Biomedical subjects

A M Wilson

Publications and source records attributed to A M Wilson.

At least 55 records · Page 3Linked to original sources

PubMed2002

A comparison of once daily fexofenadine versus the combination of montelukast plus loratadine on domiciliary nasal peak flow and symptoms in seasonal allergic rhinitis.

BACKGROUND: The combination of montelukast (ML) and loratadine (LT) has previously been shown to be superior to either drug alone in managing seasonal allergic rhinitis (SAR), whilst fexofenadine (FEX) has been shown to be better than LT as monotherapy. OBJECTIVES: We wished to compare ML + LT vs. FEX alone for effects on daily measurements (am/pm) of peak inspiratory flow (PIF) and symptoms. METHODS: Thirty-seven patients with SAR (skin prick positive to grass pollen) were randomised into a single-blind, double-dummy placebo (PL)-controlled cross-over study during the grass pollen season, comparing 2 weeks of once daily treatment with (a) 120mg FEX or (b) 10mg ML + 10mg LT. There was a 7-10 day placebo run-in and washout prior to each randomised treatment. The average of am/pm PIF (the primary outcome variable) was analysed. Patients recorded their symptom scores (from 0 to 3) twice daily, for nasal blockage, discharge, itching and sneezing with; total eye symptoms, ocular cromoglycate use, and daily activity. The total nasal symptom score was calculated as a composite (out of 24). RESULTS: There were no significant differences between baselines after the run-in and washout placebos for any variables. There were significant (P < 0.05, Bonferroni) improvements in all symptoms and PIF compared to pooled placebo with both treatments for all end-points, but no differences between the two treatment regimes (as means and within-treatment 95% confidence intervals): PIF: PL 102 (98-107), FEX 111 (107-116), ML+LT 113 (109-118); total nasal symptoms: PL 7.4 (6.7-2.0), FEX 5.0 (4.3-5.7), ML + LT 4.0 (3.3-4.7). CONCLUSIONS: Once daily FEX as monotherapy was equally effective as the combination of once daily ML + LT in improving nasal peak flow and controlling symptoms in SAR. Further studies are indicated to assess whether ML confers additional benefits to FEX in SAR.

Acetates↗

PubMed2002

Effects of fexofenadine and desloratadine on subjective and objective measures of nasal congestion in seasonal allergic rhinitis.

BACKGROUND: In vitro studies have shown much higher H1-receptor antagonist potency with desloratadine (DL) compared to fexofenadine (FEX), although it is unclear whether this has any clinical relevance on disease control parameters in seasonal allergic rhinitis (SAR), especially for nasal congestion. OBJECTIVE: To compare the relative efficacy between presently recommended doses of DL and FEX on daily measurements of peak nasal inspiratory flow (PNIF) and nasal symptoms in SAR. METHODS: Forty-nine patients with SAR were randomized into a double-blind, placebo-controlled cross-over study during the grass pollen season, comparing 2 weeks of once daily treatment with (a) 180 mg FEX or (b) 5 mg DL, taken in the morning. There was a 7-10 day placebo run-in and washout prior to each randomized treatment. Measurements were made in the morning (AM) and in the evening (PM) for PNIF (the primary outcome variable), nasal and eye symptoms. The average of AM/PM values were used for analysis. RESULTS: There were significant (P < 0.05) improvements, compared to placebo, with FEX and DL, for PNIF, nasal blockage, nasal irritation, and total nasal symptoms, but not nasal discharge or eye symptoms. There were no significant differences between active treatments. Values for PNIF (L/min) for mean placebo baseline, mean difference from baseline (95% CI for difference) were 126, 10 (4-16) for FEX; and 122, 11 (4-17) for DL. The mean difference (95% CI) between FEX vs. DL was 1 L/min (-7-8). Values for total nasal symptoms (out of 12) were: 3.2, 0.7 (0.2-1.2) for FEX; and 3.4, 0.9 (0.3-1.5) for DL, and for nasal blockage (out of 3) were: 1.1, 0.2 (0.1-0.4) for FEX; and 1.2, 0.3 (0.1-0.5) for DL. The mean difference (95% CI) in total nasal symptoms and nasal blockage between FEX vs. DL was 0.1 (-0.6-0.8) and 0.1 (-0.2-0.3), respectively. CONCLUSIONS: Recommended once daily doses of fexofenadine and desloratadine were equally effective in improving nasal peak flow and nasal symptoms in SAR.

