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Biomedical subjects

E Blanco

Publications and source records attributed to E Blanco.

At least 55 records · Page 3Linked to original sources

Propofol inhibits in vitro platelet aggregation in human whole blood.

To help clarify the mechanism of propofol-induced vasodilation, we investigated whether propofol, at concentrations ranging from 10(-6) to 10(-3) M, inhibited platelet aggregation in human whole blood. Propofol inhibited platelet aggregation induced by adenosine diphosphate, collagen, or arachidonic acid in a concentration-dependent manner, with a 50% inhibited concentration (micromol/L) of 136 +/- 9.8 for adenosine diphosphate, 77.8 +/- 6.6 for collagen, and 71.8 +/- 5.4 for arachidonic acid. In platelet-rich plasma, propofol had no significant antiaggregant effect except when arachidonic acid was used as the aggregant (50% inhibited concentration 105 +/- 9.9 micromol/L). The antiaggregant effect of propofol in platelet-rich plasma was increased in the presence of red blood cells or leukocytes in a cell number-dependent manner. We conclude that propofol reduces the platelet activity in human whole blood in vitro.

Adult↗

A large-scale evaluation of peptide vaccines against foot-and-mouth disease: lack of solid protection in cattle and isolation of escape mutants.

A large-scale vaccination experiment involving a total of 138 cattle was carried out to evaluate the potential of synthetic peptides as vaccines against foot-and-mouth disease. Four types of peptides representing sequences of foot-and-mouth disease virus (FMDV) C3 Argentina 85 were tested: A, which includes the G-H loop of capsid protein VP1 (site A); AT, in which a T-cell epitope has been added to site A; AC, composed of site A and the carboxy-terminal region of VP1 (site C); and ACT, in which the three previous capsid motifs are colinearly represented. Induction of neutralizing antibodies, lymphoproliferation in response to viral antigens, and protection against challenge with homologous infectious virus were examined. None of the tested peptides, at several doses and vaccination schedules, afforded protection above 40%. Protection showed limited correlation with serum neutralization activity and lymphoproliferation in response to whole virus. In 12 of 29 lesions from vaccinated cattle that were challenged with homologous virus, mutant FMDVs with amino acid substitutions at antigenic site A were identified. This finding suggests the rapid generation and selection of FMDV antigenic variants in vivo. In contrast with previous studies, this large-scale vaccination experiment with an important FMDV host reveals considerable difficulties for vaccines based on synthetic peptides to achieve the required levels of efficacy. Possible modifications of the vaccine formulations to increase protective activity are discussed.

Amino Acid Sequence↗

UFT modulated with leucovorin in advanced colorectal cancer: Oncopaz experience.

A phase II trial of UFT (Tegafur and Uracil) modulated by leucovorin was undertaken by the Oncopaz Cooperative Group to assess the efficacy and toxicity of this combination in patients with advanced colorectal cancer. A total of 75 patients were given 500 mg/m2 intravenous leucovorin and 195 mg/m2 of oral UFT on day 1, followed by oral leucovorin 15 mg/12 h and 195 mg/m2/12 h of oral UFT on days 2-14. An overall response rate of 39% was obtained, with seven complete responses (9%), and 22 partial responses (29%). The primary toxicity was gastrointestinal, with grade 1-2 diarrhea occurring in 8.5% of courses, and grade 3-4 in 3.5%. Hematologic toxicity was minimal, and there were no deaths due to toxicity. This regimen was active and well tolerated in patients with advanced colorectal cancer, including those 70 years of age or older.

Antineoplastic Combined Chemotherapy Protocols↗

Experience of Oncopaz Cooperative Group with oral fluoropyrimidines in tumors of the stomach, lung, head and neck, and breast.

