Biomedical subjects

P N Black

Publications and source records attributed to P N Black.

At least 19 recordsLinked to original sources

PubMed2006

Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease.

BACKGROUND: Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume and/or purulence of sputum. Because of the personal and healthcare costs associated with exacerbations, any therapy that reduces the number of exacerbations is useful. There is a marked difference between countries in terms of prescribing of mucolytics depending on whether or not they are perceived to be effective. OBJECTIVES: To assess the effects of oral mucolytics in adults with stable chronic bronchitis or COPD. SEARCH STRATEGY: We have searched the Cochrane Airways Group Specialised Register and reference lists of articles on four separate occasions, the most recent being in June 2005. This is the third major update. SELECTION CRITERIA: Randomised trials that compared oral mucolytic therapy with placebo for at least two months in adults with chronic bronchitis or COPD. Studies of people with asthma and cystic fibrosis were excluded. DATA COLLECTION AND ANALYSIS: One reviewer extracted data. Study authors and drug companies were contacted for missing information. MAIN RESULTS: Twenty six trials were included (7335 participants). Compared with placebo, there was a significant reduction in the number of exacerbations per patient with oral mucolytics (weighted mean difference (WMD) -0.05 per month, 95% confidence interval -0.05, -0.04). Using the annualised rate of exacerbations in the control patients of 2.6 per year, this is a 20% reduction. The number of days of disability also fell (WMD -0.56, 95% confidence interval -0.77, -0.35). A recent study has shown that the benefit may apply only to those patients not already receiving inhaled corticosteroids. The number of patients who remained exacerbation-free was greater in the mucolytic group (OR 2.13 (95% CI 1.86 to 2.42)). There was no difference in lung function or in adverse effects reported between the treatments. AUTHORS' CONCLUSIONS: In subjects with chronic bronchitis or COPD, treatment with mucolytics was associated with a small reduction in acute exacerbations and a reduction in total number of days of disability. Benefit may be greater in individuals who have frequent or prolonged exacerbations, or those who are repeatedly admitted to hospital with exacerbations with COPD. They should be considered for use, through the winter months at least, in patients with moderate or severe COPD in whom inhaled corticosteroids (ICS) are not prescribed.

Adult↗

PubMed2006

Once-daily dosing with budesonide/formoterol compared with twice-daily budesonide/formoterol and once-daily budesonide in adults with mild to moderate asthma.

Adherence to maintenance therapy is often poor in patients with asthma. Simplifying dosing regimens has the potential to improve both adherence and asthma-related morbidity. In this 12-week, randomized, double-blind, double-dummy, parallel-group study, 617 patients with mild to moderate persistent asthma (mean forced expiratory volume in 1s [FEV1] 78.5% predicted) who were not optimally controlled on inhaled corticosteroids (200-500 microg/day) were randomized to once-daily budesonide/formoterol (80/4.5 microg, 2 inhalations in the evening), twice-daily budesonide/formoterol (80/4.5 microg, 1 inhalation), or a corresponding dose of budesonide once-daily (200 microg, 1 inhalation in the evening). All patients received budesonide (100 microg twice daily) during a 2-week run-in. Changes in mean morning peak expiratory flow (PEF) were similar for od budesonide/formoterol (23.4 l/min) and twice-daily budesonide/formoterol (24.1 l/min), and both were greater than with budesonide (5.5 l/min; both P<0.001). Evening PEF, symptom-free days, reliever-free days, and asthma control days were improved with budesonide/formoterol therapy vs. budesonide (P<0.05 vs. budesonide for all variables). All treatments were well tolerated. Budesonide/formoterol administered once daily in the evening is a convenient treatment regimen that is as effective in improving asthma control as twice-daily dosing in patients with mild to moderate persistent asthma.

