Biomedical subjects

W K Lam

Publications and source records attributed to W K Lam.

At least 91 records · Page 5Linked to original sources

PubMed1997

Imprinting of IGF2 and H19: lack of reciprocity in sporadic Beckwith-Wiedemann syndrome.

Genomic imprinting is a novel form of control of gene expression in which the transcription of each allele of an imprinted gene is dependent on the sex of the gamete from which it was derived; to date > 15 genes have been demonstrated to show imprinting. The maintenance of a normal imprinting pattern in many loci has been shown to be essential for normal development and adult life. Many tumours, and some developmental disorders, exhibit loss of imprinting (LOI) in key genes such as insulin-like growth factor 2 (IGF2) which often results in hyperplasia and is associated with cancer. The mechanism by which the genomic imprint is first established, then maintained, is not understood. However, in the case of IGF2, the expression of a neighbouring gene, H19, has been suggested to influence its transcription by competition for a common enhancer, thereby generating a mutually exclusive and allele-specific pattern of gene expression. Associated changes in CpG methylation in discrete areas of both genes have been implicated in maintenance of the imprint. We have examined the allele-specific expression of IGF2 and H19 in fibroblasts derived from patients with sporadic Beckwith-Wiedemann syndrome (BWS), a fetal overgrowth syndrome associated with an imprinted locus on 11p15.5. We report that the majority of karyotypically normal patients show LOI of IGF2 with biallelic expression. In a proportion of these patients, loss of IGF2 imprinting was associated with complete suppression of H19 expression, as predicted by the enhancer competition model. However, in a significant number of cases, IGF2 showed biallelic expression even though H19 expression and methylation status were normal. This indicates that there must be an alternative H19-independent pathway by which allele-specific IGF2 expression is established or maintained.

Beckwith-Wiedemann Syndrome↗

PubMed1997

Inability of physicians to use metered-dose inhalers.

The effectiveness of antiasthmatic therapy with metered-dose inhalers (MDIs) is usually limited by defective inhalational technique. This study surveyed the MDI inhalation performance and knowledge of 100 physicians whose performance (demarcated into six stages) and knowledge scores correlated (r = 0.33, p < 0.001). Inhalation performance scores for shaking the canister, full expiration prior to using the MDI, breath holding thereafter, and positioning of the mouth-piece correlated with their corresponding knowledge scores (p < or = 0.02). Training of physicians entailing actual instruction and supervision of inhalational maneuvers may enhance the ability of doctors to use MDIs and facilitate better patient supervision.

Administration, Inhalation↗

PubMed1996

Detection and evaluation of p53 intron 2 polymorphism in lung carcinomas in Hong Kong.

A polymorphism in intron 2 of the p53 gene, which gives rise to 2 alleles, A1 and A2, was analyzed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct DNA-sequencing techniques. The distribution of this allele in the peripheral blood in the Chinese population comprising 27 healthy individuals, 30 bronchiectasis patients, 34 non-small-cell lung cancer (NSCLC) patients and 27 SCLC patients was analyzed. The genotypic distributions for this marker were significantly different between the blood of healthy individuals and SCLC patients. There was no significant difference between genotypes of Caucasians and Chinese. Tumors, normal lungs and peripheral blood of 83 adenocarcinoma and 10 squamous cell carcinoma patients were also studied. There was a significant difference in the distribution of the genotypes detected in tumor tissues vs. blood of adenocarcinoma patients. The frequency of detection of the A1/A1 genotype in the tumor tissues was increased in adenocarcinoma patients as compared with the blood of adenocarcinoma patients and was decreased in the blood of SCLC patients as compared with the blood of healthy individuals. Survival rates in Hong Kong adenocarcinoma patients with the A1/A1 genotype were lower than those in patients with A1/A2 and A2/A2 genotypes up to 30 months post-operation. Point mutations were detected at the p53 intron 2 polymorphic locus in NSCLC specimens, with a mutation rate of 15.4% (8/52). All mutations were GC transversions. The significance of this instability in p53 intron 2 remains to be elucidated.

Adenocarcinoma↗

PubMed1996

Analysis of L-myc and GSTM1 genotypes in Chinese non-small cell lung carcinoma patients.

