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Biomedical subjects

M C Pike

Publications and source records attributed to M C Pike.

At least 289 records · Page 16Linked to original sources

Comparison of urinary and plasma hormone levels in daughters of breast cancer patients and controls.

Plasma and urinary levels of estrogens and progesterone were studied on days 11 and 22 of the menstrual cycle in 27 teenage daughters of breast cancer patients and 25 teenage daughters of controls. Plasma and urinary values correlated well, which implied that most previous findings based on urinary levels of these hormones were applicable to their plasma levels. The "estriol ratio" (urinary estriol:urinary estrone plus estradiol) hypothesis was not supported by this study, the ratio having been no lower in the daughters of breast cancer patients than in daughters of controls. The day-11 results showed elevated plasma prolactin-estrogen values in daughters of breast cancer patients; the day-22 results did not.

Adolescent↗

Macrophage migratory dysfunction in cancer. A mechanism for subversion of surveillance.

There is considerable evidence to suggest that macrophages participate in host resistance to the development and spread of cancer. We have, therefore, studied monocytemacrophage function in humans and animals with neoplasms. Approximately 60% of patients with various types of cancer were found to have abnormal monocyte chemotactic responsiveness in vitro, and abnormal chemotaxis was an indicator of poor prognosis in patients with melanoma. By studying patients before and after surgery, it was found that abnormal chemotactic responses normalized within weeks after removal of malignant tumors, indicating that a neoplasm itself might affect the host's monocyte chemotactic responsiveness. Subsequent studies using transplantable neoplasms in mice substantiated this hypothesis in that macrophage accumulation in vivo as well as macrophage chemotactic responsiveness in vitro was depressed in animals during the early phases of tumor growth. This depression of macrophage function could be attributed to a low-molecular-weight factor contained in murine neoplasms, which when given to normal mice was extremely potent in depressing peritoneal macrophage accumulation and chemotaxis but, paradoxically, enhanced phagocytosis. The serum of tumor-bearing mice also contained potent inhibitory activity for macrophage accumulation. In contrast to the effects on macrophages, granulocyte accumulation in vivo and chemotaxis in vitro was not depressed by the presence of a neoplasm or the administration of the factor from neoplasms. By releasing factors which depress macrophage migratory function, neoplasms may protect themselves from immunologically mediated host destruction during the early phases of tumor growth.

Animals↗

Selected observations on the epidemiology of pharyngeal cancers.

The epidemiology of nasopharyngeal cancer (NPC) has been compared with that of other pharyngeal cancers in Los Angeles County. Epstein-Barr virus (EBV) antibody titers were elevated in Caucasians with pharyngeal squamous cell carcinomas regardless of subsite. As expected, an excess of NPC cases was found among Chinese. The role of various etiologic factors in NPC including EBV, inhaled carcinogens, and salted fish was discussed.

Antibodies, Viral↗

Estrogens and endometrial cancer in a retirement community.

All cases of endometrial cancer occurring among the residents of an affluent retirement community were compared with controls chosen from a roster of all women in the same community. Evidence of estrogen and other drug use and of selected medical conditions was obtained from three sources: medical records of the principal care facility, interviews, and the records of the local pharmacy. The risk ratio for any estrogen use was estimated from all available evidence to be 8.0 (95 per cent confidence interval, 3.5 to 18.1). and the for conjugated estrogen use to be 5.6 (95 per cent confidence interval, 2.8 to 11.1). Increased risk from estrogens was shown for invasive as well as noninvasive cancer, and a dose-response effect was demonstrated. For an estrogen user, the risk from endometrial cancer appeared to exceed by far the base-line risk from any other single cancer.

Age Factors↗

An inhibitor of macrophage chemotaxis produced by neoplasms.

The accumulation of macrophages at neoplastic sites may be an important event in immunologically mediated tumor killing. The implantation of syngeneic neoplasms in mice, however, was found to depress the animal's ability to localize macrophages at inflammatory sites. A low-molecular-weight (6,000 to 10,000) factor released by growing neoplasms that inhibits the accumulation of macrophages in vivo and chemotactic responsiveness in vitro was identified. The factor is active in the inhibition of macrophages and is ineffectual at retarding the migration of polymorphonuclear leukocytes. Neoplastic cells may thus abrogate immunosurveillance by releasing products that prevent potentially tumoricidal macrophages from accumulating at sites of developing malignancies.

Animals↗

Epidemiology of childhood leukaemia in greater london: A search for evidence of transmission assuming a possibly long latent period.

