Biomedical subjects
Publications and source records attributed to A Pastor.
1-Acylbenzotriazoles 1 are efficient C-acylation reagents for the regioselective conversion of ketone enolates 2 into beta-diketones 3.
We have developed a new nonradioactive assay to identify human low-density lipoprotein receptor defects. It is based on the incubation of cultured cells with colloidal gold-LDL conjugates and quantitation of the gold associated with the cells by electrothermal atomic absorption spectrometry. After an oxidative treatment with nitric and hydrochloric acids, the biological matrix interferes neither with the gold recovery nor with the gold measurements, which are linear, at least from 0.15 to 3 ng of gold. When cells expressing a functional LDL receptor are incubated with increasing amounts of colloidal-gold LDL conjugates, the obtained saturation curve parallels that described when [125I]LDL is used as ligand. Moreover, this new assay allows us to clearly distinguish among fibroblasts from normal subjects or from heterozygous or homozygous patients of familial hypercholesterolemia, a very common autosomal disease. The assay is easy to perform, is sensitive, and avoids the use of radioactive compounds. Therefore, it could be successfully employed in the clinical diagnosis of this disease. Furthermore, since the methodology developed here can be applied to quantify the association of other gold-conjugated ligands to cells, it could have a widespread use in a variety of clinical and basic research studies.
[formula: see text] Allylic amines 5 are obtained in 30-55% overall yields by the base-catalyzed hydrolysis of trialkylated allylic urazoles 3; the latter are prepared by the TAD ene reaction of the appropriate olefin and further N-alkylation with alpha-bromoacetophenone. The proposed mechanism for this novel urazole rupture is based on the generation of a carbanion adjacent to the hydrazide functionality, which induces urazole ring-opening by cleavage of the N-N bond.
[formula: see text] A high extent but opposite sense in the diastereoselectivity has been observed for the DMD and m-CPBA epoxidations of the optically active tiglic amides (S)-1 with 2,2-dimethyloxazolidines as chiral auxiliaries. This unprecedented reversed pi-facial differentiation for these two peroxidic oxidants is rationalized in terms of like (lk) and unlike (ul) transition structures: For DMD, steric interactions dominate, such that the unlike transition structure is favored, while for m-CPBA, hydrogen-bonding effects overcome these steric repulsions and the like one is preferred.
[reaction: see text] Reactions of chalcones 3a-f with bis(1H-1,2,4-triazolyl) sulfoxide 4 formed the thiazolo[3,2-b]1,2,4-triazoles 5a-f, which resemble closely some previously prepared COX-2 inhibitors. The structure of 5a was confirmed by X-ray analysis.
We report the case of a 43 year-old male with a long history of paroxysmal palpitations aborted by vagal manoeuvres, where atrial fibrillation was the only documented arrhythmia. During the electrophysiological study an AV nodal reentrant tachycardia was demonstrated with rapid degeneration into atrial fibrillation. After slow pathway ablation, nodal tachycardia became non-inducible. No palpitations were reported and no arrhythmic event was recorded after a follow-up of 20 months. In selected cases, the electrophysiological study could reveal potentially curable causes of atrial fibrillation.
Explore the source record for details and available documents.
The P450 enzyme, CYP3A4, extensively metabolizes both amprenavir and clarithromycin. To determine if an interaction exists when these two drugs are coadministered, the pharmacokinetics of amprenavir and clarithromycin were investigated in healthy adult male volunteers. This was a Phase I, open-label, randomized, balanced, multiple-dose, three-period crossover study. Fourteen subjects received the following three regimens: amprenavir, 1,200 mg twice daily over 4 days (seven doses); clarithromycin, 500 mg twice daily over 4 days (seven doses); and the combination of the above regimens over 4 days (seven doses of each drug). Twelve subjects completed all treatments and the follow-up period. The erythromycin breath test (ERMBT) was administered at baseline, 2 h after the final dose of each of the three regimens and at the first follow-up visit. Coadministration of clarithromycin and amprenavir significantly increased the mean amprenavir AUC(ss), C(max,ss), and C(min,ss) by 18, 15, and 39%, respectively. Amprenavir had no significant effect on the AUC(ss) of clarithromycin, but the median T(max,ss)for clarithromycin increased by 2.0 h, renal clearance increased by 34%, and the AUC(ss) for 14-(R)-hydroxyclarithromycin decreased by 35% when it was given with amprenavir. Amprenavir and clarithromycin reduced the ERMBT result by 85 and 67%, respectively, and by 87% when the two drugs were coadministered. The baseline ERMBT value did not correlate with clearance of amprenavir or clarithromycin. A pharmacokinetic interaction occurs when amprenavir and clarithromycin are coadministered, but the effects are not likely to be clinically important, and coadministration does not require a dosage adjustment for either drug.
