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Biomedical subjects

D R Baldwin

Publications and source records attributed to D R Baldwin.

At least 55 records · Page 3Linked to original sources
PubMed1992

Quantitative morphology and water distribution of bronchial biopsy samples.

BACKGROUND: An approach to the study of the pharmacokinetics of drugs in the lung is to measure their concentrations in bronchial biopsy specimens. The main criticism of this technique is that bronchial biopsy specimens consist of more than one tissue type and that drugs are often not distributed evenly. The morphology of bronchial biopsy specimens and the distribution of water between the extracellular and the intracellular compartments is therefore important. METHODS: Fifteen subjects undergoing fibreoptic bronchoscopy each had four bronchial biopsy samples taken. Thirty sections from 10 patients were examined and the proportion of tissue types noted, a morphometric analysis computer being used. The water distribution was investigated in the other biopsy specimens with radiolabelled markers. RESULTS: There was pronounced variation in the relative proportions of tissue types. Ciliated epithelium occupied a mean of 22.3% of the biopsy sample, submucosa 53.4%, muscle 17.6%, and glandular tissue 7.0%. There were no differences between second and the fourth generation subcarinae and macroscopic normality of the mucosa was a good predictor of histological normality. The extracellular water content was 40% of the total weight of the specimen and the total water content was 70%. CONCLUSIONS: These data provide the basis for pharmacokinetic study of drugs in bronchial mucosa. They show for pharmacokinetic study that macroscopically normal mucosa may be assumed to be histologically normal; that multiple biopsy specimens should be taken for any study, as there is considerable variation in the proportion of tissue types; that specimens from second and fourth generation subcarinae are the same; and that extracellular water contributes 40% to the total weight of the biopsy specimen.

Biopsy↗
PubMed1992

The distribution of temafloxacin in bronchial epithelial lining fluid, alveolar macrophages and bronchial mucosa.

The concentrations of temafloxacin, a new fluoroquinolone antimicrobial, in the potential sites of pulmonary infection were assessed by fibreoptic bronchoscopy with bronchoalveolar lavage. Fourteen patients received a course of temafloxacin, 600 mg twice daily, for three days prior to sampling. The mean serum concentration was 9.6 (SEM 1.2) mg.l-1, compared with 14.9(SEM 1.8) mg.kg-1 for bronchial mucosa, 26.5 (SEM 3.6) mg.l-1 for epithelial lining fluid and 83.0 (SEM 11.5) mg.l-1 for alveolar macrophage. In the ten patients who completed the protocol, site concentrations correlated well with serum concentrations. Temafloxacin was concentrated in each of the potential sites of infection examined and is, therefore, a promising new agent for the treatment of respiratory tract infection.

Anti-Infective Agents↗
PubMed1992

The effect of amiloride on the airway response to metabisulphite in asthma: a negative report.

Frusemide, a loop diuretic, has been shown to potently inhibit several indirect bronchoconstrictor challenges in asthma. The mechanism by which nebulized frusemide protects against indirect bronchoconstrictor stimuli in asthma is not known. One mechanism could be related to inhibition of sodium transport. If this is the case, then amiloride, another inhibitor of sodium transport, should also protect against indirect bronchoconstrictor challenges. Ten subjects with mild asthma were administered either 10(-2) M amiloride or placebo, by nebulizer, in a double-blind crossover fashion. After each inhalation, forced expiratory volume in one second (FEV1) was recorded at 10 min intervals for 30 min, after which a metabisulphite challenge was performed. No significant difference in the response to metabisulphite was seen between placebo and amiloride treatment. The mean difference in provocative dose of metabisulphite producing a 20% fall in FEV1 (PD20) between placebo and amiloride was 1.015 doubling doses, 95% confidence interval (95% CI) -0.201 to 2.231, (p = 0.09). This result does not support the hypothesis that frusemide is acting to protect against bronchoconstrictor challenges in asthma by an effect on sodium transport.

Administration, Inhalation↗
PubMed1991

Theophylline analysis at the chest clinic--comparison of a portable versus conventional system.

