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Biomedical subjects

I K Taylor

Publications and source records attributed to I K Taylor.

At least 37 records · Page 2Linked to original sources
PubMed1993

Relation of HIV-I in bronchoalveolar lavage cells to abnormalities of lung function and to the presence of Pneumocystis pneumonia in HIV-I seropositive patients.

BACKGROUND: HIV is present in bronchoalveolar lavage cells of some but not all HIV seropositive patients. Abnormalities of lung function have been described in such patients in the absence of clinically overt pneumonia or other respiratory infections. It is possible that the presence of HIV in alveolar macrophages could account for these abnormalities. It is also possible that the presence of HIV in alveolar macrophages contributes to immunosuppression and an increased incidence of opportunistic infections. METHODS: This was a prospective study of 157 HIV seropositive patients requiring diagnostic bronchoscopy for investigation of new respiratory symptoms, chest radiograph abnormality, or pneumonic illness. Presence of HIV in bronchoalveolar lavage cells obtained at diagnostic bronchoscopy was determined by polymerase chain reaction to detect proviral DNA and in vitro cocultivation to detect productive virus infection. With these two techniques the presence or absence of HIV in bronchoalveolar lavage was compared with the presence of abnormalities of lung function or presence of Pneumocystis pneumonia. RESULTS: HIV was detected in bronchoalveolar lavage cells in 65% of patients by means of the polymerase chain reaction and 59% with cocultivation. With both methods of detection there was no association between the presence or absence of HIV and the presence of Pneumocystis pneumonia; nor was there a relation between the presence of HIV and abnormalities of lung function. CONCLUSION: The presence of HIV in bronchoalveolar lavage cells does not predispose to an increased incidence of Pneumocystis pneumonia; nor does it contribute to abnormalities of lung function.

Bronchoalveolar Lavage Fluid↗
PubMed1993

Potent leukotriene D4 receptor antagonist ICI 204,219 given by the inhaled route inhibits the early but not the late phase of allergen-induced bronchoconstriction.

ICI 204,219 is a potent and specific leukotriene D4 receptor antagonist that blocks both the early and late responses to allergen challenge in humans when given orally at a dose of 40 mg. Here we report our findings with an inhaled formulation of ICI 204,219 against allergen-induced bronchoconstriction. A group of 10 atopic subjects (mean age 25.6 +/- 4.2; 6 females; FEV1 > 90% of predicted; on inhaled beta 2-agonists only) were studied on 2 separate days 2 to 3 wk apart. In a randomized placebo-controlled trial they inhaled eight puffs of a standard metered dose inhaler containing either ICI 204,219 (200 micrograms/puff, total dose 1,600 micrograms) or propellant alone. They underwent bronchial allergen challenge 30 min later using a single concentration of allergen previously shown to lower the FEV1 by > or = 15%. FEV1 was monitored hourly for 10 h, and urine was collected for LTE4 determination. Inhalation of ICI 204,219 was well tolerated, with no adverse clinical or biochemical effects. There was no significant effect of ICI 204,219 inhalation on basal airway caliber (change in FEV1 30 min after inhalation was -149 +/- 67 ml after placebo versus 3 +/- 38 ml after ICI 204,219; p = 0.08). The early response to allergen was significantly inhibited by ICI 204,219 (the maximum fall in FEV1 was -21.2 +/- 6.1% after ICI 204,219 compared with -38.8 +/- 6.5% on placebo; p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1992

A comparative study in atopic subjects with asthma of the effects of salmeterol and salbutamol on allergen-induced bronchoconstriction, increase in airway reactivity, and increase in urinary leukotriene E4 excretion.

