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Biomedical subjects

I Sanchez

Publications and source records attributed to I Sanchez.

At least 37 records · Page 2Linked to original sources
PubMed1995

[Role of anticholinergic agents in the treatment of cystic fibrosis].

A significant proportion of patients with cystic fibrosis (CF) demonstrate increased airways hyperreactivity, a feature that has been well documented by several authors. This bronchial lability is more pronounced in those with more severe and advanced lung disease. Several mechanisms for this increased airways responsiveness have been proposed such as chronic inflammation with impairment of mucosal permeability, increase in amount of bronchial secretions, systemic autonomic abnormality, increase in incidence of atopy and airway narrowing and changes in airway geometry induced by chronic inflammation. Several studies have assessed the change in FEV1 after beta-agonist or anticholinergic therapy in CF patients and there are studies in which the effect of the combination of drugs was tested. In a group of young CF patients, we found on average a 7% increase in FEV1 after salbutamol and a 10% improvement after ipratropium bromide (IB). After inhaling both drugs, there was a 17% increase in FEV1 from baseline. There were also significant changes in static volumes and airway-resistance measurements when salbutamol and IB were administered in combination. The influence of pretreatment of either normal saline, salbutamol or ipratropium bromide with methacholine was evaluated by Avital and co-workers in a double-blind crossover study. They found an increase in PC20 without a change in baseline FEV1 following salbutamol and an even greater change after IB. These results suggest that the adrenergic agent altered the smooth muscle contractile mechanism, and that muscarinic pathway appears to be important in the pathogenesis of expiratory airflow obstruction in some CF patients. The mechanisms of this cholinergic sensitivity are unclear.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuterol↗
PubMed1995

Drug management of noninfective complications of cystic fibrosis.

Cystic fibrosis (CF) is the commonest lethal hereditary disease in Caucasians. The disease involves a gene mutation located at the long arm of chromosome 7, and more than 300 mutations have been identified. CF is a systemic illness affecting the upper respiratory tract and airways, sweat and salivary glands, pancreas, gastrointestinal tract, liver and male reproductive system. The course is highly variable depending on the specific molecular abnormalities in the mutant gene. The current approach to therapy now involves the use of: (i) chest physiotherapy; (ii) bronchodilators when there is evidence of airways hyperreactivity; (iii) oral and intravenous antibiotics for acute pulmonary exacerbations and aerosolised antibiotics for prevention; (iv) recombinant human deoxyribonuclease I (dornase alfa) to promote airways clearance; (v) amiloride to improve sputum viscosity; (vi) pancreatic enzyme replacement therapy along with nutritional support and supplements; (vi) vitamins; and (vii) ursodeoxycholic acid in selected patients. The use of antiprotease and anti-inflammatory agents has been shown to be useful in preventing the damage secondary to chronic lung infection. In patients with severely impaired lung function, lung transplantations have been performed with good results. Finally, it seems probable that lung disease in CF patients will be ameliorated or prevented in the future with early gene therapy, using vectors such as recombinant adenoviruses, adeno-associated virus, lipofection or retrovirus. However, this require extensive basic and clinical research.

Cystic Fibrosis↗
PubMed1994

Localization of tau and other proteins of isolated marginal bands.

To determine which proteins were associated with and intrinsic to the marginal band (MB) of microtubules (MTs), we studied protein components of MBs isolated from nucleated erythrocytes by differential detergent solubilization of the membrane skeleton (MS). MBs isolated from dogfish erythrocytes contained major proteins in the tubulin M(r) range. A high molecular weight protein of approximately 290 kD that bound antibody to syncolin and to heat-stable brain MAPs was present in the whole cytoskeleton. However, most of it was solubilized by the MB isolation medium, together with the MS. Dogfish erythrocyte cytoskeletons and isolated MBs were examined with polyclonal and monoclonal antibodies against mammalian brain tau and chicken erythrocyte tau. As shown by immunofluorescence and immunoblotting, these antibodies bound to proteins in the 50 to 67 kD range, located along the length of isolated MBs. Two-dimensional SDS-PAGE revealed isolated MB proteins of pI approximately 6.8 in the same molecular weight range, as well as alpha- and beta-tubulin with pI approximately 5.4. Subtilisin or high-salt treatment of isolated MBs resulted in unbundling of MTs, indicating involvement of MAPs. MBs isolated from chicken erythrocyte cytoskeletons also contained tau as shown by anti-mammalian brain tau immunofluorescence. Both chicken and dogfish isolated MBs also bound phalloidin, but the binding was usually discontinuous and, for any given MB, matched the pattern of anti-syncolin binding. Both syncolin and F-actin were part of the MS remnant remaining after MT disassembly, supporting their assignment to a specialized MS region at the MB/MS interface. In contrast, tau protein appears to be intrinsic to the MB, where it may have an MT stabilizing and bundling function.

