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Biomedical subjects

C M Rossman

Publications and source records attributed to C M Rossman.

16 recordsLinked to original sources

Nasal polyposis: in search of a viral etiology using DNA hybridization.

The etiology of nasal polyps is unknown. Numerous theories have been proposed, with allergic and infectious causes predominant. A viral theory was postulated almost 40 years ago. In a pilot project, we studied 15 subjects comprising six controls and nine patients with nasal polyps. No known viruses were cultured from the nasal polyp tissue or nasal mucosal biopsies from the control subjects. DNA Hybridization for Epstein-Barr Virus, Herpes simplex virus, adenovirus type V, and Chlamydia trachomatis were also negative for all tissue studied. The use of molecular biological techniques is not widespread in otolaryngology and this is the first report, to the best of our knowledge, of the application of these techniques for the investigation of the viral etiology of nasal polyps.

Adult↗

Assessment of postmortem respiratory ciliary motility and ultrastructure.

Acquired and congenital abnormalities in the mucociliary transport system result in respiratory dysfunction and clinical disease. Although upper and lower respiratory epithelium can be analyzed premortem, it is uncertain whether postmortem analyses provide a valid indicator of the premortem status of the ciliary apparatus. To address this question, we studied nasal ciliary motility and ultrastructure from 2 patients 16 h after death. After placement of the epithelial samples in Krebs-Henseleit solution and warming to body temperature, normal ciliary motility and frequency were observed in both samples. The specimen then could be stored within the solution at 4 degrees C for subsequent reanalysis on later days for as long as 60 h after collection with no deterioration in ciliary motility, as assessed by video motion analysis. Quantitative assessment of the ciliary ultrastructure did not reveal any abnormality in microtubular arrangements, and good tissue preservation was seen. These studies demonstrate that postmortem collection of nasal epithelium samples can provide a valid assessment of premortem ciliary structure and function.

Aged↗

Nasal ciliary ultrastructure and function in patients with primary ciliary dyskinesia compared with that in normal subjects and in subjects with various respiratory diseases.

In an attempt to establish the relevance of ciliary ultrastructure to the pathophysiologic aspects of respiratory tract disease, we compared quantitatively the ultrastructure and function of cilia from healthy subjects (atopic and nonatopic nonsmokers, asymptomatic smokers) and patients with a variety of respiratory diseases (cystic fibrosis, chronic rhinitis, bronchiectasis associated with hypogammaglobulinemia, chronic bronchitis) with cilia from patients with primary ciliary dyskinesia (PCD). In healthy subjects and patients with non-PCD respiratory disease, approximately 5% of the cilia evaluated had ultrastructural abnormalities. Ciliary beat frequency was significantly higher in the chronic rhinitis group (15.3 +/- 1.2 Hz) than in the other non-PCD groups, which were within the normal range (12.5 +/- 1.7 Hz), and in all non-PCD cases ciliary wave form was normal. In each of these groups, normal mucociliary transport had been previously demonstrated. By contrast, in patients with PCD, the proportion of cilia with ultrastructural abnormalities was significantly greater than in the normal subjects and those with non-PCD respiratory disease (p less than 0.0001). In addition, beat frequency was significantly reduced, ciliary wave form was grossly abnormal, and pulmonary and nasal mucociliary transport were virtually absent. These findings demonstrate the relevance of ciliary ultrastructural abnormalities to altered ciliary function and lend support to the primary role of the demonstrated abnormalities in the respiratory tract disease of PCD.

Adolescent↗

Ciliary defects associated with the development of bronchopulmonary dysplasia. Ciliary motility and ultrastructure.

