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Biomedical subjects

M Ferrer

Publications and source records attributed to M Ferrer.

At least 127 records · Page 7Linked to original sources

Validity and reliability of the St George's Respiratory Questionnaire after adaptation to a different language and culture: the Spanish example.

We describe the adaptation into Spanish of the St George's Respiratory Questionnaire (SGRQ), a self-administered questionnaire developed by Jones et al. (1991) covering three domains of health in airways disease patients: symptoms, activity and impacts. For the adaptation, the forward and back-translation method by bilinguals was used, together with professional committee and lay panel. Once tested for feasibility and comprehension, 318 male chronic obstructive pulmonary disease (COPD) patients with a wide range of disease severity completed the Spanish version of the SGRQ. The clinical status of the patients was evaluated concurrently with the measurement of health status. Lung function was assessed in the 2 months before or after the questionnaire administration. The Spanish version of the SGRQ was acceptable and easy to understand. Cronbach's alpha reliability coefficient was 0.94 for the overall scale and 0.72 for "Symptoms", 0.89 for "Activity", and 0.89 for "Impacts" subscales. Correlation coefficients between the overall score and dyspnoea and % forced expiratory volume in one second (FEV1) were 0.59 and -0.45, respectively, and these correlations were higher than those observed between the clinical variables and the Nottingham Health Profile, a generic measure of health-related quality of life. Results of the study suggest that the Spanish version of the SGRQ is conceptually equivalent to the original, and similarly reliable and valid. Although further studies should complete the adaptation work, results suggest that the SGRQ may already be used in Spain and in international studies involving Spanish respiratory patients. According to the present approach, it appears to be feasible to adapt a specific questionnaire on health-related quality of life in respiratory disease to another language and culture.

Cross-Cultural Comparison↗

A mutant (Arg327-->His) GPIIb associated to thrombasthenia exerts a dominant negative effect in stably transfected CHO cells.

This work reports the structural and functional characterization of the platelet glycoprotein complex GPIIb-IIIa (integrin alpha IIb beta 3) in a patient of type II Glanzmann thrombasthenia, bearing a homozygous G-->A base transition at position 1074 of GPIIb that results in an Arg327-->His substitution. CHO cells stably transfected with cDNA encoding His327GPIIb showed a drastic reduction in the surface expression of alpha IIb beta 3 complex relative to control cells transfected with wild type GPIIb. Immunoprecipitation analysis demonstrated that GPIIb synthesis, heterodimerization, and short term maturation were not impeded, suggesting that conformational changes dependent on Arg327 of GPIIb may play an essential role in either the rate of maturation and/or transport of heterodimers to the cell surface. Cotransfection of CHO cells with equimolar amounts of cDNAs encoding wild type and mutant His327-GPIIb led to a marked reduction in the surface expression of alpha IIb beta 3. This novel observation of a dominant-negative effect of the mutant His 327 alpha IIb subunit provides a molecular basis for the reduced platelet alpha IIb beta 3 content observed in the heterozygous offspring.

Adult↗

Cloning, sequencing and functional expression of a cDNA encoding a NADP-dependent malic enzyme from human liver.

This work reports the structure of a cDNA (ME) encoding a human malic enzyme (ME) (malate NADP oxidoreductase, EC 1.1.1.40) elucidated by joining several overlapping fragments amplified by PCR from human hepatic cDNA or from cDNA libraries. The full-length cDNA has an open reading frame (ORF) of 1719 bp that encodes a 572-amino-acid protein of 64 113 Da, similar to the native monomeric, cytosolic, NADP-dependent ME isolated from human liver. The comparison of the structure of this cDNA with that of the human mitochondrial NAD(P)-dependent ME (EC 1.1.1.39) shows a homology of 63%, suggesting that these two forms originated from the same gene. The expression of the cDNA in Escherichia coli as a translational fusion (glutathione S-transferase::ME) protein yielded a product of the predicted mass. The recombinant protein shows NADP-dependent malate oxidoreductase activity and is virtually inactive with NAD. It also shows other distinct features of the native cytosolic NADP-dependent ME, like Mn2+ dependence, similar substrate (Km = 117 microM) and cofactor affinity (Km = 2 microM) constants, and a lack of allosteric regulation. In human proliferative cells, the NADP-dependent ME activity is poorly expressed and barely inducible by thyroid hormones.

Amino Acid Sequence↗

Involvement of alpha 2-adrenoceptors and protein kinase C on nicotine-induced facilitation of noradrenaline release in bovine cerebral arteries.