Actins↗
PubMed1994

Assembly and bundling of marginal band microtubule protein: role of tau.

Microtubule protein extracted from dogfish erythrocyte cytoskeletons by disassembly of marginal bands at low temperature formed linear microtubule (MT) bundles upon reassembly at 22 degrees C. The bundles, which were readily visible by video-enhanced phase contrast or DIC microscopy, increased in length and thickness with time. At steady state after 1 hour, most bundles were 6-11 microns in length and 2-5 MTs in thickness. No inter-MT cross-bridges were visible by negative staining. The bundles exhibited mechanical stability in flow as well as flexibility, in this respect resembling native marginal bands. As analyzed by SDS-PAGE and immunoblotting, our standard extraction conditions yielded MT protein preparations and bundles containing tau protein but not high molecular weight MAPs such as MAP-2 or syncolin. In addition, late fractions of MT protein obtained by gel filtration were devoid of high molecular weight proteins but still produced MT bundles. The marginal band tau was salt-extractable and heat-stable, bound antibodies to mammalian brain tau, and formed aggregates upon desalting. Antibodies to tau blocked MT assembly, but both assembly and bundling occurred in the presence of antibodies to actin or syncolin. The MTs were "unbundled" by subtilisin or by high salt (0.5-1 M KCl or NaCl), consistent with tau involvement in bundling. High salt extracts retained bundling activity, and salt-induced unbundling was reversible with desalting. However, reversibility was observed only after salt-induced MT disassembly had occurred. Reconstitution experiments showed that addition of marginal band tau to preassembled MTs did not produce bundles, whereas tau presence during MT reassembly did yield bundles. Thus, in this system, tau appears to play a role in both MT assembly and bundling, serving in the latter function as a coassembly factor.

Animals↗
PubMed1993

Acoustic vs. spirometric assessment of bronchial responsiveness to methacholine in children.

To study wheezing as an indicator of bronchial responsiveness during methacholine challenge (MC) in children, we used computer analysis of respiratory sounds and compared wheeze measurements to routine spirometry. MC was performed in 30 symptomatic subjects (sympt), age 11 +/- 3.1 years (mean +/- SD), with suspected asthma and in 12 controls (contr), age 10 +/- 3.4 years. Respiratory rate (RR), spirometry, arterial oxygen saturation (SaO2), and cough were registered until the concentration provoking a > or = 20% fall in forced expiratory flow in 1 second (FEV1;PC20), or the end point (8 mg/mL) was reached. For 1 min after each inhalation, sounds over the trachea and posterior right lower lobe were recorded together with calibrated airflow. Computer analysis of respiratory sounds was used for objective wheeze quantification. Wheezing was measured as its duration relative to inspiration (Tw/Ti) and expiration (Tw/Te). Seventeen of the sympt group developed wheezing (sympt/W) with > or = 5% Tw/Ti or > or = 5% Tw/Te. Thirteen of the sympt did not wheeze (sympt/no W). Three contr developed wheeze (contr/W) while 9 did not (contr/no W). In sympt/W, RR increased from 20 +/- 6.2 per min at baseline to 25 +/- 9.2 (P < 0.05) at the MC concentration provoking wheeze (PCw), and SaO2 decreased from 97.4 +/- 1.2% to 95.3 +/- 2.4 (P < 0.05). In contr/W, RR did not change, but SaO2 decreased from 97.3 +/- 1.5% to 95.7% +/- 1.2% (P < 0.05). Wheezing occurred at both recording sites and was as common during inspiration as during expiration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Effect of racemic epinephrine and salbutamol on clinical score and pulmonary mechanics in infants with bronchiolitis.