We have on several occasions studied the nasal respiratory epithelium of an infant with hyaline membrane disease that evolved into bronchopulmonary dysplasia and observed an association between the clinical status and naso-ciliary motion and ultrastructure. At 4 months of age, when the patient had significant respiratory disease, few cilia were present and they beat with a slow dyskinetic motion. The specimens contained primarily necrotic and squamous epithelial membranes; the occasional cilia present had swollen or ruptured membranes. Partial recovery of the epithelium was noted at 4.5 months, with 45% of the cilia having normal ultrastructure. The beat frequency was 15.2 +/- 1.5 Hz (mean +/- SD), and although some degree of dyskinesia was evident, primarily normal ciliary motion was observed. By 10 months of age, significant clinical improvement had occurred and the nasal epithelium had regenerated; 96% of the cilia had normal ultrastructure, and the ciliary beat frequency (12.4 +/- 1.2 Hz) and motion were normal.

Bronchopulmonary Dysplasia↗

Nasal cilia in normal man, primary ciliary dyskinesia and other respiratory diseases: analysis of motility and ultrastructure.

We studied the ultrastructure and function of nasal cilia from non-atopic and atopic non-smokers, smokers, patients with chronic rhinitis and cystic fibrosis, and compared these to cilia from patients with primary ciliary dyskinesia (PCD). Atypical cilia were found in normal subjects and patients with a variety of chronic respiratory tract diseases, but the proportion was small (less than 5%). Ciliary wave form, beat frequency, and mucociliary transport were normal. In patients with PCD, the proportion of atypical cilia and ultrastructural abnormalities was significantly greater than normal subjects and patients without PCD p less than 0.0001. Beat frequency was reduced, ciliary wave form was grossly abnormal, and mucociliary transport was virtually absent. These findings suggest that ciliary ultrastructural abnormalities are related to altered ciliary function and have aetiological relevance in the generalized chronic respiratory tract disease of PCD.

Cilia↗

Effect of chest physiotherapy on the removal of mucus in patients with cystic fibrosis.

We studied the effectiveness of some of the components of a physiotherapy regimen on the removal of mucus from the lungs of 6 subjects with cystic fibrosis. On 5 randomized study days, after inhalation of a 99mTc-human serum albumin aerosol to label primarily the large airways, the removal of lung radioactivity was measured during 40 min of (a) spontaneous cough while at rest (control), (b) postural drainage, (c) postural drainage plus mechanical percussion, (d) combined maneuvers (postural drainage, deep breathing with vibrations, and percussion) administered by a physiotherapist, (e) directed vigorous cough. Measurements continued for an additional 2 h of quiet rest. Compared with the control day, all forms of intervention significantly improved the removal of mucus: cough (p less than 0.005), physiotherapy maneuvers (0.005 less than or equal to p less than 0.01), postural drainage (p less than 0.05), and postural drainage plus percussion (p less than 0.01). However, there was no significant difference between regimented cough alone and therapist-administered combined maneuvers, nor between postural drainage alone and with mechanical percussion. We conclude that in cystic fibrosis, vigorous, regimented cough sessions may be as effective as therapist-administered physiotherapy in removing pulmonary secretions. Postural drainage, although better than the control maneuver, was not as effective as cough and was not enhanced by mechanical percussion. Frequent, vigorous self-directed cough sessions are potentially as useful as more complex measures for effective bronchial toilet.

Adolescent↗

Immotile cilia syndrome in persons with and without Kartagener's syndrome.

We studied the ultrastructure and function of respiratory tract cilia in a group of patients with Kartagener's Syndrome, and compared the results with those from a group of subjects with unexplained histories of chronic bronchiectasis and bronchitis. Both patient groups lacked pulmonary and nasal mucociliary transport. On electron microscopic examination of nasal mucosal biopsy tissue, all patient specimens had abnormal cilia with a highly disorganized microtubular network, and a consistent absence of dynein arms. Cilia from both groups were immotile when viewed under direct phase contrast, but could be animated by the addition of 10(-6) g/ml of ATP or ATPase to the same degree of spontaneous motility seen in normal cilia. Immotile cilia syndrome clearly includes not only patients with Kartagener's syndrome, but also some patients with chronic bronchitis and bronchiectasis.

