Search PubMed⌕ Search

Biomedical subjects

R Fernandez

Publications and source records attributed to R Fernandez.

At least 73 records · Page 4Linked to original sources

A thermal beam-shape phantom for ultrasound physiotherapy transducers.

Acoustic beam nonuniformities are not uncommon in physiotherapy ultrasound equipment and can lead to errors in delivered dose. A relatively simple thermal technique is described for mapping the intensity distribution in physiotherapy ultrasound beams that could be used for routine QA checks. The technique uses a thermochromic material sandwiched between layers that absorb ultrasound. The structure is used in a water bath to intersect the ultrasound beam. Thermal models predict that, with suitable absorbing materials and careful control of the surface temperature of the layers, sufficient spatial resolution and sensitivity can be achieved to show the intensity distribution in physiotherapy ultrasound beams. Thermal images of sections through physiotherapy ultrasound beams using this method correlate well with corresponding intensity maps generated by planar scanning with a hydrophone.

Hot Temperature↗

Surgical treatment of large cutaneous lesions of the back in children by concentric cutaneous mobilization.

Excision of large cutaneous lesions of the back, such as giant nevi in children, represents a major surgical challenge. Actually, many authors use tissue expanders. Recently, we have proposed, through a better evaluation of the biomechanical properties of the skin, a natural expansion mode using the postoperative tension. This expansion is natural and delayed. In the back the natural expansion can be created by concentric excision, which takes maximum advantage of the possibilities of cutaneous mobilization of the back. The concentric excision has been used in 12 children presenting with cutaneous lesions of the back involving more than 30 percent of the dorsal anatomic unit. Nine patients underwent total excision; two patients were treated in one stage, four patients in two stages, and three patients in three stages. Three patients could not have total excision. The follow-up was uneventful, except in one patient who presented with wound dehiscence. The follow-up was 1 to 2 years and showed a modest scar widening (< 4 mm) in three patients, moderate widening (> 4 min, < 7 mm) in three patients, and significant widening (> 10 mm) in three patients. The systematization of the cutaneous mobilization for each region of the back has allowed us to optimize the utilization of peripheral normal tissue in the surgical treatment of large cutaneous lesions of the back. In some circumstances, the gain in tissue has been superior to that we usually obtain with skin expanders and with lesser cost, lesser pain, and fewer risks.

Back↗

Physiologically based indices of volumetric capnography in patients receiving mechanical ventilation.

Several indices of ventilatory heterogeneity can be identified from the expiratory CO2 partial pressure or CO2 elimination versus volume curves. The aims of this study were: 1) to analyse several computerizable indices of volumetric capnography in order to detect ventilatory disturbances; and 2) to establish the relationship between those indices and respiratory system mechanics in subjects with normal lungs and in patients with acute respiratory distress syndrome (ARDS), both receiving mechanical ventilation. We studied six normal subjects and five patients with early ARDS mechanically ventilated at three levels of tidal volume (VT). Respiratory system mechanics were assessed by end-expiratory and end-inspiratory occlusion methods, respectively. We determined Phase III slopes, Fletcher's efficiency index, Bohr's dead space (VD,Bohr/VT), and the ratio of alveolar ejection volume to tidal volume (VAE/VT) from expiratory capnograms, as a function of expired volume. Differences between normal subjects and ARDS patients were significant both for capnographic and mechanical parameters. Changes in VT significantly altered capnographic indices in normal subjects, but failed to change ventilatory mechanics and VAE/VT in ARDS patients. After adjusting for breathing pattern, VAE/VT exhibited the best correlation with the mechanical parameters. In conclusion, volumetric capnography, and, specifically, the ratio of alveolar ejection volume to tidal volume allows evaluation and monitoring of ventilatory disturbances in patients with adult respiratory distress syndrome.

Adult↗

Adenosine deaminase activity in the aetiological diagnosis of community-acquired pneumonia.