The running cost and clinical application of a new, portable, direct-injection, high-performance, liquid chromatograph for the measurement of theophylline was compared with conventional laboratory-based analysis by studying the two methods in two parallel chest clinics. Thirty-six patients were managed with the portable method and 33 by the conventional system. They were already receiving theophylline preparations for treatment of their asthma or chronic airflow limitation. Over the 12-week period of study, the percentage of patients with levels in the therapeutic range rose from 33% to approximately 87% in both clinics, but this change was achieved in only 6 weeks using the portable system. Patients whose theophylline levels were increased into the therapeutic range had improved symptom scores as measured by visual analogue scales but we were unable to demonstrate any significant change in spirometry. The cost of the portable system compared favourably with laboratory analysis, and had the additional benefit of quicker detection of non-compliance and facility for discussion with the patients at the time of consultation.

Adult↗
PubMed1991

The penetration of cefpirome into the potential sites of pulmonary infection.

The concentrations of cefpirome, a new semi-synthetic cephalosporin, in the bronchial mucosa and serum were assessed after a single 1 g intravenous dose in 37 patients. Bronchoalveolar lavage allowed epithelial lining fluid (ELF) concentrations to be measured in eight subjects. The mean concentration for serum was 34.5 mg/L (S.E.M. 3.3), for bronchial mucosa 19.3 mg/kg (S.E.M. 1.9) and for ELF 7.2 mg/L (S.E.M. 1.1). The progressive reduction in cefpirome concentration in serum compared to that in bronchial mucosa and ELF is consistent with the permeability characteristics of beta-lactam antimicrobials and the barriers to movement of antimicrobial agents present in the lung.

Adult↗
PubMed1991

In-vitro activity and beta-lactamase stability of SR 44337, a new long acting cephalosporin.

The in-vitro activity of SR 44337 was compared with that of other broad-spectrum parenteral cephalosporins, plus imipenem and co-amoxiclav. SR 44337 showed good activity against the Enterobacteriaceae, with MIC90s of less than 0.5 mg/L against all species tested, with the exception of Citrobacter spp. (MIC90 2 mg/L) and Serratia spp. (MIC90 4 mg/L). Of the agents tested, only ceftriaxone showed consistently greater activity against this family of organisms. SR 44337 had higher activity than ceftriaxone against Acinetobacter spp. and Pseudomonas aeruginosa, and was the most active agent tested against Neisseria meningitidis (MIC90 0.004 mg/L). All strains of N. gonorrhoeae, Haemophilus influenzae and the streptococci (excluding the enterococci) were susceptible to less than or equal to 0.25 mg/L of SR 44337, which was also the most active cephalosporin tested against Staphylococcus aureus. SR 44337 was stable to hydrolysis by the TEM-1, SHV-1 and P99 beta-lactamases, and was more stable than ceftriaxone to the K-1 beta-lactamase.

Amoxicillin↗
PubMed1991

Comparative pharmacokinetic disposition of fluoroquinolones in the lung.

The problems associated with the study of the penetration of quinolones into the respiratory tract are discussed. New techniques allow the study of the penetration of these agents into bronchial mucosa, alveolar macrophages and epithelial lining fluid. In general quinolones are concentrated in bronchial mucosa approximately 1.5 times compared with serum. In alveolar macrophages, the agents are concentrated 14- to 18-fold compared with serum and the ratio of alveolar macrophage levels to those in epithelial lining fluid are 7.7 to 5.7:1. The concentrations of temafloxacin and ciprofloxacin in these sites suggests that these agents will be efficacious in the therapy of respiratory infections caused by Streptococcus pneumoniae.

Administration, Oral↗
PubMed1991

Microlavage: a technique for determining the volume of epithelial lining fluid.

