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Biomedical subjects

B K Rubin

Publications and source records attributed to B K Rubin.

At least 55 records · Page 3Linked to original sources
PubMed1996

Iodinated glycerol has no effect on pulmonary function, symptom score, or sputum properties in patients with stable chronic bronchitis.

STUDY OBJECTIVE: It has been reported that therapy with iodinated glycerol (IG) can improve the quality of life for patients with chronic bronchitis. The purpose of this study was to determine the effects of IG therapy on the quality of life, pulmonary function, and on the properties of sputum collected from adults with stable chronic bronchitis. DESIGN: Thirty-two week, double-blind, randomized, placebo-controlled cross-over study. SETTING: A university outpatient pulmonary clinic. PARTICIPANTS: Twenty-six adults with stable chronic bronchitis completed the study; 28 completed the first treatment arm. INTERVENTIONS: Sixteen weeks each of placebo or IG 60 mg qid. MEASUREMENTS: First, pulmonary function by spirometry and plethysmography. Second, symptom score measured using a questionnaire. Third, sputum bulk and surface rheology, spinnability, mucociliary transportability and cough transportability. RESULTS: There were no significant changes in pulmonary function, clinical scores, or sputum properties related to therapy with IG. There was a significant improvement in the Global Petty score after both IG (p = 0.01) and placebo (p < 0.01) when compared with baseline, but there was no difference between treatment periods. There was a positive correlation between changes in the Global score during therapy and changes in sputum spinnability (p < 0.01, r = 0.38). CONCLUSIONS: This study clearly demonstrates that in chronic bronchitis, 16 weeks of therapy with IG does not produce any appreciable effect on pulmonary function, well being, or on sputum viscoelasticity or clearability.

Adult↗
PubMed1995

A comparison of a new mucolytic N-acetylcysteine L-lysinate with N-acetylcysteine: airway epithelial function and mucus changes in dog.

A newly synthesized mucolytic agent, N-acetylcysteine L-lysinate (Nacystelyn) was studied. Tracheal mucus velocity (TMV), transepithelial potential difference (PD), rheological properties, and ion content of collected airway secretions were evaluated in six healthy mongrel dogs after placebo, Nacystelyn (NAL) and acetylcysteine (NAC) metered dose inhaler (MDI) aerosols. Although TMV was increased and viscoelasticity decreased after both treatments, the treatment effect with NAL was significantly greater. Furthermore, NAL increased the negative PD and CI- content of secretions in the trachea, an effect not observed after NAC. Both compounds increased ciliary beat frequency (CBF) on the frog palate at a concentration range similar to that approximated in dog airways. The increased mucociliary clearance could be partially explained by favourable rheological changes combined with stimulation of CBF. Since both compounds break disulfide bonds in mucus polymers, the greater change in mucus rheology and clearance rate after NAL, without change in water content, could be explained by the increase in CI- content. Nacystelyn appears to combine different modes of action which synergistically cause an increase in the clearance rate of airway secretions.

Acetylcysteine↗
PubMed1995

Species differences in the physical and transport properties of airway secretions.

The clearance of airway secretions is vital in protecting the mammalian lung from pollution and infection. Diverse animal models have been used to study lung diseases associated with impaired secretion clearance. The extrapolation of data from animal models to humans is based on the assumption that there are structural and functional similarities in the airway epithelium and secretions. This manuscript reviews regulation of mucus secretion as well as the physical and transport properties of respiratory mucus. As tracheal size increases, the rigidity of airway secretions decreases, and rigidity is inversely correlated with mucociliary transportability. These differences are placed in the context of previously reported species and regional differences in transepithelial potential difference and the tracheobronchial epithelial cell population. Tracheal mucus transport velocity varies with the species studied and has been shown to positively correlate with tracheal surface area. A progressive increase in the rate of mucus transport from the small to the large airways has also been reported. The reduction in mucus rigidity from small to large airways could be one of the mechanisms responsible for velocity gradients, which facilitate mucociliary transport. Because airway dimensions, rather than anatomic level of the airway, may better predict epithelial secretory response, studies to assess the physiologic responses in human airways require the use of an animal model with a similar-sized airway.

Animals↗
PubMed1995

Fluctuations in autonomic nervous activity during sleep displayed by power spectrum analysis of heart rate variability.

