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Biomedical subjects

C Ward

Publications and source records attributed to C Ward.

At least 127 records · Page 7Linked to original sources
PubMed1996

Bronchoalveolar lavage in asthma research.

A great deal of information about the pathophysiology of asthma and its treatment have been obtained through the use of bronchoalveolar lavage (BAL), especially in combination with airway biopsies. The introduction of highly sophisticated methods for examining BAL aspirate, including fluorocein activated cell scanning (FACS) analysis and molecular biology techniques has emphasized the potential power of this method of airway investigation. For those contemplating the use of BAL in asthma research programmes, we hope that this review will provide a useful insight into the current state of knowledge about the technique and its application, and that it will provide a solid platform for study design.

Asthma↗
PubMed1996

Intrasubject variability in airway inflammation in biopsies in mild to moderate stable asthma.

We have studied intrasubject variability with respect to counts of immunostained inflammatory cells in snap frozen endobronchial biopsies from a group of patients with clinically mild to moderate stable asthma. Fiberoptic bronchoscopy was used to obtain endobronchial biopsies from the upper and lower lobes in 12 volunteer subjects with asthma on two separate occasions 1 mo apart. During this period there was no significant change in asthma treatment, symptom scores, pulmonary function, or airway hyperresponsiveness. With the aid of immunohistochemistry and interactive image analysis, subepithelial counts for T lymphocytes, T-lymphocyte subsets, and eosinophils were made. There was wide intrasubject variability between anatomic site and with time for all the inflammatory cell counts. In each case the intrasubject variability with time was greater than lobar differences. Power calculations were made to establish the optimal sample size required for each marker. We conclude that even in stable asthma considerable biologic variability compounds sampling variability. Such sources of variability need to be borne in mind when calculating the likely power of intervention studies using biopsy data as end points. Power calculations suggest that approximately 15 subjects would be an optimal number with little advantage in increasing beyond this.

Adolescent↗
PubMed1996

Seasonal comparison of cytokine profiles in atopic asthmatics and atopic non-asthmatics.

Previous studies have suggested that peripheral blood T cell cytokine release may reflect the situation in the bronchial mucosa in atopic asthmatics. We have therefore examined spontaneous, rye grass pollen-stimulated, and PHA-stimulated secretion of IL-2, IL-4, IL-5, and IFN-gamma in cultures of peripheral blood mononuclear cells (PBMC) from atopic asthmatic, atopic non-asthmatic and normal controls in and out of the rye grass pollen season. Compared to normal controls, both atopic groups showed higher IL-2 and IL-5 production (p < 0.01 and p < 0.05) and higher percentages of CD4 cells expressing CD25 and HLA-DR (p < 0.05) in response to rye grass pollen, elevated IL-4 production in response to PHA (p < 0.01), and a non-significant trend towards lower IFN-gamma production. However, the capacity of PBMC from atopic asthmatics to produce IL-5 was greater than that for atopic non-asthmatics (p < 0.05). Furthermore, seasonal changes in symptom score, FEV1 % predicted, and PD20 methacholine correlated with seasonal elevated production of IL-5 by PBMC in the asthmatic group (r = 0.862, -0.679, and -0.620; p < 0.01, 0.02, and 0.05, respectively). Our results suggest that elevated production of IL-2 and IL-4 and higher percentages of activated CD4 T cells are associated with atopy per se, but elevated production of IL-5 also relates to the clinical expression of atopic asthma.

Adult↗
PubMed1995

Observations on midodrine in a case of vasodepressor neurogenic syncope.

A 43-year-old man presented with recurrent syncope and dizziness after he had a dual chamber pacemaker fitted for presumed sino-atrial disease. Head-up tilt produced vasodepressor neurocardiogenic syncope, despite appropriate heart rate support during pacing, and reproduced symptoms. Symptoms were not improved by disopyramide. A double-blind cross-over trial of midodrine, an alpha-receptor agonist, was effective in reducing symptoms: it abolished syncope and reduced frequency and severity of dizziness, coupled with improved haemodynamic responses to head-up tilt.

