Search PubMed⌕ Search

Biomedical subjects

D R English

Publications and source records attributed to D R English.

At least 73 records · Page 4Linked to original sources

Does intermittent sun exposure cause basal cell carcinoma? a case-control study in Western Australia.

Our report deals with the relationship of pattern and timing of sun exposure to basal cell carcinoma (BCC) in a population-based case-control study conducted in Western Australia in 1988. The main measure of intermittent exposure was based on the amount of exposure on non-working days relative to that over the whole week. Outdoor recreational activities, holidays and sunburn were also considered to be markers of intermittent exposure. We observed a statistically significant increase in risk of BCC with increasing proportion of weekly sun exposure obtained at the weekend, especially in late teenage (OR = 3.9, 95% CI 1.9-7.8 for maximum intermittency of exposure), exposure of the site of skin cancer during holidays (OR = 1.9, 95% CI 1.1-3.1 for the highest exposure quarter) and sunburn to the site (ORs of 1.8 for 3-10 and 1.5 for 11+ sunburns in a lifetime). Risk of BCC increased substantially with increasing intermittency in poor tanners but not at all in good tanners. Our data suggest that a particular amount of sun exposure delivered in infrequent, probably intense increments will increase risk of BCC more than a similar dose delivered more continuously over the same total period of time.

Adult↗

Benign melanocytic lesions: risk markers or precursors of cutaneous melanoma?

BACKGROUND: The role of benign melanocytic lesions as precursors and not only as risk markers for the development of cutaneous melanoma is controversial. OBJECTIVE: The purpose of the study was to assess the frequency of the histologic association of benign melanocytic lesions with cutaneous melanoma of a maximum thickness of 1.00 mm. The possibility that the spatial association of benign lesions with melanoma may be coincidental was also investigated. METHODS: The study subjects representing 289 cases of cutaneous melanoma of maximum thickness 1.00 mm (or less) were examined histologically for the presence of an associated benign melanocytic lesion(s), including lentiginous melanocytic proliferation; junctional, compound, or intradermal nevus; dysplastic nevus; and congenital nevus contiguous with or adjacent to the melanoma. The effects of age, tumor thickness, level of invasion, histologic type, and anatomic site on the association of benign melanocytic lesions with melanoma were assessed. In the control subjects 40 basal cell carcinomas and 38 compound nevi (not dysplastic) randomly chosen and matched for age (+/- 1 year) and site (head/neck, trunk, upper and lower limbs) with a melanoma case were examined to assess the proportion of these cases associated with benign lesions compared with the matched melanoma cases. RESULTS: A nevus was associated with melanoma in 51% of cases (n = 147). Of these, 82 (56%) were dysplastic nevi, 61 (41%) were common acquired nevi, and 4 (3%) were congenital nevi. Lentiginous melanocytic proliferation was present in the epidermis adjacent to 219 melanomas (75%) and in 44% of these cases (n = 97) a coexisting nevus was also present. CONCLUSION: The results of this study lend further support to the concept of common acquired nevi and dysplastic nevi as precursors of cutaneous melanoma. In addition, lesions diagnosed clinically as simple lentigo and solar lentigo may be important as potential precursors of melanoma, particularly in the elderly.

Adult↗

Prognostic significance of p53 over-expression in thin melanomas.

Metastasis by thin melanomas is uncommon and unpredictable. In order to assess the prognostic value of p53 expression, p53 immunohistochemical staining was evaluated in 20 thin melanomas with documented metastasis and in 20 control tumours which failed to metastasize. Tumours selected were less than 1 mm thick and were individually matched for tumour thickness, date of excision and patient age and sex. The relative risk of metastasis given p53 overexpression was 1.5 (95% confidence interval 0.4-5.3; p = 0.53). Further quantitative analysis for p53 between the two groups did not demonstrate a significant difference (p = 0.08). These results are consistent with there being no association between p53 overexpression in thin melanomas and risk of metastasis, however, the sample size was small, and the existence of such an association cannot be ruled out with confidence. For the 20 thin melanomas which metastasized, there was no association between the proportion of cells positive for p53 and length of the relapse-free period (correlation coefficient = 0.02, p = 0.94).

Case-Control Studies↗

An improved aetiologic fraction for alcohol-caused mortality.

