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Biomedical subjects

M C Pike

Publications and source records attributed to M C Pike.

At least 199 records · Page 11Linked to original sources

Familial breast cancer in a population-based series.

Breast cancer risks to sisters of breast cancer patients were examined in a population-based series of patients diagnosed in Los Angeles County between 1971 and 1975. Sisters of bilateral patients diagnosed at age 50 years or younger had substantially increased risk (relative risk (RR) = 5.5), and risk was even higher for sisters of bilateral patients diagnosed at age 40 years or younger (RR = 10.5). Half of the breast cancers in sisters of bilateral cases occurred in the family of a single bilateral patient whose disease was diagnosed at age 39 years. Sisters of unilateral patients diagnosed at age 50 years or younger did not have significantly increased risk, but sisters of unilateral patients diagnosed at age 40 years or younger appeared to have increased risk (RR = 2.4). Risk to sisters of bilateral patients was slightly higher if the patient's contralateral diagnoses were less than three years apart than if they were three years apart or greater (RR = 6.3 vs. 3.9), but this difference was not statistically significant.

Adult↗

The relationship between breast cancer and augmentation mammaplasty: an epidemiologic study.

Surgical implantation of breast prostheses for cosmetic purposes has become increasingly popular, and by 1981, it was estimated that three-quarters of a million women had had such an operation. The long-term potential risks, particularly of breast cancer, of such procedures have not been properly investigated. To evaluate the potential breast cancer risk, we have conducted a retrospective cohort study of 3111 women followed through various public and medical records for a total of 18,476 person-years, with a median of 6.2 years per person. The cases of breast cancer were detected by means of a computerized match with the Los Angeles County Cancer Surveillance Program, a population-based cancer registry. Overall, 15.7 breast cancer cases were expected and 9 were observed, a nonsignificant deficit [standardized incidence ratio (SIR) = 57 percent, 95 percent confidence limits: 26 percent, 109 percent]. The cancers were generally diagnosed at an early stage. Among the 573 women aged 40 or older at implantation, 7.1 cases were expected and 8 were observed (SIR = 113 percent). In women whose implants were performed before the age of 40, only 1 case was observed whereas 8.6 cases were expected (SIR = 12 percent, 95 percent confidence limits: 0.3 percent, 65 percent), a significant difference. These data do not support an increased risk of breast cancer following augmentation mammaplasty. The low breast cancer rate in women having augmentation mammaplasty at a young age that many such women may have a reduced amount of breast tissue, but data on this are unavailable.

Adolescent↗

Month of birth of men with malignant germ cell tumours of the testis.

A recent paper has suggested that there is a temporal cycle in birth rates of men with testis cancer with a peak in April/May. We have investigated the suggestion using data from the South Thames and Los Angeles cancer registries. There is some slight evidence of a peak in August, which is confined to teratomas. The effects demonstrated are, however, too small and inconsistent to provide any real clue to the aetiology of testis cancer.

California↗

Chemoattractant-mediated stimulation of the respiratory burst in human polymorphonuclear leukocytes may require appearance of protein kinase activity in the cells' particulate fraction.

Low doses of aliphatic alcohols produce divergent effects on the function of chemoattractant receptors on human polymorphonuclear leukocytes (PMNs) since they enhance chemotaxis but inhibit stimulation of superoxide production by chemoattractants. As such, alcohols can provide useful pharmacologic tools to probe the mechanisms of stimulus-response coupling in leukocytes. A role for protein kinase C has been implicated in the activation of the respiratory burst in PMNs. Although the vast majority of this enzyme activity is located in the cytosolic fraction of unactivated PMNs, protein kinase C activity appears in the particulate fraction of the cells when they are stimulated to produce superoxide by either chemoattractants or by phorbol myristate acetate (PMA). Doses of the alcohols that selectively inhibited stimulation of superoxide production by chemoattractants also inhibited the appearance of protein kinase C activity as well as an undefined protein kinase activity in the particulate fraction of the cells. In contrast, the alcohols did not affect either the ability of PMA to stimulate the production of superoxide in PMNs nor the appearance of protein kinase activity in the cells' particulate fraction. PMA is known to bind and activate protein kinase C directly, thus bypassing receptor-mediated events. These data suggest that alcohols inhibit the stimulation of the respiratory burst by chemoattractants in PMNs by blocking the ability of receptor occupancy to induce the appearance of protein kinase activity in particulate fractions. These results moreover suggest that the appearance of protein kinase activity in the particulate fraction may be required for activation of the respiratory burst in PMNs.