The genotypes of L-myc and GSTM1 genes were studied in normal lung tissues of 98 non-small cell lung carcinoma (NSCLC) patients from Hong Kong using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) techniques. Results showed a statistical difference in L-myc genotypes between Chinese and African Americans (P = 0.02). A significant deficit in heterozygotes resulting in the departure from Hardy-Weinberg equilibrium in lung cancer female patients was detected (0.01 < P < 0.02). There were significant differences in survival times in patients having L-L and S-S genotypes, with shorter survival times in the patients with L-L genotypes (0.01 < P < 0.05). Data on age, size of tumor, histological types, and lymph node metastasis showed no significant association with L-myc genotype. The survival time in the GSTM1-negative (null gene) group was significantly different from the GSTM1 positive group between 16 and 24 months after operation (0.01 < P < 0.05). There was no significant difference in the distribution of GSTM1 genotypes between Chinese and Caucasian Americans.

Biomarkers, Tumor↗

PubMed1996

Chromosomal 11 alterations in non-small-cell lung carcinomas in Hong Kong.

We examined 60 non-small-cell lung cancer (NSCLC) patients for evidence of genetic alterations on chromosome 11 with nine polymorphic markers by Southern blot and microsatellite marker analysis. These analyses detected genetic alterations at both the 11p and 11q arms. At the 11p15 Ha-ras locus, the loss of heterozygosity (LOH) occurred in three out of 11 (27.3%) of the informative cases; at the 11p11-q12 D11S149 locus, the LOH occurred in two out of nine (22.2%) of the informative cases; and at the 11q13 INT-2 locus, the LOH occurred in four out of 18 (22.2%) of the informative cases. Microsatellite markers in the 11q12-q13 region revealed genetic alterations for PYGM in eight out of 54 (14.8%) of the specimens studied and 10 out of 55 (18.2%) of the specimens for the INT-2 marker. The data suggest genetic alterations occur in some of the lung cancer patients in both the 11p and 11q regions.

Adult↗

PubMed1996

Bronchiectasis and related disorders.

Bronchiectasis is defined in current medical parlance as the abnormal and permanent dilatation of one or more bronchi, and in clinical practice, the condition is often characterized by features of chronic bronchial infection. Apart from occurring as a primary lung disease, bronchiectasis is a major component of two other disease entities, cystic fibrosis and diffuse panbronchiolitis. Although the three conditions have distinctly different underlying causes, they share the similarity of a predominantly neutrophilic airways inflammation, and the persistent bronchial infection by bacteria, in particular Pseudomonas aeruginosa. Hence, new knowledge in one disease may be explored and applied in the others.

Bronchiectasis↗

PubMed1996

Histidinaemia: a benign metabolic disorder.

Histidinaemia is a relatively common inherited metabolic disorder with an incidence similar to phenylketonuria. This paper reports the long term outcome of patients diagnosed by newborn screening in the north west of England. Between 1966 and 1990, 108 infants were diagnosed as having histidinaemia by a regional neonatal screening programme (incidence 1:11,083). A further five children were detected following diagnosis in a sibling. Of the 113, nine were lost to follow up. Infants diagnosed before 1981 (n = 47) were placed on a low histidine diet (225 mg/kg/d) for an average period of 21 months (SD 4.5). All patients were reviewed regularly, Griffiths developmental quotients (DQ) were assessed at 2 and 4 years, and WISC-R intelligence quotients (IQ) at 8, 12, and 18 years. IQ data were converted to standard deviation scores (IQ SDS) to account for increasing IQ norms with time. Neither DQ nor IQ correlated with plasma histidine at diagnosis or with the mean plasma histidine throughout life. Growth was normal in all patients. There was no apparent benefit from a low histidine diet in early childhood. In contrast to other studies, there was no excess of clinical symptoms. On the basis of these findings, histidinaemia is a benign metabolic disorder that does not require treatment.

Amino Acid Metabolism, Inborn Errors↗

PubMed1996

p53 mutations in non-small cell lung carcinomas in Hong Kong.