Adult↗

PubMed2002

Airway and systemic effects of hydrofluoroalkane fluticasone and beclomethasone in patients with asthma.

BACKGROUND: With the transition to hydrofluoroalkane-134a propellants in metered dose inhalers, it is important to consider the efficacy and safety profiles of formulations containing inhaled corticosteroids. We examined the airway and systemic effects of hydrofluoroalkane-134a fluticasone propionate (FLU-HFA) and beclomethasone dipropionate (BEC-HFA) at recommended labelled doses. METHODS: Twenty mild to moderate asthmatics were randomised in crossover fashion to receive 6 weeks of 500 micro g/day followed by 1000 micro g/day FLU-HFA and BEC-HFA. Measurements were made at baseline after placebo run in and washout, and after each randomised treatment. The primary airway outcome for benefit was the dose of methacholine provoking a fall in forced expiratory volume in 1 second (FEV(1)) of 20% or more (methacholine PD(20)) and for systemic adverse effects was overnight urinary cortisol/creatinine (OUCC). RESULTS: For mean responses, both doses of BEC-HFA and FLU-HFA produced significant improvements in PD(20) compared with baseline. The improvement was not significantly greater with 1000 micro g/day FLU-HFA versus BEC-HFA, a 1.69 fold difference (95% CI 0.94 to 3.04). Both doses of BEC-HFA but not FLU-HFA caused significant suppression of OUCC compared with baseline, with significantly (p<0.05) lower values at 1000 micro g/day for BEC-HFA versus FLU-HFA (1.97 fold difference (95% CI 1.28 to 3.02)). CONCLUSION: There was no difference in the airway and systemic effects in patients with mild to moderate asthma between FLU-HFA and BEC-HFA at a dose of 500 micro g/day. At 1000 micro g/day there was increased systemic bioactivity with BEC-HFA compared with FLU-HFA, without any gain in airway efficacy.

Adult↗

PubMed2002

In vitro evaluation of nonrigid support systems for the equine metacarpophalangeal joint.

Metacarpophalangeal (MCP) joint extension is primarily resisted by the digital flexor tendons and suspensory ligament. A variety of external support techniques are used to protect these supporting structures from or after injury by resisting MCP joint extension, although not all are effective and/or practical for use in an exercising horse. In this study, 7 forelimbs were loaded in vitro to determine the effect of a simple gamgee bandage, a 3-layered bandage with and without a contoured palmar splint, a neoprene exercise boot, and an innovative carbon fibre composite exercise boot (Dalmar tendon support boot). There was no significant resistance to MCP joint extension by the gamgee or neoprene exercise boot. The 3-layered bandage had a significant (P<0.01) supporting effect at MCP angles of > or = 245 degrees, and when combined with the contoured splint at angles of > or = 230 degrees. The Dalmar tendon support boot resisted MCP extension at angles of > or = 245 degrees (settings 1 and 2) and > or = 225 degrees (setting 3). These data demonstrate that the contoured splint and the Dalmar tendon support boot (which is also easily fitted for use during exercise) are useful for the management of tendon/ligament injury and during rehabilitation.

Animals↗

PubMed2002

A comparison of three horseshoeing styles on the kinetics of breakover in sound horses.

A variety of horseshoe designs are believed to 'ease' breakover, or the unloading of the foot once the heels leave the ground. In this study, conventional toe-clip shoes, quarter-clip shoes, fitted to the white line at the toe, and Natural Balance horseshoes were fitted to the front feet of 9 sound Irish Draught-cross type horses. Forceplate and video motion analyses were undertaken during trot locomotion to determine the moment arm of the ground reaction force on the distal interphalangeal (DIP) joint, the peak DIP joint moment and the peak compressive force on the navicular bone. DIP joint moment arm during breakover was reduced with both Natural Balance (mean +/- s.d. 77 +/- 7 mm) and quarter-clip shoes (78 +/- 9 mm) compared to the toe-clip shoes (86 +/- 6 mm) (P<0.01). Peak DIP joint moment was not significantly different (175 +/- 37,171 +/- 38 and 175 +/- 31 Nmm/kg, in Natural Balance, quarter-clip and toe-clip shoes, respectively) and neither was peak force on the navicular bone (5.52 +/- 1.52, 5.79 +/- 1.53 and 6.14 +/- 1.47 N/kg, respectively). Breakover duration (heel off to toe off) was not significantly reduced by the Natural Balance shoes (39 +/- 6 ms) or the quarter-clip shoes (40 +/- 6 ms) compared to toe-clip shoes (42 +/- 9 ms). This study has demonstrated that the use of Natural Balance shoes reduces the moment arm of the ground reaction force (GRF) during breakover but does not reduce the peak DIP joint moment or the force on the navicular bone.

