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Biomedical subjects

A Pye

Publications and source records attributed to A Pye.

At least 19 recordsLinked to original sources
PubMed2000

Relationship of sputum color to nature and outpatient management of acute exacerbations of COPD.

STUDY OBJECTIVES: To stratify COPD patients presenting with an acute exacerbation on the basis of sputum color and to relate this to the isolation and viable numbers of bacteria recovered on culture. DESIGN: Open, longitudinal study of sputum characteristics and acute-phase proteins. SETTING: Patients presenting to primary-care physicians in the United Kingdom. Patients were followed up as outpatients in specialist clinic. PATIENTS: One hundred twenty-one patients with acute exacerbations of COPD were assessed together with a single sputum sample on the day of presentation (89 of whom produced a satisfactory sputum sample for analysis). One hundred nine patients were assessed 2 months later when they had returned to their stable clinical state. INTERVENTIONS: The expectoration of green, purulent sputum was taken as the primary indication for antibiotic therapy, whereas white or clear sputum was not considered representative of a bacterial episode and the need for antibiotic therapy. RESULTS: A positive bacterial culture was obtained from 84% of patients sputum if it was purulent on presentation compared with only 38% if it was mucoid (p < 0.0001). When restudied in the stable clinical state, the incidence of a positive bacterial culture was similar for both groups (38% and 41%, respectively). C-reactive protein concentrations were significantly raised (p < 0.0001) if the sputum was purulent (median, 4.5 mg/L; interquartile range [IQR], 6. 2 to 35.8). In the stable clinical state, sputum color improved significantly in the group who presented with purulent sputum from a median color number of 4.0 (IQR, 4.0 to 5.0) to 3.0 (IQR, 2.0 to 4. 0; p < 0.0001), and this was associated with a fall in median C-reactive protein level to 2.7 mg/L (IQR, 1.0 to 6.6; p < 0.0001). CONCLUSIONS: The presence of green (purulent) sputum was 94.4% sensitive and 77.0% specific for the yield of a high bacterial load and indicates a clear subset of patient episodes identified at presentation that is likely to benefit most from antibiotic therapy. All patients who produced white (mucoid) sputum during the acute exacerbation improved without antibiotic therapy, and sputum characteristics remained the same even when the patients had returned to their stable clinical state.

Acute Disease↗
PubMed1995

Simple method for quantifying viable bacterial numbers in sputum.

AIMS: To establish a simple method of quantitative culture for determining the viable bacterial numbers present in expectorated sputum samples. METHODS: Sputum samples were homogenised with dithiothreitol, sterile saline or glass beads to determine which method recovered the greatest number of viable bacteria. Culture broths were also incubated with dithiothreitol and sampled over time to determine its effect on bacterial viability. Sputum samples homogenised with dithiothreitol were diluted in sterile saline and sampled using either standard bacteriological loops or a precision pipette to determine which method resulted in the least variation. RESULTS: Homogenisation of sputum using dithiothreitol increased the recovery of viable bacteria compared with sterile glass beads and/or saline, with no apparent effect on bacterial viability when incubated with culture broths. By inoculating agar plates with 10(-3), 10(-4) and 10(-5) dilutions of the homogenised sputum sample, all potential pathogens could easily be identified. A 10 microliter sample volume dispensed by precision pipette and spread with a "hockey stick" resulted in the least variation between plates (less than 16%) and an even distribution of bacterial colonies. Numbers of viable bacteria recovered from different aliquots of individual sputum samples were generally of the same order of magnitude. CONCLUSIONS: This method represents a relatively quick and simple technique for accurately quantifying viable bacteria present in sputum samples. The use of a small portion appears to be representative of the sample as a whole.

Colony Count, Microbial↗
PubMed1995

Dynamics of respiratory tract colonization by Branhamella catarrhalis in bronchiectasis.

Branhamella catarrhalis is increasingly recognized as a lower respiratory tract pathogen, particularly in chronic lung diseases. This project defines a population of patients in whom the dynamics of colonization and infection caused by this organism could be studied. A method employing pulsed field gel electrophoresis (PFGE) of genomic DNA was developed. Twenty-eight patients with bronchiectasis followed prospectively for 26.8 mo (mean) were seen monthly or bimonthly and at the time of a purulent exacerbation. Quantitative bacterial cultures were performed on sputum obtained at each visit. Six of 28 had B. catarrhalis isolated repeatedly. Viable numbers of B. catarrhalis were similar to other bacterial pathogens. Restriction fragment length polymorphism (RFLP) analysis of chromosomal DNA using PFGE was performed on 37 of the 47 isolates recovered. Each patient was colonized by two to four strains with different RFLP patterns. Duration of colonization by the same strain was 2.3 mo (mean). Strain acquisition did not correlate with exacerbation, antibiotic therapy, or season. We conclude that (1) a subset of bronchiectatic patients is colonized with B. catarrhalis, (2) RFLP is a sensitive tool to study strain acquisition, and (3) acquisition and clearance of B. catarrhalis from the respiratory tract is a dynamic process.

