Biomedical subjects

R Fernandez

Publications and source records attributed to R Fernandez.

At least 19 recordsLinked to original sources

PubMed1999

Improvement in oxygenation by prone position and nitric oxide in patients with acute respiratory distress syndrome.

OBJECTIVE: Inhaled nitric oxide (NO) and prone position improve arterial oxygenation in patients with the acute respiratory distress syndrome. This study was undertaken to assess the combined effects of NO and prone position in these patients. DESIGN: Prospective clinical study. SETTING: General intensive care service in a community teaching hospital. PATIENTS: 14 mechanically ventilated adult patients with the acute respiratory distress syndrome (mean lung injury score 3.23+/-0.27). MEASUREMENTS AND RESULTS: We measured hemodynamic and oxygenation parameters in the supine position and 2 h later in the prone position, before and during inhalation of 10 ppm NO. A positive response in oxygenation was defined as a > or =20% increment in the arterial oxygen tension/fractional inspired oxygen ratio (PaO2/FIO2). In the prone position PaO2/FIO2 increased significantly (from 110+/-55 to 161+/-89 mm Hg, p<0.01) and venous admixture decreased (from 38+/-12 to 30+/-7%, p<0.01) compared to the supine position. Ten of the 14 patients were responders in the prone position. In the supine position, inhalation of NO improved oxygenation to a lesser extent, increasing PaO2/FIO2 to 134+/-64 mm Hg (p<0.01) and decreasing venous admixture to 35+/-12%, (p<0.01). Five of the 14 patients responded to NO inhalation supine and 8 of 14 responded prone (p = 0.22). The combination of NO therapy and prone positioning was additive in increasing PaO2/FIO2 (197+/-92 mm Hg) and decreasing venous admixture (27+/-8%) (p<0.01). This combination also showed a positive oxygenation response on compared to the supine value without NO in 13 of the 14 patients (93 %). NO-induced changes in PaO2/FIO2 were correlated to changes in pulmonary vascular resistance only in the prone position. CONCLUSIONS: In patients with the acute respiratory distress syndrome, the combination of NO and prone position is a valuable adjunct to mechanical ventilation.

Administration, Inhalation↗

PubMed1999

Treatment with a nonanthracycline regimen in advanced breast cancer: vinorelbine, cyclophosphamide, and 5-fluorouracil with folinic acid.

The efficacy of combination therapy with vinorelbine, cyclophosphamide, and 5-fluorouracil was assessed in women who had received no prior therapy for locally advanced or metastatic breast cancer. Sixty patients with metastatic breast cancer who had finished any adjuvant therapy at least 6 months previously and who had not received treatment for advanced disease were entered onto the study. The schedule consisted of vinorelbine (Navelbine, Pierre Fabre Medicament) 25 mg/m2 on days 1 and 8, cyclophosphamide 500 mg/m2 on day 1, and 5-fluorouracil 500 mg/m2 followed by folinic acid 200 mg/m2 on days 1 and 8. Treatment was repeated every 21 days up to a maximum of 8 cycles. Objective responses were observed in 27 of 60 patients (45%; CI95 32.4-57.6) including 4 complete responses (6.7%; CI95 0-13) and 23 partial responses (38.3%; CI95 22.5-54.1). The responses were achieved in both visceral and nonvisceral sites and at the same rate for patients with multiple sites of disease. Neutropenia was dose limiting, with 40% of patients affected at grade 3 or 4, while other hematologic and nonhematologic toxicity was very mild. This schedule achieves good levels of response without the use of an anthracycline, so it is suitable either for patients who have been extensively exposed to anthracyclines during adjuvant therapy or for those who have other contraindications to their use.

Adult↗

PubMed1999

Effect of ventilator flow rate on respiratory timing in normal humans.

Respiratory rate (RR) increases as a function of ventilator flow rate (V). We wished to determine whether this is due to a decrease in neural inspiratory time (T In), neural expiratory time (TEn), or both. To accomplish this, we ventilated 15 normal subjects in the assist, volume cycled mode. Ventilator flow rate was varied at random, at four breaths with each step, over the flow range from 0.8 (Vmin) to 2.5 (Vmax) L/s. V T was kept constant. The pressure developed by respiratory muscles (Pmus) was calculated with the equation of motion (Pmus = V. R + V. E - Paw, where R = resistance, V = volume, E = elastance, and Paw = airway pressure). Electromyography of the diaphragm (Edi) was also done in five subjects. TIn and TEn were determined from the Pmus or Edi waveform. TIn decreased progressively as a function of V, from 1.44 +/- 0.34 s at Vmin to 0.62 +/- 0.26 s at Vmax (p < 0.00001). Changes in TEn were inconsistent and not significant. TIn/Ttot decreased significantly (0.30 +/- 0.06 at Vmin to 0.18 +/- 0.09 at Vmax; p < 0. 00001). We conclude that TI is highly sensitive to ventilator flow, and that the RR response to V is primarily related to this T In response. Because an increase in V progressively reduces T In/Ttot, and this variable is an important determinant of inspiratory muscle energetics, we further conclude that inspiratory muscle energy expenditure is quite sensitive to V over the range from 0.8 to 2.5 L/s.