OBJECTIVE: The use of an efficient noninvasive method to investigate the autonomic nervous system and cardiovascular control during sleep. BACKGROUND: Beat-to-beat heart rate variability displays two main components: a low-frequency (LF) one representing sympathetic and parasympathetic influence and a high-frequency (HF) component of parasympathetic origin. Sympathovagal balance can be defined as LF/HF ratio. METHODS/DESIGN: We reviewed normal, standardly staged all-night polysomnograms from 10 healthy children aged 6 to 17 years. Recorded 256-second traces of heart rate and respiration were sampled. Power spectra of instantaneous heart rate and respiration were computed using a fast Fourier transform method. RESULTS: The study revealed a decrease in LF during sleep, with minimal values during non-REM slow-wave sleep and elevated levels similar to those of wakefulness during REM. HF increased with sleep onset, reaching maximal values during slow-wave sleep, and behaved as a mirror image of LF. LF/HF ratio displayed changes similar to those in LF. CONCLUSION: The sympathetic predominance that characterizes wakefulness decreases during non-REM sleep, is minimal in slow-wave sleep, and surges toward mean awake levels during REM sleep. The autonomic balance is shifted toward parasympathetic predominance during slow-wave sleep. This noninvasive method used to outline autonomic activity achieves results that are in complete agreement with those obtained with direct invasive tools.

Adolescent↗
PubMed1995

"Childhood" viruses as a cause of pneumonia in adults.

Respiratory viruses are a common cause of morbidity in childhood. Except in the child with immunodeficiency, the common respiratory viruses rarely pose a serious threat to life. Because infection with most of these viruses in childhood is nearly universal and usually bestows partial immunity, the "childhood respiratory viruses" are not generally thought of as being a cause of disease in adults. However, adults who work around children, who are frequently exposed to other adults and children with respiratory tract infections (as in a hospital clinic setting), or who are military recruits appear to be at risk of infection or reinfection with one of these agents. In addition, adults with immune deficiency are at a significant risk for serious infection. The risk of serious disease can be reduced by maximizing immunity with (re)immunization and optimal treatment of any underlying disorders. Tobacco smoke and respiratory irritants should be avoided and adults at risk for severe disease should avoid contact with infected children and adults as much as possible. Specific chemotherapy for viral pneumonia, when available, may reduce morbidity in selected individuals.

Adenoviridae↗
PubMed1994

Exogenous surfactant enhances mucociliary clearance in the anaesthetized dog.

Therapy with exogenous surfactants is currently used for the treatment of respiratory distress syndrome of the newborn (RDS) and is under investigation for treatments related to adult RDS. However, the possible use of exogenous surfactant as a means of enhancing mucus clearance in other respiratory diseases has not been addressed. We therefore studied the effects of an artificial surfactant (Curosurf) on in vivo tracheal mucus velocity in intubated pentobarbital-anaesthetized dogs. Five dogs were randomly administered, on separate occasions, either vehicle (saline) or 10 mg Curosurf by means of local instillation via a catheter into the right lung. Tracheal mucus was collected by inserting a soft-bristled cytology brush to the level of the carina, and analysed for viscoelasticity by microrheometry. Mucociliary clearability in vivo, tracheal mucus velocity (TMV) in mm.min-1, was determined by bronchoscopic observation of charcoal marker particle transit times. The initial placement of charcoal was at the same level of the lower trachea that mucus was collected from. The effect of ciliary beat frequency was assessed on the frog palate assay by a videoscopic technique. In the dog, TMV was significantly increased after administration of surfactant. The values of TMV in the vehicle- and surfactant-treated dogs were 6.3 +/- 4.0 vs 25.6 +/- 6.5 mm.min-1 (SD), respectively. There were no discernible differences between prevehicle and postvehicle TMV values, and no significant differences in any mucus viscoelastic parameter, as determined by magnetic rheometry.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗
PubMed1993

Ferret tracheal mucus rheology, clearability and volume following administration of substance P or methacholine.

