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Biomedical subjects

E Sanz

Publications and source records attributed to E Sanz.

At least 19 recordsLinked to original sources
PubMed1995

Dissociation between anti-infarct effect and anti-edema effect of ischemic preconditioning.

This study tested the hypothesis that preconditioning, by reducing catabolite accumulation during ischemia, reduces osmotic swelling and myocardial necrosis during subsequent reperfusion. Farm pigs were randomly allocated to one of three groups of treatment: a control group undergoing a 48-min coronary occlusion (CO) of the middle left anterior descending artery, a preconditioned group (2 cycles of 5-min CO and 5-min reperfusion before the 48-min CO), or an intracoronary perfusion group receiving a substrate-free anoxic buffer perfusion into the area at risk between minutes 5 and 10 of the prolonged CO. Animals were killed after 30 min (n = 23) or 6 h (n = 31) of reperfusion. Compared with the control group, both ischemic preconditioning and washout of ischemic by-products by transient anoxic perfusion reduced myocardial edema after 30 min of reperfusion (P < 0.002) by 35 and 32%, respectively, but only ischemic preconditioning reduced final infarct size (by 55%, P < 0.006). Myocardial lactate content before reperfusion, measured in an additional series of 12 experiments, was reduced by 35% in animals receiving preconditioning or intracoronary perfusion. Thus ischemic preconditioning has a marked protective effect against reperfusion edema, and this effect can be explained by reduced catabolite accumulation during ischemia. However, there is no evidence from this study indicating that reduced catabolite accumulation and limited reperfusion edema explain the important anti-infarct effect of ischemic preconditioning.

Animals↗
PubMed1995

Determination of alkaline phosphatase isozymes in amniotic fluid.

A simple method for the determination of the three isozymes of alkaline phosphatase (EC 3.1.3.1) contained in amniotic fluid (fetal intestinal, placental, and liver-bone-kidney) is presented. Total alkaline phosphatase activity was assayed in 10,000 g supernatants of amniotic fluid from 30 normal women between the 16th and 20th week of pregnancy. Electrophoretic patterns and inhibition by L-phenylalanine and L-homoarginine studies showed that all the fetal intestinal isozyme was precipitated in the pellet after centrifugation at 100,000 g for 90 min. Thus, the difference between total alkaline phosphatase activity and activity in the 100,000 g supernatant corresponds to fetal intestinal alkaline phosphatase. Placental isozyme can be determined by assaying alkaline phosphatase in the 100,000 g supernatant after heating at 56 degrees C for 90 min. Liver-bone-kidney isozyme activity is obtained by subtracting placental alkaline phosphatase activity from that of the 100,000 g supernatant. Mean percentages of the total alkaline phosphatase for each of the isozymes in amniotic fluid were 81% for fetal intestinal alkaline phosphatase, 7.5% for placental alkaline phosphatase and 12.0% for liver-bone-kidney alkaline phosphatase. Determination of fetal intestinal alkaline phosphatase by this method could be applied to the diagnosis of cystic fibrosis in fetuses having a 1:4 risk of being affected.

Adult↗
PubMed1992

Selective inhibition of the contractile apparatus. A new approach to modification of infarct size, infarct composition, and infarct geometry during coronary artery occlusion and reperfusion.

