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Biomedical subjects

E J Hiller

Publications and source records attributed to E J Hiller.

At least 19 recordsLinked to original sources

C-reactive protein is not a useful indicator of intermittent bacterial colonization in early lung disease of patients with cystic fibrosis.

C-reactive protein (CRP) is a general marker of the systemic inflammatory response to bacterial infection. Serial measurement of CRP is useful in monitoring respiratory exacerbations in patients with cystic fibrosis (CF) and chronic infection with Pseudomonas aeruginosa. We hypothesized that regular monitoring of CRP in young children with CF prior to colonization with P. aeruginosa might provide an objective guide to the need for antibiotic treatment. Twenty-two children were studied prospectively over a 6 month period. We measured CRP every 2 months and at the beginning and end of respiratory exacerbations. In samples taken when the children were well, median CRP was 0.45 microgram/mL compared with 1.92 micrograms/mL when they were symptomatic with positive culture results (P < 0.05). Despite this difference there was considerable overlap between CRP levels for infected and noninfected patients. A CRP value of > 1.82 micrograms/mL (the upper 95% confidence interval for a control group of well children without CF) had a sensitivity of 49% and a specificity of 83% in determining a symptomatic exacerbation. We conclude that in this group of patients CRP measurements were of little value in monitoring respiratory exacerbations in patients who become intermittently infected with either Haemophilus influenzae or Staphylococcus aureus.

Anti-Bacterial Agents↗

The chest radiograph in cystic fibrosis: a new scoring system compared with the Chrispin-Norman and Brasfield scores.

BACKGROUND: Scoring systems for the chest radiograph in cystic fibrosis are used to compare patients and different treatment regimens, and to monitor respiratory disease in individual patients. The Northern chest radiograph score was designed to allow one person to assess the radiological features of lung involvement in cystic fibrosis in as simple, rapid and equally reproducible manner as the established Chrispin and Norman, and Brasfield scoring systems. METHODS: Forty five chest radiographs were scored by 10 physicians with a special interest in cystic fibrosis according to the Brasfield and Northern methods, and by five pairs of physicians according to the Chrispin-Norman criteria. Three individuals and two pairs rescored the radiographs after an interval of 3-5 months. The Northern score was performed with and without a lateral view, using the original posteroanterior radiograph. RESULTS: The Northern score showed a better agreement between observers for the ranking of the radiographs. It was equally well related to respiratory function tests, the Shwachman-Kulczycki score of overall clinical status, and in its discrimination between different radiographs as the other two scoring systems. The Northern score performed equally well with or without a lateral film. CONCLUSIONS: The Northern system fulfils the requirements of a chest radiograph score more successfully than the Chrispin-Norman or Brasfield systems, and does not require a lateral film.

Cystic Fibrosis↗

IgG antibodies in early Pseudomonas aeruginosa infection in cystic fibrosis.

The relationship between IgG antibodies to Pseudomonas aeruginosa and its isolation from sputum was determined in 100 patients with cystic fibrosis observed at intervals of two months for a median period of one year. Only one patient had a raised antibody titre (greater than 22.9 ELISA units) before isolation of P aeruginosa. Initially 65 patients were antibody negative, of whom 48 were also culture negative. Of 24 patients with positive sputum culture and negative antibodies, seven became antibody positive at a median (range) 15 (6-25) months later. The remaining 17 patients continued antibody negative until the end of the study at a median range 15 (1-123) months after becoming culture positive. This latter group were younger and had more intermittently positive sputum cultures. In general positive IgG antibody titres do not predate isolation of P aeruginosa, but in some patients are present soon after acquisition of infection. A positive titre indicates significant exposure to P aeruginosa and could be used to detect infection in patients unable to produce sputum and possibly indicate the effect of early antipseudomonal treatment.

Adolescent↗

Aspergillosis.

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Antifungal Agents↗

C-reactive protein measured in dried blood spots from patients with cystic fibrosis.

