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Biomedical subjects

J Segura

Publications and source records attributed to J Segura.

At least 145 records · Page 8Linked to original sources

Balloon valvuloplasty for mild mitral stenosis.

Of a total number of 288 patients with mitral stenosis treated by percutaneous balloon valvuloplasty, 21 patients had a basal mitral area equal to or greater than 1.5 cm2, as measured hemodynamically. The immediate hemodynamic results of this particular group of patients with mild mitral stenosis are described, as well as the clinical and echo doppler findings at follow-up (22 +/- 12 mo). Patients with mild mitral stenosis (group I) had more pliable valves (p less than 0.01), as assessed by echo, and higher incidence of sinus rhythm (p less than 0.02) than that observed in the remaining 267 patients (group II). After valvuloplasty the valve area increased in group I from 1.7 +/- 0.2 to 3.1 +/- 0.7 cm2 (p less than 0.0001). This mean final area was significantly different (p less than 0.0001) than that observed in group II (1.98 +/- 0.6 cm2). No patients with mild mitral stenosis developed progression of mitral regurgitation, and none had any other major complications. Most of them reached a grade I final functional status. At echo doppler follow-up studies we did not observe significant changes in the mean mitral gradient as compared with the immediate hemodynamic results. These findings suggest that early mitral balloon valvuloplasty could be an alternative in trying to favorably influence the natural course of the rheumatic mitral disease in selected patients.

Adult↗

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.

Adult↗

Selective in-vitro inhibition of hepatic oxidative metabolism by quinolones: 7-ethoxyresorufin and caffeine as model substrates.

The in-vitro inhibition of several metabolic pathways has been studied in 3-methylcholanthrene-treated rats. The specificity of the 7-ethoxyresorufin O-de-ethylase reaction has been determined in the presence and absence of ciprofloxacin, enoxacin, norfloxacin, ofloxacin, nalidixic acid, oxolinic acid and pipemidic acid. For the caffeine N3-demethylation reaction, enoxacin and pipemidic acid were used. Enoxacin (IC50 = 105 microM, Ki = 65 microM) and pipemidic acid (IC50 = 115 microM, Ki = 160 microM) significantly inhibited 7-ethoxyresorufin O-de-ethylase reaction and caffeine N3-demethylation (IC50 = 60 microM for enoxacin and IC50 = 185 microM for pipemidic acid) by a competitive mechanism. Other quinolones had lower or no (ofloxacin) inhibitory capacity. The order of inhibitory activity observed is in agreement with results obtained previously from in-vivo studies in man. No activity was detected towards ethylmorphine N-demethylation.

4-Quinolones↗

[Acute pericarditis as initial clinical manifestation of hypereosinophilia syndrome].

The case of a patient in whom acute pericarditis was the initial manifestation of an idiopathic hypereosinophilia is reported. Endomyocardial abnormalities were not found by echocardiography. Response to prednisone therapy was good; symptoms, pericardial effusion and eosinophilia early disappeared after therapy. Some clinical aspects of this uncommon disease are discussed.

Acute Disease↗

[Valvulopathies (XIV). The role of percutaneous valvuloplasty in congenital valvular diseases].

The present article describes the cooperative experience Córdoba-Las Palmas since 1983 in 123 patients with congenital right or left ventricular outflow obstructions who were treated by percutaneous balloon dilatation. Seventy of them had pulmonary stenosis (63 valvular and seven supravalvular types); two had pulmonary atresia, 25 valvular aortic stenosis and 27 discrete subaortic stenosis. In patients with valvular pulmonic stenosis the gradient and the right ventricular pressure decreased significantly. No significant changes were observed in the degree of pulmonary regurgitation. One neonate died. No other major complications occurred. After a mean follow up of 3 +/- 2 years, we did not observe significant changes in the degree of pressure relief. The mean residual gradient is 26 +/- 19 mmHg. In our 21 patients out of the neonatal period with valvular aortic stenosis the gradient and the left ventricular pressure dropped significantly. Progression of aortic regurgitation in more than I grade was observed in 4 patients (19%), although only one (5%) progressed to grade III. There were no major complications in this group. After a mean follow up period of 24 +/- 17 months they persist with the obtained pressure relief and same degree of valvular competence. All 4 neonates with critical aortic stenosis had unsuccessful dilations and they died, wether after ulterior surgery or without it. In 27 patients with discrete subaortic stenosis the gradient and the left ventricular pressure decreased markedly, without significant changes in valve competence. There were no related major complications. After dilation, a broken and mobile membrane was frequently seen. At follow up (24 +/- 18 months), 6 patients (22%) had restenosis; five of them were successfully redilated. The remaining 21 patients persist with a reduced residual gradient (24 +/- 7 mmHg) and without significant changes in valve competence.

