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Biomedical subjects

A C Green

Publications and source records attributed to A C Green.

At least 37 records · Page 2Linked to original sources
PubMed1998

p53 expression and risk factors for cutaneous melanoma: a case-control study.

Epidemiological data strongly implicate sunlight as the principal environmental cause of melanoma; however, critical molecular targets for ultraviolet (UV)-induced melanoma remain to be identified. The p53 tumor suppressor gene is one possible target, being abnormally expressed in 20-40% of primary melanomas. We undertook a population-based molecular epidemiological study with the aim of determining the environmental and phenotypic factors associated with p53-positive and p53-negative melanomas. One hundred fifty cases of melanoma were randomly ascertained from the Queensland Cancer Registry and matched to 150 electoral roll controls. Data on environmental and phenotypic exposures were collected through interviews and physical examination of all participants. Sections of tumor tissue were obtained from 134 (89%) cases and stained with the anti-p53 DO-7 monoclonal antibody (MAb) following microwave antigen retrieval. Of 121 useable sections, 22 tumors (18%) had more than 1% cells with positive staining consistent with abnormalities in p53 expression. Strongest predictors of p53-positive melanoma were inability to tan [odds ratio (OR) 6.8], history of non-melanoma skin cancer (OR 3.2) and site of melanoma: head/neck (OR 2.2) and lower limbs (OR 2.3). In contrast, factors such as nevus density and freckling propensity were strongly associated only with p53-immunonegative melanoma (OR 8.6 for >25 moles; OR 3.0 for heavy facial freckling). Overall, the determinants of p53-positive and p53-negative melanomas were independent and complementary, the former being associated with features of sun-sensitivity and chronic sun exposure, the latter with phenotypic markers of melanocytic proliferation. Our findings are consistent with at least 2 independent pathways in the pathogenesis of melanoma, characterized by environmental induction and p53 overexpression on the one hand and pigment cell instability on the other.

Age Distribution↗
PubMed1998

Segregation analysis of cutaneous melanoma in Queensland.

To investigate whether the familial clustering of cutaneous melanoma is consistent with Mendelian inheritance of a major autosomal gene, maximum likelihood segregation analyses were performed in a population-based sample of 1,912 families ascertained through a proband with melanoma diagnosed in Queensland between 1982 and 1990. Analyses were performed with the S.A.G.E. statistical package, using the REGTL program for a binary trait with a variable age of onset. We sought medical confirmation for all family members reported to have had melanoma, and only medically verified cases among relatives were included in the analyses. The hypothesis of codominant Mendelian inheritance gave a significantly better fit to the data than either dominant or recessive Mendelian inheritance, or environmental transmission. Overall, both Mendelian inheritance of a single major gene, and purely environmental transmission were rejected (P < 0.001). In both the single major gene and environmental models, there was strong evidence of familial dependence in melanoma occurrence (P < 0.001). These results are consistent with reported genetic heterogeneity in melanoma inheritance and suggest that other familial factors, such as pigmentation, skin type, and sun exposure habits, may play an important role in the familial clustering of melanoma.

Adult↗
PubMed1998

The prevalence and determinants of solar keratoses at a subtropical latitude (Queensland, Australia).

We report the association between skin pigmentation and individual sun exposure, and the occurrence of solar keratoses (SKs) in an unselected population, quantified for the first time. SKs were examined in a representative sample of 197 residents of the community of Nambour in Queensland, Australia. Estimates of sun exposure were combined with a measure of ultraviolet (UV) flux to estimate actual UV exposure, both occupational and recreational, during childhood and adult life. The number of episodes of painful sunburn was used as a measure of intermittent, intense UV exposure. Eight-three participants (43%) had at least one SK, while 35 (18%) had more than 10 SKs diagnosed. The age- and sex-adjusted odds ratios (ORs) for the development of SKs were higher in individuals with fair (OR = 14.1) or medium skin (OR = 6.5), compared with olive-skinned individuals. Individuals with poor ability to develop a suntan were similarly at increased risk compared with others. High levels of occupational UV exposure during adult life were confirmed as being strongly associated with prevalent SKs (OR = 2.4 for heavy/maximal adult exposure), with an even stronger association seen in those individuals with multiple SKs (OR = 4.3 for maximal adult exposure). Although no clear association was demonstrated between SK prevalence and accumulated childhood sun exposure, a history of even one episode of sunburn in childhood was strongly associated with SK prevalence (peak OR of 5.9 for one sunburn).

