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Biomedical subjects

A M Wilson

Publications and source records attributed to A M Wilson.

At least 73 records · Page 4Linked to original sources
PubMed2001

The effect of bilateral palmar digital nerve analgesia on the compressive force experienced by the navicular bone in horses with navicular disease.

Horses with navicular disease have an increased load on the navicular bone in early stance. This has been suggested to be a response to pain in the heel region. Seven horses with clinical, radiographic and scintigraphic signs of navicular disease underwent forceplate and kinematic analysis before and after desensitisation of the heel region with a bilateral palmar digital nerve block. The compressive force exerted on the navicular bone during stance, and stride kinematics, were determined in each state. After regional analgesia of the palmar digital nerves (PDNB) the compressive force on the navicular bone was lower throughout stance. The mean +/- s.d. peak force at the beginning of stance was 7.05+/-1.10 N/kg before, and 6.46+/-1.15 N/kg after PDNB (P = 0.01) and at the end of stance the mean peak values were 5.00+/-2.05 N/kg before, and 4.39+/-1.65 N/kg after PDNB (P = 0.05). We explained this finding as indicating that the horse responds to heel pain (including pain in the navicular region) by contracting the deep digital flexor muscle to unload the heels. This increases the compressive load on the navicular bone, which may cause remodelling and, in some horses, damage to the overlying flexor cartilage, which is then painful and identified as navicular disease. This mechanism identifies navicular disease as a possible end point for a variety of heel related conditions.

Anesthetics, Local↗
PubMed2001

Effects of monotherapy with intra-nasal corticosteroid or combined oral histamine and leukotriene receptor antagonists in seasonal allergic rhinitis.

BACKGROUND: The combination of a leukotriene receptor antagonist with an antihistamine may have beneficial effects in seasonal allergic rhinitis (SAR). OBJECTIVE: To determine how combined oral mediator blockade compares to monotherapy with intranasal corticosteroid in the treatment of SAR. METHODS: Twenty-two patients with seasonal allergic rhinitis were enrolled in a placebo controlled crossover study comparing 2 weeks therapy of either (a) 200 microg intranasal mometasone furoate (MF) once daily or (b) 10 mg oral montelukast plus 10 mg oral cetirizine once daily (MON/CZ), with a 7-10 day placebo period prior to each treatment period. Domiciliary measures of symptoms and nasal flow were recorded daily. Measurements of posterior rhinomanometry, acoustic rhinometry and nasal nitric oxide were made after all treatment and placebo periods. RESULTS: There were significant (P < 0.05) improvements in domiciliary peak nasal flow (l/min) with both MF (133 (3.8)) and MON/CZ (124 (3.8)) compared to pooled placebo (110 (4.0). Both treatments also showed significant improvement in terms of nasal blockage (units) (PL: 1.1(0.1), MF: 0.5 (0.1), MON/CZ 0.7 (0.1); and total nasal symptoms (units) (PL: 3.5 (0.3), MF 1.6 (0.3), MON/CZ 1.7 (0.3)), although there was no significant difference between the two active treatments. There were no significant differences between placebo and treatment for rhinomanometry, acoustic rhinometry or nitric oxide. CONCLUSIONS: Both intranasal mometasone furoate as monotherapy and oral cetirizine plus montelukast as cotherapy were equally effective for objective and subjective measures of treatment response in SAR. Domiciliary measurements of symptoms and peak flow were more sensitive than laboratory measurements of rhinomanometry, acoustic rhinometry and nasal nitric oxide.

Acetates↗
PubMed2001

Evaluation of the importance of head and probe stabilisation in acoustic rhinometry.

As yet there is no established procedure to ensure the repeatability of acoustic rhinometry measurements although anecdotal evidence suggests that instrument fixation improves repeatability. The aim of this study is to validate the methodology of acoustic rhinometry and determine whether instrument fixation and head stabilisation is necessary. Four methods were compared in fifteen healthy volunteers, after nasal decongestion: A) Patient holding the probe (patient-held), B) Probe fixed in a probe stand (probe-stand), C) Probe fixed in stand and head stabilised in head rest (head-rest), D) Examiner holding the probe (examiner-performed). The two minimum cross-sectional areas and volume between 0 and 5 cm were recorded. The examiner-performed and probe-stand methods were consistently less variable than the other methods. With examiner-performed method, this was significant (p < 0.05) versus head-rest and patient-held methods for both measures of minimum cross-sectional area. For nasal volume the examiner-performed method was significantly (p < 0.05) less variable than the head-rest method. In conclusion, examiner-performed acoustic rhinometry is more repeatable than combined head stabilisation and instrument fixation and therefore the use of a head-rest may be unnecessary. Instrument fixation or examiner performed test is also preferable to allowing the patient to position the probe. The repeatability of the probe-stand method was similar to the examiner-performed method.