1. Incubation of bovine cerebral vessels (previously exposed to [3H]-noradrenaline) with nicotine for 30 sec produced a facilitation of the electrically-induced noradrenaline release, which was antagonized by hexamethonium, a blocker of nicotinic receptors. This facilitation was not observed when the incubation time was increased to 20 or 75 min. 2. Rauwolscine, an alpha 2-adrenoceptor blocker, enhanced and phorbol 12, 13-dibutyrate reduced the facilitator effect produced by 30 sec exposure to nicotine. 3. These data suggest: (1) presynaptic nicotinic receptors produce a facilitation of stimulated noradrenaline release; these receptors are easily desensitized by increasing the incubation time with nicotine; (2) protein kinase C and alpha 2-adrenoceptors appear to be involved in this process.

Adrenergic alpha-2 Receptor Agonists↗

Partially folded, molten globule and molten coil states of bovine pancreatic trypsin inhibitor.

Three denatured states of bovine pancreatic trypsin inhibitor have been characterized, using two chemically synthesized analogues designed for study of folding intermediates. One analogue, [14-38]Abu, retains only the 14-38 disulphide. At pH 4.5-6 and 1-7 degrees C, [14-38]Abu is a highly ordered beta-sheet molten globule; it has the circular dichroism (CD), ANS-binding and folding kinetics of a molten globule; is partially folded by NMR analysis; and undergoes cooperative thermal denaturation. At low temperature [14-38]Abu also forms an acid state at pH 1.5, as well as a denatured state at pH 2.5. A second BPTI analogue with all three disulphide bridges eliminated, [R]Abu, lacks detectable secondary and tertiary structure but has stable hydrophobic surfaces and is collapsed. We term this species a 'molten coil'.

Anilino Naphthalenesulfonates↗

Use of elastin fibre detection in the diagnosis of ventilator associated pneumonia.

BACKGROUND: Elastin fibre detection could be a simple and reliable marker of ventilator associated pneumonia. To confirm this, a prospective study was undertaken to evaluate the diagnostic yield of elastin fibre detection in the diagnosis of ventilator associated pneumonia. METHODS: Seventy eight mechanically ventilated patients were evaluated by examining endotracheal aspirates for the presence of elastin fibres. All patients were previously treated with antibiotics. Quantitative bacterial cultures of endotracheal aspirates and protected specimen brush samples were also performed. Patients were classified into three diagnostic categories: group 1, definite pneumonia (n = 25); group 2, probable pneumonia (n = 35); and group 3, controls (n = 18). RESULTS: Patients with definite and probable pneumonia were grouped together. The presence of elastin fibres in endotracheal aspirate samples was more frequent in groups 1 and 2, being found in 19 of the 60 patients compared with five of the control group. Although the presence of elastin fibres had a low sensitivity (32%), it was a reasonably specific marker (72%) of pneumonia. This specificity increased to 86% and 81% respectively when only Gram negative bacilli and Pseudomonas aeruginosa pneumonia were considered. Again, calculated sensitivity was 43% and 44% when analysing cases infected by Gram negative bacilli and Ps aeruginosa, respectively. The negative predictive value of the detection of elastin fibres in pneumonia caused by Ps aeruginosa was 81%. Detection was more frequent with infection by Gram negative bacilli (14/19), particularly with Ps aeruginosa (8/14). By contrast, pneumonia due to Gram positive cocci or non-bacterial agents uncommonly resulted in positive elastin fibre preparations (4/19, 21%). When analysing patients with and without chronic obstructive pulmonary disease, the diagnostic value of elastin fibre detection did not change. CONCLUSIONS: Potassium hydroxide preparation of elastin fibres is a rapid and simple specific marker of ventilator associated pneumonia and may be a useful technique to help diagnose pulmonary infections in mechanically ventilated patients, although this assessment is at present limited to patients without adult respiratory distress syndrome.

Adult↗

Re-intubation increases the risk of nosocomial pneumonia in patients needing mechanical ventilation.