Adult↗
PubMed1998

The epidemiology of Parkinson's disease in an Australian population.

A prevalence study of Parkinson's disease (PD) was conducted in the rural town of Nambour, Australia. There were 5 cases of PD in a study population of 1207, yielding a crude prevalence ratio of 414 per 100,000 (95% confidence interval; 53-775). We performed a separate case-control study involving 224 patients with PD and 310 controls from South East Queensland and Central West New South Wales, to determine which factors increase the risk for PD in Australia. A positive family history of PD was the strongest risk factor for the development of the disease (odds ratio = 3.4; p < 0.001). In addition, rural residency was a significant risk factor for PD (odds ratio = 1.8, p < 0.001). Hypertension, stroke and well water ingestion were inversely correlated with the development of PD. There was no significant difference between patients and controls for exposure to herbicides and pesticides, head injury, smoking or depression. The high prevalence of PD in Nambour may be explained by rural residency. However, the most significant risk factor for PD was a positive family hisotry. This demonstrates the need for improved understanding of the genetic nature of the disease.

Age of Onset↗
PubMed1998

Predictive factors of age at menopause in a large Australian twin study.

Various studies have investigated potential predictors of age at natural menopause but have produced inconsistent results. The relationship between age at natural menopause and socioeconomic, reproductive, and health behavioral factors was evaluated using longitudinal data from 5961 Australian female twins, aged 17 to 88 years at the time of study. The sample consisted of women voluntarily enrolled in the Australian Twin Registry. Failure-time analysis was the principal statistical method used to handle censored observations. Kaplan-Meier estimates showed the overall median age at natural menopause to be 51 years (95% confidence interval, 50-51). Median age at menopause was earlier for women with earlier birth year, women with late age of menarche, women who had no children, or women who were smokers. Differences in age at menopause between social, occupational, and educational groups were statistically significant (Mantel-Cox test, p < 0.001) for education, major occupational classification, combined income, and self-rated social class, with higher age at menopause for higher levels of each variable. A Cox proportional hazards model was used to estimate the odds ratio of the occurrence of natural menopause among different sub-groups, adjusted to reflect simultaneous effects of all other significant covariates. This large study provided clear trends of association in predictors relating to age at menopause. These trends may help to resolve uncertainties and conflicting results identified in studies of comparable white samples. The nature of the twin data also sets a solid background for future analyses of genetic and environmental variance components using statistical modeling or related methods.

Adolescent↗
PubMed1997

Risk factors for childhood melanoma in Queensland, Australia.

The causes of cutaneous melanoma among children under 15 years are largely unknown. We report the findings of an epidemiological study of childhood melanoma in Queensland, Australia, which has the highest incidence rates in the world. All 61 cases of melanoma in children less than 15 years notified to the Queensland Cancer Registry 1987-1994 were eligible to participate in a population-based, case-control study. Data were collected through structured, face-to-face interviews with parents and skin examinations of the 52 participating cases and 156 age- and sex-matched controls. The strongest determinants of melanoma risk found among Queensland children were constitutional factors, including the presence of more than 10 naevi greater than 5 mm in diameter (RR 9.9, 95% CI 2.5-38.9), heavy facial freckling (RR 6.4, 95% CI 1.9-21.6), an inability to tan on exposure to the sun (RR 8.8, 95% CI 2.1-36.2) and a family history of melanoma (RR 4.2, 95% CI 1.9-9.3). These factors remained significantly associated with melanoma after adjusting for other risk factors. No measures of acute or chronic exposure to solar UV radiation were associated with childhood melanoma in our study. Established risk factors, including giant congenital naevi and xeroderma pigmentosum, were not present among any of the children in the study. Melanoma in childhood appears to have similar epidemiologic characteristics to the adult form of the disease, being associated with a cluster of phenotypic attributes indicating cutaneous sensitivity to the effects of sun exposure. Our findings support the contention that childhood melanoma occurs in susceptible individuals with a low threshold for pigment cell tumorigenesis. From a public-health perspective, children at elevated risk for melanoma can be identified on the basis of phenotype and family history.

