimental sessions in which the effects of intramuscular tramadol 100 and 300mg and placebo were evaluated. Tramadol neither produced morphine-like effects nor precipitated a withdrawal syndrome; its subjective, behavioural and physiological effects were not different from those of placebo. Although the results of this study suggest that tramadol has a low abuse liability in opioid-dependent subjects, higher doses should be tested to confirm these data.

Creating a transatlantic research enterprise for preventing Alzheimer's disease.

In recognition of the global problem posed by Alzheimers disease and other dementias, an international think‐tank meeting was convened by Biocat, the Pasqual Maragall Foundation, and the Lou Ruvo Brain Institute in February 2009. The meeting initiated the planning of a European Union‐North American collaborative research enterprise to expedite the delay and ultimate prevention of dementing disorders. The key aim is to build parallel and complementary research infrastructure that will support international standardization and inter‐operability among researchers in both continents. The meeting identified major challenges, opportunities for research resources and support, integration with ongoing efforts, and identification of key domains to influence the design and administration of the enterprise.

Effect of subject expectancy on the THC intoxication and disposition from smoked hashish cigarettes

Subject expectancy on cannabis effects was assessed in a balanced-placebo study in experienced consumers who smoked cigarettes containing hashish (200 mg hashish with 11.5% THC per 1 g tobacco cigarette) (n = 24) or placebo (n = 24). Although statistically significant differences were not found between subjects who received the drug with positive or negative expectancy, a tendency toward more marked subjective effects was shown in subjects who expected and received the drug. This trend was supported by the significant difference observed in the mean AUC0-25 of the heart rate between subjects who smoked hashish with positive or negative expectancies. In subjects who received hashish, the sum AUC0-205 of THC and COOH-THC of those who expected the drug was greater than in those who did not expect it (p less than 0.05). The ratio THC/COOH-THC AUC0-205 was lower in those with positive expectancy than in those with negative expectancy (p less than 0.02). An increased metabolism of THC was shown in subjects with positive expectancy. Positive expectancy induced powerful subjective effects in the absence of active THC. Expectancy appeared to influence smoking behavior, as seen in higher plasma levels of cannabinoids for the group who received the drug.