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Biomedical subjects

H P Lee

Publications and source records attributed to H P Lee.

At least 19 recordsLinked to original sources
PubMed1997

The relationship between dietary fat intake and risk of colorectal cancer: evidence from the combined analysis of 13 case-control studies.

The objective of this study was to examine the effects of the intake of dietary fat upon colorectal cancer risk in a combined analysis of data from 13 case-control studies previously conducted in populations with differing colorectal cancer rates and dietary practices. Original data records for 5,287 cases of colorectal cancer and 10,470 controls were combined. Logistic regression analysis was used to estimate odds ratios (OR) for intakes of total energy, total fat and its components, and cholesterol. Positive associations with energy intake were observed for 11 of the 13 studies. However, there was little, if any, evidence of any energy-independent effect of either total fat with ORs of 1.00, 0.95, 1.01, 1.02, and 0.92 for quintiles of residuals of total fat intake (P trend = 0.67) or for saturated fat with ORs of 1.00, 1.08, 1.06, 1.21, and 1.06 (P trend = 0.39). The analysis suggests that, among these case-control studies, there is no energy-independent association between dietary fat intake and risk of colorectal cancer. It also suggests that simple substitution of fat by other sources of calories is unlikely to reduce meaningfully the risk of colorectal cancer.

Adult↗
PubMed1996

Non-Hodgkin's lymphoma in an Asian population: 1968-1992 time trends and ethnic differences in Singapore.

BACKGROUND: Non-Hodgkin's lymphoma has increased in incidence in many countries, particularly in the West. Advances in diagnostic methods and the understanding of the disease over time pose a challenge to the interpretation of these trends. The aim of this study was to determine if the disease has increased in Singapore, a newly industrialized Asian country, and to examine the possible factors that may account for any observed changes. METHODS: Data from the population-based Singapore Cancer Registry for the period 1968 to 1992 were reviewed to determine time trends based on sex and ethnic group. The Poisson regression model was fitted to the cross-tabulated data to obtain the adjusted incidence density ratios. RESULTS: A total of 1988 cases of non-Hodgkin's lymphoma were included in the analysis. There was an overall increase in incidence among both Chinese and Malaysians. However, the rate of increase was greater in females (age-standardized rate from 1.8 per 100,000 in 1968-1972 to 4.5 per 100,000 in 1988-1992) than in males (3.2 per 100,000 to 5.9 per 100,000 in the same time periods). Between ethnic groups, Malay females were at higher overall risk compared with their Chinese counterparts (incidence density ratio 1.32; 95% confidence interval, 1.08-1.61). Although a substantial proportion of patients diagnosed with Hodgkin's disease between 1968 and 1972 were reclassified on review, using present criteria, as having non-Hodgkin's lymphoma, it is unlikely that this, and other recent changes in histologic interpretation, could have accounted for an increase of this magnitude. CONCLUSIONS: Non-Hodgkin's lymphoma has increased in incidence among the Chinese and Malay populations in Singapore. The pattern of increase differs from that of the common cancer sites, and suggests the need to look for environmental and genetic factors that have not yet been elucidated.

China↗
PubMed1996

Breast cancer in Singapore: trends in incidence 1968-1992.

BACKGROUND: Breast cancer is the most commonly occurring cancer among women in Singapore, a country which has experienced significant changes in lifestyle over the past three decades. The increase in incidence of the disease is a matter of some concern. METHODS: Data from the population-based Singapore Cancer Registry for 1968-1992 were used to determine time trends, inter-ethnic differences and the contributions of age, period and cohort effects to the incidence of the disease. RESULTS: Our results revealed an average annual increase of 3.6% over the 25-year period for all women, form 20.2 per 100,000 women in the period 1968-1972 to 38.8 per 100,000 in 1988-1992. There was a statistically significant difference between the three major ethnic groups, the rate of increase being highest in Malays (4.4%) and lowest in Indians (1.4%). The overall increase was attributable to a strong cohort effect that remained significant when adjusted for time period for Chinese women and for all ethnic groups combined. The risk was observed to increase in successive birth cohorts from the 1890s to 1960s. CONCLUSIONS: Our results suggest that breast cancer incidence rates are likely to continue to increase more sharply in the future as women born after the mid-20th century reach the high-risk age groups. They also suggest the pattern by which important aetiological factors for the disease in our population have exerted their effects, and provide support for the role of demographic and lifestyle changes as possible risk factors.

