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Biomedical subjects

D J Shale

Publications and source records attributed to D J Shale.

At least 55 records · Page 3Linked to original sources
PubMed1993

Tumour necrosis factor alpha in severe congestive cardiac failure.

OBJECTIVE: To examine the concentration of circulating tumour necrosis factor alpha (TNF alpha) in patients with severe congestive heart failure (New York Heart Association class IV) during one year and to correlate changes in this cytokine with changes in plasma noradrenaline, plasma renin activity, and weight. DESIGN: A prospective study of the role of TNF alpha in severe chronic heart failure. Blood samples were collected at intervals of three months. SETTING: Medical research centre of a teaching hospital. PATIENTS: 16 patients with chronic stable severe heart failure. INTERVENTIONS: Vasodilator treatment with captopril or flosequinan. MAIN OUTCOME MEASURES: Changes in TNF alpha and the correlation with changes in plasma noradrenaline, plasma renin activity, and weight during optimal medical treatment for one year. RESULTS: The mean concentration of TNF alpha was greater than the upper 95% confidence interval for healthy controls throughout the year of the study but there was considerable between and within patient variation. No correlation was seen between TNF alpha and plasma noradrenaline, plasma renin activity, or weight. CONCLUSIONS: The stimulus resulting in enhanced plasma concentrations of TNF alpha in congestive heart failure remains unclear and concentrations at any particular time were not prognostic.

Body Weight↗
PubMed1993

Effect of cardiopulmonary bypass on systemic release of neutrophil elastase and tumor necrosis factor.

Leukocyte counts, plasma neutrophil elastase, tumor necrosis factor-alpha and C-reactive protein were determined serially in 19 patients undergoing elective coronary artery surgery with cardiopulmonary bypass. Neutrophil counts (mean +/- standard deviation 3.85 +/- 1.20 x 10(9)/L preoperatively) peaked 4 hours postoperatively at 10.35 +/- 4.24 x 10(9)/L (p < 0.001) and remained significantly elevated 48 hours postoperatively at 7.80 +/- 2.70 x 10(9)/L, p < 0.05. Plasma neutrophil elastase level (187 +/- 74 ng/ml preoperatively) peaked at 698 +/- 323 ng/ml at the end of surgery (p < 0.001) and remained significantly elevated at 424 +/- 146 ng/ml 48 hours postoperatively (p < 0.01). Peak elastase levels correlated significantly with duration of bypass (r = 0.47, n = 19, p < 0.05). Monocyte counts (0.29 +/- 0.19 x 10(9)/L preoperatively) peaked 4 hours postoperatively (0.87 +/- 0.41 x 10(9)/L, p < 0.001) and fell to baseline levels by 48 hours postoperatively. Plasma tumor necrosis factor-alpha, detectable in 10 of the 19 patients preoperatively (median 0.39 U/ml, range up to 10.1 U/ml), did not change significantly during or after bypass. Plasma C-reactive protein level (median 1.67 [range 0.69 to 34.33] micrograms/ml preoperatively) rose significantly to 3.99 (range 1.95 to 12.55) micrograms/ml 4 hours postoperatively (p < 0.01) and rose 48 hours postoperatively at 303 (210 to 410) micrograms/ml, p < 0.001. Oxygenation, determined by the respiratory index, was impaired at the end of operation (2.07 +/- 0.82) and remained impaired 24 hours postoperatively (2.48 +/- 0.83). Impairment of oxygenation was temporally related to elevated elastase levels, but neither peak elastase levels nor the change in elastase levels with lung reperfusion correlated significantly with the area under the respiratory index curve up to 6 hours postoperatively. This study demonstrates neutrophil elastase release during cardiopulmonary bypass but fails to show a definite role for neutrophil activation or tumor necrosis factor-alpha in the etiology of pulmonary dysfunction after cardiopulmonary bypass.

Aged↗
PubMed1992

In vitro displacement of vasoactive mediators from plasma proteins: a possible mechanism for pseudo-allergic reactions to neuromuscular blocking drugs.

We have studied the release of prostaglandin F2 alpha (PGF2 alpha) and histamine from serum proteins by neuromuscular blocking drugs using equilibrium dialysis, with tracer quantities of radio-labelled mediators as probes. Small concentrations (0.05-0.25 mmol litre-1) of competitive neuromuscular blocking drugs displaced 16-67% of bound histamine. Greater concentrations of suxamethonium (2 mmol litre-1) were required for histamine displacement (19%). There was a significant release of PGF2 alpha by atracurium 1 mmol litre-1 and pancuronium 0.69 mmol litre-1. These findings suggest an alternative mechanism of histamine release by neuromuscular blocking drugs which may be relevant to adverse reactions during use.

Blood Proteins↗
PubMed1992

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↗
PubMed1992

Precipitins and specific IgG antibody to Aspergillus fumigatus in a chest unit population.

