Michael Robinson

Evidence for spread of a clonal strain of Pseudomonas aeruginosa among cystic fibrosis clinics

Recent advances in molecular typing techniques have led to the identification of a dominant clonal strain of Pseudomonas aeruginosa within several cystic fibrosis (CF) clinics ([2][1]-[6][2], [8][3], [9][4]). These strains have been described as “hypertransmissible,” and “patient-to-patient

Regional mucociliary clearance in patients with cystic fibrosis.

This paper reports on a large retrospective analysis of mucociliary clearance (MCC) studies in a group of 59 patients with cystic fibrosis (CF) and 17 age-matched healthy subjects. As many of the CF patients were studied on multiple occasions, a total of 184 patient studies are presented. MCC was measured using a radioaerosol and gamma camera technique. In addition to whole lung clearance, MCC was measured from the central, intermediate, peripheral, basal, mid and apical regions of the lung. MCC was markedly decreased in the CF patient group. Not only was whole lung clearance (14.2 +/- 1.4% vs. 28.0 +/- 3.7%) impaired, but also clearance from the central (19.1 +/- 1.9% vs. 35.6 +/- 4.3%), intermediate (10.7 +/- 1.6% vs. 25.5 +/- 3.7%), apical (12.4 +/- 2.6% vs. 31.6 +/- 4.6%) and mid (14.0 +/- 1.9% vs. 30.4 +/- 4.0%) regions. Attempts were made to identify factors that may have influenced MCC in both the normal subjects and CF patients. Age, gender, body mass index, patient genotype, penetration index, spontaneous cough, and various lung function parameters were entered into a stepwise multiple regression model, but none of the factors proved to be statistically important in determining MCC. Both intrasubject repeatability and intersubject variability estimates are presented for the patients and normal subjects that had multiple studies. The values were found to be remarkably similar for both CF patients and normal subjects and for both intra- and intersubject repeatability. With marked deviation from normal ranges and good repeatability, the measurement of MCC in CF patients would seem to be a valuable outcome measure for clinical trials involving new pharmaceuticals and physical therapy designed to improve removal of secretions from the airways.

Osmotic Stimuli Increase Clearance of Mucus in Patients with Mucociliary Dysfunction

Mucociliary dysfunction results in mucus accumulation, airway obstruction, bacterial colonization, recurrent infective exacerbations, and an increase in morbidity and mortality. Studies in patients with cystic fibrosis, established that inhalation of hypertonic saline (HS) increases clearance of mucus acutely in a dose-dependent manner. Clearance over 90 min was 23.8 +/- 4.0% and 26.0 +/- 3.1% in response to 7% and 12% saline, which was significantly enhanced compared to 12.7 +/- 1.4% and 19.7 +/- 3.1% in response to 0.9% and 3% saline. Mannitol (approximately 300 mg) inhaled as a dry powder had a marked acute effect in patients with bronchiectasis. Clearance over 75 min was 34.0 +/- 5.0% with mannitol, 17.4 +/- 3.8% with control, and 11.7 +/- 4.4% at baseline. Further studies in patients with bronchiectasis showed that mannitol reduces the 24-h retention of radiolabeled mucus, suggesting that the effect of mannitol extends beyond the acute phase. Mannitol helped patients to clear mucus within 2 h that would have taken 24 h to clear without mannitol. A further study in CF patients showed that mannitol was equally effective as 6% HS at improving ciliary and cough clearance. The total clearance over 120 min with mannitol (27.6 +/- 3.7%) and with HS (31.0 +/- 5.5%) was significantly increased compared to their respective controls (18.6 +/- 3.8% and 20.9 +/- 3.6%). These preliminary results suggest that long-term treatment with HS or mannitol may benefit patients with mucociliary dysfunction.

Effect of a short course of rhDNase on cough and mucociliary clearance in patients with cystic fibrosis

The aim of the study was to measure the effect of a short course of recombinant human deoxyribonuclease I (rhDNase) on ciliary and cough clearance in a group of cystic fibrosis patients, using a radioaerosol and gamma camera technique. Patients were initially randomized to receive either rhDNase (2.5 mg qd) or placebo. Following the measurement of baseline clearance, patients were given a 7‐day course of either rhDNase or placebo. The patient then returned on the seventh day for follow‐up clearance measurements. This was followed by a 2‐week washout period before the whole process was repeated with the alternative inhalation solution. On each of the study days, mucociliary clearance was initially measured for a period of 60 min (IC). This was followed by cough clearance (CC) measurements for 30 min, during which patients were requested to cough a total of 120 times. Post‐cough clearance (PCC) was then measured for a further 60 min.

Effect of Burkholderia cepacia infection in the clinical course of patients with cystic fibrosis: a pilot study in a Sydney clinic

Background: Colonisation with Burkholderia cepacia complex in patients with cystic fibrosis (CF) has been associated with adverse outcomes. The aim of the present study was to determine the actuarial survival of CF patients colonized with B. cepacia and to evaluate the efficacy of the Royal Prince Alfred Hospital segregation policy. A secondary aim was to characterize the specific genomovars and strains of B. cepacia isolated in an Australian clinic.

Simultaneous emission and transmission measurements as an adjunct to dynamic planar gamma camera studies

Anatomical imaging provides useful information which complements functional imaging performed using a gamma camera. We have previously used transmission measurements in single-photon emission tomography acquired simultaneously with the emission scan using either a plane flood source or a moving line source for attenuation and scatter correction. This approach is equally applicable in planar imaging and provides useful information to assist in detecting patient motion and in defining regions of interest in dynamic studies. We have adapted a moving transmission line source to acquire dynamic geometric mean measurements in the study of the mucociliary clearance of inhaled technetium-99m labelled colloids with a single-headed rotating gamma camera. The line source makes a return pass for each emission acquisition frame (alternating anterior/posterior views), each pass being initiated by a signal from the gamma camera. The result is a dynamic sequence of emission and transmission measurements obtained from a single acquisition. In this application transmission measurements are used to define the lung outline for clearance determination and to check for subject movement throughout the duration of the study.

The Diastolic Murmur of Renal Failure

A characteristic and transient early diastolic precordial murmur is commonly heard in patients with renal failure. On the basis of its clinical characteristics, this murmur has previously been attributed to functional aortic incompetence. We undertook a formal cardiac investigation, including aortography, in six of eight patients with renal failure in whom such a bruit developed. Aortic regurgitation was detected in only one of the six. Echocardiography revealed no abnormality of aortic-valve function but did indicate the presence of a small pericardial effusion in each of the five patients examined. We conclude that the early diastolic murmur associated with renal failure does not usually arise from functional aortic incompetence but may be a sound of pericardial origin.