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Biomedical subjects

J S Elborn

Publications and source records attributed to J S Elborn.

At least 73 records · Page 4Linked to original sources
PubMed2000

Clinical features associated with a delayed diagnosis of cystic fibrosis.

BACKGROUND: The majority of patients with cystic fibrosis (CF) are diagnosed in the first decade of life. In a small number of patients, the diagnosis is not made until later. OBJECTIVE: In this study, the clinical and genetic features of patients diagnosed after the age of 10 were examined. METHODS: All living patients in Northern Ireland diagnosed prior to 1983, when neonatal screening was introduced, were studied. A total of 103 patients were identified of whom 18 were diagnosed after the age of 10. The relationships between late diagnosis and clinical presentation, sputum microbiology, pancreatic sufficiency, nutritional status, genotype and distance from the regional CF centres was determined by multiple regression analysis. RESULTS: All 18 late-diagnosed patients had a sweat (chloride >70 mmol/l). Late diagnosis was significantly related to carriage of the R117H mutation (r(2) = 0.45) and pancreatic sufficiency (r(2) = 0.37). There was a weak relationship with pulmonary function (r(2) = 0.09). CONCLUSIONS: In Northern Ireland, late diagnosis in mainly associated with pancreatic function and carriage of the R117H mutation.

Adolescent↗
PubMed1999

Repeatability and methodology of resting energy expenditure in patients with cystic fibrosis.

In this study, intra-individual variation of resting energy expenditure (REE) in adults with cystic fibrosis (CF) and the effect of measurement duration were determined. Twelve adults with CF and chronic Pseudomonas aeruginosa (Ps. aeruginosa) infection and 12 healthy volunteers, matched for age and sex were studied whilst clinically stable on days 1.2, and 15. Respiratory gas exchange was monitored by continuous measurement of oxygen uptake (VO2) and carbon dioxide production (VCO2) using a ventilated hood indirect calorimeter. Coefficients of variation (CVs) were 4.3% in patients and 2.4% in controls comparing days 1 and 2. The CV for patients was 5.0% and for controls 2.9% comparing days 1 and 15. The effect of measurement duration on REE was assessed in eight of the CF patients. REE remained stable for 40 min but tended to rise by 80 min. Plasma catecholamine concentrations were stable between study days in patients but fell with time in controls suggesting some adaptation to experimental procedure. The greater variability of REE in patients was related to change in serum CRP over 2 weeks. REE is a repeatable measurement in clinically stable patients with CF, though variability was greater in patients than healthy subjects. This has implications for the design and interpretation of longitudinal studies of REE in patients with chronic lung disease.

Adrenal Cortex Hormones↗
PubMed1999

Cystic fibrosis: inflammatory response to infection with Burkholderia cepacia and Pseudomonas aeruginosa.

Pulmonary colonization by Burkholderia cepacia in cystic fibrosis (CF) may be associated with enhanced deterioration of pulmonary function. This may be due to a more florid host inflammatory response than in colonization by Pseudomonas aeruginosa, leading to greater lung injury. Circulating markers of inflammation were determined during infective exacerbations and periods of clinical stability in an 18 month prospective study in adults with CF colonized by P. aeruginosa (n=41). B. cepacia (n=13) and in adults who intermittently grew B. cepacia (n=6). There were no differences between the levels of the inflammation markers measured in the three groups (P. aeruginosa, B. cepacia, B. cepacia intermittent) at any of the assessment points. When clinically stable, levels of inflammatory markers in all groups were elevated compared to a matched non-CF population, indicating, continuous inflammation and the potential for lung damage between infective exacerbations. This study does not support the hypothesis that pulmonary colonization with Burkholderia cepacia is associated with a heightened inflammatory response compared with Pseudomonas aeruginosa colonization.

Adult↗
PubMed1998

Buccal absorption of enalapril and lisinopril.

