Community-acquired pneumonia in the Far East.
Explore the source record for details and available documents.
Humans↗
Biomedical subjects
K P Hui
Publications and source records attributed to K P Hui.
Asthma--new drugs on the horizon?
Over the last ten years, much new knowledge about the pathophysiology of asthma is learnt. In parallel, a plethora of new drugs is developed for the treatment of asthma. Many of these drugs were initially enthusiastically heralded as therapeutic breakthroughs, but few were shown to have real clinical benefits. This review concisely discusses important recent developments on several classes of drugs: novel drugs such as ion channel blockers, thromboxane and leukotriene receptor antagonists, platelet activating factor (PAF) antagonists; newer developments of established drugs (in particular long-acting beta 2-adrenergic receptor agonists); and immunoregulatory drugs. The emphasis of the discussion is on clinical evaluations that are relevant in the treatment of asthmatic patients.
Asthma↗
Factors influencing pulse oximetry as compared to functional arterial saturation in multi-ethnic Singapore.
Noninvasive oximetry provides continuous monitoring of arterial oxygen saturation and hence, early detection of hypoxia. This has proved to be a useful adjunct to patients' safety, and is considered indispensable in certain settings. However, errors may be present in the pulse oximeter estimation (SpO2) of arterial oxygen saturation (SaO2), which may be due to various parameters. We have studied a multi-ethnic population where the skin pigmentation is different, and also under different conditions comparing SpO2 with SaO2. Our results showed that SpO2 estimation of SaO2 amongst the three racial groups (Chinese, Malays, and Indians) varied significantly (ANOVA, p < 0.05). The over-estimation was more pronounced by hypoxic conditions and jaundice. Haemoglobin and systolic blood pressure did not affect the difference between SpO2 and SaO2.
Adult↗
Acute physiology and chronic health evaluation (APACHE II) scoring in the Medical Intensive Care Unit, National University Hospital, Singapore.
The intensive care unit provides multisystem support and therapy to critically ill patients, and represents an expensive part of hospital medicine. This survey validates the use of APACHE II as a severity scoring system that allows reliable prediction of outcome of intensive care patients in Singapore. The mortality rate of 37.4% in our medical intensive care unit compares favourably with the other established intensive care units in the United States of America. Our results also indicate that the aged fared as well as their younger counterparts. Patients with sepsis fared poorer than expected from their APACHE II scores, and stroke patients needing intensive care admission had an extremely poor prognosis (mortality rate of 85.7%). High APACHE II scores are associated with invasive haemodynamic monitoring.
Adolescent↗
Thrombocytopenia in sepsis: a predictor of mortality in the intensive care unit.
Disseminated intravascular coagulation (DIC) and thrombocytopenia are well-known complications of sepsis, but the relationship between these coagulation abnormalities and outcome have not been well documented. We studied the incidence of thrombocytopenia and DIC in our Medical Intensive Care Unit, and evaluated their usefulness as prognostic risk factors for mortality. Platelet count was not found to be an independent risk factor associated with overall mortality in the 107 patients studied. In the sub-group of 53 patients with sepsis, 22 (42%) developed DIC, 31 (58%) developed thrombocytopenia (< 150,000 x 10(9)/L) and 27 (51%) died. Thrombocytopenia was associated with presence of DIC (p = 0.003), but not with the type of infecting organism. The platelet count in non-survivors (mean +/- sem, 97 +/- 18 x 10(9)/L) was significantly lower than survivors (194 +/- 27 x 10(9)/L, p < 0.005). Multiple regression analysis showed that thrombocytopenia was a risk factor for mortality, independent of the APACHE II score. The presence of DIC surprisingly was not an independent risk factor. We conclude that DIC and thrombocytopenia are common in our adult Medical Intensive Care patients with sepsis, but only the latter is a prognostic factor in addition to the APACHE II score. The incidence of DIC in our patients (mainly Chinese) seems to be more than that of 10 to 20% reported in other series of Caucasian patients. We would, therefore, like to emphasise the importance of platelet count as an prognostic risk factor in sepsis.
Adolescent↗
Prospective study of the aetiology of adult community acquired bacterial pneumonia needing hospitalisation in Singapore.
A prospective survey of 96 consecutive adult patients with community acquired pneumonia requiring hospitalisation was carried out at National University Hospital, Singapore. Causative pathogens were identified in 58% of patients. Mycobacterium tuberculosis was the most common pathogen (21%), followed by Streptococcus pneumoniae (12%), Haemophilus influenzae (5.2%), Mycoplasma pneumoniae (5.2%) and Staphylococcus aureus (4.2%). Gram-negative organisms (apart from Haemophilus influenzae) were found in 10% of pneumonia patients. More than half of the patients had pre-existing illness, the most common was diabetes mellitus (21%).
Adolescent↗
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↗
Difficulties in the ventilation of asthmatic patients.
Explore the source record for details and available documents.
Acute Disease↗