After years of development, radiofrequency ablation of common flutter circuits is a well established procedure. Once the structure of the circuit, and its critical isthmus, were defined, effective approaches to ablation have been developed, improving initial results. The problem of recurrence has been largely controlled, and the present recurrence rate is 10-15%. The large majority of recurrences can be treated successfully by a new ablation, with a very low incidence of second recurrence. Nevertheless, isthmus ablation is not a curative procedure, because it does not address the cause of flutter, only a necessary link in the circuit. The electrophysiologic and/or anatomic abnormalities of the atrium or atria persist after ablation. Perhaps for this reason there is an incidence of atrial fibrillation in 25-30% of cases after successful flutter ablation. On the other hand, some clinical data suggest that a first episode of flutter has a low incidence of recurrence after cardioversion. For all these reasons flutter ablation should not be considered as first line treatment in all episodes of atrial flutter, but of those with recurrences and/or poor tolerance.
Anomalous continuation of the inferior vena cava with an azygous vein is a rare vacular anomaly. The enlarged venous system may simulate adenopathies or mediastinal and retroperitoneal masses on the radiographs. We describe the case of a patient with lung cancer - a pathological condition which may cause adenopathies at these sites - and a dilated azygous-hemiazygous system resulting from failure of formation of the hepatic segment of the inferior vena cava.
STUDY OBJECTIVE: To determine the effects of coadministration of amprenavir and ketoconazole on the pharmacokinetics of both drugs, and to assess the utility of the erythromycin breath test (ERMBT) to predict and explain these effects. DESIGN: Open-label, randomized, balanced, single-dose, three-period crossover study. SETTING: University research center. SUBJECTS: Twelve healthy men. INTERVENTION: Subjects received amprenavir 1200 mg, ketoconazole 400 mg, and amprenavir 1200 mg plus ketoconazole 400 mg. Each treatment was separated by 14 days. MEASUREMENTS AND MAIN RESULTS: Serial plasma samples for amprenavir and ketoconazole concentrations were measured by high-performance liquid chromatography. Coadministration of the drugs increased amprenavir area under the curve extrapolated to infinity (AUCinfinity) by 31% and reduced its maximum concentration (Cmax) by 16%. Amprenavir increased the AUCinfinity of ketoconazole by 44% and increased the drug's half-life and Cmax by 23% and 19%, respectively. Both agents resulted in substantial inhibition of ERMBT. CONCLUSION: Coadministration of ketoconazole and amprenavir results in a statistically significant increase in AUC for both agents, but the changes are not likely to be clinically important.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
"Less aggressive" burst stimulation is more effective in terminating spontaneous monomorphic ventricular tachycardia with a lesser acceleration rate. Higher ventricular tachycardia cycle length and use of 91% coupling interval were independent predictors for pacing termination.
Human cytomegalovirus (HCMV)-specific antibody responses in HIV-1 infected individuals either with or without HCMV end-organ disease were examined to determine the whether development of HCMV disease was associated with a particular deficit in the antibody response. Antiwhole HCMV, anti-glycoprotein B (gB), and neutralizing antibody levels were higher in HIV-1 infected individuals than in healthy immunocompetent subjects, particularly in patients with AIDS either with or without HCMV-associated disease. Irrespective of location and spread of HCMV disease, patients who had received anti-HCMV therapy prior to sampling exhibited significantly higher anti-gB and neutralizing antibody titers than those who remained untreated. Likewise, patients with HCMV disease who were antigenemic or viremic had significantly lower anti-gB and neutralizing antibody titers than those who tested negative in either assay. Patients with untreated HCMV disease had significantly lower antibody titers than AIDS patients without disease. Analysis of the IgG subclass antibody responses to gB revealed no significant differences among HIV-1 infected individuals. These results suggest that levels of detectable anti-gB and HCMV neutralizing antibodies are inversely related to systemic viral load. Thus, antibodies with such specificities may be relevant in preventing the establishment of HCMV-associated disease or in modulating its progression.
