Oestrogen and the breast.
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Biomedical subjects
Publications and source records attributed to D Ingram.
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This article describes the development of an interactive videodisc program to support professional education in the field of cancer for the primary health care team. Based on a survey of needs, it concentrates on common symptoms and their control, and problems in communication. The educational approach adopted was chosen on the basis of an extensive consideration of the needs, and what was felt most appropriate for adult learners. Plans were carefully reviewed at each stage, with external advisers, and the prototype system independently evaluated in four sites before completing the package. With financial backing from the 'Europe against Cancer' initiative of the European Commission, and close cooperation with national practitioners, Dutch, German, Greek and Portuguese versions of the package have been developed. Local differences in practice are taken into account and translations of key aspects are provided.
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Breast cancer is a common cause of suffering and death in Australia. Improvements in detection and therapy will make only small inroads into mortality, and will not reduce suffering. Reducing the incidence of breast cancer by preventive measures is a logical step, and this paper reviews how it might be achieved. Reducing the population's exposure to known risk factors for breast cancer is logical; however, the potential for improvement is limited. Reduction in age at first pregnancy is impractical and measures such as weight reduction and reducing consumption of fat and alcohol are likely to be only partially successful. Increasing activity in youth is a concept that requires further investigation, but is a possible area of promise. Exogenous hormone use probably contributes little to the incidence of breast cancer, but prescribing patterns for post-menopausal oestrogens are changing and require monitoring. The use of hormone manipulation to prevent breast cancer has considerable potential benefit. Two approaches have been proposed. The first involves reversible suppression of ovarian function by luteinizing hormone-releasing hormone (LHRH) agonists after child-bearing has finished, combined with low-dose conjugated equine oestrogen to compensate for oestrogen loss. The other involves the use of the anti-oestrogen, tamoxifen. Both measures have the potential to halve breast cancer incidence. There is some evidence that non-hormonal chemoprevention is possible, but clinical trial data are lacking.
Stereotactic fine needle aspiration biopsy (SFNB) was carried out on 404 mammographically detected impalpable breast lesions from 389 women between October 1988 and January 1990. Seventy-three lesions were excised, and 38 were carcinomas. Thirty-six of the 38 carcinomas had been diagnosed as atypical, suspicious or malignant by cytology; in the remaining 2 only fat and fibrous tissue were present in smears. The sensitivity of cytological diagnosis in detecting malignancy was therefore 94.8% (36 of 38 cases). A cytological diagnosis of malignancy was made in 23 cases (5.7%) and in 5 (1.2%) the findings were suspicious of malignancy. All of these were confirmed as carcinoma histologically; the predictive value of a positive cytological diagnosis was therefore 100%. In 32 cases (7.9%) the cytological findings were atypical but inconclusive. Twenty-three of these lesions were excised, and 8 proved to be carcinoma (34.8%). No case assessed radiologically and cytologically as benign has subsequently proven to be malignant. Twenty-two of 28 cases of invasive carcinoma were given an unequivocal cytological diagnosis of malignancy; 2 were suspicious of malignancy, and in 3 the findings were atypical but inconclusive. Of the 10 pure duct carcinoma-in-situ (DCIS) lesions, (26.3% of the cancers) 1 was diagnosed cytologically as malignant, 3 as suspicious of malignancy, and 5 as atypical. The sensitivity of SFNB in detecting DCIS lesions was therefore similar to invasive carcinomas, but cases of DCIS were more likely to be given a suspicious or atypical diagnosis rather than a definite diagnosis of malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)
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Patients with diabetes are prone to silent myocardial infarction and silent exertional ischemia. Although the mechanism is not clear, it may reflect a specific impairment of the sensory innervation of the heart. To test this hypothesis, anginal perceptual threshold was measured in 32 diabetic patients and 36 nondiabetic control patients, all of whom had typical exertional angina. Anginal perceptual threshold was defined as the time from onset of 0.1 mV ST depression to the onset of chest pain during treadmill stress electrocardiography. Although ST depression occurred earlier in the diabetic than in the nondiabetic group (111 +/- 82 versus 216 +/- 162 s, p less than 0.005), the anginal perceptual threshold in the diabetic group was delayed by a mean of 86 s (149 +/- 76 versus 63 +/- 59 s, p less than 0.001), with 95% confidence intervals of 53 to 119 s. Autonomic function tests were abnormal in the diabetic group, and in both groups regression analyses (using a third order polynomial) showed marked prolongations of anginal perceptual threshold as the heart rate responses to the Valsalva maneuver decreased to below the normal range (r = 0.5, p less than 0.001). There was a similar though less pronounced relation between anginal perceptual threshold and the heart rate responses to deep breathing (r = 0.3, p less than 0.02). These data suggest that prolongation of the anginal perceptual threshold may be caused by autonomic neuropathy involving the sensory innervation of the heart. To test sensory function, median nerve conduction studies were performed in 19 patients (10 diabetic and 9 nondiabetic).(ABSTRACT TRUNCATED AT 250 WORDS)
Natamycin, a fungicide marketed as Tymasil, is claimed to reduce house dust mite numbers and would therefore be expected to improve asthma in children with mite sensitivity. We have tested this assertion by a double-blind, placebo-controlled trial. There was no significant effect on levels of Der p I in mattress dust between active and placebo groups at the end of the spraying period. Histamine inhalation challenge PC20, clinic visit symptom scores and lung function tests reflecting either large or small airways obstruction were also unchanged. Therefore this product is not a therapeutic option for mite-allergic patients using the manufacturer's recommended dose and method of administration. Other factors influencing the Der p I levels were also investigated. Of these, only month of measurement and bedroom wall humidity showed any association.