In order to confirm that re-intubation can be a risk factor of nosocomial pneumonia in mechanically ventilated patients, a case-control study was performed. Forty consecutive patients needing re-intubation were selected as cases. Each case was paired with a matched control for the previous duration of mechanical ventilation (+/- 2 d). Nineteen (47%) of the cases developed pneumonia after re-intubation compared with 4 (10%) of the controls (odds ratio [OR] = 8.5; 95% confidence interval [CI] 1.7 to 105.9; p = 0.0007). After adjusting for age, sex, and presence of prior bronchoscopy, the conditional logistic regression analysis demonstrated that re-intubation was the only significant factor related to the development of pneumonia (OR: 5.94; 95% CI 1.27 to 22.71; p = 0.023). Sixteen (73%) of the 22 patients lying semirecumbent during the interval between extubation and re-intubation developed nosocomial pneumonia versus three (16%) of the 18 in supine position (p = 0.001). These results indicate that semirecumbency during the period between extubation and re-intubation may play a role in nosocomial pneumonia development in patients who need re-intubation. Total intensive care unit stay (19.4 +/- 10 versus 13.9 +/- 11.9 days, p = 0.0008) and crude mortality (35 versus 20%, p = 0.14) were also higher in re-intubated patients when compared with controls. We conclude that re-intubation is a risk factor for ventilator-associated pneumonia and might be avoided in a substantial number of cases.

Case-Control Studies↗

Semirecumbent position protects from pulmonary aspiration but not completely from gastroesophageal reflux in mechanically ventilated patients.

The aim of this study was to evaluate the effect of two body positions (supine and semirecumbency) on the dynamics of gastroesophageal reflux (GER) in 15 patients requiring mechanical ventilation and having a nasogastric tube in place. Samples of gastric contents, pharyngeal and bronchial secretions, and blood were obtained at baseline and every hour during a period of 5 h after nasogastric tube isotopic instillation of 37 megabecquerels of Tc99m. Radioactivity counting (RAc) was performed using a gamma counter with correction for decay. Irrespective of the body position, all patients showed at 3, 4, and 5 h after the isotope instillation a significant increase in RAc of the oropharyngeal contents (p < 0.05, each), indicating GER. Although RAc values in the pharynx were higher in supine from 1 through 4 h (p < 0.05), at the end of the study (5 h) the values did not differ between each position. Likewise, the slopes of the regression lines of sequential oropharyngeal RAc values were not different between each position (0.39 +/- 0.09 versus 0.45 +/- 0.11, respectively). In contrast, RAc values in bronchial secretions were higher at 5 h in the supine position compared with baseline (p < 0.05) and to semirecumbency (p < 0.01). These results strongly support that GER in mechanically ventilated patients with a nasogastric tube is a feature occurring irrespective of body position. Semirecumbent position does not protect completely from GER and subsequently from oropharyngeal colonization from gastric origin.

Cross Infection↗

Servocontrolled generator to measure respiratory impedance from 0.25 to 26 Hz in ventilated patients at different PEEP levels.

Assessing respiratory impedance (Zrs) in ventilated patients over a wide frequency band, ranging from breathing rates to typical forced oscillation frequencies, during end-expiratory pauses at different positive end-expiratory pressures (PEEP) is of potential interest to assess a patient's respiratory mechanics. Zrs measurements under these conditions are not possible with the present variants of the forced oscillation technique. The aim of this work was to design a forced oscillation generator operating from spontaneous breathing frequencies whilst withstanding PEEP. To this end, we constructed a generator based on a servocontrolled loudspeaker. This allowed the loudspeaker cone to remain at its resting position regardless of the external PEEP applied. The system was optimized by using a mechanical analogue. The clinical applicability of the servocontrolled generator was assessed by measuring Zrs in mechanically-ventilated chronic obstructive pulmonary disease (COPD) patients during end-expiratory pauses at different transrespiratory pressures. The forced oscillation generator designed may be easily applicable in practice since it is small and light. The system is able to withstand transrespiratory pressures of up to 17 hPa and allows the application of forced oscillation of sufficient amplitude ( > 2 hPa peak-to-peak, 0.25-26 Hz) to obtain reliable respiratory resistance and reactance data. The servocontrolled generator permits the assessment of respiratory mechanics over a wide frequency band ranging from breathing frequencies to the most typical forced oscillation frequencies during end-expiratory pauses at PEEPs within the conventional range.

Equipment Design↗

Human-associated staphylococcal infection in Spanish imperial eagles.

At Doñana National Park, Spain, we compared the prevalence of Staphylococcus spp. infections in the Spanish imperial eagle (Aquila adalberti) in 66 nestlings handled with bare hands and in 46 nestlings handled with gloved hands, 1986 to 1993. We detected staphylococcal infections in 30 (45%) of 66 chicks handled without gloves, and in two (4%) of 46 chicks handled with gloves.