OBJECTIVE: Since the 1990's radiofrequency ablation radiofrequency ablation of atrial flutter has evolved in its methods and results. We have reviewed the long term outcome in 62 patients with typical (common) or reversed (clockwise) flutter undergoing radiofrequency ablation between 1990 and 1997. PATIENTS AND METHODS: Fifty men and 12 women, aged 22-78 years (57 +/- 12) with flutter recurring after cardioversion and antiarrhythmic drugs make this series. Flutter was typical in 59 cases and reversed in 3. There was no heart disease in 14, bronchopulmonary disease in 10, coronary disease in 9, cardiomyopathies in 6 and other processes in the remainder. In 5 cases with previous surgery for atrial or ventricular septal defect, Ebstein's anomaly or myxoma, we treated also a macro-reentry tachycardia around the atriotomy in the right atrium. Radiofrequency ablation was directed to the inferior vena cava-tricuspid isthmus in typical and reversed flutter, and to the isthmus between the inferior end of the atriotomy and the inferior vena cava, in the lateral right atrium, in the atriotomy tachycardias. We subdivided our patients in Group 1 (24 patients), treated until the end of 1994, and Group 2 (38 patients) treated since 1995 using specially designed catheters and trying to produce isthmus block as the endpoint of the procedure. RESULTS: Radiofrequency ablation interrupted flutter in 61 of 62 cases (98.4%), and the atriotomy tachycardia in all 5. The number of application in Group 1 was 18.6 +/- 10.1 vs 12 +/- 10 in Group 2 (p < 0.05). Follow-up was 40 +/- 24 months in Group 1 vs 16 +/- 9.5 in Group 2. Flutter recurred in 58% of Group 1 and 13% of Group 2 patients (p < 0.001), usually 1-3 months after radiofrequency ablation and they were successfully treated by new radiofrequency ablation with a small number of applications. There was no recurrence of atriotomy tachycardia. Atrial fibrillation occurred in 14 patients (23%) (11 paroxysmal, 3 persistent), with equal incidence in both groups. At the end of follow-up 85% of the patients were in sinus rhythm, although 6 needed pacemakers for sinus node dysfunction (3) or AV ablation (3). Antiarrhythmic drugs were used by 46% of patients in Group 1 and 26% in Group 2 (p = NS) for atrial arrhythmias or recurrent flutter. CONCLUSIONS: Radiofrequency ablation is an effective treatment for flutter and macro-reentry atriotomy tachycardia. Progress in methods have improved results significantly. Atrial fibrillation can still be a problem in 20-25% of the patients after flutter control.
The aim of this study was to evaluate the diagnostic value of a new tumour marker, cytokeratin fragment 19 (CYFRA 21-1), in bronchoalveolar lavage fluid (BALF) for the diagnosis of lung cancer. The cross-sectional study included 36 patients with lung cancer, 19 with benign lung diseases and 13 control subjects. In the group with cancer, BAL was performed in the cancer-involved lung and in the opposite lung. Results in BALF were expressed both as absolute concentrations (ng ml-1) and referred to total protein (TP) (ng mg-1 TP), and results in plasma were expressed in ng ml-1. In BALF, there was no significant different between cancer and control groups. Using the 95th percentile of levels obtained in benign lung disease in BALF (specificity 95%) as the cut-off point, the sensitivity of CYFRA 21-1 was 13%. Positive and negative predictive values (PPV and NPV) at different pretest probabilities, and positive and negative gains were obtained applying a Bayesian analysis. Results showed low positive gains for PPV (maximal increase of 22%) and almost none for NPV (negative gains < 5%). In plasma, CYFRA 21-1 provided a sensitivity of 65%. The combination of BALF and plasma tumour marker levels showed a sensitivity of 69%. Therefore, measurement of CYFRA 21-1 in BALF has poor diagnostic value in lung cancer.
The in vitro activity of fluconazole against 65 Candida albicans isolated from blood culture in 1995, 1996 and 1997 was studied by macrodilution and disk diffusion methods. The MIC ranged from 0.03 to 64 microg/ml, with 93.6% of strains being inhibited with 1 microg/ml fluconazole; the mode MIC was 0.25 microg/ml. Using this method, only one strain was resistant and another was susceptible depending on the dose. By diffusion, eight strains were susceptible, 53 intermediate, and four resistant. The strains susceptible by dilution were also susceptible by diffusion, but the strains resistant by diffusion were not always resistant by dilution. We find it therefore useful to determine the MIC of fluconazole to the C. albicans resistant by diffusion.