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Biomedical subjects

Paul Jones

Publications and source records attributed to Paul Jones.

At least 19 recordsLinked to original sources
PubMed2007

Implications of chronic obstructive pulmonary disease (COPD) on patients' health status: a western view.

AIM: To assess and compare health status among chronic obstructive pulmonary disease (COPD) patients presenting for treatment in six countries and in two healthcare settings using a generic health status instrument. METHODS: A population based cross-sectional survey was conducted among 2703 patients and their physicians (1381 in primary and 1322 in specialty care) in five EU countries and the USA. Information was collected on demographic and clinical characteristics, exacerbations and health status estimated using EQ-5D. RESULTS: The mean EQ-5D score for COPD patients was similar between primary and specialty settings in all countries except Italy. Approximately, half of the patients indicated some impairment in health status on mobility, usual activities, pain/discomfort and anxiety/depression domains of EQ-5D. Approximately, 5% of patients in EU countries except UK had health status valued as worse than death based on valuations of the general population. Patients suffering from severe breathlessness, experiencing > or =3 exacerbations in the previous year, categorised as severe according to GOLD criteria, and experiencing day-time and night-time symptoms had significantly impaired health status. CONCLUSION: COPD patients classified as moderate/severe in clinical practice have worse health status compared to mild patients. This impairment is similar in primary and specialty setting across western countries.

Age Distribution↗
PubMed2007

Layer-by-layer assembly of pH-responsive, compositionally controlled (co)polyelectrolytes synthesized via RAFT.

Homo- and block copolyelectrolytes that have well-defined structures and are responsive to pH were synthesized via reversible addition-fragmentation chain-transfer (RAFT) polymerization and employed to produce layer-by-layer (LBL) films. Acrylamido monomers with carboxylate, sulfonate, and amine functionality were utilized to provide both strong and weak homopolyelectrolytes and mixed strong/weak copolyelectrolyte systems. Multilayer films were prepared under specified conditions of pH and ionic strength and analyzed via atomic force microscopy and ellipsometry to study the effects of changes in the local molecular environment on film morphologies. The pH responsiveness and integrity of the multilayer assemblies were investigated by exposing films to solutions of varying pH in a fluid cell and performing in situ AFM analysis. The multilayer dimensions, morphology, and integrity were found to depend on the molecular architecture of the polyelectrolytes, with changes in segmental type and repeating unit distribution producing dramatic differences in film characteristics. These results suggest the possibility of producing LBL assemblies of precisely controlled dimensions and properties by specifically tailoring copolymer structure. To our knowledge, this is the first report of LBL assembly of RAFT-synthesized homo- and copolyelectrolyte multilayer complexes.

Journal Article↗
PubMed2006

The potential impact of poison control centers on rural hospitalization rates for poisoning.

OBJECTIVE: This study tested the hypothesis that underutilization of poison control centers is associated with increased rates of hospitalizations attributable to poisonings in rural areas. METHODS: To measure the potential impact of poison control centers on hospitalization rates in rural areas among people who visit emergency departments because of poisoning, we estimated the reduction in hospitalization rates associated with increased rates of calls to centers. We used the 2003 State Inpatient Database and State Emergency Department Database from the Healthcare Cost and Utilization Project to calculate the numbers of emergency department visits and hospitalizations for each county in the 12 states analyzed. We used Toxic Exposure Surveillance System data from the American Association of Poison Control Centers to calculate the number of human exposure calls per capita according to county. RESULTS: In rural counties, a 1% higher poison control center human poison exposure call rate was associated with a 0.19% lower hospitalization rate among people who visited emergency departments because of poisoning. If the observed association is causative, then 43.3 calls would prevent 1 hospital admission, yielding 7321 dollars in net cost savings and a return on investment of 5.9:1 (from the health care system perspective). CONCLUSIONS: Our results establish the existence of the hypothesized association between rural poison control center utilization rates and hospitalization rates among emergency department-treated poisoning patients.

Child↗
PubMed2005

Measuring the effects of COPD on the patient.

