Testing an Adapted Auditory Verbal Learning Test Paradigm for fMRI to Lateralize Verbal Memory in Patients with Epilepsy.

BACKGROUND AND PURPOSE: fMRI is a noninvasive tool for predicting postsurgical deficits in candidates with pharmacoresistant temporal lobe epilepsy. We aimed to test an adapted paradigm of the Rey Auditory Verbal Learning Test to evaluate differences in memory laterality indexes between patients and healthy controls and its association with neuropsychological scores. MATERIALS AND METHODS: We performed a prospective study of 50 patients with temporal lobe epilepsy and 22 healthy controls. Participants underwent a block design language and memory fMRI. Laterality indexes and the hippocampal anterior-posterior index were calculated. Language and memory lateralization was organized into typical and atypical on the basis of laterality indexes. A neuropsychological assessment was performed with a median time from fMRI of 8 months and was compared with fMRI performance. RESULTS: We studied 40 patients with left temporal lobe epilepsy and 10 with right temporal lobe epilepsy. Typical language occurred in 65.3% of patients and 90.9% of healthy controls (P = .04). The memory fMRI laterality index was obtained in all healthy controls and 92% of patients. The verbal memory laterality index was bilateral (24.3%) more frequently than the language laterality index (7.69%) in patients with left temporal lobe epilepsy. Atypical verbal memory was greater in patients with left temporal lobe epilepsy (56.8%) than in healthy controls (36.4%), and the proportion of bilateral laterality indexes (53.3%) was larger than right laterality indexes (46.7%). Atypical verbal memory might be associated with higher cognitive scores in patients. No relevant differences were seen in the hippocampal anterior-posterior index according to memory impairment. CONCLUSIONS: The adapted Rey Auditory Verbal Learning Test paradigm fMRI might support verbal memory lateralization. Temporal lobe epilepsy laterality influences hippocampal memory laterality indexes. Left temporal lobe epilepsy has shown a higher proportion of atypical verbal memory compared with language, potentially to memory functional reorganization.

Estabilidad de parecoxib en dilución con otros fármacos y administración en perfusión continua IV para el control del dolor postoperatorio / Stability of parecoxib in dilution with other drugs and administered in continuous

Objetivo. Evaluar la estabilidad de parecoxib en un sistema de infusión continua elastomérica portátil IV para 24 horas, en dilución con opiáceos (cloruro mórfico, meperidina ó tramadol), antieméticos y suero fisiológico, durante las 24 horas del postoperatorio; así como, comprobar el resultado analgésico, la aparición de efectos secundarios y el grado de satisfacción de pacientes intervenidos de cirugía mayor susceptibles de tratamiento con dichos fármacos. Material y Métodos. El infusor es un dispositivo desechable y ligero con un depósito elastomérico para administrar medicación. Se realizaron varias pruebas mezclando parecoxib, opiáceos, antieméticos y suero fisiológico y se observó su estabilidad durante 24 horas. Procedimos a observar la mezcla en repetidas ocasiones y la dilución siempre permaneció estable, clara, sin partículas y transparente; por lo que se decidió utilizar dicha mezcla en el infusor IV para el tratamiento del dolor postoperatorio, siempre bajo la supervisión de un anestesiólogo. Se estudiaron un total de 118 pacientes, 46 mujeres (39%) y 72 hombres (61%), ASA I-IV, edad media 59,75 +/- 14,25 (18-89), 92 (78%) fueron intervenidos de cirugía general y 26 (22%) de urología. El llenado del infusor según ASA, edad y tipo de intervención del paciente, se realizó con: parecoxib 80 mg + metoclopramida Cl H 20 ó 30 mg + suero fisiológico en los 118 pacientes, se añadió cloruro mórfico en 65 pacientes, meperidina en 30 y tramadol en 23, a administrar en 24 horas tras la intervención quirúrgica. Se valoró la intensidad del dolor según EAV a la llegada a la Sala de Despertar y a las 24 horas, resultado analgésico, efectos secundarios y grado de satisfacción. Resultados. El resultado analgésico fue muy bueno en 60 pacientes (50,85%); bueno en 40 (33,90%); regular en 12 (10,17%) y suspendido el tratamiento en 6 (5%) por efectos secundarios. Los efectos secundarios aparecieron en 30 casos (25%): 4 con sudoración (3%), 1 con desorientación (0,8%) y 7 con somnolencia y mareo (6%) 3 de ellos con interrupción del tratamiento. En cuanto a las náuseas y/o vómitos: 18 pacientes necesitaron rescate antiemético, y en 3, hubo que suspender el tratamiento. El grado de satisfacción del paciente fue: muy satisfactorio en 56 pacientes (47,5%); satisfactorio en 46 (39%), deficiente en 10 (8,5%) y suspendido el tratamiento en 6 (5%) por efectos secundarios. Conclusiones. La posibilidad de utilizar parecoxib sólo o unido a otros fármacos en perfusión continua IV para el tratamiento del dolor agudo postoperatorio, es una opción a considerar