Administration, Inhalation↗

PubMed2006

Functional variants of antioxidant genes in smokers with COPD and in those with normal lung function.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is predominantly the consequence of chronic smoking exposure, but its development may be influenced by genetic variants that affect lung remodelling, inflammation, and defence from oxidant stress. A study was undertaken to determine whether genetic variants within genes encoding the antioxidant enzymes superoxide dismutase (SOD) and catalase may be associated with the development of impaired lung function. METHODS: In a case-control study, the allele and genotype frequencies of functional polymorphisms from SOD1 (CuZnSOD), SOD2 (MnSOD), SOD3 (extracellular SOD), and catalase (CAT) were compared in chronic smokers with normal lung function (resistant smokers) and in those with COPD. RESULTS: Significantly higher frequencies of the G allele and CG/GG genotype of the 213 SOD3 polymorphism were found in resistant smokers (odds ratios (ORs) 4.3 (95% CI 1.5 to 13.3) and 4.2, 95% CI 1.4 to 13.3), Bonferroni corrected p = 0.02 and p = 0.02, respectively) than in those with COPD. There were no differences between the COPD and resistant smokers for the SOD1, SOD2, or CAT polymorphisms tested. CONCLUSIONS: The 213Gly variant of the SOD3 gene may, through antioxidant or anti-inflammatory effects, confer a degree of resistance in some smokers to the development of COPD.

Adult↗

PubMed2006

Accuracy of information on medicines in hospital discharge summaries.

BACKGROUND: At Auckland Hospital, patients have been given handwritten summaries on discharge from hospital with a copy posted to the general practitioner. A typed summary is often not completed so the list of medicines on the handwritten summary needs to be accurate and complete. METHODS: We selected 100 patient charts from the general medical service and 100 charts from the general surgical service and recorded the medicines on admission, on the inpatient medication chart and on the discharge summary. We noted errors in the recording of medicines on the discharge summary and rated the severity of errors. RESULTS: Surgical patients were discharged on 7.88 (95% confidence interval (CI) 7.40-8.64) medicines and medical patients on 8.58 (95% CI 7.87-9.29) medicines. During the admission there were 0.59 (95% CI 0.38-0.80) changes to the medicines for the surgical patients and 1.70 (95% CI 1.39-2.01) for the medical patients (P < 0.0001). There were 0.81 (95% CI 0.65-1.02) errors per surgical discharge summary and 1.42 (95% CI 1.20-1.67) errors per medical summary (P = 0.006). Four errors were graded as having the potential to cause readmission to hospital, 24 as potentially serious, 83 as potentially troublesome and 111 as minor. DISCUSSION: Error rates were high and although the majority were minor, a number of them had the potential to cause serious consequences. There were more medication changes in the medical patients and this may contribute to higher error rates in this group. There is a need to improve the accuracy of recording medicines on discharge summaries. Strategies to improve this problem are discussed.

Adolescent↗

PubMed2005

Physical training for asthma.

BACKGROUND: Physical training programmes have been designed for asthmatic subjects with the aim of improving physical fitness, neuromuscular coordination and self-confidence. Habitual physical activity increases physical fitness and lowers ventilation during mild and moderate exercise thereby reducing the likelihood of provoking exercise induced asthma. Exercise training may also reduce the perception of breathlessness through a number of mechanisms including strengthening respiratory muscles. Subjectively, many asthmatics report that they are symptomatically better when fit, but results from trials have varied and have been difficult to compare because of different designs and training protocols. OBJECTIVES: The purpose of this review was to assess evidence for the efficacy and effectiveness of physical training in asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register, SportDiscus and the Science Citation Index up to May 2005. SELECTION CRITERIA: Randomised trials in asthmatic subjects undertaking physical training. Subjects had to be eight years and older. Physical training had to be undertaken for at least 20 to 30 minutes, two to three times a week, over a minimum of four weeks. DATA COLLECTION AND ANALYSIS: Eligibility for inclusion and quality of trials were assessed independently by two reviewers. MAIN RESULTS: Thirteen studies (455 participants) were included in this review. Physical training had no effect on resting lung function or the number of days of wheeze. The results of this review have shown that lung function and wheeze is not worsened by physical training in patients with asthma. Physical training improved cardiopulmonary fitness as measured by an increase in maximum oxygen uptake of 5.4 ml/kg/min (95% confidence interval 4.2 to 6.6) and maximum expiratory ventilation 6.0 L/min (95% confidence interval 1.5 to 10.4). There were no data concerning quality of life measurements. AUTHORS' CONCLUSIONS: In people with asthma, physical training can improve cardiopulmonary fitness without changing lung function. It is not known whether improved fitness is translated into improved quality of life. It is comforting to know that physical training does not have an adverse effect on lung function and wheeze in patients with asthma. Therefore, there is no reason why patients with asthma should not participate in regular physical activity.