Adolescent↗
PubMed1997

ATP acting on P2Y receptors triggers calcium mobilization in Schwann cells at the neuroelectrocyte junction in skate.

Schwann cells are integral cellular components of the dense cholinergic presynaptic plexus (nerve plate) which innervates each electrocyte in skate electric organ. Using the Ca2+-sensitive dye fura-2, we have followed the response in these cells to various chemical challenges. In K+ depolarized nerve plates nerve terminals consistently responded with a rapid and sustained Ca2+ signal. Schwann cell responses to depolarization were rarely seen but, when observed, were always delayed in onset when compared to nerve terminal response (6-10 s later). The possibility that these responses were triggered by mediators released from nerve terminals was tested by direct application of candidate substances. Schwann cells were found to respond to adenosine triphosphate and adenosine diphosphate with a biphasic increase of intracellular Ca2+ concentration, a rapid peak response being followed in the majority of cells by a sustained plateau phase. In the absence of external Ca2+ only the transient peak response was observed. Depletion of internal Ca2+ stores with thapsigargin completely inhibited the adenosine triphosphate-stimulated rise in Schwann cell Ca2+. The response to adenosine triphosphate was concentration-dependent (EC50 2.8 microM) and was reversibly blocked by two antagonists of P2 purinoceptors: suramin and reactive blue 2. Adenosine diphosphate and 2-methylthio-adenosine triphosphate were equipotent with adenosine triphosphate and at high concentrations (100 microM) diadenosine tetraphosphate produced responses comparable to low concentrations of adenosine triphosphate. Adenosine, adenosine monophosphate, the alpha beta-methylene analogues of adenosine triphosphate and adenosine diphosphate, uridine triphosphate, cytidine triphosphate and guanosine triphosphate were without significant effect. These results show that, in skate electric organ Schwann cells, the release of Ca2+ from intracellular stores is triggered by adenosine triphosphate acting on P(2gamma) receptors and suggest that Schwann cells may be targets for synaptically-released adenosine triphosphate in the electric organ model of the neuromuscular junction.

Acetylcholine↗
PubMed1997

Patterns of excision and referral from primary care of melanocytic lesions.

There is debate about the margin of normal tissue that should be included with excisions of melanocytic lesions of the skin, and about which lesions should be referred for specialist care. We describe the determinants of the margins of excised melanocytic skin lesions and of referral patterns from primary care. Copies of the pathology reports of melanocytic skin lesions excised from two cities in tropical Queensland were obtained; questionnaires about each lesion were administered to the excising doctor. Data about 3275 lesions (2914 naevi, 130 lentigos, 151 melanomas, 51 dysplastic naevi, 21 Hutchinson's melanotic freckles and eight other melanocytic lesions) were analysed. Twenty-one per cent of the treatment sessions involved the excision of more than one lesion; 5% involved three lesions or more. Most lesions were managed by one doctor. The overall mean margin of excision was 2.8 mm. It was greater for longer qualified doctors, surgeons and college-affiliated general practitioners, for lesions excised to address malignancy (3.0 mm) rather than cosmetic appearance (2.4 mm), for Hutchinson's melanotic freckles (5.9 mm) and melanomas (5.1 mm) compared with benign lesions (2.7 mm) (P < 0.001) and for older patients (2.6 mm for those < or = 15, 3.5 mm for those > 40 years) (P = 0.001). Wider excisions of skin melanocytic lesions are performed by older and more experienced doctors, on older patients, and for lesions in which malignancy is being addressed.

Adolescent↗
PubMed1997

Do public media campaigns designed to increase skin cancer awareness result in increased skin excision rates?

