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Biomedical subjects

D Honeybourne

Publications and source records attributed to D Honeybourne.

At least 37 records · Page 2Linked to original sources

A study to investigate the ability of subjects with chronic lung diseases to activate the roadside Lion Alcolmeter SL-400.

The Lion Alcolmeter SL-2 is widely used for road-side breath-testing by police in the UK. However, some individuals with lung diseases have difficulty in activating the device. This study describes an investigation that we have carried out on a new device called the Lion Alcolmeter SL-400 which has recently been introduced into use by police forces in the UK. The manufacturers state that the machine requires a minimum continuous expiratory flow rate of 25 litres per minute and a minimum expired volume of 1.5 litres, after which a breath sample is automatically taken and analysed. Our study was designed to investigate the ability of subjects with a variety of lung diseases to activate this device. The 40 adult subjects investigated consisted of 10 normal controls, 10 with asthma, 10 with chronic obstructive pulmonary disease and 10 with restrictive lung disease. After baseline lung function tests were performed, the subjects were then given alcohol to drink, the amount of which was based upon their body weight. After a gap of at least 20 minutes, the subjects were then asked to attempt up to three blows into the Alcolmeter. Our results showed that three asthmatic subjects, four with chronic obstructive pulmonary disease and two with restrictive lung disease, failed to successfully activate the device even after three attempts. All of the subjects who failed to activate the device had an expired breath volume of more than 1.5 litres, but seven out of these nine subjects had a Forced Expiratory Volume (FEV1) of less than 1.1 litres. In conclusion, this study has shown that some subjects with lung diseases may have difficulty in activating the SL-400 roadside alcolmeter device.

Adult↗

Chlamydia pneumoniae infection and ethnic origin.

OBJECTIVES: To test the association of Chlamydia pneumoniae infection with ethnic origin. DESIGN: A prospective study by micro-immunofluorescence of antibodies to C. pneumoniae in patients admitted to one hospital with a variety of non-pulmonary, non-cardiovascular disorders. SETTING: A large district general hospital serving a multi-ethnic inner-city population in Birmingham, UK. SUBJECTS: There were 1518 patients, 1061 of whom were Caucasian, 290 Asian and 167 Afro-Caribbean. Each of 169 Asians and 141 Afro-Caribbeans was matched with two Caucasians for age, sex, smoking habit, steroid medication and date of admission, and logistic regression methods were used to compare the effects on C. pneumoniae antibody levels of ethnic origin, these confounding variables, diabetes mellitus and social deprivation. OUTCOME MEASURES: Serological evidence of acute C. pneumoniae infection or reinfection (defined by titres of IgM > or = 8, a four-fold rise in IgG or IgG > or = 512) and previous infection (IgG 64-256 or IgA > or = 8). RESULTS: Results showed 4.8% of Caucasians, 6.6% of Asians and 10.2% of Afro-Caribbeans had antibody titres suggesting acute (re)infection; and 11.2% of Caucasians, 13.4% of Asians and 21.0% of Afro-Caribbeans had titres suggesting previous infection. On chi 2 analysis, the distributions of the three possible serological outcomes (acute, previous and no infection) differed significantly (p < 0.05) between the Afro-Caribbean and Caucasian groups, but not between Asians and Caucasians or between Afro-Caribbeans and Asians. After adjusting for possible confounding variables, odds ratios for Afro-Caribbean versus Caucasian origin were 5.5 (95% confidence intervals 2.0-15.0) for acute (re)infection and 1.9 (1.0-3.7) for previous infection. CONCLUSIONS: Our results suggest that C. pneumoniae infection may be more prevalent among Afro-Caribbean than among Caucasian people, and that Asians may lie somewhere between them in this respect. The behaviour of this pathogen in different ethnic groups deserves further investigation. Future studies of this organism should give due attention to the ethnic origins of patients.

Adolescent↗

Chlamydia pneumoniae and asthma.

BACKGROUND: This study was designed to test the association of Chlamydia pneumoniae infection with asthma in a multi-racial population, after adjustments for several potential confounding variables. METHODS: Antibodies to C pneumoniae were measured by microimmunofluorescence in 123 patients with acute asthma, 1518 control subjects admitted to the same hospital with various non-cardiovascular, non-pulmonary disorders, and 46 patients with severe chronic asthma, including some with "brittle" asthma. Acute infection or reinfection was defined by titres of IgG of > or = 512 or IgM > or = 8 or a fourfold rise in IgG, and previous infection by IgG 64-256 or IgA > or = 8. Logistic regression was used to control for likely confounders, including ethnic origin, age, sex, smoking habit, steroid medication, diabetes mellitus and social deprivation, on antibody levels. RESULTS: Antibody titres consistent with acute C pneumoniae infection were found in 5.7% of patients with acute asthma and 5.7% of control patients, while 14.6% of patients with acute asthma and 12.7% of control patients had titres suggesting previous infection. These two groups did not differ significantly. However, titres suggesting previous infection were found in 34.8% of patients with severe chronic asthma: the difference between this group and the control group was statistically significant with an adjusted odds ratio of 3.99 (95% confidence interval 1.60 to 9.97). CONCLUSIONS: These data raise important questions about the previously demonstrated association of C pneumoniae infection with asthma, and suggest that future studies of this association should give particular attention to the presence or absence of a history of severe chronic asthma.