Adult↗
PubMed1996

Clinical utility of calculated creatinine clearance as a guide to chemotherapy in patients with gynecologic malignancies.

OBJECTIVE: To examine the relationship between calculated and measured creatinine clearance, and also to evaluate the clinical utility of calculated creatinine clearance before administration of chemotherapy in patients with gynecologic malignancies. METHODS: In 38 patients with gynecologic malignancies, a total-69 paired creatinine clearance measured by 24-hour urinary creatinine clearance and calculated were compared. RESULTS: The significant correlation (r = 0.597, p < 0.0001) was observed between creatinine clearances determined by both methods. There were 26 (37.7%) 24-hour urine collections. The correlation between two methods improved when these inaccurate samples were excluded (r = 0.876, p < 0.0001). In addition, if a creatinine clearance of 50 ml/min is set as a threshold for dose modification, only 2.9% of the patients would have received reduced doses inappropriately, by using the calculated creatinine clearance alone. CONCLUSION: These results suggest that in patients with gynecologic malignancies, a calculated creatinine clearance prior to chemotherapy is sufficient for evaluation of renal function and measured creatinine clearance would be determined only when calculated creatinine clearance is below the threshold for dose modification.

Adult↗
PubMed1996

Smoking-associated mortality in a cohort of Singaporeans observed for 20 years.

Smoking is well established as a main cause of preventable mortality throughout the world, but little data are available on Asian populations and none on Singapore. This study is the first to provide data specific to Singapore on the increased mortality among smokers, and is one of the few such studies on Asians. In 1974, smoking history data were taken from a random sample of 3579 adults living in Singapore. Of these, 3361 (1522 men and 1839 women) were eligible for follow-up and vital status was determined as at 31 December 1993. Cox regression analysis was used to estimate the relative risks of variety of causes of death for smokers compared to non-smokers, adjusted for age and ethnicity. Smoking was categorized as ever or never and also as none, light or heavy. As at 31 December 1993, 330 (21.7%) of the men and 249 (13.5%) of the women had died. Relative risk values were clearly elevated for male and female smokers for all-cause mortality (1.42 and 1.52, respectively), lung cancer (13.2, 6.37) and death due to chronic obstructive pulmonary disease (COPD) (4.71, 8.50). Relative risk values for death from cancer of the larynx or oesophagus, ischaemic heart disease and cerebrovascular disease were elevated but not significantly different from 1.0. A trend of increasing risk with increasing smoking intensity was seen for all-cause mortality among men and for lung cancer and COPD mortality, among both sexes. Ethnicity was associated with ischaemic heart disease mortality among men, with elevated risks in both the Indians (2.55) and the Malays (1.66) relative to the Chinese. These results should serve to strengthen the anti-smoking campaigns in Singapore.

Adult↗
PubMed1996

Regression analysis of biomedical research data based on a repeated measure or cluster sample.

Research in biology and medicine often entails estimating the effect of an exposure variable X on a response variable Y from a cluster sample, that is, where X and Y may be measured repeatedly from the same subject (cluster), or X and Y may be measured from two or more subjects based on some related grouping such as a litter or household (cluster). Typically, regression analysis of the data is performed ignoring the subject or grouping (cluster) identity. This analytical approach has two drawbacks. First, the statistical inference of the regression coefficient of Y on X (beta) ignored cluster identity will likely be biased. More serious though, is that beta ignored cluster identity will likely be quite discrepant from the average within-cluster beta. It is the latter that is of relevance to the research question. Indeed it is not clear what beta ignored cluster identity really conveys. We describe a multiple regression model for the analysis of data from a cluster sample. The model treats the cluster as a nominal confounding variable to be adjusted. The idea is to represent the cluster by a set of dummy variables to be included as explanatory variables in the regression model. This model gives the average within-cluster beta with valid statistical inference. Numeric examples were used to illustrate the application of the dummy variable multiple regression model. This statistical method can be implemented by any software package that includes multiple regression, and virtually all commercial packages include this procedure.

Cluster Analysis↗
PubMed1996

Biomarkers: a molecular approach to cancer epidemiology.