Evaluation of the effectiveness of treatment for chronic obstructive pulmonary disease (COPD) requires the assessment of both clinical and physiological measures. Parameters such as the forced expiratory volume in 1 s are well established in providing an indication of the degree of airflow limitation. However, additional measurements, such as dyspnoea, functional status and health status, are required to provide a complete picture of COPD. Indeed, dyspnoea is the predominant symptom of COPD experienced by the patient, which treatment is designed to reduce. Methods of assessing dyspnoea have developed over the previous five decades. The most widely used instruments for assessing the impact of dyspnoea are the baseline dyspnoea index, the transition dyspnoea index and the Medical Research Council Questionnaire. A more comprehensive approach to the assessment of disability caused by dyspnoea and fatigue is provided by assessments of functional status, such as the pulmonary functional status and dyspnoea questionnaire. Respiratory-specific health status questionnaires, such as the St. George's Respiratory Questionnaire, attempt to capture the wide range of effects of COPD into a single score that reflects the overall impact of the disease. Developing the means to measure the effects of COPD is important, both in terms of understanding disease pathophysiology for research purposes, and in terms of accurately assessing the effects of treatment on the patient. Future developments will include computerising these methodologies to permit faster and more individual patient-centred measurements.

Dyspnea↗
PubMed2005

Proposal for a multidimensional staging system for chronic obstructive pulmonary disease.

The severity of chronic obstructive pulmonary disease (COPD) is currently assessed using a single physiological measurement, the forced expiratory volume in 1s (FEV1). COPD, however, has complex effects on other aspects of respiratory function, and in many patients is associated with important systemic changes. We hypothesized that a multidimensional staging system for COPD could provide a more complete assessment of the disease's impact. We considered over 40 potential staging variables, evaluating them according to sensitivity to change, measured reproducibly, independence of the information they provide and prognostic value. We finally selected three: FEV1 (including arterial blood gas measurements when FEV1 falls below 35% predicted), Medical Research Council dyspnea scale and body mass index (BMI). Each measure correlates independently with prognosis in COPD, is supported by a significant body of literature and serves as a surrogate for other potentially important variables. We then used principal components analysis (PCA) to determine the degree of association between 30 of the potential variables measured in 813 stable COPD patients. Using PCA, six groups of measurements defined independent categories of patient information: pulmonary function (including FEV1), symptoms of cough and sputum, dyspnea, health status, bronchodilator reversibility and BMI. These include the three principal variables selected for the staging system. Although the staging boundaries were based on existing literature, they have proven useful in predicting survival. We conclude that a multidimensional grading system is useful to assess the impact of COPD.

Age Factors↗
PubMed2004

Clinically meaningful outcomes in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow limitation, gas exchange abnormalities, hyperinflation, and other pathophysiologic events. However, patients are usually unaware of these physical changes and only seek medical attention when distressing symptoms, such as dyspnea and exercise limitation, begin to appear. Therefore, it is reasonable to directly assess these clinical areas of importance to the patient, both as determinants of the impact of the disease process and as outcomes following intervention. Although many of the physiologic abnormalities of COPD are only partially or poorly reversible with treatment, dyspnea, exercise performance, and health status often show impressive gains with therapy. Incorporating clinically relevant outcome assessments complements traditional physiologic measurements and provides the clinician with a yardstick to determine whether a particular intervention is causing a meaningful improvement in the patient. This article discusses these clinical assessments and provides specific examples of their applicability and usefulness in treating patients with COPD.

Clinical Trials as Topic↗
PubMed2004

Can contact-angle measurements determine the disjoining pressure in liquid nanofilms on rigid substrates?

The disjoining pressure of lubricant nanofilms used in the magnetic recording industry controls the equilibrium wetting, the dynamics of film restoration, and the evaporation kinetics of the film. It has been claimed that by measuring the contact angle of nonpolar and polar liquids on lubricant films, the disjoining pressure can be extracted using the method of Girafalco and Good, and such analyses have appeared in the literature. The approximations underlying the method have been discussed before in the literature. In view of the importance of measuring disjoining pressure in nanofilms of lubricants, it is timely to revisit these assumptions to understand the validity of the contact-angle method presently in use. We re-derive the relevant equations using a thermodynamic-interaction-energy approach which is free of the problems inherent in the original derivation and make explicit the assumptions which must be made in the derivation. General interaction energy arguments are then invoked to demonstrate that it does not appear possible to obtain the disjoining pressure in the film from contact-angle measurements in an unambiguous manner.