To test the efficacy of a combined alpha- and beta-receptor agonist in acute bronchiolitis, we compared inhaled racemic epinephrine with salbutamol in a double-blind, crossover, randomized protocol. Twenty-four infants, 4.6 +/- 0.5 (mean +/- SEM) months of age, with their first episode of bronchiolitis were tested. After sedation with chloral hydrate, a clinical score and pulmonary mechanics measurements using simultaneous signals of airflow volume and transpulmonary pressure were recorded. After baseline measurements, infants received either nebulized salbutamol, 0.03 ml/kg, or racemic epinephrine, 0.1 ml/kg. Thirty minutes later, there was a significant decrease in clinical score after treatment with racemic epinephrine compared with the baseline score (p < 0.001); this difference was not present after salbutamol inhalation (p = 0.42). Only 13 patients had a decrease in clinical score after salbutamol therapy, in comparison with 20 infants treated with racemic epinephrine (p < 0.01). Both drug decreased respiratory rate, but the decrease was greater after the use of racemic epinephrine (p < 0.001). There was a significant decrease in inspiratory, expiratory, and total pulmonary resistance after treatment with racemic epinephrine compared with baseline values (p < 0.01) but no significant change after salbutamol inhalation. There was no significant correlation between the clinical score and pulmonary mechanics either at baseline or after drug treatment. We conclude that racemic epinephrine is superior to salbutamol in the treatment of infants with their first episode of acute bronchiolitis.

Administration, Inhalation↗
PubMed1993

Wheezing and airflow obstruction during methacholine challenge in children with cystic fibrosis and in normal children.

To study wheeze as an indicator of bronchial responses during standardized methacholine challenge (MCH), we used computerized analysis of respiratory sounds in children with cystic fibrosis (CF) and in healthy control subjects. We recorded tracheal and lung sounds from 10 young CF = yCF patients, mean age 5.7 yr (range 4 to 7 yr), 13 older CF = oCF, age 10.5 yr (8 to 18 yr), 7 young normal subjects = yNO, age 5.3 yr (4 to 7 yr), and 11 older normal subjects = oNO, age 11 yr (8 to 16 yr). Spirometry was obtained after each doubling concentration of methacholine until the concentration provoking a > or = 20% fall in FEV1 (PC20) or the end point (8 mg/ml) was reached. Sound and calibrated flow signals were recorded on tape and later analyzed by respirosonography. The concentration of methacholine associated with wheeze (PCw) was noted. Wheezing was quantified by its duration during inspiration (Tw/TI) and expiration (TW/TE). We found a positive response to MCH in 11 of 13 oCF (PC20 0.75 mg/ml, range 0.08 to 3.0) and in 3 of 11 oNO (PC20 4.2 mg/ml, range 2.5 to 6.5). Wheezing occurred in 6 oCF (PC20 < 8 mg/ml). In 7 yCF PC20 or PCW developed (1.51 mg/ml, range 0.125 to 4.0) versus 4 yNO (4.0 mg/ml, range 2.0 to 8.0). In 10 oCF subjects who performed MCH on three occasions within a 2-wk period, both positive and negative wheeze responses were reproducible. Patients who wheezed had a lower FRC compared with patients who did not (109 versus 147% of predicted, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Tracheal sound spectra depend on body height.

Tracheal sounds originate from turbulent flow in upper and central airways. Turbulent flow characteristics are influenced by conduit dimensions. Because tracheal dimensions are a function of body height, we hypothesized that there should be a correlation between sound spectra and body length. We recorded tracheal sounds at standardized airflows in 21 healthy children 9.1 +/- 0.6 yr of age (mean +/- SE) and in 24 healthy adults 30.2 +/- 0.8 yr of age. A contact sensor was attached at the suprasternal notch of the sitting subject, and airflow was measured at the mouth with a calibrated pneumotachograph. Tracheal sounds were low-pass-filtered at 2.4 kHz and digitized at 10 kHz. A 2048 point FFT was applied at a successive 100-ms intervals, using a Hanning data window. Resulting spectra were normalized to a reference power of 0.1 (mV)2/5 Hz. We applied a gating algorithm to extract sounds at inspiratory flows of 1 L/s (+/- 10% tolerance), and we computed average power spectra from the collected samples. We calculated the average spectral power (Pavg), the quartile frequencies below which 25% (Q1), 50% (Q2), and 75% (Q3) of the power in the range of 50 to 2,000 Hz was contained, the spectral edge frequency (SE95) below which 95% of the power was found, and the frequency where spectral power rolled off sharply (Fcut).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Morbidity and mortality patterns of ventilator-dependent children in a home care program.

