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Biomedical subjects

Bruce K Rubin

Publications and source records attributed to Bruce K Rubin.

At least 37 records · Page 2Linked to original sources
PubMed2005

Quantification of biopolymer filament structure.

The quantitative analysis of a polymer network is important for understanding its role in biological function. We developed a Matlab program to recognize and segment filaments in a 2-D image, and measure and describe the structure. Our algorithm improved the speed of the Lichtenstein Fiberscore segmentation algorithm by using matrix convolutions, compared filament length by the algorithms of Kulpa, Lichtenstein, and Kimura, and measured the number of branchpoints and Euler number. A user interface was added to easily manipulate algorithm parameters, select images, and visualize results. We used the program to compare the DNA biopolymer network of cystic fibrosis (CF) sputum with mucus from patients without respiratory problems. We also examined an image of fibrin. The images were taken with a laser scanning confocal microscope after staining the specimens with Yo-Yo-1. Computation using matrix convolutions reduced the execution time (Pentium III) of a 512 x 512 TIF image from 18 min to 15s. The Kimura length estimation appeared best at describing filament length because it varied least with filament orientation. The image of CF sputum showed increased filament length, more branchpoints, and more negative Euler number compared to the normal sample. These quantitative descriptions of the network can be correlated to material, mechanical, diffusion, or flow properties, physiological processes, or therapy.

Actins↗
PubMed2005

The role of airway secretions in COPD--clinical applications.

It has been established that mucus hypersecretion and decreased mucus clearance contribute to the morbidity of chronic obstructive pulmonary disease (COPD). Indeed, the classic definition of chronic bronchitis relies on determining the frequency and duration of sputum expectoration. Despite the well recognized importance of this symptom, there are few therapies routinely used to decrease the sputum production or to improve clearance. There are fewer well conducted clinical trials of existing medications and this has led many regulatory agencies, notably the Food and Drug Administration (FDA), to refuse to register these medications or approve their sale. Similarly, airway clearance devices and chest physical therapy have not been well studied in COPD. Carefully conducted studies of interventions to improve airway clearance, similar to those done in cystic fibrosis (CF), may help us to identify effective therapies and possibly novel diagnostic tests for the management of COPD.

Expectorants↗
PubMed2005

Inhaled mannitol for the treatment of mucociliary dysfunction in patients with bronchiectasis: effect on lung function, health status and sputum.

OBJECTIVE: Inhaled mannitol increases mucus clearance in patients with bronchiectasis by an unclear mechanism. The effect of mannitol on lung function, health status and sputum properties was investigated. METHODOLOGY: Nine patients with bronchiectasis inhaled 400 mg of mannitol once daily for 12 days. Health status was assessed using the St George's Respiratory Questionnaire (SGRQ). Sputum was analysed for viscosity, elasticity, spinnability, surface tension, contact angle, solids, mucociliary transportability (MCTR) on a frog palate, and cough transportability (CTR) on a simulated cough machine. RESULTS: Lung function was unchanged with treatment (baseline FEV1 82.0 +/- 16.2%) apart from an improvement in FEF from 85.4 +/- 13% (baseline) to 90.7 +/- 14.4% (P < 0.05; 12th treatment; visit 7). The total SGRQ score (mean +/- SD) of 49.3 +/- 13.8 at baseline, decreased by 12.4 +/- 10.2 (P < 0.01; visit 7) and 10.1 +/- 9.4 units (P < 0.02) 6-10 days after treatment cessation. The baseline subscores for symptoms (72.9 +/- 11.8), activity (44.7 +/- 20.9) and impact (44.4 +/- 14.3) were reduced by 0.8 +/- 9.1 (P > 0.7), 8.4 +/- 16.0 (P > 0.1) and 19.2 +/- 13.7 (P < 0.005) units, respectively (visit 7). Mannitol reduced the baseline (mean +/- SE) surface tension from 94.5 +/- 1.4 to 84.7 +/- 2.1 mN/m (P < 0.0001), contact angle from 51.1 +/- 2.8 to 33.2 +/- 2.4 degrees (P < 0.0001), spinnability from 11.6 +/- 0.4 to 10.0 +/- 0.2 mm (P < 0.005), and solids from 5.7 +/- 0.4 to 4.3 +/- 0.7% (P < 0.02), acutely (visit 7). Viscosity, elasticity and MCTR did not change significantly, while CTR was increased from 25.8 +/- 1.0 to 34.1 +/- 2.7 mm (P < 0.003). CONCLUSION: Mannitol significantly improved the health status over 12 days and this improvement was maintained for 6-10 days after cessation of treatment. In addition, mannitol reduced the tenacity, increased the hydration of mucus acutely and improved cough clearability in patients with bronchiectasis.