Adult↗
PubMed2001

Effects of leukotriene receptor antagonist therapy in patients with chronic rhinosinusitis in a real life rhinology clinic setting.

Although there is evidence from randomised controlled trials that leukotriene receptor antagonists are efficacious in chronic rhinosinusitis there are still little data on their use in everyday real life clinical practice. We report on a pragmatic case series of 32 patients referred from primary care with uncontrolled chronic rhinosinusitis (allergic or non-allergic) who have been treated with montelukast in our joint medical/surgical rhinology clinic. Patients' symptoms were scored according to "facial pain", "headache", "nasal blockage", "nasal discharge", "sense of smell" and "daily activity", and measurements of peak inspiratory nasal flow were made, before and after the introduction of montelukast 10 mg/day. There were significant (p < 0.05) improvements in subjective scoring for headache, nasal discharge & blockage, sense of smell and daily activity but not for facial pain, when montelukast was added along with other alterations in chronic rhinosinusitis medication (all receiving intra-nasal corticosteroids). Subgroup analysis of 10 patients, were the addition of montelukast was the only change to medical therapy, showed significant (p < 0.05) improvements in headache, nasal discharge and blockage and their daily activity. There was no significant improvements in nasal peak inspiratory flow or spirometry. In conclusion, montelukast may be a useful therapeutic option in addition to standard therapy (i.e. intra-nasal corticosteroids or anti-histamines) when treating patients with chronic rhinosinusitis in a real life clinical setting.

Acetates↗
PubMed2000

Effects of adding a leukotriene antagonist or a long-acting beta(2)-agonist in asthmatic patients with the glycine-16 beta(2)-adrenoceptor genotype.

PURPOSE: In the United Kingdom, about 40% of patients with asthma are homozygous for the glycine-16 beta(2)-adrenoceptor polymorphism, which predisposes them to agonist-induced down-regulation and desensitization of the beta(2)-adrenoceptor. We assessed the effects of adding treatment with either a long-acting beta(2)-agonist (inhaled formoterol, 12 microg twice daily) or a leukotriene receptor antagonist (oral zafirlukast, 20 mg twice daily) to inhaled corticosteroid therapy in patients with this genotype. SUBJECTS AND METHODS: We enrolled 24 patients with mild to moderate asthma who were being treated with inhaled corticosteroids. Patients were randomly assigned to receive one of three treatments (placebo, zafirlukast, or formoterol in addition to inhaled corticosteroids) for 1 week each in a crossover fashion, separated by a 1-week placebo run-in and washout period. Measurements of bronchoprotection (measured as the provocative dose of methacholine that produced a 20% decline in forced expiratory volume in 1 second [FEV(1)]), exhaled nitric oxide (a surrogate marker of airway inflammation), and symptoms were made before each treatment and 12 hours after the last dose of each treatment. RESULTS: Both formoterol and zafirlukast were equally effective in maintaining asthma control compared with placebo: the geometric mean-fold difference in the methacholine provocative dose was 1.5-fold (95% confidence interval [CI]: 1.1- to 2.2-fold) for zafirlukast and 1.9-fold (95% CI: 1.2- to 2.9-fold) for formoterol. As compared with placebo, zafirlukast caused a significant suppression in exhaled nitric oxide (1.7-fold difference in geometric mean values, 95% CI: 1.1- to 2.6-fold) but formoterol did not (1.2-fold difference, 95% CI: 0.8- to 1.9-fold). Diary cards showed significant (P <0.05) improvements in the peak flow with formoterol (morning and evening) and zafirlukast (evening) as compared with placebo. CONCLUSIONS: Formoterol and zafirlukast maintained asthma control in patients who might be genetically predisposed to fare worse with long-acting beta(2)-agonists. The reduction in exhaled nitric oxide with zafirlukast suggests that it may have anti-inflammatory effects in addition to those seen with inhaled corticosteroids.