The rapidly evolving field of molecular epidemiology represents a paradigm shift in medical research, illustrating the convergence of basic, clinical and epidemiologic research, as well as the application of laboratory methods to population studies. As a complement and improvement to traditional epidemiologic approaches, the use of biomarkers offers more accurate exposure assessment at an individual level, better understanding of the biological mechanism of carcinogenesis by tracking a continuum of events between exposure and disease, as well as the ability to discern host or genetic factors that may account for variations in cancer susceptibility among individuals or ethnic populations. Further, biomarkers have also proved useful in cancer diagnosis and prognosis. This article attempts to review the latest progress in molecular cancer epidemiology and to summarise the current state of research in Singapore.

Biomarkers, Tumor↗
PubMed1996

Molecular epidemiology: issues in study design and statistical analysis.

Traditional analytical epidemiology is directed at identifying the association between risk factors and occurrence of disease by using crude exposure data derived from questionnaires or clinical measures, and taking clinical disease as the end point. With the rapid development in molecular biology and laboratory methods, it is now possible to use biomarkers which are capable of identifying molecular events for epidemiologic research. This improved sensitivity enables us to develop a mechanistic understanding of disease causation: a step closer to the unravelling of the "black box" of traditional epidemiology. Biomarkers may be classified as internal indicators of exposure (biomarkers of exposure), indicators of preclinical adverse effect (biomarkers of effect) or indicators of an intrinsic or acquired susceptibility to disease (biomarkers of susceptibility). Biomarkers provide a better definition of exposure and disease status and consequently they could help to reduce misclassification bias in both exposure and disease, reduce the follow-up time in prospective studies, as well as identify possible interactions between risk factors on disease occurrence. However, a biomarker needs to be validated and its distribution in large populations described before it can be used profitably for aetiologic research. Also, the use of biomarkers in epidemiologic research raises other interesting epidemiological and statistical issues like confounding, effect modification and the analysis of repeated measurements. Molecular epidemiology is a multidisciplinary endeavour which comprises molecular biology, epidemiology and biostatistics. Clearly then, to carry out research in this field profitably, the molecular biologist, epidemiologist and biostatistician must acquire not only expertise in their respective fields, but also an integrated understanding of all three fields. The molecular biologist is not merely a laboratory bench worker; the epidemiologist, a field data-collector and the biostatistician, a number cruncher. They must work together to pry open the "black box" to gain a greater insight into how risk factors operate to initiate disease onset and ultimately to make use of this knowledge base to implement preventive measures.

Biomarkers↗
PubMed1996

Review of published clinical trials conducted in Singapore from 1959 to 1994.

Trials are increasingly being used to evaluate the effectiveness of health care interventions. As has been recognised by those active in these activities, there is a need, not only to search for all published materials, but also to evaluate their quality and usefulness. This paper is an attempt to provide information and to examine the areas of focus and quality of information on all published clinical trials conducted in Singapore from 1959 to 1994. The searches were conducted using the MEDLINE CD-ROM for the period from 1966 to 1994 and manual search for the period before 1966. All published studies involving drugs or procedures (surgical techniques or instrumentation) on human subjects performed in Singapore were included in the study. Out of a total of 136 papers obtained, 90 fulfilled our criteria. There is an increase in the number of publications over the years especially in the last 10 years; with the biggest surge in the last 5 years. Most of the clinical trials were pharmacological intervention studies (57.8%) although there is a steady rise in non-pharmacological studies recently. As the number of clinical trials increases, coupled with the rising cost, it would be useful for the relevant authorities to consider setting up a registry to co-ordinate the trials that are being conducted.

Clinical Trials as Topic↗
PubMed1996

The advance directive--a review.

The advance directive is a document that enables a competent individual to specify the form of health care he would like to have, in the event that he is unable to make such decisions in the future. This review paper traces the development of the advance directive from 1967, when it was first proposed by Luis Kutner. The Karen Ann Quinlan case and the Nancy Cruzan case are cited as examples of the case for the advance directive. The argument is that advance directives assist doctors, patients, family members and other carers with the increasingly complex health care decision making. Reservations have been expressed about the anticipatory nature of the decision, possible conflict with personal and religious ethics and the risk of cost containment considerations being over-riding concerns. The advance directive in America has undergone changes since the California Natural Death Act 1976 was passed. In the 1980s, "terminal" included permanent unconsciousness and advanced dementia. The declarant was also given a wider choice of treatment procedures that they wish to be withheld. Proxy directives were also introduced. In the 1990s, the declarant is even allowed to request the use of life-prolonging procedures. When appropriately implemented, the advance directive can perform its intended functions of clarifying the patient's perspective on life, death and medical care. When it is vague in terminology or applied to patients with uncertain prognoses, it can cause confusion to the patient's carers; and when improperly used, it can become an instrument not of patient's preferences, but of economic purpose, family bias, or physician's values.