Alcohols↗

Higher maternal levels of free estradiol in first compared to second pregnancy: early gestational differences.

Serum samples drawn from 34 women in the early part of both their first and their second pregnancies were assayed for estradiol (E2), percentage of free E2, and sex hormone-binding globulin-binding capacity (SHBG-bc). Subjects were participants in the Collaborative Perinatal Study conducted by the National Institute of Neurological and Communicative Disorders and Stroke (Bethesda, MD) to evaluate factors related to adverse pregnancy outcome. All pregnancies were full term, and no offspring had a congenital malformation. After adjustment for week of pregnancy, the percentage of free E2 was 9% higher (two-sided P = .007) and the amount of free E2 was 17% higher (two-sided P = .03) in first-pregnancy sera. Total E2 was also 7% higher in first-pregnancy sera after adjustment for week of pregnancy; SHBG-bc was 7% lower after adjustment for week of pregnancy and 9% lower after simultaneous adjustment for week of pregnancy and weight at the start of pregnancy; but these differences were not statistically significant. These findings confirm our previously published hypothesis that the early part of a woman's first pregnancy differs endocrinologically from her second and may provide further insight into pregnancy-related risk factors for testis cancer and cryptorchidism and into the protection afforded by first full-term pregnancy against breast cancer.

Adult↗

Do regular ovulatory cycles increase breast cancer risk?

The "estrogen window hypothesis" of the etiology of breast cancer proposes that unopposed estrogen stimulation is the most favorable state for tumor induction and that normal postovulation progesterone secretion reduces susceptibility. The authors believe that epidemiologic and experimental studies suggest rather that the opposite is true, i.e., that breast cancer risk is directly related to the cumulative number of regular ovulatory cycles. Unlike the endometrium, breast tissue mitotic activity is enhanced in the luteal phase of the menstrual cycle. Regular vigorous physical activity is one method of reducing the frequency of ovulatory cycles, and such exercise could markedly reduce a woman's lifetime risk of developing breast cancer.

Adolescent↗

Statistical errors invalidate conclusions in "Caffeine and unsaturated fat diet significantly promotes DMBA-induced breast cancer in rats".

The conclusion drawn in a recent paper by Minton and associates (Cancer 1983; 51:1249-1253), that caffeine and an unsaturated fat diet significantly promoted dimethylbenz(a)anthracene (DMBA)-induced breast cancer in rats, is based on fallacious statistical reasoning. Minton and associates based their conclusion on the mean latency to first tumor appearance for rats diagnosed with tumors. However, evaluation of percentages of tumor-bearing rats yields contrary results. Using data from a totally negative hypothetical two-group experiment, we demonstrate how such "conflicting" results could arise from differential intercurrent mortality in the two groups. The correct statistical analysis of this hypothetical experiment allows for differential intercurrent mortality and no conflict arises; the data of Minton and associates need to be analyzed by these methods.

9,10-Dimethyl-1,2-benzanthracene↗

Some tautologous aspects of the comparison of carcinogenic potency in rats and mice.

