Search PubMed⌕ Search

Biomedical subjects

D R English

Publications and source records attributed to D R English.

At least 55 records · Page 3Linked to original sources
PubMed1998

Prognostic significance of MIB-1 proliferative activity in thin melanomas and immunohistochemical analysis of MIB-1 proliferative activity in melanocytic tumors.

Metastasis from thin melanomas is rare and unpredictable. In order to assess the prognostic value of the proliferation marker, MIB-1, immunohistochemical staining was evaluated in a retrospective case-control study of 11 thin melanomas with documented metastasis and 11 control tumors that failed to metastasize. Tumors selected were < 1-mm thick and were individually matched for tumor thickness, date of excision, and patient age and sex. Analysis of MIB-1 expression as both a mean and a maximum level for the case and control groups revealed no association with metastasis. Wilcoxon's matched-pairs signed-rank test had p-values of 0.45 for the maximum values and 0.79 for the mean values. For the 11 thin melanomas that metastasized, there was a weak, yet statistically insignificant, correlation between the proportion of cells positive for MIB-1 and the length of the relapse-free period [Spearman's correlation coefficient = 0.20 for the maximum level (p = 0.56) and 0.19 for the mean level (p = 0.58)]. These results suggest that MIB-1 expression may be of limited value as a prognostic marker for increased risk of metastasis in patients with thin melanomas. MIB-1 immunohistochemistry was also performed on 25 benign and 70 malignant paraffin-embedded melanocytic tumors to evaluate the level of MIB-1 expression at different stages of tumor progression. A progressive increase in MIB-1 expression was seen from benign tumors through to primary melanomas, with the highest level seen in metastatic melanomas. Within the group of primary melanomas, the MIB-1 score was shown to correlate significantly with tumor thickness and Clark's level of invasion (Spearman's correlation coefficient = 0.71 for level and 0.77 for thickness).

Adolescent↗
PubMed1998

p16 and p21WAF1 protein expression in melanocytic tumors by immunohistochemistry.

To determine whether variation in the level of expression of p16 and p21WAF1 (p21) is associated with critical stages in cutaneous melanoma development or progression, the expression of these antigens was analyzed by immunohistochemistry in 110 benign and malignant melanocytic lesions. Differential expression of p16 protein has been reported in cutaneous melanocytic lesions, with loss of expression associated with the invasive stage of tumor development. Expression of p16 was seen in 31 of 35 benign melanocytic tumors (89%), 11 of 12 in situ melanomas (92%), 19 of 38 invasive primary melanomas (50%), and 16 of 25 metastatic melanomas (64%). There was a significant difference in the expression level of p16 observed in in situ versus invasive primary melanomas (p = 0.006), which is consistent with loss of normal p16 activity occurring in association with malignant tumor invasion. Overall, p21 levels were found to be low or undetectable in the majority of benign lesions, with greater p21 expression seen in malignant tumors. p21 was expressed in 28% of nevi, 60% of in situ melanomas, 61% of invasive melanomas, and 48% of metastatic melanomas. Among primary invasive tumors, the frequency of p21 expression increased with level of invasion (p < 0.01) and with increasing thickness (p < 0.01). However, differences in p21 expression were not clearly related to a particular stage of melanoma development.

Cyclin-Dependent Kinase Inhibitor p16↗
PubMed1998

Reproducibility of reported measurements of sun exposure in a case-control study.

