Pseudomonas aeruginosa rhamnolipid causes ciliostasis and cell membrane damage to rabbit tissue, is a secretagogue in cats, and inhibits epithelial ion transport in sheep tissue. It could therefore perturb mucociliary clearance. We have investigated the effect of rhamnolipid on mucociliary transport in the anesthetized guinea pig and guinea pig and human respiratory epithelium in vitro. Application of rhamnolipid to the guinea pig tracheal mucosa reduced tracheal mucus velocity (TMV) in vivo in a dose-dependent manner: a 10-microgram bolus caused cessation of TMV without recovery; a 5-micrograms bolus reduced TMV over a period of 2 h by 22.6% (P = 0.037); a 2.5-microgram bolus caused no overall changes in TMV. The ultrastructure of guinea pig tracheal epithelium exposed to 10 micrograms of rhamnolipid in vivo was normal. Application of 1,000 micrograms/ml rhamnolipid had no effect on the ciliary beat frequency (CBF) of guinea pig tracheal rings in vitro after 30 min, but 250 micrograms/ml stopped ciliary beating after 3 h. Treatment with 100 micrograms/ml rhamnolipid caused immediate slowing of the CBF (P less than 0.01) of human nasal brushings (n = 7), which was maintained for 4 h. Mono- and dirhamnolipid had equivalent effects. The CBF of human nasal turbinate organ culture was also slowed by 100 micrograms/ml rhamnolipid, but only after 4 h (CBF test, 9.87 +/- 0.41 Hz; control, 11.48 +/- 0.27 Hz; P less than 0.05, n = 6), and there was subsequent recovery by 14 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Background -Primary ciliary dyskinesia is characterised by chronic rhinosinusitis, chronic bronchial sepsis (usually with bronchiectasis), dextrocardia in approximately 50% of cases, and male infertility. The latter, described in patients attending infertility clinics, results from immotile but viable spermatozoa. Experience in a respiratory clinic suggests that infertility in men is not invariable. Methods -The seminal fluid of 12 men with primary ciliary dyskinesia, six with dextrocardia, who presented consecutively with upper and lower respiratory tract sepsis was examined. Nasal ciliary beating was dyskinetic or absent in ali cases, and nasal ciliary ultrastructure was abnormal in those 11 patients examined. Results -Viable but immotile spermatozoa with abnormal tail ultrastructure were found in the ejaculate of only two patients. Two other patients had apparently fathered children; seminology in both these cases showed a normal spermatozoa count, one with normal spermatozoal motility and normal ultrastructure, the other with moderately reduced spermatozoal motility and abnormal ultrastructure (dynein arm deficiency on the peripheral microtubule doublets). A further two patients had normal spermatozoa counts, normal spermatozoa tail ultrastructure, and normal or only moderately reduced motility of spermatozoa. The spermatozoa of one patient were normally motile but there was severe oligozoospermia, and five patients were azoospermic. Conclusions -Not all men with primary ciliary dyskinesia have immotile spermatozoa. Seminal analysis is recommended in men with primary ciliary dyskinesia so that accurate counselling about reproductive capability may be given.inner and outer dynein arms which interact with neighbouring microtubules to produce movement.Primary ciliary dyskinesia is a congenital condition characterised by purulent rhinosinusitis, chronic bronchial sepsis which is usually associated with bronchiectasis, and, frequently, male infertility.2' About 50% of patients have dextrocardia with or without situs inversus and meet the criteria for Kartagener's syndrome. The characteristic seminal analysis in primary ciliary dyskinesia is a normal number of viable but immotile spermatozoa. A common defect -usually partial or complete deficiency of one or both sets of dynein arms -may account for the dyskinetic beating of the respiratory cilia and the immotility of spermatozoan tails in this condition.2Most men with primary ciliary dyskinesia are infertile because of immotile spermatozoa.45 This may be because of a bias in case selection towards those attending for investigation of infertility whose respiratory symptoms were only fully investigated once immotile spermatozoa were noted. There are single case reports of men presenting with respiratory disease due to primary ciliary dyskinesia with normal seminal analysis6 and azoospermia.7 We examined the fertility of men with primary ciliary dyskinesia who presented consecutively with respiratory symptoms. Methods PATIENTSAll patients with persistent resp...
Streptococcus pneumoniae infections are common, but how they cause host tissue injury and death is incompletely understood. Immunization with pneumolysin, a thiol-activated toxin produced by the pneumococcus, partially protects animals during subsequent infection. The mechanism by which pneumolysin contributes to disease is not known. The aim of the present investigation was to determine the histologic changes induced by recombinant pneumolysin in the rat lung and to compare them with the changes induced by live organisms. Injection of either toxin (200 or 800 ng) or bacteria into the apical lobe bronchus was associated with the development of a severe lobar pneumonia restricted to the apical lobe. The changes induced by the toxin were greater at the higher concentration, and changes were most severe in those animals in which there was partial ligation of the apical lobe bronchus. The pneumonitis was less severe following injection of a modified toxin with decreased hemolytic activity, generated by site-directed mutagenesis of the cloned pneumolysin gene, indicating that this property of the toxin was important in generating pulmonary inflammation. There was still considerable pneumonitis after injection of a modified toxin with decreased capacity to activate complement.
Products of the bacterium Pseudomonas aeruginosa have been shown to slow the beating of human respiratory tract cilia in vitro. We have tested the effects of two of these compounds, pyocyanin and 1-hydroxyphenazine (given as a bolus dose dissolved in 2 microliters Ringer solution), on tracheal mucus velocity of radiolabeled erythrocytes in anesthetized guinea pigs. 1-Hydroxyphenazine (200 ng) caused a rapid slowing of tracheal mucus velocity (maximum fall 47% at 20 min) with recovery by 1 h. The effect of pyocyanin was slower in onset, 600 ng causing 60% reduction in tracheal mucus velocity at 3 h, and no recovery occurred. A combination of pyocyanin and 1-hydroxyphenazine produced an initial rapid slowing equivalent to the same dose of 1-hydroxyphenazine given alone, but the later slowing attributed to pyocyanin was greater than the same dose administered alone. This study demonstrates one mechanism by which products of P. aeruginosa may facilitate its colonization of the respiratory tract.
Computed tomography is widely used in the investigation of patients in whom bronchiectasis is suspected, despite considerable variation in its reported sensitivity and specificity. The findings with 3 mm high resolution computed tomography were compared at segmental level with bronchography by two radiologists independently in 27 patients (aged 20-67 years) undergoing investigation of chronic sputum production. Fifteen patients were found to have bronchiectasis by both investigations. Five were identified by computed tomography alone, including two in whom disease was revealed in segments underfilled at bronchography. The sensitivity of computed tomography compared with bronchography in the diagnosis of bronchiectasis at segmental level was 84% and the specificity 82%. The predictive value of computed tomography in the diagnosis of bronchiectasis was 38% overall, but increased to 75% when only those segmental bronchi moderately or severely dilated on the computed tomography scan were considered. There was no relation between the degree ofbronchial wall thickening on the computed tomogram and the diagnosis of bronchiectasis by bronchography. Bronchography may be avoided in patients being considered for surgical resection of their bronchiectasis in whom computed tomography shows diffuse disease.
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