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Biomedical subjects

K P Hui

Publications and source records attributed to K P Hui.

16 recordsLinked to original sources

Structural features of tracheal tube biofilm formed during prolonged mechanical ventilation.

The dissemination of tracheal tube biofilm into the mechanically ventilated lung has been proposed as a contributory factor in the pathogenesis of ventilator-associated pneumonia. In the present study, conventional light microscopy, confocal laser scanning microscopy, and scanning electron microscopy were used to examine luminal tracheal tube biofilm in tubes from ten consecutive medical intensive care patients. Biofilms also were cultured. No tube contained a predominantly microbial aggregate. Microorganisms were either dispersed throughout the biofilm or restricted to the most superficial layer. Neutrophil polymorphonuclear cells were present in all biofilms in a pattern suggesting that a layering or stratification had taken place. The distribution of neutrophils and microorganisms was consistent with a progressive accretion of respiratory secretions, rather than formation of a predominantly microbial biofilm.

Adult

Ventilatory function measured with the Micro Spirometer: performance evaluation and reference values.

The performance of the Micro Spirometer was compared with that of the Vitalograph by assessing the extent of agreement between the instruments and the repeatability of measurements with each instrument. The Micro Spirometer tended to give lower readings of forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) than the Vitalograph, with wide limits of agreement. The values of these ventilatory functions measured with the Micro Spirometer were, therefore, not directly comparable with those obtained from the Vitalograph, and it is also not satisfactory to predict readings on the Micro Spirometer from those made on the Vitalograph. In the management of asthma patients, the PEFR would still be preferably measured with the mini Wright peak flow, given its low cost and established reliability compared with the standard Wright peak flow meter. The Micro Spiromoter has the practical advantages of portability, ease of operation and relative cheapness for the baseline and long-term assessment of FEV1 and FVC in ambulatory care, as well as in epidemiological studies. However, local users should not employ reference values provided by the manufacturer or those published in the literature, but those reported in this paper.

Adolescent

Klebsiella bacteraemia: a report of 101 cases from National University Hospital, Singapore.

One hundred and one cases of Klebsiella bacteraemia from the National University Hospital, Singapore, were reviewed retrospectively. There were 54 (53.5%) males and 47 (46.5%) females. Mean (+/- SE) age was 54 (+/- 2.4) years. Overall mortality was 26%. Nosocomial infections accounted for 20%. Underlying diabetes mellitus and malignancy were present in 36 and 26% respectively. The source of the bacteraemia was not known in 33% of cases, 17% had liver abscess, 29% had urinary tract infections, 9% had pneumonia, 10% had an abscess separate from the liver, and 3% had biliary sepsis. Elevated alkaline phosphatase (> 100 U-1) was seen in all cases of liver abscess (sensitivity 100%, specificity 27%). Nonsurvivors had a significantly lower platelet count than survivors (104 +/- 25 x 10(9)/l vs. 176 +/- 15 x 10(9)/l, unpaired t-test P < 0.05), and a platelet count of less than 150 x 10(9)/l was associated with a significantly higher mortality (37% vs. 11%, chi 2 P < 0.01). Nosocomial infection was associated with 45% mortality, whereas community-acquired infection had a lower rate of 21%, this was not statistically significant. Seventy-eight per cent of these Klebsiella isolates were sensitive to gentamicin and cotrimoxazole, and 100% to imipenem.

Anti-Bacterial Agents

Inhaled beta 2-adrenergic agonists in asthma: the evolving dilemma.

Inhaled beta 2-adrenergic agonists have been used in the treatment of asthma since the 1970's. They are extremely effective bronchodilators in all situations of bronchoconstriction, and are generally well tolerated by patients. The recent advent of long-acting beta 2-adrenergic agonists will extend the clinical applications of this group of drugs. On the other hand, doubts have recently emerged on the safety of inhaled beta 2-adrenergic agonists. Recent well controlled studies also examined the manners whereby inhaled beta 2-adrenergic agonists are used in asthmatics, and the long term effects on lung functions. Although at least two decades have passed since the introduction of inhaled beta 2-adrenergic agonists, strategies on their optimum use have only emerged from these recent findings. This review briefly discusses as the most important developments leading to the rationalisation of the way inhaled beta 2-adrenergic agonists should be used in clinical asthma.

