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Biomedical subjects

M Ferrer

Publications and source records attributed to M Ferrer.

At least 91 records · Page 5Linked to original sources

[Factors predicting return home of hospitalized aged patients].

BACKGROUND: The identification of predictors of return home and nursing home placement in elderly patients, at the moment of admission to a Geriatric Convalescence Unit, may allow to make a discharge planning for these patients, and also may improve efficiency in the unit. PATIENTS AND METHODS: A number of 445 patients over 65 years were consecutively admitted to the unit. Analyzed variables at admission were; age, sex, diagnostic, comorbidity, functional status prior to admission, degree of independence in activities of daily living (Barthel index), cognitive function (Folstein Mini-Mental) and social support (modified version of social-familiar evaluation scale of Gijón). All these variables were used in two models of logistic regression analysis: 1 [symbol: see text] (dependent variable: return home after discharge versus other destinations), and 2 [symbol: see text] (dependent variable: nursing home placement on discharge versus other destinations). RESULTS: The variables significatively associated with greater probability of at home discharge were: moderate dependency for activities of daily living (Barthel index = 31-59), odds ratio (OR) = 2.46 (95% confidence interval: 1.43-4.22); mild dependency (Barthel index > or = 60), OR = 3.67 (1.96-6.87); normal cognitive function (Mini-Mental > or = 21), OR = 3.14 (1.76-5.60), and a favourable social support (social-familiar scale < 12), OR = 7.33 (3.18-16.91). The only variable significatively associated with the probability of nursing home placement after discharge was an impaired social function (social-familiar scale > or = 12), OR = 4.53 (2.25-9.12). CONCLUSIONS: Probability of return home after discharge is associated with functional status, cognitive function and social support. Definitively nursing home placement was only related with de degree of familiar support.

Activities of Daily Living↗

Androgen deprivation facilitates acetylcholine-induced relaxation by superoxide anion generation.

The aim of the present study was to assess the role of superoxide anions in the relaxation induced by acetylcholine (ACh) in aortic segments from male rats, and to investigate if their production is altered by sex hormone deprivation. In segments precontracted with 10 nmol/l noradrenaline, ACh (0.1 nmol/l-10 micromol/l) induced concentration-dependent relaxation, which was greater in segments from castrated compared with control animals. ACh-induced relaxation was abolished in segments from control rats, and reduced in those from castrated rats, by 0.1 mmol/l N(G)-nitro-L-arginine methyl ester (L-NAME; a nitric oxide synthase inhibitor). Indomethacin (1 micromol/l; a cyclo-oxygenase blocker) decreased the ACh-induced relaxation in arteries from control males only. Incubation of segments with superoxide dismutase (SOD; 100 units/ml; a superoxide anion scavenger) enhanced and reduced relaxation in segments from control and castrated animals respectively. For arteries from castrated animals, the presence of SOD plus L-NAME abolished such responses. In these arteries, incubation with L-NAME abolished the relaxation caused by ACh when the segments were precontracted with 30 mmol/l KCl. In segments obtained from castrated rats and pretreated with L-NAME, 1 mmol/l tetraethylammonium or 0.4 micromol/l charybdotoxin [blockers of Ca(2+)-sensitive and large-conductance Ca(2+)-sensitive (BK(Ca)) K(+) channels respectively] abolished the relaxation induced by ACh. These results suggest that ACh generates endothelial NO and superoxide anions from the arterial wall in both control and castrated animals; these agents negatively modulate ACh-induced relaxation in control rats by destruction of NO, and positively modulate ACh-induced relaxation in castrated rats by activation of BK(Ca) channels.

Acetylcholine↗

Truncation of glycoprotein (GP) IIIa (616-762) prevents complex formation with GPIIb: novel mutation in exon 11 of GPIIIa associated with thrombasthenia.