A method is proposed for estimation of alcohol-caused mortality in which the aetiologic fraction of deaths is derived from an exposure contrast between the 'unsafe' drinker and 'safe' drinker; not between the drinker and the nondrinker. The method is consistent with the objectives of public health intervention in the alcohol education field. The 'safe' drinker is the reference exposure category and aetiologic fractions are obtained for the single categories of a multiple-level exposure scale, using separate relative risks for the 'unsafe' drinker and the nondrinker. Preliminary application of the method to Australian data yields an estimate of the number of deaths caused by misuse of alcohol that is larger than those obtained under the old conceptual model. Thus, the public health importance of unsafe alcohol consumption has been underrepresented.

Alcohol Drinking↗

DNA repair capacity as a risk factor for non-melanocytic skin cancer--a molecular epidemiological study.

Capacity to repair UV-induced DNA damage was studied by use of host cell reactivation assay in T lymphocytes isolated from 86 cases and 87 controls (aged 44-68 years) who were participants in a population-based case-control study of basal cell (BCC) or squamous cell (SCC) carcinoma of the skin in Geraldton, Western Australia. Lymphocytes were cultured and transfected with either control or UV-irradiated plasmids (254 nm, 350 J/m2) containing a reporter gene [the chloramphenicol-acetyltransferase (CAT) gene], and the repair capacity was determined by measuring CAT gene expression in protein extracts prepared from the transfected cells. DNA repair activity was 1.07 (95% confidence interval 0.94-1.26) times greater in BCC cases than in controls for each 350 J/m2 increment in UV dose to the plasmids, and 1.04 (95% confidence interval 0.85-1.26) times greater in SCC cases than in controls, though the differences were not statistically significant. DNA repair activity showed little association with age, sex and viability of the lymphocytes, though it was positively associated with their blastogenic rate (p = 0.055).

Adult↗

Melanocytic nevi in children. I. Anatomic sites and demographic and host factors.

A survey of benign melanocytic nevi was conducted among schoolchildren in Perth, Western Australia, in 1985, with the aim of describing the prevalence and causes of nevi. Children were recruited from Perth public schools that were chosen to be representative of the socioeconomic and geographic distribution of the population. Of 4,898 eligible children, 2,595 (53%) had all of their nevi counted by one member of a team of five nurses. Analysis was restricted to 2,552 children aged 5-14 years. Children of European origin (i.e., white children), who comprised the majority of the sample (2,376 children), had many more nevi than did children of other ethnic origins. Among white children, the prevalence of nevi increased progressively with age, although the number of nevi per unit of skin area reached a plateau at about 9 years of age. Boys had more nevi at all ages than did girls. The number of nevi per unit of area was highest on the lateral surfaces of the upper limbs and the face and neck, and was lowest on the lower limbs. Children whose parents had been born in Southern Europe were likely to have few nevi. Children with red hair had relatively few nevi, but children with light skin generally had more nevi than children with darker skin. Ability to tan and propensity to burn were also associated with number of nevi, although not in a simple fashion; numbers of nevi were highest in intermediate categories of these two variables. The relation with freckling was also complex; the mean number of nevi increased with increasing freckling until the freckling became moderate to heavy, after which it fell.

Adolescent↗

Melanocytic nevi in children. II. Observer variation in counting nevi.

A survey of benign melanocytic nevi was conducted among children in Perth, Western Australia, in 1985. Children were examined by one of a team of five nurses who counted all of their nevi. Linear regression was performed on the logarithmically transformed mole counts to assess the degree of interobserver variation. Among 2,354 white children aged 5-14 years, 3.9% of the variation in numbers of nevi of all sizes and 7.7% of the variation in nevi 2 mm or more in diameter was attributed to variation among observers. The observer variation was less for the back than for any other body site. Differences between observers were greater in children with heavy freckling than in children with little or no freckling. However, the interaction between degree of freckling and observer accounted for more than 1% of the variation in counts only at sites where freckling was common (the face and neck and the upper limbs). The reproducibility of counts made by pairs of observers on 236 of the children, estimated by intraclass correlation coefficients, was 0.79 for all nevi and 0.65 for nevi 2 mm or more in diameter. The mean count of nevi on the back obtained by examining photographs of 100 children aged 8-9 years (11.9 nevi) was similar to that recorded by the examiners (12.3; p = 0.31), and the two measures were highly correlated (r = 0.89).

Adolescent↗

Calcium overload during reperfusion is accelerated in isolated hypertrophied rat hearts.