We evaluated the effectiveness of the Home Care Program of Children's Hospital of Winnipeg for ventilator-dependent children by retrospectively examining morbidity and mortality from February 1, 1979, to July 31, 1992. For the 22 study subjects, the cause of chronic respiratory failure was neurologic disorders for 14 (64%) (group A) and pulmonary disorders for eight (36%) (group B). There were no significant differences between groups A and B in the average number of hospital days, readmission rate, or length of stay per admission. Eleven patients have remained ventilator-dependent at home, four no longer require mechanical ventilation, and seven died. Factors such as diagnosis, type of family, home location, age at initiation of mechanical ventilation, and initial duration of hospital stay did not influence morbidity or mortality in either group. Within the overall mortality rate of 32% is a higher rate among patients whose disorders initially carried a poor prognosis. Ventilator-dependent children can be successfully managed at home, with few nonelective hospital readmissions, through a well-organized home care program.

Adolescent↗
PubMed1993

The effect of high doses of inhaled salbutamol and ipratropium bromide in patients with stable cystic fibrosis.

The effect of large doses of salbutamol (S) and ipratropium bromide (IB) were tested in a double-blind, randomized, crossover study. Nine patients with cystic fibrosis (CF), aged 12.8 +/- 2 years (mean +/- SE), were studied for 8 h on 2 separate days. Pulmonary function tests (PFTs) included spirometry (FEV1), lung volumes (FRC), and airway resistance (Raw) measured by body plethysmography. Heart rate (HR) and oxygen saturation (SaO2) were measured before each test. On 1 day patients received S 200 micrograms, S 400 micrograms, and IB 80 micrograms, by inhalation at 45-min interval (sequence A). On the other day, the sequence was IB 80 micrograms, S 200 micrograms, and S 400 micrograms (sequence B). The PFTs were obtained at baseline, 45 min after each inhalation, and 4 and 8 h after baseline measurements. Baseline PFTs (mean +/- SE) were not significantly different on the 2 study days (FEV1, 1.48 +/- 0.1 vs 1.42 +/- 0.1 L; FRC, 2.77 +/- 0.6 vs 2.87 +/- 0.6 L; Raw, 4.04 +/- 0.2 vs 4.00 +/- 0.3 cm H2O/L/s). The FEV1 and Raw improved from baseline after each inhalation, and at 4 and 8 h during both days (p < 0.05). Forty-five minutes after S 200 micrograms, plus S 400 micrograms, FEV1, FRC, and Raw were not significantly different compared with the values 45 min after IB 80 micrograms, plus S 200 micrograms (1.67 +/- 0.1 vs 1.63 +/- 0.1 L; 2.81 +/- 0.6 vs 2.65 +/- 0.5 L; and 2.98 +/- 0.2 vs 2.66 +/- 0.1 cm H2O/L/s, respectively). The PFTs were not significantly different after maximal doses of IB (80 micrograms) compared with S (600 micrograms). The HR and SaO2 were not significantly different from baseline throughout the study period. These results indicate that both single and sequential therapy have a similar acute bronchodilator effect provided that large doses are used. We speculate that adrenergic and muscarinic pathways are equally important in airflow obstruction in patients with CF.

Administration, Inhalation↗
PubMed1992

Efficacy of salbutamol and ipratropium bromide in decreasing bronchial hyperreactivity in children with cystic fibrosis.

A proportion of patients with cystic fibrosis (CF) suffer from increased airway hyperreactivity but their response to bronchodilators is variable. Adrenergic agents may produce an increase, no change or a decrease in forced expiratory volume in 1 second (FEV1). We hypothesized that the variable response might be related to poor aerosol distribution caused by the presence of secretions. Therefore, in 11 children with CF and airway hyperreactivity the influence of pretreatment with either 0.9% saline, salbutamol, or ipratropium bromide on the methacholine challenge test was evaluated in a double-blind, randomized, cross-over study. FEV1 (mean +/- S.E.) did not change following pretreatment with saline, salbutamol, or ipratropium (1.64 +/- 0.22, 1.63 +/- 0.16 and 1.67 +/- 0.19, respectively). All patients demonstrated airway hyperreactivity with a PC20 below 8 mg/mL (geometric mean, 0.41 mg/mL) after saline pretreatment. Salbutamol inhalation significantly increased the PC20 to 1.24 mg/mL (P less than 0.01), but ipratropium bromide was found to be even more effective than salbutamol (PC20 = 7.37 mg/mL) (P less than 0.0001). We conclude that the variable response to bronchodilator is not secondary to impaired aerosol distribution since ipratropium bromide effectively blocked the response to methacholine. The improvement in PC20 without a change in baseline FEV1 following salbutamol suggests that the adrenergic agent altered the contractile mechanism of smooth muscle.

