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Biomedical subjects

C K Lai

Publications and source records attributed to C K Lai.

104 records · Page 6Linked to original sources
PubMed1990

Inhaled PAF fails to induce airway hyperresponsiveness to methacholine in normal human subjects.

The effects of three increasing doses of platelet-activating factor (PAF) on airway caliber and methacholine bronchial responsiveness were studied. On separate occasions nine normal subjects inhaled a single cumulative provocation concentration of methacholine (control) causing a 40% fall (PC40 Vp30) in maximum expiratory flow rate at 70% of base-line vital capacity below total lung capacity during a partial forced expiratory maneuver or 100 or 200 micrograms PAF, and seven subjects inhaled a further dose of 400 micrograms PAF. Methacholine responsiveness was measured before, at 3 and 7 h, then on days 1, 2, 3, 4, 7, 10, and 14 after each challenge. The maximum falls in Vp30 appeared dose dependent, but a significant difference between the magnitude of the responses was only observed between the 400- and 100-micrograms PAF dose (P less than 0.05). During the control period repeated methacholine challenges resulted in a progressive increase in cumulative provocation concentration of an agonist causing a 20% fall in forced expiratory volume in 1 s from base line, reaching significance on days 1 and 2 (2.44- and 2.4-fold of base line, respectively, P less than 0.01) before returning to base line on day 7. No difference was seen in methacholine responsiveness after any of the three doses of PAF compared with that after the control. We conclude that PAF causes dose-dependent bronchoconstriction but does not change airways responsiveness to methacholine and that repeated high-dose methacholine challenge leads to loss of responsiveness to this agonist.

Administration, Inhalation↗
PubMed1990

Effect of 15-(s)-hydroxyeicosatetraenoic acid on allergen-induced asthmatic responses.

15-(s)-hydroxyeicosatetraenoic acid (15-HETE), a major oxidative metabolite of arachidonic acid in human lungs, has complex actions on the 5-lipoxygenase pathway in different cell systems. We have examined the effect of inhaled 15-HETE on the early and late asthmatic responses (EAR and LAR) and the associated change in nonspecific bronchial responsiveness to inhaled allergen in 10 subjects with atopic asthma. On 2 separate days 3 wk apart, subjects inhaled either 70 nmol 15-HETE or the diluent (sodium phosphate buffer) in a randomized and double-blind fashion, followed by a dose of allergen that had previously been shown to produce a 25% fall in baseline FEV1. Analysis of the area under the FEV1 response time course curves (AUC) in the first hour revealed that preinhalation with 15-HETE increased the EAR by 39% from that achieved after the diluent (p less than 0.05). In the seven subjects who were classified as dual responders by developing a LAR previously (greater than 15% fall in baseline FEV1 3 to 8 h after allergen challenge), 15-HETE did not cause any significant change in the magnitude of the LAR when compared with that observed after placebo. The values of the provocation concentration of histamine causing a 20% fall in FEV1 (Pc20) at 8 h postchallenge were significantly reduced on both study days when compared with the corresponding preallergen challenge values, whether analyzed for the whole group or for the seven dual responders (p less than 0.05). 15-HETE had no effect on this allergen-acquired airway hyperresponsiveness to histamine when compared with the diluent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

The influence of cyclooxygenase inhibition on the loss of bronchoconstrictor response to repeated bradykinin challenge in asthma.

Bradykinin is a naturally occurring nonapeptide which may contribute to the pathogenesis of bronchial asthma. When inhaled by asthmatic subjects it is a potent bronchoconstrictor, but with repeated challenge airways responsiveness to the peptide decreases markedly. In vitro studies suggest that loss of bradykinin responsiveness may be due to the secondary generation of relaxant prostanoids. We have used the potent cyclooxygenase inhibitor flurbiprofen to investigate the potential role of prostanoid generation in bradykinin tachyphylaxis in eight asthmatic patients. The effects of oral flurbiprofen (150 mg) and matched placebo were observed on two consecutive dose response studies with inhaled bradykinin and histamine in a double-blind, randomized study. Venous blood was taken to measure the serum concentration of thromboxane B2 (TxB2) as a check on the extent of cyclooxygenase blockade achieved by flurbiprofen. Following recovery from the first challenge with bradykinin, the asthmatic airways showed a reduced response to a second challenge with this nonapeptide, the provocative concentration producing a 20% fall from baseline (PC20) increasing from 0.07 to 0.42 mg.ml-1 (p less than 0.01). The airway response to inhaled histamine after the second bradykinin challenge was not significantly changed. In the presence of demonstrable cyclooxygenase inhibition, flurbiprofen failed to prevent the development of reduced responsiveness to bradykinin observed on the second challenge, the PC20 increasing from 0.10 to 0.48 mg.ml-1 (p less than 0.01). This study demonstrates that repeated exposure to inhaled bradykinin results in loss of the bronchoconstrictor response which appears specific for this agonist and not secondary to the increased generation of protective prostanoids.

Adolescent↗
PubMed1990

The effect of inhaled 15-(s)-hydroxyeicosatetraenoic acid (15-HETE) on airway calibre and non-specific responsiveness in normal and asthmatic human subjects.

