Hormone replacement therapy, hormone levels, and lipoprotein cholesterol concentrations in elderly women.

OBJECTIVE: Our purpose was to assess the relationships of lipid and lipoprotein cholesterol levels to hormone replacement therapy and hormone levels in elderly women. STUDY DESIGN: A sample of 292 postmenopausal women 55 to 99 years old (mean 76 years) was drawn from Leisure World Laguna Hills, California, an upper-middle-class, white independent-living population. We compared 84 women receiving unopposed estrogen replacement therapy and 38 women taking combination hormone replacement therapy with 170 women who had never used hormone replacement therapy. Nonparametric tests for differences in lipid and lipoprotein cholesterol levels among groups and multiple stepwise regression models were used. RESULTS: Estrogen users (with and without progestin) had lower total and low-density lipoprotein cholesterol and higher high-density lipoprotein and high-density lipoprotein subfraction types 2, 2a, and 2b cholesterol levels. High density lipoprotein type 3 subfractions were lower in combination hormone replacement therapy users but higher in unopposed estrogen users relative to nonusers. The conjugated equine estrogen dose was negatively correlated with total (p = 0.0009) and low-density lipoprotein cholesterol (p <0.0001) levels and positively correlated to high-density lipoprotein cholesterol (p = 0.002) and its subfractions. The medroxyprogesterone acetate dose showed no consistent effect on cholesterol levels. CONCLUSION: The associations found here reaffirm the significant role of estrogen replacement therapy on lipid and lipoprotein cholesterol levels and provide no evidence of a reduction in the beneficial effect of estrogen with the addition of a progestational agent to the replacement regimen.

Gonadotropin hormone releasing hormone agonists [GnRHA] and prevention of familial breast cancer.

The use of GnRHA to induce a "medical" oophorectomy may be a useful method of prevention of breast carcinoma. The addition of ERT and intermittent progestogen to the GnRHA would be expected to prevent the adverse effects of estrogen deprivation, and still provide a significant reduction in breast cancer risk. Evaluation of the regimen in a high risk group such as sisters or daughters of index cases of early onset breast cancer is justifiable.

Lymphocyte immunophenotyping in an elderly population: age, sex and medication effects--a flow cytometry study.

Flow cytometry studies of 179 individuals aged 55-95 years reveal correlations of various hematological and immune cell measures (quantification of leukocytes, leukocyte subtypes, platelets, and erythrocytes) with age, sex, common medications (aspirin, ulcer therapy, estrogen replacement therapy), and health history variables (minor arthritis, allergy, smoking, stress and exercise). Possible reasons for some of these findings are discussed.

Cancer incidence in the islands of the Pacific.

The South Pacific Commission Cancer Registry has been operational since 1977, and reasonably complete cancer incidence rates are available for New Caledonia, Fiji, Micronesia, the Cook Islands, and Niue. In addition, less complete reporting is available from American Samoa, Papua New Guinea, and French Polynesia. Cancers of the lung, oral cavity, esophagus, liver, and cervix are potentially preventable but prevalent in many Pacific island countries. Unusually low rates of many cancers were observed in Fiji, the most notable being lung and colon-rectum. Thyroid cancer rates are elevated in some but not all female populations. These and other variations in cancer by site are important areas for further research.

Kaposi's sarcoma in Los Angeles, California.

The demographic characteristics of "classic" Kaposi's sarcoma (KS) and of "epidemic" KS in Los Angeles, CA, were compared with the use of data from the Cancer Surveillance Program, the population-based tumor registry in Los Angeles County. The data obtained document the magnitude of the excess risk of classic KS for Jewish men of European (especially Eastern and Southern European) origin. The data also show in a systematic way the magnitude of the increase in acquired immune deficiency syndrome-related KS in one large urban area of the United States. In addition, they demonstrate that the demographic risk factors of religion and birthplace for classic KS are unrelated to epidemic KS and that the clinical presentation in terms of stage and primary site of classic KS is distinct from that of the epidemic form of the disease.

Retrovirus and malignant lymphoma in homosexual men.