Animals↗

PubMed2001

Trichloroethylene oxidative metabolism in plants: the trichloroethanol pathway.

Trichloroethylene (TCE) is a widespread and persistent environmental contaminant. Recently, plants, poplar trees in particular, have been investigated as a tool to remove TCE from soil and groundwater. The metabolism of TCE in plants is being investigated for two reasons: one, plant uptake and metabolism represent an important aspect of the environmental fate of the contaminant; two, metabolism pattern and metabolite identification will help assess the applicability of phytoremediation. It was previously shown that TCE metabolites in plants are similar to ones that result from cytochrome P450-mediated oxidation in mammals: trichloroethanol, trichloroacetate and dichloroacetate. Our measurements indicate that one of these metabolites, trichloroethanol, is further glycosylated in tobacco and poplar. The glycoside was detected in all tissues (roots, stems and leaves) in comparable levels, and was at least 10 fold more abundant than free trichloroethanol. The glycoside in tobacco was identified as the ss-D-glucoside of trichloroethanol by comparison of the mass spectra and the chromatographic retention time of its acetylation product to that of the synthesized standard. Trichloroethanol and its glucoside did not persist in plant tissue once plants are removed from TCE contaminated water, indicating further metabolism.

Ethylene Chlorohydrin↗

PubMed2001

Effects of topical corticosteroid and combined mediator blockade on domiciliary and laboratory measurements of nasal function in seasonal allergic rhinitis.

BACKGROUND: Both domiciliary and laboratory measures of nasal function have been used to evaluate treatment response in allergic airways disease; however, these measures have not been compared. OBJECTIVE: To determine the relationship of domiciliary measures (daily symptoms, peak inspiratory nasal flow, and nasal oral index) and laboratory measures (rhinomanometry, acoustic rhinometry) in assessing treatment response with topical steroids and specific inflammatory mediator blockage. METHODS: Twenty-one patients with seasonal allergic rhinitis and asthma were enrolled into a single-blind, placebo-controlled, crossover study comparing 2 weeks of 1) 400 microg inhaled plus 200 microg intranasal budesonide once daily and 2) 10 mg montelukast plus 10 mg cetirizine once daily. Before each treatment, patients received 7 to 10 days of placebo period. Laboratory measurements were made of nasal resistance by posterior rhinomanometry, and nasal volume between 0 and 5 cm by acoustic rhinometry after both placebo and active treatment periods. Daily domiciliary recordings were made of allergic rhinitis nasal symptoms scores and peak nasal and oral inspiratory flow rate (enabling the calculation of a nasal/oral index) throughout the study. RESULTS: There were significant (P < 0.05) improvements for all allergic rhinitis symptoms with both therapies, after factoring for pollen count. Spearman's rank correlation for comparison among nasal symptoms and the objective responses were: nasal inspiratory flow rate (R = -0.50, P = 0.02); nasal/oral index (R = -0.55 P = 0.01); rhinomanometry (R = 0.24, P = 0.30); and acoustic rhinometry (R = -0.21, P = 0.36). CONCLUSIONS: Both treatments were effective in managing allergic rhinitis symptoms, and patients' symptoms were more closely associated with domiciliary measurements of nasal flow than laboratory measurements of nasal function.

Acetates↗

PubMed2001

Dose-response for adrenal suppression with hydrofluoroalkane formulations of fluticasone propionate and beclomethasone dipropionate.

