Biomedical subjects

R Fernandez

Publications and source records attributed to R Fernandez.

At least 55 records · Page 3Linked 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

Permeation of NH3/NH4+ and cell pH in colonic crypts of the rat.

Colon cells are subjected to high concentrations of NH3 and NH4+, and a sizeable portion of this buffer is absorbed. The flux of these components into cells causes opposite effects on their pH; this effect is largely used to induce an acid load and to observe the mechanism of acid extrusion from cells. We studied cells of microdissected colon crypts loaded with BCECF and superfused with NH4Cl-containing Krebs-Ringer solution. We found a marked transient reduction in pH measured by ratiometric fluorescence microscopy, from a control value of 7.51 +/- 0.041 to 7.15 +/- 0.041 (n = 21), instead of the initial alkalinization found in most cells. This pH was reached at a rate of 0.95 +/- 0.07 pH units/min. Addition of 1 mmol/l furosemide, a blocker of Na+,K+,2Cl- cotransport, to the ammonium solution inverted this acidification toward alkalinization (pH 7.89 +/- 0.041, n = 5), and superfusion with furosemide plus 0.1 mmol/l hexamethylene amiloride, a specific blocker of Na+/H+ exchange, increased this initial alkalinization further to 8.10 +/- 0.117 (n = 7). When Krebs-Ringer with 0 Cl- containing (NH4)2SO4 instead of NH4Cl was superfused, the acid transient was also reverted to alkalinization; however, a higher degree of alkalinization was observed either when 1 mmol/l furosemide was added to the superfusing sulfate solution (when a pH of 7.78 +/- 0.010 was reached), or when ammonium gluconate was used instead of ammonium sulfate. The addition of Ba2+ to the superfusion solution did not alter the initial acidification. These data indicate that in colon crypt cells, basolateral membrane transporters, in particular the Na+,K+,2Cl- cotransporter and the Na+/H+ exchanger (but not Ba(2+)-sensitive K+ channels), mediate the predominant influx of NH4+ ions leading to the initial transient acidification.

Amiloride↗

PubMed1999

Volumetric capnography in patients with acute lung injury: effects of positive end-expiratory pressure.

The aim of the study was to analyse the effects of positive end-expiratory pressure (PEEP) on volumetric capnography and respiratory system mechanics in mechanically ventilated patients. Eight normal subjects (control group), nine patients with moderate acute lung injury (ALI group) and eight patients with acute respiratory distress syndrome (ARDS group) were studied. Respiratory system mechanics, alveolar ejection volume as a fraction of tidal volume (VAE/VT), phase III slopes of expired CO2 beyond VAE and Bohr's dead space (VD/VT(Bohr)) at different levels of PEEP were measured. No differences in respiratory system resistances were found between the ALI and ARDS groups. VD/VT(Bohr) and expired CO2 slope beyond VAE were higher in ALI patients (0.52+/-0.01 and 13.9+/-0.7 mmHg x L(-1), respectively) compared with control patients (0.46+/-0.01 and 7.7+/-0.4 mmHg x L(-1), p<0.01, respectively) and in ARDS patients (0.61+/-0.02 and 24.9+/-1.6 mmHg x L(-1), p<0.01, respectively) compared with ALI patients. VAE/VT differed similarly (0.6+/-0.01 in control group, 0.43+/-0.01 in ALI group and 0.31+/-0.01 in ARDS group, p<0.01). PEEP had no effect on VAE/VT, expired CO2 slope beyond VAE and VD/VT(Bohr) in any group. A significant correlation (p<0.01) was found between VAE/VT and expired CO2 slope beyond VAE and lung injury score at zero PEEP. Indices of volumetric capnography are affected by the severity of the lung injury, but are unmodified by the application of positive end-expiratory pressure.

Adult↗

PubMed1999

Homeopathic terminology: a consensus quest.

The aim of this project is to develop a common homeopathic terminology to improve communication. A questionnaire was sent by email to an international group of experts. As a result of an iterative process we propose that a number of terms which are inaccurate, unclear or have become outdated should be replaced by new terms. The main areas in which terminology should be updated are: concepts relating to: homeopathic pharmacology, research, homeopathic medicine, the principle of similarity, homeostasis and disease imitation, miasms, experimental homeopathy, provings and pathogenic trials.