OBJECTIVE: The buccal absorption of captopril does not exhibit the classical pH/partition hypothesis, suggesting that mechanisms other than passive diffusion are involved in its absorption; animal studies have suggested that a peptide carrier-mediated transport system may be responsible for its absorption. The present study evaluated the effects of pH on octanol partitioning, and on the buccal absorption of enalapril and lisinopril, using in vitro techniques and buccal partitioning in human volunteer subjects. METHODS: The partitioning of enalapril and lisinopril into n-octanol was examined over the pH range of 3 9 at room temperature. RESULTS: Enalapril exhibited maximal partitioning into the organic phase at pH 4 5; minimal partitioning was recorded at pH values 8 and 9. The partitioning of lisinopril into n-octanol was found to be maximal at pH 9 and minimal at pH 3. Using the buccal absorption technique, the partitioning of enalapril and lisinopril (0.5 mg), was examined in six healthy male volunteers from buffered solutions (pH 3, 4, 5, 6, 7, 8 and 9). In the case of enalapril, lowest buccal partitioning occurred at pH 3, 8 and 9, while maximal partitioning occurred at pH 5; absorption of lisinopril was not extensive at any pH, but was greatest at pH 6. These results, in addition to the n-octanol partition coefficients, indicated that enalapril obeyed the normal lipid partition hypothesis with respect to buccal absorption. The buccal absorption of lisinopril also obeyed the lipid partition hypothesis over the pH range 3-7. These findings are in direct contrast to those for captopril. The buccal partitioning experiments were repeated at the maximal pH for absorption for each angiotensin converting enzyme (ACE) inhibitor, but with the addition of cephradine (0.05 mmol x l(-1)). CONCLUSION: The data indicated that the presence of this peptide transport inhibitor had no effect on the buccal absorption of enalapril (0.06 mmol x l(-1)) and lisinopril (0.057 mmol x l(-1)), which suggests that both drugs do not share a common buccal absorption pathway with cephradine.

Administration, Buccal↗
PubMed1998

Nutrition in adults with cystic fibrosis.

Improved survival has been associated with better nutritional status in patients with cystic fibrosis (CF). In this study we examined the relationship between nutritional state and other measures of clinical severity in adult patients with CF, attending a regional centre. Eighty-one patients (median age 21 years) were studied. Patients with CF were significantly under weight, compared to healthy individuals but were of similar height. Measurements of lung function, FEV1 and FVC were significantly related to body mass index. Lung function was poorer in patients with chronic pseudomonal infection but body weight and body mass index were not significantly different compared to those without such infection. In 53 patients who were alive 4 years later, FEV1 had declined by -10.5 (2.1)% (P < 0.001) but there was no significant change in body weight 1.5 (6.5) kgs. In 23 patients who died or had lung transplantation the change from 1994 to the date of death or transplantation the FEV1 was reduced by -7.9 (11.2)% (P = 0.004) and body weight -2.8 (4.4) kgs (P < 0.01). In 12 patients who had supplemental enteral feeding, the median increase in body weight was 7|kgs over a period of 12 months. This study confirms that young adult patients with CF are significantly under weight and declining health is associated with significant weight loss. In patients with severe malnutrition significant improvement can be achieved by enteral feeding.

Adolescent↗
PubMed1998

Circulating immunoreactive interleukin-6 in cystic fibrosis.

We measured circulating and sputum-sol concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), neutrophil elastase-alpha1-antiproteinase complex (NEAPC), and C-reactive protein (CRP) in an exacerbation, after antibiotic treatment, and in clinically stable patients with cystic fibrosis and chronic pulmonary infection with Pseudomonas aeruginosa. The aim was to determine the compartmental patterns of a proinflammatory and anti-inflammatory cytokine compared with other markers of inflammatory activity in cystic fibrosis. IL-6, NEAPC, CRP, and absolute neutrophil count were reduced after antibiotic treatment, p < 0.01. IL-6 and CRP concentrations were greater, p = 0.007, and p = 0.01, respectively, in a stable group of patients compared with those at the end of an exacerbation. IL-6 and CRP concentrations were related (r = 0.836, p < 0.0001), and both were greater than in matched control subjects (p < 0.001) at all times studied. Sputum-sol concentrations of IL-6 after treatment were positively related to FEV1 and FVC and inversely related to concentrations of neutrophil elastase. The separation between patients and healthy subjects, and the reduction of IL-6 after antibiotic treatment indicates it could be used as a marker of inflammation, but its relationship to other markers depends on the compartment in which it is measured.

Adult↗
PubMed1997

Thromboembolism related to a Port-a-Cath device in a patient with cystic fibrosis.

The case is described of a potentially life threatening complication relating to the use of a totally implantable venous access device (Port-a-Cath) in a 28 year old patient with cystic fibrosis. The device was inserted in 1990 and used repeatedly for antibiotic therapy without any complications. In 1995, during assessment for double lung transplantation, a 3 cm thrombus was found at the tip of the catheter in the right atrium. Embolisation of the thrombus to the pulmonary arteries occurred after the infusion of recombinant tissue plasminogen activator (rt-PA). Thrombus formation may be associated with totally implantable venous access devices and thromboembolism may occur following the use of thrombolytic agents in the treatment of such thrombosis.

Adult↗
PubMed1996

Neuroendocrine changes in chronic cardiac failure.