A new technique ("microlavage") was used to determine the volume of epithelial lining fluid recovered by bronchoalveolar lavage. A standard bronchial brush tube is used to lavage a peripheral lung subsegment rapidly with 20 ml of normal saline and the concentrations of urea and total protein are measured in the aspirated fluid. Using a very short dwell time for fluid (less than 20 seconds), this technique allows the urea dilution method to be used to quantify the epithelial lining fluid protein concentration, which is then used as an endogenous marker of the epithelial lining fluid in conventional bronchoalveolar lavage fluid. The reproducibility of the calculation of the concentration of the lining fluid protein was assessed in 10 patients by performing the method in three separate lung subsegments. The mean coefficient of variation of the urea to protein ratio was 9.0%. A comparison of microlavage and conventional lavage was made in a further 28 patients. The differential cell counts were similar by the two methods, suggesting that similar epithelial lining fluid was sampled. The application of the microlavage technique to the calculation of epithelial lining fluid volume gave a lower value than the urea dilution method in association with conventional lavage. Microlavage should provide more accurate quantification of epithelial lining fluid volume and could be used in conjunction with conventional lavage, which is still required for an adequate harvest of alveolar cells.

Aged↗
PubMed1991

Bone collagen, mineral and trace element composition, histomorphometry and urinary hydroxyproline excretion in chronically-treated alcohol-fed rats.

(1) We examined the possibility that enhanced fragility of the bony skeleton in alcohol abusers may be a consequence of a reduction in collagen composition. Male rats were fed a liquid diet containing 36% of total calories as ethanol; controls were pair-fed iso-caloric glucose. At 3, 7 and 14 days of treatment, collagen contents of tibia were unaltered, but small and significant reductions (15-30%) were observed at 28 and 42 days of treatment. Urinary hydroxyproline excretion was increased by 40-60% at 42 days of treatment, suggesting enhanced collagen degradation. (2) Bones of rats treated with ethanol for 42 days had significantly reduced mineral content (approximately 20%) with accompanying reductions in phosphate, calcium, copper and magnesium, but not sodium or potassium. Water content was unaltered, but tibial zinc and iron were increased by approximately 15%. (3) Histomorphometric analysis of bones taken at 42 days showed significant reductions in cortical bone thickness of lower tibia (by 28%). The thickness of the upper cortices and cancellous bone of the tibia was unaffected. Reductions in trabecular bone volume (approx. 25%) did not achieve statistical significance. (4) These observations are consistent with the known enhanced fragility of bones in alcoholic rats. The regional susceptibility of the tibia may be related to reduced load bearing as a result of muscle atrophy.

Alcohol Drinking↗
PubMed1990

Concentrations of temafloxacin in serum and bronchial mucosa.

The bronchial mucosal concentrations of temafloxacin hydrochloride were determined in specimens obtained at fibreoptic bronchoscopy and compared with simultaneous serum concentrations. The 18 patients studied were given an oral dose of 400 mg b.i.d for three days to achieve steady state levels. The mean serum concentration was 6.9 mg/l (SD 2.5 mg/l) and the mean bronchial mucosal concentration 12.2 mg/kg (SD 4 mg/kg). The mucosal levels exceeded those required to inhibit most of the common respiratory pathogens, including Streptococcus pneumoniae and Pseudomonas aeruginosa. These data support the use of temafloxacin for therapy of bronchial infections.

4-Quinolones↗
PubMed1990

Cefepime concentrations in bronchial mucosa and serum following a single 2 gram intravenous dose.

The concentrations of cefepime in bronchial mucosa were measured after intravenous administration of a single 2 g dose in 20 patients undergoing diagnostic fibreoptic bronchoscopy. These concentrations were compared with simultaneous serum concentrations. The mean bronchial mucosal concentration was 24.1 mg/kg (s.d. 17.8 mg/kg) and the mean serum concentration was 40.4 mg/l (s.d. 28.1 mg/l). The mean percentage penetration was 59.8% (s.d. 12.5%). We conclude that a twice daily dosing of cefepime would be adequate for most respiratory infections although an 8-hourly dose may be necessary in pseudomonal infections.

Biological Assay↗
PubMed1990

Concentrations of oral lomefloxacin in serum and bronchial mucosa.

