Effect of osmolality on mucociliary transportability and rheology of cystic fibrosis and bronchiectasis sputum.

Objective: Water is the main constituent of mucus, and its concentration is likely to be important in all aspects of mucus function, including ciliary clearance. The objective of this study was to investigate the effect of water content and osmolality of the mucus on mucociliary transportability.

Methodology: Rheology and ciliary transportability of 10 sputum samples that had been subjected to various manipulations were measured using a mucus-depleted bovine trachea model.

The effect of erythromycin on mucociliary transportability and rheology of cystic fibrosis and bronchiectasis sputum.

Background: Erythromycin has been shown to diminish sputum production in hypersecretory states by a mechanism that is still unclear.

Objectives And Methods: We have investigated the effect of erythromycin on the ciliary transportability of cystic fibrosis and non-cystic fibrosis bronchiectasis sputum in vitro using the mucus-depleted bovine trachea.

Results: Additional erythromycin in concentrations up to 20 microg/g did not significantly alter the ciliary transportability of sputum from 6 cystic fibrosis and 6 bronchiectasis patients.

Mucus transportability: the bovine trachea and frog palate models compared.

For nearly 30 yrs, the mucus-depleted frog palate has been used to measure the ciliary transportability of respiratory and other mucus gels, but the data obtained from this amphibian digestive system may not be applicable to human airway mucociliary clearance. This study compared this model with the mucus-depleted bovine trachea, a mammalian respiratory system. Assessments were made of the reproducibility of each model, and of the behaviour of sputum subjected to changes to its salinity or hydration.

Ischemia-reperfusion lung injury: contribution of ischemia, neutrophils, and hydrostatic pressure.

We used an isolated, blood-perfused rat lung model to evaluate the separate roles of ischemia and reperfusion time, the changes in pulmonary artery pressure (Ppa), and the circulating neutrophil number in mediating ischemia-reperfusion lung injury. Extravascular albumin accumulation was used to quantify changes in the permeability of the alveolar capillary membranes. In animals subjected to 30 and 45 min of ischemia without reperfusion, extravascular albumin accumulation was significantly higher than in controls subjected to continuous perfusion (P < 0.

Determinants of transplant-related coronary calcium detected by ultrafast computed tomography scanning.

Coronary calcium detected by ultrafast computed tomography (CT) has been shown to be a marker of coronary artery disease in heart transplant recipients. The objective of this study was to examine the possible determinants of coronary calcium after heart transplantation. Over a 15-month period, 102 consecutive cardiac transplant recipients (mean age 53 years, 88 men) underwent ultrafast CT scanning of the heart, in addition to coronary angiography, to determine coronary calcium score on their annual follow-up (a median of 4.

The effect of mutations in genes required for lipopolysaccharide synthesis on Haemophilus influenzae type b colonization of human nasopharyngeal tissue.

Haemophilus influenzae type b (Hib) is an upper respiratory tract commensal that can cause invasive disease, particularly in young children. Lipopolysaccharide (LPS) has been implicated as a major virulence determinant of Hib, and changes in LPS structure may influence bacterial interactions with the respiratory mucosa. We have examined the effect of variations in LPS on the interaction of Hib with human nasal turbinate tissue maintained in an organ culture model with an air-interface, by using isogenic derivatives of strains RM153 (Eagan) and RM7004 expressing truncated LPS due to mutations in genes contained within the chromosomal loci lic1 and lic2 (lic1lic2) or in the galE and galK genes (galEK).

Short-term recombinant human DNase in bronchiectasis. Effect on clinical state and in vitro sputum transportability.

We report a double blind placebo-controlled phase II study of the efficacy and safety of nebulized recombinant human DNase (rhDNase) administered for 14 d to adults with bronchiectasis not caused by cystic fibrosis. All were in a stable clinical state at the commencement of the study, and they received (1) rhDNase 2.5 mg twice daily, (2) rhDNase once daily, or (3) placebo (excipient only) inhalation.

Paradoxical facilitation of acetylcholine release from parasympathetic nerves innervating guinea-pig trachea by isoprenaline.

1. Previous studies have provided evidence that activation of beta-adrenoceptors on cholinergic nerve terminals can inhibit neurotransmission in the airways. However, in most cases, this conclusion has been based on indirect evidence obtained from mechanical experiments where changes in airways smooth muscle tone were measured.

A human respiratory-tissue organ culture incorporating an air interface.

The immersion of respiratory tissue in organ cultures is unphysiologic and may influence the interactions of the tissue with experimental agents. We have assessed an organ culture of human nasal turbinate tissue with an air interface by light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM), with and without replacement of culture medium. Without replacement of medium, ciliary beat frequency (CBF) was normal (11.

Ciliary disorientation alone as a cause of primary ciliary dyskinesia syndrome.

Ciliary disorientation has been proposed as a variant of primary ciliary dyskinesia (PCD); cilia have normal ultrastructure and normal or near normal ciliary beat frequency (CBF) but lack efficacy because their beat direction is disorientated. We have identified 11 patients, including two siblings, with the clinical features of PCD, who satisfy these criteria. A chest radiograph, pulmonary function tests, nasal mucociliary clearance (NMCC), CBF, ciliary ultrastructure, and orientation were assessed in each subject.

Localized intraoperative cardiac tamponade.

A 65-year-old lady had undergone mitral and aortic valve replacement following an open mitral valvotomy and aortic valve exploration 5 years earlier. At reoperation, following sternotomy, extensive adhesions were encountered and it was decided to perform minimal dissection of the heart. Both the aortic and mitral valves were replaced using 23 mm and 29 mm St.