We studied the effects of substances P administration on tracheal mucus viscoelasticity, water content, clearability and secretion rate. Six neutered adult male ferrets (weight 1.1-1.5 kg) were studied, on four occasions each. They were anaesthetized with ketamine and xylazine, and intubated shallowly. Control mucus (pre- and post-Ringer instillation) was compared with the mucus obtained following instillation of 200 microliters of 10(-6), 10(-5), and 10(-4) M substance P (SP), and 10(-4) M methacholine chloride as a reference. Tracheal mucus was collected by inserting a soft-bristled cytology brush to the level of the carina, and leaving it in contact with the mucosa for 30 min. After withdrawing the brush, the adherent mucus was quickly scraped off and layered with paraffin oil to prevent evaporation. The mucus was analysed for viscoelasticity by magnetic rheometry and solids content by evaporation to dryness. Mucus transportability was assessed by comparison with model gels, and also by means of the frog palate assay, which indicates how well mucus is cleared by normal ciliary action. There was a dose-related increase in mucus volume, and a dose-related decrease in mucus viscosity and elasticity, with substance P administration. Mucus transportability increased with both substance P and methacholine. The effects of 10(-4) SP and methacholine were comparable in terms of viscoelasticity and volume; with both methacholine and SP, there appeared to be an additive effect. The mucus solids content did not correlate with the viscoelastic changes for SP administration, whereas it did for methacholine. These observations suggest that the hypersecretion induced by these two agents might involve different pathways.

Analysis of Variance↗
PubMed1992

Changes in the CA 19-9 antigen and Lewis blood group with pulmonary disease severity in cystic fibrosis.

The altered carbohydrate structure of sputum from patients with cystic fibrosis (CF) has been thought to be due to the inflammatory airway response. Carcinoembryonic antigen (CEA) and CA 19-9 detect sialosylated carbohydrates in mucus. The epitope of CA 19-9 is part of the Lewis A (Le(a)) blood group antigen. Serum concentrations of CEA and CA 19-9 were determined by radioimmunoassay in 41 CF patients, aged 6-34 years; 16 were asymptomatic Outpatients, and 25 had been admitted for pulmonary exacerbations. There was no difference in CEA between groups. The CA 19-9 serum concentration was elevated in 90% of patients who had at least one of the two Lewis antigens. The CA 19-9 concentration of Inpatients with exacerbations was 2.7 times that of stable Outpatients (263 +/- 44 versus 99 +/- 13 U/mL; P less than 0.02). CA 19-9 correlated significantly with age (r = 0.35, P less than 0.05), Brasfield score (r = 0.39, P less than 0.015), pulmonary function tests, cough severity (r = 0.50, P less than 0.001) and NIH clinical score (r = 0.57, P less than 0.001). CA 19-9 concentration of Inpatients decreased by 44% from admission to discharge (302 +/- 45 to 169 +/- 39, P less than 0.02). Fourteen of 25 (56%) of the Inpatients were Le(a) positive versus only 3/15 (20%) of Outpatients who had milder lung disease (P less than 0.002). Of the Inpatients, 25% with more advanced lung disease were Le(a+b+), a rare blood group in the normal population, and one not observed in the Outpatients with milder disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Is there a seasonal variation in mucus transport and nutrient absorption in the leopard frog?

We postulated that as a hibernating species, frogs might have variable demands for nutrients at different seasons of the year and that this must be reflected in seasonal variations of physiologic processes related to nutrient transport and absorption. We examined the rate of mucus transport on the ciliated palate and the movement of nutrients across the intestinal lumen of leopard frogs, Rana pipiens. Mucus transport on the frog palate was strongly influenced by season, with maximal transport occurring in late June (Julian day 178, p = 0.0001; r = 0.58). This increased transport rate was associated with a summertime increase in mucus recoil (lower tangent delta) and a decrease in mucus hydration (increase in percent solids composition). Intestinal transport of leucine, lysine, and galactose did not appear to exhibit seasonal variability. These data suggest that different mechanisms may operate in determining seasonal variability in physiologic responses.

Animals↗
PubMed1992

Respiratory mucus from asymptomatic smokers is better hydrated and more easily cleared by mucociliary action.