There was no significant difference in C-reactive protein concentration determined in paired serum and eluates from dried blood spots collected on Guthrie cards; mean difference 0.6 microgram/ml (95% CI -3.3-2.2 micrograms/ml; n = 101). Dried blood spot samples were stable for up to 21 days and were unaffected by posting to the laboratory. In eight patients with cystic fibrosis undergoing specific antibiotic treatment for Pseudomonas aeruginosa pulmonary infection the fall in C-reactive protein concentration was not significantly different between serum and dried whole blood spot specimens. This method could be used to monitor infection and the response to antibiotic treatment.

Adolescent↗

Inflammatory markers in cystic fibrosis.

Plasma neutrophil elastase-alpha 1 antiproteinase complex, lactoferrin and C-reactive protein (CRP) were determined over a 15-month period in 26 patients with cystic fibrosis, of whom 21 were chronically infected with Pseudomonas aeruginosa. Median concentrations of both neutrophil products and CRP were greater in patients who were clinically stable than in healthy subjects without cystic fibrosis. CRP concentrations increased further at the onset of symptomatic exacerbations. Thirty-five courses of intravenous antibiotics and 22 courses of oral ciprofloxacin were reviewed and revealed similar improvements in clinical scores and lung function tests for both forms of treatment. Intravenous antibiotics reduced the plasma concentrations of both neutrophil products and CRP, while oral ciprofloxacin only significantly reduced the concentration of neutrophil elastase-alpha 1 antiproteinase complex. Plasma concentrations of inflammatory markers were significantly greater in exacerbations associated with fever and leukocytosis. Statistical modelling demonstrated negative within-patient relationships between lung function and both CRP and lactoferrin, and positive relationships between the three inflammatory markers. Neutrophil granule products and CRP reflect the pulmonary inflammatory state in cystic fibrosis and may be of value in monitoring treatment.

Adolescent↗

Plasma tumour necrosis factor alpha in cystic fibrosis.

Plasma tumour necrosis factor alpha (alpha) concentration is increased in acute Gram negative sepsis, but the effect of chronic infection on plasma concentrations is unknown. A study was carried out in patients with cystic fibrosis to determine the effect of chronic lung infection with Pseudomonas aeruginosa on the plasma concentration of tumour necrosis factor and two other indicators of the inflammatory response, circulating C reactive protein and neutrophil elastase-alpha 1 antiproteinase complex (elastase complex). The concentration of immunoreactive tumour necrosis factor in plasma was greater than the upper 95% confidence interval for healthy subjects (2.6 U/ml) on 129 out of 189 occasions in 14 patients observed for about a year. The increase in tumour necrosis factor was associated with increased circulating C reactive protein and elastase complex. Twelve patients with an exacerbation of respiratory symptoms were studied before and after two weeks' treatment with anti-pseudomonal antibiotics. All three indicators of the inflammatory response fell after treatment, though median tumour necrosis factor (4.8 U/ml) and elastase complex (0.41 microgram/ml) concentrations remained above the upper limits for healthy subjects. During a period of clinical stability plasma tumour necrosis factor was increased in 10 of the 12 patients, elastase complex was increased in 10 of the 12, and C reactive protein was increased in seven. Increased plasma immunoreactive tumour necrosis factor was a feature of the near continuous inflammatory response to chronic P aeruginosa infection in cystic fibrosis and may be a factor contributing to the progressive lung destruction seen in this disease.

Adolescent↗

Haemophilus infection in cystic fibrosis.

Twenty seven patients with cystic fibrosis under the age of 12 years and 27 matched patients with asthma were followed up in a prospective study for one year. The isolation rate of non-capsulated strains of Haemophilus influenzae from cough swabs and sputum specimens taken at routine clinic visits every two months was significantly greater in cystic fibrosis than in asthma. Haemophilus para-influenzae was equally common in both groups. During exacerbations the isolation rate of H influenzae in cystic fibrosis was significantly greater than at other times, whereas in asthma there was no significant difference. The distribution of biotypes of H influenzae and H parainfluenzae was similar in the two groups. In cystic fibrosis, biotype I was associated with exacerbations. Biotype V was more common than in previous studies, but was not associated with exacerbations.

Bacterial Typing Techniques↗

Nyctalopia and conjunctival xerosis indicating vitamin A deficiency in cystic fibrosis.