Administration, Inhalation↗
PubMed2000

Enhanced metabolism of halogenated hydrocarbons in transgenic plants containing mammalian cytochrome P450 2E1.

Chlorinated solvents, especially trichloroethylene (TCE), are the most widespread groundwater contaminants in the United States. Existing methods of pumping and treating are expensive and laborious. Phytoremediation, the use of plants for remediation of soil and groundwater pollution, is less expensive and has low maintenance; however, it requires large land areas and there are a limited number of suitable plants that are known to combine adaptation to a particular environment with efficient metabolism of the contaminant. In this work, we have engineered plants with a profound increase in metabolism of the most common contaminant, TCE, by introducing the mammalian cytochrome P450 2E1. This enzyme oxidizes a wide range of important pollutants, including TCE, ethylene dibromide, carbon tetrachloride, chloroform, and vinyl chloride. The transgenic plants had a dramatic enhancement in metabolism of TCE of up to 640-fold as compared with null vector control plants. The transgenic plants also showed an increased uptake and debromination of ethylene dibromide. Therefore, transgenic plants with this enzyme could be used for more efficient remediation of many sites contaminated with halogenated hydrocarbons.

Animals↗
PubMed2000

Dose-response evaluation of the therapeutic index for inhaled budesonide in patients with mild-to-moderate asthma.

PURPOSE: Inhaled corticosteroids have beneficial effects on pulmonary function and inflammation in patients with asthma, but they also cause systemic adverse effects, such as adrenal suppression. We evaluated the therapeutic index of inhaled corticosteroids in asthmatic patients by comparing their dose-response effects on lung function, surrogate markers of airway inflammation, and tests of adrenal function. SUBJECTS AND METHODS: After a 10-day placebo run-in, we evaluated the effects of 200 microg, 400 microg, and 800 microg of inhaled budesonide, each dose given twice daily sequentially for 3 weeks in 26 patients, aged 35 +/- 12 years (mean +/- SD), with mild-to-moderate asthma. Measurements were made of bronchial reactivity, exhaled nitric oxide (a marker of airway inflammation), spirometry, serum eosinophilic cationic protein concentration, and 10-hour overnight urinary cortisol excretion. Plasma cortisol levels were measured at 8 AM and after stimulation with human corticotropin releasing factor. RESULTS: For measurements of pulmonary function and exhaled nitric oxide, there was a plateau in the mean response to budesonide between 400 microg (low dose) and 800 microg (medium dose) per day, whereas for eosinophilic cationic protein and bronchial challenge, maximal benefits occurred between 800 and 1,600 microg (high dose) per day. Effects on plasma cortisol levels showed maximal suppression at 1,600 microg of budesonide per day. The proportion of patients with an optimal therapeutic index, in terms of a good airway response (fourfold decrease in bronchial hyperreactivity) and minimal systemic response (overnight urinary cortisol greater than 20 nmol), was similar at low-dose (46%) and at high-dose (52%) budesonide. The proportion of patients with a suboptimal therapeutic index, a good airway response with a marked systemic response (overnight urinary cortisol greater than 20 nmol), increased from 4% at low dose to 38% at high dose. CONCLUSIONS: In patients with mild-to-moderate atopic asthma, there were dose-related effects of budesonide on surrogate markers of inflammation (bronchial hyperreactivity and serum eosinophilic cationic protein), although higher doses were associated with adrenal suppression and a decrease in the therapeutic index.

Administration, Inhalation↗
PubMed2000

Dissociation of analgesic and rewarding effects of endomorphin-1 in rats.

The mu-receptor is the primary mediator of the effects of morphine and the endogenous opiates, endomorphin-1 and endomorphin-2. Here we demonstrate a dissociation of the analgesic and rewarding effects of endomorphin-1 in rats. Tail-flick results revealed that endomorphin-1 produced significant analgesic effects within 10-min after injection. However, it failed to show reward properties in the standard 45- min conditioned place preference (CPP) paradigm or in an abbreviated 10-min pairing which paralleled the time frame of the tail-flick findings. Morphine induced both analgesia and reward. Endomorphin-1 therefore is the first mu opiate shown to produce potent analgesia in the absence of reward behavior, and thus may have significant clinical potential.