Growth hormone activation of human monocytes for superoxide production but not tumor necrosis factor production, cell adherence, or action against Mycobacterium tuberculosis.

We have previously demonstrated that growth hormone (GH) is a human macrophage-activating factor which primes monocytes for enhanced production of H2O2 in vitro. This report extends our observations to other monocyte functions relevant to infection. We find that GH also primes monocytes for O2- production, to a degree similar to the effect of gamma interferon.

Clenbuterol induces hypertrophy of the latissimus dorsi muscle and heart in the rat with molecular and phenotypic changes.

Background: Skeletal muscle assistance of the circulation for patients in end-stage heart failure requires electrical training of the latissimus dorsi flap to produce fatigue resistance. This process of electrical transformation and the development of postmobilization atrophy results in a profound loss in peak power generated. The beta 2-adrenoceptor agonist clenbuterol was used to investigate its potential to selectively induce skeletal muscle hypertrophy, particularly the latissimus dorsi muscle (LDM), independent of adverse effects on cardiac muscle.

Inspiratory muscle strength is a determinant of maximum oxygen consumption in chronic heart failure.

Objective: To investigate the significance of respiratory muscle weakness in chronic heart failure and its relation both to maximum oxygen consumption during cardiopulmonary exercise testing and to skeletal muscle (quadriceps) strength.

Subjects: Seven healthy men aged 54.9 (SEM 4.

Suppression of lipopolysaccharide-induced tumor necrosis factor-alpha generation from human peripheral blood monocytes by inhibitors of phosphodiesterase 4: interaction with stimulants of adenylyl cyclase.

We assessed the role of cyclic nucleotides in modulating lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) generation in human peripheral blood monocytes. Exposure of monocytes to LPS (3 ng/ml) evoked a delayed, time-dependent generation of TNF-alpha that reached a maximum level 5-6 hr after LPS challenge and remained constant for up to 24 hr. This effect was concentration dependent and resulted in a 20-40-fold increase in the release of TNF-alpha that was sensitive to actinomycin D and cycloheximide.

Early signalling events implicated in leukotriene B4-induced activation of the NADPH oxidase in eosinophils: role of Ca2+, protein kinase C and phospholipases C and D.

The early signalling events that may ultimately contribute to the assembly and subsequent activation of the NADPH oxidase in guinea-pig peritoneal eosinophils were investigated in response to leukotriene B4 (LTB4). LTB4 promoted a rapid, transient and receptor-mediated increase in the rate of H2O2 generation that was potentiated by R 59 022, a diradylglycerol (DRG) kinase inhibitor, implicating protein kinase C (PKC) in the genesis of this response. This conclusion was supported by the finding that the PKC inhibitor, Ro 31-8220, attenuated (by about 30%) the peak rate of LTB4-induced H2O2 generation under conditions where the same response evoked by 4 beta-phorbol 12,13-dibutyrate (PDBu) was inhibited by more than 90%.

The effects of low concentrations of antibiotics on epithelial damage caused by non-typable Haemophilus influenzae and bacterial morphology.

Sterile culture filtrates from non-typable Haemophilus influenzae (NTHi) grown in medium containing no antibiotics or 0.25 MIC of amoxycillin, ciprofloxacin or loracarbef were examined for their effect on the ciliary beat frequency (CBF) and structure of human respiratory epithelium. CBF slowing was significantly (P < 0.

Purification and characterization of factors produced by Aspergillus fumigatus which affect human ciliated respiratory epithelium.

The mechanisms by which Aspergillus fumigatus colonizes the respiratory mucosa are unknown. Culture filtrates of eight of nine clinical isolates of A. fumigatus slowed ciliary beat frequency and damaged human respiratory epithelium in vitro.

Bronchitis.

Acute bronchitis in previously fit individuals is a common condition that is usually mild and self limiting. Chronic bronchitis remains a common cause of morbidity and mortality, and the cost to the nation due to lost working days and to health services is enormous. Cigarette smoking is the major etiologic factor, although exacerbations may be caused by viruses, environmental pollutants, allergic responses, and bacterial infections.

Interaction of fimbriated and nonfimbriated strains of unencapsulated Haemophilus influenzae with human respiratory tract mucus in vitro.

Adherence to mucus may influence bacterial colonization of the respiratory tract. Clinical isolates of nontypable Haemophilus influenzae (NTHi) from the respiratory tract are often fimbriated. We wondered whether fimbriated strains have a different adherence from related nonfimbriated strains.

Phenotype of cells positive for interleukin-4 and interleukin-5 mRNA in allergic tissue reactions.

We have investigated the phenotype of cells positive for IL-4 and IL-5 mRNA in the nasal mucosa of subjects with allergic rhinitis and in bronchoalveolar lavage and bronchial biopsies from atopic asthmatic subjects. The method employed was immunochemistry followed by in situ hybridization using either 35S- or digoxigenin-labelled riboprobes. With nasal and bronchial tissue, this double ICC/ISH method revealed that more than 70% of IL-4 and IL-5 mRNA+ cells were T cells.

The ciliary transportability of sputum is slow on the mucus-depleted bovine trachea.

Mucus retention in the lungs is a feature of several chest diseases. It is unclear to what extent suboptimal mucus transportability is responsible for the poor clearance of lung secretions. We described a new model, the mucus-depleted bovine trachea, for measurement of the ciliary transportability of respiratory mucus.