Salmeterol (SM) is a novel beta 2-adrenoceptor agonist with a duration of action in excess of 12 hours. Evidence from in vitro studies has also demonstrated that, unlike the short-acting beta 2-agonists, such as salbutamol (SB), it may have some anti-inflammatory properties. With a randomized, double-blind, crossover design, we have compared the inhibitory effects of SM (50 micrograms) and SB (200 micrograms) delivered by metered-dose inhaler on allergen-induced bronchoconstriction, changes in airway reactivity, and urinary leukotriene (LT) E4 excretion in 12 atopic subjects with mild asthma. The immediate bronchoconstriction to allergen was significantly reduced by both beta 2-agonists (p less than 0.005), when reduction was expressed either in terms of maximum fall in FEV1 at 15 minutes after allergen (percent fall in FEV1, mean +/- SEM: 6.2 +/- 4.9, SM; 5.7 +/- 2.5, SB; 40.4 +/- 6.3, placebo) or the area under the FEV1 time curve (AUC) for the first 120 minutes after allergen. Four hours after challenge, results in the SB-treated and placebo-treated groups were not significantly different and demonstrated a small persistent bronchoconstriction compared to bronchodilatation in the SM-treated group (percent fall in FEV1, respectively, 9.3 +/- 3.7, 14.3 +/- 7.1, and -6.3 +/- 2.7; p less than 0.005, SM versus SB; p less than 0.02, SM versus placebo). Expressed in terms of AUC, only SM significantly reduced bronchoconstriction in the period 120 to 240 minutes after allergen (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1992

Comparison of polymerase chain reaction amplification of two mycobacterial DNA sequences, IS6110 and the 65kDa antigen gene, in the diagnosis of tuberculosis.

BACKGROUND: Knowledge of the sequences of mycobacterial genes and the availability of DNA amplification techniques have raised the possibility that identification of mycobacterial DNA may offer a rapid and specific diagnostic test for tuberculosis. The correlation between the presence of Mycobacterium tuberculosis DNA and clinical tuberculosis, however, is not known. This study compared the results of polymerase chain reaction amplification of two M tuberculosis DNA sequences, IS6110 and the gene encoding the 65kDa heat shock protein (65kDa Ag), from sputum, bronchoscopy washings, and bronchoalveolar lavage fluid and related these findings to the presence of active and past tuberculosis. METHODS: Highly specific primers were used for amplification of IS6110 and 65kDa Ag DNA. Analysis was performed on one or more samples from 87 patients. RESULTS: IS6110 DNA was identified in samples from all six patients with active tuberculosis, from 15 to 18 patients with past tuberculosis, from five of nine contacts of patients with tuberculosis, and from nine of 54 patients with lung disease unrelated to tuberculosis. The 65kDa Ag DNA was identified in samples from all patients with active and past tuberculosis, from contacts of patients with tuberculosis, and from 14 of 42 patients with non-tuberculous lung diseases. CONCLUSION: These data suggest that the presence of IS6110 DNA correlates more closely with a tuberculosis related diagnosis than that of 65kDa Ag DNA and that both DNAs are found in most subjects with past tuberculosis or contacts of patients with tuberculosis. This may limit the clinical usefulness of these tests.

Base Sequence↗
PubMed1992

Urinary leukotriene E4 excretion in exercise-induced asthma.

Recent evidence suggests that the cysteinyl-leukotrienes (LTC4, LTD4, and LTE4) may be important in the pathogenesis of exercise-induced asthma. To evaluate the role of these mediators further, nine asthmatic subjects with exercise-induced bronchoconstriction were studied on two occasions. On visit 1, subjects performed 6 min of treadmill exercise; the mean maximal percent fall in FEV1 was 38.0 +/- 5.3%. On visit 2, maximal bronchoconstriction observed after exercise was matched with aerosolized methacholine. Urine was collected in two 90-min fractions (0-90 and 90-180 min) after challenges and analyzed by high-performance liquid chromatography-radioimmunoassay for LTE4. There were no significant differences in urinary LTE4 excretion between exercise and methacholine challenges for the periods 0-90 min (16.9 +/- 5.4 vs. 20.4 +/- 4.2 ng/mmol urinary creatinine), 90-180 min (24.9 +/- 8.2 vs. 20.1 +/- 5.5), or 0-180 min (21.5 +/- 6.5 vs. 18.8 +/- 4.1). Thus in contrast to allergen-induced bronchoconstriction, there is little evidence for enhanced cysteinyl-leukotriene generation in exercise-induced bronchoconstriction as assessed by urinary LTE4. If local release and subsequent participation of functionally active cysteinyl-leukotrienes in the pathways that ultimately lead to bronchoconstriction after exercise challenge do occur, these are of insufficient magnitude to perturb urinary LTE4 excretion.