Analgesics↗
PubMed2000

Subjective and objective markers of treatment response in patients with seasonal allergic rhinitis.

BACKGROUND: Although there is a recognized association between upper and lower allergic airways disease, it is unknown how seasonal allergic rhinitis (SAR) therapy will effect sensitive markers of airway function in patients with no history of asthma. OBJECTIVE: To prospectively evaluate subjective and objective markers of treatment response in 26 patients with SAR who have been screened to exclude a diagnosis of asthma. METHODS: The patients' usual treatment, with antihistamine alone (n = 13) or in combination with intranasal corticosteroid (n = 13), was withheld for 1 week to achieve a baseline and then resumed. Measurements were made after baseline and after 2 and 4 weeks of treatment for nasal peak inspiratory flow rate (nPIFR); airways resistance (Raw) and specific conductance (sGaw); and nasal nitric oxide (NO). Patients reported their symptom (nasal, throat and eye) scores, daily activity scores, and ocular sodium cromoglycate usage over the preceding 24 hours. RESULTS: Compared with baseline, there were significant (P < .05) improvements with nPIFR, symptom scores and cromoglycate usage at 2 and 4 weeks of treatment. There was no significant suppression for NO at 2 or 4 weeks. There was a significant correlation between nPIFR and nasal symptoms (r = -0.52, P < .001). After 4 weeks of treatment there were significant (P < .05) improvements in sGaw (143.3% predicted) and Raw (91.6% predicted) compared with baseline (sGaw: 111.8%, Raw: 104.2% predicted). CONCLUSION: Treatment of SAR improves upper and lower airway parameters but not NO. Nasal PIFR correlates significantly with nasal symptoms.

Adult↗
PubMed2000

Low-dose continuous chemotherapy (LBCMVD-56) for refractory and relapsing lymphoma.

BACKGROUND: Although lymphoid malignancies are generally chemosensitive, relapse is common. The use of high-dose therapy can make subsequent cytotoxic therapy intolerable. There is a need to develop regimens with low acute toxicity which are suitable for use in patients post-high dose therapy and following the failure of standard protocols. PATIENTS AND METHODS: Twenty-six patients with lymphomas, fifteen of whom had received high-dose therapy, were treated with a novel regimen consisting of low-dose lomustine, chlorambucil, daily subcutaneous bleomycin, vincristine and methotrexate with dexamethasone on an eight-week cycle (LBCMVD-56). A median of three cycles was given. RESULTS: The overall response rate at 12 weeks was 67% (21% complete remission (CR)) with a median overall survival of 13 months. A symptomatic response was seen in 72%. Previous high-dose therapy did not compromise the response rate. Toxicity was acceptable with grade 3-4 haematological toxicity seen in 27% of cycles, gastrointestinal toxicity seen in 11% and pulmonary toxicity seen in 8%. Thirty-one percent of patients required hospitalisation at some point during this treatment most commonly for neutropenic sepsis. CONCLUSIONS: LBCMVD-56 is an inexpensive, outpatient-based regimen with low acute toxicity and a high response rate in this heavily pre-treated group of patients.

Adolescent↗
PubMed2000

Widening of scars: foe coaxed into a friend? The Millard technique revisited.

Widening of scars is a frustrating event that most if not all plastic surgeons have encountered. Several therapeutic modalities have been proposed, but frequently the result is disappointing. During revision surgery, it is advocated that the dermal scar be used in providing support to the tissues instead of being discarded. The author proposes a technique by which tension on the wound is carried by tough scar tissue instead of the suture line, thereby reducing the incidence of postoperative widening. This technique was used to treat 35 nonburn scars that had widened: 31 scars were facial (24 patients) and 4 were inframammary (2 male patients). All scars were at least 4 months old. The operations were performed between February of 1996 and December of 1998; follow-up was 9 to 14 months. Only one scar widened during the follow-up period. Overall, 71 percent of patients rated the improvement as marked. This is a revisiting of the original Millard's technique, which seems to have fallen into oblivion. The author recommends this technique in dealing with widened scars during revision surgery.

Adolescent↗
PubMed2000

Fitting second-order finite mixture models to data with many censored values using maximum likelihood estimation.

