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Biomedical subjects

C C Hardy

Publications and source records attributed to C C Hardy.

At least 19 recordsLinked to original sources
PubMed1992

99Tcm-Technegas and krypton-81m ventilation scintigraphy: a comparison in known respiratory disease.

Krypton-81m gas, by virtue of its imaging characteristics, is often considered the "gold standard" for ventilation scintigraphy but its use is restricted by its high cost and limited availability. The new radiopharmaceutical 99Tcm-Technegas, a suspension of ultrafine technetium-99m labelled carbon particles, produces high-quality images of ventilation and has the advantage of continuous availability. As part of our evaluation of Technegas the two were compared in 40 patients with a variety of established respiratory diseases. Disparities were seen in five patients in five diagnostic groups and may be a consequence of the differing physical properties of the two agents and the different inhalation techniques used. In addition two interesting features were noted on the Technegas images. (1) Hot spots were seen in 50% of patients, particularly in those with a degree of airways obstruction; (2) preferential basal deposition of activity was seen in 30%, particularly in patients with idiopathic pulmonary fibrosis. Both features were significantly associated with parameters of pulmonary function indicating obstructive lung disease in the former case and restrictive lung disease in the latter.

Adult↗
PubMed1991

Inhaler therapy.

Explore the source record for details and available documents.

Acute Disease↗
PubMed1989

Asthma in pregnancy complicated by iatrogenic pulmonary oedema.

We report a unique case of near fatal acute pulmonary oedema developing with intravenous ritodrine, given in an attempt to suppress premature labour. The novel aspect of the case is that the patient had also been treated in the previous week with high dose nebulized beta-agonists for an episode of acute severe asthma, demonstrating that this idiosyncratic reaction to beta-adrenergic agents only occurs with the intravenous route of administration. The management of acute severe asthma occurring in pregnancy is discussed with a review of previous literature regarding possible mechanisms of beta 2-agonist-induced pulmonary oedema.

Acute Disease↗
PubMed1988

The metabolism of prostaglandin D2 after inhalation or intravenous infusion in normal men.

Tritium-labelled prostaglandin D2 (PGD2) was administered to normal volunteers by either intravenous infusion or inhalation in order to establish which metabolites of PGD2 are initially found in human plasma. Inhaled PGD2 was rapidly absorbed from the airways, as indicated by the rapid appearance of tritium in the plasma. Metabolites chromatographically similar to 9 alpha,11 beta-PGF2 and 13,14-dihydro-15-keto-9 alpha,11 beta-PGF2 were found after both routes of administration. At later time points, other unidentified compounds were present. Only after intravenous infusion was there evidence of metabolites with 9 alpha,11 alpha stereochemistry of the ring hydroxyl functions. In human lung, 9 alpha,11 beta-PGF2 was metabolized in the presence of NAD+ to compounds tentatively identified by gas chromatography/mass spectrometry (GC/MS) as 15-keto-9 alpha,11 beta-PGF2 and 13,14-dihydro-15-keto-9 alpha,11 beta-PGF2. Thus, after 11-ketoreductase-dependent metabolism of PGD2 to the biologically active compound 9 alpha,11 beta-PGF2, further metabolism probably proceeds by the combined action of 15-hydroxyprostaglandin dehydrogenase/15-ketoprostaglandin-delta 13-reductase (15-PGDH/delta 13R). Both 9 alpha,11 beta-PGF2 and its 13,14-dihydro-15-keto metabolite may be useful analytes for the measurement of PGD2 turnover, and may therefore prove to be important in understanding the pathophysiological significance of this putative mediator.

Administration, Inhalation↗
PubMed1988

Bronchoconstrictor and antibronchoconstrictor properties of inhaled prostacyclin in asthma.

Prostacyclin (PGI2) is generated in appreciable amounts during allergic reactions in human lung tissue. To define its activity on human airways we have studied the effects of doubling concentrations of inhaled PGI2 and its hydrolysis product 6-oxoprostaglandin F1 alpha (6-oxo-PGF1 alpha) on specific airway conductance (sGaw), maximum expiratory flow at 30% vital capacity (Vmax30), forced expiratory volume in 1 s (FEV1), and static lung volumes in subjects with mild allergic asthma. In a second study the effect of inhaled PGI2 on bronchoconstriction provoked by increasing concentrations of inhaled prostaglandin (PG) D2 and methacholine was observed. Inhalation of PGI2 up to a concentration of 500 micrograms/ml had no significant effect on sGaw but produced a concentration-related decrease in FEV1 and Vmax30 in all subjects. In two of four subjects inhalation of PGI2 also increased residual volume and decreased vital capacity but had no effect on total lung capacity. PGI2, but not 6-oxo-PGF1 alpha, protected against bronchoconstriction provoked by either PGD2 or methacholine whether airway caliber was measured as sGaw, FEV1, or Vmax30. The apparent disparity between the bronchoconstrictor and antibronchoconstrictor effects of PGI2 might be explained by its potent vasodilator effect in causing airway narrowing through mucosal engorgement and reducing the spasmogenic effects of other inhaled mediators by increasing their clearance from the airways.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

9 alpha,11 beta-prostaglandin F2, a novel metabolite of prostaglandin D2 is a potent contractile agonist of human and guinea pig airways.