A prospective study was undertaken to assess the usefulness of serum adenosine deaminase (ADA) activity in the aetiological diagnosis of 75 patients (mean age 58 years) with community-acquired pneumonia who required hospitalization. Measurements of ADA were also carried out in 35 healthy subjects (mean age 52 years). The serum ADA activity in patients with typical bacterial pneumonia (TBP) was 21 +/- 7 IU/l and in controls 22 +/- 9 IU/l. In 43 patients with atypical pneumonia (AP), ADA levels (43 +/- 23 IU/l) were significantly higher than in the previously related groups (p < 0.001). Analysis within the group of atypical pneumonia showed significant differences for infections caused by Coxiella burnetii (61 +/- 19 IU/l, p < 0.001), Mycoplasma pneumoniae (44 +/- 26 IU/l, p < 0.001) and Legionella pneumophila (39 +/- 15 IU/l, p < 0.05), as compared with patients with bacterial pneumonia and normal control subjects. We conclude that serum ADA in patients with community-acquired pneumonia requiring hospitalization may provide useful additional diagnostic information on the aetiology of pulmonary infection.

Adenosine Deaminase↗

Guidelines for treatment of head injury in adults. Opinions of a group of neurosurgeons.

There are a number of parallel activities world wide to devise guidelines for the treatment of head injuries. A Group of neurosurgeons from various European countries worked on guidelines during three informal meetings, which may serve as a base for discussion of national or local protocols. Three levels of certainty were distinguished: Measures that must be taken which such a high degree of certainty, that they have not seriously been challenged-principles. Measures, that should be taken, as there is reasonable evidence in the literature about its efficacy-recommendations and measures that may be taken, but proof of its efficacy is lacking-optional measures. Protocols based on these guidelines are felt to help young neurosurgeons in training, define neurosurgical needs for other specialities and enhance the general efficacy of care for the head injured patient including multiple injuries.

Adult↗

Transforming growth factor-beta1 stimulates degranulation and oxidant release by adherent human neutrophils.

The signal transduction pathways that are activated by cytokines and growth factors binding to their receptors on human neutrophils (PMN) are poorly understood. When PMN in suspension encounter many of these agonists they are not activated, but rather are primed for subsequent activation. We and others reported that when PMN are plated onto fibrinogen and stimulated with cytokines or with the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) they respond by releasing hydrogen peroxide (H202) and the specific granule component lactoferrin. Transforming growth factor-beta1 (TGF-beta1) is released by many cells including PMN. It has been reported that TGF-beta1 stimulates chemotaxis but not exocytosis or superoxide production by cells in suspension. We hypothesized that TGF-beta1 would activate PMN to release H202 when they were adherent to fibrinogen, a response mediated by beta2++integrin receptors. In this study, we determined whether TGF-beta1 stimulated H202 and lactoferrin release by PMN adherent to fibrinogen. TGF-beta1 stimulated H202 and lactoferrin release from adherent PMN in a concentration-dependent manner, with effects seen in the range of 0.1 to 100 pg/mL. Both H202 and lactoferrin release were detected by 60 min and continued for at least 180 min. Adhesion and spreading of PMN paralleled H202 and lactoferrin release. Ethanol (200 mM) blocked both H202 and lactoferrin release, suggesting the involvement of the phospholipase D pathway. In PMN labeled with lyso-[3H]phosphatidylcholine, we observed that TGF-beta1 treatment caused an increase in [3H]phosphatidate. Propranolol (150 microM), an inhibitor of phosphatidate phosphohydrolase, blocked both H202 and lactoferrin release, suggesting that the conversion of phosphatidic acid to diradylglycerol is an important step in PMN activation by TGF-beta1. Overall, these results are similar to those reported for fMLP activation of adherent PMN and suggest that a common pathway is involved in both chemoattractant and cytokine activation.

Butanols↗

Induction of cytochrome P4501A1 and P4504A1 activities and peroxisomal proliferation by fumonisin B1.