Journal Article↗
PubMed2004

Effects of atrazine on metamorphosis, growth, and gonadal development in the green frog (Rana clamitans).

Embryos of the green frog (Rana clamitans) were collected from the field and exposed to 1 of 6 water-borne treatments for 273 d (mid July 2001 to mid April 2002). The treatments were 0, 10, or 25 microg/L atrazine, 0.005% ethanol (EtOH), or 0.1 mg/L estradiol or dihydrotestosterone carried in 0.005% EtOH. Treatments were applied in a static renewal system with a 50% test solution replacement approximately every 3 d. Following the exposure period, tadpoles were reared in freshwater until metamorphosis or until study termination (at d 506). Time to initiate and complete metamorphosis, stage-specific mortality, length and weight at metamorphosis, and gross morphology and histology of the gonads were examined. At environmentally relevant concentrations, atrazine did not consistently affect growth or metamorphosis. Compared to controls, the length of the larval period was greater in tadpoles exposed to 10 microg/L atrazine. However, the length of the larval period was not markedly different between tadpoles in the control and 25 microg/L atrazine treatments. Neither gross gonadal morphology nor histopathology of the gonads in postmetamorphic frogs was significantly altered in response to atrazine exposure. This study provides evidence that environmentally relevant concentrations of atrazine do not adversely affect the growth or reproductive development of R. clamitans.

Animals↗
PubMed2004

Retrospective cohort study of false alarm rates associated with a series of heart operations: the case for hospital mortality monitoring groups.

OBJECTIVE: To examine the efficacy of different methods of detecting a high death rate and determining whether an increase in deaths after heart transplantation could be explained by chance. DESIGN: Retrospective analysis of deaths after heart transplantation. Seven methods were used: mortality above national average, mortality excessively above national average, test of moving average mortality, test of number of consecutive deaths, sequential probability ratio test (SPRT), cusum graph with v-mask, and CRAM chart. The national average mortality was not available and a rate of 15% was used instead as the benchmark. SETTING: Regional cardiothoracic unit. PARTICIPANTS: All 371 patients who received a heart transplant in the programme, 1986-2000. MAIN OUTCOME MEASURES: 30 day survival after transplantation. RESULTS: All methods provided evidence that the 30 day mortality had been high at some stage. The probability that the finding was a false positive depended on which test was used. At the end of the series the average mortality, sequential probability ratio, and cusum tests indicated a level of deaths higher than the benchmark while the remaining four tests yielded negative results. CONCLUSIONS: If the decision to test for outlying mortality is made retrospectively, in the light of the data, it is not possible to determine the false positive rate. Prospective on-site mortality monitoring with the CRAM chart is recommended as this method can quantify the death rate and identify periods when an audit of cases is indicated, even when data from other institutions are not available. A hospital mortality monitoring group can routinely monitor all deaths in the hospital, by specialty, using hospital episode statistics (HES) data and appropriate statistical methods.

Cohort Studies↗
PubMed2004

Development of a primary-care tool to assess treatment success in COPD: consensus report from a closed meeting of respiratory and primary-care specialists.

A 1-day meeting, attended by invited respiratory and primary-care specialists all of whom had an international profile and a specific interest in Chronic Obstructive Pulmonary Disease (COPD), considered specific research recommendations from the Global Initiative in Obstructive Lung Disease (GOLD) workshop report. Attendees discussed developing a tool to complement spirometry and help primary-care physicians assess treatment success in patients with chronic obstructive pulmonary disease. Discussion focused on the requirement of such a tool, and the limitations of existing tools. Proposals followed for a simple, cost-effective checklist for primary-care. This paper is a consensus report of the discussions from the meeting. Decisions reached on the proposed questionnaire were unanimous.

Journal Article↗
PubMed2004

Gender does not influence the response to the combination of salmeterol and fluticasone propionate in COPD.