Adult↗
PubMed1992

In vivo and in vitro effects of glucocorticosteroids on arachidonic acid metabolism and monocyte function in nonasthmatic humans.

Glucocorticosteroids are used as anti-inflammatory agents in a range of diseases, however, their mechanism of action is unknown. Recently, inhibition of arachidonic acid metabolism has been suggested as one possible mechanism of action. A series of experiments were undertaken in nonasthmatic humans to examine the effects of oral prednisolone and dexamethasone and inhaled budesonide on the excretion of the urinary leukotriene E4 (LTE4), an established marker of total body leukotriene generation in vivo. In addition, the effect of the drugs on the in vitro and ex-vivo function of monocytes was examined. In vitro dexamethasone greater than 10(-8) M inhibited the thromboxane A2 (TxA2) release from human monocytes, an effect which recovered within 24 h. In vivo, neither inhaled budesonide (1.6 mg.day-1 for 7 days), nor a standard therapeutic dose of oral prednisolone (30 mg.day-1 for 3 days), nor high doses of oral dexamethasone (8 mg.day-1 for 2 days) altered the excretion of urinary LTE4, despite the latter completely suppressing endogenous cortisol production. The ex-vivo zymosan stimulated release of TxA2 release from monocytes was not altered by the standard dose prednisolone, but was reduced by high dose dexamethasone and inhaled budesonide. This study shows that high doses of systemic steroids have little effect on arachidonic acid metabolism in normal nonasthmatic humans. Inhaled budesonide, however, does reduce arachidonic acid metabolism in circulating monocytes, presumably by affecting these cells during their passage through the lung.

Administration, Topical↗
PubMed1991

Gas chromatographic-mass spectrometric assay to measure urinary N tau-methylhistamine excretion in man.

An assay has been developed for N tau-methylhistamine, a major metabolite of the autocoid histamine, based on gas chromatography-electron-capture negative-ion chemical ionisation mass spectrometry. N tau-Methylhistamine was extracted from urine by cation-exchange chromatography and converted to its di-(3,5-bistrifluoromethylbenzoyl) derivative. The latter has good chromatographic properties and gives a negative-ion mass spectrum with the molecular ion (M., m/z 605) as base peak. A commercially available trideuterated analogue of N tau-methylhistamine was used as internal standard. Basal urinary excretion of N tau-methylhistamine in five normal subjects was found to be 0.21 +/- 0.05 mumol/h (289 +/- 74 mumol/mol of creatinine). This value was not significantly altered in these subjects following the infusion of a subpharmacological dose of histamine. In eight atopic volunteers, basal urinary excretion of N tau-methylhistamine was also not significantly changed following challenge with inhaled allergen.

Adult↗
PubMed1991

Effect of cysteinyl-leukotriene receptor antagonist ICI 204.219 on allergen-induced bronchoconstriction and airway hyperreactivity in atopic subjects.

The effects of a highly selective leukotriene D4 receptor antagonist, ICI 204.219, on allergen-induced bronchoconstriction and changes in airway reactivity were evaluated in a double-blind, placebo-controlled, crossover trial. Ten atopic subjects were selected for the study on the basis of an immediate fall in forced expiratory volume in 1 s (FEV1) of at least 15% and a least a doubling dose fall in their PC20-histamine (the concentration of histamine needed to reduce FEV1 by 20%) after antigen challenge. Baseline PC20-histamine was determined before the ingestion of a single oral 40 mg dose of ICI 204.219 or matched placebo. 2 h later subjects were challenged with aerosolised allergen; FEV1 was measured for the next 6 h then PC20-histamine was remeasured. Two subjects did not complete the study for reasons not related to the trial medication. ICI 204.219 significantly attenuated the early and late phase bronchoconstriction to inhaled allergen (mean treatment difference in area under the FEV1-time curves 2529 [95% Cl 1085-3972] delta %FEV1.min; p less than 0.005: and 3537 [528-6545] delta %FEV1.min; p less than 0.03) and suppressed the allergen-induced increase in non-specific bronchial reactivity (mean treatment difference 1.03 [0.34-1.71] doubling dilutions of histamine; p less than 0.01). These findings suggest that ICI 204.219 may be a disease-modifying agent in asthma. Further studies are under way to evaluate its clinical efficacy.