Administration, Inhalation↗
PubMed2005

An in vitro evaluation of the effectiveness of endotracheal suction catheters.

INTRODUCTION: Tracheal suction catheters (TSCs) are used to clear mucus from an endotracheal tube (ETT). The clearance rate is critical because airway mucus stasis leads to obstruction, but prolonged catheter suctioning can lead to hypoxemia. The rate of mucus clearance from an ETT is thought to be influenced by the properties of the mucus, the pressure used to suction the mucus, and the diameter of the catheter. In this study, different adult TSCs were evaluated for their ability to suction mucus simulants that had properties similar to airway mucus. METHODS: Six different 14F TSC designs were evaluated. All catheters had the same end hole size, but the two side holes were sized at 3 mm, 4 mm, or 5 mm. A coagulant (Polyox Water Soluble Resin Coagulant NF; Dow Chemical Company; Cary, NC) was mixed with water at concentrations of 0.5%, 1.5%, and 3.0% to simulate mucus or sputum. Suction effectiveness was evaluated by the mass percentage of the coagulant suctioned over 10 s at 100 mm Hg from an 8.0 ETT. MEASUREMENTS AND RESULTS: The 1.5% and 3.0% simulants had properties comparable to human airway mucus and sputum. Suction effectiveness was less with the 3.0% coagulant simulant compared with the 1.5% and 0.5% simulants. Suction effectiveness was greater (p < 0.01) with TSCs that had nonparallel holes and a side hole diameter of 5 mm when tested with the 1.5% and 3.0% simulants. However, no best catheter could be identified among TSCs when tested with the more liquid-like 0.5% simulant. CONCLUSIONS: Greater TSC side hole diameter and nonparallel positioning was important for suctioning mucus simulants that are similar to mucus or sputum. The distance between side holes, end hole size, suction force, and duration of suctioning were not tested but could also have an effect on TSC performance.

Catheterization↗
PubMed2005

Optimizing aerosol delivery by pressurized metered-dose inhalers.

The modern era of aerosol therapy began with the introduction of the Medihaler Epi in 1956, after a 13-year-old asthmatic told her father, an officer in the Riker company, that asthma medications should be as convenient to use as hair spray and she complained that the bulb atomizer leaked in her school bag. Since then, advances in technology have made aerosol delivery much more efficient, so that it is now the most widely used mode of medication delivery for chronic airways diseases. Today the pressurized metered-dose inhaler (pMDI) is a metal canister containing a mixture of propellants, surfactants, preservatives, and drug. However, pMDIs are underused in the United States. One barrier to use is the misconception related to pMDI effectiveness relative to small-volume nebulizers, especially among pediatricians. This is despite the strongest evidence of pMDI superiority, from well-controlled pediatric studies. In this manuscript we discuss ways to optimize the use of medications given via pMDI and examine recent changes in pMDI technology that will make drug delivery more efficient and consistent.

Administration, Inhalation↗
PubMed2005

Problems with inhaler use: a call for improved clinician and patient education.

