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PubMed1998

Association of persistent bronchial hyperresponsiveness with beta2-adrenoceptor (ADRB2) haplotypes. A population study.

Bronchial hyperresponsiveness (BHR) is a hallmark of asthma and represents a strong risk factor for the disease. However, not all asthmatics have BHR and it can be observed in normal subjects too, probably because of genetic predisposition. Increasing attention is being focused on the beta2-adrenoceptor gene (ADRB2), whose genetic variability at amino acids 16 and 27 has been shown to correlate with some clinical features of asthma, including airways reactivity. To verify whether ADRB2 gene polymorphisms can influence BHR at a broader level, we studied a large, highly homogeneous sample of individuals sharing race, gender, age, and current living environment. BHR was strictly defined as a constant positive response to serial methacholine challenge tests and an improved definition of genetic variability at the ADRB2 locus was used, by identifying the haplotypic combinations of polymorphisms 16 and 27. We observed that the ADRB2 haplotype with a Gly at position 16 and a Gln at position 27 is associated with BHR in our sample. The association persisted also after correction for potentially confounding variables such as specific and total IgE levels. This observation suggests therefore that ADRB2 gene can confer genetic susceptibility to BHR, rather than having only a disease-modifying effect in asthma.

Adolescent↗

PubMed1975

[Epidemiological assessment of the system of indices characterizing the quality of vaccine preparations].

The authors discuss the methodology and the method of formation of the medico-technical requirements to newly-elaborated or modified vaccine preparations. The following are considered among the principal parameters responsible for the formation of the quality of the vaccines: the prophylactic activity, the extent of the injurious effect, the technological and the exploitation properties. A close association of these parameters in the determination of the quality of the vaccine and the dependence of the efficacy of its use on the character of the epidemic situation was shown. A possibility of using the method of calculation of the efficacy of immunization for detection of the main (leading) parameters of the quality of the vaccine elaborated which should be used in composing the medico-technical requirements. It is emphasize that one of the principal directions of the investigations is the elaboration and the assessment of the correctness of the immunological and laboratory methods of standardization and control of the methods of objective measurement of the parameters forming the quality of the vaccine preparations.

Evaluation Studies as Topic↗

PubMed1989

Alcohol, cancer, and immunomodulation.

There is a great deal of epidemiological evidence indicating that chronic, excessive alcohol consumption is a major risk factor for cancers in humans. However, the experimental basis for the increased cancer risk associated with alcohol intake is not clear. Since it appears that ethanol alone is not carcinogenic, ethanol effects must be explained in terms of its modifying the actions of other causal agents. Current studies indicate that ethanol and its congeners may act as tumor promoters, thereby enhancing the effect of initiating carcinogens from the environment. Available evidence also shows that ethanol is immunosuppressive. Clearly, cirrhosis due to high, prolonged alcohol intake is an indicator of the immunosuppressive effects of ethanol. It is less clear that more moderate intakes of alcohol could have as profound an effect on immune systems. However, changes do occur yielding alterations in lymphocyte sensitivity to alcohol in vitro and in cell development, as shown by increased NK cell function at low concentrations. Since other conditions, such as cytotoxic drugs which suppress cellular immune functions, are clearly associated with increased cancer risk. It is intriguing to think that prolonged exposure to ethanol-induced immunosuppression may be a cofactor in the promotion of cancer. The tumor promotion may take place via a variety of mechanisms as discussed in this paper, including reduced host defenses by direct effects of ethanol, its metabolites, and/or malnutrition. It may be beneficial to test methods for immunostimulation in prolonged alcohol abusers, where cessation of use is unsuccessful or residual immunosuppression remains, to reduce the risk of development or growth of initiated tumors.

Alcoholism↗

PubMed1988

Correlates of cognitive function in an elderly community population.

In 1982 and 1983, brief, structured performance tests of selected areas of cognitive function were administered to 3,682 (82.1 per cent) of the residents aged 65 years and older of the geographically defined community of East Boston, Massachusetts, a center of the Established Populations for Epidemiologic Studies of the Elderly program. There was a strong inverse relation between age and performance on all four cognitive tests in analyses adjusted for sex only as well as in those adjusted for the effects of other variables. Similarly, fewer years of formal education, increasing level of disability on the modified Katz Activities of Daily Living Scale, and less prestigious occupations, as measured by the modified Duncan Socioeconomic Index, were each independently related to lower performance on all four tests.

Activities of Daily Living↗

PubMed1999

Determinants of long term survival after surgery for cancer of the lung: A population-based study.