We examined the reproducibility of the measurement of sun exposure in a cohort study of nonmelanocytic skin cancer in Geraldton, Western Australia. Two analyses were undertaken: a comparison of cutaneous sun damage with sun exposure reported at interview, and an analysis of test-retest reproducibility of reported exposure. Skin cancers and cutaneous indicators of sun damage (cutaneous microtopography and solar elastosis of the neck) were recorded at a survey in 1987. A case-control study was conducted in 1988 in which subjects were interviewed about their lifetime sun exposure. All subjects had European ancestry. A subset of these subjects was reinterviewed using the same interview schedule in 1993. The comparison of reported exposure with skin damage was restricted to 201 cases of basal cell carcinoma and 700 controls, all of whom were born in Australia and had no southern European ancestors. The analysis of test-retest reproducibility included 62 cases with basal cell carcinoma and 162 controls. After adjustment for the skin's sensitivity to sunlight, cutaneous microtopography explained 7% and solar elastosis of the back of the neck explained 13% of the variance in the reported time spent outdoors. The intraclass correlation between time spent outdoors reported in the two interviews was 0.77 [95% confidence interval (CI), 0.71-0.83], whereas for exposure to a specific anatomical site, it was 0.65 (95% CI, 0.55-0.73). The reported site-specific exposure was lower on the second occasion in controls but higher in cases. The hours of exposure on vacations and the proportion of exposure that occurred on nonworking days had poor reproducibility. Furthermore, cases reported a more intermittent pattern of weekly exposure on the first occasion than on the second, whereas the controls showed little difference in their pattern on the two occasions. The weighted kappa statistic for lifetime painful sunburns was 0.53 (95% CI, 0.41-0.66), and for lifetime number of blistering sunburns, it was 0.54 (95% CI, 0.44-0.65). Thus, the reported sun exposure showed only moderate agreement with biological markers of sun damage. Total sun exposure and, to a lesser extent, site-specific exposure showed good agreement on the two occasions. However, indicators of intermittent sun exposure had poor agreement, and sunburn had only fair agreement.

Adult↗
PubMed1997

Incidence of non-melanocytic skin cancer in Geraldton, Western Australia.

To measure the rate at which non-melanocytic skin cancers develop, we conducted a population-based, longitudinal study in Geraldton, Western Australia. Subjects were residents of Geraldton, Western Australia, who were between 40 and 64 years of age and registered on the electoral roll in 1987. In 1987 and again in 1992, dermatologists examined participants for skin cancers. They examined all skin areas, apart from those covered by underwear or hair. Subjects were asked about skin cancers that they had had treated between the 2 surveys. When all skin cancers were counted, the incidence rates of basal cell carcinoma were 3,379 per 100,000 person-years in women and 7,067 per 100,000 in men; those of squamous cell carcinoma were 501 per 100,000 in women and 775 per 100,000 in men. Sixteen percent of men and 14% of women developed at least one basal cell carcinoma; 2.8% of men and 2.2% of women had at least one squamous cell carcinoma. Most incident skin cancers were diagnosed at the second examination. More than half of the subjects who had a skin cancer at the first examination developed another. Squamous cell carcinomas occurred almost exclusively on parts of the body that are usually exposed. Basal cell carcinomas were common on the head, neck and trunk but not on the forearms and backs of hands. A quarter of people with a skin cancer on an exposed site also had one on the trunk. Our results show that skin cancer is extremely common in this population and frequently undiagnosed. Multiple skin cancers occur commonly, and skin cancers on exposed sites often are associated with skin cancers on less exposed sites.

Adult↗
PubMed1997

Glycogen metabolism in the aerobic hypertrophied rat heart.

BACKGROUND: Rates of glycolysis from exogenous glucose are accelerated in hypertrophied hearts. In this study, we determined whether alterations in the metabolism of glycogen, an endogenous storage form of glucose, also occur in hypertrophied hearts. METHODS AND RESULTS: Rates of glycolysis ([3H]H2O production) and oxidation ([14C]CO2 production) from exogenous glucose and glycogen were measured in isolated working hearts from control and aortic-banded rats. Hearts in which glycogen was prelabeled with [5-(3)H]- or [U-(14)C]glucose were perfused with buffer containing 11 mmol/L [5-(3)H]- or [U-(14)C]glucose (different from the isotope used to prelabel glycogen), 0.4 mmol/L palmitate, 0.5 mmol/L lactate, and 100 microU/mL insulin. Rates of glycolysis from exogenous glucose were greater (3471+/-114 versus 2665+/-194 nmol glucose x min(-1) x g dry wt(-1), P<.05, n=4 to 6, mean+/-SEM) and rates of exogenous glucose oxidation (445+/-36 versus 619+/-16 nmol glucose x min(-1) x g dry wt(-1), P<.05, n=4 to 6) were lower in hypertrophied hearts than in control hearts. Rates of glycolysis and oxidation from glycogen were not different between hypertrophied and control hearts. A greater proportion of glycogen was oxidized (80% to 100%) than the proportion of exogenous glucose oxidized (13% to 24%) in both groups. Additionally, 10.5+/-1.4 and 12.3+/-1.0 micromol/g dry wt of glycogen was synthesized in hypertrophied and control hearts, respectively, indicating that simultaneous synthesis and degradation (ie, glycogen turnover) occurred in both groups. CONCLUSIONS: Thus, aerobic myocardial glycogen metabolism in the hypertrophied heart is similar to that observed in the normal heart even though exogenous glucose metabolism is altered in the hypertrophied heart.