Adrenergic alpha-Agonists↗
PubMed1995

Evaluation of propanediol, ethylene glycol, sucrose and antifreeze proteins on the survival of slow-cooled mouse pronuclear and 4-cell embryos.

Mouse pronuclear and 4-cell embryos were cryopreserved by slow cooling to -33 degrees C in 1.5 M 1,2-propanediol or 1.5 M ethylene glycol, with or without 0.1 M sucrose. Straws were thawed by immersion into a 37 degrees C water bath, immediately after their removal from liquid nitrogen (protocol 1), or after being held in air for 15 (protocol 2) or 30 s (protocol 3). Others were held in air until the ice melted (protocol 4). Embryos which formed blastocysts that hatched and attached to the Petri dish in vitro (plated) were considered viable. The thawing protocol did not significantly influence the viability of embryos frozen in propanediol with 0.1 M sucrose (52-72% of pronuclear and 69-97% of 4-cell embryos plated). In the other solutions tested, propanediol without sucrose and ethylene glycol with/without sucrose, only protocol 2 resulted in uniformly high development of both pronuclear (45-65% plating) and 4-cell embryos (70-97% plating). Thawing protocol 4 significantly reduced development, in particular for embryos frozen in ethylene glycol (0% 1-cell; 0-25% 4-cell plating). The difference between thawing protocols 2 and 4 was reduced by continuing slow cooling of ethylene glycol solutions to lower temperatures (-41 degrees C). Adding antifreeze proteins type I or III did not improve survival or development. Thus, although mouse pronuclear and 4-cell embryos can be frozen-thawed in either ethylene glycol or propanediol without significant loss of viability, an appropriate thawing protocol is essential for embryos frozen in ethylene glycol or propanediol-sucrose.

Animals↗
PubMed1995

Effect of high dose inhaled fluticasone propionate on airway inflammation in asthma.

Inhaled corticosteroids are now first-line therapy for most patients with asthma. However, it has been shown that there is ongoing airway inflammation and airway hyperresponsiveness even in the presence of low dose inhaled corticosteroids. To ensure a maximal therapeutic potential we investigated the effect of 3 mo of a very high dose of a new inhaled corticosteroid, fluticasone propionate (FP) (equivalent to 4,000 micrograms daily of beclomethasone dipropionate [BDP]. Twenty asthmatics with mild-to-moderate disease were recruited into this single-blind study. Baseline data were compared with those from 26 normal subjects. Differences in inflammatory indices between asthmatics and normal subjects were detected in both BAL and endobronchial biopsies. After the FP treatment period there was a significant improvement in symptom scores, lung function, and airway responsiveness by a mean 2.8 doubling dilutions of methacholine. Reduction in the airway lymphocyte load and lymphocyte activation was demonstrated and is likely to be an important mechanism mediating the effects of inhaled corticosteroids. Decreased mast cell numbers and activity in atopic asthma suggest that corticosteroids may have additional targets in different types of asthma. Reduced lymphocyte and mast cell activity was found with high dose FP even in those receiving low dose maintenance BDP prior to the study, suggesting a dose-response effect of inhaled corticosteroids on airway inflammation. BAL eosinophilia was still present after FP, indicative of a component of asthmatic airway inflammation that is relatively resistant to corticosteroid therapy.

Administration, Inhalation↗
PubMed1995

Intrasubject variability in airway inflammation sampled by bronchoalveolar lavage in stable asthmatics.

Despite the increasing complexity of bronchoalveolar lavage (BAL) studies in asthmatics there are few published data concerning the variability of inflammatory parameters measured using this technique. We studied the intrasubject variability of cellular and solute parameters in 20 clinically stable, symptomatic, mild-to-moderate asthmatics, in repeat 180 mL BAL procedures performed 1 month apart. During the study, there was no change in disease activity or medication. Mean (SD) forced expiratory volume in one second (FEV1) was 3.2 (1.09) L at the first BAL and 3.05 (0.98) L at the second. The geometric mean dose of methacholine provoking a 20% decrease in FEV1 (PD20) was 23 micrograms (range 2-1,170 micrograms) at the first BAL and 28 micrograms (range 2-400 micrograms) at the second. There was considerable variability in the BAL cellular and solute parameters measured over the two procedures. Estimates of power calculated for subsequent studies involving this type of subject group were made from the observed variability. Sample sizes of less than 15 mean that differences have to be large in order to be detected in repeat BAL samples. However, there is little improvement in the power of BAL studies for sample sizes greater than 20, indicating that there is little gain in recruiting more than this number of subjects. Thus, our study indicates that although studies of the pathophysiology underlying asthma using BAL require considerable commitment, they are practicable.