15-hydroxyeicosatetraenoic acid (15-HETE) is the predominant oxidative metabolite of arachidonic acid in human lung. We have studied its effects on airway calibre and non-specific bronchial responsiveness (NSBR) in eight normal and eight asthmatic subjects. 15-HETE, at doses up to 70 nmol, had no effect on airway calibre in either group of subjects. However, 3 h after its administration, 15-HETE reduced NSBR in the normal subjects (geometric mean methacholine PD40 Vp30 increased by 2.29-fold from baseline compared with a corresponding 1.14-fold increase after diluent, p less than 0.05). Similarly, 4 h after inhaled 15-HETE, the spontaneous increase in NSBR in the asthmatics was completely inhibited (geometric mean histamine PD40 Vp30 decreased significantly to 0.41-fold of baseline after diluent (p less than 0.01) compared with a 1.1-fold increase after 15-HETE, p less than 0.01). These data suggest 15-HETE may play an autacoid role in airway function.

Administration, Inhalation↗
PubMed1989

Effect of an inhaled mast cell stabiliser, N-acetyl-aspartyl-glutamate (Zy15109) on allergen-induced immediate bronchoconstriction.

We have studied the effect of a mast cell stabiliser, the magnesium salt of N-acetyl aspartyl glutamic acid (NAAGA) on allergen-induced immediate bronchoconstriction in 12 atopic subjects. Inhaled NAAGA, at a dose of 60 mg thrice daily for 1 week, offered no protective effect on the airways against allergen challenge when compared with a matched placebo. The drug was well tolerated with no adverse effects observed.

Adult↗
PubMed1989

The effect of an increase in inhaled allergen dose after terfenadine on the occurrence and magnitude of the late asthmatic response.

We have attempted to use a potent and selective histamine H1-receptor antagonist terfenadine to allow a larger dose of allergen to be administered to previous single early responders to investigate if an increased dose of allergen could induce a late asthmatic response. Pre-treatment with 180 mg of terfenadine enabled a geometric mean increase in allergen dose of 4.12-fold to be inhaled by eight atopic subjects with mild asthma, who initially were classified as single early responders, with maximal fall in FEV1 3-8 hr after allergen challenge (Lmax) of less than 15% from baseline value. The magnitude of early asthmatic response was similar to that obtained on the control day when allergen challenge was performed in the absence of terfenadine. Two subjects were converted to dual responders with Lmax of 23.1 and 24.3%, which occurred with a 32- and 65-fold increase in allergen dose respectively, and a 6- and 4.9-fold decrease in non-specific airways responsiveness measured as the cumulative provocative concentration of methacholine that caused a 20% fall in FEV1 from baseline. The remaining six subjects failed to achieve an Lmax of greater than 10% even with a 1.29-2.66-fold increase in allergen dose. For the group as a whole an increase in allergen dose was associated with an increase in overall bronchoconstrictor response 3-8 hr after challenge. These results indicate that it is possible to induce a late asthmatic response in a subject who previously demonstrated only an early response by increasing the dose of allergen inhaled.

Administration, Inhalation↗
PubMed1989

The effect of an increase in inhaled allergen dose after rimiterol hydrobromide on the occurrence and magnitude of the late asthmatic response and the associated change in nonspecific bronchial responsiveness.

We have used a short-acting beta 2-adrenoceptor agonist, rimiterol hydrobromide, to allow a larger dose of allergen to be administered to previous single "early allergen responders" to investigate if an increased dose of allergen could induce a late asthmatic response (LAR) and whether this would influence the subsequent level of allergen-acquired nonspecific bronchial hyperresponsiveness. Pretreatment with inhaled rimiterol hydrobromide 400 microgram enabled an increase in allergen dose inhaled by a geometric mean of 8.9-fold (range, 2 to 29.1) in eight atopic subjects with mild asthma who initially were classified as single early responders with a maximal fall in FEV 3 to 8 h after allergen challenge (Lmax) of less than 15% from baseline value. The magnitude of the early asthmatic response was similar to that obtained on the control day when allergen challenge was performed in the absence of rimiterol hydrobromide. Five subjects were converted to dual allergen responders with Lmax of greater than 15% from premedication baseline value. For the whole group, there was a significant increase in the magnitude of LAR whether calculated as Lmax (p less than 0.05) or as area under the FEV1 time response curve between 3 and 8 h postchallenge (p less than 0.01). The provocation concentrations of methacholine causing a 20% fall in FEV1 (PC20) at 8 h postchallenge were significantly reduced on both days when compared with the corresponding prechallenge values (p less than 0.05 on control day, p less than 0.01 on rimiterol day). However, despite the increase in the magnitude of LAR on the rimiterol day, the reduction in postchallenge PC20 did not differ significantly from that occurring on the control day.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Frank rectal bleeding: a prospective study of causes in patients over the age of 40.