Objective. To evaluate the stability of parecoxib in a portable elastomeric pump system for IV infusion in dilution with opioids (morphine chloride, pethidine or tramadol), antiemetics and saline solution during 24 hours in the postoperative period; as well as to verify the analgesic result, the incidence of side effects and the degree of satisfaction in patients undergoing major surgery that were eligible for treatment with these drugs. Material and Methods. The infuser pump is a light disposable device with an elastomeric deposit to administer the medication. Several tests combining parecoxib, opioids, antiemetics and saline solution were carried out and its stability was demonstrated during 24 hours. The mixture was then observed in several occasions and was shown that the dilution always remained stable, clear, with no particles and transparent; therefore it was decided to use that combination in the IV infuser for the treatment of postoperative pain, always under the anaesthesiologist supervision. A total of 118 patients were studied, 46 women (39%) and 72 men studied (61%), ASA I-IV, mean age 59.75 +/- 14.25 (18-89); 92 (78%) underwent general surgery procedures and 26 (22%) urologic ones. The filling of infuser according to ASA, age and type of surgery of the patient, was made with: parecoxib 80 mg + metoclopramide CL H 20 or 30 mg + saline solution for the 118 patients, morphine chloride was added in 65 patients, petidine in 30 and tramadol in 23, during 24 hours after surgery. Pain was assessed using a VAS in both at arrival in the PACU and 24 hours after the surgical procedures. Analgesic outcome, side effects and degree of satisfaction were recorded. Results The analgesic outcome was very good in 60 patients (50.85%); good in 40 (33.90%); regular in 12 (10.17%) and the treatment was interrupted 6 (5%) due to side effects. Side effects were present in 30 (25%) cases: 4 with perspiration (3%), 1 with disorientation (0.8%) and 7 with somnolence and dizziness (6%) 3 of them with interruption of the treatment. For nausea and vomiting, 18 patients needed antiemetics rescue, and in 3 cases it was necessary to suspend the treatment. The degree of satisfaction reported by patients was: very satisfactory in 56 patients (47.5%); satisfactory in 46 (39%), inadequate in 10 (8.5%) and the treatment was suspended in 6 (5%) due to side effects. Conclusions. The possibility of using parecoxib alone or in combination with other drugs in continuous IV perfusion for acute postoperative pain is an important option to be considered

Solid-phase total synthesis of trunkamide A(1).

Marine organisms are a rich source of novel, biologically active compounds. Herein, the solid-phase total synthesis of trunkamide A, currently in preclinical trials, is presented. Trunkamide A contains a thiazoline heterocycle and two residues of Ser and Thr with the hydroxy function modified as reverse prenyl (rPr). Cornerstones of the synthesis are as follows: (i) solid-phase peptide chain elongation using a quasi-orthogonal protecting scheme with tert-butyl and fluorenyl based groups, on a chlorotrityl resin; (ii) concourse of HOAt-based coupling reagents; and (iii) cyclizations in solution. Furthermore, the following synthetic steps are discussed: (i) preparation of the reverse prenyl derivatives of Ser and Thr; (ii) introduction of precursor of thiazoline as a protected amino thionoacid derivative; and (iii) formation of the thiazoline ring with DAST. All these features make this strategy particularly suitable for the large-scale synthesis of trunkamide A and other peptides containing the same motifs.

Search for metabolites of ecteinascidin 743, a novel, marine-derived, anti-cancer agent, in man.