Adult↗
PubMed1995

The isolation and characterization of non-typeable Haemophilus influenzae from the sputum of adult cystic fibrosis patients.

The role of non-typeable Haemophilus influenzae in cystic fibrosis (CF) remains unclear. We wanted, therefore, to determine the presence and characteristics of non-typeable H. influenzae in sputum samples from patients with CF. In order to do this, we have assessed sputum samples from 55 consecutive clinically stable patients seen routinely at an adult CF out-patient clinic. Quantitative bacterial culture was performed using a selective media containing cefsoludin, and isolates were characterized by biotyping and outer membrane protein profile analysis. In 17 (30%) of these samples, non-typeable H. influenzae was isolated and was present in similar viable numbers (mean 7.7 x 10(8) colony-forming units (cfu).mL-1; SEM 3.1) to Pseudomonas aeruginosa (mean 8 x 10(8) cfu.mL-1: SEM 2.4). All non-typeable H. influenzae isolates recovered were beta-lactamase negative and sensitive to a range of antibiotics. Several biotypes and outer membrane protein profiles were observed, with no apparent association between these two phenotypic characteristics. The study showed that large numbers of non-typeable H. influenzae are often present in sputum from adult patients with CF. Further longitudinal studies of outer-membrane protein profile analysis are required to determine the dynamics of non-typeable H. influenzae colonization in individual patients and the clinical significance.

Adolescent↗
PubMed1995

In vivo study of indomethacin in bronchiectasis: effect on neutrophil function and lung secretion.

Bronchiectasis is associated with sputum containing high levels of the proteolytic enzyme elastase, which is thought to be involved in the pathogenesis of the disease. Agents which inhibit neutrophil function and interfere with neutrophil elastase release may have a beneficial effect on the development and progression of such diseases. We have studied the effects of the nonsteroidal anti-inflammatory agent indomethacin on neutrophil function in nine patients with clinically stable bronchiectasis. All patients remained clinically stable during the study. We observed a significant reduction in peripheral neutrophil chemotaxis to 10 nmol.L-1 N-formyl-methionyl-leucyl-phenylalanine (FMLP) from a mean of 19.86 (SEM 1.35) to 8.46 (0.68) cells.field-1 after 4 weeks of therapy. There was also a significant reduction in fibronectin degradation both by resting and FMLP-stimulated neutrophils, from a mean of 1.90 (0.19) micrograms x 3 x 10(5) cells at the start of therapy to 0.87 (0.08) micrograms after 4 weeks, and from 3.17 (0.35) micrograms to 1.48 (0.05) micrograms, respectively. There was no effect on spontaneous or stimulated superoxide anion generation by neutrophils. Despite the marked changes in peripheral neutrophil function, no adverse effect was observed on viable bacterial load in the bronchial secretions. In addition, there was no difference in sputum albumin, elastase or myeloperoxidase levels, and only minor changes in the chemotactic activity of the sputum. These results suggest that nonsteroidal anti-inflammatory agents have a major effect on peripheral neutrophil function but do not appear to have an adverse effect on bacterial colonization of the airways.

Adult↗
PubMed1994

Sputum and serum pharmacokinetics of loracarbef (LY163892) in patients with chronic bronchial sepsis.

Sputum and serum pharmacokinetics of loracarbef (LY163892) were performed in 19 patients with purulent bronchiectasis. Nine of the patients received 200 mg twice daily and ten patients, 400 mg twice daily, for a total of 14 days. beta-Lactamase activity was measurable in the lung secretions of all 19 patients at the start of therapy. Mean peak serum concentrations of 11.7 mg/L (S.E.M. 1.7) were recorded at 1 h after administration of 200 mg doses on day 2 of therapy and were 18.5 mg/L (S.E.M. 1.9) at 1.5 h in the 400 mg group. Loracarbef was shown to penetrate lung secretions even in the presence of beta-lactamase activity. Mean peak sputum concentrations were achieved between 2 and 4 h following dosing and were 0.2 mg/L (S.E.M. 0.05) in the 200 mg group and 0.4 mg/L (S.E.M. 0.08) in the 400 mg group. On days 7 and 14 of therapy, sputum loracarbef concentrations were similar 4 h after the morning dose (0.23 mg/L following 200 mg; 0.35 mg/L after 400 mg). These concentrations were approximately 2% of the peak serum concentration and penetration into lung secretions is similar to other beta-lactams.