The Oncopaz Cooperative Group designed a chemotherapy regimen to modulate UFT (Tegafur and Uracil) with leucovorin. The regimen consisted of a high intravenous dose of leucovorin, followed by oral UFT and oral leucovorin twice daily for 14 days. Based on the promising results obtained with this regimen in patients with advanced colorectal cancer, the Oncopaz group performed several phase II trials using this combination with other drugs to treat advanced gastric, lung, head and neck, and breast cancers. When combined with etoposide in gastric cancer, the regimen was shown to be active and well tolerated. However, when used with cisplatin to treat non-small cell lung cancer, a low response rate and high toxicity precluded its recommendation for further study. The addition of carboplatin in the treatment of head and neck cancer demonstrated moderate activity with low toxicity. In an ongoing trial of advanced breast cancer, preliminary results indicate that the combination of idarubicin, UFT, and leucovorin is active, with moderate, primarily hematologic toxicity. Trials of new combinations are warranted to take advantage of the pharmacokinetic properties and oral bioavailability of UFT and leucovorin.

Adenocarcinoma↗

Treatment of patients with advanced gastric carcinoma with the combination of etoposide plus oral tegafur modulated by uracil and leucovorin. A phase II study of the ONCOPAZ Cooperative Group.

BACKGROUND: Both the biochemical modulation and the continuous administration of 5-fluorouracil (5-FU) have achieved promising results in patients with gastric carcinoma. Conversely, several studies on gastric carcinoma have demonstrated that the combination of etoposide (VP-16), leucovorin (LV), and 5-FU (ELF) is efficacious and moderately toxic. UFT is a combination of uracil and tegafur (ftorafur) in a 4:1 molar ratio. It can be administered orally for several weeks, thus stimulating the effects of a continuous infusion of 5-FU. Its combination with LV increased the efficacy of UFT. We conducted a Phase II study on patients with gastric carcinoma using the combination VP-16-LV-UFT. This combination is administered mainly orally (p.o) and could yield a good response rate and low toxicity. METHODS: Forty-six patients with bidimensionally measurable disease were entered into the study. Patients received VP-16 100 mg/m2 IV on Day 1 and 200 mg/ m2 p.o. on Days 2 and 3; LV 500 mg/m2 administered intravenously (i.v.) on Day 1, followed by p.o. LV 15 mg every twelve hours on Days 2 to 14. Patients also received UFT p.o. 390 mg/m2/day on Days 1 to 14. Treatment was repeated every 28 days for a minimum of 3 courses per patient. All courses were given on an outpatient basis. RESULTS: Four patients (9%) had a complete response, and 12 a partial response (26%) for an overall response rate of 35% (95% confidence interval: 22-51%). The median duration of response was 10 months. The median overall survival was 9 months. The main side effects were gastrointestinal. Grade 3 to 4 toxicity was encountered as follows: diarrhea in 17% of the patients, nausea/vomiting in 11%, anemia in 13%, mucositis and leukopenia in 4% each, and thrombocytopenia in 2%. One patient died of sepsis and neutropenia. CONCLUSIONS: VP-16-LV-UFT has an activity comparable to that of other schemes and a low incidence of side effects. Furthermore, since it is administered mainly orally, hospitalization is avoided, which makes this scheme suitable for patients with advanced gastric carcinoma.

Administration, Oral↗

Selenium speciation by coupling vesicle mediated HPLC with off-line ETAAS and on-line focused microwave digestion HG-AAS detection.

A novel High Performance Liquid Chromatography (HPLC) method for the separation of selenium species with specific detection by off-line Electrothermal Atomization Atomic Absorption Spectrometry (ETAAS) or on-line focused microwave digestion (MW) Hydride Generation Atomic Absorption Spectrometry (HG-AAS) is described. Vesicular mobile phases of the cationic surfactant didodecyldimethylammonium bromide (DDAB) have been evaluated for the liquid chromatographic separation of inorganic selenium (selenite and selenate) and different selenoaminoacids (selenocystine, selenomethionine and selenoethionine) on a C(18) reversed-phase column modified by DDAB molecules. The effects of different parameters (pH, buffer and vesicle concentrations) of the mobile phase on the retention times have been determined. The detection limit for selenium with the proposed off-line HPLC-ETAAS method has been found to be 5 microg/L of Se. The detection limit using HPLC-"on line" focused microwave digestion-HG-AAS has been found to be 1 microg/L of Se, with a precision (repeatability) better than +/- 5%. The latter proved to be an exceptional on-line real-time chromatographic detector for selenium speciation purposes.