Adolescent↗
PubMed1994

Wegener's granulomatosis and the heart.

Three cases of Wegener's granulomatosis with cardiac complications are described and the relevant published reports are reviewed. The first case of Wegener's granulomatosis was associated with aortic regurgitation and required aortic valve replacement. The second and third cases were associated with pericardial disease requiring pericardiectomy for constructive pericarditis in one case, and haemorrhagic pericarditis with pericardial effusion in the other. Aortic valve involvement in Wegener's granulomatosis is uncommon and valve replacement has been described on only one previous occasion. Pericardial involvement is relatively common pathologically, but pericardial surgery has been described in this condition only twice, once for tamponade and once for constrictive pericarditis after pericardiocentesis. Cardiac involvement is not uncommon in patients with Wegner's granulomatosis and may be clinically important. Diagnosis is aided by estimation of the anti-neutophil cytoplasmic antibody titre.

Adult↗
PubMed1994

Frequency of arylsulphatase A pseudodeficiency associated mutations in a healthy population.

Arylsulphatase A (ASA, EC 3.1.6.1) is a lysosomal enzyme that catalyses cerebroside sulphate degradation. ASA deficiency is associated with metachromatic leucodystrophy (MLD), a rare autosomal recessive disorder, which is characterised by the storage of cerebroside sulphate. Low ASA activities can be also observed in clinically healthy persons, a condition termed ASA pseudodeficiency. Two mutations responsible for the majority of pseudodeficiency alleles have been defined in the ASA gene. These are both A-->G transitions. One causes an asparagine to serine substitution (N350S). The second changes the first polyadenylation signal downstream of the stop codon (1524 + 95A-->G), which causes a severe deficiency of one ASA mRNA species. The incidence of the pseudodeficiency allele is estimated to be high in the general population and can be found in families carrying MLD associated mutations. We report a reliable stratagem for detecting the two PD associated mutations separately, which we have applied to a healthy population. Two homozygotes for the N350S and 1524 + 95A-->G mutations were detected, which gives a population frequency of 2.6%. The overall frequencies of the ASA-PD mutations were shown to be 17.5% for the N350S change and 13.0% for the 1524 + 95A-->G change, estimating each mutation separately. In addition, the frequency of both PD associated mutations occurring together on the same chromosome was found to be 12.3% in our population. The study has also allowed us to establish a new control ASA activity range, which was based on assay of blood from persons who had been shown at the DNA level not to carry ASA PD associated mutations.

Base Sequence↗
PubMed1994

Effect of eight weeks of treatment with salmeterol on bronchoalveolar lavage inflammatory indices in asthmatics.

Using BAL, we studied the effects of 8 wk of treatment with salmeterol on airway inflammation in nine asthmatic subjects in a double-blind crossover placebo-controlled protocol. The study patients were all receiving regular inhaled corticosteroid therapy (400 to 1,000 micrograms beclomethasone dipropionate per day) and inhaled albuterol for symptomatic relief, i.e., subjects who might be considered suitable for treatment with salmeterol. The asthmatic group had significant differences in numbers of epithelial cells and eosinophils in BAL compared with a group of 15 normal control subjects (p < 0.01). During salmeterol treatment mean morning and evening peak flow rates were increased (p < 0.05). There was no significant change in BAL cell profile and no change in percentages of CD4 and CD8 lymphocytes or proportion of lymphocytes expressing HLA-DR after salmeterol. In conclusion, we were unable to demonstrate any significant anti-inflammatory effect of regular salmeterol therapy on airway inflammation using BAL in these asthmatic patients. At the same time, there was equally no evidence of a deterioration in the underlying inflammatory disease process.