Homeopathy↗

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

Necrosis of schwann cells during tellurium-induced primary demyelination: DNA fragmentation, reorganization of splicing machinery, and formation of intranuclear rods of actin.

We present a cytological, immunocytochemical, and biochemical study of the cell death of mature myelinating Schwann cells (SCs) in the primary demyelinating neuropathy induced by tellurium (Te). Weaned rats were fed a diet containing 1.1% elemental Te. The animals were killed daily within the first week of Te diet. After 4 to 6 days of Te treatment some SCs underwent degeneration and necrosis. By electron microscopy analysis, degenerating SCs showed chromatin condensation, detachment from the nuclear envelope of condensed chromatin clumps, aggregation of interchromatin granule clusters, formation of intranuclear bundles of microfilaments, and cytoplasmic vesiculation. By confocal laser fluorescence microscopy, chromatin regions were stained with the TUNEL method for in situ labeling of DNA fragmentation and exhibited a progressive reduction of histone signal. In addition, splicing small nuclear ribonucleoprotein (snRNP) factors were redistributed in a few large nuclear domains and bright foci of intranuclear actin were observed. DNA electrophoresis revealed a smear pattern of DNA fragmentation in sciatic nerve samples from Te-treated animals. Upon Te treatment, no degradation of the caspase substrates poly (ADP-ribose) polymerase and lamin B was detected by Western blots or immunocytochemistry, respectively. The peculiar structural rearrangement of the transcription and splicing machinery as well as the vesicular degeneration of the cytoplasm in degenerating SCs support an autophagic cell death of the necrotic type. Unlike the apoptosis of pre-remyelinating SCs (11), this caspase independent cell death of necrotic type involves mature pre-demyelinating SCs and eliminates SCs injured by the neurotoxic effect of Te.

Actins↗

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↗

PubMed1999

Toxicokinetics and oral bioavailability of fumonisin B1.

The kinetics of fumonisin B1 (FB1) after single doses of 10 mg FB1/kg (po) or 2 mg FB1/kg (i.v.) were studied in male Wistar rats. Serial blood samples were obtained after p.o and i.v. administration. Liver and kidney tissue samples were also obtained after p.o administration. Plasma, liver and kidney concentrations of FB1 were determined by a reversed-phase high-performance liquid chromatographic assay using precolumn 0-phthaldialdehyde derivatisation with fluorescence detection. The FB1 plasma profile could be adequately described by a 2-compartment open model. For FB1, the elimination half-life from plasma was 1.03 h after i.v. and 3.15 h after p.o administration. The apparent volume of distribution and volume of distribution at steady state for FB1 were 0.11 and 0.072 L, respectively, after i.v. administration. The total plasma clearance of FB1 was the same for both the p.o and i.v. routes, 0.072 L/h. After the single p.o dose, FB1 was rapidly absorbed with a Tmax of 1.02 h. The maximum plasma concentration of FB1 was 0.18 microgram/mL. The p.o bioavailability of FB1 was 3.5%. The tissue concentration time data for FB1 fit a 1-compartment open model. Considerable concentrations of FB1 were found in the liver and kidney tissues. The elimination half-lives for FB1 were longer for liver (4.07 h) and kidney (7.07 h) than for plasma (3.15 h). Tissue accumulation of FB1 was evidenced by the tissue/plasma area under the concentration-time curve (AUC) ratios; the AUCtissue/AUCplasma for FB1 was 2.03 in liver and 29.89 in kidney.

Administration, Oral↗

PubMed1999

Leadership 99. Interview by Terese Hudson.

Cost control, customer service and collaboration among health care sectors rank as top concerns with panelists in H&HN's annual Leadership Report. Efforts to improve community health are a priority, too, but are often frustrated by financial and other constraints. The 16 panelists represent managed care, physicians, and hospitals and health systems.

Attitude of Health Personnel↗

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↗