In risk estimation, the results of rodent carcinogenesis experiments are often used to quantitatively predict effects in man. The justification for this approach has in large part been dependent upon the good correlation of carcinogenic potency found between mice and rats over large numbers of test chemicals. Using the data base of chemicals tested by the NCI Bioassay Program, we observe that there is a very high correlation of the maximum doses tested (max-d) for rats and mice on a milligram per kilogram body weight per day basis. Next we show that the calculated carcinogenic potency (b-defined in the paper) is restricted to an approximately 30-fold range surrounding log(2)/max-d, which has a biological as well as a statistical basis. Since the max-d's for the set of NCI test chemicals vary over many orders of magnitude, it necessarily follows statistically that the carcinogenic potencies will be highly correlated. This "artifact" of potency estimation does not imply that there is no basis for extrapolating animal results to man. It does suggest, however, that the interpretation of correlation studies of carcinogenic potency needs much further thought.

Animals↗

Estrogen and sex hormone-binding globulin levels in nulliparous and parous women.

The hormone profiles of nulliparous and parous women on day 11 of their menstrual cycle have been studied in an attempt to seek evidence for the hormonal basis of the protective effect of first birth on breast cancer risk. A previous publication reported that there were significantly lower (26%) early morning prolactin levels in parous women as compared to those levels in nulliparous women but that there were no differences in plasma and urinary estrogen levels. The present study shows, however, that parous women had significantly shorter cycle lengths than nulliparous women of the same age, and the data were reevaluated with this difference being taken into account. After adjustment for cycle length (within the range of 24-32 days) and age, estrogen levels were significantly lower (22%) in parous women compared to those in nulliparous women. Two further aspects of estrogen metabolism were measured in the plasma samples of these women: the binding capacity of sex hormone-binding globulin (SHBG) and the percentage of free estradiol (E2). SHBG levels were 12% higher in parous women, but there was no difference in percentage of free E2. In the previous publication it was suggested that the protective effect of first birth on breast cancer risk was mediated in part by permanently lowering prolactin levels. The current findings suggest that changes in estrogen metabolism also are a factor.

Adult↗

Smoking and other risk factors for lung cancer in women.

A case-control study among white women in Los Angeles County was conducted to investigate the role of smoking and other factors in the etiology of lung cancer in women. A total of 149 patients with adenocarcinoma (ADC) and 71 patients with squamous cell carcinoma (SCC) of the lung and their age- and sex-matched controls were interviewed. Personal cigarette smoking accounted for almost all of SCC and about half of ADC in this study population. Among nonsmokers, slightly elevated relative risk(s) (RR) for ADC were observed for passive smoke exposure from spouse(s) [RR = 1.2; 95% confidence interval (Cl) = 0.5, 3.3] and at work (RR = 1.3; 95% Cl = 0.5, 3.3). Childhood pneumonia (RR = 2.7; 95% Cl = 1.1, 6.7) and childhood exposure to coal burning (RR = 2.3; 95% Cl = 1.0, 5.5) were additional risk factors for ADC. For both ADC and SCC, increased risks were associated with decreased intake of beta-carotene foods but not for total preformed vitamin A foods and vitamin supplements.

Adenocarcinoma↗

Apparent doubling of frequency of undescended testis in England and Wales in 1962-81.

Examination of Hospital Inpatient Enquiry data for England and Wales for the years 1962-81 shows that the annual number of discharges with a diagnosis of undescended testicle has risen by a factor of 2.3. Cohort analysis suggests that the cumulative rate to age 15 of discharge for undescended testis has risen from 1.4% for the 1952 birth-cohort to 2.9% for the 1977 birth-cohort. Whether this is a reflection of an increase in true cryptorchidism is not known. Changes in known risk factors for cryptorchidism--exogenous oestrogen exposure, being first-born, and low birth-weight--cannot fully account for the apparent increase. With the tendency to carry out orchidopexies on apparently undescended testes at younger ages in order to preserve fertility, it is possible that a considerable number of boys with retractile testes that would have descended naturally at puberty are now being operated upon.

Adolescent↗