Adolescent↗

[Comparative multicentric study of omeprazole versus ranitidine in the treatment of duodenal ulcer].

A total of 158 patients, aged 19-78 years and with endoscopically verified duodenal ulcer of at least 5 mm in maximum diameter were recruited. 79 patients were randomised to treatment with omeprazole, a proton-pump inhibitor of the parietal cell, and 79 patients were treated with ranitidine. This double blind study is the first clinical trial with omeprazole in Spain. Using "intention to treat" analysis there was no difference in healing rates at 2 weeks between the omeprazole group (70%) and the ranitidine group (59%) with p = 0.13. At four weeks, however, omeprazole healed significantly more patients (92%) than ranitidine (76%) with p = 0.005. Using per protocol analysis a similar result was obtained with no significant difference between omeprazole (71%) and ranitidine (63%) at two weeks (p = 0.3) but significantly greater healing on omeprazole at 4 weeks (97%) compared with ranitidine (83%) with p = 0.008. The influence of additional prognostic factors was assessed using a multivariate analysis. At two and four weeks, there was a significant effect of ulcer size on healing rate. At four weeks there was also a significant effect of treatment. Symptom relief was rapid in both treatments but the omeprazole group had significantly fewer days of pain and better patient's overall evaluation than ranitidine group. No serious adverse events were reported. In conclusion omeprazole healed significantly more duodenal ulcers than ranitidine and symptom relief was more rapid during omeprazole therapy.

Adult↗

[Coronary permeability and left ventricular function following thrombolytic therapy].

We study 40 patients, 55 +/- 7 years old with acute myocardial infarction treated early by thrombolytic therapy (20 STK and 20 rt-PA). All patients were angiographically studied in the following conditions: 1) baseline, before initiating therapy. 2) Three hours after treatment. 3) Twenty four hours later. 4) Before discharge. The infarct related artery was patent 24 hours after treatment in 31 patients (78%); five of them were patent before treatment, and we observed an early reperfusion in 20 patients (57%) and late reperfusion in 6 patients (17%). The number of patients with angiographic evidence of intraluminal thrombus decreased progressively through conditions while the grade TIMI of coronary perfusion increased in the absence of reocclusion. Final regional wall motion of infarct related myocardial zones and their degree of recovery were significantly higher in recanalized patients, as compared with non-reperfused patients. Similarly, left ventricular functional recovery was higher in patients with antegrade of collateral flow to the infarct area, as compared with totally occluded patients.

Coronary Angiography↗

Factors influencing progression of mitral regurgitation after transarterial balloon valvuloplasty for mitral stenosis.

This study analyzes the clinical, echocardiographic and hemodynamic factors affecting progression of mitral regurgitation (MR) after transarterial balloon valvuloplasty in 200 consecutive patients with rheumatic mitral stenosis. After valvuloplasty, the mitral valve area increased in all patients, from 1.03 +/- 0.36 to 2.06 +/- 0.71 cm2 (p less than 0.0001). With regard to the basal stage, the mitral valve was competent in 139 patients and there was mild MR in 61 (grade I in 53, and grade II in 8). Three patients had progression of MR induced by a technical deficiency and they were excluded from analysis. Patients were classified into 2 groups on the basis of the degree of MR before and after valvuloplasty: group A--no progression of MR (n = 167; 85%) when the degree of MR did not change, disappeared after valvuloplasty, or increased from grade 0 to I; group B--progression of MR (n = 30; 15%) when the degree of MR increased to greater than or equal to grade II. Progression of MR was observed more frequently in older patients with presence of chronic atrial fibrillation, larger left atrial size and left ventricular volumes, baseline MR, more severe stenosis and a lower ejection fraction. Multivariate analysis selected age, left ventricular volumes and ejection fraction as independent predictors of progression of MR. All these factors suggest that progression of MR after balloon valvuloplasty could be related to a more advanced degree of disease.