BACKGROUND: Myocardial reperfusion is associated with calcium overload and cell contracture, mechanisms that may precipitate cell death. In this study, we tested the hypothesis that in vivo inhibition of this contracture could lead to cell preservation in an open-chest large animal model. METHODS AND RESULTS: Regional myocardium function was measured during a selective intracoronary infusion of 2,3-butanedione monoxime (BDM), a specific inhibitor of actin-myosin coupling, in the control state (10 pigs) and in a protocol of a 51-minute coronary occlusion followed by reperfusion (40 pigs). The effects on coronary artery blood flow in the basal state were also studied (seven pigs). Intramyocardial distribution of the infusate during coronary occlusion, myocardial water content after 30 minutes of reperfusion and area at risk, infarct size, type of histological necrosis, and infarct geometry after 24 hours of reperfusion were assessed. Methods used included electromagnetic flowmeter, radiolabeled microspheres, subendocardial sonomicrometers, fluorescein, triphenyl tetrazolium chloride and Masson's trichrome staining, and computer quantification of infarct edges. In the absence of ischemia, BDM infusion inhibited regional shortening in a dose-dependent manner up to full systolic bulging while producing marked regional increase in coronary blood flow. During early reperfusion, BDM reduced end-diastolic length 76% more than the control infusion (p less than 0.05) and increased systolic bulging by 420% compared with no change in control animals. The ratio of infarct size/area at risk was reduced by 31% with BDM (p less than 0.05), with striking modifications of infarct histology and infarct geometry; specifically, the extent of contraction band necrosis was reduced by 63% from 105.5 +/- 18.2 to 39.2 +/- 13.6 mm2 (p less than 0.02), and more patches of necrosis (6.5 +/- 2.1 versus 1.6 +/- 0.4, p less than 0.05) and higher contour (7.7 +/- 1.2 versus 5.03 +/- 0.2, p less than 0.05) and fractal (12.1 +/- 1.3 versus 7.8 +/- 0.2, p less than 0.05) indexes were found. CONCLUSIONS: Selective intracoronary infusion of BDM at doses inhibiting regional wall motion decreased infarct size after reperfusion. The effects of BDM on regional function, the reduction in contraction band necrosis at histology, and the peculiar configuration of these infarcts all suggest that inhibition of contracture can interfere with cell-to-cell progression of myocardial necrosis, supporting a role for contracture in reperfusion-induced cell death.

Actins↗
PubMed1992

Late prosthetic valve endocarditis. Immediate and long-term prognosis.

From 1975 to 1989, 307 consecutive episodes of infective endocarditis were diagnosed in our hospital. Of those, 35 were cases of late prosthetic valve endocarditis, defined as those occurring after 12 months of valvular replacement. Blood cultures grew streptococci in 15 patients (43 percent), staphylococci in seven (20 percent), enterococci in five (14 percent), Gram-negative bacilli of HACEK group in four (11.5 percent), and Candida in one. Blood cultures were negative in three cases (prosthetic infection was confirmed at surgery). Heart failure due to prosthetic dysfunction occurred in seven patients (20 percent) and emboli in 12 (34 percent). Early valvular replacement was performed in six patients (17 percent). Complications and mortality were dependent on the infective agent. Overall mortality was 23 percent, no death occurred from streptococcal infection, whereas mortality with endocarditis by organisms of the HACEK group and Staphylococcus was 50 percent and 43 percent, respectively. During a mean follow-up of five years, 11 patients (those with prosthetic leaks diagnosed during the active infection and patients with biologic prostheses) required surgery. There was one relapse in a patient with staphylococcal endocarditis and one recurrence, six years after the initial episode. We conclude that immediate prognosis of late prosthetic valve endocarditis depends on the infective agent. Although the immediate prognosis of streptococcal infections is good, the need for early reoperation during follow-up due to progressive perivalvular leak is high. Also, it appears that deterioration of bioprostheses proceeds swiftly after the cure of infection.

Adolescent↗
PubMed1992

[Clinical and angiographic course after coronary angioplasty. Analysis of predictor factors of restenosis].

In order to know the restenosis rate and its predictive factors and the short-term clinical outcome (6-12 months) after coronary angioplasty (PTCA), we prospectively followed 200 consecutive patients with 231 coronary stenoses successfully dilated (residual stenosis < 50%). Patients have been clinically and angiographically followed 6-9 months after the procedure. Forty-nine clinical, hemodynamic, angiographic and technical variables were analyzed. Restenosis (stenosis > or = 50% in late angiographic control) rate was 51.5%, and 61% of the study population was symptomless. Variables associated with restenosis in the univariate analysis were: pre-PTCA positive exercise test (p = 0.004); stenosis severity pre-PTCA (p = 0.04); eccentricity (p < 0.0001) and irregularity (p < 0.0001) of the pre-PTCA stenosis; total dilation time (p = 0.02) and post-PTCA dissection (p = 0.002). The multivariate analysis revealed the following variables as independent predictors of restenosis: presence of dissection after PTCA, eccentricity and irregularity of pre-PTCA stenosis, positive pre-PTCA stress test and duration of symptoms before the procedure. These data suggest that the probability of restenosis after PTCA is predominantly determined by the characteristics of the lesion being dilated and the degree of intimal injury produced during the procedure. These variables could define high and low risk populations and may modify PTCA indications and follow up strategies.