Lung resections from 50 Chinese patients in Hong Kong diagnosed as having non-small cell lung carcinoma were examined for the presence of mutations in the p53 gene by polymerase chain reaction single-stranded conformation polymorphism methods and for aberrant protein expression by immunostaining techniques. Eight-point mutations in the evolutionarily conserved exon 5 through 8 regions were detected. Abnormal expression of p53 detectable by immunostaining techniques was seen in 23 specimens tested. There was no statistically significant correlation between the detection of p53 aberrations and age, sex, smoking history, histologic type, and tumor stage. Aberrant p53 protein levels detectable by immunostaining were significantly associated with the clinical and nodal staging of the tumors.

Adenocarcinoma↗

PubMed1995

Pulmonary infections in bone marrow transplantation: the Hong Kong experience.

The pattern of pulmonary infections in 59 consecutive bone marrow transplantations in Hong Kong was reviewed. Compared with published data from other marrow transplant units, we had a lower incidence of cytomegalovirus pneumonitis (1.7%) and a higher incidence of mycobacterial infections (5%). The latter is probably related to the high background prevalence of tuberculosis in the local population. Treatment with antituberculous drugs was effective.

Bacterial Infections↗

PubMed1995

A comparison of the effect of enalapril and metoprolol on renal function, potassium balance, lipid profile, cardiac function, exercise tolerance and quality of life in hypertensive dialysis patients.

26 patients with hypertension while on hemodialysis or continuous ambulatory peritoneal dialysis for end-stage renal diseases were treated first with enalapril and then changed to metoprolol. Both drugs were shown to be similarly effective in controlling blood pressure. There was no difference between the two drugs in their effects on renal function, potassium balance, lipid profile, cardiac function, exercise tolerance, and quality of life. Mild worsening of anemia was observed during treatment with enalapril. No serious side effects were reported. Use of enalapril is safe in the treatment of hypertension in dialysis patients.

Adult↗

PubMed1994

Quality-of-life in DDDR pacing: atrioventricular synchrony or rate adaptation?

Although differences in exercise performance have been observed between different rate adaptive modes, the relative impact of atrioventricular (AV) synchrony and rate adaptation on quality of life (QOL) have not been determined. Thirty-three patients with either sinoatrial disease (18) or complete atrioventricular (AV) block (15) received DDDR pacemakers (16 minute ventilation sensing, 17 activity sensing). There were 11 males and 22 females, with a mean age of 66 +/- 1 (range 39-78) years. The study was a double-blind, triple cross-over study comparing DDDR, DDD, and VVIR modes. At the end of each 8-week study period in each mode, QOL was assessed by a questionnaire evaluating patients' functional class (Classes I-IV), physical malaise inventory (41 items), illness perception (43 items), and overall QOL rating based on a 48 items measure covering different aspects of the patients' daily life adjustment. Two patients required early crossover from VVIR mode during the study. Patients experienced significantly fewer physical malaise such as temperature intolerance, dyspnea, and palpitations in the DDDR mode, compared with either DDD or VVIR pacing. DDDR pacing reduced the perception of illness in 5 of 43 items compared to VVIR pacing, and improved stamina and appetite compared to DDD pacing. The overall QOL score was 102 +/- 2, 105 +/- 2, 113 +/- 2 in the DDDR, DDD, and VVIR modes, respectively, with a higher score indicating a poorer QOL (DDDR/DDD vs VVIR, P < 0.02). There was no change in functional classes between the three pacing modes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Pulmonary toxicity in patients with non-Hodgkin's lymphoma treated with bleomycin-containing combination chemotherapy.

Subclinical and clinical bleomycin-induced pulmonary toxicity (BIP) were investigated retrospectively in 109 patients with non-Hodgkin's lymphoma treated by combination chemotherapy containing bleomycin. A decrease in carbon monoxide diffusing capacity (DLCO) was found in 12.8% of patients. The cumulative risk of abnormal DLCO increased with the increasing total cumulative dose of bleomycin. No significant difference in the rate of BIP was observed between patients receiving bleomycin/Adriamycin/cyclophosphamide/vincristine/prednisone (BACOP; bleomycin given at 10 mg/m2 for 4 weeks) and bleomycin/Adriamycin/cyclophosphamide/vincristine/dexamethasone/methotre xate/ folinic acid (m-BACOD; bleomycin given at 4 mg/m2 for 3 weeks, methotrexate given at 200 mg/m2. Monitoring for subclinical BIP should be considered in patients with non-Hodgkin's lymphoma even if only a low dose of bleomycin was given in the presence of other chemotherapeutic agents.