BACKGROUND: The enzyme linked immunosorbent assay (ELISA) for detecting IgG antibodies to Aspergillus fumigatus is more sensitive than the measurement of Aspergillus precipitins. The relation of the results from both techniques to the clinical pattern of disease in a large unselected group of patients from a large referral centre is unknown. METHODS: The clinical relation of precipitins to Aspergillus fumigatus to clinical disease was determined retrospectively in 98 patients attending a primary referral centre. Precipitin results were compared with the specific IgG antibody to A fumigatus in 88 of the sera. Precipitins were determined by the agar gel double diffusion test and specific IgG antibody to A fumigatus by a quantitative ELISA. RESULTS: Precipitins were detected in the unconcentrated serum of 51 patients. Thirty nine of these had a mycetoma or allergic bronchopulmonary aspergillosis, 34 having specific IgG antibody to A fumigatus more than the control range. Forty seven patients had precipitins only after threefold concentration of serum or to only one of the four A fumigatus antigen extracts. Most of these had specific IgG in or near the control range. Thirty of these had A fumigatus skin test negative asthma or bronchiectasis, in which aspergillus was probably not pathogenic. There was a close relation between the level of antibody detected by the ELISA and the number of precipitin lines. CONCLUSIONS: This study reaffirmed the supportive role of aspergillus precipitins in the diagnosis of pulmonary aspergillosis. No additional benefit in the routine use of the ELISA was seen. It also showed that care should be taken in interpreting positive precipitin results from concentrated serum and that using several rather than one A fumigatus antigen extract is helpful for identifying allergic aspergillosis.

Antibodies, Fungal↗
PubMed1992

In vitro tumor necrosis factor-alpha secretion by monocytes from patients with cystic fibrosis.

Immunoreactive tumor necrosis factor-alpha (TNF-alpha) concentration is increased in plasma from patients with cystic fibrosis and chronic Pseudomonas aeruginosa pulmonary infection. To determine if circulating monocytes could be the source of plasma TNF-alpha, we determined in vitro basal and endotoxin-stimulated TNF-alpha secretion by monocytes. In 10 adult patients studied at the time of a symptomatic respiratory exacerbation, basal secretion of TNF-alpha was significantly less than that for 10 matched healthy controls (median 265 pg/micrograms DNA, nonparametric 95% confidence interval 193 to 463 pg/micrograms DNA versus 575, 298 to 923 pg/micrograms DNA; P less than 0.006), although both groups responded equally effectively to added Escherichia coli endotoxin at greater than or equal to 25 ng/ml. In six patients and six matched controls, monocyte culture was repeated after completion of 2 wk anti-pseudomonal antibiotic treatment in the patients. The reduced basal TNF-alpha secretion in the patients had reversed and was not significantly different to that of controls. This effect mirrored a significant reduction in plasma immunoreactive TNF-alpha in these patients (mean +/- SD, 258 +/- 59.3 pg/ml pretreatment versus 133 +/- 47.8 pg/ml post-treatment; P less than 0.05). These findings suggest that a reversible downregulation of TNF-alpha secretion occurred at the time of a symptomatic respiratory deterioration in the presence of chronic P. aeruginosa infection. This may represent a physiologic regulatory mechanism to maintain a local inflammatory response to chronic pulmonary infection in cystic fibrosis.

Adolescent↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

Cystic fibrosis: current survival and population estimates to the year 2000.

BACKGROUND: Survival from cystic fibrosis is increasing rapidly. Estimates of the extent of this improvement should allow health care facilities to be planned to deal with the expanding population of patients with cystic fibrosis. Estimates of life expectancy are also essential if accurate information on current prognosis is to be given to parents of an affected child, or to prospective parents deciding whether to proceed with a pregnancy where the fetus may be affected. METHODS: Survival trends in the national data on cystic fibrosis have been analysed to produce estimates of the likely size of the cystic fibrosis population over the next decade and to predict the life expectancy of children born with cystic fibrosis in the years up to 1990. RESULTS: In England and Wales the estimated number of patients with cystic fibrosis is at present about 5200, of whom 3300 (63%) are aged under 16 years. By the year 2000 the total population will increase to 6000, with 3400 (57%) aged under 16. Thus the number of children with cystic fibrosis will remain fairly constant over the next 10 years, whereas adult numbers will increase by about 36% (from 1901 to 2577). The median life expectancy of children with cystic fibrosis born in 1990 is estimated to be 40 years, double that of 20 years ago. CONCLUSION: This study suggests that health service provision for children will not need to change substantially over the next 10 years whereas services for adults will need to increase by about a third. Parents can be counselled that the median life expectancy of a newborn child with cystic fibrosis is currently likely to be of the order of 40 years.

Age Factors↗
PubMed1991

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↗
PubMed1989

Diagnostic criteria for adult respiratory distress syndrome: time for reappraisal.

To assess whether current diagnostic criteria for the adult respiratory distress syndrome (ARDS) may limit research to patients with a range of severity of respiratory failure and risk factors for ARDS were studied. In 28 patients ARDS did not develop; in 9 it did; and the other 13 met the diagnostic criteria at their first assessment. Plasma concentration of neutrophil elastase-alpha 1-antitrypsin complex was higher in all groups than in controls. For all patients, plasma elastase-complex was related to worsening hypoxia and to increased bronchoalveolar lavage protein content. Elastase-complex was present in all bronchoalveolar lavage samples and was related to protein content and differential neutrophil counts. Patients at risk of or with ARDS had a spectrum of respiratory failure to which intravascular and intra-alveolar neutrophil elastase release and capillary permeability were related. This suggests that the state recognised as ARDS is not a distinct pathophysiological entity.

Adult↗
PubMed1989

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↗