Administration, Inhalation

Modulation of neurally mediated airway microvascular leakage in guinea-pig airways by beta 2-adrenoceptor agonists.

The effect of two beta 2-adrenoceptor agonists, salbutamol (100 micrograms/kg i.v.) and broxaterol (100 micrograms/kg i.v.), on airway microvascular leakage induced by vagal stimulation was studied in anaesthetised guinea pigs. Airway microvascular leakage was measured by Evans blue extravasation. Broxaterol, but not salbutamol, inhibited Evans blue dye extravasation at all airway levels, an effect prevented by pretreatment with propranolol (1 mg/kg). Neither of the beta 2-agonists had any effect on substance P-induced Evans blue dye extravasation. Broxaterol inhibits the prejunctional release of tachykinins from airway sensory nerves by stimulation of beta-receptors. The mechanism by which beta-adrenoceptor agonists prevent airway microvascular leakage deserves further study.

Adrenergic beta-Agonists

Ovalbumin aerosol challenge in actively sensitized guinea pigs: relationship between airway microvascular leakage and airflow obstruction.

Airway inflammation is a common feature of asthma, and one of the cardinal features of inflammation is increased microvascular permeability. We investigated the characteristics of inhaled ovalbumin challenge-induced airflow obstruction and airway microvascular leakage in vivo in mechanically ventilated guinea pigs actively sensitized to ovalbumin. A method was used to quantify both airflow obstruction and airway microvascular leakage in order to investigate the relationship between these 2 pathophysiological features in the same animal. Airway microvascular leakage was assessed by Evans blue dye extravasation into airway tissues. Actively sensitized guinea pigs developed both acute airflow obstruction (increased lung resistance and reduced dynamic lung compliance) and Evans blue dye extravasation in response to exposure to aerosolised ovalbumin. Evans blue dye extravasation was preferentially distributed in the distal airways and correlated with airflow obstruction. The results show that inhaled allergen induced both acute airflow obstruction and airway microvascular leakage.

Acute Disease

Lung function improvement in asthma with a cysteinyl-leukotriene receptor antagonist.

In a double-blind study ten asthmatic patients with impaired lung function received the cysteinyl-leukotriene receptor antagonist ICI 204,219 (40 mg by mouth) and placebo in random order on 2 days at least 1 week apart. The increase in forced expiratory volume in 1 s (FEV1) above baseline was significantly greater after ICI 204,219 than after placebo. This effect persisted after nebulised salbutamol. These findings suggest that cysteinyl-leukotrienes are one of the causes of persistent bronchoconstriction in chronic asthma.

Administration, Inhalation

A comparison of sustained release verapamil versus atenolol for 24 h protection from exercise-induced angina pectoris.

We have compared the efficacy of a once daily 360 mg sustained release preparation of verapamil (SRV) with that of once daily 100 mg atenolol in exercise-induced angina. The study was randomized, double-blind and cross-over in design involving 30 patients with chronic stable angina. A 2-week run-in placebo phase was followed by two 4-week periods of active treatment. Patients underwent exercise stress tests at 6 and 24 h post-dose at the end of each treatment phase. After the placebo phase, patients had significantly increased times to both 1 mm ST depression and angina at 6 h (afternoon stress test) compared to 24 h post-dose (morning test). The two treatments were found to be equivalent in terms of several indices of anti-anginal efficacy. The only significant differences between treatments were in relation to indices of heart rate, which were consistently lower with atenolol than with SRV. We conclude that once daily sustained release verapamil 360 mg has equivalent anti-anginal efficacy to once daily atenolol 100 mg. A lower angina threshold seems to occur in the morning in patients with ischaemic heart disease suggesting a diurnal variation.

Angina Pectoris

Capsaicin pretreatment does not inhibit allergen-induced airway microvascular leakage in guinea pig.

We have studied the effects of tachykinin-depletion on airway microvascular leakage induced by allergen challenge in ovalbumin-sensitised guinea pigs. Tachykinin-depletion was obtained by capsaicin pretreatment 1 week before inhaled allergen challenge. Capsaicin pretreatment did not change airway microvascular permeability induced by allergen challenge. Thus, sensory neuropeptides may not be important in allergen-induced acute airway microvascular leakage in guinea pig in vivo.

Airway Obstruction

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

Attenuation of inhaled allergen-induced airway microvascular leakage and airflow obstruction in guinea pigs by a 5-lipoxygenase inhibitor (A-63162).