Asthma↗

PubMed2005

Comparison of the effects of nebulised and inhaled salbutamol on breathlessness in severe COPD.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often report greater relief of breathlessness with nebulised bronchodilators than with the same medicine administered from a metered dose inhaler (MDI). This suggests that the nebulised medicines may have an effect on breathlessness over and above changes in lung function resulting from bronchodilatation. METHODS: Twenty-four subjects with COPD and breathlessness at rest participated in this randomised, crossover trial. The mean age was 72 years and the mean FEV(1) was 26% of predicted. Subjects were studied on four separate days. On two days they were treated with nebulised salbutamol and on the other 2 days with salbutamol from an MDI and spacer. With each method of delivery, local anaesthetic cream was applied to the face on one day and to the back of the hand on the other. RESULTS: Five minutes after administration of salbutamol the subjects were significantly less breathless with nebulised salbutamol but by 45 min both treatments resulted in equivalent relief. There was no difference between the treatments in the change in FEV(1) or VC and application of local anaesthetic to the face did not influence the response. CONCLUSION: There was a small early benefit with nebulised salbutamol but this was not sustained and was not affected by topical anaesthesia. The benefit of nebulisation does not appear to be large enough to warrant the routine, widespread use of nebulised bronchodilators for the treatment of stable COPD.

Aged↗

PubMed2005

Risk factors for atopic dermatitis in New Zealand children at 3.5 years of age.

BACKGROUND: The prevalence of atopic dermatitis (AD) is increasing in Western societies. The hygiene hypothesis proposes that this is due to reduced exposure to environmental allergens and infections during early life. OBJECTIVES: To examine factors associated with a diagnosis of AD at 3.5 years of age, especially those factors implicated by the hygiene hypothesis. METHODS: The Auckland Birthweight Collaborative study is a case-control study of risk factors for small for gestational age babies. Cases were born at term with birthweight < or = 10th centile; controls were appropriate for gestational age, with birthweight > 10th centile. The infants were assessed at birth, 1 year and 3.5 years of age. Data were collected by parental interview and examination of the child. AD was defined as the presence of an itchy rash in the past 12 months with three or more of the following: history of flexural involvement; history of generally dry skin; history of atopic disease in parents or siblings; and visible flexural dermatitis as per photographic protocol. Statistical analyses took into account the disproportionate sampling of the study population. RESULTS: Analysis was restricted to European subjects. Eight hundred and seventy-one children were enrolled at birth, 744 (85.4%) participated at 1 year, and 550 (63.2%) at 3.5 years. AD was diagnosed in 87 (15.8%) children seen at 3.5 years. The prevalence of AD did not differ by birthweight. AD at 3.5 years was associated with raised serum IgE > 200 kU L(-1), and wheezing, asthma, rash or eczema at 1 year. In multivariate analysis, adjusted for parental atopy and breastfeeding, AD at 3.5 years was associated with atopic disease in the parents: maternal atopy only, adjusted odds ratio (OR) 3.83, 95% confidence interval (CI) 1.20-12.23; paternal atopy only, adjusted OR 3.59, 95% CI 1.09-11.75; both parents atopic, adjusted OR 6.12, 95% CI 2.02-18.50. There was a higher risk of AD with longer duration of breastfeeding: < 6 months, adjusted OR 6.13, 95% CI 1.45-25.86; > or = 6 months, adjusted OR 9.70, 95% CI 2.47-38.15 compared with never breastfed. These findings remained significant after adjusting for environmental factors and a personal history of atopy. AD at 3.5 years was associated with owning a cat at 3.5 years (adjusted OR 0.45, 95% CI 0.21-0.97) but not with owning a dog at 3.5 years, pets at 1 year, nor with older siblings. Furthermore, AD at 3.5 years was not associated with gender, socioeconomic status, maternal smoking, parity, damp, mould, immunizations, body mass index or antibiotic use in first year of life. CONCLUSIONS: A personal and a parental history of atopic disease are risk factors for AD at 3.5 years. Duration of breastfeeding was associated with an increased risk of AD. No association was found with those factors implicated by the hygiene hypothesis. This study suggests that breastfeeding should not be recommended for the prevention of AD.