We report malignant lymphoma in 27 homosexual men, of whom 22 had high-grade lymphomas (B-cell immunoblastic sarcoma or small non-cleaved lymphoma) and five had low-grade disease. Antibody to human T-cell lymphotropic virus type III (HTLV-III) was present in 13 (87%) of 15 with high-grade lymphoma and in two (40%) of five with low-grade disease. In contrast, only one (9%) of 11 "control" heterosexual patients with high-grade lymphoma had antibody to HTLV-III, while such antibody was found in none of 40 asymptomatic heterosexual controls and in 17 (55%) of 31 asymptomatic homosexual men. Of the homosexual lymphoma patients, 85% presented with disease in extranodal sites, including the central nervous system and rectum, and 81% had reversed T-helper/suppressor ratios. Median survival, despite treatment, is eight months. The acquired immunodeficiency syndrome-related lymphomas in homosexual men are extranodal, high-grade, B-lymphoid tumors, associated with exposure to HTLV-III and unusual clinical characteristics.

Primary central nervous system lymphoma in homosexual men. Clinical, immunologic, and pathologic features.

Primary central nervous system lymphoma constitutes one of the criteria for the acquired immune deficiency syndrome (AIDS), yet a paucity of information is currently available regarding the clinical, immunologic, or pathologic features of these patients. Six homosexual men presenting with primary central nervous system lymphoma were evaluated. Five of these patients presented with altered mental status. All lymphomas were intracranial. B cell immunoblastic sarcoma was found in five. Immune phenotyping studies performed in five patients revealed monoclonal lambda light chain in three, whereas one expressed only IgG heavy chain, and one demonstrated another B cell (LN-1) surface antigen. Hypodense, contrast-enhancing lesions were apparent on computed axial tomographic scanning of the brain, in sharp contrast to isodense or hyperdense lesions reported in primary central nervous system lymphomas without underlying immunodeficiency. Immunologic abnormalities in these patients were similar to those in AIDS presenting as Kaposi's sarcoma or with opportunistic infections. In spite of therapeutic interventions, survival was short, and only one patient is currently alive.

B-cell lymphoma in two monogamous homosexual men.

Opportunistic infections and malignant neoplasms have been described in homosexual men in association with immunologic abnormalities. We observed the development of malignant B-cell lymphomas in two homosexual men who had had a monogamous relationship for two years. Patient 1 had an aggressive, monoclonal, small, noncleaved, non-Burkitt's lymphoma ("undifferentiated lymphoma"), associated with severe immunocompromise. Patient 2 manifested a monoclonal, small, cleaved, follicular center cell lymphoma, with a follicular pattern, two months later. No common acute infection was detected. Staining for Epstein-Barr nuclear antigen in malignant tissue was negative in the second patient. However, the possibility of a transmissible agent as a causative factor cannot be excluded, and further study of similar patients is warranted.

Immune responses of healthy humans 83-104 years of age.

The immune responses of 19 healthy people 83-104 years of age were compared to those of younger healthy persons. A decline in mitogen response to concanavalin A and pokeweed mitogen, but not to phytohemagglutinin, was observed. Positive skin test to two recall antigens occurred in only 5 of the 19 aged people; 4 of these 5 reported a history of blood transfusion. Antibody titers were elevated for persistent DNA viruses but not for RNA viruses. An excess of ABO blood type B was found, but no human leukocyte antigen (HLA)-A or HLA-B type was found in elevated proportion.

Asbestos exposure and lymphomas of the gastrointestinal tract and oral cavity.

An epidemiological case-control study of non-Hodgkin's lymphomas revealed an excess of male patients with large-cell lymphomas primary to the gastrointestinal tract and oral cavity who had evidence of substantial exposure to asbestos. Between 1977 and 1981, 28 men with large-cell lymphomas primary to these sites were interviewed about previous environmental exposure. Pathology slides from 26 of these cases were reviewed by haematopathologists, who confirmed each to be non-Hodgkin's lymphoma of large-cell type. Neighbourhood controls were matched to patients for age, race, and sex. 13 matched pairs were discordant for asbestos exposure, and in 12 of these the exposed individual was a lymphoma patient. 10 patients and 1 control also reported a history of malaria.

Risk factors for nodular sclerosis and other types of Hodgkin's disease.