Adolescent↗

PubMed1993

Effect of antibiotics on sputum inflammatory contents in acute exacerbations of bronchiectasis.

We studied the changes in sputum neutrophil chemotactic activity (NCA) and elastolytic activity (EA) in acute exacerbations of bronchiectasis before and after treatment with oral antibiotics. Twelve patients who chronically produced sputum were assessed in the stable state, and when they subsequently developed symptoms of acute exacerbations, prior to initiation of antibiotics, during 2 weeks of antibiotics, and at 2 and 6 weeks after stopping antibiotics. NCA was measured using modified Boyden's technique with multiwell chemotaxis chamber, and EA with N-succinyl-trialanine-p-nitroanilide as elastase substrate. All 12 patients had NCA (49.3 +/- 8.69% FMLP response) and EA (50.5 +/- 17.1 mU per 100 microliters) in their sputum in the stable state. At acute exacerbation, there was significant increase in NCA (P < 0.001) and EA (P < 0.05). All responded clinically after 1 week of antibiotics, and this was associated with a decrease in NCA and EA back to the levels in stable state. A further week of antibiotics did not result in further decline of NCA or EA. Three patients had another acute exacerbation clinically between 2-6 weeks after stopping antibiotics and their NCA and EA rose again. In the other nine patients, both NCA and EA at 2 and 6 weeks post-treatment were similar to pre-exacerbation levels. Our findings suggest that short course antibiotics effectively control the upsurge in inflammatory activity in acute exacerbations, but has little effect on chronic airway inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1993

Multivariate analysis of factors affecting pulmonary function in bronchiectasis.

Impaired pulmonary function is of prognostic importance in bronchiectasis. To assess the factors affecting pulmonary function in bronchiectasis, we studied the clinical features, atopic status, bronchial responsiveness, systemic inflammatory indices, and sputum characteristics including volume, purulence, leucocyte count, neutrophil chemotactic activity, elastolytic activity (EA) and bacteriology in 82 Chinese patients. The majority of patients had impaired spirometry with airflow obstruction but normal carbon monoxide diffusing capacity. Multivariate analysis showed that factors significantly associated with worse lung function were: bronchial hyperresponsiveness, concomitant asthma, higher serum globulin, higher peripheral leucocyte count, lower serum albumin, greater sputum volume, diffuse disease and older age. When subjects with clinical asthma were excluded, similar factors were identified, and in addition, longer duration of disease, presence of eosinophils in sputum and higher sputum EA were significantly related to worse spirometry. Most of the identified factors reflect a state of inflammation. Thus the findings suggest that persistent inflammation plays an important role in the deterioration of lung function in bronchiectasis.

Bronchial Provocation Tests↗

PubMed1993

An audit of antiasthmatic drug inhalation technique and understanding.

Inhaled rather than oral antiasthmatic therapy is accepted as more advantageous but depends on patient technique and understanding. In 74 asthmatic outpatients, technique using metered-dose inhaler (MDI) was poor; in 56 patients inhaling beta-agonist, the mean peak expiratory flow rate (PEFR) increase was only 15 L/min (6%) greater than in 18 controls, p < 0.05, 95% confidence intervals 2-27 L/min or 2-11%. Tilting the head back and actuation "stopping" inspiration produced the least favorable PEFR responses; taken together, regression analysis yielded a statistically significant negative correlation with absolute or percentage PEFR change (R2 = 0.15; p < 0.02). Patients were unclear about which drugs to inhale as required or regularly. Among 19 patients reassessed inhaling beta-agonist, only 8 had baseline PEFR values within 10% of each other during both assessments. In the latter, the mean postinhalation PEFR increase was 36 L/min (or 13%) greater than the corresponding increase (or % change) at first assessment, p = 0.05 (0.08), 95% confidence intervals 0-73 L/min (-2 to 29%). Thus, MDI users should avoid tilting the head back, actuation stopping inhalation, and be more aware of prophylactic (steroid) versus symptomatic (beta-agonist) treatment.

Administration, Inhalation↗

PubMed1993

Trends in asthma therapy in Hong Kong, 1987-1992.