Acute Disease↗

Differences in asthma management between white European and Indian subcontinent ethnic groups living in socioeconomically deprived areas in the Birmingham (UK) conurbation.

BACKGROUND: Hospital admission rates for asthma have been higher for Asian (Indian subcontinent, ISC) ethnic minority groups in the UK than for white Europeans (W/E). As this may in part be due to differences in the uptake or delivery of preventative health care strategies, the extent to which targeted education and treatment programmes reach these groups needs to be determined. METHODS: Six hundred and eighty nine asthmatic subjects (345 W/E, 344 ISC) of mean (SD) age 34.5 (15) years (range 11-59) and mean forced expiratory volume in one second (FEV1) 80% predicted from districts of high ethnicity and socioeconomic deprivation within inner city Birmingham were reviewed in the appropriate dialect (English, Punjabi, Hindi, Urdu) in a community based study. RESULTS: Data adjusted for age and analysed separately for men (M) and women (F) showed no significant differences in the numbers reporting previous asthma education, assessment of delivery techniques, or being taught about medications, but there were significant differences for advice on trigger factors (M: 52% vs 42%; F: 56% vs 42%), recognition of symptoms (M: 51% vs 43%; F: 53% vs 33%), and ownership of peak flow meters (M: 35% vs 22%; F: 36% vs 24%) for W/E and ISC groups, respectively. Anti-inflammatory asthma medications were highly prescribed, but self reported drug compliance (M: 73% vs 62%), understanding medications (F: 59% vs 39%), and self management (F: 23% vs 12%) varied significantly. Asthma follow up in the community was low for both groups with more of the ISC subjects also being followed up by hospital. CONCLUSIONS: The management of both ethnic groups has centred on drug prescription, delivery techniques and compliance, but has been deficient, particularly in the ISC group, in developing understanding of the disease and self management.

Adult↗

Chlamydia pneumoniae antibodies in severe essential hypertension.

Several studies have implied an association between Chlamydia pneumoniae (C. pneumoniae) and cardiovascular disease. Our study was designed to determine whether this organism is associated with severe essential hypertension in a multiracial British population. Antibodies to C. pneumoniae were measured by microimmunofluorescence in 123 patients with chronic severe hypertension and 123 control subjects, matched for ethnic origin, age, sex, and smoking habit, admitted to the same hospital with various noncardiovascular, nonpulmonary disorders. Previous infection was defined by IgG 64 to 256, provided that there was no detectable IgM. Multiple regression analyses of matched and unmatched data were used to investigate the influences of antibody levels and potential confounding factors (ethnic origin, age, sex, smoking habit, diabetes mellitus, and social deprivation) on hypertension. A portion of the hypertensive patients underwent echocardiography, estimation of left ventricular mass index, and measurements of fibrinogen, D-dimer, and von Willebrand factor concentrations. Thirty-five percent of hypertensive patients and 17.9% of matched control subjects had antibody titers consistent with previous C. pneumoniae infection. The hypertensive patients differed significantly from their matched control subjects in their level of previous infection, with an odds ratio of 2.5 (95% confidence interval, 1.3 to 4.7). There were no significant differences in antibody levels between patients with left ventricular hypertrophy and those without it. Fibrinogen, D-dimer, and von Willebrand factor concentrations were not significantly associated with antibody levels. These data support an association of C. pneumoniae with severe essential hypertension. They provide no evidence of a predisposition to develop left ventricular hypertrophy in hypertensive patients with C. pneumoniae infection or of associations with hypercoagulability or endothelial dysfunction.

Antibodies, Bacterial↗

Chlamydia pneumoniae antibody titers are significantly associated with acute stroke and transient cerebral ischemia: the West Birmingham Stroke Project.