Adult↗
PubMed1993

Cochlear damage in guinea pigs following contralateral sound stimulation with and without gentamicin.

The effect of a minimally damaging sound exposure and a sub-ototoxic dose of gentamicin on cochlear hair cells contralateral to the sound exposure was evaluated. The cochleae of pigmented guinea pigs exposed to an 8 kHz pure tone at 116 dB SPL for 1 h and/or 50 mg/kg/day of gentamicin for 10 consecutive days and repeated after an interval of 3 weeks, were used for this purpose. Hair cell loss was found to have occurred in the contralateral cochleae following the sound exposure alone. The occurrence of potentiation, synergism and differential synergism between the agents in the contralateral ears was also seen. Possible explanations for these phenomena are proposed.

Acoustic Stimulation↗
PubMed1991

Interaction between sound and gentamicin: immediate threshold and stereociliary changes.

Our aim was to determine whether the immediate effects of a just-damaging sound exposure (8 kHz at 116 dB SPL for 1 h) might be potentiated by a single sub-ototoxic dose of gentamicin (50 mg kg-1). Auditory brainstem responses in pigmented guinea pigs were measured before and after treatment and used to calculate threshold shift (TS). Histological disturbances to sensory hair cells were assessed by scanning electron microscopy. All experimental ears excepting the gentamicin only group showed TS and histological changes. The largest TSs occurred at half an octave above the exposure frequency, and were greatest in the gentamicin + sound (G + S) group. First row outer hair cells showed most histological disturbances, followed by inner hair cells. The severest histological damage occurred at the exposure frequency and basally from it, the G + S group being most affected. Generally, there was good correlation between the severity of TS and histological damage. Results from both analyses indicated greater changes with gentamicin present.

Acoustic Stimulation↗
PubMed1989

A comparison of initial and permanent surface changes to guinea pig hair cells after acoustic overstimulation.

Groups of pigmented guinea pigs were exposed unilaterally to a 15 kHz pure tone at 133 dB SPL for 7.5 min. The inner ears of one group were examined by light microscopy to count damaged hair cells 3 weeks after exposure. Four other groups were investigated using scanning electron microscopy to assess the progression of initial surface changes after sound exposure. Hair cells were examined at 0, 10 and 30 min and compared with those seen at 3 weeks. Drastic stereociliary disturbances were present immediately after this short sound stimulation. Changes initially affected the first row of outer hair cells, followed by the inner hair cell row, and then spread to all rows at the centre of a damaged area. These changes appeared more advanced in specimens from the later groups. At 3 weeks, primarily phalangeal scars were seen at the main damaged area, with partially degenerating cells at the periphery. The latter still showed stereociliary disturbances, but the types predominating were different from those seen initially. However, no differences were found in the extens of damage when the various exposure groups were compared. No changes due to overstimulation were present in the contralateral ears.

Acoustic Stimulation↗
PubMed1987

Comparison of various short noise exposures in albino and pigmented guinea pigs.

Albino and pigmented guinea pigs were exposed to 20 kHz at 120 dB SPL for exposure durations of 30, 7.5, 6.5, 5 and 3.25 min. In a second series of experiments, the two shortest exposures were repeated after an interval of 6 or 24 h. Sensory hair cell loss was assessed 3 weeks post-exposure by surface preparations and quantified as percentage cell loss per segment per row, total numbers of outer and inner hair cells lost and the area of total outer hair cell damage. A variable but discrete area of damage resulted from these exposures. The main differences between the two strains were that in albino guinea pigs fewer ears were damaged after the shortest single exposures and generally more damage occurred after repeated exposures. However, no differences were detected in either strain when the interval between repeated exposures was changed.

Animals↗
PubMed1984

The effects of short noise exposures in the guinea pig.