We compared the physical and transport properties of tracheal mucus collected from 16 asymptomatic smokers and from 18 nonsmokers. The smokers produced a larger volume of mucus (wet weight 18.6 versus 11.2 mg; p = 0.04) with a lower solids content (11.5 versus 16.3%; p = 0.02) and a lower modulus of rigidity (log G* 2.37 versus 2.62; p = 0.04). Although the smokers mucus had a 40% faster mucociliary transport rate on the frog palate (p = 0.04), the cough clearability was nearly identical to the mucus from nonsmokers. The differences are similar to those observed in rats or dogs chronically exposed to cigarette smoke. These data suggest both a quantitative and a qualitative difference in the composition of mucus from asymptomatic smokers. The increased volume of a watery mucus with increased mucociliary clearability may help to protect the airways from the injurious effects of inhaled smoke.

Adult↗
PubMed1992

Mucus rheology and transport in neonatal respiratory distress syndrome and the effect of surfactant therapy.

BACKGROUND: Neonatal respiratory distress syndrome (RDS) is caused by a deficiency of pulmonary surfactant. Alveolar collapse and obstruction of conducting airways leads to mismatch of ventilation and perfusion and profound hypoxemia. We postulated that surfactant deficiency could alter the properties of respiratory mucus in such a way that it would be poorly cleared from airways and promote airway luminal obstruction and that these changes might be reversed by the exogenous administration of a synthetic surfactant preparation. METHODS: Respiratory mucus coating an endotracheal tube (ETT) or suction catheter was collected from 14 neonates (gestational age, 24 to 36 weeks; birth weight, 600 to 2,400 g) with RDS who required tracheal intubation and ventilation. Eight of these neonates received 5 ml/kg of an intratracheal artificial surfactant preparation (Exosurf), given between 2 and 10 h of age and six neonates received 5 ml/kg of air. Mucus viscoelasticity, hydration (percentage of solid composition of mucus), and mucociliary clearability (NFPTR) were measured for each specimen. RESULTS: The total volume of mucus collected from the surfactant-treated and control infants was similar, but mucus hydration was significantly less in babies with RDS who did not receive Exosurf (percentage of solid composition of mucus 18.7 vs 11.4; p = 0.013). Ciliary transportability was also less in the untreated babies (NFPTR 0.39 vs 0.86; p = 0.018) and this mucus was more rigid (increased viscoelasticity: log G* 1 rad/s 2.28 vs 1.50; p = 0.0001). CONCLUSIONS: These data suggest that airway obstruction in RDS may be due, in part, to abnormal mucus properties and impaired ciliary transport. Surfactant therapy appears to improve mucus clearability. Exogenously administered surfactant may also be beneficial for the treatment of other selected respiratory conditions associated with impaired mucus clearance.

Drug Combinations↗
PubMed1991

Recurrent respiratory infections in a child with fucosidosis: is the mucus too thin for effective transport?

Fucosidosis is caused by a deficiency of the lysosomal enzyme alpha-L-fucosidase (ALF) leading to an accumulation of glycoproteins in a variety of cells. Infants and young children with this disorder are prone to recurrent sinus and pulmonary infections and often die of pneumonia. We studied the mucociliary and systemic immune function in a 6 year old girl with fucosidosis and recurrent respiratory infections. All measurements of systemic immune function were normal. Sweat chloride was normal when measured on angiokeratotic skin but was greater than 65 mg/L on uninvolved areas. During the placement of tympanic ventilation tubes, tracheal mucus was gently aspirated and a mucosal biopsy was taken. Tracheal mucus transport was not measured. The biopsy material was examined under phase contrast microscopy and revealed ciliated cells with apparently normal beating. TEM of these cells showed a characteristic pattern of vacuoles in the cytoplasm as described in other tissues from patients with fucosidosis. Ciliary ultrastructure was normal. Mucus viscoelasticity was measured in a magnetic microrheometer. The loss tangent was 2 SD above the mean for normal mucus and mechanical impedance was about 2 SD below the mean. These changes are similar in direction but double in magnitude to what has been described with methacholine administration in dogs. The high compliance of the mucus may be due to incomplete assembly of mucus glycoprotein or to decreased secretion of glycoproteins in respiratory secretions. This leads to mucus that is abnormally watery and thus difficult to clear from the airway.

Child↗
PubMed1991

Neonatal capsaicin treatment alters basal pulmonary mechanics and response to methacholine in F344 rats.