The effects of repeated exposure to fumonisin B1 (FB1) on hepatic and renal mixed function oxidase activities and peroxisomal proliferation has been examined in rats following intraperitoneal administration at three dose levels (0.125, 0.25, and 2.5 mg/kg) once a day for 6 days. At the two highest doses, FB1 increased the renal and hepatic N-demethylation of erythromycin (CYP3A1) and the hepatic O-deethylation of ethoxyresorufin (CYP1A1). FB1, at the highest dose of 2.5 mg/kg, also increased the renal O-deethylation of ethoxyresorufin. The liver, but not the kidney, was also susceptible to FB1-dependent induction of the 12- and 11-hydroxylation of lauric acid, suggesting induction of the CYP4A subfamily. Immunoblot studies employing solubilized microsomes from FB1-treated rats revealed that FB1, at the two highest doses, increased the apoprotein levels of CYP1A1 and CYP4A1. The same treatment with FB1 increased the beta-oxidation of palmitoyl-coenzyme A (CoA) in liver homogenates, and immunoblot analysis showed an increase in the apoprotein levels of the trans-2-enoyl-CoA hydratase trifunctional protein. The possible implications of these findings to the hepatocarcinogenicity of this mycotoxin are discussed.

Animals↗

Ventilatory factors affecting inhaled nitric oxide concentrations during continuous-flow administration.

PURPOSE: Inhaled nitric oxide has been reported to be useful in acute respiratory distress syndrome and other lung diseases characterized by pulmonary hypertension and hypoxemia. The best site to inject the NO is still controversial, as is whether it can be affected by changes in ventilatory settings. The objective of this study was to examine the impact of various ventilator settings (tidal volume [Vt], inspiratory-to-expiratory [I:E] ratio, added dead space) in the final NO concentrations reached when NO is administered as a continuous flow near the endotracheal tube. METHODS: A test lung model was ventilated using a ServoVentilator 300 Siemens with square wave flow. A continuous flow of NO was administered between the Y piece and the endotracheal tube. The flow was adjusted with an NO precision flowmeter (range, 0.2 to 1.5 L/min) attached to a cylinder containing 800 ppm of NO. Actual NO concentrations in the lung model were measured by chemiluminescence (NOX 2000; Seres). The effects of changing Vt (from 300 to 1300 mL) and I:E ratio (from 1:4 to 2:1) and the addition of dead space (100 mL) were examined. RESULTS: At each step of the study, the measured NO concentration was higher than predicted. Biases from predicted NO concentration due to tidal volume were 17% at 1,300 mL Vt, 21% at 1,100 mL Vt, 25% at 900 mL Vt, 28% at 700 mL Vt, 35% at 500 mL Vt, and 48% at 300 mL Vt. Changes in I:E ratio induced increases in No concentration of 4% at 2:1, 5% at 1:1, 22% at 1:2, and 31% at 1:4. The addition of dead space enhanced these differences: 62% at 2:1, 104% at 1:1, 230% at 1:2, and 322% at 1:4. CONCLUSION: According to our lung model, continuous-flow administration of NO near the endotracheal tube is influenced strongly by changes in ventilatory settings.

Humans↗

Identification of casein as the major allergenic and antigenic protein of cow's milk.

The objective of this study was to analyze both the allergenicity and immunogenicity of cow's milk proteins. To this end, 80 milk-atopic patients were selected on the basis of the presence of cow's milk-specific IgE antibodies in serum and compatible clinical history. Fifteen patients allergic to other allergens and 10 nonatopic subjects were studied as controls. The specificity of serum IgG and IgE antibodies was determined by immunoblotting, employing both cow's milk and milk components, i.e., alpha- and beta-casein, beta-lactoglobulin, and alpha-lactalbumin separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The experiments showed that casein-specific IgE antibodies were present in all (80/80) sera examined; 10/80 showed reactivity to beta-lactoglobulin, and 5/80 showed reactivity to alpha-lactalbumin. None of the 25 negative control sera analyzed showed the presence of specific IgE antibodies against milk proteins. These results were similar to those corresponding to the detection, by the radioallergosorbent test, of IgE antibodies against the milk components coupled to paper disks. All sera from milk-atopic patients also showed IgE reactivity against a high-molecular-mass fraction that hardly enters the gel. This fraction, after separation by gel filtration and treatment with beta-mercaptoethanol and urea, was shown by SDS-PAGE analysis to be formed by casein monomers. All sera analyzed by immunoblotting reacted against the components corresponding to casein monomers. Inhibition of immunoblotting by adsorption with different milk components confirmed that those high-molecular-mass aggregates are formed by casein components. The results presented here strongly suggest that casein is the major allergenic component of cow's milk.