BACKGROUND AND PURPOSE: Several studies have implied an association between Chlamydia pneumoniae and atherosclerosis. Our research was designed to investigate the association of this organism with strokes and transient cerebral ischemia. METHODS: Antibodies to C pneumoniae were measured in 176 patients with stroke or transient cerebral ischemia and 1518 control subjects with noncardiovascular, nonpulmonary disorders. Acute infection or reinfection was defined by IgG > or =512 or IgM > or =8 or fourfold rise in IgG, and previous infection was defined by IgG 64 to 256 or IgA > or =8. Logistic regression was used to examine the influences of ethnic origin, age, sex, smoking habit, diabetes mellitus, steroid medication, and social deprivation on antibody levels. Some patients underwent CT and carotid ultrasound examinations and cholesterol, triglyceride, fibrinogen, and von Willebrand factor estimations. RESULTS: We found that 13.6% of stroke/transient ischemic attack (TIA) patients and 5.7% of control subjects had antibody titers suggesting acute C pneumoniae (re)infection, while 32.4% of stroke/TIA patients and 12.7% of control subjects had titers suggesting previous infection (P<.05). Stroke/TIA patients differed from control subjects in their levels of acute and previous infection, with adjusted odds ratios of 4.2 (95% CI, 2.5 to 7.1) and 4.4 (95% CI, 3.0 to 6.5), respectively. These did not differ notably between strokes resulting from major nonhemorrhagic infarcts, small-vessel infarcts, or hemorrhage. Cholesterol, triglyceride, fibrinogen, and von Willebrand factor concentrations showed no apparent association with titers. CONCLUSIONS: These data support the association of cerebral vascular disease with previous C pneumoniae infection and the association of stroke and transient cerebral ischemia with recrudescence of infection.

Adolescent↗

Concentrations of trovafloxacin in bronchial mucosa, epithelial lining fluid, alveolar macrophages and serum after administration of single or multiple oral doses to patients undergoing fibre-optic bronchoscopy.

Concentrations of trovafloxacin were measured in serum, alveolar macrophages, epithelial lining fluid and bronchial mucosa following single and multiple oral doses. Concentrations were determined using a microbiological assay method. There were 18 subjects in the single dose and nine subjects in the multiple dose groups. After single dosing, mean concentrations in serum, alveolar macrophages, epithelial lining fluid and bronchial mucosa at 6, 12 and 24 h were as follows: 6 h, 1.41 mg/L, 19.06 mg/L, 3.01 mg/L and 1.52 mg/kg; 12 h, 0.85 mg/L, 16.22 mg/L, 4.8 mg/L and 1.01 mg/kg; 24 h, 0.37 mg/L, 10.23 mg/L, 0.93 mg/L, and no measurable concentration, respectively. After multiple dosing (approximately 6 h post-dose) the corresponding concentrations were 1.47 mg/L, 34.3 mg/L, 10.21 mg/L and 1.67 mg/kg, respectively. These concentrations exceed the MIC90s for the common respiratory pathogens, Haemophilus influenzae 0.06 mg/L, Moraxella catarrhalis 0.008 mg/L and Streptococcus pneumoniae 0.12 mg/L and suggest that trovafloxacin should be efficacious in the treatment of community- and hospital-acquired respiratory infections.

Administration, Oral↗

Concentrations of levofloxacin (HR 355) in the respiratory tract following a single oral dose in patients undergoing fibre-optic bronchoscopy.

Concentrations of levofloxacin were measured in bronchial biopsies, alveolar macrophages (AM), epithelial lining fluid (ELF) and serum following a single oral dose. Concentrations were measured by a microbiological assay method. A total of 35 patients undergoing fibre-optic bronchoscopy were studied. Mean serum, AM, ELF and biopsy concentrations were as follows. 0.5 h: 4.73 mg/L, 19.1 mg/L, 4.74 mg/L and 4.3 mg/kg; 1 h: 6.6 mg/L, 32.5 mg/L, 10.8 mg/L and 8.3 mg/kg; 2 h: 4.9 mg/L, 41.9 mg/L, 9.0 mg/L and 6.5 mg/kg; 4 h: 4.1 mg/L, 27.7 mg/L, 10.9 mg/L and 6.0 mg/kg; and 6-8 h: 4.0 mg/L, 38.4 mg/L, 9.6 mg/L and 4.0 mg/kg respectively. Mean serum and AM concentrations at 12-24 h were 1.2 and 13.9 mg/L respectively (concentrations in biopsy and ELF were only measurable in three of the six patients). These concentrations exceed the MIC90s of the common respiratory pathogens, Haemophilus influenzae (0.015 mg/L), Moraxella catarrhalis (0.06 mg/L) and Streptococcus pneumoniae (1 mg/L) and suggest that levofloxacin should be efficacious in the treatment of community- and hospital-acquired respiratory infection.

