Randall A. Coates

Treatment of Small Cell Lung Cancer in the Elderly

Objective: Since both the incidence of lung cancer and the proportion of the population over age 65 are increasing rapidly in North America, we undertook a retrospective review of elderly patients with small cell lung cancer (SCLC) in an attempt to assess the effect of age on treatment decisions, response, survival, and toxicity.

Using serial observations to identify predictors of progression to aids in the Toronto Sexual Contact Study

The Toronto Sexual Contact Study comprises a cohort of 249 male sexual contacts of men with HIV disease which has been followed every 3 months for almost 5 years. On enrollment 143 were seropositive and 16 seroconverted during the follow-up period. By 31 December 1989, 41 of the 159 seropositive cohort members had developed AIDS. Using Cox relative risk regression models, we investigated the association of a number of laboratory and clinical variables and progression to AIDS. Fixed covariate models examined laboratory variables from the enrollment visit of cohort members, with time calculated from this date. In models assessing time dependent covariates, time was calculated from the estimated date of HIV infection. In the univariate models of either fixed or time dependent covariates, many variables were significantly associated with risk of progression to AIDS (T4 cell count, T4/T8 ratio, blastogenic responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen, serum IgA, appearance of p24 antigen, and the development of oral hairy leukoplakia, thrush, or herpes zoster). Appearance of persistent generalized lymphadenopathy was not associated with increased risk of progression. In the multivariate model which evaluated fixed laboratory covariates, T4/T8 ratio, IgA level, and PHA response at enrollment were significantly associated with elevated risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Ongoing high-risk sexual behaviors in relation to recreational drug use in sexual encounters Analysis of 5 years of data from the Toronto sexual contact study

The current study investigated the association between the use of recreational drugs at the time of sexual activity and high-risk sexual behavior in a Toronto cohort of 249 homosexual and bisexual men over a 5-year period commencing in 1984 to 1985 and concluding in 1989 to 1990. The main analysis was based on a total of 2536 visits. Univariate and multivariate Liang-Zeger regression models were used to relate the log of the sexual activity score (SARS) to the independent variables over the 20 follow-up visits while controlling for intercorrelations between variables from the same respondent. We found that there was a significant decline, over time, in the sexual activities that pose a higher risk of infection with human immunodeficiency virus. Recreational drugs still appear to be playing an important role in the continuation of higher-risk sexual activities. The use of poppers in conjunction with sex is a strong predictor of high-risk activity, as is use of alcohol and marijuana in conjunction with sex. Also, simultaneously strongly associated with higher-risk score is the Centers for Disease Control classification II. More emphasis needs to be placed on educating the population about the potential risks of combining reactional drugs with sexual activity.

Alcohol consumption and blood pressure: analysis of data from the Canada Health Survey.

Recent epidemiologic studies report a significant association between alcohol consumption and elevations in both systolic (SBP) and diastolic (DBP) blood pressures. To test this hypothesis, we conducted a multivariate analysis of physical examination and other data on 721 men and 697 women aged 20 or more collected during the Canada Health Survey in 1978-1979. SBP and DBP were considered as separate dependent variables in multiple regression models with the following independent variables: age, alcohol consumption (measured as a 7-day recall history and as an average frequency of consumption), serum cholesterol, plasma glucose, physical activity, Quetelet index, parental history of hypertension, cigarette consumption, income, education, and exogenous hormonal use in women. In both weighted and unweighted multiple regression analyses, we could not demonstrate for either sex, a significant association between alcohol consumption (as recorded and following quadratic and logarithmic transformations) and either SBP or DBP. For both sexes, only age and Quetelet index were highly significantly (P less than 0.0001) and consistently associated with both SBP and DBP. No other independent variables were consistently associated, for either sex, with SBP and DBP. Further, the dose-response patterns noted by other investigators suggesting either a positive and linear relationship or a curvilinear relationship were not found in either our univariate or multivariate analyses. Rather, the alcohol-blood pressure curves showed no consistent patterns of any kind in either sex. These findings do not support recent claims that alcohol consumption is a determinant of elevations in either SBP or DBP.