Angioplasty, Balloon, Coronary↗
PubMed1992

Do knowledge and attitudes about influenza and its immunization affect the likelihood of obtaining immunization?

A telephone survey was conducted on 190 patients in Barcelona, Spain, at high-risk for influenza to evaluate the relationship between their knowledge and attitudes toward influenza and influenza immunization and whether they received the immunization. A discriminant function correlates (r = 0.86) with the immunization behavior and predicts the behavior before flu immunization in 84% of cases if we know the previous immunization behavior and adequately classifies the behavior in 82% if we don't know it (r = 0.75). Modifiable factors that predict immunization are self-identification as high-risk, belief that the immunization will not cause discomfort, intention to be immunized, and physician assigned. Those not immunized had a prevalent feeling that the shot is not effective, that they are not susceptible to the illness, and that the health center does not offer satisfactory organization to provide immunization. Furthermore, they felt that they had received controversial information through the mass media. We therefore believe that health education activities regarding influenza immunization should be specifically directed to increasing awareness of those who belong to a high-risk group, as well as to emphasizing susceptibility to the illness and the innocuousness of the immunization.

Aged↗
PubMed1991

Steady-state concentrations and dosage of digoxin in relation to kidney function in hospitalized patients over 70 years of age.

Steady-state serum digoxin concentrations were determined and related to renal function in 62 hospitalized patients 70-93 years of age. Renal function was assessed by serum creatinine concentration, and creatinine clearance was estimated by a formula employing the serum creatinine concentration and adjusting for body weight, sex and age. The steady-state digoxin concentration was inversely related to the estimated creatinine clearance. As there was no correlation between serum creatinine and age, a simplified estimation of creatinine clearance capacity, disregarding age and sex and allowing only for body weight and serum creatinine, was applied. It is suggested that this simplified calculation is suitable for bedside use. If the body weight/serum creatinine ratio is less than 0.5 (kg x 1/mumol), approximately one-third of our patients would have digoxin concentrations that are close to or above the upper reference limit (2.6 nmol l-1) at the maintenance dose of 0.13 mg digoxin daily. A digoxin dose of 0.07 mg daily thus appears to be suitable for many patients aged greater than 70 years when the body weight/serum creatinine ratio is less than 0.5, and also when the serum creatinine level is normal or only slightly elevated. The half-life of digoxin in serum was determined in 12 patients for whom digoxin treatment was withdrawn due to clinical signs of intoxication, and these half-lives were markedly prolonged: 3.5-6 days at a body weight/serum creatinine ratio of 0.5-0.3. The seven patients with prolonged half-lives had serum creatinine concentrations in the range of 80-140 mumol l-1.

Aged↗
PubMed1990

Intravascular and interstitial fluid dynamics in rats treated with minoxidil.