Numerous hormonal and neuroendocrine changes have been described in patients with chronic cardiac failure. These affect the balance of vasodilator and vasoconstrictor factors in favour of the latter, to the detriment of the circulation. Whether this is a reaction to central cardiac (haemodynamic) abnormalities, or is an integral part of the syndrome of heart failure, remains to be determined. Catecholamine levels are increased, especially in severe heart failure, and contribute to the vasoconstriction and probably also to lethal ventricular arrhythmias. The renin-angiotensin-aldosterone system (RAAS) is also activated, causing fluid retention and further vasoconstriction. In the earlier stages, some of this increase may be iatrogenic due to the use of loop diuretics or inhibitors of angiotensin converting enzyme, but there is evidence for independent RAAS activation in more severe grades of heart failure. The role of vasoconstrictor peptides such as neuropeptide Y and endothelin is briefly considered. Counterbalancing these are vasodilator peptides, in particular atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP). The possibility of therapeutic interventions to increase circulating natriuretic hormone levels is discussed.

Atrial Natriuretic Factor↗
PubMed1996

Totally implantable venous access devices in adult patients with cystic fibrosis.

Between September 1987 and April 1995, 33 totally implantable venous access devices (TIVADs) were implanted at the Cardiff Adult Cystic Fibrosis Centre, U.K., for the purpose of intermittent antibiotic therapy, including 22 PORT-A-CATH (Simcare Ltd.) devices (PCs) to 18 patients, and 11 P.A.S.PORT (Simcare Ltd.) devices (PPs) to nine patients. There were 50 complications during 25 824 days of catheter function which were severe enough to lead to removal of the devices in eight patients (six PCs and four PPs). Overall, patients' acceptance of these devices was excellent. Despite a shorter functional time and a higher rate of complications in PPs compared with PCs, PPs were preferred by many patients for cosmetic reasons. Totally implantable venous access devices provide safe, effective and convenient means of venous access in cystic fibrosis patients requiring intermittent antibiotic therapy.

Adolescent↗
PubMed1996

Resting energy expenditure and oxygen cost of breathing in patients with cystic fibrosis.

BACKGROUND: Resting energy expenditure (REE) is often increased and may contribute towards energy imbalance in patients with cystic fibrosis. Several mechanisms may lead to increased REE including the gene defect, the effect of chronic infection, and abnormal pulmonary mechanics. Increased oxygen cost of breathing (OCB) has been demonstrated in patients with chronic obstructive pulmonary disease (COPD), but has not been the subject of extensive study in cystic fibrosis. METHODS: Ten clinically stable patients with cystic fibrosis and 10 healthy control subjects were studied. OCB was estimated using the dead space hyperventilation method. Mixed expired gas fractions were measured by online gas analysers and ventilation by a pneumotachograph. After measurement of resting ventilation and gas exchange, minute ventilation (VE) was stimulated by 6-10 1/min by the addition of a dead space and OCB calculated from the slope of the differences in oxygen uptake (VO2) and VE. REE and the non-respiratory component of REE were calculated from gas exchange data. To assess the repeatability of OCB all subjects had a further study performed one week later. RESULTS: The patients had lower weight, fat free mass (FFM), forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and transfer factor for carbon monoxide (TLCO) than controls. Resting respiratory rate, VE, and oxygen uptake per kilogram of FFM (VO2/kg FFM) were higher in patients (20 (7), 10.4 (1.4) 1/min and 5.5 (0.8) ml/kg FFM/min) than in controls (13 (4), 7.0 (1.2), and 4.2 (0.5), respectively.) The error standard deviation for replicated measures of OCB was 0.5 ml O2/l VE in controls and 0.8 ml O2/l VE in patients with coefficients of variation of 24% in controls and 28% in patients. The mean OCB in patients was 2.9 (1.4) ml O2/l VE and 2.1 (0.7) ml O2/l VE in controls. OCB, expressed as ml/min (VO2resp) was 28.5 (11.7) in patients and 14.0 (3.6) in controls. REE was higher in patients (125.9 (14.0)% predicted) than in controls (99.0 (9.4)%). The estimated non-respiratory component of REE was 112.1 (14.9)% for patients and 93.0 (10.0)% for controls. CONCLUSIONS: In clinically stable patients with cystic fibrosis the OCB at rest is increased but is not the sole explanation for increased metabolic rate. This contrasts with the finding in COPD where the increase in REE is largely explained by increased OCB. This study also showed poor repeatability and OCB measurements similar to earlier studies, which indicates that the technique is not suitable for longitudinal studies.

Adult↗
PubMed1995

The effect of pH on the buccal and sublingual absorption of captopril.