Tamoxifen is widely used in the management of breast cancer, including long-term use in women with early disease to reduce recurrence and mortality. Although remarkably side-effect free, concern has been expressed that its anti-oestrogen activity may extend to lipid metabolism and so result in the premature development of coronary heart disease. In a study of breast cancer patients, those taking Tamoxifen tended to have lower cholesterol concentrations (predominantly low-density lipoprotein cholesterol) and raised triglyceride concentrations. These changes are likely to be protective for coronary heart disease, suggesting Tamoxifen has an oestrogenic rather than anti-oestrogenic effect as regards lipid metabolism.
An Australian study of 513 women evaluated associations between obesity and both benign and malignant breast disease, and in particular investigated the role of female sex hormones. Women who gained more than 10 kg from early womanhood had a two-fold increase in risk of developing breast cancer, whereas lean women had a greater risk of being treated for benign breast disease. Obese women with breast cancer were more likely to have Stage II tumors but there was no significant association between obesity and tumor size or estrogen and progesterone receptor status. Obesity was strongly associated with the proportions of nonprotein-bound and albumin-bound estradiol, and inversely associated with sex hormone binding globulin (SHBG) levels and the proportion of SHBG-bound estradiol. In addition, age at menarche was inversely associated, and age at menopause directly associated with recalled weight at those time periods. These data demonstrate weight gain as a risk factor for breast cancer, and suggest a possible mechanism supporting its development.
Breast cancer development is believed to be associated with both dietary fat consumption and the proportion of biologically available estradiol in the serum. A study was undertaken to determine if a reduction in fat consumption would influence the binding, and thus the bioavailability, of estradiol. Groups of pre- and postmenopausal women were randomized to begin either a standard western diet (40% energy from fat) or a low-fat diet (20% energy from fat). After two months, each woman changed over to the alternate diet. Blood samples were taken at the end of each dietary period. Change of diet made no significant difference to the proportions of nonprotein-bound (free), albumin-bound, or sex hormone binding globulin-bound estradiol in this study. However, the number of women studied and the duration of change were relatively small.
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719 first-degree relatives of diabetic children were followed up to assess the value of HLA haplotype sharing and of islet-cell antibodies (ICA) for prediction of insulin-dependent diabetes (IDDM). Within a maximum of 8 years' follow-up (3384 patient-years of observation) 16 unaffected relatives (5 parents and 11 siblings) became insulin dependent. The cumulative risk of becoming insulin dependent by age 25 was 16% for siblings sharing two HLA haplotypes with the proband, 9% for those sharing one haplotype, and zero for those sharing none. 13 of 24 (54%) subjects positive for complement-fixing ICA on three or more occasions became insulin dependent, as against 1 of 30 (3%) with noncomplement-fixing ICA alone and 2 of 665 (0.3%) ICA-negative subjects; by life-table analysis the risks after 8 years of known ICA status are 76%, 3%, and 0.6%, respectively. In terms of total time at risk ICA-positive family members had a relative risk of 75.2 compared with ICA-negative individuals. With positivity for complement-fixing ICA the relative risk was 188.5.
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One hundred and sixty seven children, ranging in age from 5 weeks to 16 years, with chronic upper or lower respiratory tract problems, or both, were investigated for ciliary dyskinesia. Abnormal ciliary function was found in 18 cases all of whom had chronic lower respiratory disease and most of whom also had upper respiratory problems. Fifteen of the 18 cases had reduced ciliary beat frequencies (less than 10 Hz) associated with dyskinesia and the other three showed apparent absence of ciliated cells. Of the 15 cases with reduced ciliary beat frequencies, ciliary ultrastructure was normal in seven cases but abnormal with missing dynein arms and occasional abnormalities of microtubular arrangement in eight. Respiratory symptoms in the perinatal period were more common in children with abnormal ciliary function and present in all those with ultrastructural abnormalities or absence of ciliated cells compared with 34 (26%) of 132 children, in whom symptoms were recorded, with normal ciliary function. This study would suggest that all children with unexplained chronic respiratory disease, in particular those with symptoms starting in the perinatal period, should be investigated for ciliary dyskinesia.
It is suggested that in motor neuron disease there is a long preclinical period of relative tolerance and compensation before presentation with apparently focal features. During this phase the disease becomes disseminated through the motor system. The mode of acquisition of the disease, its relation to a possible genetic factor, and the processes leading to tolerance, to latency or progression, to the relative involvement of upper and lower motor neurons, to involvement of spinocerebellar pathways, and to asymmetry are fundamental problems in understanding the disease.
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