Age Factors↗

Pharmacokinetic determination of relative potency of quinolone inhibition of caffeine disposition.

Quinolone is reported to interact with caffeine, often resulting in an increase both in the plasma half-life and AUC, a decrease in total plasma clearance, and little change in the absorption rate constant and maximum plasma level. These complex changes in the pharmacokinetics of caffeine were analyzed experimentally and from published reports in order to determine the nature of the interaction, which is thought to be due to inhibition of caffeine metabolism by quinolones. A simple pharmacokinetic model for the caffeine-quinolone interaction was developed, which provides a unified method for evaluation and comparison of the effect of quinolones on the disposition of caffeine. The model is applicable to other methylxanthines, such as theophylline. The relative potency of the interactions of quinolones with caffeine in humans has been established as enoxacin (100), pipemidic acid (29), ciprofloxacin (11), norfloxacin (9) and ofloxacin (0).

Caffeine↗

Assay of caffeine metabolism in vitro by human liver microsomes using radio-high-performance liquid chromatography.

The low turnover of caffeine in vitro by human liver microsomes makes the study of the metabolic pathways of this compound difficult. Analytical methods with high sensitivity and specificity are needed for the detection of its metabolic products. A method based on the on-line radiometric determination of [8C-3H]caffeine and its principal metabolite (paraxanthine) in man has been developed using reversed-phase high-performance liquid chromatography. The method has been successfully employed in preliminary studies of the kinetics of this reaction.

Biotransformation↗

Determination of morphine and codeine in urine by gas chromatography-mass spectrometry.

GC-MS is one of the recommended analytical techniques for the identification and confirmation of opiates in urine. A method for the qualitative detection and quantitation of codeine and morphine in urine samples by this technique has been developed. This method is also suitable for the detection of their main metabolites in urine: norcodeine and normorphine. It also allows the identification of 6-monoacetylmorphine in urine, which can be used as a confirmatory marker of heroine abuse. The derivatized compounds are separated by capillary gas chromatography (GC) and identified by mass spectrometry (MS) in the selective ion monitoring acquisition mode (SIM). The recoveries from urine at concentrations of 1000 ng ml-1 are 72% for codeine and 80% for morphine. The method is linear in the range studied (0-1000 ng ml-1) for codeine and morphine.

Codeine↗

Simultaneous detection in urine of cocaine and its main metabolites.

The simultaneous detection in urine of cocaine (CO), and the main biotransformation products, benzoylecgonine (BE) and ecgonine methyl ester (EME), is difficult due to their different physicochemical properties. The method presented involves a bonded silica solid-phase extraction procedure that allows mixed ionic and apolar interactions with the analyte. After extraction the compounds are derivatized sequentially with ethyliodide to obtain the BE ethyl ester derivative, and with N-methyl-N-trimethylsilyl trifluoroacetamide (MSTFA) to obtain the O-TMS derivatives. The derivatized compounds are then analysed by a capillary (methylphenylsilicone) gas chromatographic system equipped with a specific nitrogen-phosphorus detector. The method is suitable for the confirmation and quantitation of CO and its main metabolites in urine. BE levels in urine samples (n = 20) measured by the described method and by an immunological technique were in close agreement (r = 0.999).

Chemical Phenomena↗

Furafylline is a potent and selective inhibitor of cytochrome P450IA2 in man.