To audit the clinical practice in drug treatment of bronchial asthma in Hong Kong, two questionnaire surveys were conducted in 1987 and 1992. The questionnaire was adapted from the 1984 European Audit. The response rate was 40% (248 of 615 mailings) in 1987 and 32% (207 of 652 mailings) in 1992. A total of 86% and 87% of responders were general practitioners (GP), respectively, and the others were chest physicians (CP). For treatment of acute severe asthma in adults, parenteral aminophylline was the first drug used by GP in 1987, whereas inhaled beta-agonist was used in 1992. Parenteral steroid was more often used by both GP and CP in 1992. In children, inhaled beta-agonist was always the first choice and parenteral steroid ranked higher in 1992, overtaking parenteral aminophylline. For maintenance therapy of chronic asthma in adults, inhaled beta-agonist ranked first in both surveys. Inhaled steroid has become much more popular with GP, ranking second in 1992, overtaking oral bronchodilators. With CP, inhaled steroid was already ranking second in 1987, and it was used as the first drug, as frequently as inhaled beta-agonist, in 1992. In children, in 1987, inhaled beta-agonist was the first drug of choice, and prophylactic drugs ranked lower than oral bronchodilators with both GP and CP. In 1992, cromoglycate and inhaled steroids were much more often used, so much so that among CP, inhaled steroid ranked first, just ahead of inhaled beta-agonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1992

Incidence of ras oncogene activation in lung carcinomas in Hong Kong.

BACKGROUND: In Hong Kong, lung carcinomas contribute to the majority of cancer deaths among Chinese. Point mutational activation of ras oncogenes has been observed in several populations. The incidence of these mutations in Hong Kong lung carcinomas was investigated. METHODS: Lung resections obtained from 52 Chinese patients whose conditions were newly diagnosed as non-small cell lung cancer, paraffin sections from 29 Chinese patients with previously diagnosed adenocarcinoma of the lung, and paraffin sections from 49 squamous cell carcinomas were examined for the presence of point mutations in Ki-ras codon 12, N-ras codon 61, and Ha-ras codon 12 oncogenes by allele-specific hybridization after specific amplification of appropriate regions of the DNA using the polymerase chain reaction. RESULTS: Among the 130 lung carcinomas investigated, Ki-ras point mutations were detected in seven cases, of which six were adenocarcinomas and one a squamous cell carcinoma. No mutations were detected in the N-ras and Ha-ras codons. CONCLUSIONS: The incidence of Ki-ras codon 12 point mutational activation in Chinese patients with adenocarcinomas was 6 of 63 (9.5%). The incidence of Ki-ras 12 point mutational activation among men with lung adenocarcinomas in Hong Kong (6 of 32 patients, 18.8%) is significantly different from that in women in Hong Kong (0 of 31 patients, 0%). Although ras oncogenes are implicated as having a role in the development of lung adenocarcinomas, especially among smokers, it is clear from these data that they are not associated with the unusually high incidence of lung adenocarcinomas among women in Hong Kong.

Adenocarcinoma↗

PubMed1992

High prevalence of asthma in patients with bronchiectasis in Hong Kong.

Eighty five Chinese patients with diffuse or localized bronchiectasis (non-cystic fibrosis) were studied regarding the prevalence of asthma. Twenty three of the 85 had concomitant asthma, diagnosed by history and reversibility on lung function testing either spontaneously or after bronchodilator. None fulfilled the diagnostic criteria of allergic bronchopulmonary aspergillosis (ABPA). Asthma preceded the onset of bronchiectasis in 13 patients and developed after long duration of bronchiectasis in seven, while the temporal onset could not be differentiated in three patients. Patients with both asthma and bronchiectasis had inferior spirometric values, higher prevalence of bronchial hyperresponsiveness to methacholine, higher prevalence of skin atopy, elevated serum immunoglobulin E (IgE), and more sputum eosinophilia, compared with their non-asthmatic counterparts. Possible mechanisms by which asthma and bronchiectasis predispose to each other include asthmatic obstruction contributing to development of bronchiectasis, and sensitization of airways with increased lability due to microbial colonization of the ectatic bronchial tree.

Aspergillosis, Allergic Bronchopulmonary↗