Ecteinascidin 743 (ET-743) is a potent anti-tumoral agent of a marine origin. It is currently being tested in phase II clinical trials using a 3-weekly 24-h i.v. infusion of 1500 microg/m(2) and 3-h infusions of 1650 microg/m(2). Knowledge of the metabolism of ET-743 is, however, still scarce. In the present study, a qualitative chromatographic discovery of metabolites of ET-743 in man is reported. ET-743 and its demethylated analog ET-729 were incubated at 37 degrees C in the presence of enzyme systems, pooled human microsomes, pooled human plasma and uridine 5'-diphosphoglucuronyltransferase, respectively, in appropriate media. Reaction products were investigated chromatographically using photodiode array and ion spray-mass spectrometric detection (LC-MS). The main reaction products in microsomal incubations of ET-743 resulted from a remarkable breakdown of the molecule. In plasma the drugs were deacetylated, and the transferase did actually yield a glucuronide of both ET-743 and ET-729. In contrast, screening of urine, plasma and bile, collected from patients treated with ET-743 at the highest dose levels, using a sensitive LC-MS assay, did not result in detection of ET-729 and metabolites which were generated in vitro. The urinary excretion of ET-743 in man was lower than 0.7% of the administered dose for a 24-h infusion.

Adaptación de las nuevas tecnologías en sanidad / Adaptation of New Technologies in Health

No disponible

No disponible

La gestión del conocimiento en sanidad / No disponible

No disponible

Nuevas Tecnologías: La historia clínica electrónica (parte 2) / New Technologies: The Computerised Clinical History (2nd part)

No disponible

No disponible

Nuevas tecnologías: La Historia Clínica Electrónica (parte 1) / New Technologies: Computerised Clinical Histories

No disponible

No disponible

Advances in the chemistry and pharmacology of ecteinascidins, a promising new class of anti-cancer agents.

Ecteinascidins are marine natural products consisting of two or three linked tetrahydroisoquinoline subunits and an active carbinolamine functional group. Their potent antiproliferative activity against a variety of tumor cells has made them attractive candidates for development as anticancer agents. The lead compound, ecteinascidin 743 (ET 743), is currently in phase II clinical trials but the low amounts present in its natural source, the tunicate Ecteinascidia turbinata, made it necessary to develop efficient synthetic procedures. Recent improvements on the original synthesis are reviewed as well as new strategies starting from readily available cyanosafracin B. ET 743 is known to bind to the minor groove of DNA giving rise to a covalent adduct with the exocyclic amino group at position 2 of a guanine in a fashion similar to saframycin antibiotics. Some of the resulting complexes have been studied by a variety of biochemical and spectroscopic methods and also by computer simulations. The rules for sequence specificity have been well established (preferred targets are RGC and YGG, where R and Y stand for purine and pyrimidine, respectively), and it has been shown that binding of ET 743 to DNA is accompanied by minor groove widening and DNA bending towards the major groove. Although the precise target for antitumor action remains to be unambiguously defined, a role in affecting the transcriptional regulation of some inducible genes is rapidly emerging.

Synthesis of ecteinascidin ET-743 and phthalascidin Pt-650 from cyanosafracin B.

An efficient new process is described for the synthesis of ecteinascidin ET-743 (1) and phthalascidin (2), starting from readily available cyanosafracin B (3).

Synthesis and preliminary pharmacological evaluation of thiophene analogues of viloxazine as potential antidepressant drugs.

A series of eight thienyloxymethylmorpholines, thiophene analogues of viloxazine, have been synthesized by three different routes. The preliminary pharmacological evaluation of this series shows antidepressant properties on the mice models used with a light sedative action. The structure-activity relationship is established in a first approximation.

In vitro activity of aplidine, a new marine-derived anti-cancer compound, on freshly explanted clonogenic human tumour cells and haematopoietic precursor cells.

Aplidine is a new marine anti-cancer depsipeptide isolated from the Mediterranean tunicate Aplidium albicans. We have evaluated its antiproliferative action against a variety of freshly explanted human tumour specimens. Concentration ranges of 0.01-1.0 microM and 0.0001-1.0 microM were used in short- and long-term exposure schedules respectively. After exposure for 1 h in 49 evaluable specimens, aplidine showed a clear concentration-dependent anti-tumour effect. At 0.05 microM, 85% of the specimens were markedly inhibited. Continuous exposure for 21-28 days in 54 tumour specimens also led to a concentration-dependent activity relationship. Fifty per cent and 100% tumour inhibitions were achieved with 0.001 microM and 0.05 microM respectively. A head to head evaluation assessing short vs continuous exposure was carried out, resulting in evidence of an activity-time of exposure relationship. Breast, melanoma and non-small-cell lung cancer appear to be sensitive to low concentrations of aplidine. In addition the evaluation of the effects of aplidine on haematopoietic cells showed a concentration-dependent toxicity. However, under continuous exposure, active concentrations induced mild bone marrow toxicity, indicating that a therapeutic window at marginally myelotoxic concentrations might exist.