AIMS: With the recent introduction of hydrofluoroalkane (HFA) inhalers it is important to know the relative systemic safety profiles of inhaled corticosteroids. We therefore decided to compare systemic bioavailability of HFA-beclomethasone dipropionate (BDP) vs HFA-fluticasone propionate (FP). METHODS: Sixteen healthy volunteers were randomised in placebo-controlled single blind cross-over fashion to receive 3 weeks with HFA-FP or HFA-BDP, given as 1 week cumulative doubling doses (nominal ex-valve) of 500, 1000 and 2000 microg day(-1), with a 1 week placebo run-in and wash-out. Overnight (22.00 h to 08.00 h) and early morning (08.00 h) urinary cortisol/creatinine excretion and 08.00 h serum cortisol were measured after each placebo and dosing period. All data were log-transformed to normalize their distribution. RESULTS: Urine and serum cortisol were suppressed by 2000 microg FP and BDP vs placebo and by 1000 microg BDP vs placebo for urinary cortisol/creatinine (P < 0.05). Overnight urinary cortisol/creatinine ratio (the primary endpoint) was suppressed more by 1000 microg BDP vs 1000 microg FP (P < 0.05), amounting to a geometric mean fold difference (95% CI) of 1.64 (1.04-2.56). There were also more individual low values less than 3 nmol mmol(-1) with BDP than FP at 1000 microg: n = 8/16 vs n = 2/16 (P < 0.05). CONCLUSIONS: There was dose-related suppression of corrected urinary cortisol/creatinine with the HFA formulations of BDP and FP. Suppression of overnight urinary cortisol/creatinine ratio was significantly greater with HFA-BDP than HFA-FP at 1000 microg. This suggests that the greater glucocorticoid potency of HFA-FP may be offset by the greater lung bioavailability of HFA-BDP.

Administration, Inhalation↗

PubMed2001

A comparison of topical budesonide and oral montelukast in seasonal allergic rhinitis and asthma.

BACKGROUND: Allergic rhinitis and asthma commonly coexist and are both mediated by similar inflammatory mechanisms. Leukotriene antagonists may therefore be an alternative to corticosteroid therapy. OBJECTIVE: To compare oral montelukast with inhaled plus intranasal budesonide in patients with seasonal allergic rhinitis and asthma. PATIENTS AND METHODS: A single-blind double-dummy placebo-controlled crossover study was performed comparing once daily 10 mg oral montelukast with 400 microg inhaled plus 200 microg intranasal budesonide in 12 patients with allergic rhinitis and asthma: mean (S.E.) age 34.0 years (2.7), forced expiratory volume in 1 s (FEV1) 91.2 (3.8)% predicted. Each treatment was for 2 weeks with a 1-week placebo run-in and washout. Measurements were made after each active treatment and placebo for: adenosine monophosphate bronchial challenge, exhaled and nasal nitric oxide. Patients also recorded their domiciliary peak expiratory flow, nasal peak inspiratory flow, asthma and seasonal allergic rhinitis symptoms. RESULTS: There were no significant differences between the placebos for any measurement. For adenosine monophosphate PC20, geometric mean fold differences (95% confidence interval (CI) for difference) were 6.4 (2.2-18.6) for placebo vs. budesonide, 2.9 (1.0-8.4) for placebo vs. montelukast, and 2.1 (1.1-4.5) for budesonide vs. montelukast. For exhaled nitric oxide (p.p.b.) there was significant (P < 0.05) suppression with both montelukast (10.9) and budesonide (10.1) compared with placebo (18.8). For nasal nitric oxide and nasal peak flow there were only significant differences with budesonide compared with placebo. Both treatments reduced total seasonal allergic rhinitis symptoms but only budesonide had a significant effect on nasal symptoms. CONCLUSION: Once-daily inhaled plus intranasal budesonide and once daily montelukast showed comparable efficacy on lower airway, but only the budesonide had significant efficacy on upper airway inflammatory markers. Both treatments significantly reduced allergic rhinitis symptoms.

Acetates↗

PubMed2001

Mural endocarditis caused by Salmonella virchow: survival with conservative treatment.

We describe a case of endocarditis caused by Salmonella enterica serotype virchow, which was treated conservatively with antibiotics alone. It is the only reported case of survival from salmonella endocarditis with conservative treatment, and the first reported case of endocarditis caused by Salmonella virchow. The changing prevalence, virulence patterns and importance of salmonella species in endocarditis are discussed.