Animals↗
PubMed1997

Regression of cardiac hypertrophy normalizes glucose metabolism and left ventricular function during reperfusion.

It is not yet known if the alterations in myocardial glucose metabolism and the exaggerated left ventricular dysfunction that occur during reperfusion in hypertrophied hearts are reversible. Thus, we studied isolated working hearts from aortic-banded (n = 29) and sham-operated control (n = 32) male Sprague-Dawley rats with or without enalapril maleate treatment (25.6 +/- 0.8 mg/kg per day, p.o.) to determine the effect of regression of cardiac hypertrophy on myocardial glucose metabolism and post-ischemic heart function. Hearts were perfused with buffer containing 1.2 mM palmitate, 11 mM [5-3H]/[U-14C]-glucose, 0.5 mM lactate and 100 microU/ml insulin. Glucose metabolism [rates of glycolysis (3H2O production) and rates of oxidation (14CO2 production) of exogenous glucose] and heart function (heart rate x peak systolic pressure) were measured during 30 min pre-ischemic perfusion and 60 min of reperfusion following 20 min of global, no-flow ischemia. Hearts from untreated aortic-banded rats were hypertrophied, being 27.6 +/- 1.8% larger than hearts from untreated control rats. Enalapril treatment caused regression of cardiac hypertrophy that normalized heart weight in aortic-banded rats. Rates of glycolysis of exogenous glucose in hearts from untreated aortic-banded rats were accelerated compared to rates in hearts from untreated control rats during pre-ischemic perfusion (4391 +/- 97 v 2652 +/- 69 nmol glucose/min per g dry wt, respectively, P < 0.05) and reperfusion (2402 +/- 58 v 1597 +/- 88 nmol glucose/min per g dry wt. respectively, P < 0.05). In contrast, rates of glycolysis of exogenous glucose in hearts from enalapril-treated aortic-banded rats were normalized before and after ischemia. Rates of glycolysis of exogenous glucose in hearts of control rats were not affected by enalapril treatment. Oxidation of exogenous glucose was not different among groups either before or after ischemia. Function of hearts from untreated aortic-banded rats at the end of reperfusion was significantly less than that of hearts from untreated control rats (23.9 +/- 2.6 v 32.2 +/- 0.7 mmHg x beats per min/1000, respectively, P < 0.05). As with myocardial glucose metabolism function of hearts from aortic-banded rats treated with enalapril was normalized during reperfusion. Thus, pharmacologically induced regression of pressure-overload cardiac hypertrophy normalizes glucose metabolism as well as left ventricular function during reperfusion.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Sunlight and cancer.

Epidemiologic evidence on the relation between sunlight and cancer is reviewed. Strong evidence implicates sunlight as a cause of skin cancer, although, for melanoma and basal cell carcinoma, the relationship is complex. Both types of cancer are associated more strongly with nonoccupational exposure than with occupational exposure, and the pattern and amount of exposure each appear to be important. Squamous cell carcinoma appears to be related more strongly to total (i.e., both occupational and nonoccupational) exposure to the sun. The evidence that sunlight causes melanoma of the eye is weak. It shows no latitude gradient and the results of case-control studies are conflicting. There is inadequate evidence to suggest that sunlight does or does not cause any other type of cancer.

Australia↗
PubMed1997

Sun exposure and skin cancer.