Adult↗

PubMed1998

Type IV pili, transient bacterial aggregates, and virulence of enteropathogenic Escherichia coli.

Type IV bundle-forming pili of enteropathogenic Escherichia coli are required for the localized adherence and autoaggregation phenotypes. Whether these pili are also required for virulence was tested in volunteers by inactivating bfpA or bfpT (perA) encoding, respectively, the pilus subunit and the bfp operon transcriptional activator. Both mutants caused significantly less diarrhea. Mutation of the bfpF nucleotide-binding domain caused increased piliation, enhanced localized adherence, and abolished the twitching motility-dispersal phase of the autoaggregation phenotype. The bfpF mutant colonized the human intestine but was about 200-fold less virulent. Thus, BfpF is required for dispersal from the bacterial aggregate and for full virulence.

Adolescent↗

PubMed1998

Syk activation is required for spreading and H2O2 release in adherent human neutrophils.

Chemoattractant-stimulated polymorphonuclear leukocytes (PMNs) that are adherent to extracellular matrix proteins exhibit a massive, sustained respiratory burst that requires cell spreading. However, the signaling pathways culminating in PMN spreading are not well characterized. Studies showing that protein tyrosine phosphorylation increases with PMN spreading suggest that phosphorylation is critical for this process. In the present study, we observed increased tyrosine phosphorylation of both focal adhesion kinase and Syk in FMLP-activated PMNs that had been plated onto fibrinogen; an increase in Syk activity, but not focal adhesion kinase activity, was apparent. The time course of Syk phosphorylation correlated with the initiation of cell spreading and H2O2 release. Pretreatment of PMNs with piceatannol, a Syk-selective inhibitor, blocked Syk activity, cell spreading, and H2O2 release, indicating that Syk activity was required for the activation of adherent PMNs. Paxillin is a cytoskeletally associated protein that is also tyrosine phosphorylated during PMN spreading and H2O2 release. Paxillin phosphorylation is kinetically slower than Syk phosphorylation and is inhibited with piceatannol, suggesting that paxillin is a substrate for Syk. An analysis of Syk immunoprecipitates indicated that Syk and paxillin associate during PMN spreading. This interaction is not mediated by the src kinases Lyn and Fgr, since neither kinase coprecipitated with Syk. Syk from FMLP-activated, adherent PMNs phosphorylated paxillin-glutathione S-transferase, suggesting that paxillin is a substrate for Syk in vivo. These results indicate that PMN spreading and H2O2 release require a Syk-dependent signaling pathway leading to paxillin phosphorylation.

Cell Adhesion Molecules↗

PubMed1998

The effect of two antipodal fluorine-induced sugar puckers on the conformation and stability of the Dickerson-Drew dodecamer duplex [d(CGCGAATTCGCG)]2.

UV thermal melting studies, CD and NMR spectroscopies were employed to assess the contribution of antipodal sugar conformations on the stability of the canonical B-DNA conformation of the Dickerson-Drew dodecamer duplex [[d(CGCGAATTCGCG)]2, (ODN 1)]. Different oligodeoxynucleotide versions of ODN 1 were synthesized with modified thymidine units favoring distinct sugar conformations by using a 3'- endo (north) 2'-fluoro-2'-deoxyribofuranosyl thymine (1) or a 2'- endo (south) 2'-fluoro-2'-deoxyarabinofuranosyl thymine (2). The results showed that two south thymidines greatly stabilized the double helix, whereas two north thymidines destabilized it by inducing a more A-like conformation in the middle of the duplex. Use of combinations of north and south thymidine conformers in the same oligo destabilized the double helix even further, but without inducing a conformational change. The critical length for establishing a detectable A-like conformation in the middle of a B-DNA ODN appears to be 4 bp. Our results suggest that manipulation of the conformation of DNA in a sequence-independent manner is possible.

DNA↗

PubMed1998

Bilateral renal lymphangiomatosis: US and CT findings.

A case of bilateral renal lymphangiomatosis in an asymptomatic 50-year-old female is presented. Ultrasound and CT studies were performed. A finely septated fluid collection surrounding both kidneys and traversing the midline was found. Surgical biopsy was obtained and revealed findings compatible with lymphangiomatosis. A review of the literature of renal lymphangiomatosis is given.

Diagnosis, Differential↗

PubMed1998

Infant botulism during a one year period in San Luis, Argentina.

Five cases of infant botulism which occurred during the period from May 1995 to May 1996 in San Luis, Argentina, are reported. Infant botulism was confirmed in all patients by isolation of Clostridium botulinum type A from stool culture and by the toxin assay. Toxin was found in the serum of one of them. All patients required hospitalization with treatment consisting of supportive especially respiratory and nutritional care. At the time of discharge from the hospital, three patients had a good recovery, although two of them had mild difficulties in sucking or constipation. C. botulinum was not detected in samples of honey which had been given to two of the patients.