The prevalence of chronic obstructive pulmonary disease (COPD) in women is increasing worldwide. Women may have greater susceptibility to COPD progression than men, and differences in efficacy and safety of respiratory medications by gender are largely unexplored. We aimed to determine whether the response to treatment in women with COPD differed from men in a large, 1-year double-blind trial ('TRISTAN'). In a sensitivity analysis, we compared 539 male and 180 female COPD patients, who were randomized to the saLmeterol/fluticasone combination 50/500mcg bid or placebo for 12 months. Combination therapy improved pre-treatment FEV1 significantly more than placebo in women by 152 ml (95% confidence interval 95-208) and in men by 127 ml (94-159). Similarly, a reduction in COPD exacerbation rates of 31% in women (9-48%) and of 23% in men (8-35%) was observed. Combination therapy reduced COPD exacerbations requiring treatment with oral corticosteroids by 36% in women and by 41% in men. Finally, combination treatment produced a better improvement in health status than placebo with a decrease in the SGRQ scores in women by -2.3 (-4.6 - 0.1) and in men by -2.1 (-3.5 to -0.8). No gender interaction was found for any outcome. Treatments were well tolerated with no difference in the frequency of adverse events in women and men. In this trial, therapy with the salmeterol/fluticasone combination produced significant improvements compared to placebo on all main endpoints and the magnitude of these improvements was similar for both men and women.

Adrenergic beta-Agonists↗
PubMed2004

Pentameric procyanidins isolated from Theobroma cacao seeds selectively downregulate ErbB2 in human aortic endothelial cells.

Flavonoids isolated from cocoa have biological activities relevant to oxidant defenses, vascular health, tumor suppression, and immune function. The intake of certain dietary flavonoids, along with other dietary substances such as tocopherols, ascorbate, and carotenoids, is epidemiologically associated with a reduced risk of cardiovascular disease. Flavonoids have also been shown to modulate tumor pathology in vitro and in animal models. We took advantage of the conserved sequences found in tyrosine kinases to study the influence of cocoa fractions and controls on gene expression. We report that the pentameric procyanidin (molecular weight of 1442 daltons) fraction isolated from cocoa was a potent inhibitor of tyrosine kinase ErbB2 expression, a receptor important in angiogenesis regulation. Consistent with this primary observation, the cocoa flavonoid fraction also suppressed human aortic endothelial cell (HAEC) growth and decreased expression of two tyrosine kinases responsive to ErbB2 modulation, namely VEGFR-2/KDR and MapK 11/p38beta2. These inhibitory effects were observed when HAECs were treated with the flavonol fraction (molecular weight 280 daltons) isolated from cocoa, which comprise the structural subunits from which the procyanidin flavonoid subclass is biosynthetically constructed. Down-regulation of ErbB2 and inhibition of HAEC growth by cocoa procyanidins may have several downstream implications, including reduced vascular endothelial growth factor (VEGF) activity and angiogenic activity associated with tumor pathology. These results suggest specific dietary flavonoids are capable of selectively inhibiting ErbB2 and therefore may offer important insight into the design of therapeutic agents that target tumors overexpressing ErbB2.

Antioxidants↗
PubMed2004

Cocoa procyanidins inhibit proliferation and angiogenic signals in human dermal microvascular endothelial cells following stimulation by low-level H2O2.

Procyanidins extracted from cocoa play a role in the defense against oxidative stress, as well as in vascular and immune functions. We previously reported that pentameric procyanidins isolated from cocoa inhibit the expression of the tyrosine kinase ErbB2 gene, thus slowing the growth of cultured human aortic endothelial cells. We herein investigate the further consequences of such inhibition by cocoa procyanidins, particularly regarding the protein level in phosphorylation patterns and the effects on the proliferation of human dermal microvascular endothelial cells (HDMECs) following angiogenic stimulation with low-level H2O2. We report herein that both the pentameric and octameric procyanidin fractions of cocoa inhibit the proliferation of HDMECs, whereas the pentameric fraction modulates the activity of several crucial proteins in angiogenic signaling by altering their tyrosine phosphorylation. Similar to aortic endothelial cells, the pentameric procyanidin fraction down-regulates the expression of ErbB2 tyrosine kinase in HDMECs. In conclusion, we report evidence suggesting that polyphenols may influence endothelial growth signaling, thus affecting angiogenesis in vitro. If these observations are applicable in vivo, they suggest a beneficial effect for cells overexpressing ErbB2, such as in specific neoplasias

Biflavonoids↗
PubMed2004

Short-term and long-term outcomes of moxifloxacin compared to standard antibiotic treatment in acute exacerbations of chronic bronchitis.