In this study, calcium overload during reperfusion and the severity of morphologically evident ischemic myocardial injury were compared in hypertrophied and normal hearts. Hypertrophied hearts isolated from rats where a clip had been placed on the proximal thoracic aorta for 6 weeks were compared to those from sham-operated rats in an isolated state perfused with Krebs-Henseleit buffer containing 3% albumin, 1.2 mM palmitate and 11 mM glucose. The isolated hearts were exposed to global, no-flow, normothermic ischemia following potassium arrest and were reperfused. Following ischemia and reperfusion, left ventricular end diastolic pressure was increased (39 +/- 7 v 13 +/- 2 mmHg, P < 0.05), and percentage recovery of left ventricular systolic function was decreased (34.4 +/- 8.9 v 77.1 +/- 6.3% P < 0.05), in hypertrophied hearts compared to control hearts. Calcium overload during reperfusion was two and one-half times greater in the hypertrophied hearts than in the control hearts and showed significant relationships with recovery of left ventricular systolic function (r = -0.86, P < 0.001) and left ventricular end diastolic pressure (r = 0.78, P < 0.005). Myocardial energy charge did not differ between the two groups at the end of reperfusion. Ischemic myocardial injury was quantitated morphologically by point counting techniques in a comparable series of control and hypertrophied hearts. After ischemia, hearts were either exposed to a monoclonal antimyosin antibody to identify and measure irreversibly injured myocardium by light microscopy or fixed by perfusion with 2.5% glutaraldehyde to quantitate the morphologic changes ultrastructurally. Control and hypertrophied hearts were not significantly different in severity of myocardial injury due to ischemia as assessed morphologically. Thus, the data suggest that calcium overload during reperfusion plays a significant role in post-ischemic left ventricular dysfunction of the hypertrophied heart. The accelerated calcium overload that occurs in the hypertrophied rat heart during reperfusion cannot be explained by differences in severity of myocardial injury during ischemia which indicates that other mechanisms are responsible.

Animals↗

Sun exposure and non-melanocytic skin cancer.

Non-melanocytic skin cancer has long been regarded as one of the harmful effects of solar ultraviolet (UV) radiation on human health. In this review, we examine epidemiologic evidence linking sun exposure and skin cancer coming from both descriptive studies in populations and analytical studies involving estimates of exposure in individuals. Particular attention is given to the quality of the published data. The epidemiologic evidence that sun exposure causes skin cancer is mainly indirect. Incidence or mortality is inversely related to latitude in populations of mainly European origin (e.g., the United States, Australia), and is higher in people born in Australia (high ambient solar radiation) than in migrants to Australia from the United Kingdom (lower ambient radiation). Skin cancer occurs mainly at sun-exposed body sites and in people who are sensitive to the sun; a reduced capacity to repair UV-induced DNA damage appears to increase the risk. The direct evidence linking sun exposure and skin cancer is weaker with few well-conducted studies of sun exposure in individuals. Mostly, studies of total sun exposure have not found statistically significant positive associations; those that did, had not adjusted for potential confounding by age and gender and thus their interpretation is limited. Studies of occupational sun exposure had relative risks not greater than 2.0; recreational exposure has been little studied. Other measurements, less direct but potentially less prone to measurement error, are sunburn (not evidently associated with skin cancer risk) and indicators of benign cutaneous sun-damage (strongly associated but lacking empirical evidence that sun exposure is their main cause). Many questions remain about the relationship between sun exposure and skin cancer.

Adult↗

Contribution of oxidative metabolism and glycolysis to ATP production in hypertrophied hearts.

The contribution of glycolysis and oxidative metabolism to ATP production was determined in isolated working hypertrophied hearts perfused with Krebs-Henseleit buffer containing 3% albumin, 0.4 mM palmitate, 0.5 mM lactate, and 11 mM glucose. Glycolysis and glucose oxidation were directly measured by perfusing hearts with [5-3H/U-14C]glucose and by measuring 3H2O and 14CO2 production, respectively. Palmitate and lactate oxidation were determined by simultaneous measurement of 3H2O and 14CO2 in hearts perfused with [9,10-3H]palmitate and [U-14C]lactate. At low workloads (60 mmHg aortic after-load), rates of palmitate oxidation were 47% lower in hypertrophied hearts than in control hearts, but palmitate oxidation remained the primary energy source in both groups, accounting for 55 and 69% of total ATP production, respectively. The contribution of glycolysis to ATP production was significantly higher in hypertrophied hearts (19%) than in control hearts (7%), whereas that of glucose and lactate oxidation did not differ between groups. During conditions of high work (120 mmHg aortic afterload), the extra ATP production required for mechanical function was obtained primarily from an increase in the oxidation of glucose and lactate in both groups. The contribution of palmitate oxidation to overall ATP production decreased in hypertrophied and control hearts (to 40 and 55% of overall ATP production, respectively) and was no longer significantly depressed in hypertrophied hearts. Glycolysis, on the other hand, was accelerated in control hearts to rates seen in the hypertrophied hearts. Thus a reduced contribution of fatty acid oxidation to energy production in hypertrophied rat hearts is accompanied by a compensatory increase in glycolysis during low work conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Regional myocardial capillary erythrocyte transit time in the normal resting heart.