This work reports the molecular genetic study of a patient who suffered from Glanzmann thrombasthenia (GT). Structural analysis of the glycoprotein (GP) IIb and GPIIIa genes showed the presence of a homozygous G1846-->T transversion in exon 11 of GPIIIa that changes Glu616-->Stop. Cytometric and immunochemical analysis indicated that platelet GPIIb-IIIa was absent in the proband but present at normal levels in the heterozygous relatives. The following observations indicate that this mutation is responsible for the thrombasthenic phenotype of the proband. (1) We failed to detect mutations other than [T1846]GPIIIa in the coding region of both GPIIb and GPIIIa genes. (2) The G1846-->T mutation was observed in either parent and a brother of the proband, but none of 100 unrelated individuals carried this defect. (3) Pulse-chase and immunoprecipitation analysis of GPIIb-IIIa complexes in cells transiently cotransfected with cDNAs encoding normal GPIIb and [T1846]GPIIIa showed neither maturation of GPIIb nor complex formation and surface exposure of GPIIb-triangle upGPIIIa. These observations indicate that the sequence from Glu616 to Thr762 in GPIIIa is essential for heterodimerization with GPIIb. Polymerase chain reaction-based analysis demonstrated the presence of normal levels of full-length GPIIIa-mRNA in the proband and in heterozygous relatives. In addition, a shortened transcript, with a 324-nucleotide deletion, resulting from in-frame skipping of exons 10 and 11, was detectable upon reamplification of the DNA. Thus, unlike other nonsense mutations, [T1846]GPIIIa does not lead to abnormal processing or reduction in the number of transcripts with the termination codon.

Adult↗

Radioprotective effect of sodium diethyldithiocarbamate (DDC) and S-2-aminoethyl-isothioronicadenosin-5-triphosphate (adeturon) in gamma-irradiated Escherichia coli cells.

The effect of sodium diethyldithiocarbamate (DDC) and S-2-aminoethyl-isothiouronicadenosin-5-triphosphate (adeturon) in the induction of Escherichia coli SOS response promoted by gamma-irradiation was studied by measuring the induction of sulA gene and the induction of lambda prophage. Furthermore, as a way of measure the exonuclease activity in gamma-irradiated cells in the presence or absence of both compounds, the DNA degradation was determined. Adeturon did not affected DNA degradation, but inhibited the induction of the SOS functions studied. On the contrary, DDC inhibited DNA degradation as well as the induction of the sulA gene, but enhanced lambda induction in E. coli lysogenic strains. These results indicate that both compounds diminish the DNA damage produced by gamma-irradiation and also suggest that the mechanisms of radioprotection must be different. Thus, radioprotection mediated by DDC should involve free hydroxyl radical scavenging and a minor activity of exonuclease. The enhancement of phage induction in E. coli cells that DDC produces could be attributed to its quelant effect and this would not be not probably directly related to radioprotection. Adeturon, as thiols, may serve also as scavenging agent of free hydroxyl radicals, diminishing indirectly the DNA damage level. In addition, adeturon must interact with DNA in the same form that other aminothiol compounds do it. This interaction, mediated by amino groups of adeturon, may serve to concentrate these compounds near of the DNA damage site, increasing the potential for the thiol portion of the molecule to donate hydrogen, decreasing the damage level on DNA molecule. However, adeturon do not modify the exonuclease activity. Some topic about the possible clinical application of both compounds are discussed.

Adenosine Triphosphate↗

Homologue scanning mutagenesis of heregulin reveals receptor specific binding epitopes.

The EGF domain of heregulin has all the receptor binding characteristics of full-length heregulin and has strong homology to the ligands for erbB-1. Despite this, it does not bind erbB-1 but instead binds erbB-3 and erbB-4. The sequence similarity between HRG and the erbB-1 ligands suggest that a few residues are responsible for receptor binding specificity. To determine the sequences involved in receptor binding, we performed homologue scanning mutagenesis on the EGF domain of HRGalpha using sequences of TGFalpha or EGF. We found three sets of mutations in the N-terminal subdomain that were responsible for receptor binding specificity. Mutations in the C-terminal subdomain affected the binding affinity, but did appear to confer any specificity.

Adenocarcinoma↗

Gastrointestinal helminth parasites in stray cats from the mid-Ebro Valley, Spain.

Gastrointestinal helminths were collected from 58 necropsied stray cats (Felis catus) in the mid-Ebro Valley, North-East Spain, from December 1989 to March 1992. The prevalence was 89.7%, with those of individual parasites being Toxocara cati 55.2%C, Ancylostoma tubaeforme 29.3% Joyeuxiella pasqualei 55.2%, Diplopylidium acanthotetra 20.7%, Dipylidium caninum 20.7%, Mesocestoides spp. 13.8%, Taenia taeniformis 8.6% and Diplopylidium nölleri 8.6%. In relation to sex, the differences were not significant. However, the season of the year significantly affected the prevalence of A. tubaeforme and D. acanthotetra.

Ancylostoma↗

Effect of age on the vasorelaxation elicited by cromakalim. Role of K+ channels and cyclic GMP.