Journal Article↗

A three-dimensional virtual model of the head generated from digitalized CT or MR images for anatomical-radiological and neurosurgical evaluations.

A computer-generated virtual model has been developed that reconstructs the head in three dimensions from digitalized images obtained with magnetic resonance and computerized tomography. Through programming and the use of commercial graphic animation software, we have developed the whole process of the rotation of the head on different spatial planes. The procedure permits multidirectional anatomical sections to be made on the structure of the head, providing a true dynamic and user-friendly anatomical-radiological atlas. The system serves as a virtual model for the localization of an ideal surgical approach to any lesion thus avoiding possible neurological lesions.

Anatomy, Artistic↗

A phase II trial of weekly high dose continuous infusion 5-fluorouracil plus oral leucovorin in patients with advanced colorectal cancer. The Spanish Cooperative Group for Gastrointestinal Tumor Therapy (TTD).

BACKGROUND: In a previous Phase II trial, the authors showed that a weekly continuous infusion of 5-fluorouracil (5-FU) at a dose of 3.5 g/m2 for 48 hours is an active treatment for advanced colorectal cancer. The overall response rate was 38.5%, and the median survival was 12 months. These data were comparable to those achieved by biochemical modulation of 5-FU with leucovorin. To study the modulation of this weekly, high dose, continuous infusion 5-FU with oral leucovorin, a new Phase II trial was planned. METHODS: From December 1991 to July 1992, 43 previously untreated patients with measurable advanced colorectal cancer were included in a multicenter study. They received on an outpatient basis 5-FU at a weekly dose of 3 g/m2 by continuous infusion for 48 hours until progression or toxicity. Oral leucovorin (60 mg every 6 hours) also was given during the infusion of 5-FU. RESULTS: Patients received a median dose intensity of 5-FU of 2.2 g/m2/week (range, 0.76-3 g/m2/week). One complete response and 11 partial responses were observed. The overall response rate was 29% (95% confidence interval [CI], 16-45%). Median time to progression was 7 months, and the median survival was 15 months. World Health Organization Grades 3 and 4 diarrhea were observed in 19 (45%) and 6 (14%) patients, respectively. Grade 3 mucositis also was observed in 10 (24%) patients, and Grade 4 mucositis was observed in 1. Grade 3 nausea and vomiting were reported in seven (17%) patients. Grade 3 hand-foot syndrome was detected in only two (2.5%) patients. No leukopenia or thrombocytopenia was observed. CONCLUSIONS: Oral leucovorin modulation of a weekly 48-hour infusion of 5-FU at a dose of 3 g/m2 of leucovorin is a toxic regimen, always requiring dose reduction, with diarrhea and mucositis as the main limiting toxicities. Its antitumor activity does not seem superior to that observed with a weekly 48-hour infusion of 5-FU alone at a dose of 3.5 g/m2.

Administration, Oral↗

Efficacy of oral tegafur modulation by uracil and leucovorin in advanced colorectal cancer. A phase II study.

A phase II study was performed to assess the efficacy and toxicity of UFT (tegafur-uracil in the molar ratio 1:4) modulated with leucovorin (LV) in previously untreated patients with advanced colorectal carcinoma (CRC). 79 patients with measurable advanced colorectal cancer (CRC) and no prior chemotherapy were included. 75 patients were evaluable for toxicity and response. The regimen consisted of LV 500 mg/m2 administered intravenously on day 1, followed by oral UFT 390 mg/m2 on days 1-14. Patients received oral LV 15 mg every 12 h on days 2-14. Treatment was repeated every 28 days for a minimum of four courses per patient. Three hundred and ninety-eight cycles of chemotherapy were delivered (median five per patient). 7 patients (9%) had a complete response, and 22 a partial response for an overall response rate of 39%. Mild gastrointestinal toxicity was dose limiting: grade 3-4 diarrhoea appeared in 9% of patients. Other grade 3-4 toxicities were nausea/vomiting and mucositis in 4% of patients, gastric pain and leucopenia in 3%. Oral UFT modulated by oral LV is active in advanced CRC and can be administered on an outpatient basis with no significant toxicity requiring hospitalisation. Given its excellent tolerance profile and low toxicity, the regimen should be thoroughly studied and compared with 5-fluorouracil modulated by LV.