Argentina↗

PubMed1998

A new indole derivative from the red alga Chondria atropurpurea. Isolation, structure determination, and anthelmintic activity.

Chondriamide C (3), a new bis(indole) amide, was isolated from the red alga Chondria atropurpurea, and its structure was established from spectroscopic data and chemical transformations. A new natural product, 3-indoleacrylamide (4), and the previously described chondriamides A and B (1, 2) and 3-indoleacrylic acid (5) were also isolated. The anthelmintic activities of compounds 1, 3, 4, and 6 (the O,N1,N1'-trimethyl derivative of compound 2) against Nippostrongylus brasiliensis in vitro were evaluated.

Albendazole↗

PubMed1997

Beta2 integrins are not required for tyrosine phosphorylation of paxillin in human neutrophils.

Although many of the receptors mediating neutrophil (polymorphonuclear leukocyte (PMN)) adhesion to extracellular matrix (ECM) proteins have been identified, the signal transduction pathways leading to cell spreading are not clearly defined. Studies showing that protein tyrosine phosphorylation increases with PMN adhesion suggest that phosphorylation is critical for adhesion-dependent processes. In other cells, increased tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin are thought to play pivotal roles in ECM-mediated signaling. In the present study we compared the tyrosine phosphorylation of FAK and paxillin in PMNs plated onto thrombospondin (TSP) or laminin (LN). Increased tyrosine phosphorylation of paxillin correlated with adhesion and spreading of PMNs plated onto LN or TSP. In PMNs adherent to LN, the kinetics of FAK phosphorylation preceded the kinetics of paxillin phosphorylation, suggesting that paxillin may be a downstream target of FAK. In contrast, FAK was not phosphorylated in PMNs spread on TSP. These findings suggested activation of different signaling pathways in TSP- vs LN-adherent PMNs. Others have proposed that paxillin phosphorylation requires beta2 integrins. Therefore, we used PMNs from a patient with leukocyte adhesion deficiency (LAD), lacking beta2 integrins, to determine whether these receptors were necessary for paxillin phosphorylation. LAD PMNs did not adhere to LN, and consequently, there was no tyrosine phosphorylation of FAK or paxillin. In contrast, paxillin, but not FAK, was phosphorylated in LAD PMNs adherent and spread on TSP. These results indicate that ECM-beta2 integrin-mediated signaling initiates the FAK/paxillin signaling pathway(s), while TSP-mediated signaling results in paxillin phosphorylation independent of FAK phosphorylation.

CD18 Antigens↗

PubMed1997

Mechanisms and regulation of H+ transport in distal tubule epithelial cells.

The mechanism of acidification in the cortical distal tubule of mammalian kidney was analysed by "in vivo" microperfusion and using MDCK cells in culture, by electrophysiological and by cell pH microfluorescence techniques. An electrogenic effect of the vacuolar H(+)-ATPase, which has been localized to the intercalated cells of the cortical distal tubule (connecting segment and initial collecting duct) was only observed after blocking Cl- channels by NPPB. In MDCK cells, the recovery of cell pH after an acid pulse in Na(+)-free medium was also depressed by NPPB, indicating that Cl- ions have an important role in the function of H+ ATPase. The regulation by hormonal agents of distal H+ transport due to Na+/H+ exchange and to vacuolar H+ ATPase, was also studied by microperfusion and cell pH techniques. Angiotensin and vasopressin at picomolar concentrations stimulated both transport mechanisms in late distal tubule, and only Na+/H+ exchange in the early segment. In MDCK cells, cell pH recovery in the presence of Na+ was stimulated by picomolar concentrations of angiotensin and vasopressin, and inhibited by micromolar levels, both effects being reverted by micromolar ANP. Studies with specific antagonists suggest that the luminal effect of angiotensin is mediated by AT1 receptors, and of vasopressin by V1 receptors. There is evidence that cell Ca2+ may have an important regulatory role in the action of these hormones.

Acid-Base Equilibrium↗

PubMed1997

Effects of long-term storage on properties of an alginate impression material.

STATEMENT OF PROBLEM: Storage stability is a critical characteristic for perishable dental materials. PURPOSE: The purpose of this shelf-life study was to document changes in the properties of an alginate impression material on exposure to various environmental conditions for more than 78 months. MATERIAL AND METHODS: Properties measured included recovery from deformation, strain in compression, compressive strength, tear strength, working time, and creep compliance. RESULTS: Results revealed increases in strength and working time and a decrease in recovery from deformation at 30 to 50 months: strength and recovery then remained constant past 6 years, whereas working time and creep compliance decreased. Only the most stressful environmental conditions (heat and humidity) caused spontaneous failure of the material to set. CONCLUSIONS: We concluded that, under most storage conditions, properties of the alginate material tested remain within ADA specification limits well past manufacturer's designated shelf life. ADA specifications should require manufacturers to verify that the shelf life of each perishable material is based on valid data. An accelerated aging test was developed to simulate real time property changes and to assist in evaluating similar materials.

Alginates↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1996

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↗