Edema is a major complication of vasodilatory therapy. However, the pathophysiologic mechanisms leading to the formation of vasodilator-mediated edema are insufficiently understood. The present study therefore examined the effect of the chronic administration of the potent arteriolar vasodilator, minoxidil (Mx), on extracellular fluid dynamics in rats. Extracellular volume (ECV), plasma volume (PV), interstitial fluid volume (IV), arterial pressure (AP), and interstitial fluid pressure (IP) were measured in rats treated for 10 days with Mx (1.5 mg/kg/day) and in control animals. In addition to a decreased AP, Mx-treated animals had diminished water and sodium excretion. ECV, PV, and IV and plasma renin concentration (PRC) were also increased in the Mx-treated rats. IP, which was subatmospheric in control rats (-2.6 +/- 0.04 mm Hg), was near zero in Mx-treated animals (-0.2 +/- 0.02 mm Hg, p less than 0.05). Saline ECV expansion (20 min, Ringer infusion, 3% body weight) or rat albumin injection (300 mg/2 ml) induced similar changes in the volume of the extracellular fluid compartments in both groups. However, changes in IP were blunted in Mx-treated rats. These results, therefore, show that Mx-treated rats have changes in interstitial fluid dynamics prior to any macroscopic evidence of edema accumulation. These alterations in the extracellular compartment dynamics may be a consequence of the sustained arteriolar vasodilation induced by Mx.

Aldosterone↗
PubMed1990

Diuretic effect and diuretic efficiency after intravenous dosage of frusemide.

1. Frusemide was given intravenously at a dose of 5 mg kg-1 to five healthy volunteers and the diuresis was assessed by frequent spontaneous voiding over 5 h. Urinary volume and contents of sodium, chloride, potassium and frusemide were measured. 2. Diuretic response was evaluated using the sigmoid Emax model and non linear regression of diuresis vs frusemide excretion rate. The time courses of diuresis (pharmacological effect) and diuretic efficiency were constructed from the fitted parameters of the sigmoid Emax model. 3. The frusemide excretion rate associated with maximum efficiency was found, as predicted theoretically, to be less than the excretion rate associated with 50% of maximum effect in four of the five subjects in whom the slope factor was less than 2. 4. The effect over time is dependent both on the instantaneous drug effect but also on its pharmacokinetic properties and mode of administration. An intravenous bolus is the least efficient mode of administration while a controlled input producing a frusemide excretion at maximum efficiency should yield up to a 2.3 times higher diuretic response.

Adult↗
PubMed1990

OX48, a monoclonal antibody against a 70,000 MW rat activation antigen expressed by T cells bearing the high-affinity interleukin-2 receptor.

The monoclonal antibody (mAb) OX48 recognizes a 70,000 MW cell-surface protein present in a small percentage of activated rat T cells and in CD8+ rat x BW5147 interleukin-2 (IL-2)-dependent T-cell hybridomas, but not in resting spleen cells or in IL-2-independent T-cell hybrids. OX48 antibody added simultaneously with concanavalin A (Con A) to resting spleen cells inhibits the cell proliferation and reduces the IL-2 production. However, addition of IL-2 does not restore the mitogenic response. Growth of rat blast T cells or IL-2-dependent hybrids is not affected by the OX48 antibody. There is a close correlation between the expression of high-affinity IL-2 receptors (IL-2R) and the OX48 antigen in T-cell hybridomas. In spite of this striking correlation, OX48 mAb does not inhibit the binding of 125I-IL-2 to the IL-2-dependent hybrids, and is unable to immunoprecipitate any of the proteins chemically cross-linked to 125I-IL-2. Therefore, the OX48 molecule represents a new rat activation antigen, undefined in other species, and probably involved in the early steps of T-cell activation.

Animals↗
PubMed1989

IL-2 protects T cell hybrids from the cytolytic effect of glucocorticoids. Synergistic effect of IL-2 and dexamethasone in the induction of high-affinity IL-2 receptors.

IL-2-independent CD8+ rat x BW5147 T cell hybridomas are highly sensitive to treatment with 10(-6) M dexamethasone. This glucocorticoid analog induces a rapid DNA fragmentation with a pattern similar to that observed during glucocorticoid-induced killing of mouse thymocytes, which suggests the activation of a similar specific endonuclease. Among these hybrids, we select variants expressing low affinity IL-2R, as measured by IL-2 binding assay and by the cell surface expression of the IL-2Rp55 Ag (rat CD25 recognized by OX-39 mAb). These OX-39+ IL-2 independent hybrids (named V type) are protected from the toxic action of dexamethasone by IL-2. The addition of IL-2 to V type cells induces the expression of a low number of high affinity IL-2R, which is strongly potentiated by the simultaneous addition of dexamethasone. Furthermore, dexamethasone is strongly synergistic with IL-2 in the induction of mRNA p55/IL-2R, which could be observed 6 h after the treatment. These data suggest that the utilization of the IL-2-R signaling pathway may induce an effective protection against glucocorticoid toxicity in mature T cells. Finally, we proved that the upregulation of IL-2R by IL-2 is strongly potentiated by glucocorticoids, which implies a new role for these agents in the immune system.