Abscess↗

Treatment with the anabolic steroid, nandrolone, reduces vasoconstrictor responses in rabbit arteries.

The objective of this study was to analyze the effect of chronic treatment of rabbits for 4, 8 and 12 weeks with the anabolic steroid, nandrolone, on the contractile responses induced by different agents in segments of thoracic aorta and mesenteric and femoral arteries. In the three types of arteries, the contractions elicited by noradrenaline, 5-hydroxytryptamine and angiotensin II were increased by endothelium removal. The treatment reduced the contractions elicited by the three agents (mainly those caused by 5-hydroxytryptamine) in aorta, and only those caused by 5-hydroxytryptamine in mesenteric arteries. Ca(2+)-free medium containing 0.1 mM ethylene glycol bis (beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA) reduced the responses elicited by 1 microM noradrenaline, 10 microM 5-hydroxytryptamine and 0.1 microM angiotensin II in aorta segments from control rabbits. Addition of CaCl2 to this medium restored the initial responses elicited by the three agents in normal medium, both in arteries from control and treated rabbits. In aorta, the contractions elicited by phorbol 12,13-dibutyrate (PDB), an activator of protein kinase C, were reduced by the treatment. Staurosporine, an inhibitor of protein kinase C, reduced the responses evoked by PDB. Likewise, the contractions caused by noradrenaline, 5-hydroxytryptamine and especially by angiotensin II were also reduced by staurosporine. These results suggest that the thoracic aorta is the most affected by the treatment, and that the reduction of contractile responses appears to be due to changes in protein kinase C activity and/or in a mechanism situated beyond protein kinase C activation.

Alkaloids↗

Utility of selective digestive decontamination in mechanically ventilated patients.

OBJECTIVE: To assess selective digestive decontamination for preventing nosocomial pneumonia and mortality in mechanically ventilated patients. DESIGN: Prospective, randomized, placebo-controlled, double-blind study. SETTING: Respiratory intensive care unit of a 1000-bed teaching hospital. PATIENTS: 80 patients receiving mechanical ventilation for more than 72 hours. INTERVENTIONS: Patients received selective digestive decontamination using polymyxin E, tobramycin, and amphotericin B through a nasogastric tube and also topically in the oropharynx; control patients received placebo. All patients received intravenous cefotaxime for 4 days or other systemic antibiotics if required. MEASUREMENTS: Bacteriologic surveillance (three times a week) was done by quantitatively culturing tracheal aspirates, pharyngeal swabs, and gastric juice. The diagnosis of pneumonia was based on quantitative cultures of protected specimen brush samples (> or = 10(3) CFU/mL [colony forming units/mL]) or bronchoalveolar lavage fluid (> or = 10(4) CFU/mL) and autopsy findings. RESULTS: Bronchial, oropharyngeal, and gastric colonization by gram-negative bacilli and Candida species was lower in the selective digestive decontamination group compared with the placebo group. Nonsignificant differences were found in the incidence of nosocomial infections (28% compared with 37%; odds ratio, 0.66; 95% CI, 0.35 to 1.25) and nosocomial pneumonia (18% compared with 24%; odds ratio, 0.7; CI, 0.33 to 1.46) and in the crude mortality rate (31% compared with 27%; odds ratio, 1.21; CI, 0.63 to 2.34) when comparing digestive decontamination with placebo, respectively. CONCLUSIONS: Selective digestive decontamination in our mechanically ventilated patients significantly decreased the colonization rate of gram-negative bacilli and of Candida species but not of Staphylococcus aureus. It did not decrease the incidence of nosocomial pneumonia, mortality, length of stay, or the duration of mechanical ventilation.

Adult↗

Chronic treatment with the anabolic steroid, nandrolone, inhibits vasodilator responses in rabbit aorta.