Relationship between hepatitis B surface antigen prevalence, per capita alcohol consumption and primary liver cancer death rate in 30 countries

The relationships between the prevalence of hepatitis B surface antigen (HBsAg), mean annual per capita alcohol consumption and primary liver cancer (PLC) death rates were explored in 30 countries. HBsAg prevalence was associated, significantly, with the logarithm of the primary liver cancer death rate (simple correlation coefficient = 0.44, p less than 0.05). This significant association increased following adjustment for a countrys mean annual per capita alcohol consumption (partial correlation coefficient = 0.53, p less than 0.01). A logarithmic linear relationship was also found between per capita alcohol consumption and the primary liver cancer death rate after adjustment for the countrys prevalence of HBsAg (partial correlation coefficient = 0.38, p less than 0.05). Results from both correlation and regression analyses showed that prevalence of HBsAg was more significantly associated with PLC death rates than was alcohol consumption. However, these two variables were independently related to the PLC death rate in a stepwise multiple regression model. We could not demonstrate an interaction between the two variables. These findings are consistent with the prevailing view that chronic hepatitis B infection is the major factor in the most common form of primary liver cell cancer, hepatocellular carcinoma. In addition, they support the notion that alcohol consumption contributes significantly and independently, although probably to a lesser extent than hepatitis B, to deaths from that disease.

Sexual Modes of Transmission of the Human Immunodeficiency Virus (HIV)

Soon after the Acquired Immunodeficiency Syndrome (AIDS) was initially described, the epidemiology of the syndrome suggested that a blood-borne, sexually transmitted agent was an important factor in the development of the syndrome. The identification and isolation of the human immunodeficiency virus (HIV) as the etiologic agent of AIDS, followed by the development of sensitive and specific assays for the detection of antibodies to its viral proteins, facilitated the study of specific forms of transmission of the virus as well as the natural history of HIV infections. In this paper, the current evidence is reviewed regarding the modes of sexual transmission of HIV in homosexuals and heterosexuals. Several well designed studies support the efficient transmission of HIV via receptive and insertive anal intercourse and by vaginal intercourse. There is no current evidence, despite detailed study, to suggest that kissing, oral-genital, or oral-anal sexual contact provides an efficient means of viral transmission. Activities which promote or result in anorectal or vaginal mucosal injury appear to facilitate infection with this virus.

Assessment of generalized lymphadenopathy in aids research: The degree of clinical agreement

The degree of clinical agreement amongst different physicians on the presence or absence of generalized lymphadenopathy was assessed in 32 randomly selected participants from a prospective study of male sexual contacts of men with AIDS or an AIDS-related condition (ARC). Three physicians completed the same standard examination that was developed for the main project and conducted the examination of the anatomic regions in the same order on each person, at approximately the same time, and in random order. One physician (Doctor A) was the physician responsible for conducting examinations on the main cohort from which these participants were selected. Intra-observer agreement was assessed by comparing Doctor As examinations on these participants with those he had recently conducted within a one and a half month period in the main study. Acceptable levels of intra-observer agreement (kappa = 0.72) and interobserver agreement (kappa = 0.66) were demonstrated for the presence or absence of generalized lymphadenopathy for Doctor A and Doctor B, a physician who periodically replaced Doctor A in the main project. Agreement between Doctors A, B, and C, was less satisfactory (kappa of 0.45 and 0.39, respectively). Doctor C was the least experienced with the standardized examination. However, during the progress of this study, agreement between the three doctors improved (kappa values for the latter 16 participants ranged from 0.60 to 0.86) suggesting that experience with the criteria and the standardization of the examination may enhance agreement.(ABSTRACT TRUNCATED AT 250 WORDS)

Human Immunodeficiency Virus Infection and the Acquired Immune Deficiency Syndrome: A Review

We are currently witnessing a global epidemic of a group of diseases which are known as AIDS and which have in common an underlying profound impairment of the host immune system. The causative agent, human immunodeficiency virus (HIV), has been identified and testing for antibodies to this virus has demonstrated its spread into many populations around the world. HIV is now known to give rise to a wide clinical spectrum including asymptomatic infection, progressive central nervous system infection, and the fatal immune deficiency termed AIDS. The proportion of HIV-infected persons who will eventually develop AIDS cannot be known with precision at this time although it is likely to be at least 40% and could be as high as 100%. AIDS and HIV have been reported in over half of the countries in the world including the USSR and China. The global distribution follows 3 epidemiologic patterns: that of the developed countries where the virus has primarily affected homosexual/bisexual men and intravenous drug users; that of Central Africa and parts of the Caribbean where it is essentially a heterosexually transmitted disease; and that of Asia and most of Central and South America where the disease is still rare. Although HIV has been recovered from peripheral blood, semen, saliva, tears, alveolar fluid, cerebrospinal fluid, brain tissue, and cervical and vaginal secretions, there is much data to indicate that its modes of spread are limited to sexual, parenteral (i.e. contaminated needles), iatrogenic (i.e. blood and blood products, transplantation, etc.), and perinatal (i.e. mother to offspring). There is now substantial evidence to indicate that casual contact, that is the type of non-sexual personal contact that might occur in the household, school setting, or workplace, does not give rise to HIV transmission. Similarly, transmission of HIV by insect vectors, e.g, mosquitoes, has also been effectively ruled out.