Allergens↗

PubMed2005

Does atopy protect against enteric infections?

Allergic sensitization to inhaled allergens and foods is common and is linked to the development of asthma, allergic rhinitis and eczema. In view of the morbidity associated with these diseases it is not clear why the genetic predisposition to atopy is so common. Children who are atopic are less likely to develop oral tolerance to ingested foods and as a result are more likely to have manifestations of food allergy including wheezing, skin rashes and gastrointestinal symptoms. Oral tolerance also develops to micro-organisms in the gastrointestinal tract. Children who are atopic may be protected against enteric infections in early childhood because they are less likely to be tolerant of these organisms. This may explain why individuals who are atopic are less likely to have evidence of previous infection with hepatitis A and other enteric organisms although they are just as likely to have been infected with respiratory pathogens.

Disease Susceptibility↗

PubMed2004

Use of a preprinted sticker to improve the prescribing of prophylactic antibiotics for hip fracture surgery.

PROBLEM: Antibiotic prophylaxis has been shown to reduce the number of postoperative infections following surgery for hip fracture. At Auckland Hospital the policy for antibiotic prophylaxis for hip fracture surgery is for the patient to receive the first dose of antibiotic at the induction of anaesthesia followed by two more doses at 8 hour intervals. A previous audit found that patients often received too many doses of antibiotic. A retrospective audit was performed of 100 patients undergoing surgery for a hip fracture. The primary problem was over-prescribing; 68 patients (68%) received more than three doses. The number of patients who received three doses according to the guidelines was 29 (29%, 95% CI 21 to 40). SETTING: Auckland Hospital which provides acute orthopaedic services for a population of 500,000. STRATEGY FOR CHANGE: A sticker was introduced with the prescription printed on it. The sticker was applied to the medication chart by the anaesthetist when the initial dose of antibiotic was given. Charts of a further 100 patients were reviewed after the introduction of the sticker and compared with those from another hospital in Auckland where the sticker was not used. EFFECTS OF CHANGE: The number of patients who received three doses, in accordance with the guidelines, improved to 74 (74%, 95% CI 64 to 82, p<0.001). These changes were observed even though the sticker was only used in 44 patients (44%, 95% CI 34 to 54). At the other hospital the number of patients who received three doses was 10 (20%, 95% CI 10 to 42) and 13 (26%, 95% CI 15 to 40, p = 0.37) for the same two periods. LESSONS LEARNT: The use of a preprinted sticker is a simple intervention which improves the use of antibiotic prophylaxis at the time of surgery. This improvement occurred even though the sticker was used in slightly fewer than half the cases.

Adult↗

PubMed2004

Transforming growth factor-beta1 genotype and susceptibility to chronic obstructive pulmonary disease.