Journal Article↗

PubMed2001

Predominant 4-hydroxylation of estradiol by constitutive cytochrome P450s in the female ACI rat liver.

The ACI rat is extremely sensitive to estrogens as mammary carcinogens, whereas the Sprague-Dawley strain is relatively resistant. Comparison of the disposition and effects of estrogens in these two strains should provide insights into the mechanisms of estrogen carcinogenicity. We have begun this investigation by comparing the metabolism of [(3)H]17beta-estradiol (E2) by liver microsomes prepared from female rats from each strain. Both strains produce estrone (E1) as the major product at E2 concentrations >1 microM, with smaller amounts of 2-hydroxy-E2 formed. As the E2 concentration is decreased, however, aromatic hydroxylation becomes a more dominant pathway for both strains. At starting E2 concentrations as low as 3 nM, Sprague-Dawley liver microsomes produced comparable yields of 2-hydroxy-E2 and E1. In contrast, ACI liver microsomes yielded a profound shift to aromatic hydroxylation as the dominant pathway as E2 concentrations dropped below 1 microM, and this shift reflected the production of 4-hydroxy-E2 as the predominant product. The apparent K(m) for 4-hydroxylation of E2 is <0.8 microM, as opposed to approximately 4 microM for 2-hydroxylation, suggesting that different cytochrome P450s (CYPs) are responsible. Western immunoblotting of the liver microsomal preparations from ACI and Sprague-Dawley rats for CYPs known to catalyze 2- and 4-hydroxylation of E2 revealed that both strains contained comparable amounts of CYP 2B1/2 and 3A1/2, but no detectable amounts of CYP 1B1, the proposed E2 4-hydroxylase. Although this enzyme is not a constitutive CYP in Sprague-Dawley rat liver, its presence in ACI liver could provide a ready explanation for the predominance of 4-hydroxy-E2 as a product. The identity of the estradiol 4-hydroxylase in ACI rat liver and the role of this unique reaction in the heightened sensitivity to E2 carcinogenicity remain to be elucidated.

Animals↗

PubMed2001

Reproductive and developmental risks from ethylene oxide: a probabilistic characterization of possible regulatory thresholds.

Ethylene oxide is a gas produced in large quantities in the United States that is used primarily as a chemical intermediate in the production of ethylene glycol, propylene glycol, non-ionic surfactants, ethanolamines, glycol ethers, and other chemicals. It has been well established that ethylene oxide can induce cancer, genetic, reproductive and developmental, and acute health effects in animals. The U.S. Environmental Protection Agency is currently developing both a cancer potency factor and a reference concentration (RfC) for ethylene oxide. This study used the rich database on the reproductive and developmental effects of ethylene oxide to develop a probabilistic characterization of possible regulatory thresholds for ethylene oxide. This analysis was based on the standard regulatory approach for noncancer risk assessment, but involved several innovative elements, such as: (1) the use of advanced statistical methods to account for correlations in developmental outcomes among littermates and allow for simultaneous control of covariates (such as litter size); (2) the application of a probabilistic approach for characterizing the uncertainty in extrapolating the animal results to humans; and (3) the use of a quantitative approach to account for the variation in heterogeneity among the human population. This article presents several classes of results, including: (1) probabilistic characterizations of ED10s for two quantal reproductive outcomes-resorption and fetal death, (2) probabilistic characterizations of one developmental outcome-the dose expected to yield a 5% reduction in fetal (or pup) weight, (3) estimates of the RfCs that would result from using these values in the standard regulatory approach for noncancer risk assessment, and (4) a probabilistic characterization of the level of ethylene oxide exposure that would be expected to yield a 1/1,000 increase in the risk of reproductive or developmental outcomes in exposed human populations.

Animals↗

PubMed2001

The force and contact stress on the navicular bone during trot locomotion in sound horses and horses with navicular disease.

Mechanical overload due to poor conformation or shoeing has been suggested to contribute to the development of navicular disease. While studies have determined the compressive force exerted on the navicular bone in normal horses, this has not been reported for horses with navicular disease. Also, the force has not been converted to stress by correction for contact area. In this study we developed a technique for the determination of the contact area between the deep digital flexor tendon and the navicular bone in vivo, and used a forceplate system to determine the force and stress on the bone at trot in 6 normal and eight diseased horses. The mean +/- s.d. peak force and peak stress were 5.62+/-1.45 N/kg and 2.74+/-0.76 MPa for the normal group and 6.97+/-1.50 N/kg and 3.07+/-0.55 MPa for the navicular disease group. The peak force and peak stress were similar for both groups but the force and stress in the horses with navicular disease were approximately double control group values early in the stance phase. This was due to a higher force in the deep digital flexor tendon, which was attributed to a contraction of the deep digital flexor muscle in early stance in an attempt to unload the heels.