STUDY OBJECTIVES: To compare the effectiveness of oral moxifloxacin with standard antibiotic therapy in acute exacerbation of chronic bronchitis (AECB). DESIGN: Multicenter, multinational, randomized, double-blind study of two parallel treatment arms. PATIENTS: Outpatients >or= 45 years old with stable chronic bronchitis, smoking history of >or= 20 pack-years, two or more AECBs in the previous year, and FEV(1) < 85% of predicted value. Patients were enrolled when in a stable condition, and patients with exacerbations within 12 months of enrollment were randomized. INTERVENTIONS: Randomization (stratified on steroid use) between moxifloxacin (400 mg qd for 5 days) and standard therapy (amoxicillin [500 mg tid for 7 days], clarithromycin [500 mg bid for 7 days], or cefuroxime-axetil [250 mg bid for 7 days]). MEASUREMENTS: Assessment at enrollment, randomization (Anthonisen type 1 exacerbation), 7 to 10 days after treatment, and monthly until next AECB or up to 9 months. The primary efficacy variable was clinical success (sufficient improvement, no alternative antimicrobial therapy required) 7 to 10 days after therapy. Secondary predefined end points were clinical cure (return to pre-exacerbation status), further antimicrobial use, time to next AECB, and bacteriologic success. RESULTS: Three hundred fifty-four patients received moxifloxacin, and 376 patients received standard therapy. At 7 to 10 days after therapy, clinical success rates were similar in intention-to-treat (ITT) patients (95% confidence interval [CI], - 0.7 to 9.5) and per-protocol (PP) patients (95% CI, - 3.0 to 8.5). Moxifloxacin showed superior clinical cure rates over standard therapy in both ITT patients (95% CI, 1.4 to 14.9) and PP patients (95% CI, 0.3 to 15.6), and higher bacteriologic success in microbiologically valid patients (95% CI, 0.4 to 22.1). Fewer ITT patients required antimicrobials after treatment with moxifloxacin than standard therapy (p < 0.01). Time to next exacerbation was longer with moxifloxacin; median and mean times to new AECBs in ITT patients who did not require any further antibiotics were 131.0 days and 132.8 days in moxifloxacin, and 103.5 days and 118.0 days in standard therapy, respectively (p = 0.03). The occurrence of failure, new exacerbation, or any further antibiotic was less frequent in moxifloxacin-treated patients for up to 5 months of follow-up (p = 0.03). CONCLUSIONS: Moxifloxacin was equivalent to standard therapy for clinical success and showed superiority over standard therapy in clinical cure, bacteriologic eradication, and long-term outcomes.

Acute Disease↗
PubMed2003

Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial.

BACKGROUND: Inhaled long-acting beta2 agonists improve lung function and health status in symptomatic chronic obstructive pulmonary disease (COPD), whereas inhaled corticosteroids reduce the frequency of acute episodes of symptom exacerbation and delay deterioration in health status. We postulated that a combination of these treatments would be better than each component used alone. METHODS: 1465 patients with COPD were recruited from outpatient departments in 25 countries. They were treated in a randomised, double-blind, parallel-group, placebo-controlled study with either 50 microg salmeterol twice daily (n=372), 500 microg fluticasone twice daily (n=374), 50 microg salmeterol and 500 microg fluticasone twice daily (n=358), or placebo (n=361) for 12 months. The primary outcome was the pretreatment forced expiratory volume in 1s (FEV1) after 12 months treatment' and after patients had abstained from all bronchodilators for at least 6h and from study medication for at least 12h. Secondary outcomes were other lung function measurements, symptoms and rescue treatment use, the number of exacerbations, patient withdrawals, and disease-specific health status. We assessed adverse events, serum cortisol concentrations, skin bruising, and electrocardiograms. Analysis was as predefined in the study protocol. FINDINGS: All active treatments improved lung function, symptoms, and health status and reduced use of rescue medication and frequency of exacerbations. Combination therapy improved pretreatment FEV1 significantly more than did placebo (treatment difference 133 mL, 95% CI 105-161, p<0.0001), salmeterol (73 mL, 46-101, p<0.0001), or fluticasone alone (95 mL, 67-122, p<0.0001). Combination treatment produced a clinically significant improvement in health status and the greatest reduction in daily symptoms. All treatments were well tolerated with no difference in the frequency of adverse events, bruising, or clinically significant falls in serum cortisol concentration. INTERPRETATION: Because inhaled long-acting beta2 agonists and corticosteroid combination treatment produces better control of symptoms and lung function, with no greater risk of side-effects than that with use of either component alone, this combination treatment should be considered for patients with COPD.