The bronchial mucosal concentrations of lomefloxacin were determined for specimens obtained by fiber-optic bronchoscopy and compared with simultaneous concentrations in serum. The 23 patients studied were given an oral dose of 400 mg once daily for 4 days to achieve steady-state levels. The median concentration in serum was 2.5 micrograms/ml (range, 1.0 to 5 micrograms/ml), and the median bronchial mucosal concentration was 5.0 micrograms/g (range, 0.7 to 18.6 micrograms/g). The median percent penetration was 177% (range, 69 to 541%). The concentrations in serum and mucosa exceeded the MIC for 90% of strains of organisms causing bronchial infections but not sufficiently to recommend lomefloxacin for the routine treatment of pneumococcal infections.

4-Quinolones↗
PubMed1990

Changes in hospital management of acute severe asthma by thoracic and general physicians in Birmingham and Manchester during 1978 and 1985.

Hospital management of acute severe asthma in 14 large hospitals in Birmingham and Manchester was audited in a random 20% of 1196 patients aged 15-45 years admitted in 1985. Of the 239 admissions randomised, 192 were suitable for study. Results were compared with those from a study in the same hospitals using the same methods in 1978. The age and sex of the patients and their smoking history, duration of asthma, and hospital attendance were similar in 1978 and 1985. A much smaller proportion of patients presented with symptoms of over seven days' duration in 1985 (8.5%) than in 1978 (26%). The inpatient management of asthma appears to have improved in both thoracic and general units, with more thorough functional assessments, more frequent performance of relevant investigations (arterial blood gases and peak expiratory flow rates) and more frequent use of recommended treatment (nebulised bronchodilators, oral and intravenous corticosteroids). Less difference was found in 1985 between units with a specialist thoracic interest and those without, though some differences remained in 1985 in monitoring of peak expiratory flow rate and arterial blood gases, outpatient prescribing, and follow up arrangements. Inhaled preventive medication was prescribed more frequently than in 1978. In 1985 there was a 56% increase in admissions for asthma. The proportion of severely ill patients was similar to that in 1978, but in the most severe functional grade mean arterial carbon dioxide tension was higher in 1985 and more patients were ventilated. Our results suggest that hospital management by thoracic and general physicians has improved over the period 1978-85. Patients presented earlier in 1985, though there seems to have been an increase in asthma of all grades of severity.

Adolescent↗
PubMed1990

Azithromycin concentrations at the sites of pulmonary infection.

Azithromycin is a new macrolide antimicrobial. The distribution to the potential sites of pulmonary infection was assessed after the administration of a single 500 mg oral dose to 22 patients undergoing fibreoptic bronchoscopy. Concentrations of azithromycin in sputum, bronchial mucosa, eptihelial lining fluid (ELF) and alveolar macrophages (AM) were determined at intervals up to 96 h after dosing. The mean serum concentration was low at 12 h (0.13 micrograms.ml-1, SEM 0.05) but was still detectable at 96 h (0.01 micrograms.ml-1). In contrast, peak sputum ELF, bronchial mucosal and AM levels were found at 48 h. Bronchial mucosal concentrations were significantly greater than ELF concentrations, which were in turn greater than sputum concentrations. Mean peak AM concentrations were sixfold greater than bronchial mucosal concentrations (23 micrograms.ml-1, SEM 5.1 and 3.89 micrograms.ml-1, SEM 1.2, respectively). The high intracellular concentrations indicate that azithromycin is likely to be effective for sensitive intracellular pathogens and the favourable penetration into sputum, ELF and bronchial mucosa suggest that it should be useful in pneumonia and bronchial infections.

Azithromycin↗
PubMedDate not supplied

Management of intravenous hazardous materials and hazardous wastes in the work environment.

Exposure to hazardous materials and hazardous wastes has become a critical issue. There is now a greater awareness of the potential health risks associated with these substances. Because intravenous nurses encounter hazardous substances on a daily basis, they must adhere to appropriate precautionary measures. Mandatory compliance, however, is not enough. The I.V. nurse needs to understand the rationale for these measures and the basis for the federal and professional regulations regarding the handling of hazardous materials and wastes. This article focuses on the definitions of hazardous substances, the regulations governing these substances, and the principles concerning the handling and disposal of hazardous materials in the practice setting.

Hazardous Substances↗