By 1927 for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), and by 1955 for melanoma, the broad grounds for relating sun exposure to skin cancer had been established: that these are more frequent in residents of areas of high ambient solar irradiance, are more frequent in sun-sensitive people, occur mainly on sun-exposed body sites, are more frequent in people with high sun exposure, and are more frequent in people with benign sun-related skin conditions. The past 40 years have added both quantity and quality to the epidemiological evidence and, most recently, provided direct evidence that sun exposure is the cause of mutations in critical tumour suppressor genes in BCC, SCC and melanoma. Complete or more convincing answers are still needed to many questions of detail. They include whether the pattern of sun exposure is really important in, and acts independently of amount of sun exposure in, affecting the risk of melanoma and BCC; what the shape of the relationship between the amount of sun exposure and risk of BCC and melanoma is when the pattern of exposure is held constant; whether there really is a plateau in risk of BCC and melanoma beyond some level of the amount of exposure; whether this exposure-response relationship depends on cutaneous sensitivity to the sun and in what way; whether sunburn makes a specific contribution to the risk of skin cancer independent of the amount of sun exposure; whether sun exposure close to the time of diagnosis of skin cancer contributes anything to the development of the cancer; what the solar radiation action spectrum is for each kind of skin cancer; and whether sunscreens are effective in protecting against skin cancer.

Australia↗
PubMed1997

Assessing the relationship between maternal cocaine use and abruptio placentae.

Abruptio placentae during pregnancy can result in significant morbidity and mortality to both mother and infant. A comprehensive literature search of publications from 1966 to April 1995 identified 11 studies on the association between maternal cocaine use and abruptio placentae. Their results were combined in a meta-analysis. The pooled odds ratio for abruptio placentae and maternal cocaine use was 3.92 (95% confidence interval 2.77-5.46). The strength and consistency of the association, its biological plausibility and the results of experimental studies in animals all suggest that cocaine use during pregnancy causes abruptio placentae.

Abruptio Placentae↗
PubMed1997

Maternal cannabis use and birth weight: a meta-analysis.

AIMS: To estimate the effect of maternal cannabis use on birth weight. DESIGN: Meta-analysis of published observational studies adjusted for cigarette smoking. Separate analyses were performed for studies of low birth weight and mean birth weight. We used fixed and random effects models, but in all cases the results were identical. SETTING: From the Medline database, we identified 10 studies in which the results were adjusted for cigarette smoking. In seven studies, information on cannabis use was collected prenatally. Five studies reported results for differences in mean birth weight associated with maternal cannabis use. PARTICIPANTS: 32,483 women giving birth to live-born infants. MEASUREMENTS: Mean birth weight and odds ratio for low birth weight. FINDINGS: Three analyses of the studies on mean birth weight were conducted to avoid double-counting women from one study. The largest reduction in mean birth weight for any cannabis use during pregnancy was 48 g (95% confidence interval (CI) 83-14 g), with considerable heterogeneity among the five studies. Mean birth weight was increased by 62 g (95% CI 8 g reduction-132 g increase; p heterogeneity 0.59) among infrequent users (< or = weekly) whereas cannabis use at least four times per week had a 131 g reduction in mean birth weight (95% CI 52-209 g reduction; p heterogeneity 0.25). From the five studies of low birth weight, the pooled odds ratio for any use was 1.09 (95% CI 0.94-1.27, p heterogeneity 0.19). CONCLUSIONS: There is inadequate evidence that cannabis, at the amount typically consumed by pregnant women, causes low birth weight.

Birth Weight↗
PubMed1997

Maternal cocaine use and low birth weight newborns: a meta-analysis.

AIM/DESIGN: Many epidemiological studies published on the association between maternal cocaine/crack use and birth weight have either lacked precision or failed to control for major confounding, predominantly by tobacco smoking. Meta-analysis enables a single summary measure of effect to be calculated by combining data from any number of individual studies, thus enhancing statistical power. We undertook a number of meta-analyses using only studies that had adjusted for tobacco smoking to estimate more precisely the effect of maternal cocaine use on birth weight. FINDINGS: A meta-analysis of five studies presenting data for 'any' prenatal cocaine exposure, adjusted for tobacco smoking but unadjusted for gestational age, produced a pooled relative risk estimate from a fixed effects analysis of 2.15 (95% CI 1.75-2.64). However, there was substantial heterogeneity among studies (p < 0.001), and the relative risk from a random effects analysis was smaller (1.65) with a confidence interval that included unity (95% CI 0.94-2.83). Addition of a further study adjusted for gestational age had minimal effect on the pooled estimate: the fixed effects relative risk was 2.14 (1.77-2.60) and the random effects estimate 1.77 (1.15-2.71). When data on more intense prenatal exposure were analysed, the fixed and random effects analysis produced the same pooled estimate of the relative risk of 4.42 (2.24-8.71), suggesting that more frequent cocaine exposure was associated with a higher relative risk for low birth weight. Data from studies on mean reduction in birth weight produced a pooled estimate of 112 g (95% CI 62-161 g). CONCLUSIONS: The current study suggests that maternal cocaine use causes low birth weight, and that the effect is greater with heavier use. However, despite the adjustment for tobacco and the adjustment by some studies for other confounders such as race, maternal age, gravidity and socio-economic status, it could be argued that other life-style factors not controlled for may account for the observed effects. While this argument is not supported by some other types of study, the issue of residual confounding can only be finally addressed by analytical studies which adequately control for important variables.