Leukotrienes, products of the 5-lipoxygenase pathway in the metabolism of arachidonic acid, are potent mediators of airway microvascular leakage and smooth muscle contraction in guinea pigs. We studied the effect of a specific 5-lipoxygenase inhibitor, A-63162, on airway microvascular leakage and airflow obstruction following inhaled ovalbumin in actively sensitized guinea pigs. Airway microvascular leakage was assessed by extravasation of Evans blue dye into airway tissues. Inhaled ovalbumin caused increased lung resistance (RL) with decreased dynamic compliance (CL) and increased extravasation of Evans blue dye at all airway levels. A-63162 reduced the changes in RL and CL at 1.0 mumol/kg (p less than 0.05) but not at lower doses of 0.1 and 0.3 mumol/kg. A-63162 reduced Evans blue dye extravasation in airway tissues at all three doses, however, being most effective in the distal airways (p less than 0.01), and these reductions were greater than those in RL and CL. A 5-lipoxygenase inhibitor thus reduced airway microvascular leakage to a greater extent than airflow obstruction, suggesting that leukotrienes have a larger contribution to changes in airway microvascular permeability than smooth muscle contraction following inhaled allergen challenge in actively sensitized guinea pigs in vivo.

Acetamides

Airflow obstruction after substance P aerosol: contribution of airway and pulmonary edema.

We have studied the effects of aerosolized substance P (SP) in guinea pigs with reference to lung resistance and dynamic compliance changes and their recovery after hyperinflation. In addition, we have examined the concomitant formation of airway microvascular leakage and lung edema. Increasing breaths of SP (1.5 mg/ml, 1.1 mM), methacholine (0.15 mg/ml, 0.76 mM), or 0.9% saline were administered to tracheostomized and mechanically ventilated guinea pigs. Lung resistance (RL) increased dose dependently with a maximum effect of 963 +/- 85% of baseline values (mean +/- SE) after SP (60 breaths) and 1,388 +/- 357% after methacholine (60 breaths). After repeated hyperinflations, methacholine-treated animals returned to baseline, but after SP, mean RL was still raised (292 +/- 37%; P less than 0.005). Airway microvascular leakage, measured by extravasation of Evans Blue dye, occurred in the brain bronchi and intrapulmonary airways after SP but not after methacholine. There was a significant correlation between RL after hyperinflation and Evans Blue dye extravasation in intrapulmonary airways (distal: r = 0.89, P less than 0.005; proximal: r = 0.85, P less than 0.01). Examination of frozen sections for peribronchial and perivascular cuffs of edema and for alveolar flooding showed significant degrees of pulmonary edema for animals treated with SP compared with those treated with methacholine or saline. We conclude that the inability of hyperinflation to fully reverse changes in RL after SP may be due to the formation of both airway and pulmonary edema, which may also contribute to the deterioration in RL.

Aerosols

Inhibition of hepatic S-3-hydroxy-3-methylglutaryl-CoA reductase and in vivo rates of lipogenesis by a mixture of pure cyclic monoterpenes.

A proprietary mixture of pure cyclic monoterpenes (Rowachol) inhibited hepatic HMGCoA reductase by 50-60% when measured 17 hr after the oral administration of a single dose to rats. The extent of this inhibition was independent of the normal activity range of HMGCoA reductase within its diurnal cycle and the same inhibition (65%) was found in 24 hr starved animals where the control reductase activity was less than 20% that of normal fed rats. De novo sterol and fatty acid synthesis in intact, fed rats was measured by incorporation of 3H from injected H2O. In rats treated with Rowachol the rate of sterol synthesis in vivo was inhibited 52% in liver and 44% in testis with no significant effects in other tissues. The synthesis of non sterol (isoprenoid) compounds in testis was unaffected and the inhibition of sterol synthesis in this tissue probably reflects decreased acquisition of newly synthesized material from liver rather than any effect on the endogenous process. In the same animals the rate of fatty acid synthesis was inhibited 55% in liver. These effects were associated with a significant depletion of liver glycogen which may account for the reduction in rate of fatty acid synthesis. We conclude that the reported cholelitholytic action of monoterpenes is associated with the physiological inhibition of hepatic sterol synthesis mediated by decrease HMGCoA reductase activity.

Animals