Finite mixture models, that is, weighted averages of parametric distributions, provide a powerful way to extend parametric families of distributions to fit data sets not adequately fit by a single parametric distribution. First-order finite mixture models have been widely used in the physical, chemical, biological, and social sciences for over 100 years. Using maximum likelihood estimation, we demonstrate how a first-order finite mixture model can represent the large variability in data collected by the U.S. Environmental Protection Agency for the concentration of Radon 222 in drinking water supplied from ground water, even when 28% of the data fall at or below the minimum reporting level. Extending the use of maximum likelihood, we also illustrate how a second-order finite mixture model can separate and represent both the variability and the uncertainty in the data set.

Algorithms↗
PubMed2000

Antiasthmatic effects of mediator blockade versus topical corticosteroids in allergic rhinitis and asthma.

To compare the antiasthmatic efficacy of inflammatory mediator blockade versus topical corticosteroid therapy in patients with seasonal allergic rhinitis (SAR) and asthma, 14 patients were enrolled into a single-blind, double-dummy, placebo-controlled crossover study comparing 2 wk therapy of (1) 400 microgram orally inhaled budesonide plus 200 microgram intranasal budesonide (BUD) or (2) 10 mg oral montelukast plus 10 mg oral cetirizine (ML + CZ). Before each treatment period, patients received 7 to 10 d placebo washout. All treatments were given once daily in the morning. Throughout the study, patients recorded the following domiciliary measures: peak expiratory flow (PEF), rescue inhaler requirement, asthma symptoms, and daily activity score. Laboratory measurements were made at trough of adenosine monophosphate (AMP) bronchial challenge and exhaled nitric oxide (NO). Compared with pooled placebo (PL), there were significant (p < 0.05) improvements in all domiciliary measures with both treatments (mean PEF [L/min] PL: 463; BUD: 478; ML + CZ: 483). For geometric mean AMP PC(20) (mg/ml), there was an improvement (p < 0.05), compared with PL (47), for ML + CZ (133) but not for BUD (51); whereas for NO (ppb) there was significant suppression with BUD (7.6) but not ML + CZ (11.5) compared with PL (13.6). In conclusion, both combined mediator blockade and combined topical corticosteroids are equally effective antiasthma therapy in patients with asthma and SAR.

Acetates↗
PubMed2000

Asthma and Cushing's syndrome.

A female patient was treated with high-dose inhaled fluticasone propionate for her asthma. Over 2 years, she developed features of Cushing's syndrome with proximal myopathy, osteopenia, hypertension, depressive psychosis, and cushingoid appearance. She had biochemical evidence of marked adrenal suppression with a 9:00 AM serum cortisol of 20 nmol/L that returned to normal (315 mol/L) after her therapy was changed to budenoside, 0.8 mg/d. Her appearance, mental state, and myopathy also improved with no loss of asthma control. This case illustrates the potential for developing clinically relevant adverse effects of inhaled corticosteroids when given at licensed doses.

Administration, Inhalation↗
PubMed2000

Additive bronchoprotective and bronchodilator effects with single doses of salmeterol and montelukast in asthmatic patients receiving inhaled corticosteroids.

OBJECTIVE: We wished to evaluate whether the combination of a leukotriene receptor antagonist and long-acting beta(2)-agonist might confer additive beneficial effects in terms of bronchoprotection and bronchodilatation, in mild to moderate asthmatic patients who were suboptimally controlled on inhaled corticosteroids alone. METHODS: Twelve asthmatic patients were enrolled into a single-blind, placebo-controlled, crossover study, receiving additive therapy as either of the following: (1) montelukast alone, 10 mg (ML(10)); (2) inhaled salmeterol alone, 50 microg (SM(50)); (3) ML(10) and SM(50); (4) ML(10) and inhaled salmeterol, 100 microg (SM(100)); or (5) placebo inhaler and tablet. Trough measurements were made of adenosine monophosphate (AMP) bronchial challenge (the provocative concentration of a drug [AMP] causing a fall of >/= 20% in FEV(1) [PC(20)]) as the primary end point, and spirometry, following single doses of either placebo or active treatments (12 h after salmeterol, and 24 h after monteleukast, respectively). RESULTS: Compared to placebo, all active treatments led to significant improvements (p < 0.05) in geometric mean AMP-PC(20): placebo, 42 mg/mL; ML(10), 106 mg/mL; SM(50), 115 mg/mL; ML(10) and SM(50), 183 mg/mL; and ML(10) and SM(100), 247 mg/mL. The effects of montelukast and salmeterol were numerically additive, with ML(10) and SM(100) being significantly different (p < 0.05) from ML(10) alone. For mean FEV(1) and forced expiratory flow rate between 25% and 75% of vital capacity, there were significant differences (p < 0.05) between both combination therapies vs ML(10) alone. CONCLUSIONS: Our results suggest additive benefits of a single dose of a long-acting beta(2)-agonist and leukotriene antagonist, in terms of bronchoprotection and bronchodilation. Further studies in more severe asthmatics are required to evaluate long-term clinical effects.