Prostaglandin (PG) D2, the predominant prostanoid released from activated mast cells in humans is initially metabolized by reduction of the C-11 keto function to yield 9 alpha,11 beta-PGF2. In this study the airways effects of 9 alpha,11 beta-PGF2 were compared with those of its epimer 9 alpha,11 alpha-PGF2 (PGF2 alpha) and PGD2. 9 alpha,11 beta-PGF2 was a potent contractile agonist of isolated guinea pig trachea and 4-mm human airways in vitro; the potencies of the PGs relative to PGD2 (= 1.00) being 0.65 (NS) and 4.08 (P less than 0.001) for 9 alpha,11 beta-PGF2, and 0.52 (P less than 0.01) and 2.40 (P less than 0.001) for PGF2 alpha, respectively. When inhaled by asthmatic subjects, 9 alpha,11 beta-PGF2 was a potent bronchoconstrictor agent, being approximately equipotent with PGD2 and 28-32 times more potent than histamine (P less than 0.01). These studies suggest that 9 alpha,11 beta-PGF2 is at least equipotent with PGD2 as a bronchoconstrictor agonist, and in being a major metabolite of PGD2, could contribute to the bronchoconstrictor effect of this mast cell-derived mediator in asthma.

Adult↗
PubMed1986

The combined effects of two pairs of mediators, adenosine with methacholine and prostaglandin D2 with histamine, on airway calibre in asthma.

Mediators released from mast cells and secondary effector cells in the airways contribute to bronchoconstriction of allergic asthma. This study investigates methods for defining the effect of two inflammatory mediators on airway calibre in asthma. In an initial study on three asthmatic subjects, subconstrictor (subthreshold) concentrations of two mast cell derived mediators, histamine and prostaglandin (PG) D2, produced similar displacement to the left of a histamine concentration-specific airways conductance (sGaw) response curve. With both agonists enhancement of histamine-induced bronchoconstriction was greater at low histamine concentrations. Since potentiation of histamine-induced bronchoconstriction was independent of the class of subconstrictor agent given, it is likely to represent a physiological rather than a pharmacological interaction. During provoked asthma different constrictor mediators are likely to be released simultaneously into the airways. A method was therefore devised to investigate the combined effect of equiconstrictor concentrations of two mediators on airway calibre. Two pairs of inhaled bronchoconstrictor agonists were chosen for study: adenosine with methacholine and PGD2 with histamine. For each agonist, concentration-sGaw response curves were constructed, from which were derived the provocation concentrations of agonist causing a 25% fall in sGaw from baseline (PC25) and required to further this to 50% (PC50-25). On separate days, eight subjects received paired inhalations of methacholine-adenosine, methacholine-methacholine and adenosine-adenosine. The concentration used for the first inhalation was the PC25 value and for the second inhalation the PC50-25 value. Before, immediately after the first inhalation, and at regular intervals after the second inhalation, sGaw was followed for 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1986

Evidence against the formation of 13,14-dihydro-15-keto-prostaglandin F2 alpha following inhalation of prostaglandin D2 in man.

There is evidence that an important step in the metabolism of prostaglandin D2 (PGD2) involves 11-keto-reduction and that such a conversion might account for the reported increase in plasma concentrations of 13,14-dihydro-15-keto-PGF2 alpha in allergic asthmatic subjects challenged with inhaled allergen. Plasma concentrations of immunoreactive 13,14-dihydro-15-keto-PGF2 alpha were measured by specific radioimmunoassay both before and after inhalation of PGD2 and PGF2 alpha in 7 normal and 7 asthmatic men. In both groups of subjects, PGF2 alpha produced an approximate two fold increase in plasma concentrations of 13,14-dihydro-15-keto-PGF2 alpha that was maximal 5-7 min after inhalation. There was no significant difference in response between the normal and asthmatic subjects. In contrast, PGD2 failed to produce a change in plasma 13,14-dihydro-15-keto-PGF2 alpha concentration in either group. These results provide evidence that the conversion of PGD2 to PGF2 alpha with subsequent metabolism to 13,14-dihydro-15-keto-PGF2 alpha is unlikely to occur when PGD2 is released from mast cells in the airways.

Adult↗