Adolescent↗

The Drosophila insulin receptor activates multiple signaling pathways but requires insulin receptor substrate proteins for DNA synthesis.

The Drosophila insulin receptor (DIR) contains a 368-amino-acid COOH-terminal extension that contains several tyrosine phosphorylation sites in YXXM motifs. This extension is absent from the human insulin receptor but resembles a region in insulin receptor substrate (IRS) proteins which binds to the phosphatidylinositol (PI) 3-kinase and mediates mitogenesis. The function of a chimeric DIR containing the human insulin receptor binding domain (hDIR) was investigated in 32D cells, which contain few insulin receptors and no IRS proteins. Insulin stimulated tyrosine autophosphorylation of the human insulin receptor and hDIR, and both receptors mediated tyrosine phosphorylation of Shc and activated mitogen-activated protein kinase. IRS-1 was required by the human insulin receptor to activate PI 3-kinase and p70s6k, whereas hDIR associated with PI 3-kinase and activated p70s6k without IRS-1. However, both receptors required IRS-1 to mediate insulin-stimulated mitogenesis. These data demonstrate that the DIR possesses additional signaling capabilities compared with its mammalian counterpart but still requires IRS-1 for the complete insulin response in mammalian cells.

Amino Acid Sequence↗

The Drosophila insulin receptor homolog: a gene essential for embryonic development encodes two receptor isoforms with different signaling potential.

We report the cloning and primary structure of the Drosophila insulin receptor gene (inr), functional expression of the predicted polypeptide, and the isolation of mutations in the inr locus. Our data indicate that the structure and processing of the Drosophila insulin proreceptor are somewhat different from those of the mammalian insulin and IGF 1 receptor precursors. The INR proreceptor (M(r) 280 kDa) is processed proteolytically to generate an insulin-binding alpha subunit (M(r) 120 kDa) and a beta subunit (M(r) 170 kDa) with protein tyrosine kinase domain. The INR beta 170 subunit contains a novel domain at the carboxyterminal side of the tyrosine kinase, in the form of a 60 kDa extension which contains multiple potential tyrosine autophosphorylation sites. This 60 kDa C-terminal domain undergoes cell-specific proteolytic cleavage which leads to the generation of a total of four polypeptides (alpha 120, beta 170, beta 90 and a free 60 kDa C-terminus) from the inr gene. These subunits assemble into mature INR receptors with the structures alpha 2(beta 170)2 or alpha 2(beta 90)2. Mammalian insulin stimulates tyrosine phosphorylation of both types of beta subunits, which in turn allows the beta 170, but not the beta 90 subunit, to bind directly to p85 SH2 domains of PI-3 kinase. It is likely that the two different isoforms of INR have different signaling potentials. Finally, we show that loss of function mutations in the inr gene, induced by either a P-element insertion occurring within the predicted ORF, or by ethylmethane sulfonate treatment, render pleiotropic recessive phenotypes that lead to embryonic lethality. The activity of inr appears to be required in the embryonic epidermis and nervous system among others, since development of the cuticle, as well as the peripheral and central nervous systems are affected by inr mutations.

Amino Acid Sequence↗

Comparison of the signaling abilities of the Drosophila and human insulin receptors in mammalian cells.

Chimeric receptors encoding either the whole or a portion of the cytoplasmic domain of the drosophila insulin receptor (IR) with the extracellular domain of the human IR were expressed either transiently in COS cells or stably in Chinese hamster ovary cells and compared with the wild-type human IR. All three receptors bound insulin equally and exhibited an insulin-activated tyrosine kinase activity. The ability of the drosophila cytoplasmic domain to mediate the tyrosine phosphorylation of insulin receptor substrate 1, stimulate cell proliferation, and activate MAP kinase was found to be indistinguishable from that of the human IR. The chimeric drosophila receptors did not bind more phosphatidylinositol 3-kinase than the human IR, despite containing a C-terminal extension with potential tyrosine phosphorylation sites in the motif recognized by the SH2 domain of this enzyme. Thus, the essential signal-transducing abilities of the IR appear to have been conserved from invertebrates to mammals, despite the considerable differences in the sequences of these receptors.