We report on an observational study of one city in Queensland over a 30-month period to evaluate the effects of two public skin cancer campaigns on the excision rates of melanocytic skin lesions. The numbers of melanomas, the numbers of potentially malignant melanocytic lesions (Hutchinson's melanotic freckles and dysplastic naevi) whose excision might have benefited the patient, and the total number of melanocytic skin lesions submitted to pathology services were recorded. A total of 3221 melanocytic skin lesions were excised. More lesions were excised during summer than non-summer periods (rate ratio 1.22, 95% CI 1.06, 1.40) and, independently, during campaign periods than non-campaign periods (rate ratio 1.24, 95% CI 1.11, 1.37). There were 145 melanomas (4%), of which 116 were < 0.76 mm thick, and an additional 53 (2%) other potentially malignant lesions. During campaigns, proportions of neither type increased significantly, nor was there a significant reduction in excised melanoma thickness. Doctors reported more often that the reason for excision was to exclude malignancy during the campaigns, although they felt themselves to be under less pressure from patients to excise lesions. There may be considerable cost associated with primary prevention campaigns in the form of increased excision of benign skin lesions, which should be addressed in future skin cancer public awareness campaigns.

Australia↗
PubMed1996

Reliability of computer image analysis of pigmented skin lesions of Australian adolescents.

BACKGROUND: The diagnosis of melanomas at an early stage is associated with improved survival, so the recognition of changes in pigmented skin lesions over time is important. We have developed a computer imaging system with the aim of assisting clinicians in differentiating early melanomas from benign pigmented skin lesions. The objective of this study was to investigate the system's reliability over time in measuring diagnostic characteristics of pigmented skin lesions, including their color, size, shape, and distinctness of boundary. METHODS: We captured video images of 5 lesions, all larger than 2 mm in greatest dimension, on each of 66 Australian adolescents on 2 occasions approximately 1 month apart. Features extracted by computer image analysis included area, perimeter, and regularity of outline of the lesions, the mean and standard deviation of reflectance at red, green, and blue wavelengths, and the mean and standard deviation of the gradients of red, green, and blue reflectance at the lesion boundary. RESULTS: All measurements showed moderate to high reliability (intraclass correlation coefficients 0.66-0.94), except for the standard deviations of the color gradients, whose reliability improved to moderate levels (0.68-0.71) when the mean of 5 lesions was considered. For most outcomes, reasonable within subject reliability was achieved when five lesions per subject were measured. CONCLUSIONS: These results, in combination with previous work demonstrating the reasonable ability of this computer imaging system to discriminate between malignant melanomas and other pigmented lesions, indicates that the system has the potential to become a useful tool for clinicians in following people with pigmented lesions over time to detect early malignant changes.

Adolescent↗
PubMed1996

Polyamine amides are neuroprotective in cerebellar granule cell cultures challenged with excitatory amino acids.

Primary cultures of rat cerebellar granule cells have been used to assess the potential neuroprotective effects of philanthotoxins and argiotoxin-636 (ArgTX-636). These polyamine amides are potent antagonists of ionotropic L-glutamate (L-Glu) receptors. In granule cells loaded with fluo-3, ArgTX-636 and philanthotoxin-343 (PhTX-343) antagonised increases of intracellular free calcium concentration ([Ca2+]i) that were stimulated by N-methyl-D-aspartate (NMDA). The antagonism was use-dependent. Antagonism by PhTX-343 was fully reversible, but recovery following antagonism by ArgTX-636 was slow and only partial during the time-course of an experiment. Neither compound inhibited K(+)-induced increases in [Ca2+]i. In excitotoxicity studies with cerebellar granule cells, the release of lactate dehydrogenase (LDH) and morphological observations were used to assess cell death. A 20-30 min exposure to 500 microM NMDA, 100 microM L-Glu or 500 microM kainate was sufficient to kill > 90% of the cells after 18-20 h. When added 5 min prior to, and during agonist exposure, PhTX-343 and ArgTX-636 provided total neuroprotection. ArgTX-636 was about 20-30 fold more potent than PhTX-343 against NMDA, but was approximately equipotent with PhTX-343 against a kainate challenge. Neither of the toxins showed any inherent toxicity even at 400 microM and 100 microM respectively. Some analogues of PhTX-343 are more potent, both in terms of antagonism of NMDA-stimulated increases of [Ca2+]i and neuroprotection, than PhTX-343 and ArgTX-636.