Animals↗

PubMed2001

Modification of a force plate system for equine gait analysis on hard road surfaces: a technical note.

Studies on horseshoe materials have been limited to the analysis of kinematic data to determine slip times and distances, since equine force plate analysis is traditionally undertaken on a rubber-surfaced force plate. The purpose of this study was to modify a force plate for measuring ground reaction forces on a road surface and report preliminary data from the system. A steel-reinforced concrete top plate of 18 mm thickness and mass 23 kg, and a 12 mm thick top plate of 6 mm bituminous macadam wear coat (road surface) contained in a tray constructed of 2 mm thick steel, mass 21 kg, were constructed. The top plates were bolted to a forceplate and resonance frequency of the force plate top plate combinations were 278 Hz (concrete) and 218 Hz (roadway), respectively. Simultaneous kinetic and kinematic data were collected while a horse, shod in steel horseshoes, was trotted over the concrete-topped force plate until 8 foot placements were recorded. The foot slipped for mean +/- s.d. 35 +/- 7 mm in 29 +/- 8 ms after impact and both Fy and Fz increased during foot slip. The ratio of Fy/Fz during slip was relatively constant at 0.56 +/- 0.05. The top plates have proved resilient in use and have withstood a variety of horseshoe designs and tungsten-capped stud nails with minimal damage. They enable measurement of ground reaction forces on hard surfaces and the calculation of the energy dissipated via foot slippage by integration of the craniocaudal force-foot position data after impact.

Analysis of Variance↗

PubMed2001

The effect of shoe material on the kinetics and kinematics of foot slip at impact on concrete.

Previous studies on shoeing have demonstrated that shoe material alters the time taken from foot impact to the foot stopping sliding (slip time) and the distance slid. These are assumed to reflect differences in the craniocaudal ground reaction force (GRF) between the shoe and the ground during foot slip. This study tested the hypothesis that the slip time and distance are reflected in the resistance to slippage of the foot after impact. The forefeet of 8 horses were shod in horseshoes constructed of steel, plastic and rubber. Each horse was trotted for 8 placements per forefoot in each shoe type over a concrete topped forceplate and simultaneous kinematic data recorded at 240 Hz. Slip distance and slip time were calculated from the kinematic data and craniocaudal (Fy), and vertical (Fz) GRFs determined during slip the averaged for each shoe type. The slip time and distance were variable between runs in all 3 shoe types, and there was no significant difference between the mean values for the 3 shoe types. Fy reached a value of 0.98 +/- 0.17 N/kg during slip in the plastic shoes which was significantly lower than the rubber shoes, at 1.13 +/- 0.17 N/kg, P = 0.02. The Fy/Fz ratio (a measure of dynamic friction) was significantly lower in the plastic shoes, 0.34 +/- 0.08, compared to the steel shoes, 0.46 +/- 0.04, P = 0.003. This study is being extended to investigate effects of shoe slippage at the end of the stance phase and the energy dissipation during foot slip in the different shoe types. Future investigations should aim to identify the optimum slip characteristics to modulate loading (magnitude and rate) during impact, with the aim of reducing the risk of injury.

Animals↗

PubMed2001

Lymphangioleiomyomatosis. A series of three case reports illustrating the link with high oestrogen states.

Lymphangioleiornyomatosis is a rare lung disorder characterised by cystic air spaces and smooth muscle proliferation. The condition, which most commonly presents with dyspnoea, pneumothoraces or cough, is only described in females and is most commonly diagnosed during childbearing years. Three cases are presented which illustrate typical features of the disease and the association with high oestrogen levels. The first had recurrent pneumothoraces during her first pregnancy. The second lady was post menopausal at diagnosis but her symptoms predated her menopause. The third, presented with dyspnoea, abnormal chest sensations and a pneumothorax. She had a history of hyperprolactinaemia with secondary amenorhoea due to low oestrogen levels which had been corrected prior to her presentation. All three patients had reduced gas transfer and abnormalities in spirometry, two had reticular shadowing on their chest radiograph and all had typical appearances on lung computerised tomography. Although disease progression was variable, all patients showed a gradual decline in lung function.