The objective of this study was to investigate whether age induces changes on vasodilator response induced by cromakalim, an ATP-sensitive K+ (K(ATP)) channel opener, as well as the underlying mechanism involved in this possible alteration. For this purpose, aortic segments from young (3-5 months) and old (3 years) rabbits were used, which were precontracted with noradrenaline (NA, 1 microM). The vasodilator response induced by cromakalim (0.01-100 microM) was reduced in intact segments from old rabbits, and endothelium removal reduced and did not modify this effect in young and old animals, respectively. In both groups of animals, glibenclamide (10 microM), a blocker of K(ATP) channels, significantly reduced the response elicited by cromakalim, which was not modified by the large conductance Ca2+-activated K+ channel blocker charybdotoxin (ChTX, 0.4 microM). Acetylcholine (ACh, 10 microM) and sodium nitroprusside (SNP, 100 microM) induced a lesser vasodilator effect in aortic segments from old compared with young rabbits. In segments precontracted with NA, 10 microM ACh or 100 microM SNP similarly increased cGMP levels in both groups of animals. However, basal cGMP level was reduced in segments from old rabbits. Incubation with 8-bromo-cGMP (100 microM) increased the response induced by cromakalim in both groups of animals, reaching similar maximum values in young and old rabbits. The response induced by cromakalim plus 8-bromo-cGMP was markedly decreased by glibenclamide and unmodified by ChTx in both types of animals. These results suggest that aging decreases the vasodilator response to cromakalim, mechanism in which appears to be involved the maintained low cGMP levels observed in old rabbits, and that this messenger modulates the degree of K(ATP) channel activation.

8-Bromo Cyclic Adenosine Monophosphate↗

Comparative studies of functional and binding assays for IgG anti-Fc(epsilon)RIalpha (alpha-subunit) in chronic urticaria.

BACKGROUND: Recent data suggest that a subpopulation of patients with chronic urticaria have an autoimmune disorder that is caused by the presence of antibodies to the IgE receptor. The actual incidence of these antibodies is uncertain. OBJECTIVE: We sought to assess the incidence of autoimmunity to the IgE receptor in patients with chronic urticaria and to compare functional and binding assays. METHODS: We isolated skin mast cells and studied a large number of patient sera (68) for their ability to activate these cells and isolated basophils. We then compared the results with those obtained by immunoblotting using cloned alpha-subunit of the IgE receptor. RESULTS: Sera from patients with chronic urticaria released significant histamine (> 15% of basal) on incubation with basophils (48%) and mast cells (46%). By immunoblotting we obtained positive results in 64% of subjects tested and also identified a small subpopulation that is active on cells but does not bind Fc(epsilon)RIalpha. CONCLUSION: Our data suggest that approximately 45% to 50% of patients with chronic urticaria have a cutaneous autoimmune disorder. Immunoblotting may provide a rapid screening method for anti-Fc(epsilon)RIalpha detection in such patients.

Autoantibodies↗

Testing the measurement properties of the Spanish version of the SF-36 Health Survey among male patients with chronic obstructive pulmonary disease. Quality of Life in COPD Study Group.

The aim of this article is to evaluate the measurement properties of the Spanish version of the SF-36 Health Survey (SF-36). In total, 321 male chronic obstructive pulmonary disease (COPD) patients attending hospital outpatient or primary health clinics were cross-sectionally administered the SF-36, the St. George's Respiratory Questionnaire (SGRQ), and a dyspnea scale. A clinical measure of respiratory function, the proportion of the predicted Forced Expiratory Volume in 1 second (%FEV1) was also obtained. Internal consistency, central tendency, and dispersion statistics of scores were calculated, as well as the percentage of respondents with the highest and lowest scores for each scale and correlations between health status and clinical measures. All patients completed the SF-36 questionnaire, and less than 1% of items were missing. The proportion of patients with the worst possible score (floor effect) ranged from 0.9-20.1% among the different scales. The proportion of patients achieving the best possible score (ceiling effect) ranged from 0-61%. Cronbach's alpha coefficients were above 0.75 except for one scale (Social Functioning, alpha = 0.55). SF-36 scores were moderate to highly correlated with SGRQ scores (coefficients ranged from -.41 to -.79). Correlations were moderate to high with dyspnea and lower but statistically significant with %FEV1. A clear gradient of SF-36 scores was found according to dyspnea levels and disease staging based on %FEV1 impairment, the gradient being more marked for the Physical Functioning, Role-Physical, and General Health scales. Data presented suggest that the Spanish version of the SF-36 is acceptable, valid, and reliable in COPD patients. Although more studies are needed, this version is adequate in international comparisons of health outcomes.