Adenosine Triphosphatases↗

The dyskinetic cilia syndrome. Ciliary motility in immotile cilia syndrome.

Ciliary motility was studied in three patients with Kartagener syndrome who had previously been found to have absent nasal and pulmonary mucociliary transport and missing dynein arms in nasal cilia. A video system was used to record movement of cilia obtained by nasal brushings for analysis of wave form and beat frequency. Two patterns of abnormal ciliary beat were observed; an oscillating and a rotating type of motion. There was no evidence of planar coordination of metachronicity. This abnormal motion was present in up to 40 percent of cells and the remainder were totally immotile. Thus, in Kartagener syndrome many ciliated cells are motile, but the motion is abnormal. We suggest that "immotile cilia syndrome" is a misnomer, and recommended it be renamed "dyskinetic cilia syndrome."

Adenosine Triphosphatases↗

Activation of nasal cilia in immotile cilia syndrome.

Nasal biopsy specimens were obtained from 5 normal subjects and from 7 patients with immotile cilia syndrome. Of the latter, 3 had Kartagener's syndrome, one had Kartagener's forme fruste, and 3 had bronchiectasis and sinusitis. An in vitro motility test was used to assess ciliary movement. Exogenous adenosine triphosphate and adenosine triphosphatase activated the immotile cilia to levels equal to or slightly greater than the spontaneous activity seen in normal subjects. Absence of dynein arms on ciliary peripheral microtubule doublets was a consistent finding in the patients' specimens and is suggested to be the basic defect in this syndrome that is responsible for immotility and absence of mucociliary clearance.

Adenosine Triphosphatases↗

Aerosol therapy with Sch 1000. Short-term mucociliary clearance in normal and bronchitic subjects and toxicology in normal subjects.

The anticholinergic bronchodilator drug, Sch 1000, was administered as an aerosol by a metered-dose inhaler (200 microgram) to six normal and six bronchitic subjects. The short-term effect on mucociliary clearance was assessed and compared to a placebo (propellant and dispersal agent) in a double-blind crossover study. Mucociliary clearance in the normal group was significantly faster with administration of Sch 1000 than with placebo (P less than 0.01). There was no significant difference between the effects of administration of Sch 1000 and placebo on mucociliary clearance in the bronchitic group. Pulmonary function was significantly increased by therapy with Sch 1000 (as compared to administration of placebo) in the bronchitic group for two hours (P less than 0.05) and in the normal group for one hour (P less than 0.05). In another study, 12 normal subjects inhaled aerosols containing 40 microgram of placebo or 400 microgram of Sch 1000 from metered-dose inhalers on separate days in a randomized double-blind fashion. A significant sustained improvement in pulmonary function (P less than 0.05) and a transient fall in diastolic blood pressure were observed after administration of Sch 1000.

Adult↗

Sulfur dioxide and tracheobronchial clearance in man.

Tracheobronchial clearance was measured in nine healthy, nonsmoking adults. Technetium Tc 99m albumin aerosol (mass median diameter, 3 mu; geometric standard deviation, 1.6) was inhaled as a bolus under controlled conditions to achieve reproducible deposition in large airways. Each subject was studied in three seperate three-hour experiments: twice under control conditions and once exposed to 5 ppm sulfur dioxide (pollutant exposure after aerosol inhalation). Lung retention of activity was measured using a gamma camera interfaced to a data storage and retrieval system. The study showed that (1) Both deposition and clearance were highly reproducible in individuals in repeat control studies. (2) Acute exposure to 5 ppm sulfur dioxide had no significant effect (P greater than .05) on mucocillary clearance in resting healthy subjects, except perhaps for a small transient change (P=.05) after one hour. (3) Pulmonary function tests showed a decrease in maximal midexpiratory flow (P less than .01) but no other significant changes.

Adult↗