Patient education is a critical factor in the use and misuse of medication inhalers. Inhalers represent advanced technology that is considered so easy to use that many patients and clinicians do not receive adequate training in their use. Between 28% and 68% of patients do not use metered-dose inhalers or powder inhalers well enough to benefit from the prescribed medication, and 39-67% of nurses, doctors, and respiratory therapists are unable to adequately describe or perform critical steps for using inhalers. Of an estimated 25 billion dollars spent for inhalers annually, 5-7 billion dollars is wasted because of inhaler misuse. Reimbursement and teaching strategies to improve patient education could substantially reduce these wasted resources. Problems with inhaler use, the cost of inhalers, and myths associated with inhalers are reviewed, with recommendations for strategies and techniques to better educate patients in inhaler use.

Administration, Inhalation↗
PubMed2004

MUC5AC and MUC5B Mucins Are Decreased in Cystic Fibrosis Airway Secretions.

Cystic fibrosis (CF) is characterized by progressive airway obstruction. Although it has been postulated that this is due in part to mucus hypersecretion, there are no published data showing an increase in the gel-forming mucins MUC5AC or MUC5B in CF secretions. We used confocal microscopy to assess the amount of mucin-like glycoprotein and DNA in CF sputum and found more mucin in bronchitis sputum and a much greater amount of DNA in CF sputum. We then used antibodies to MUC5AC and MUC5B with Western gels and dot-blot to quantify mucin in sputum from 12 patients with CF and 11 subjects without lung disease. There was a 70% decrease in MUC5B and a 93% decrease in MUC5AC in CF sputum (P < 0.005 for both). We conclude that the vol/vol concentration of MUC5AC and MUC5B are decreased in the CF airways relative to normal mucus. This may be due to a relative increase in other components of sputum in the CF airway or to a primary defect in mucin secretion in CF.

Adolescent↗
PubMed2004

Effect of meconium on the surface properties of perflubron.

OBJECTIVE: Meconium passage with pulmonary aspiration in utero is associated with surfactant inactivation and is a major cause of neonatal morbidity and mortality. Ventilation with low surface tension perfluorocarbon in animal models of meconium aspiration has been shown to improve both oxygenation and lung compliance. Exogenously administered surfactant is inactivated by meconium. We wished to determine whether meconium would alter the surface properties of perfluorooctyl bromide (perflubron). DESIGN: Biophysical analysis using novel methods. SETTING: University research laboratory. SUBJECTS: Healthy newborns. INTERVENTIONS: First pass meconium was obtained from healthy newborns. MEASUREMENTS AND MAIN RESULTS: We evaluated the surface-active properties of perflubron after exposure to meconium-saline dilutions using the de Noüy ring distraction technique to measure interfacial tension and the sessile contact angle of meconium-saline suspensions. Both were assessed in the absence and presence of perflubron. Meconium-saline suspensions inhibited surfactant activity. In contrast, the surface properties of perflubron were unaffected by the presence of meconium-saline suspensions. CONCLUSIONS: These data are consistent with reported observations of increased lung compliance in perfluorocarbon-treated animals with meconium aspiration. In addition to these clinical implications, the novel interfacial tension technique described here could prove useful for assessing the interfacial properties of other poorly miscible biological fluids.

Biological Products↗
PubMed2004

Immunomodulatory activity and effectiveness of macrolides in chronic airway disease.

The use of troleandomycin as adjunctive therapy for the treatment of patients with corticosteroid-dependent asthma first suggested an immunomodulatory effect of the macrolide antibiotics. This led to studies of the macrolides in other chronic airway diseases, such as diffuse panbronchiolitis (DPB), a disease occurring primarily in East Asia. The use of macrolides for the therapy of patients with DPB has led to dramatic improvements in pulmonary function and prolonged survival. Similar benefits have been documented in Japanese studies of bronchiectasis, chronic bronchitis, and sinobronchial syndrome. Clinical and pathologic similarities between DPB and cystic fibrosis (CF) led to the investigation of macrolides for the treatment of CF. Data now suggest that persons with CF will benefit from macrolide therapy. In vitro and in vivo studies suggest that macrolides may inhibit the pulmonary influx of neutrophils, inhibit the release of proinflammatory cytokines, protect the epithelium from bioactive phospholipids, and improve the transportability of airway secretions. The immunomodulatory effects of the macrolides also may be beneficial for the treatment of other chronic inflammatory conditions.