Administration, Inhalation↗
PubMed1991

Effect of a 5-lipoxygenase inhibitor on leukotriene generation and airway responses after allergen challenge in asthmatic patients.

The effect of a single oral dose (800 mg) of zileuton (A-64077), a specific 5-lipoxygenase inhibitor, on the early and late airway responses to inhaled allergen was studied in a randomised, double blind, placebo controlled, and crossover trial in nine subjects with atopic asthma. Leukotriene generation was also assessed in vivo by measuring urinary leukotriene (LT) E4 excretion, and ex vivo by measuring calcium ionophore stimulated whole blood LTB4 production. Zileuton almost completely inhibited ex vivo LTB4 production but reduced urinary excretion of LTE4 by only about half. There was a trend for the early asthmatic response to be less on the day of zileuton treatment, but this did not reach statistical significance (p = 0.08). The zileuton induced reduction in maximum fall in FEV1 in the early asthmatic response was, however, significantly related to the reduction in urinary LTE4 excretion (r = 0.8), but not to the reduction in LTB4 generation ex vivo. There was no significant change in the allergen induced late asthmatic response, or in the increase in airway responsiveness to methacholine following antigen. The results provide some support for the hypothesis that the cysteinyl leukotrienes have a role in the allergen induced early asthmatic response. More complete in vivo inhibition of 5-lipoxygenase may be needed to produce a significant reduction in airway response to allergen challenge.

Adult↗
PubMed1991

Inhaled PAF stimulates leukotriene and thromboxane A2 production in humans.

Platelet-activating factor (PAF) is a potent bronchoconstrictor in humans and has been implicated as an inflammatory mediator in asthma. This study was performed to evaluate whether PAF-induced bronchoconstriction in vivo could be mediated through the release of the bronchoconstrictor eicosanoids, thromboxane (Tx) A2 and the cysteinyl leukotrienes. Ten asthmatic subjects were studied on three occasions after bronchial challenges with aerosolized PAF, methacholine, or isotonic saline. PAF caused bronchoconstriction in all 10 subjects (mean maximal percent fall in specific airway conductance 48.2 +/- 4.6) and was matched by methacholine challenge. Saline caused no changes in specific airway conductance. Urinary leukotriene E4 was significantly elevated after inhaled PAF (366.0 +/- 66.9 ng/mmol creatinine, P less than 0.01) compared with methacholine (41.6 +/- 13.3) and saline (33.6 +/- 4.6). The major urinary TxA2 metabolite 2,3-dinor TxB2 was elevated after inhaled PAF (41.3 +/- 7.1 ng/mmol creatinine, P less than 0.01) compared with methacholine (14.0 +/- 2.7) and saline (17.1 +/- 3.9). Urinary 2,3-dinor 6-oxo-prostaglandin F1 alpha after PAF (22.2 +/- 1.4) was raised with respect to the methacholine challenge (13.9 +/- 1.8, P less than 0.02), although no significant increase was observed compared with the saline control (18.6 +/- 3.3). Inhaled PAF leads to the secondary generation of cysteinyl leukotrienes and TxA2, and it is possible that these mediate some of the acute effects of inhaled PAF in vivo.

Administration, Inhalation↗
PubMed1991

Thromboxane A2 biosynthesis in acute asthma and after antigen challenge.