Animals↗

Secretion of HCO3-/OH- in cortical distal tubule of the rat.

Secretion of bicarbonate has been described for distal nephron epithelium and attributed to apical Cl-/HCO3- exchange in beta-intercalated cells. We investigated the presence of this mechanism in cortical distal tubules by perfusing these segments with acid (pH 6) 10 mM phosphate Ringer. The kinetics of luminal alkalinization was studied in stationary microperfusion experiments by double-barreled pH (ion-exchange resin)/1 M KCl reference microelectrodes. Luminal alkalinization may be due to influx (into the lumen) of HCO3- or OH-, or efflux of H+. The magnitude of the Cl-/HCO3- exchange component was measured by perfusing the lumen with solutions with or without chloride, which was substituted by gluconate. This component was not different from zero in control and alkalotic (chronic plus acute) Wistar rats. Homozygous Brattleboro rats (BRB), genetically devoid of antidiuretic hormone, were used since this hormone has been shown to stimulate H+ secretion, which could mask bicarbonate secretion. In these rats, no evidence for Cl-/HCO3- exchange was found in control BRB and in early distal segments of alkalotic animals, but in late distal tubule a significant component of 0.14 +/- 0.033 nmol/cm2.sec was observed, which, however, is small when compared to the reabsorptive flow found in control Wistar rats, of 0.95 +/- 0.10 nmol/cm2.sec. In addition, 5 x 10(-4) M SITS had no effect on distal bicarbonate reabsorption in controls as well as on secretion in alkalotic Wistar and Brattleboro rats, which is compatible with the absence of effect of this drug on the apical Cl-/HCO3- exchange in other tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗

Incest revisited: delayed post-traumatic stress disorder in mothers following the sexual abuse of their children.

The case histories of four women who developed symptoms of post-traumatic stress disorder following the disclosure of the sexual abuse of their daughters are presented. These individuals also exhibited comorbid symptoms of depression and personality disorders. Awareness of the sexual abuse of their daughters catalyzed a reliving of their own childhood victimization. The psychodynamics operating in these cases, as well as treatment strategies are also presented. A brief follow-up of three of the four cases is included.

Adult↗

Dynamics of human keratin 18 phosphorylation: polarized distribution of phosphorylated keratins in simple epithelial tissues.

Phosphorylation of keratin polypeptides 8 and 18 (K8/18) and other intermediate filament proteins results in their reorganization in vitro and in vivo. In order to study functional aspects of human K18 phosphorylation, we generated and purified a polyclonal antibody (termed 3055) that specifically recognizes a major phosphorylation site (ser52) of human K18 but not dephosphorylated K18 or a ser52-->ala K18 mutant. Pulse-chase experiments followed by immunoprecipitation and peptide mapping of in vivo 32PO4-labeled K8/18 indicated that the overall phosphorylation turnover rate is faster for K18 versus K8, and that ser52 of K18 is a highly dynamic phosphorylation site. Isoelectric focusing of 32PO4 labeled K18 followed by immunoblotting with 3055 showed that the major phosphorylated K18 species contain ser52 phosphorylation but that some K18 molecules exist that are preferentially phosphorylated on K18 sites other than ser52. Immunoblotting of total cell lysates obtained from cells at different stages of the cell cycle showed that ser52 phosphorylation increases three to fourfold during the S and G2/M phases of the cell cycle. Immunofluorescence staining of cells at different stages of mitosis, using 3055 or other antibodies that recognize the total keratin pool, resulted in preferential binding of the 3055 antibody to the reorganized keratin fraction. Staining of human tissues or tissues from transgenic mice that express human K18 showed that the phospho-ser52 K18 species are located preferentially in the basolateral and apical domains in the liver and pancreas, respectively, but no preferential localization was noted in other simple epithelial organs examined. Our results support a model whereby phosphorylated intermediate filaments are localized in specific cellular domains depending on the tissue type and site(s) of phosphorylation. In addition, ser52 of human K18 is a highly dynamic phosphorylation site that undergoes modulation during the S and G2/M phases of the cell cycle in association with filament reorganization.