The effect of pH on the buccal and sublingual absorption of captopril was evaluated using in vitro techniques and human studies. Partitioning of captopril into n-octanol was lowest over the pH range 5 to 8 and highest at pH values 3, 4 and 9. Using the buccal absorption technique, the partitioning of captopril (2 mg) was examined in six healthy male volunteers from buffered solutions (pH 3, 4, 5, 6, 7, 8, and 9). Lowest buccal partitioning occurred at pH 3 while maximal buccal partitioning occurred at pH 7. These data clearly indicated that the buccal absorption of captopril pharmacokinetic and pharmacodynamic parameters were determined after administration of buffered sublingual captopril (pH 7, optimal hP for absorption as determined from the buccal partitioning data) and unbuffered sublingual captopril. The study was performed in eight healthy volunteers in a randomised single-blind cross-over fashion. The tmax for captopril was found to be approximately 11 minutes earlier after buffered versus unbuffered sublingual administration and AUC0-30 min increased by approximately 30% in the case of buffered captopril. Cpmas, AUC0-180 min and relative bioavailability did not differ between the buffered and unbuffered administration. Pharmacodynamic parameters (BP, heart rate and plasma renin activity) did not differ significantly between buffered and unbuffered sublingual administration. The increased rate of captopril absorption after buffered sublingual administration was small and is likely to offer little therapeutic advantage over conventional sublingual formulation.

1-Octanol↗
PubMed1995

Perfusion/ventilation mismatch during exercise in chronic heart failure: an investigation of circulatory determinants.

BACKGROUND: The ventilatory cost of carbon dioxide (CO2) elimination on exercise (VE/VCO2) is increased in chronic heart failure (CHF). This reflects increased physiological dead space ventilation secondary to mismatching between perfusion and ventilation during exercise. The objectives of this study were to investigate the relation of this increased VE/VCO2 slope to the syndrome of CHF or to limitation of the exercise related increase of pulmonary blood flow, or both. PATIENTS AND METHODS: Maximal treadmill exercise tests with respiratory gas analysis were performed in 45 patients with CHF (defined as resting left ventricular ejection fraction < 40% on radionuclide scan); 15 normal controls; 23 patients with coronary artery disease and normal resting left ventricular function; and 13 pacemaker dependent patients (six with and seven without CHF) directly comparing exercise responses in rate responsive and fixed rate mode. RESULTS: Patients with CHF had a steeper VE/VCO2 slope than normal controls: this was related inversely to peak VO2 below 20 mol/min/kg. In patients with coronary artery disease in whom peak VO2 (at respiratory exchange ratio > 1) was as limited as in the patients with CHF but resting left ventricular function was normal, the VE/VCO2 slope was normal. In pacemaker dependent patients fixed rate pacing resulted in lower exercise capacity and peak VO2 than rate responsive pacing; the VE/VCO2 slope was normal in patients without CHF but steeper than normal in patients with CHF; the VE/VCO2 slope was steeper during fixed rate than during rate responsive pacing in these patients with CHF. CONCLUSIONS: These findings suggest that the perfusion/ventilation mismatch during exercise in CHF is related to the chronic consequences of the syndrome and not directly to limitation of exercise related pulmonary flow. Only when the syndrome of CHF is present can matching between perfusion and ventilation be acutely influenced by changes in pulmonary flow.

Adult↗
PubMed1995

Exercise ventilation after balloon dilatation of the mitral valve.

BACKGROUND: Exertional dyspnoea is a limiting symptom in many patients with mitral stenosis but its causes remain incompletely understood. Ventilation during exercise is abnormal in chronic heart failure of all causes and there is increased ventilatory cost of carbon dioxide production. PATIENTS: 23 patients with rheumatic mitral stenosis undergoing percutaneous balloon dilatation of the mitral valve were studied to investigate exercise ventilation. METHODS: Treadmill exercise tests with respiratory gas analysis were performed before and 1 day, 7 days, and 10 weeks after balloon dilatation of the mitral valve. The relation between ventilation (VE) and production (VCO2) was analysed by linear regression. RESULTS: The VE/VCO2 slope was linear in all patients and before balloon dilatation of the mitral valve it correlated inversely with peak minute oxygen consumption (VO2) (rs = -0.47, P < 0.05), exercise duration (rs = -0.66, P < 0.01), and mitral valve area (rs = -0.5, P < 0.05). The VE/VCO2 slope declined acutely after balloon dilatation of the mitral valve (n = 10) (mean (SD) 41 (4) v 36 (2.9), P < 0.05) and did not change again thereafter. At 10 weeks (n = 23) exercise duration (460 (230) v 630 (240) s, P < 0.01) and peak VO2 (12.7 (4.3) v 14.9 (4.8) ml/kg/min, P < 0.05) increased significantly. CONCLUSIONS: Patients with rheumatic mitral stenosis have a similar increase in the VE/VCO2 slope to that of patients with heart failure from other causes. Successful balloon dilatation of the mitral valve is associated with an acute reduction in the exercise VE/VCO2 slope.

Adult↗