Amides↗
PubMed1996

The Queensland Familial Melanoma Project: study design and characteristics of participants.

Family history of melanoma is associated with an increased risk for the disease. Neither the relative contributions of genetic and shared environmental factors to familial risk nor how genetic susceptibility is mediated are known. The Queensland Familial Melanoma Project was undertaken to investigate (a) the role of genetic susceptibility as indicated by skin type, pigmentation and the prevalence of naevi and (b) exposure to solar ultraviolet radiation, and their interaction in the aetiology of familial melanoma. After obtaining doctor's consent, a brief family history questionnaire was mailed to all Queensland residents with a first primary cutaneous melanoma diagnosed between 1982 and 1990. Detailed information on melanoma history and standard melanoma risk factors was sought from all responding twins and familial cases, from a sample of non-familial cases and from cases' relatives. Medical confirmation was sought for all relatives reported to have had melanoma. The final sample comprises 15,907 persons in the 1,912 families of 2,118 melanoma cases, including 509 families in which there are two or more individuals with confirmed melanoma. Melanoma history and risk factors were obtained for 9,746 relatives, including 94 twins of cases. This is the largest family and twin study of cutaneous melanoma yet conducted in an unselected, geographically-defined population. We describe the design of the study and the characteristics of the total study population.

Adult↗
PubMed1995

Gastric emptying in acute overdose: a prospective randomised controlled trial.

OBJECTIVE: To test the hypothesis that administration of activated charcoal is as efficacious and safe as the combination regimen of gastric emptying plus charcoal in adults after acute oral overdose. DESIGN: Prospective randomised controlled trial, with subjects presenting on odd-numbered dates allocated to the emptied group (E), and those on even-numbered dates to the not-emptied group (NE). SETTING: Princess Alexandra Hospital, Brisbane (a tertiary referral hospital), which serves an adult urban community, between 4 January 1988 and 11 June 1990. SUBJECTS: Consecutive patients (13 years or older) who presented to the Emergency Department after ingesting an overdose of one or more compounds able to be adsorbed by activated charcoal. INTERVENTIONS: All patients received charcoal by the oral or nasogastric route. Those in the E group also had gastric emptying by ipecac-induced emesis or gastric lavage. OUTCOME MEASURES: Clinical course during the first six hours after treatment began, length of hospital stay, complications. RESULTS: 876 patients were eligible for the study. There were no significant differences between the E and NE groups in age and sex distribution, severity of the overdose or other characteristics, except the mean interval between presentation and administration of charcoal (91 min [SD, 52] for E group and 55 [SD, 41] for NE group; P = 0.0001). There were no significant differences between the E and NE groups in outcome, even when the groups were stratified for severity of the overdose or into subgroups that presented sooner or later than one hour after ingestion. CONCLUSIONS: Gastric emptying can be omitted from the treatment protocol for adults after acute oral overdose.

Adolescent↗
PubMed1995

Aid to diagnosis of melanoma in primary medical care.

OBJECTIVE: To evaluate an intervention designed to reduce the number of benign melanocytic lesions excised from the skin. DESIGN: A randomised controlled field trial based in the medical practices of two cities. Examination of histopathological reports of 5823 melanocytic skin lesions excised over the intervention period and in the preceding six months. INTERVENTION: Medical practitioners were offered an algorithm and use of an instant developing camera. SETTING AND SUBJECTS: Over 50 medical practitioners, mostly in general practice, in each of two cities in tropical Queensland, Australia. MAIN OUTCOME MEASURES: Percentages of benign (neither malignant nor potentially malignant) melanocytic lesions excised during the two year intervention period. RESULTS: There were no significant differences in the percentages of benign lesions reported in the intervention and control cities before the intervention started (93.6% and 94.0%, respectively), but there was a significant difference afterwards (88.8% and 93.8%, P < 0.001). There was no difference in the percentage of invasive melanomas excised per month in the intervention city (3.4%) compared with control city (3.4%). CONCLUSION: Clinical diagnostic accuracy may be enhanced by offering to clinicians managing suspicious melanocytic skin lesions a simple algorithm and a camera with which to record the appearance of lesions objectively.

Adult↗