Thirty-one Cystic Fibrosis patients were investigated for clinical and biochemical evidence of Vitamin A deficiency. All had been prescribed oral pancreatic enzyme replacements and twice the recommended daily requirement of Vitamin A (5000IU). None were aware of any ocular symptoms, but 3 out of 31 (10 per cent) were found to have frank conjunctival xerosis and six (19 per cent) to have abnormal dark adaptation. There was no correlation between the above findings and abnormal liver function or clinical disease severity. All patients with cystic fibrosis should have regular Vitamin A estimations with ophthalmological assessment if serum levels fall below 30 microgram/dl.

Adolescent↗

Pseudomonas aeruginosa antibodies in blood spots from patients with cystic fibrosis.

The formation of antibodies to Pseudomonas aeruginosa may be the earliest indicator of pulmonary infection in patients with cystic fibrosis. To enable easy sampling in babies and young children an enzyme linked immunosorbent assay (ELISA) based on a blood spot sample taken on to blotting paper was developed. A sample of approximately 20 microliters of blood was required. A high correlation and level of absolute agreement was shown between paired finger prick and venepuncture blood spots, and between blood spot, serum spot, and serum samples. Healthy controls and non-infected patients with cystic fibrosis had low titres of antibody compared with patients with intermittent and chronic infection. The latter groups had significantly greater antibody titres than normal controls. This assay permits serial measurement of antibodies to P aeruginosa in patients of all ages with cystic fibrosis and may provide a means of assessing the value of such measurements in the detection and management of early infection.

Antibodies, Bacterial↗

Night blindness and conjunctival xerosis caused by vitamin A deficiency in patients with cystic fibrosis.

Forty three patients with cystic fibrosis, aged 8-44 years (median 16 years), were examined for evidence of vitamin A deficiency. Eight patients had abnormal dark adaptation tests and three had conjunctival xerosis. Serum vitamin A and retinol binding protein concentrations were significantly lower in the affected patients who were also more likely to have abnormal liver function tests. Five patients were treated with 100,000-200,000 IU water miscible vitamin A orally and their daily vitamin supplements were increased to maintain normal concentrations. In four patients dark adaptation tests were repeated. Three were normal, but one patient required three further doses of water miscible vitamin A and a daily supplement of 12,000 IU vitamin A before her dark adaptation threshold returned to normal. Adolescents with cystic fibrosis are liable to develop night blindness and conjunctival xerosis, particularly if they have liver disease or fail to take daily vitamin supplements.

Adolescent↗

Two minute walking distance in cystic fibrosis.

We have evaluated the 'two minute walking distance' in children with cystic fibrosis as an objective measurement of exercise tolerance. There was a strong correlation between walking distance and height in 89 normal children (r = 0.72). Fifty children with cystic fibrosis showed a similar correlation (r = 0.56) with a mean result of 94% of that expected for height compared with the normal children. There was a training effect in the normal children with the second walk being significantly better than the first, but this was not evident in children with cystic fibrosis. The test was reproducible with no significant change in 12 children retested after one to three months. Sixteen children with cystic fibrosis admitted for treatment of chest disease showed a significant improvement in walking distance with treatment. Children as young as 5 years old can perform a walking distance test. It seems to be an objective way of assessing exercise tolerance and can help in evaluating response to treatment.

Adolescent↗

Nebulised beclomethasone dipropionate suspension.

We compared nebulised beclomethasone dipropionate suspension against placebo in 16 children with moderately severe asthma in double blind crossover fashion. Three children withdrew due to deterioration while on placebo. Of the remaining 13, eight were better on beclomethasone and five on placebo. These trends in favour of nebulised beclomethasone were not significant and do not suggest that the suspension is as effective as inhaled powder or aerosol topical steroid formulation.

Asthma↗

Face mask physiotherapy in cystic fibrosis.

The use of the 'PEP' mask with forced expiratory coughing was compared with conventional physiotherapy over a one month period. No difference was shown in symptom scores, sputum production, or simple lung function tests. The mask was well accepted and allowed independent treatment by older patients.

Adolescent↗