A major determinant of oxygen transport to the myocardium is the time spent by the erythrocytes (red blood cells [RBCs]) traversing the microcirculation. Although it has been shown that the myocardium has regional differences in blood volume, blood flow, metabolism, and sensitivity to ischemic injury, the regional distribution of RBC transit times through the myocardial capillaries has not been previously measured. The present study was designed to measure the regional myocardial capillary RBC transit time by a new technique to determine whether there are regional differences in the capillary RBC transit time in the normal resting heart. Anesthetized open-chest male New Zealand White rabbits (3.0-3.7 kg, n = 8) were studied. Regional myocardial blood volume was determined using chromium-51-labeled RBCs, and regional blood flow was measured using a reference flow technique and a left atrial injection of 15-microns-radiolabeled (gadolinium-153, 10-20 muCi) microspheres. Capillary blood volume was determined by multiplying the regional blood volume by the histologically determined fraction of the total blood volume that was in the capillaries. Capillary RBC transit time was calculated as the quotient of capillary blood volume and blood flow. The myocardial capillary blood volume was the same in the endocardium and the epicardium (4.67 +/- 0.67 ml/100 g for endocardium versus 4.52 +/- 0.70 ml/100 g for epicardium, p = NS), whereas myocardial blood flow tended to be greater in the endocardium (6.09 +/- 0.73 ml/sec per 100 g for endocardium versus 5.47 +/- 0.75 ml/sec per 100 g for epicardium), although this was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effects of surgical treatment on survival and local recurrence of cutaneous malignant melanoma.

All patients with a diagnosis of cutaneous malignant melanoma (CMM) in Western Australia from 1980 to 1981 were observed for up to 6 years to determine vital status and to detect the development of local recurrences of the primary lesion. Approximately 35% of all patients had their tumors excised with surgical margins of less than 1 cm. When compared with patients whose tumors were excised with margins of at least 2 cm, the fatality rate in those with narrow margins was slightly less (rate ratio, 0.60; 95% confidence interval [CI], 0.20% to 1.80% for margins of 5 to 9 mm; rate ratio, 0.69; 95% CI, 0.26% to 1.87% for margins of 1 to 4 mm); however, this difference could have been caused by chance alone. The risk of local recurrence within 5 years after diagnosis was 2% (95% CI, 1% to 4%). The risk was strongly related to age and tumor thickness, but did not appear to be influenced by the width of excision (greater than 1 cm versus less than 1 cm: rate ratio, 1.03; 95% CI, 0.25% to 4.34%). The apparent lack of effect could be caused by to chance alone because the number of local recurrences was small.

Adult↗

Survival among patients with clinical stage I cutaneous malignant melanoma diagnosed in Western Australia in 1975/1976 and 1980/1981.

Five-year survival rates were slightly higher for patients with cutaneous malignant melanoma (CMM) diagnosed in Western Australia in 1980/1981 (89% in men and 95% in women) than in those whose melanomas were diagnosed in 1975/1976 (88% in men and 91% in women). The improvement in survival was probably due to a decrease in median tumor thickness from 1.29 mm in 1975/1976 to 0.77 mm in 1980/1981 because tumor thickness was the most important histologic index of prognosis. Tumor cell type and cross-sectional profile were the only other histologic characteristics that independently influenced fatality rates. Prognosis was significantly worse in males than in females and in patients with tumors on the posterior head and neck. Ten-year survival rates of patients whose melanomas were diagnosed in 1975/1976 was 82% in men and 87% in women, indicating that these patients continued to experience some excess mortality up to 10 years after diagnosis. The comparatively small improvement in prognosis in the 5-year period between these two groups suggests that survival might be expected to continue to improve only gradually unless there is a sharp absolute decrease in the number of thick tumors diagnosed.