Adult↗

PubMed2001

Comparative in vivo lung delivery of hydrofluoroalkane-salbutamol formulation via metered-dose inhaler alone, with plastic spacer, or with cardboard tube.

STUDY OBJECTIVE: To compare the lung delivery of chlorofluorocarbon-free salbutamol via a pressurized metered-dose inhaler (pMDI) alone, a pMDI with a small-volume plastic spacer, and a pMDI with a cardboard tube. DESIGN: A randomized, single (investigator)-blind, three-way, crossover study. SETTING: The Asthma and Allergy Research Group, Ninewells Hospital, University of Dundee, Dundee, Scotland, UK. PARTICIPANTS: Twelve healthy volunteers aged 16 to 65 years. INTERVENTIONS: The subjects were administered 400 microg of salbutamol via a pMDI alone, via a pMDI plus a small-volume plastic spacer, or via a pMDI plus a cardboard tube. MEASUREMENTS AND RESULTS: Blood samples for plasma salbutamol concentrations were taken at 5 min, 10 min, and 20 min after inhalation, to measure lung bioavailability as a surrogate for relative lung dose. The addition of the plastic spacer resulted in a significantly higher maximal plasma salbutamol concentration (CMAX) and average plasma salbutamol concentration (CAV) than the pMDI used alone. This amounted to a 1.48-fold (32%) difference (95% confidence interval [CI], 1.03 to 2.13) for CMAX and a 1.42-fold (30%) difference (95% CI, 1.01 to 2.00) for CAV. There was no significant difference in the CMAX or CAV comparing the addition of the cardboard tube with the plastic spacer or the pMDI alone. CONCLUSIONS: Using a chlorofluorocarbon-free pMDI with a plastic spacer produced statistically, but not biologically, significant greater lung delivery of salbutamol. If a spacer is required for reasons other than increasing delivered drug dose, then the addition of a readily available cardboard tube will fulfill many of the required functions with no expense to the patient.

Administration, Inhalation↗

PubMed2001

Evaluation of salmeterol or montelukast as second-line therapy for asthma not controlled with inhaled corticosteroids.

OBJECTIVE: To assess the addition of a leukotriene receptor antagonist and a long-acting beta(2)-agonist as second-line therapy in asthma. DESIGN: Placebo-controlled, double-dummy, crossover study. SETTING: Outpatient clinic. PATIENTS: Twenty patients with persistent asthma not controlled with inhaled corticosteroid therapy. INTERVENTIONS: Montelukast 10 mg once daily, or salmeterol, 50 microg bid, each for 2 weeks with 1-week run-in and washout placebo periods. MEASUREMENTS AND RESULTS: Adenosine monophosphate (AMP) bronchial challenge, blood eosinophil count (EOS), exhaled nitric oxide, and lung function after both placebo periods and after the first and last doses of each active treatment. Patients recorded their domiciliary peak expiratory flow (PEF), asthma symptoms, and rescue bronchodilator requirement (RES) twice daily throughout the study. For the primary end point of the provocative concentration of AMP causing a 20% fall in FEV(1), compared to placebo (47.5 +/- 13.0 mg/mL), there were significant differences with the first (114.1 +/- 36.9 mg/mL) and last (94.2 +/- 30.4 mg/mL) doses of montelukast as well as the first (160.1 +/- 64.5 mg/mL) but not the last (70.1 +/- 23.7 mg/mL) dose of salmeterol. Only montelukast produced significant suppression of the EOS. Neither drug affected exhaled nitric oxide levels. There were significant improvements with the first doses of salmeterol for all parameters of lung function. After 2 weeks of treatment, there were significant improvements with both drugs for RES and morning PEF. There were no significant differences between drugs for any end points except EOS. CONCLUSIONS: Montelukast and salmeterol exhibited significant improvements in asthma control when given as second-line therapy. Montelukast also produced significant effects on AMP challenge and EOS suggesting anti-inflammatory activity.

Acetates↗