Amino Acid Sequence↗

Pharmacokinetics and tissue residues of norfloxacin and its N-desethyl- and oxo-metabolites in healthy pigs.

The pharmacokinetic properties of norfloxacin were determined in healthy pigs after single intramuscular (i.m.) and intravenous (i.v.) dosage of 8 mg/kg body weight. After i.m. and i.v. administration, the plasma concentration-time graph was characteristic of a two-compartment open model. After single i.m. administration, norfloxacin was absorbed rapidly, with a tmax of 1.46 +/- 0.06 h. The elimination half-life (t1/2 beta) and the mean residence time of norfloxacin in plasma were 4.99 +/- 0.28 and 6.05 +/- 0.22 h, respectively, after i.m. administration and 3.65 +/- 0.16 and 3.34 +/- 0.16 h, respectively, after i.v. administration. Intramuscular bioavailability was found to be 53.7 +/- 4.4%. Plasma concentrations greater than 0.2 microgram/mL were achieved at 20 min and persisted up to 8 h post-administration. Maximal plasma concentration was 1.11 +/- 0.03 micrograms/mL. Statistically significant differences between the two routes of administration were found for the half-lives of both distribution and elimination phases (t1/2 alpha, t1/2 beta) and apparent volume of distribution (Vd(area)). In pigs, norfloxacin was mainly converted to desethylenenorfloxacin and oxonorfloxacin. Considerable tissue concentrations of norfloxacin, desethylenenorfloxacin, and oxonorfloxacin were found when norfloxacin was administered intramuscularly (8 mg/kg on 4 consecutive days). The concentration of the parent fluoroquinolone in liver and kidney ranged between 0.015 and 0.017 microgram/g on day 12 after the end of dosing.

Absorption↗

The effect of short-term instillation of a mucolytic agent (mesna) on airway resistance in mechanically ventilated patients.

STUDY OBJECTIVE: To determine whether bolus instillation of a mucolytic agent (mesna) could diminish airway resistance, endotracheal tube resistance, or both in patients mechanically ventilated for acute respiratory failure. DESIGN: Randomized, double-blind, placebo-controlled, crossover trial. SETTING: Medical-surgical ICU of a county hospital covering 350,000 inhabitants. PATIENTS: Twenty sedated and paralyzed patients with an endotracheal tube (ET) in place more than 72 h. INTERVENTIONS: Data were recorded in three steps: (1) basal; (2) 10 min after endotracheal instillation of 3 mL of either saline solution or mesna; and (3) 10 min after instillation of the opposite drug. A 2-h washout period was allowed between data collection. MEASUREMENTS AND RESULTS: We measured tidal volume (VT), inspiratory flow (VI), auto-PEEP, peak pressure (both at airway opening [Pmax.aw] and trachea [Pmax-.tr]) and plateau pressure (Pplat), and we calculated respiratory system compliance (Crs) and the inspiratory resistances of airways+tube (Rmax.aw), airways (Rmax.tr), and ET (Rtube). We found significant differences after the instillation of mesna compared with baseline in the following: airway plus tube resistance (Rmax.aw) (16.9 +/- 7.1 vs 18.9 +/- 7.7 cm H2O); airways resistance (Rmax.tr) (9.8 +/- 6.2 vs 12.0 +/- 6.4 cm H2O), PaO2 (96 +/- 28.5 vs 80 +/- 24.8 mm Hg), PaO2/PAO2 (0.360 +/- 0.152 vs 0.296 +/- 0.127), and PaCO2 (42 +/- 12.9 vs 43 +/- 14.1 mm Hg). We found no changes in compliance, auto-PEEP, and hemodynamics during the study. Instillation of saline solution had no effect on the physiologic variables studied. CONCLUSIONS: In our patients, bolus tracheal instillation of mesna does not improve airway resistance; in fact, mesna instillation induces episodes of bronchospasm that disappear 2 h later.

Aged↗