BACKGROUND: Only a few long term smokers develop symptomatic chronic obstructive pulmonary disease (COPD) and this may be due, at least in part, to genetic susceptibility to the disease. Transforming growth factor beta1 (TGF-beta1) has a number of actions that make it a candidate for a role in the pathogenesis of COPD. We have investigated a single nucleotide polymorphism at exon 1 nucleotide position 29 (T-->C) of the TGF-beta1 gene that produces a substitution at codon 10 (Leu-->Pro). METHODS: The frequency of this polymorphism was determined in 165 subjects with COPD, 140 healthy blood donors, and 76 smokers with normal lung function (resistant smokers) using the polymerase chain reaction and restriction enzyme fragment length polymorphism. RESULTS: The distribution of genotypes was Leu-Leu (41.8%), Leu-Pro (50.3%), and Pro-Pro (7.9%) for subjects with COPD, which was significantly different from the control subjects (blood donors: Leu-Leu (29.3%), Leu-Pro (52.1%) and Pro-Pro (18.6%), p=0.006; resistant smokers: Leu-Leu (28.9%), Leu-Pro (51.3%) and Pro-Pro (19.7%), p=0.02). The Pro10 allele was less common in subjects with COPD (33%) than in blood donors (45%; OR=0.62, 95% CI 0.45 to 0.86, p=0.005) and resistant smokers (45%; OR=0.59, 95% CI 0.40 to 0.88, p=0.01). CONCLUSIONS: The proline allele at codon 10 of the TGF-beta1 gene occurs more commonly in control subjects than in individuals with COPD. This allele is associated with increased production of TGF-beta1 which raises the possibility that TGF-beta1 has a protective role in COPD.

Adult↗

PubMed2003

Prophylactic antibiotic therapy for chronic bronchitis.

BACKGROUND: The use of prophylactic antibiotics to reduce the frequency and severity of acute exacerbations of chronic bronchitis is controversial. OBJECTIVES: To determine if prophylactic antibiotics reduce the frequency of exacerbations and/or days of disability in subjects with chronic bronchitis. SEARCH STRATEGY: We searched the Cochrane Airways Group Register of Clinical Trials and the bibliographies of relevant articles. SELECTION CRITERIA: Randomised controlled trials of prophylactic antibiotics in patients with chronic bronchitis and/or COPD were selected. DATA COLLECTION AND ANALYSIS: The eligibility of studies for inclusion was evaluated by three independent reviewers. MAIN RESULTS: Nine trials involving 1055 subjects were included in the analysis. All were performed before 1970. Concealment of allocation was assessed as clearly adequate in only 3 studies. The likelihood of having a exacerbation at any time during the course of the study was decreased with treatment (Relative Risk 0.91, 95% Confidence Intervals (CI) 0.84, 0.99). There was a small reduction in the number of exacerbations per patient per year with prophylactic antibiotics but this was not statistically significant ( Weighted Mean Difference (WMD) -0.15, 95%CI -0.34, 0.04 ). There was a modest but significant reduction of 22% in the number of days of disability per patient per month treated ( WMD -0.95, 95%CI -1.89 to - 0.01 ). A parallel reduction in the days of disability for each exacerbation (WMD -2.08, 95% CI -4.08 to -0.07) was seen. There was a small increase in adverse effects with antibiotics. REVIEWER'S CONCLUSIONS: Prophylactic antibiotics in chronic bronchitis / COPD have a small but statistically significant effect in reducing the days of illness due to exacerbations of chronic bronchitis. They do not have a place in routine treatment because of concerns about the development of antibiotic resistance and the possibility of adverse effects. The available data are over 30 years old, so the pattern of antibiotic sensitivity may have changed and there is a wider range of antibiotics in use.

Antibiotic Prophylaxis↗

PubMed2001

Trial of roxithromycin in subjects with asthma and serological evidence of infection with Chlamydia pneumoniae.