1. Furafylline (1,8-dimethyl-3-(2'-furfuryl)methylxanthine) is a methylxanthine derivative that was introduced as a long-acting replacement for theophylline in the treatment of asthma. Administration of furafylline was associated with an elevation in plasma levels of caffeine, due to inhibition of caffeine oxidation, a reaction catalysed by one or more hydrocarbon-inducible isoenzymes of P450. We have now investigated the selectivity of inhibition of human monooxygenase activities by furafylline. 2. Furafylline was a potent, non-competitive inhibitor of high affinity phenacetin O-deethylase activity of microsomal fractions of human liver, a reaction catalysed by P450IA2, with an IC50 value of 0.07 microM. 3. Furafylline had either very little or no effect on human monooxygenase activities catalysed by other isoenzymes of P450, including P450IID1, P450IIC, P450IIA. Of particular interest, furafylline did not inhibit P450IA1, assessed from aryl hydrocarbon hydroxylase activity of placental samples from women who smoked cigarettes. 4. It is concluded that furafylline is a highly selective inhibitor of P450IA2 in man. 5. Furafylline was a potent inhibitor of the N3-demethylation of caffeine and of a component of the N1- and N7-demethylation. This confirms earlier suggestions that caffeine is a selective substrate of a hydrocarbon-inducible isoenzyme of P450 in man, and identifies this as P450IA2. Thus, caffeine N3-demethylation should provide a good measure of the activity of P450IA in vivo in man. 6. Although furafylline selectively inhibited P450IA2, relative to P450IA1, in the rat, this was at 1000-times the concentration required to inhibit the human isoenzyme, suggesting a major difference in the active site geometry between the human and the rat orthologues of P50IA2.

Adolescent↗

Species variation in the response of the cytochrome P-450-dependent monooxygenase system to inducers and inhibitors.

1. In the safety evaluation of drugs and other chemicals it is important to evaluate their possible inducing and inhibitory effects on the enzymes of drug metabolism. 2. While many similarities exist between species in their response to inducers and inhibitors, there are also important differences. Possible mechanisms of such variation are considered, with particular reference to the cytochrome P-450 system. 3. Differences in inhibition may be due to differences in inhibitory site of the enzyme involved, which is not always the active site of the enzyme, in competing pathways or in the pharmacokinetics of the inhibitor. 4. Differences in induction could be due to differences in the nature of the induction mechanism, in the isoenzyme induced, in tissue- or age-dependent regulation, in competing pathways for the substrate or its products, or in the pharmacokinetics of the inducing agent. 5. Examples of each of these possible differences are considered, often from our own work on the P450 IA subfamily, and results in animals are compared with those in humans, where possible. 6. At present, the differences between species in their response to inducers and inhibitors make extrapolation to humans from the results of animal studies difficult, so that ultimately such effects should be studied in the species of interest, humans.

Allosteric Regulation↗

[Role of percutaneous valvuloplasty in rheumatic mitral valve stenosis. Córdoba-Las Palmas cooperative study].

This article describes our findings on a prospective and cooperative study (Córdoba-Las Palmas) in 203 patients with mitral stenosis who underwent balloon valvuloplasty using a retrograde transarterial technique. We analyzed the immediate and mid-term results, and studied the factors determining an optimal result and those related to the new appearance or worsening of mitral incompetence after the procedure. On the other hand, we analyzed the results of mitral valvuloplasty in patients with previous mitral surgery, mild mitral stenosis and patients dilated while having an acute pulmonary edema. We observed a marked decrease in mean mitral gradient (17 +/- 7 to 6 +/- 3 mmHg; p less than 0.001) as well as a significant increase in mitral valve area (1.02 +/- 0.4 to 2.04 +/- 0.7 cm2; p less than 0.001). Echo-Doppler follow-up did not show significant changes in the residual mitral valve gradient. Multivariate analysis selected, as independent predictors of an optimal result, the presence of a pliable valve and the absence of basal mitral regurgitation. On the other hand, the presence of a lower ejection fraction, an older age and a higher baseline left ventricular endiastolic volume were independent factors determining progression of mitral regurgitation. In patients with previous mitral surgery, the clinical, echo and hemodynamic profiles, as well as the immediate results, were similar to those observed in patients with unoperated mitral stenosis. In the subgroup of mild mitral stenosis, we observed and optimal result in all cases, without major complications. Mitral valvuloplasty was dramatically effective in 8 patients treated during acute pulmonary edema.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