In order to determine the frequency of tumours in patients presenting with frank rectal bleeding, a prospective study was carried out in 337 patients over the age of 40 attending our Proctology Clinic. After making a clinical diagnosis, flexible sigmoidoscopy followed by barium enema was performed. Excluding 7 digitally palpable rectal cancers, there were 30 cancers (9.1%), 34 polyps (10.3%), 7 proctocolitis (2.1%) and 25 diverticula (7.6%) detected, giving a total diagnostic yield of 29.1%. A clinical diagnosis of bleeding sources other than haemorrhoids was made in 80% of the cancers. Flexible sigmoidoscopy detected 93.3% of the cancers and 88.2% of the polyps. Barium enema diagnosed the remaining cancers and polyps but there was a false-positive rate of 3.8%. From our results, we conclude that patients with frank rectal bleeding should be screened routinely for left-colon cancer irrespective of the clinical diagnosis. The flexible sigmoidoscope is a quick and useful tool. However, barium enema should be recommended to individuals with strong clinical suspicion of rectal bleeding other than haemorrhoids.

Adult↗
PubMed1985

Colorectal carcinoma in the young.

Four hundred and five patients with colorectal adenocarcinoma were seen over a five year period in the Department of Surgery, University of Hong Kong. These patients were divided into two concurrent groups according to the age of 40. Thirty patients (7.4%) were below age of 40 at the time of presentation. This young group of patients had both a higher combined proportion of C and D tumors (76.6% to 50%) and a higher proportion of poorly differentiated tumours (20% to 5.5%). The curative and palliative resections rates were similar. Life tables of patients who underwent curative resections showed young patients to have a significantly poorer overall disease-free interval as well as overall determinant survival. In comparing only the Dukes C patients, the young patients still showed a higher recurrence rate.

Adenocarcinoma↗
PubMed1983

Synthesis of 3 alpha,7 alpha-dihydroxy-5 beta-androstan-17-one.

A short and efficient method for the stereospecific synthesis of 3 alpha,7 alpha-dihydroxy-5 beta-androstan-17-one was accomplished from the readily available 4-androstene-3,17-dione. Key steps are the stereospecific and selective epoxidation of 4,6-androstadiene-3,17-dione, followed by hydrogenations with carefully selected reagents, solvents and reaction conditions.

Androstenedione↗
PubMedDate not supplied

Comparison of oral ciprofloxacin and amoxycillin in treating infective exacerbations of bronchiectasis in Hong Kong.

A randomised double-blind controlled clinical trial was conducted to compare oral ciprofloxacin (500 mg b.d.) and amoxycillin (1 g t.d.s.) in the treatment of infective exacerbations of bronchiectasis. The commonest organism isolated from sputum was Pseudomonas aeruginosa, which accounted for 34% of all positive sputum cultures. Other Pseudomonas species and Haemophilus influenzae, accounted for 19%, respectively. Ciprofloxacin produced better clinical response, a higher sputum to serum antibiotic level (mean of 0.65 in the ciprofloxacin group vs. 0.18 in amoxycillin group, p = 0.0001), broader spectrum of antibacterial activity and less side-effect. It was also better tolerated by patients. The findings suggest that ciprofloxacin is an effective treatment of infective exacerbations of bronchiectasis.

Administration, Oral↗
PubMedDate not supplied

A training workshop on late-stage dementia care for family caregivers.

Training workshops have been considered a useful intervention in helping family caregivers of people with dementia to cope with the stress of caregiving. However, there are no reports in the literature with regard to training and support of families specifically looking after individuals who are in the late stage of dementia. This paper reports the experience and evaluation of a training workshop aimed at preparing family caregivers for late-stage dementia care. Eighty-eight percent of the participants completed the client satisfaction questionnaire. The results from the questionnaire gave a very positive response, showing 90.9 percent of respondents were satisfied with the workshop, and 77.3 percent of respondents indicated that their caregiving needs were met. Eleven participants who attended this workshop joined a focus group feedback session. The Kruskal-Wallis test found no significant differences between the overall profile of the participants and that of the focus group in terms of age, gender, educational background, whether they were primary caregivers, for whom they cared (e.g., parents or spouse), or whether the care recipient stayed at home or in a nursing home. Findings from the focus group session provide a somewhat different picture from that of the questionnaire. Three focus group participants provided more critical comments of the workshop. Although the majority of the focus group agreed that the workshop had been useful, they disagreed on whether it is necessary to discuss psychosocial issues in this workshop. Findings from the focus group have enabled the project team to reflect on their design and operation of the workshop and provided valuable insight for future development as well as for further study.

Alzheimer Disease↗
PubMedDate not supplied

Should PAF inhalation challenge be used as an experimental model of bronchial hyperresponsiveness in man?

Present evidence suggests that PAF-induced bronchial hyperresponsiveness (BHR) is a variable phenomenon in man. Even in the responders, the magnitude of change is small and the response is poorly reproducible. Endobronchial biopsy and bronchial lavage studies following inhaled PAF did not show any increase in the number of activation of eosinophils, which are pivotal in the pathogenesis of BHR. Unless and until the characteristics of responders are identifiable, PAF inhalation challenge should not be used as a human model of BHR.

Biopsy↗