Full methacholine dose-response curves were performed on anesthetized tracheostomized Fischer 344 adult rats treated neonatally with capsaicin (50 mg/kg) or with vehicle alone. Capsaicin, the hot extract of pepper, releases substance P (SP) from nonmyelinated sensory nerve endings and causes acute bronchoconstriction and airway microvascular leakiness. Chronic treatment with capsaicin leads to depletion of SP and other tachykinins from afferent C-fibers and can therefore be used as a tool to investigate the contribution of SP innervation to airway responses. The rats (9 controls and 6 treated with capsaicin) were paralyzed with succinylcholine and mechanically ventilated at a constant tidal volume and frequency. Airway resistance (RL) and dynamic compliance (Cdyn) were determined at each dose of methacholine from measurements of volume, flow, and transpulmonary pressure. Capsaicin-treated rats were found to have a significantly reduced baseline RL [0.150 +/- 0.039 (SD) vs. 0.225 +/- 0.050 cmH2O.ml-1.s, P = 0.009] and a correspondingly significantly elevated Cdyn (0.371 +/- 0.084 vs. 0.268 +/- 0.053 ml/cmH2O, P = 0.012). There was no significant difference in sensitivity to methacholine, but the maximal response to methacholine was significantly greater in the capsaicin-treated rats. In terms of RL, the maximal response for capsaicin-treated rats was 6.03 x baseline +/- 0.98 vs. 4.30 x baseline +/- 1.80 (P = 0.05) for controls, and for Cdyn changes the maximal decrease was 5.75 x baseline +/- 1.22 vs. 3.83 +/- 0.69 (P = 0.002). The observed differences in RL and Cdyn coupled with the differences in maximal responses can be attributed to the selective destruction of a subpopulation of pulmonary afferent C-fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1991

Pulmonary function, nutrition, and self-concept in cystic fibrosis summer campers.

Children with cystic fibrosis (CF) often attend special summer camps. We postulated that beyond the simple fun of camp, attendance at camp might improve the clinical status and self-image of the campers. We therefore studied lung function, nutrition, and self-image in 45 children between the ages 6 and 12 years after a two-week CF summer camp. Although there was a 10 percent fall in respiratory rate during camp, spirometry did not change significantly. There were, however, significant gains in weight, skin fold thickness, and midarm circumference after two weeks at camp, and these increases were positively correlated with the number of pancreatic enzymes taken daily by the child. The Primary Self-Concept Inventory test was completed by each camper on the first and last days of camp. Although there was a trend toward increasing self-concept during camp, this did not reach statistical significance. Two weeks' attendance at summer camp appears to be associated with improved nutrition in children with CF. This may be due to increased emphasis on weight gain and appropriate use of pancreatic enzymes or to other factors, like avoidance of tobacco smoke exposure, that are unique to the summer camp setting.

Camping↗
PubMed1990

Exposure of children with cystic fibrosis to environmental tobacco smoke.

BACKGROUND: In children, passive exposure to environmental tobacco smoke has been associated with growth suppression and an increased frequency of respiratory tract infections. On the assumption that this association would be more pronounced in children with chronic pulmonary disease, we examined the growth, nutritional status, lung function, and clinical condition of children with cystic fibrosis in relation to their exposure to environmental tobacco smoke. METHODS: We studied 43 children (age, 6 to 11 years) on entry to a summer camp and then again after two weeks in this smoke-free environment. Twenty-four of the children (56 percent) came from homes with smokers. RESULTS: There appeared to be a dose-dependent relation between the estimate of smoke exposure (cigarettes smoked per day in the home) and overall severity of disease, as assessed by the age-adjusted rate of hospital admissions (r = 0.58), peak expiratory flow rate (r = -0.39), and measures of growth and nutrition, including weight percentile (r = -0.37), height percentile (r = -0.44), midarm circumference (r = -0.42), and triceps skin-fold thickness (r = -0.31). These effects were most evident in the girls. When only the 24 children from homes with smokers were analyzed, however, the dose-dependent relation was present only for the number of hospital admissions and for height. Among the children with good lung function (n = 21) or with normal weight for height (n = 27) at the start of camp, those who had been exposed to tobacco smoke gained significantly more weight during the two weeks of camp than did the children from smoke-free homes. CONCLUSIONS: These data suggest that passive exposure to tobacco smoke adversely affects the growth and health of children with cystic fibrosis, although the possibility cannot be ruled out that social, economic, or other factors determined both the smoking status of the household and the nutritional status of the children.

Arm↗