Administration, Oral↗

Antibiotic penetration in the respiratory tract and implications for the selection of antimicrobial therapy.

There has been an increasing amount of information published recently about the ability of different antimicrobial agents to penetrate specific areas of the lung. Initially, whole lung concentrations were reported, but this methodology has been refined so that levels are now measured in potential sites of infection, such as the bronchial mucosa, epithelial lining fluid, and alveolar macrophages, as well as in sputum. Distinct differences in the ability to concentrate in these sites have been shown among beta-lactams, quinolones, and macrolides. Considerable intracellular concentration of quinolones and macrolides, but not beta-lactams, occurs. This intracellular accumulation has been used for the treatment of atypical mycobacteria. The potential effects of high antibiotic levels on cellular function have also been investigated. The clinical relevance of these findings for the choice of antimicrobial agent, dosage, formulation (eg, liposomal), and route of administration (eg, nebulized) are increasingly being explored.

4-Quinolones↗

An audit of bronchoscopy practice in the United Kingdom: a survey of adherence to national guidelines.

BACKGROUND: Both patient and staff safety are of major importance during the procedure of fibreoptic bronchoscopy. Patient safety depends partly on adequate disinfection of instruments and accessories used as well as careful monitoring during the procedure. Adequate facilities, manpower and training are also essential. Staff safety depends partly on adequate procedures to minimise any risks of sensitisation to agents such as glutaraldehyde. An audit was carried out of bronchoscopy procedures in hospitals in the UK and the findings were compared with published guidelines on good practice and clinical consensus. METHODS: A postal questionnaire was sent to 218 bronchoscopy units in the UK. Findings were then compared with published evidence of good practice in the areas of disinfection, including the use of glutaraldehyde, patient monitoring, manpower, facilities, and training. RESULTS: A 73% response rate was obtained. Recommended minimum disinfection times before and after routine bronchoscopies were not achieved by 35% of units. No disinfection was carried out in 34% of units before emergency bronchoscopies and in 19% of units after suspected cases of tuberculosis. Adequate rinsing of the bronchoscope with sterile or filtered water was not carried out by 43% of units. Contrary to recommendations, 31% of departments were still using glutaraldehyde in the patient examination room and inadequate room ventilation was common. Protective clothing was often not worn by staff during bronchoscopy. Inadequate intravenous access and use of supplementary oxygen were found in many units. Practice standards were higher in departments where dedicated bronchoscopy/endoscopy units of the hospital were used, and also where staff had been on external training courses. CONCLUSIONS: This audit has shown that many units do not adhere to guidelines on disinfection procedures and patient monitoring. Unnecessary potential risks due to staff exposure to glutaraldehyde were apparent. National guidelines on good practice are not being followed in areas which may potentially affect patient and staff safety.

Bacterial Infections↗

Distribution of cefdinir, a third generation cephalosporin antibiotic, in serum and pulmonary compartments.

The distribution of a new cephalosporin, cefdinir, in serum, epithelial lining fluid (ELF), bronchial mucosa and alveolar macrophages was studied in 17 adults following a single oral dose of 300 or 600 mg of cefdinir; tissue samples being obtained by diagnostic bronchoscopy approximately 4 h after this dose. Mucosal biopsies were taken, alveolar macrophages harvested by lavage, and ELF volume derived from urea concentrations in bronchial lavage fluid and blood. A microbiological assay for cefdinir was performed in serum, bronchial mucosa, ELF and alveolar macrophages. In patients taking 300 mg of cefdinir, the median concentrations of cefdinir were 2.00 mg/L (range 1.40-8.00) in serum, 0.78 mg/L (range 0-1.33) in bronchial mucosa, and 0.29 mg/L (range 0-4.73) in ELF. In patients taking 600 mg, the median concentrations were 4.20 mg/L (range 3.05-6.40) in serum, 1.14 mg/L (range 0-1.92) in bronchial mucosa, and 0.49 mg/L (range 0-0.59) in ELF. Cefdinir did not penetrate macrophages.

Administration, Oral↗

A review of the penetration of sparfloxacin into the lower respiratory tract and sinuses.

There are a number of potential sites of infection in the lower respiratory tract. This review summaries the nature of these sites and the ways in which antibiotic penetration can be studied. The results of a single-dose and a multiple-dose study of the penetration of sparfloxacin into the respiratory tract are also provided. After a single oral dose of sparfloxacin 400 mg or a 400 mg loading dose on day 1 followed by 200 mg daily for 2 days, sparfloxacin concentrations in the bronchial mucosa, epithelial lining fluid and alveolar macrophages were higher than the corresponding concentrations in serum. Compared with other fluoroquinolones, sparfloxacin achieves higher concentrations at these sites. Sparfloxacin diffusion into maxillary sinus mucosa has been studied in patients with chronic maxillary sinusitis undergoing surgery. High concentrations of sparfloxacin were detected in sinus mucosa 2 to 5 h after administration of a single dose of sparfloxacin 200 or 400 mg.