Acetates↗
PubMed2000

Effects of once-daily formoterol and budesonide given alone or in combination on surrogate inflammatory markers in asthmatic adults.

OBJECTIVES: We wished to evaluate the effects of once-daily combination therapy on surrogate inflammatory markers. METHODS: Fifteen patients with atopic persistent asthma were evaluated (mean age, 32.4 years; FEV(1), 75.2% predicted) in a randomized, double-blind, double-dummy, placebo-controlled crossover study with a 1-week placebo washout period, comparing the following once-daily nighttime treatments: (1) formoterol (FM), 12 microg, for 2 weeks and FM, 24 microg, for 2 weeks; or (2) budesonide (BUD), 400 microg, for 2 weeks and BUD, 800 microg, for 2 weeks; or (3) FM, 12 microg, plus BUD, 400 microg, for 2 weeks and FM, 24 microg, plus BUD, 800 microg, for 2 weeks. Adenosine monophosphate (AMP) bronchial challenge, exhaled nitric oxide (NO), and serum eosinophilic cationic protein (ECP) were evaluated at 12 h postdosing after administration of each placebo and after 2 and 4 weeks of each treatment. RESULTS: The results of AMP challenge (provocative concentration causing a 20% fall in FEV(1)) at 4 weeks showed significant (p<0.05) improvements after patients had received all active treatments compared to placebo (20 mg/mL), with FM plus BUD, 261 mg/mL, being superior (p<0.05) to FM alone, 82 mg/mL, but not to BUD, 201 mg/mL. NO and ECP showed significant (p<0.05) reductions compared to placebo with FM plus BUD or BUD alone but not with FM alone. Combination therapy was associated with optimal patient preference (rank order, FM plus BUD > FM > BUD; p<0.0005), highest domiciliary peak expiratory flow, and lowest rescue inhaler usage. All three treatments produced equivalent improvements in spirometry. CONCLUSIONS: Patients preferred once-daily combination therapy, but this had no greater effect on inflammatory markers than therapy with BUD alone. FM alone had no anti-inflammatory activity but exhibited bronchoprotection. This emphasizes the importance of first optimizing anti-inflammatory control with inhaled corticosteroids before considering adding a regular long-acting beta(2)-agonist.

Adenosine Monophosphate↗
PubMed2000

In vitro evaluation of a novel prosthesis for laryngoplasty of horses with recurrent laryngeal neuropathy.

A prosthesis, composed of a steel cable and stress-reducing washers, was developed to prevent failure of laryngoplasty, a common treatment for horses affected by recurrent laryngeal neuropathy. Laryngoplasties were performed on 15 cadaveric larynges using a polyester suture on one side and the cable prosthesis on the other. Each prosthesis was distracted at a displacement rate of 20 mm/s using a servohydraulic materials testing machine until laryngoplasty failed. Distraction force and actuator displacement were recorded and analysed. All 15 laryngoplasties performed with a suture failed at the muscular process at a mean +/- s.d. force of 55.8 +/- 13.1 N. Six laryngoplasties performed with the cable prosthesis failed at the muscular process at mean force 219.6 +/- 125.0 N. In the other 9, the arytenoid cartilage was avulsed from the larynx at mean force 206.4 +/- 75.3 N, and the cable then tore through the muscular process at mean force 357.0 +/- 32.0 N. The difference in force required to cause failure of laryngoplasty was significant (P<0.0001). Although the prosthesis resisted substantially higher forces than did the suture, the effects of the prosthesis in vivo must be evaluated.

Animals↗