An association has been reported between chronic infection with Chlamydia pneumoniae and the severity of asthma, and uncontrolled observations have suggested that treatment with antibiotics active against C. pneumoniae leads to an improvement in asthma control. We studied the effect of roxithromycin in subjects with asthma and immunoglobulin G (IgG) antibodies to C. pneumoniae > or = 1:64 and/or IgA antibodies > or = 1:16. A total of 232 subjects, from Australia, New Zealand, Italy, or Argentina, were randomized to 6 wk of treatment with roxithromycin 150 mg twice a day or placebo. At the end of 6 wk, the increase from baseline in evening peak expiratory flow (PEF) was 15 L/min with roxithromycin and 3 L/min with placebo (p = 0.02). With morning PEF, the increase was 14 L/min with roxithromycin and 8 L/min with placebo (NS). In the Australasian population, the increase in morning PEF was 18 L/min and 4 L/min, respectively (p = 0.04). At 3 mo and 6 mo after the end of treatment, differences between the two groups were smaller and not significant. Six weeks of treatment with roxithromycin led to improvements in asthma control but the benefit was not sustained. Further studies are necessary to determine whether the lack of sustained benefit is due to failure to eradicate C. pneumoniae.

Adult↗

PubMed2001

The Acyl-CoA synthetases encoded within FAA1 and FAA4 in Saccharomyces cerevisiae function as components of the fatty acid transport system linking import, activation, and intracellular Utilization.

Exogenous long-chain fatty acids are activated to coenzyme A derivatives prior to metabolic utilization. In the yeast Saccharomyces cerevisiae, the activation of these compounds prior to metabolic utilization proceeds through the fatty acyl-CoA synthetases Faa1p and Faa4p. Faa1p or Faa4p are essential for long-chain fatty acid import, suggesting that one or both of these enzymes are components of the fatty acid transport system, which also includes Fat1p. By monitoring the intracellular accumulation of the fluorescent long-chain fatty acid analogue 4,4-difluoro-5-methyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoic acid, long-chain fatty acid transport was shown to be severely restricted in a faa1 Delta faa4 Delta strain. These data established for the first time a mechanistic linkage between the import and activation of exogenous fatty acids in yeast. To investigate this linkage further, oleoyl CoA levels were defined following incubation of wild type and mutant cells with limiting concentrations of exogenous oleate. These studies demonstrated oleoyl CoA levels were reduced to less than 10% wild-type levels in faa1 Delta and faa1 Delta faa4 Delta strains. Defects in metabolic utilization and intracellular trafficking were also found in the fatty acyl-CoA synthetase-deficient strains. The faa1 Delta faa4 Delta strain had a marked reduction in endogenous acyl-CoA pools, suggesting these enzymes play a role in maintenance of endogenous acyl-CoA pools, metabolism and trafficking. In addition, this strain had levels of in vivo beta-oxidation of exogenous oleate reduced 3-fold when compared with the isogenic parent. Northern analyses demonstrated an additional defect in fatty acid trafficking as FAA1 or FAA4 were required for the transcriptional regulation of the genes encoding the peroxisomal enzymes acyl-CoA oxidase (POX1) and medium-chain acyl-CoA synthetase (FAA2). These data support the hypothesis that fatty acyl-CoA synthetase (Faa1p or Faa4p) functions as a component of the fatty acid import system by linking import and activation of exogenous fatty acids to intracellular utilization and signaling.

Acyl Coenzyme A↗

PubMed2001

Oral mucolytic drugs for exacerbations of chronic obstructive pulmonary disease: systematic review.

