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Biomedical subjects

E Sanz

Publications and source records attributed to E Sanz.

At least 55 records · Page 3Linked to original sources

A novel anti-Vpre-B antibody identifies immunoglobulin-surrogate receptors on the surface of human pro-B cells.

Vpre-B and lambda 5 genes, respectively, encode V-like and C-like domains of a surrogate immunoglobulin light chain (psi L). Such psi L complex is expressed in early progenitor B (pro-B) cells, before conventional immunoglobulin heavy (microH) and light (L) chains are produced. We raised a wide panel of monoclonal antibodies (mAbs) against soluble recombinant Vpre-B proteins to study early events in human B cell development. One of these antibodies, B-MAD688, labeled surrogate Ig-complexes on the surface of microH- pro-B cell lines and normal bone marrow cells in immunofluorescence assays. Immunoprecipitations using surface-labeled pro-B cells and B-MAD688 mAb indicated that human psi L is associated with high molecular weight components homologous to the surrogate heavy (psi H) chains described in mouse. Using B-MAD688 and SLC2 mAbs, we were able to distinguish between psi H psi L and microH psi L complexes on the surface of human pro-B and later precursor, pre-B, cells. The finding of psi H psi L complexes in mouse and man lead us to hypothesize a role for psi H-containing receptors in B cell development.

Amino Acid Sequence↗

[Analysis of adverse drug reactions detected in a primary health care center].

OBJECTIVE: To determine the incidence and epidemiological characteristics of adverse drug reactions (ADR) and to assess their relevance in primary health care. DESIGN: An open prospective descriptive study. PATIENTS: All patients cared for in one primary health care centre during 2 months. MEASUREMENTS AND MAIN RESULTS: 73 ADR were detected during the period of study (two of which corresponded to pediatric patients) with an incidence of 1.35% in adult general medicine and 0.36% in pediatric medicine. 67% of the patients were female, and all adult patients were distributed into three age groups (15-44, 45-64 and > or = 65 years of age). The frequency of ADR was similar in all three age groups. The ADR were most present in the GI tract, central nervous system, general symptoms and skin. Among the most frequently pharmacological groups implicated in the ADR were cardiovascular drugs, antibiotics and drugs for the central nervous system. Only in 12 cases the ADR was considered as clinically relevant, according with the criteria of the participating physicians; in 6 cases they were evaluated as avoidable. CONCLUSIONS: The ADR are not a relevant clinical problem, nor are they frequent in the outpatients primary health care. In most cases there are slight and self-limiting, which appeared in a limited number of patients. However clinically relevant and important ADRs appeared in 0.1-0.3% of the consultations, which, in practice, represent one to two serious ADRs per month and physician.

Adolescent↗

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↗

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↗

[Pathology of the heart transplant].

The endomyocardial biopsy is the best diagnostic procedure of the rejection in the cardiac transplant. In this paper we analize the more frequent findings observed in the biopsies and in the dead patient's hearts after a transplant. Due to the fact that the rejection' lesions have a focal distribution the biopsy has to contain at least four fragments. The diagnostic criteria for rejection was stablished since 1990. There are other lesions that can suppose a problem being the most frequent the ischemia, the infectious miocarditis and the Quilty effect. The post mortem studies permit the diagnostic of vascular lesions that are not identified in the routine biopsies.

Biopsy↗

Glucocorticoid hormones upregulate interleukin 2 receptor alpha gene expression.

We present evidence that glucocorticoid hormones increase expression of IL-2Rec alpha chain on T cells by regulating IL-2Rec alpha gene transcription. We have previously reported that glucocorticoids can upregulate IL-2Rec alpha mRNA and protein expression in some T cell hybrids. In the present study we show that the glucocorticoid analogue dexamethasone increases mRNA levels of the endogenous IL-2Rec alpha gene and the expression of plasmids containing 5'-flanking sequences of the IL-2Rec alpha gene linked to CAT reporter genes transiently transfected into different cell lines. We show that the dexamethasone effect depends on cis-acting regulatory elements in a segment (-1835/-802) of the mouse gene that also contains cytokine response elements and a inducible DNase I-hypersensitive site. Dexamethasone responses of IL-2Rec alpha-CAT reporter gene constructs were observed in a CTL line, in an IL-3-dependent bone marrow-derived cell line, and in COS7 monkey kidney cells. In the latter the response depended on cotransfection of a glucocorticoid receptor expression vector. The biological relevance of the glucocorticoid-mediated upregulation of the IL-2Rec alpha gene is discussed.

Animals↗

[Follicular mantle lymphoma: clinicopathologic and cell proliferation of 11 cases].