Cocaine↗
PubMed1997

The relationship between maternal use of heroin and methadone and infant birth weight.

UNLABELLED: AIMS/DESIGN: Reduction in mean birth weight and increased incidence of low birth weight are both associated with exposure to illicit heroin in pregnancy. Many studies examining neonatal outcomes in pregnant heroin users treated with methadone report improvements in birth weight. As a consequence, methadone treatment has become the 'gold standard' for the management of the pregnant heroin user. However, not all studies report significant birth weight increases associated with methadone. We undertook a number of meta-analyses on reduction in mean birth weight and incidence of low birth weight to estimate more precisely the effect of illicit heroin and methadone. FINDINGS: Results showed mean reduction in birth weight associated with heroin use: 489 g (95% CI 284-693 g), compared with methadone: 279 g (229-328 g). Similarly, the pooled relative risk estimate for low birth weight for maternal heroin use was 4.61 (95% CI 2.78-7.65), compared with 1.36 (0.83-2.22) for methadone. Analysis of data on combined heroin and methadone use produced a pooled mean reduction in birth weight of 557 g (403-710 g), with a pooled relative risk estimate for low birth weight of 3.28 (2.47-4.39). Pooling 'any' methadone data, regardless of heroin use, produced an estimated reduction in birth weight of 395 g (311-478 g) and a relative risk estimate for low birth weight of 1.90 (1.29-2.81). Combining all data in an 'any' opiate use analysis also produced a mean reduction in birth weight of 483 g (386-583 g) and a relative risk estimate for low birth weight of 3.81 (2.57-5.65). CONCLUSIONS: The current findings suggest that heroin use while receiving methadone may counteract the birth weight advantage gained from methadone alone. Whether this is due to fetal exposure to heroin plus methadone, to reduced antenatal care, other behavioural and environmental factors associated with concurrent use of heroin and methadone or a combination of these is unclear. Nevertheless, these results challenge the current belief that the pregnant user is always better off receiving methadone than not, and suggests that methadone may not be the appropriate treatment for the pregnant women who continue to use illicit heroin.

Birth Weight↗
PubMed1996

Meta-analysis of alcohol and all-cause mortality: a validation of NHMRC recommendations.

OBJECTIVE: To compare the National Health and Medical Research Council (NHMRC) recommendations on responsible, hazardous and harmful alcohol intake with their effects on all-cause mortality in men and women and on the occurrence of 10 specific neoplastic, cardiovascular and alimentary diseases. DESIGN: Meta-analyses of relative risks of mortality in relation to usual level of alcohol intake pooled from 16 cohort studies (mostly of adults over 35 years), and alcohol and selected conditions from a further 132 epidemiological studies. Results reported by authors were assigned to sex-specific exposure categories defined by the NHMRC based on median alcohol intakes. Pooled estimates of relative risk were calculated using precision-based weighting. SETTING: The assessment was part of comprehensive meta-analysis of epidemiological research undertaken for the National Drug Strategy. RESULTS: Relative risk of all-cause mortality in male drinkers compared with abstainers fell to 0.84 at 1.0-1.9 standard drinks per day, returned to 1.01 by 3.0-3.9 drinks, and increased to 1.37 at six or more drinks. In female drinkers the lowest relative risk (of 0.88) was at 0-0.9 drinks per day, and by 2.0-2.9 drinks the risk exceeded that in abstainers by 1.13; at six drinks the relative risk was 1.58. Based on NHMRC categories, the relative risks of mortality were 0.93 (0.93-0.94) in responsible drinkers, 1.24 (1.22-1.27) in hazardous drinkers and 1.37 (1.35-1.49) in harmful drinkers. Risk of cancers of the oropharynx, oesophagus, liver, larynx and female breast and of cirrhosis of the liver increased with increasing alcohol intake level. CONCLUSIONS: A pattern of usual alcohol intake consistent with the NHMRC recommendations will confer a mortality risk similar to or less than that observed in abstainers. The biologically effective dose of alcohol on mortality in women is approximately two standard drinks per day less than in men. Our validation is most reliable for drinkers aged 35 years or older.