Administration, Oral↗

Morphological findings of an interrelationship among the neurosecretory axons of the neural lobe of the hypophysis.

In order to establish whether osmotic stimuli induce variations in the contact regions among neurosecretory axons of the neural lobe of the hypophysis, adult Sprague-Dawley rats of both sexes were treated with furosemide, a diuretic drug. Contacts between adjacent membranes with no condensations of the axolemma but increase in their osmiophilia were observed. After treatment with furosemide interaxonal contacts were significantly increased (p < 0.01, in relation to control animals). Additionally, following treatment with furosemide, axo-axonic synapses among the axons of the neural lobe were found. These findings suggest the existence of interactions among activated neurosecretory axons of the neural lobe of the adult rat.

Animals↗

Comparison of maintenance and recovery characteristics of sevoflurane-nitrous oxide and enflurane-nitrous oxide anaesthesia.

We compared maintenance of anaesthesia and recovery using either sevoflurane or enflurane anaesthesia in ASA I-III patients undergoing surgery with an anticipated minimum duration of 3 h. Serum fluoride concentrations were also measured to assess the potential for renal toxicity. After induction of anaesthesia with thiopentone, patients received, for maintenance, either 1.5% end-tidal sevoflurane (0.73 MAC) with N2O 58% (0.58 MAC) (n = 40) or 1.2% end-tidal enflurane (0.7 MAC) with N2O 57% (0.57 MAC) (n = 40). Other drugs administered during anaesthesia were similar in all groups. Haemodynamic measurements, recovery times, as well as post-operative nausea and vomiting were comparable in both groups. The mean peak plasma inorganic fluoride ion concentrations were reached 4 h after operation in both groups (27.7 microM L-1 for sevoflurane and 16.75 microM L-1 for enflurane, P < 0.05) declining 50% within 24 h in both groups. A positive correlation (P < 0.05) was found between anaesthetic exposure (MAC h) and fluoride concentrations in the two groups. Sevoflurane anaesthesia resulted in similar haemodynamic stability, recovery times and post-operative side effects as enflurane anaesthesia, but produced significantly greater serum fluoride levels.

Analgesics, Opioid↗

Coexistence of NADPH-diaphorase with vasopressin and oxytocin in the hypothalamic magnocellular neurosecretory nuclei of the rat.

Coexistence of NADPH-diaphorase with vasopressin and oxytocin was studied in the magnocellular neurosecretory nuclei of the rat hypothalamus by use of sequential histochemical and immunocytochemical techniques in the same sections. Coexistence was found in all the nuclei examined (supraoptic, paraventricular, circular, fornical, and in some isolated neurons located in the hypothalamic area between the paraventricular and supraoptic nuclei). The ratios of neurons expressing both markers (NADPH-diaphorase and vasopressin, NADPH-diaphorase and oxytocin) in each of the nuclei were very similar. Although further studies must be carried out, the partial coexistence found in all nuclei suggests that NADPH-diaphorase is probably not related to general mechanisms involving vasopressin and oxytocin, but rather in specific functions shared by certain hypothalamic neuronal cell populations.

Animals↗

Localization of tyrosine hydroxylase mRNA in the axons of the hypothalamo-neurohypophysial system.

With in situ hybridization we examined the localization of mRNA coding for tyrosine hydroxylase (TH) in the rat hypothalamo-neurohypophysial system (HNS) under conditions of acute osmotic stress. Fifteen min after salt loading, hybridization signal of TH mRNA could be located in the magnocellular hypothalamic nuclei and in the median eminence (ME). In untreated animals, TH mRNA was detected only in the ME. In osmotically challenged animals that had been pretreated with colchicine, signals for TH mRNA remained confined to the ME, while pretreatment of salt loaded rats with a polymerase II transcription inhibitor resulted in labelling of the magnocellular perikarya but a decrease of the hybridization signal in the ME. Our results suggest that also TH mRNA is among the RNAs which are axonally transported in the HNS. TH mRNA can probably be stored in axons of the hypothalamo-neurohypophysial tract, to be transported retrogradely and translated upon certain stimuli.