Adrenergic beta-Agonists↗
PubMed1994

A nervous disorder in cattle, caused by the plants Ficus ingens var. ingens and Ficus cordata subsp. salicifolia.

Two outbreaks of neurotoxicoses are reported in cattle browsing on the leaves of Ficus spp. In the first outbreak, three animals died and one became ill. A sheep developed severe nervous signs, including tetanic spasms, when dosed with the leaves of Ficus ingens var. ingens from the toxic camp where the cattle had died. The second outbreak resulted in the death of 12 heifers within 48 h of ingestion of the leaves of F. cordata subsp. salicifolia. Clinical signs included hyperaesthesia, ataxia, muscle tremors and padding motions while in lateral recumbency. Similar signs were reproduced by drenching the incriminated leaves to a steer. The sheep dosed with F. ingens var. ingens and two cattle, one of which had died during the second outbreak and the steer drenched with F. cordata subsp. salicifolia, were necropsied. Light microscopical examination consistently revealed oedema of the central nervous system. In the steer, focal demyelination was evident in localized areas of the brain and spinal cord. Liver lesions ranged from mild degeneration to focal disseminated necrosis of hepatocytes.

Animals↗
PubMed1994

125I radioimmunoassay for the dual detection of amphetamine and methamphetamine.

A radioimmunoassay that exhibits a nearly equivalent response to D-amphetamine and D-methamphetamine in urine over the assay range of 0 to 1000 ng/mL while displaying low cross-reactivity to L-amphetamine and L-methamphetamine (4.6% and 2.4%, respectively) has been developed. In addition, methylenedioxy-amphetamine (MDA) and methylenedioxymethamphetamine (MDMA) were detectable in the assay with cross-reactivity levels of > 100% and 77% respectively. Little cross-reactivity was observed with the commonly encountered over-the-counter (OTC) drugs and this cross-reactivity was further reduced by the addition of sodium periodate into the reaction mixture to oxidize the beta-hydroxylamines. The double (second) antibody assay uses 125I-radiolabeled derivatives of both D-amphetamine and D-methamphetamine as tracers in combination with two highly specific sheep antisera directed against D-amphetamine and D-methamphetamine. The assay exhibits a dose-response of approximately 90,000 dpm from 0 to 1000 ng/mL of D-amphetamine or D-methamphetamine with a minimum detectable dose for either drug of approximately 25 ng/mL. With a cut-off level of 500 ng/mL, the assay gave a positive result for 100% of the 111 clinical samples containing GC/MS confirmed (at or above the NIDA GC/MS cut-off values) levels of amphetamine and/or methamphetamine. Eighty-eight samples that screened negative in a clinical laboratory were all negative in the assay. Nineteen samples which were incorrectly identified as positive by other commercially available amphetamine assays were negative in this RIA.

Amphetamine↗
PubMed1994

A day of day plastic surgery in a district general hospital.

In spite of the suitability of the day surgery environment for most patients undergoing elective plastic surgery, day plastic surgery has not been universally adopted in the United Kingdom. The experience of one plastic surgeon gained in treating 5970 patients as day cases out of a total of 12,461 patients over 10 years is described, with emphasis on the organisation of the service by only the consultant surgeon in collaboration with a medical secretary. Thus, neither the trainee surgeon nor GP clinical assistant in the team have any administrative duties. Within a day surgery unit with a twin theatre and 12 beds, it was possible on 1 day each week between July 1991 and June 1992 to treat 954 patients of whom 678 were treated under local anaesthesia and 276 under general anaesthesia. Three patients required admission to the main hospital overnight. By this day of day plastic surgery an effective service is provided to patients convenient to their home while also releasing facilities in the main regional centre which is equipped and staffed to a higher level of reconstructive expertise. However, the patients themselves should also play a part in improving the service intended for them, and a failure to attend for surgery without prior warning adds an avoidable element of inefficiency.

Adult↗