Adult↗
PubMed1996

Multiple sclerosis in Australia: socioeconomic factors.

The data from an epidemiological study on multiple sclerosis in Australia have been analysed to determine the relation between the prevalence of the disease and educational level, and the association between level of disability and employment status. There was a significantly higher frequency of multiple sclerosis in those who left school at an older age and achieved a higher educational level. The explanation of this finding remains speculative and may be related to genetic or environmental factors. The study confirmed the recognised association between moderate-severe disability and divorce-separation and lower rates of employment.

Adolescent↗
PubMed1996

Ought low alcohol intake to be promoted for health reasons?

There is increasingly widespread acceptance that alcohol taken in moderation by the population aged 35 years or older reduces the risks of ischaemic heart disease and all-cause mortality. Ten causal criteria are used to evaluate the scientific evidence for a protective effect of low alcohol intake on ischaemic heart disease. Inferences for public policy are then assessed using the principles of beneficence, non-maleficence, justice and autonomy to support a framework of nine ethical considerations: intervention versus causation; effect modification by gender, smoking, biogenetic and other factors; inappropriate adoption of recommendations; competing hazards between atherosclerotic disease and cancer; opportunity cost; equity of access; the value system used to judge outcomes; the degree of social influence warranted; and consent and responsibility. We conclude that in the absence of more adequate scientific knowledge and informed community debate it is unethical to promote low alcohol intake as a preventive health measure.

Alcohol Drinking↗
PubMed1996

Molecular epidemiology of skin cancers: DNA repair and non-melanocytic skin cancer.

Exposure to sunlight has been clearly associated with non-melanocytic skin cancer, however individual susceptibility differs considerably. Ethnic origin and pigmentary characteristics are generally accepted as risk factors. Another important defense mechanism is the ability to repair DNA photoproducts. In the inherited disorder xeroderma pigmentosum the inability to repair such DNA damage, associated with a high incidence of skin cancers, suggests an important role for DNA repair capacity in the etiology of this cancer. The development of an in vitro repair assay based on human peripheral blood lymphocytes, has allowed the evaluation of DNA repair capacity as a risk factor in population based studies. This article reviews recent developments in this field.

Animals↗
PubMed1995

A dose-response curve for sun exposure and basal cell carcinoma.

A population-based case-control study of sun exposure and basal cell carcinoma (BCC) was conducted in Western Australia in 1988. Its aim was to examine the relationship between risk of BCC and the amount and pattern of sun exposure. This report deals with amount of exposure. The odds ratios (ORs) for BCC on the head and neck and limbs decreased with increasing total exposure, whereas the opposite was observed for BCC on the less heavily exposed trunk, with the highest OR in those with the greatest exposure. In an analysis of all body sites together in which the total hours of exposure to the specific site was treated as a continuous variable, an initial rise in risk of BCC was seen with a peak OR of 1.4 at about 35,000 hr of exposure, followed by a fall. In contrast to these site-specific patterns, lifetime accumulated sun exposure of the whole body showed no appreciable association with BCC either in total or for working days only. Risk of BCC was positively associated with lifetime exposure on non-working days, however, with an OR for higher than baseline categories of around 1.7. There was a significant interaction between ability to tan and total and occupational sun exposure. Risk increased with increasing exposure in those who tanned well but not in those who tanned poorly. This pattern is consistent with other observations which indicate that beyond a certain level of sun exposure risk of BCC does not increase further.

Adult↗