Animals↗
PubMed1989

Loss of interleukin 2 dependence in cloned interleukin 2-dependent rat T lymphocyte x BW5147 hybridomas is not associated with segregation of a specific pair of rat chromosomes.

A fusion between the mouse AKR thymoma BW5147 and a culture of homogeneously OX8+ (CD8) rat T lymphoblasts yield interleukin (IL) 2-dependent T cell hybridomas when selected in HAT medium supplemented with IL 2-containing supernatants of concanvalin A-activated cells and dexamethasone. IL 2-independent variants can be selected from cloned IL2-dependent hybrids in the absence of conditioned medium. Karyotype analysis was used to test a previously proposed hypothesis according to which IL2-independent variants arise through loss of a specific cytotoxic T lymphocyte (rat) chromosome carrying a gene responsible for IL2 dependence. Comparison of karyotypes of several independently derived hybrids with those of their IL 2-independent variants showed that the hybrids contain at least one homologue of all rat chromosomes, and that no pair of rat chromosomes is consistently absent in the IL 2-independent variants.

Animals↗
PubMed1989

Importance of genetic factors in the regulation of diazepam metabolism: relationship to S-mephenytoin, but not debrisoquin, hydroxylation phenotype.

Single oral 10 mg doses of diazepam and demethyldiazepam were given on different occasions to 16 healthy subjects. The subjects included four poor hydroxylators of debrisoquin and three poor hydroxylators of mephenytoin. There was a correlation between the total plasma clearance of diazepam and demethyldiazepam (rs = 0.83; p less than 0.01). There was no relationship between benzodiazepine disposition and debrisoquin hydroxylation. Poor hydroxylators of mephenytoin had less than half the plasma clearance of both diazepam (p = 0.0008) and demethyldiazepam (p = 0.0001) compared with extensive hydroxylators of mephenytoin. The plasma half-lives were longer in poor hydroxylators than they were in extensive hydroxylators of mephenytoin for both diazepam (88.3 +/- SD 17.2 and 40.8 +/- 14.0 hours; p = 0.0002) and demethyldiazepam (127.8 +/- 23.0 and 59.0 +/- 16.8 hours; p = 0.0001). There was no significant difference in volume of distribution of the benzodiazepines between the phenotypes. This study shows that the metabolism of both diazepam (mainly demethylation) and demethyldiazepam (mainly hydroxylation) is related to the mephenytoin, but not to the debrisoquin, hydroxylation phenotype.

Adult↗
PubMed1989

Growth requirements of T cell hybridomas obtained by the fusion between a mouse cytolytic T cell line and the rat tumor C58NTD.

T23 are hybrids derived from the fusion between an IL-2-dependent mouse cell line, C10 and the rat lymphoma C58NTD. Supernatants from exponentially growing T23 cells induce the growth of CTLL2, and IL-2-dependent cell line, suggesting that these hybrids secrete interleukin 2. Addition of recombinant IL-2 to slowly growing T23 cells increases the rate of growth. Using an 125I IL-2 binding assay, a low number of cell surface IL-2 receptors were detected. T23 hybrids contain mouse but not rat IL-2 receptor genes as revealed by Southern blot analysis. These receptors are functional because the growth of exponentially growing hybrids is inhibited by an anti-mouse IL-2 receptor antibody. These data suggest an autocrine-like mechanism as responsible for the growth of these T cell hybridomas.

Animals↗