Adolescent↗

Principles behind practice. 7. Case-control studies.

The case-control study is often a very simple, cheap and quick way to test the hypothesis that a particular factor causes a disease or that a particular treatment is helping patients who receive it. There also seems to be an inherent logic in comparing patients and well people to see how they differed in the past, or in comparing those who did and did not survive a certain illness to see how their treatment differed. Despite these appealing features, the case-control approach is subject to a number of pitfalls. These can usually be avoided by an appropriately designed study, and by careful collection and analysis of the data. Even so, the results of a case-control study are a lower order of evidence than those produced from a properly conducted randomised controlled trial.

Bias↗

Pigmentary and cutaneous risk factors for non-melanocytic skin cancer--a case-control study.

The roles of ethnic origin, pigmentary traits, sun sensitivity and other cutaneous characteristics as risk factors for basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) were examined in a case-control study of prevalent and incident cases of histopathologically confirmed skin cancers. Two hundred and twenty six confirmed cases of BCC, 45 of SCC and 1,015 controls with no lesions were identified in a population-based survey of skin cancer in 1987 in Geraldton, Western Australia. The risk of both cancers was higher in native-born Australians than in migrants. The risk of BCC decreased with increasing age at arrival in Australia. Southern European ancestry was strongly protective against BCC (for any southern European grandparents) and SCC (no case of SCC had any grandparents of southern European origin). Inability to tan was the strongest pigmentary risk factor for both BCC and SCC. Among factors that incorporated a measure of sun exposure as well as sun sensitivity, freckling on the arm in childhood was important for both cancers, the number of moles on the back was important for BCC, and forearm skin colour and having a permanent colour difference between the neck and adjacent protected areas were important for SCC. Among measures of sun damage to the skin, solar elastosis of the neck was a strong risk factor for both BCC and SCC, loss of fine texture of the skin of the back of the hands (as measured by cutaneous microtopography) was important for BCC and telangiectasia of the face for SCC. When all important variables for each cancer were examined together in a single model with age, sex, migrant status or age at arrival in Australia, and ethnicity, in ability to tan, solar elastosis of the neck, and the number of moles on the back were independently significant risk factors for BCC and solar elastosis of the neck and having a permanent colour difference between the neck and adjacent protected areas were independently significant risk factors for SCC. The effects of age at arrival or migrant status and ethnic origin remained important in the models incorporating these factors. A history of ever having acne and a history of warts were protective for BCC and a history of acne was protective for SCC.

Adult↗

Skin cancer in Geraldton, Western Australia: a survey of incidence and prevalence.

A survey of the incidence and prevalence of non-melanocytic skin cancer in Geraldton, Western Australia, was undertaken in November 1987. All residents aged 40 to 64 years whose names were on the electoral roll on August 1, 1987 were invited to undergo a whole-body skin examination by a dermatologist. When a skin cancer was suspected, participants were referred for treatment to their usual medical practitioner. Subjects were asked to recall incident skin cancers over the preceding two years, and medical records were searched for confirmatory evidence. Histological confirmation of all lesions, both prevalent and incident, was sought and sections were obtained for a standardized review. The prevalence of confirmed non-melanocytic skin cancer in those aged 40 to 64 years was 7.0% in men and 4.7% in women. The prevalence of basal-cell carcinoma (BCC) was 6.5% in men and 4.5% in women while the prevalence of squamous-cell carcinoma (SCC) was 1.2% in men and 0.3% in women. The estimated incidence rate of non-melanocytic skin cancer in this age group was 1560 per 100,000 person-years. The estimated incidence rate of BCC in men was 1335 per 100,000 person-years, and in women 817 per 100,000, while in men the estimated incidence rate of SCC was 890 per 100,000 person-years, and in women it was 289 per 100,000 person-years.

Adult↗

A review of the effects of random measurement error on relative risk estimates in epidemiological studies.

Many articles in the recent epidemiological literature have discussed the effects of random error and misclassification on effect estimation, but many of these have been unclear and hard to follow. This paper reviews and interprets many of these and summarizes the use of the correlation coefficient in assessing the likely effect of measurement error on relative risk estimates for variables that are either continuous or ordered. A table of expected values of relative risks (RRs) calculated in different ways for different levels of random error is presented and the typically large expected attenuation in RR values is shown. The recommendation of taking repeated or multiple measurements whenever possible is endorsed.

Confounding Factors, Epidemiologic↗