Advance Directives↗
PubMed1995

Beliefs and attitudes as determinants of cervical cancer screening: a community-based study in Singapore.

BACKGROUND: The investigation of cervical cancer screening acceptance in relation to health beliefs and attitudes presents a challenge in a multiethnic population such as Singapore's, where the uptake is currently suboptimal in high-risk groups. This study attempts to identify cognitive barriers to screening activity in order to suggest possible directions for cervical cancer prevention efforts. METHODS: A cross-sectional survey consisting of a household interview of 640 randomly selected women ages 21-65 years was performed. The screening history and future intention to have a Pap smear were elicited, and attitudes toward cancer and the Pap smear as expressed in 14 statements were measured on a five-point scale. RESULTS: Of the respondents, 73.1% were aware of the Pap smear, and about half (49.7%) had obtained the information from a doctor or nurse. Overall, the belief in personal susceptibility to cancer was low (58.9%) and a substantial proportion (48.7%) of women were of the attitude that cancer could not be prevented. The effect on a future intention to have a smear varied between women who had had and women who had not had a smear. Among the former, perceived barriers such as discomfort and embarrassment had a significant influence, while a belief in personal susceptibility was an important determinant for the latter group. CONCLUSIONS: The means of increasing the acceptance of the Pap smear, both for the first time and subsequently, are culture-specific and must address the appropriate health beliefs and attitudes. In Singapore, such efforts should include not only influencing awareness and perceptions through public education but also reducing barriers by creating an appropriate environment for the delivery of this important health service.

Adult↗
PubMed1995

Chili--protective factor against peptic ulcer?

The aim of the present study was to determine the frequency and amount of chili taken by peptic ulcer patients and control subjects. One hundred three Chinese patients with peptic ulcer and 87 control patients were interviewed using a standard questionnaire. Those subjects who deliberately avoided chili use because of symptoms or advice from friends or medical practitioners were excluded. The median number of times of chili use per month was eight in the ulcer group (25-75% quartiles 1-30) compared to 24 (8-56) in the control group (P < 0.001). The median amount of chili used per month was 312 units (25-75% quartiles 38-899) in the ulcer group compared to 834 units (274-1892) in the control group (P < 0.001). The odds ratio of having peptic ulcer disease, adjusted for age, sex, analgesic use, and smoking by multiple logistic regression, was 0.47 (95% confidence intervals: 0.25-0.89) for subjects who had a higher intake of chili both in terms of frequency as well as amount used compared to those who took less chili. Our data support the hypothesis that chili use has a protective effect against peptic ulcer disease.

Adult↗
PubMed1995

Codon 249 mutation of the p53 gene is a rare event in hepatocellular carcinomas from ethnic Chinese in Singapore.

The present study characterised p53 mutations in 44 hepatocellular carcinomas (HCCs) from Chinese patients residing in a high-incidence area. Twelve point mutations (27%) were detected in tumour tissues using single-strand conformation polymorphism analysis followed by direct DNA sequencing. Remarkably, no mutations were observed at codon 249. This is in contrast to HCCs from other high HCC incidence areas with endemic aflatoxin exposures, in which codon 249 is a mutational hot spot. It is therefore suggested that risk factors other than dietary exposure to aflatoxin may contribute to the high HCC incidence in Singapore.

Adult↗
PubMed1995

Randomized trial of epirubicin and cisplatin chemotherapy followed by pelvic radiation in locally advanced cervical cancer. Cervical Cancer Study Group of the Asian Oceanian Clinical Oncology Association.

PURPOSE: Pelvic radiation is standard treatment for women with stage IIb to IVa cervical cancer, but treatment results are disappointing, particularly for women with bulky tumors. We investigated the role of primary chemotherapy followed by pelvic radiotherapy in a randomized trial. PATIENTS AND METHODS: Two hundred sixty patients with stage IIb and IVa cervical cancer received either standard pelvic radiotherapy or primary chemotherapy with cisplatin 60 mg/m2 and epirubicin 110 mg/m2 administered at 3-week intervals for three cycles, followed by pelvic radiotherapy. RESULTS: Ninety-nine patients have relapsed with a median follow-up duration of 1.3 years; in 62 patients, the first site of progressive disease was the pelvis. Patients who received primary chemotherapy had a significantly higher pelvic failure rate than those who received radiotherapy alone (P < .003). Seventy-six patients have died, and those who received primary chemotherapy had significantly inferior survival compared with those who received radiotherapy alone (P = .02). Tumor response following chemotherapy was observed in 63%. After radiotherapy, tumor response occurred in 72% of those who received combined modality treatment, compared with 92% of those who received radiotherapy alone. CONCLUSION: Primary chemotherapy with epirubicin and cisplatin, although resulting in tumor response in a significant proportion of patients, is accompanied by an inferior local control rate and survival compared with standard pelvic radiotherapy alone.