Thromboxane A2 is a potent bronchial smooth muscle spasmogen in vitro, and it has been implicated in airway inflammation and in the genesis of bronchial hyperresponsiveness in asthma. We have examined the urinary excretion of a variety of products derived from thromboxane A2 (thromboxane B2, 2,3-dinor, and 11-dehydro-thromboxane B2) and prostacyclin (6-oxo-PGF1 alpha and 2,3-dinor-6-oxo-PGF1 alpha) using gas chromatography-mass spectrometry in patients admitted acutely to hospital with severe asthma and in atopic volunteers after bronchial antigen challenge. Urinary excretion of all thromboxane-derived products was markedly increased in a number of patients with severe acute asthma compared with that in a nonsmoking control population, in some cases approaching those previously described in myocardial infarction: TXB2, 31.6 +/- 12.0 versus 6.5 +/- 0.9; 2,3-dinor-TXB2, 79.0 +/- 19.2 versus 29.5 +/- 2.7; and 11-dehydro-TXB2, 234.3 +/- 65.3 versus 25.0 +/- 2.1 ng/mmol creatinine (p less than 0.001). Urinary prostacyclin-derived products were also significantly raised in acute asthma. In contrast, after inhaled allergen challenge in atopic volunteers, which caused significant bronchoconstriction, urinary excretion of thromboxane-derived products was not significantly elevated: TXB2, 5.6 +/- 1.1 versus 5.7 +/- 1.0; 2,3-dinor-TXB2, 41.2 +/- 12.5 versus 28.5 +/- 6.9; and 11-dehydro-TXB2, 69.8 +/- 17.6 versus 39.7 +/- 11.2 ng/mmol creatinine. In a separate experiment, less than 2% of exogenously administered TXB2 to the airway appeared as urinary thromboxane-derived products, suggesting that production of greater than or equal to 1 microgram of TXA2 in vivo would be required to increase urinary thromboxane excretion twofold.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1990

Urinary N tau-methylimidazole acetic acid excretion in respiratory disease.

N tau-methylimidazole acetic acid (N tau-MIAA) is the principal urinary metabolite of histamine. The basal urinary excretion rate of N tau-MIAA was determined as 0.117 +/- 0.008 (SE) mg/h, with a renal clearance for N tau-MIAA of 273 +/- 27 ml/min implying active secretion. After subpharmacological infusion of histamine (50 ng.kg-1.min-1 over 2 h) in five volunteers that increased plasma histamine from 0.28 +/- 0.04 to 0.71 +/- 0.15 ng/ml, urinary excretion of N tau-MIAA over 8 h was increased by less than 17% compared with a control saline infusion. Urinary N tau-MIAA excretion in normal controls (273 +/- 14 micrograms/mmol creatinine) was similar to that observed in patients with severe acute asthma (253 +/- 22 micrograms/mmol), antigen-induced bronchoconstriction (269 +/- 21 micrograms/mmol), seasonal allergic rhinitis (304 +/- 31 micrograms/mmol), and clinically stable bronchiectasis (270 +/- 22 micrograms/mmol). In contrast, large increases in metabolite excretion (greater than 7,000 micrograms/mmol creatinine) were observed in a patient with systemic mastocytosis where very high plasma histamine levels were recorded (greater than 500 ng/ml) and marked systemic hemodynamic effects occurred. We conclude that urinary N tau-MIAA will only be increased in pathologies where sustained hyperhistaminemia occurs and that increased local histamine production in the lung or the upper airway does not cause a measurable change in the basal urinary excretion of this metabolite.

Adult↗
PubMed1989

Assay for N tau-methylimidazoleacetic acid, a major metabolite of histamine, in urine and plasma using capillary column gas chromatography-negative ion mass spectrometry.

A gas chromatographic-mass spectrometric assay has been developed for the measurement of N tau-methylimidazoleacetic acid in urine and plasma. The method uses the isopropyul ester 3,5-bistrifluoromethylbenzoyl derivative of N tau-methylimidazoleacetic acid and electron capture negative ion chemical ionisation mass spectrometry. The derivative has very good chromatographic properties and a negative ion mass spectrum which contains only a molecular ion at m/z 422. When this ion is specifically monitored, an amount of derivative equivalent to 1 pg of parent compound can be detected. A deuterated analogue of N tau-methylimidazoleacetic acid was synthesised for use as an internal standard and this allowed the development of an assay for N tau-methylimidazoleacetic acid, in urine with a precision of 2.9% and in plasma with a precision of 1.5%.

Chemical Phenomena↗
PubMed1975

Muscarinic receptors in rat intestinal muscle: comparison with the guinea pig.

The properties of muscarinic receptors in rat intestinal muscle have been investigated by examining the binding of 3H-propylbenzilylcholine mustard, 3H-PrBCM, a specific and virtually irreversible muscarinic antagonist. It is shown that the properties of these muscarinic receptore correspond in general closely to those observed in the guinea pig, in particular the binding curve inferred for carbachol shows the same apparent negative cooperativity, but there is a notable difference in the rate of binding 3H-PrBCM.

Animals↗