Adolescent↗
PubMed1992

Response to inhaled bronchodilators and nonspecific airway hyperreactivity in children with cystic fibrosis.

We tested the hypothesis that children with CF who have a significant response to bronchodilator (BD) would respond positively to standard methacholine (Mch) challenge. Our objective was to correlate the response to BD with the concentration that produced a 20% fall (PC20) in forced expiratory volume in 1 second (FEV1). We studied 22 patients (12 males), aged 10.5 +/- 0.7 years (mean +/- SE), with a Shwachman-Kulczycki score 82 +/- 2.6 and baseline FEV1 of 80 +/- 4.5% predicted. Baseline expiratory flows, static lung volumes, and airway resistance were measured before and 30 min after inhaled salbutamol. On a separate day, within 2 weeks, a Mch challenge was given, with doubling concentrations from 0.03 to 8.0 mg/mL. A positive challenge was defined as a PC20 less than or equal to 2.0 mg/mL, and a positive response to BD as a greater than 6% of FEV1 increase. Mch challenge yielded 17 responders (R) with a PC20 of 0.5 +/- 0.1 mg/mL, and 5 nonresponders (NR) with a PC20 of 8.8 +/- 2.9 mg/mL. Baseline FEV1 was 77 +/- 5.3% predicted in R compared to 89 +/- 6.3% in NR (P = less than 0.001). History of springtime rhinitis was positive in 9/17 R and 2/5 NR. No significant correlation was found between baseline FEV1 and PC20, or between change in FEV1 post-BD and PC20. A greater than 6% increase in FEV1 was seen in 14/17 R (83% sensitivity) and in none of the 5 NR (100% specificity). In R, 8/17 patients had baseline FEV1 less than 80% predicted, compared to 1/5 in NR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Rigid bronchoscopy in the pediatric age group: diagnostic effectiveness.

Over a 15-year period, 277 diagnostic bronchoscopic procedures were carried out at the Winnipeg Children's Hospital using rigid bronchoscopic instrumentation. The objective of the review is to examine contribution to final diagnosis made by the procedure. The patient population included 60% male and 40% female patients ranging from the first day of life to 18 years (mean age, 6 years). Indications for bronchoscopy fell into two large groups, including 60% of patients with evidence of lower airway disease and 30% of patients with evidence of upper airway obstruction. In patients with upper airway obstruction, half were found to have a congenital underlying cause and half were due to an acquired lesion. In 85% of patients, a specific diagnosis was reached and this proved to correlate positively with the preoperative diagnosis in 80% of patients and negatively in 20%. Definitive treatment in patients with upper airway obstruction included surgical intervention in one third of patients. Patients with lower airway disease were diagnosed as having consolidation in 43%, atelectasis in 39%, and bronchiectasis in 18%. Disease localized most frequently to the left lower and right upper lobes and in only 10 of 168 patients was a congenital cause determined. Among 168 patients, 30 had surgical treatment as the definitive management with the majority of patients treated medically. Bronchoscopy was shown to contribute to diagnosis in 88% of patients examined. Bronchoscopy was carried out with a complication rate of 3% and no mortality.

Adolescent↗
PubMed1992

Tracheal sounds in upper airway obstruction.

A boy with subglottic narrowing secondary to laryngotracheitis presented with noisy breathing. Acoustic measurements of tracheal sounds at standardized air flows correlated well with the clinical course and with spirometric assessments. This indicates the potential value of respiratory sound characterization in patients with upper airway obstruction.

Child↗
PubMed1992

Effects of betamethasone and thyroid hormone on fetal rat lung maturation in vivo.

We studied the effect of maternal administration at various intervals of betamethasone, triiodothyronine (T3), or both, on fetal rat lung maturation. T3 alone did not enhance choline incorporation to phosphatidylcholine by 20-day fetal lung explants, or morphometric lung maturation. Betamethasone, and betamethasone plus T3, increased both of those parameters over control and T3 values. However, addition of T3 offered no advantage over administration of betamethasone alone. Significant enhancement of morphometric lung maturation was already present after only 24 h of exposure to beta-methasone, or to the combination of hormones. However, choline incorporation to phosphatidylcholine only increased significantly by 36 h of exposure to betamethasone with or without T3.

Animals↗