The effect of chronic treatment of rabbits for 4, 8 and 12 weeks with the anabolic steroid, nandrolone, on vasodilator responses was studied in segments of different arteries. The treatment abolished endothelium-dependent relaxation caused by acetylcholine and the Ca(2+)-ionophore, A23187, in thoracic aorta, and reduced endothelium-independent relaxations induced by exogenous nitric oxide (NO) or sodium nitroprusside. The inhibitor of NO synthesis, NG-monomethyl-L-arginine, abolished vasodilator responses to acetylcholine and A23187. In contrast, relaxation induced by acetylcholine, NO or sodium nitroprusside in mesenteric and femoral arteries was unaltered by nandrolone treatment. Bioassay experiments using donor segments and endothelium-denuded bioassay rings from thoracic aorta show that acetylcholine, applied either through control or treated (12 weeks) donor segments, produced similar relaxation in bioassay rings from control rabbits, but this relaxation was markedly reduced in rings from treated rabbits. The increases of cyclic GMP levels induced by acetylcholine or sodium nitroprusside in segments from thoracic aorta were abolished by nandrolone treatment. These results suggest that the treatment with nandrolone reduces NO-mediated relaxation only in thoracic aorta by inhibition of guanylate cyclase, endothelial NO production and vasodilator machinery being unaltered.

Animals↗

Disaccharidase activities in pregnant and lactating rats.

The changes in intestinal disaccharidase activities in pregnancy and lactation could be explained as a result of an adaptation to the energy demands of each reproductive stage. To examine these changes, disaccharidase activities (lactase, sucrase, maltase, and trehalase) were measured in the jejunum and ileum of virgin, pregnant and lactating Wistar rats. Minor changes in disaccharidase activities were observed in pregnancy, whereas an increase of disaccharidase activities per small intestine length normalized to body mass was observed in lactation.

Animals↗

Angiotensin modulation of vascular tone and adrenergic neurotransmission in cat femoral arteries.

1. AI and AII induced contractions in cat femoral arteries, which were inhibited by saralasin. 2. The response to AI was reduced by captopril and endothelium removal and by chymostatin in endothelium-denuded segments. 3. AII contractions were increased by indomethacin, L-NAME and endothelium removal. 4. AII and AI facilitated the adrenergic neurotransmission. This facilitation was inhibited by saralasin and/or captopril. 5. These data suggest: (1) AI is converted into AII in the endothelial and adventitial layer; (2) the contractions caused by AI and AII are mediated by AII receptors and are modulated by endothelial release of NO and PGI2; and (3) the existence of presynaptic AII receptors mediating the facilitation of neurotransmission caused by AI and AII.

Analysis of Variance↗

Morphological adaptive changes of small intestinal tract regions due to pregnancy and lactation in rats.

In order to know the adaptive changes of small intestine regions (duodenum, and proximal, medial and distal jejunum-ileum) due to the reproductive stage (virgin, pregnancy and lactation), the weight, mucosal proportion, mucosal DNA and protein contents and protein/DNA ratio in female Wistar rats were measured. Pregnancy induces hypertrophy of the proximal half of the small intestine (duodenum and proximal jejunum-ileum), whereas lactation induces hyperplasia in all small intestinal regions and also hypertrophy but only in the duodenum.

Animals↗

Validation of different techniques for the diagnosis of ventilator-associated pneumonia. Comparison with immediate postmortem pulmonary biopsy.

To assess the accuracy of clinical parameters for the diagnosis of ventilator-associated (VA) pneumonia, as well as the diagnostic value of several invasive techniques, such as protected specimen brush (PSB), bronchoalveolar lavage (BAL), fiberoptic bronchial aspirates (FBAS), and percutaneous lung needle aspiration (PLNA), we compared the results of these techniques with the histopathology of immediate postmortem pulmonary biopsies, considered the "gold standard" reference test. We studied 30 mechanically ventilated patients (age 52 +/- 21 yr; mechanical ventilation period 9 +/- 7 days) who died in an intensive care unit. All patients received prior antibiotic treatment. The following procedures were performed immediately after death: bilateral PSB, BAL, FBAS, and PLNA, as well as bilateral minithoracotomies to obtain pulmonary biopsies as close as possible to the area sampled with the other techniques. According to the histopathology 18 patients had pneumonia and 12 did not. The presence of fever (sensitivity 55%, specificity 58%), purulent secretions (sensitivity 83%, specificity 33%), and chest radiograph infiltrates (sensitivity 78%, specificity 42%) could not differentiate in all instances presence from absence of pneumonia. Quantitative bacterial cultures of lung biopsies using 10(3) cfu/g as a cutoff point had low sensitivity (40%) and low specificity (45%) and could not differentiate the histologic absence or presence of pneumonia. Considering the histopathology of pulmonary biopsies as a gold standard, we found the following sensitivities for PSB, BAL, FBAS, and PLNA: 36, 50, 44, and 25%. The specificities were 50, 45, 48, and 79%, respectively. The sensitivities and specificities of different invasive techniques are much lower than those reported in clinical studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