OBJECTIVE: To assess the effects of oral mucolytics in adults with stable chronic bronchitis and chronic obstructive pulmonary disease. DESIGN: Systematic review of randomised controlled trials that compared at least two months of regular oral mucolytic drugs with placebo. STUDIES: Twenty three randomised controlled trials in outpatients in Europe and United States. MAIN OUTCOME MEASURES: Exacerbations, days of illness, lung function, adverse events. RESULTS: Compared with placebo, the number of exacerbations was significantly reduced in subjects taking oral mucolytics (weighted mean difference -0.07 per month, 95% confidence interval -0.08 to -0.05, P<0.0001). Based on the annualised rate of exacerbations in the control subjects of 2.7 a year, this is a 29% reduction. The number needed to treat for one subject to have no exacerbation in the study period would be 6. Days of illness also fell (weighted mean difference -0.56, -0.77 to -0.35, P<0.0001). The number of subjects who had no exacerbations in the study period was greater in the mucolytic group (odds ratio 2.22, 95% confidence interval 1.93 to 2.54, P<0.0001). There was no difference in lung function or in adverse events reported between treatments. CONCLUSIONS: In chronic bronchitis and chronic obstructive pulmonary disease, treatment with mucolytics is associated with a reduction in acute exacerbations and days of illness. As these drugs have to be taken long term, they could be most useful in patients who have repeated, prolonged, or severe exacerbations of chronic obstructive pulmonary disease.

Acute Disease↗

PubMed2001

Case management may reduce length of hospital stay in patients with recurrent admissions for chronic obstructive pulmonary disease.

OBJECTIVES: The aim of the study was to determine whether the case management of patients with recurrent hospital admissions for chronic obstructive pulmonary disease (COPD) can reduce hospital days without reducing quality of life. METHODOLOGY: Sixteen subjects (mean forced expiratory volume in 1 second; FEV1 0.64 L) with at least four admissions for COPD in the previous 2 years were case managed by a clinical nurse specialist. Admissions and hospital bed days were recorded before and after the introduction of case management, and compared with data for 16 controls at another hospital who received usual care. Quality of life was measured serially in the case-managed group. RESULTS: In the first year of case management, the number of hospital bed days fell to eight per patient from 22 per patient in the previous year. This was mainly due to a reduction in the length of stay from 5.6 to 3.5 days. In the control group length of stay did not change. Admissions in both groups declined. Case-managed patients had a significant improvement in their quality-of-life scores. CONCLUSIONS: In a group of patients with severe COPD and recurrent admissions, case management reduced the number of days in hospital while improving the quality of life. These findings need to be confirmed in a randomized, controlled trial.

Aged↗

PubMed2000

Affinity labeling fatty acyl-CoA synthetase with 9-p-azidophenoxy nonanoic acid and the identification of the fatty acid-binding site.

Fatty acyl-CoA synthetase (FACS, fatty acid:CoA ligase, AMP-forming, EC ) catalyzes the esterification of fatty acids to CoA thioesters for further metabolism and is hypothesized to play a pivotal role in the coupled transport and activation of exogenous long-chain fatty acids in Escherichia coli. Previous work on the bacterial enzyme identified a highly conserved region (FACS signature motif) common to long- and medium-chain acyl-CoA synthetases, which appears to contribute to the fatty acid binding pocket. In an effort to further define the fatty acid-binding domain within this enzyme, we employed the affinity labeled long-chain fatty acid [(3)H]9-p-azidophenoxy nonanoic acid (APNA) to specifically modify the E. coli FACS. [(3)H]APNA labeling of the purified enzyme was saturable and specific for long-chain fatty acids as shown by the inhibition of modification with increasing concentrations of palmitate. The site of APNA modification was identified by digestion of [(3)H]APNA cross-linked FACS with trypsin and separation and purification of the resultant peptides using reverse phase high performance liquid chromatography. One specific (3)H-labeled peptide, T33, was identified and following purification subjected to NH(2)-terminal sequence analysis. This approach yielded the peptide sequence PDATDEIIK, which corresponded to residues 422 to 430 of FACS. This peptide is immediately adjacent to the region of the enzyme that contains the FACS signature motif (residues 431-455). This work represents the first direct identification of the carboxyl-containing substrate-binding domain within the adenylate-forming family of enzymes. The structural model for the E. coli FACS predicts this motif lies within a cleft separating two distinct domains of the enzyme and is adjacent to a region that contains the AMP/ATP signature motif, which together are likely to represent the catalytic core of the enzyme.