Studies of space-time clustering of cases of childhood leukaemia have yielded equivocal results. This might be because the disease has a long and variable latent period, in which case the usual statistical tests for such clustering are inappropriate. A new statistical method is described which allows for such latent periods. For each patient, periods of "susceptibility" and "infectivity" are defined in which it is assumed he respectively "caught" and could "transmit" the disease. The measure of clustering is taken as the number of patients who were in the "right" place at the "right" time to "catch" the disease from another patient. This test is applied to childhood acute lymphoblastic leukaemia (death before age 6) in Greater London in the period 1952-65. Cases are postulated to be "susceptible" at various times before clinical onset of leukaemia, including in utero, and "infective" at various times around onset. Their effective "contacts" at these times are defined as circles of radius up to 4 km around their places of residence at these times. Slight evidence of clustering was found associated with certain of the defined times and distances, but the degree of clustering was small and could reasonably be attributed to chance. It is suggested, however, that this method of analysis might usefully be applied to other sets of such data. No evidence was found to add to our previously reported finding of space-time clustering of the dates and places of birth of children with leukaemia.

Child, Preschool↗

Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design.

The Medical Research Council has for some years encouraged collaborative clinical trials in leukaemia and other cancers, reporting the results in the medical literature. One unreported result which deserves such publication is the development of the expertise to design and analyse such trials. This report was prepared by a group of British and American statisticians, but it is intended for people without any statistical expertise. Part I, which appears in this issue, discusses the design of such trials; Part II, which will appear separately in the January 1977 issue of the Journal, gives full instructions for the statistical analysis of such trials by means of life tables and the logrank test, including a worked example, and discusses the interpretation of trial results, including brief reports of 2 particular trials. Both parts of this report are relevant to all clinical trials which study time to death, and wound be equally relevant to clinical trials which study time to other particular classes of untoward event: first stroke, perhaps, or first relapse, metastasis, disease recurrence, thrombosis, transplant rejection, or death from a particular cause. Part I, in this issue, collects together ideas that have mostly already appeared in the medical literature, but Part II, next month, is the first simple account yet published for non-statistical physicians of how to analyse efficiently data from clinical trials of survival duration. Such trials include the majority of all clinical trials of cancer therapy; in cancer trials,however, it may be preferable to use these statistical methods to study time to local recurrence of tumour, or to study time to detectable metastatic spread, in addition to studying total survival. Solid tumours can be staged at diagnosis; if this, or any other available information in some other disease is an important determinant of outcome, it can be used to make the overall logrank test for the whole heterogeneous trial population more sensitive, and more intuitively satisfactory, for it will then only be necessary to compare like with like, and not, by chance, Stage I with Stage III.

Clinical Trials as Topic↗

Burkitt's lymphoma in the Mengo Districts of Uganda: epidemiologic features and their relationship to malaria.

An epidemiologic study of 123 patients residing in the Mengo Districts of Uganda, with onset of symptoms of diagnosed Burkitt's lymphoma (BL) in the period 1959-68, revealed a substantial decline in incidence of BL during that decade. Other significant findings included differences by ethnic group in age of patient at onset of BL, a change in the proportions of patients by ethnic group over the decade, a lower incidence rate of BL in the countries of higher altitude, and a seasonal pattern of onset. There was no evidence of the time space clustering previously reported for BL in Uganda. The changing pattern of BL in the Mengo Districts was consistent with the hypothesis that severe malaria infection not only is important in the development of BL but also precipitates onset.

Adolescent↗

Exogenous estrogens and breast cancer in women with natural menopause.

Age, age at menopause, and calendar year at menopause were controlled as factors related to estrogen use. Data on 90 breast cancer patients and 83 conrols--all of whom had a natural menopause--showed no relationship between breast cancer and estrogen usage after the start of menopause symptoms.

Age Factors↗

Current epidemiological evidence for transmission of Hodgkin's disease.

The epidemiological evidence relating to the possibility of person-to-person transmission of Hodgkin's disease is reviewed. A number of studies are found to be difficult to interpret because of the absence of control data. It is concluded that, although certain studies are consistent with the hypothesis of person-to-person transmission, the evidence is a present weak and further epidemiological studies are needed.

Disease Outbreaks↗

Effects of neoplasms on inflammation: depression of macrophage accumulation after tumor implantation.

The local accumulation of macrophages at sites of neoplasms may be a critical event in immunologically mediated tumor killing. Individuals with neoplasms, however, have been noted to have depressed monocyte chemotactic responsiveness in vitro. To determine the effect of neoplasms on macrophage migration, mice were implanted subcutaneously with either sarcoma or hepatoma cells and their macrophage migratory function quantified in vivo and in vitro. The ability of tumor-bearing animals to mobilize macrophages to an inflammatory site in vivo was depressed by as much as 61% by 6 days after tumor implantation. The in vitro chemotactic responsiveness of macrophages recovered from the peritoneal cavities of tumor-bearing animals was also markedly depressed. Macrophage migration was not affected by implantation of normal syngeneic or allogeneic tissues. In addition, the accumulation of polymorphonuclear leukocytes in vivo was not depressed in tumor-bearing animals. These findings suggest that neoplasms themselves may depress the host's ability to localize macrophages at inflammatory sites in vivo and thereby hinder immunologically mediated tumor destruction.

Animals↗