Anti-Infective Agents↗

Clinical aspects of Chlamydia pneumoniae infection.

This recently recognised member of the genus Chlamydia is one of the most widespread pathogens of man, though up to 90% of infected people have few or no symptoms. Several studies have estimated the population prevalence of antibodies to C. pneumoniae at 40-55% in the northern hemisphere, and over 60% in under-developed countries. The incidence of infections follows a cyclical pattern, with peaks at regular intervals of 2-10 years, but no apparent seasonal periodicity. Nosocomial transmission may be mediated by environmental surfaces as well as aerosols, and immunosuppression, for example by the human immunodeficiency virus, predisposes to infection. Chlamydia pneumoniae causes predominantly atypical pneumonia, often severe in adults, especially the elderly; including 5-10% of community-acquired pneumonia in Scandinavian countries. Serological evidence indicates associations with asthma, bronchitis, exacerbations of chronic airflow obstruction, otitis media and bronchiolitis. Several studies, using both serological and morbid anatomical techniques, also indicate associations with vascular atheroma and ischaemic heart disease, and with acute myocardial infarction. Chronic, latent and recurrent infections have been documented, and it is postulated that, like chronic or recurrent C. trachomatis infections, these may produce disease as a consequence of the host's immunological hypersensitivity. Several techniques are available for serological diagnosis: the technique of choice is micro-immunofluorescence, using fixed whole elementary or reticulate bodies as antigen, but antibody responses are highly variable. Traditional alternatives, antigen detection (by direct immunofluorescence or enzyme immunoassay) and cell culture, have major disadvantages. Polymerase chain reactions have not yet been widely applied to the clinical setting. tetracycline antibiotics, erythromycin and quinolones are not very efficacious in the treatment of C. pneumoniae infection. The azalide antibiotic, azithromycin, and the macrolide, clarithromycin, are active in vitro against C. pneumoniae, and may become treatments of choice. The development of anti-chlamydial vaccines remains an important research goal.

Adolescent↗

Concentrations of OPC-17116, a new fluoroquinolone antibacterial, in serum and lung compartments.

The efficacy of an antibiotic is usually predicted from serum concentration and MICs for likely pathogens, but in the lung, tissue concentrations may be more relevant. This study compares concentrations of a new fluoroquinolone, OPC-17116, in serum, epithelial lining fluid (ELF), alveolar macrophages and bronchial mucosa, in 24 adults. OPC-17116 400 mg was given daily for 4 days, and diagnostic bronchoscopy was performed up to 13 h after the final dose. Mucosal biopsies were taken from macroscopically normal sites, alveolar macrophages were harvested by lavage, and ELF volume was derived from urea concentrations in bronchial lavage fluid and blood. A microbiological assay, using Escherichia coli, was used to assay OPC-17116 concentration in serum, bronchial mucosa, ELF and alveolar macrophages. The mean concentration of OPC-17116 in serum was 1.2 mg/L. Serum concentrations were significantly exceeded in bronchial mucosa (mean ratio 3.13) in ELF (mean ratio 12.21) and in macrophages (mean ratio 194.52). Penetrations of these compartments considerably exceeded those reported for other fluoroquinolones, and concentrations in all tissues were substantially higher than previously reported MIC90 levels for a variety of bacteria, including Streptococcus pneumoniae. A clinical role for OPC-17116 is suggested in a wide range of respiratory infections, including those due to intracellular bacteria.

Adult↗

Determination of OPC-17116, a new fluoroquinolone, in human alveolar macrophages and other biological matrices by high performance liquid chromatography (HPLC).

A sensitive and reproducible high performance liquid chromatography (HPLC) assay was developed for the determination of cell-associated levels of the new fluoroquinolone antimicrobial agent, OPC-17116 (Otsuka Pharmaceutical Co. Ltd.). The assay consisted of a reverse phase C18 analytical column with fluorescence detection at 288 nm and was used to measure levels of OPC-17116 in the constituents of bronchoalveolar lavage (epithelial lining fluid and alveolar macrophages). Thus it was possible to measure drug concentration at specific sites in the respiratory tree. This is especially important because of differences that may exist between these levels and those found in serum. In addition, a good correlation was found between the HPLC assay and an established microbiological assay.

Anti-Infective Agents↗