Affinity Labels↗

PubMed2000

The amino-terminal region of the long-chain fatty acid transport protein FadL contains an externally exposed domain required for bacteriophage T2 binding.

The fatty acid transport protein FadL from Escherichia coli is predicted to be rich in beta-structure and span the outer membrane multiple times to form a long-chain fatty acid specific channel. Proteolysis of FadL within whole cells, total membranes, and isolated outer membranes identified two trypsin-sensitive sites, both predicted to be in externally exposed loops of FadL. Amino acid sequence analysis of the proteolytic fragments determined that the first followed R93 and yielded a peptide beginning with 94S-L-K-A-D-N-I-A-P-T-A104 while the second followed R384 and yielded a peptide beginning with 385S-I-S-I-P-D-Q-D-R-F-W395. Proteolysis using trypsin eliminated the bacteriophage T2 binding activity associated with FadL, suggesting the T2 binding domain within FadL requires elements within one of these extracellular loops. A peptide corresponding to the amino-terminal region of FadL (FadL28-160) was purified and shown to inactivate bacteriophage T2 in a concentration-dependent manner, supporting the hypothesis that the amino-proximal extracellular loop of the protein confers T2 binding activity. Using an artificial neural network (NN) topology prediction method in combination with Gibbs motif sampling, a predicted topology of FadL within the outer membrane was developed. According to this model, FadL spans the outer membrane 20 times as antiparallel beta-strands. The 20 antiparallel beta-strands are presumed to form a beta-barrel specific for long-chain fatty acids. On the basis of our previous studies evaluating the function of FadL using site-specific mutagenesis of the fadL gene, proteolysis of FadL within outer membranes, and studies using the FadL28-160 peptide, the predicted extracellular regions between beta-strands 1 and 2 and beta-strands 3 and 4 are expected to contribute to a domain of the protein required for long-chain fatty acid and bacteriophage T2 binding. The first trypsin-sensitive site (R93) lies between predicted beta-strands 3 and 4 while the second (R384) is between beta-strands 17 and 18. The trypsin-resistant region of FadL is predicted to contain 13 antiparallel beta-strands and contribute to the long-chain fatty acid specific channel.

Bacterial Outer Membrane Proteins↗

PubMed2000

Physical training for asthma.

BACKGROUND: Physical training programmes have been designed for asthmatic subjects with the aim of improving physical fitness, neuromuscular coordination and self-confidence. Habitual physical activity increases physical fitness and lowers ventilation during mild and moderate exercise thereby reducing the likelihood of provoking exercise -induced asthma. Exercise training may also reduce the perception of breathlessness through a number of mechanisms including strengthening respiratory muscles. Subjectively, many asthmatics report that they are symptomatically better when fit, but results from trials have varied and have been difficult to compare because of different designs and training protocols. OBJECTIVES: The purpose of this review was to assess evidence for the efficacy and effectiveness of physical training in asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register, Sportdiscus and Science citation index. SELECTION CRITERIA: Randomised trials in asthmatic subjects undertaking physical training. Subjects had to be 8 years and older. Physical training had to be undertaken for at least 20 to 30 minutes, 2 to 3 times a week, over a minimum of four weeks. DATA COLLECTION AND ANALYSIS: Eligibility for inclusion and quality of trials were assessed independently by two reviewers. MAIN RESULTS: Eight studies could be included in this review. Physical training had no effect on resting lung function or the number of days of wheeze. Physical training improved cardiopulmonary fitness as measured by an increase in maximum oxygen uptake of 5.6 ml/kg/min (95% confidence interval 3. 9 to 7.2). There were no data concerning quality of life measurements. REVIEWER'S CONCLUSIONS: In people with asthma, physical training can improve cardiopulmonary fitness without changing lung function. It is not known whether improved fitness is translated into improved quality of life.

Asthma↗