The age-adjusted incidence rates of nodular sclerosis in Los Angeles County from 1972 to 1975 were 58% lower in Mexican-Americans and 42% lower in blacks than in other whites. They were the same for each sex among other whites and the curve of age-specific incidence peaked in young adulthood. The incidence of nodular sclerosis was directly associated with social class. In contrast, the rates for other histological varieties of Hodgkin's disease (lymphocyte predominance, mixed cellularity, lymphocyte depletion) were only 12% lower in Mexican-Americans but 34% lower in blacks. In other whites, the rates were 92% higher in men and increased gradually with age while there were no clear trends with social class. These characteristics support the hypothesis that, at least for purposes of etiology, the nodular sclerosis form of this disease should be considered a distinct entity. Self-administered questionnaire were completed by 218 of the 1972 to 1973 Hodgkin's disease patients and 218 individually matched neighbourhood controls. Significantly high risk ratios for Hodgkin's disease were found for prior appendectomy (risk ratios = 1.9, p = 0.01) and for past amphetamine use (risk ratios = 3.0, p = 0.01). The elevated risk associated with amphetamine use had been found in a previous study.

Immune function in healthy relatives of patients with malignant disease.

Immune function studies of healthy members of families with multiple lymphoreticular neoplasms were compared with those of healthy members of families with multiple cancers and families with no known history of cancer. The lymphoma family group had a significantly elevated serum level of IgM and diminished responses to the Candida albicans skin test antigen and the T-cell mitogen concanavalin A. Subjects with Epstein-Barr virus-viral capsid antigen titers greater than or equal to 160 had lower responses to mitogens.

FeLV epidemiology in Los Angeles cats: Appraisal of detection methods.

We investigated the reliability of the fixed cell indirect fluorescent antibody (IFA) peripheral blood smear test as an index of systemic infection with FeLV. Positive results with this test were found to correlate well with detectable FeLV p30 antigen in bone-marrow smears by IFA, in serum and tissue by competition immunoassays, and with type-C particles in bone marrow or spleen by electron microscopy. Most cats with lymphoma, anemia or infectious peritonitis were positive for FeLV and showed a poor or absent antibody response to FeLV p30, gp70, and FOCMA antigens. Most older cats with lymphoma, carcinoma, or sarcoma were negative for FeLV expression and also lacked these FeLV-related antibodies. Detectable immunologic response to FeLV p30 and gp70 proteins and a high-titered FOCMA antibody response were generally restricted to certain healthy cats exposed to FeLV. Antibody to endogenous RD-114 viral p30 and gp70 was not detected in any of a large number of feline sera tested. The prevalence of FeLV-related diseases and immunologic responses to FeLV in healthy cats was directly correlated with the degree of FeLV exposure. By using the IFA blood smear and FOCMA antibody tests one can monitor the horizontal spread of FeLV in multi-cat household and accurately predict the FeLV disease susceptibilty or resistance of individual cats in each environments.

Lower motor neuron disease in wild mice caused by indigenous type C virus and search for a similar etiology in human amyotrophic lateral sclerosis.

In certain genetically susceptible populations of wild mice a progressive motor neuron disease with a long latent period is caused by indigenous type C leukemia virus. Neuronal damage appears to be due primarily to a direct neurotropic effect of the virus and not to an immunogenic mechanism. The disease can be prevented by antiviral genetic means. Search for a similar virus in humans with ALS has been negative.

Excess leukemia in cohorts of children born following influenza epidemics.

Two series of data from the California State Department of Health and one from Children's Hospital of Los Angeles were analyzed to determine whether an association exists between influenza epidemics and incidence of leukemia in children born following such outbreaks. Of leukemic children born in areas for which information on past influenza activity was available, the population-based Alameda County Cancer Registry recorded 89 cases during 1960-1969, the California Tumor Registry recorded 653 cases during 1950-1970, and Children's Hospital recorded 575 cases during 1957-1972. Flu epidemics were identified and flu cohorts constructed such that leukemic children who could have been in utero during a flu epidemic constituted a flu cohort. Based on the total number of leukemia cases reported and the proportion of at-risk weeks contributed by the flu cohort, expected numbers of leukemia cases from the flu cohort were computed for each age. In each series, there was an excess of leukemia cases in the flu cohort, contributed primarily by the 0-4 age group. Trimester analysis indicated that the greatest excess occurred in children who were in the first trimester of gestation during a flu epidemic. Incidence data from the Cancer Incidence System of the San Francisco Bay Area Resource for Cancer Epidemiology and the Third National Cancer Survey show a relative risk of 3.4 for this group. Due to sources of misclassification in this study, such as analysis of flu cohorts rather than individuals whose mothers actually had influenza during pregnancy, the results tend to be diluted. If influenza is a causative factor, the actual increase in leukemia risk is likely to be much greater than this analysis indicates.