Adrenergic beta-Agonists↗
PubMed2003

Is naturopathy as effective as conventional therapy for treatment of menopausal symptoms?

BACKGROUND: Although the use of alternative medicine in the United States is increasing, no published studies have documented the effectiveness of naturopathy for treatment of menopausal symptoms compared to women receiving conventional therapy in the clinical setting. OBJECTIVE: To compare naturopathic therapy with conventional medical therapy for treatment of selected menopausal symptoms. DESIGN: A retrospective cohort study, using abstracted data from medical charts. SETTING: One natural medicine and six conventional medical clinics at Community Health Centers of King County, Washington, from November 1, 1996, through July 31, 1998. PATIENTS: Women aged 40 years of age or more with a diagnosis of menopausal symptoms documented by a naturopathic or conventional physician. MAIN OUTCOME MEASURES: Improvement in selected menopausal symptoms. RESULTS: In univariate analyses, patients treated with naturopathy for menopausal symptoms reported higher monthly incomes ($1848.00 versus $853.60), were less likely to be smokers (11.4% versus 41.9%), exercised more frequently, and reported higher frequencies of decreased energy (41.8% versus 24.4%), insomnia (57.0% versus 33.1%), and hot flashes (69.6% versus 55.6%) at baseline than those who received conventional treatment. In multivariate analyses, patients treated with naturopathy were approximately seven times more likely than conventionally treated patients to report improvement for insomnia (odds ratio [OR], 6.77; 95% confidence interval [CI], 1.71, 26.63) and decreased energy (OR, 6.55; 95% CI, 0.96, 44.74). Naturopathy patients reported improvement for anxiety (OR, 1.27; 95% CI, 0.63, 2.56), hot flashes (OR, 1.40; 95% CI, 0.68, 2.88), menstrual changes (OR, 0.98; 95% CI, 0.43, 2.24), and vaginal dryness (OR, 0.91; 95% CI, 0.21, 3.96) about as frequently as patients who were treated conventionally. CONCLUSIONS: Naturopathy appears to be an effective alternative for relief of specific menopausal symptoms compared to conventional therapy.

Anxiety↗
PubMed2003

A biomechanical analysis of the acute effects of complex training using lower limb exercises.

The aim of this study was to investigate the current practice of complex training using a lower body combination of exercises. It was hypothesized that a bout of heavy resistance exercise (HRE), as typically used in complex training, would lead to enhanced performance (in the form of counter-movement [CMJ] and drop [DJ] jump height) and increased electromyographical (EMG) activity in subsequent plyometric exercise, also typical of complex training. Eight strength trained men performed 2 conditions: HRE or control (no-HRE) in a counter-balanced order. Both conditions involved 4 sets of 6-jump trials (3-CMJ/ 3-DJ). The first set of jumps was used as a baseline. For the HRE condition, 5-squats at 85% of 1 repetition maximum (1RM) followed shortly after the first set, while the second, third and fourth sets followed at 3-, 10-, and 20-minutes post-HRE, respectively. The control condition involved the same procedure, but no exercise separated the first 2-sets. There were no significant main effects (p > 0.05) for any CMJ performance variable or EMG activity regardless of muscle or phase of jump. There were no significant (p > 0.05) main effects of heavy resistance exercise on DJ performance variables. Only the biceps femoris during the propulsive phase of the DJ was significantly higher (p < 0.05) following HRE compared to no-HRE. Some trends in the data were evident and the power of the statistical tests was low. It was concluded that no evidence was found to support the experimental hypothesis although the absence of a treatment effect could not be ruled out. From a practical point of view, undertaking a bout of HRE had no adverse effects on subsequent plyometric performance and so some of the advantages of complex training still remain.

Analysis of Variance↗