Adolescent↗
PubMed2004

How do patients determine that their metered-dose inhaler is empty?

STUDY OBJECTIVE: To evaluate how patients determined that pressurized metered-dose inhaler (pMDI) canisters were empty and to measure pMDI depletion under different circumstances in the laboratory. SETTING: Most of the study was performed in a university research laboratory. PARTICIPANTS: Fifty consecutive patients attending the Brenner Children's Hospital Asthma Center were initially questioned regarding pMDI use, and they demonstrated their use of the inhaler. MEASUREMENTS AND RESULTS: Of the 50 children and parents questioned, 74% did not know how many actuations were in their canisters, and all used their pMDI until they could not longer "hear" the medication when actuating. Only half shook the canister before actuating. In the laboratory, chlorofluorocarbon (CFC) canisters typically had 86% more actuations than the nominal dose, and hydrofluoroalkane (HFA) canisters had 52% more. Canister flotation was ineffective in identifying when a pMDI was depleted, and water obstructed the valve opening 27% of the time. For CFC inhalers, shaking the pMDI before firing increased the number of actuations per canister (p = 0.009 [vs not shaking]), but this was not true for HFA inhalers. CONCLUSIONS: If patients are not taught to recognize when a pMDI is empty, they may continue to use the medication for up to twice the intended duration. Until accurate dose counters are added to pMDIs, counting the number of doses administered is the only accurate method with which to tell when the canister should be discarded.

Aerosols↗
PubMed2003

The delivery of inhaled medication to the young child.

The effective and efficient delivery of aerosol medications involves physician factors (correct diagnosis and correct prescription of appropriate medications), device factors, and patient factors. For nearly all infants and children, the authors administer asthma medications either using a pMDI with a valved holding chamber or a DPI. Regardless of the device chosen, parent and patient education is critical for the appropriate use of the device, and frequent reinforcement of the educational message will often improve adherence and correct use.

Administration, Inhalation↗
PubMed2003

Macrolides as biological response modifiers in cystic fibrosis and bronchiectasis.

For 50 years, macrolide antibiotics have been used to treat community acquired pneumonia and atypical infections such as Chlamydia pneumonia and Mycoplasma. In the late 1960s it was noted that when the 14-member ring macrolide antibiotic troleandomycin was given to asthma patients who required large doses of systemic corticosteroids, they could often reduce their steroid dose or even stop steroids completely without exacerbation of their asthma. Because of this experience, Prof. S. Kodoh and colleagues first used erythromycin as an immunomodulatory agent to treat diffuse panbronchiolitis (DPB). DPB is a cystic fibrosis (CF)-like condition seen predominantly in young, nonsmoking adults in Japan and Korea. The introduction of erythromycin profoundly improved survival, and in many of these very ill patients the illness disappeared. Since then, research has focused attention on many non-antibacterial, disease modifying effects of this class of compounds. These include downregulation of proinflammatory cytokines via an effect on nuclear transcription factors, reduction in adhesion molecule expression, suppression of inducible nitric oxide synthase (iNOS), reduced neutrophil chemotaxis and degranulation, inhibition of neutrophil elastase, cytoprotection against bioactive phospholipids, improvement in the rheological properties of mucus, reduction in bronchial hyperreactivity, and, perhaps, modulation of neutrophil death by apoptosis pathways, and in the end, airway remodeling. Additionally, they have unconventional effects on microorganisms, including inhibiting Pseudomonas aeruginosa twitching motility and thus biofilm formation. There are small case series and three large randomized controlled trials that have established unequivocal evidence of benefit in CF. There is less evidence for an immunomodulatory effect in bronchiectasis. Future work is likely to focus on the development of macrolides with disease-specific modes of action.

Journal Article↗