Adult↗

In vitro antigen-specific sulphidoleukotriene production in patients allergic to Dermatophagoides pteronyssinus.

BACKGROUND: Sulphidoleukotrienes (slt) are important mediators in allergic diseases that are synthesized after allergen-specific stimulation. OBJECTIVES: The aim of this study is to determine in vitro slt production after allergen-specific (Dermatophagoides pteronyssinus) stimulus of peripheral blood leucocytes and to observe whether histamine release in whole blood with the same allergen correlates with slt production. We also wanted to evaluate whether a correlation exists between the release of slt and histamine and other diagnostic procedures as well as various clinical situations. METHODS: We studied 62 patients sensitive to Dermatophagoides pteronyssinus (Der p), 30 atopic controls and 12 healthy donors. We determined slt production using the CAST-ELISA technique and histamine release using two concentrations of Der p extract (20 and 2 ng/mL). We also carried out quantification of specific and total IgE levels, skin tests and pulmonary function test on each patient. RESULTS: We observed a significantly increased slt release after in vitro stimulation with Der p. There was a significant difference in the slt release between controls and sensitive patients (P < 0.001) and between atopic controls and sensitive patients (P < 0.001). The data are similar to those obtained with histamine release. We noted a positive correlation (P < 0.001) between slt and histamine release (r = 0.71, at 2 ng/mL and r = 0.83 at 20 ng/mL). We also found a positive (P<0.001), although weak (r=0.4 with at 2ng/mL, and r = 0.34 with P = 0.003 at 20 ng/mL) correlation between slt release and specific IgE levels as well as between slt release and skin-test reactivity (r = 0.49 at 2 ng/mL and r = 0.45 at 20 ng/mL; P < 0.001). No significant correlation between slt release and asthma severity was observed, although a trend toward higher slt production in severe and moderate asthma was detected. We found a significant (P<0.001) but weak (r=-0.3) negative correlation between age and slt release. With respect to sex-related differences, we found significant differences (P < 0.05) in slt release between the sexes with a higher slt release in men than in women. CONCLUSION: We conclude that CAST-ELISA for quantification of slt production is a useful in vitro method for diagnosing sensitization to Der p. There also exists a close correlation between slt release and other parameters of allergic sensitization in vitro as well as in vivo.

Adolescent↗

Pattern of expression of tetraspanin antigen genes in Burkitt lymphoma cell lines.

Tetraspanin antigens are implicated in the prognosis of different types of tumours. In this study we determine by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) the level of 13 tetraspan messages in 21 Burkitt lymphoma (BL) cell lines. All tumour cell lines have a common pattern of tetraspanin gene expression. There are five antigens which are detected in 90% of cell lines at high levels, CD53, CD81, CD63, SAS and CD82. Another two, CD9 and CD37, were detected in 60% of cell lines, and have a very variable level of expression. The remaining antigens, A15, CoO29, KRAG, L6, TI-1 and il-TMP, are expressed at low levels in very few cell lines without any specific pattern. The level of gene expression corresponds with the level of cell surface antigen determined by flow cytometry. The average number of tetraspan proteins expressed per cell line is six. These proteins may form subunits of an oligomeric structure with 24 transmembrane domains. There are no major differences in tetraspan expression pattern among sporadic or endemic tumours, type of translocation or Epstein-Barr virus status, suggesting the original cell of these tumours is the same, probably a late pre-B cell, at the CD9 to CD37 transition point. Tetraspanin gene expression is consistent with BL being a single entity, despite variations in other parameters.

Antigens, CD↗

Effect of inverse I:E ratio ventilation on pulmonary gas exchange in acute respiratory distress syndrome.