BACKGROUND: The aim of the present was to study the biologic behavior of the lymphomas of the follicular mantle by analysis of different indexes of neoplastic cell proliferation and their relation with the clinical symptoms, prognosis and survival of the patients. METHODS: Light microscope, ultrastructural, and frozen and paraffin immunohistochemical studies were performed including the proliferative markers Ki-67 and PC10, flow cytometry and analysis of cell cycle in biopsy samples. Clinical data of 11 patients were collected in addition to therapeutic response and survival. RESULTS: Lymphoma of the follicular mantle is constituted by small sized cell elements with a variable pattern of tumoral growth in the lymph nodes. In normal lymphocytes of the follicular mantle the immunophenotype shows expression of IgM + IgD and a light chain in the cell surface. From a clinical point of view, massive splenomegaly and disseminated stage are the most outstanding characteristics. One third of the cases analyzed presented an aneuploid neoplastic population. According to the PC10 marker, the proliferative index ranged from 2.9 to 14.7% of neoplastic cellularity (mean 7.0). The percentage of cells in the phases S, G2 and M of the cell cycle by flow cytometry varied from 14 to 35 (mean 23%). Neither the cell ploidy nor the tumoral proliferative index were related with the survival of the patients (53 +/- 51 months). CONCLUSIONS: Lymphoma of the follicular mantle is a clinical pathological entity of low biologic aggressivity. Cell aneuploidy or ploidy and the tumoral proliferative index did not establish differences in prognosis or survival in this series.

Adult↗

Analysis of myocardial oedema by magnetic resonance imaging early after coronary artery occlusion with or without reperfusion.

OBJECTIVE: The aim was to analyse the relationship between magnetic resonance (MR) imaging parameters and myocardial water content early after coronary occlusion with or without reperfusion. METHODS: 21 pigs were used. After 78 min of coronary occlusion (n = 7) or 48 min of coronary occlusion and 30 min of reperfusion (n = 14) the heart was excised. In seven animals in the reperfusion protocol the area at risk was perfused for 5 min with an anoxic buffer, starting 5 min after coronary occlusion. Serial T2 weighted and density weighted images of the heart were obtained from apex to base, by using a 1.5 tesla magnetic resonance imager. Water content was measured in samples from control and at-risk myocardium and relaxation parameters were measured in corresponding areas of the magnetic resonance images. RESULTS: Water content was 399(SEM 2) ml x 100 g-1 dry tissue in control myocardium, 427(8) in ischaemic myocardium, and 511(8) in reperfused myocardium (p < 0.001). Reperfused myocardium that had received intracoronary infusion contained less water than myocardium that did not: 498(9) v 534(4) ml x 100 g-1 (p = 0.003). T2 relaxation time and T2 weighted signal intensity in the different sampling sites of magnetic resonance images correlated well with water content in the corresponding myocardial samples (r = 0.76 and r = 0.83) and with the relative volume of extracellular space, as calculated by quantitative histology (r = 0.58 and r = 0.59, p < 0.001). The increase in T2 weighted signal intensity in the area at risk with respect to control myocardium allowed differentiation between ischaemic and reperfused myocardium [9(8)% v 63(3)% respectively]. The area at risk measured by MR imaging correlated very well with that determined at pathology by the fluorescein method (r = 0.92). CONCLUSIONS: Magnetic resonance imaging allows evaluation of myocardial oedema associated with acute coronary occlusion and reperfusion, and analysis of its spatial distribution. Changes in myocardial water content occurring early during acute myocardial infarction allow quantification of the area at risk and detection of reperfusion by magnetic resonance imaging.

Animals↗

[Biology of secondary nodal follicular b-lymphomas. A patho-dynamic study].

PURPOSE: To assess the aggressivity factors and tumour prognosis in a series of non-Hodgkin lymphomas by the use of computer-quantified specific antibodies and flow cytometry. PATIENTS AND METHODS: Sixty-one cases of follicular B-cell lymphoma: 34 of the germinal centre (24 centroblastic-centrocytic, CB-CC, and 10 centroblastic, CC) and 27 of the follicular cortex (FCL), were studied. All the cases had been diagnosed between 1971 and 1992 at the Pathology Department of the Fundación Jiménez Díaz. Morphologic and immunophenotype diagnosis was made on each case. Tumour proliferation studies were performed after labelling nuclei with proliferent nucleic acid-associated protein (PC 10); the positive nuclear areas were later quantified in a CAS-200 image analyser by means of proliferation programmes (PI) and nuclear receptors (ER). A flow cytometry study of ploidy was carried out on each case. The values attained were correlated with survival in months. The Wilcoxon's test for independent variables was used for the statistical study. RESULTS: The PI programme showed lowest proliferation for FCL (7.4%) followed by intermediate proliferation in CB-CC (16.9%) and high proliferation in CB (31.7%). The PC-10 results attained with both PI and ER programmes showed statistically significant correlation (p < 0.01). The correlation between ploidy, as quantified by flow cytometry, and survival showed statistically significant differences between diploid and aneuploid cases (p < 0.01); similar findings apply for diploids and diploids with high synthesis phase (p < 0.01). CONCLUSION: These findings support the usefulness of cell kinetics studies in lymphoma, and contribute to validate different evolutive patterns in accordance with the histologic subtype.

Biomarkers, Tumor↗

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↗

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↗

[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↗

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↗

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↗