Adenocarcinoma↗
PubMed1995

Risk factors for birth defects in Singapore: a case control study.

To explore possible risk factors for birth defects, a matched case-control study was carried out at Kandang Kerbau Hospital in Singapore from January 1986 to December 1988. Cases and controls were selected from livebirths born in that hospital during that period. Cases were babies who were clinically detected as having defects at birth and the diagnosis reconfirmed at 6 weeks post partum. Each case was matched to a control by maternal age, ethnic background of mother, the same class of maternity ward and time of delivery. Five hundred and seventy-two matched pairs were accrued for the study. The parents of both cases and controls were interviewed at 6 weeks post partum. Information on the medical and birth history of both mother and baby was obtained from medical records. Using conditional logistic regression analysis to adjust for potential confounders, the strongest risk factors for birth defects were family history of birth defects (OR 3.3; 95% CI 1.8-6.4) and parents having a previous abnormal baby (OR 2.4; 95% CI 1.1-5.3). Other notable risk factors included drug history during pregnancy (OR 1.2; 95% CI 0.8-2.0), the ingestion of traditional medicine during pregnancy (OR 1.4; 95% CI 1.0-2.0), injuries or accidents during pregnancy (OR 2.2; 95% CI 1.5-3.2) and maternal diabetes mellitus (OR 1.3, 95% CI 0.3-7.1). Mothers in professional occupations (OR 1.4, 95% CI 0.7-2.6) and those in production occupation (OR 1.2, 95% CI 0.9-1.7) had an increased risk for birth defects compared to housewives.(ABSTRACT TRUNCATED AT 250 WORDS)

Case-Control Studies↗
PubMed1995

Mutations of the tumour suppressor gene p53 in colorectal and hepatocellular carcinomas.

The present study describes mutations of the tumour suppressor gene p53 in a local collection of colorectal and hepatocellular carcinomas (HCCs). Tumour DNA was extracted from both fresh and paraffin-embedded tissues and exons 5-8 of the p53 gene were amplified by polymerase chain reaction (PCR). Mutations were detected by single-strand conformation polymorphism (SSCP) analysis followed by direct DNA sequencing. Of the 38 colorectal carcinomas and 42 HCCs examined, 15 (39%) and 13 (31%), respectively, showed p53 mutations. Two-thirds (10/15) of the mutations in colorectal carcinomas were base transitions with a predominance at CpG dinucleotide sites--a pattern characteristic to an endogenous process in cancer development. Three mutational hotspots at codons 175, 248 and 282 were also identified. Mutations did not correlate with histological grade, Dukes stage, or metastasis. However, tumours at the distal site of the colorectum showed a higher proportion of mutations than the proximal site. In the case of HCCs, majority (9/13) of the mutations were base transitions and no mutations were observed at codon 249. This is in contrast to results from other high-incidence areas such as Africa and China, where aflatoxin is believed to be a major aetiologic factor for liver cancers. The results therefore suggest that other risk factors, rather than dietary exposure to aflatoxin, may contribute to the high HCC incidence in Singapore.

Adenocarcinoma↗
PubMed1995

Sample size estimation for clinicians.

The purpose of this paper is to describe the importance of an adequate sample size in clinical research and to enable clinicians to estimate their own sample size requirements for the more common types of studies (comparison of two means or two proportions). Four pieces of information are required to determine sample size: the desired level of statistical power, the level of statistical significance, the variability of the data, and the smallest difference between the study groups that is considered to be of clinical significance. Worked examples from the literature are used to illustrate how clinicians may easily do their own sample size calculations using published tables or available computer software, or both. The consideration of sample size and power during the planning stages of clinical research is crucial to the subsequent interpretation of study results, especially if the study is negative, and yet this point is often neglected in the medical literature. Attention to these simple guidelines will help ensure that research results lead to valid conclusions.

Biometry↗