BACKGROUND: It is not known whether inverse I:E ratio ventilation (IRV) offers any real benefit over conventional mechanical ventilation with positive end-expiratory pressure (CMV-PEEP) at similar levels of end-expiratory pressure. METHODS: The effects of volume-controlled and pressure-controlled IRV (VC-IRV and PC-IRV, respectively) on VA/Q inequality were compared with those of CMV-PEEP at a similar level of end-expiratory pressure and with CMV without PEEP (CMV) in eight patients in the early stages of acute respiratory distress syndrome (ARDS). Respiratory blood gases, inert gases, lung mechanics, and hemodynamics were measured 30 min after the onset of each ventilatory mode. RESULTS: Recruitment of nonventilated, poorly ventilated (or both) but well-perfused alveoli increased the partial pressure of oxygen (PaO2) during CMV-PEEP (+13 mmHg) and IRV-VC (+10 mmHg; P < 0.05) compared with CMV. In contrast, PC-IRV did not affect PaO2 but caused a decrease in PaCO2 (-7 mmHg; P < 0.05). The latter was due to a concomitant decrease in dead space (P < 0.01) and shift to the right of VA/Q distributions. During PC-IRV, the increase in the mean of blood flow distribution (mean Q; P < 0.01) without a change in the dispersion (log SD Q) did not result in an increase in PaO2, probably because it reflected redistribution of blood flow within well-ventilated areas. CONCLUSIONS: Short-term PC-IRV improved carbon dioxide clearance, but the lung became less efficient as an oxygen exchanger. Furthermore, based on mean airway and plateau pressures, the risk of barotrauma was not reduced with this type of ventilation.

Adult↗

Rapid selection in modified BHK-21 cells of a foot-and-mouth disease virus variant showing alterations in cell tropism.

With persistent foot-and-mouth disease virus (FMDV) in BHK-21 cells, there is coevolution of the cells and the resident virus; the virulence of the virus for the parental BHK-21 cells is gradually increased, and the cells become partially resistant to FMDV. Here we report that variants of FMDV C3Arg/85 were selected in a single infection of partially resistant BHK-21 cells (termed BHK-Rb cells). Indirect immunofluorescence showed that the BHK-Rb cell population was heterogeneous with regard to susceptibility to C3Arg/85 infection. Infection of BHK-Rb cells with C3Arg/85 resulted in an early phase of partial cytopathology which was followed at 6 to 10 days postinfection by the shedding of mutant FMDVs, termed C3-Rb. The selected C3-Rb variants showed increased virulence for BHK-21 cells, were able to overcome the resistance of modified BHK-21 cells to infection, and had acquired the ability to bind heparin and to infect wild-type Chinese hamster ovary (CHO) cells. A comparison of the genomic sequences of the parental and modified viruses revealed only two amino acid differences, located at the surface of the particle, at the fivefold axis of the viral capsid (Asp-9-->Ala in VP3 and either Gly-110-->Arg or His-108-->Arg in VP1). The same phenotypic and genotypic modifications occurred in a highly reproducible manner; they were seen in a number of independent infections of BHK-Rb cells with viral preparation C3Arg/85 or with clones derived from it. Neither amino acid substitutions in other structural or nonstructural proteins nor nucleotide substitutions in regulatory regions were found. These results prove that infection of partially permissive cells can promote the rapid selection of virus variants that show alterations in cell tropism and are highly virulent for the same cells.

Amino Acid Substitution↗

Role of the alpha-subunit 326GRV sequence in the surface expression of fibrinogen and vitronectin receptors.

The platelet GPIIb-GPIIIa heterodimer (integrin alphaIIbbeta3) binds fibrinogen with high affinity in response to activation by agonists, leading to platelet aggregation and formation of a hemostatic plug. The 326GRV motif in GPIIb is highly conserved in the alpha-subunit of other integrins, suggesting that it might play an important functional role. Moreover, Arg327-->His substitution in GPIIb has been associated with defective platelet surface expression of GPIIb-IIIa and thrombasthenic phenotype. This work aimed at elucidating whether the absence of Arg327 or its substitution by His was responsible for the impaired surface expression of GPIIb-IIIa complexes. Transfection of cDNA encoding [Ala327]GPIIb, [Gln327]GPIIb, or [Phe327]GPIIb into Chinese hamster ovary cells inherently expressing GPIIIa permitted surface exposure of GPIIb-IIIa complexes, whereas [Glu327]GPIIb did not. These observations indicate that it is not the loss of [Arg327]GPIIb but the presence of His327 or a negatively charged residue like Glu at position 327 of GPIIb that prevents the surface exposure of GPIIb-IIIa heterodimers. In contrast, changing Gln344, the homologue to Arg327 in the alpha-subunit of the vitronectin receptor, to His did not prevent the surface expression of alphav-GPIIIa complexes. Thus the conformational constraint imposed by His327 seems to be rather specific for the heterodimerization and/or processing of GPIIb-IIIa complexes.

Amino Acid Sequence↗