Guinea pigs have been exposed to 20 kHz at 120 dB SPL for exposure durations of 7.5, 6.5, 5.0, and 3.25-min and killed either 3 or 12 weeks post-exposure. One series of guinea pigs exposed for 30-min had cochlear potentials recorded 3 weeks post-exposure. The damage was assessed by surface preparations and quantified as percentage hair cell loss per segment in every row, total number of outer, and inner hair cells missing and the area of total outer hair cell damage. A significantly smaller number of ears were found to be damaged after the shortest exposures, but no significant differences could be detected in the amounts of damage when all the series were compared. Myelinated nerve fibre degeneration had increased after the longer post-exposure interval, but no such differences were observed in the sensory hair cell degeneration.

Animals↗
PubMed1984

Sensory hair cell damage from high frequency noise exposure.

Fifteen guinea pigs were exposed to the noise of an 'ultrasonic' cleaning bath which gave maximum airborne radiation at 12.5 kHz amounting to 104 dB SPL in the one-third octave band. The animals were exposed for 2.5, 8 or 16 h and killed either 4 or 8 weeks after exposure, following which any damaged sensory hair cells were quantified. One third of the cochleae showed no sign of damage, but one animal had quite severe, scattered hair cell loss throughout both cochleae. The remainder showed some scattered hair cell loss, but only in the basal turn. Great variation was found in the damage to the cochleae of the exposed animals.

Animals↗
PubMed1981

Acoustic trauma effects with varying exposure times.

Guinea pigs have been exposed to 20 kHz for 2 h, 1 h, 30 min, 15 min, or 7.5 min, and the resultant damage was observed 3, 6, and 12 weeks post exposure. The areas of outer hair cell damage were statistically compared. Significant differences were obtained after a 3-week survival time with the shorter exposure times, but this difference was no longer apparent after 12 weeks. Myelinated nerve fibre and inner hair cell damage occurred only with total outer hair cell loss.

Animals↗
PubMed1979

Acoustic trauma effects from doubling the exposure time.

Guinea pigs were exposed to 20 kHz for a period of 1 or 2 h, with and without an intermediate recovery period. Statistically smaller areas of damage were obtained after doubling the exposure time, especially without a recovery period. For a double exposure with a recovery period the areas of damage were the same as for the single exposures.

Animals↗
PubMed1978

Acoustic trauma effects from doubling the exposure time.

Guinea pigs were used to test acoustic trauma effects from doubling the exposure time. Previously, two frequencies (20 kHz and 4 kHz) were used in conjunction with each other (ie double exposure) to see whether a prior exposure of the cochlea to one frequency would alter the extent of damage caused by a secondary frequency, when compared with damage caused by either frequency alone. A reduced area of damage was attained after double exposures. To complete the series, the same two frequencies were used separately, but the exposure time was doubled. The results from the 20 kHz series surprisingly indicated that a reduced area of damage was obtained after doubling the exposure time. No significant differences were found in the 4 kHz series.

Acoustic Stimulation↗
PubMed1975

Insect immunity. 11. Simultaneous induction of antibacterial activity and selection synthesis of some hemolymph proteins in diapausing pupae of Hyalophora cecropia and Samia cynthia.

We have previously shown that pupae of the giant silkmoth Samia cynthia have a humoral antibacterial activity, which was induced by viable, nonpathogenic gram-negative bacteria (H.G. Boman et al., 1974). We show here that this activity was formed simultaneously with a selective incorporation of amino acids into eight polypeptide chains characterized by their electrophoretic behavior. If actinomycin D or cycloheximide were given at an early time, no antibacterial activity was found. If the inhibitors were given at the time of maximum activity, there was no effect with actinomycin D but a rapid decrease of the activity in the case of cycloheximide. The results imply that the messenger ribonucleic acid was stable, but that at least one protein component was turning over. Hemolymph from immunized pupae of another giant silkmoth, Hyalophora cecropia, was fractionated by ammonium sulfate precipitation. This procedure, together with the isotope distribution after co-electrophoresis in polyarylamide gels, was used for comparing the response to injury and to different infections. Almost identical polypeptide patterns were obtained as a response to an infection with either viable Enterobacter cloacae or Bacillus subtilis. These patterns differed both qualitatively and quantitatively from the injury effect created by an injection as such. There was only a low antibacterial activity in each of the four fractions obtained by ammonium sulfate precipitation. However, a combination of three fractions restored a high killing activity. Fractionation of hemolymph from untreated pupae provided evidence for at least one preexisting factor which stimulated the killing of Escherichia coli. The osmotic pressure of the bacteria contributed to the antibacterial activity towards E. coli, but not towards B. subtitlis. The killing of E. coli was inhibited by liped A and, to a lesser extent, by an inhibitor of proteolytic enzymes. The similarities and differences with the mammalian complement system are discussed.

Animals↗