Animals↗

Comparison of two chemotherapeutic regimens--mitomycin + vindesine + cisplatin (MVP) vs. mitomycin + ifosfamide + cisplatin (MIP)--in advanced non-small-cell lung cancer. ONCOPAZ Cooperative Group.

BACKGROUND: A prospectively randomized trial was performed to compare the efficacy and toxicity of two chemotherapeutic regimens widely used in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: From January 1989 to March 1992, 196 patients with measurable disease were included in the trial. Ninety-three patients received mitomycin-vindesine-cisplatin (MVP) and 94 mitomycin-ifosfamide-cisplatin (MIP). RESULTS: The objective response rate (complete plus partial remissions) was 28% (26/93 patients, 95% confidence interval 20%-40%) in the MVP arm and 30% (28/94 patients, 95% confidence interval 20.5%-40%) in the MIP arm. The median survival was 8.5 and 9 months, respectively. Neither the response rates nor the median survivals were significantly different. Grade III-IV leukopenia was more frequent with MVP (13% vs. 2% of the courses, p < 0.001), as well as grade I-II neurologic toxicity (30% vs. 6%, p < 0.001). In contrast, grade I-II anemia and grade I-II urologic toxicity were more frequent with MIP (7% vs. 25%, p < 0.001 and 1% vs. 11%, respectively). CONCLUSION: Given the low efficacy of both schemes in the treatment of advanced NSCLC, their use cannot be recommended outside of clinical trials.

Adult↗

Changes in the neurosecretory axons of the neural lobe of the hypophysis of rats treated with met-enkephalin. An ultrastructural study.

Following administration of met-enkephalin into the third ventricle of rats of both sexes, an ultrastructural-morphometric study was carried out of the neural lobe of the hypophysis, comparing the results with those obtained in untreated animals, controls (injected intraventricularly with distilled water) and animals previously receiving naloxone intraperitoneally. In the untreated and control animals, both males and females, there was a high percentage (about 70%) of neurosecretory axons considered to have a normal morphology; after met-enkephalin administration, this percentage decreased and was accompanied by a rise (slightly more pronounced in the females) in the percentage of degranulated axons and a slight rise in axons with a morphology indicative of regenerative and degenerative phases. Previous administration of the opiate antagonist naloxone led to a rise in the number of axons in the degenerative phase with respect to the other groups of animals; this occurred in both sexes.

Animals↗

Repercussion of craniopharyngioma on the morphology of the rostral wall of the III ventricle. A combined TEM and SEM study.

Using a combined scanning and electron microscope technique, the repercussion on the rostral wall of the III ventricle in a patient affected with a retrochiasmatic craniopharyngioma with growth in the ventricular direction were analysed. The apical surface of the ependymocytes was found to be free of cilia, although there were numerous microvilli. The most striking finding appreciated with the scanning electron microscope was the presence of bulbous protrusions towards the lumen of the ventricle; these were formed of cells with shapes, sizes and surface characteristics different from the rest of the ependyma, which appeared flattened. The ultrastructural study revealed the presence of large numbers of filaments and junction complexes both in the ependymal and subependymal cells. Additionally, the protruded zones corresponded to areas showing different degrees of cellular disorganization.

Cerebral Ventricles↗

One year's experience with an acute pain service in a Spanish University Clinic hospital.

We describe the experience of the acute pain service of the University Hospital of Galicia, Spain since its inception. We have treated 1214 patients using either patient-controlled analgesia (PCA) with morphine (72%), or patient-controlled epidural analgesia with fentanyl + bupivacaine (22%). Three hundred and five patients had minor complications, mainly pruritus (35%) in patients with patient-controlled epidural analgesia. Three (0.33%) patients using PCA had respiratory depression treated with naloxone; no patient with patient-controlled epidural analgesia had respiratory depression. In our experience the creation of an acute pain service and the associated development of pain-treatment protocols and the training of hospital personnel produced excellent results.

Academic Medical Centers↗