BACKGROUND: Even if some determinants of lung cancer (LC) prognosis have been established, their independent effect on long term survival remains to be seen. The objective of the current study was to identify the prognostic indicators of long term survival among LC patients treated by surgery. METHODS: All patients with LC recorded at the Geneva Cancer Registry between 1977 and 1987 were analyzed by logistic regression, considering as cases (n = 98) those patients alive 10 years after their initial diagnosis and as controls (n = 330) all other patients, excluding those who did not undergo putative curative surgery. The effect of each prognostic factor was evaluated after accounting for age and gender ("crude" effect) and also for other a priori confounding factors (adjusted effect). Additional models considered two staging variables simultaneously to identify the strongest staging determinant. Results were presented as relative risk estimates of long term (>/=10 years) survival. RESULTS: Age, histology, and stage of disease significantly influenced prognosis regardless of the confounding factors considered. Gender also emerged as a discriminated factor in LC outcome, with a 2.1-fold increased chance (95% confidence interval, 1.6-3.5) of long term survival for women compared with men. Method of discovery, presence of symptoms, period of diagnosis, socioeconomic status, and tumor differentiation did not appear to be associated with long term survival. Extent and size of the tumor were found to be the most reliable prognostic staging factors, whereas adenopathy had no effect after accounting for extension. CONCLUSIONS: The current population-based study quantifies the independent effect of the factors modifying the chances of curability in patients with LC. In particular, it provides additional evidence that gender strongly influences long term survival.

Adult↗

PubMed2005

Ozone exposure and mortality: an empiric bayes metaregression analysis.

BACKGROUND: Results from time-series epidemiologic studies evaluating the relationship between ambient ozone concentrations and premature mortality vary in their conclusions about the magnitude of this relationship, if any, making it difficult to estimate public health benefits of air pollution control measures. We conducted an empiric Bayes metaregression to estimate the ozone effect on mortality, and to assess whether this effect varies as a function of hypothesized confounders or effect modifiers. METHODS: We gathered 71 time-series studies relating ozone to all-cause mortality, and we selected 48 estimates from 28 studies for the metaregression. Metaregression covariates included the relationship between ozone concentrations and concentrations of other air pollutants, proxies for personal exposure-ambient concentration relationships, and the statistical methods used in the studies. For our metaregression, we applied a hierarchical linear model with known level-1 variances. RESULTS: We estimated a grand mean of a 0.21% increase (95% confidence interval = 0.16-0.26%) in mortality per 10-microg/m increase of 1-hour maximum ozone (0.41% increase per 10 ppb) without controlling for other air pollutants. In the metaregression, air-conditioning prevalence and lag time were the strongest predictors of between-study variability. Air pollution covariates yielded inconsistent findings in regression models, although correlation analyses indicated a potential influence of summertime PM2.5. CONCLUSIONS: These findings, coupled with a greater relative risk of ozone in the summer versus the winter, demonstrate that geographic and seasonal heterogeneity in ozone relative risk should be anticipated, but that the observed relationship between ozone and mortality should be considered for future regulatory impact analyses.

Air Pollutants↗

PubMed2006

Genetics of dopamine and its contribution to cocaine addiction.

Cocaine addiction is a major health and social problem for which there are presently no effective pharmacotherapies. Many of the most promising medications target dopamine based on the large literature that supports its role in addiction. Recent studies show that genetic factors are also important. Rodent models and gene knock-out technology have helped elucidate the involvement of specific genes in the function of the dopamine reward system and intracellular cascades that lead to neuronal changes in this system. Human epidemiological, linkage, and association studies have identified allelic variants (polymorphisms) that give rise to altered metabolism of dopamine and its functional consequences. Individuals with these polymorphisms respond differently to psychostimulants and possibly to pharmacotherapies. Here we review the literature on genetic variations that affect dopamine neurotransmission, responses to psychostimulants and potential treatments for cocaine addiction. Behavioral responses to psychostimulants in animals with different or modified genetics in dopamine signaling are discussed. We also review polymorphisms in humans that affect dopaminergic neurotransmission and alter the subjective effects of psychostimulants. Pharmacotherapies may have increased efficacy when targeted to individuals possessing specific genetic polymophisms in dopamine's metabolic and intracellular messenger systems.

Animals↗

PubMed2000

Hormone replacement therapy in the prevention and treatment of atherosclerosis.

As the population ages, the increasing number of women at risk for cardiovascular disease represents both a potential crisis and an opportunity in healthcare management. Although the overall death rate from cardiovascular disease in the general population is decreasing, the absolute numbers for women are increasing. A reduction in modifiable risk factors in women must be aggressively pursued by clinicians and health systems. Menopause is associated with many adverse effects on cardiovascular-disease risk factors in women. Estrogen replacement therapy has been shown to favorably influence many risk factors for cardiovascular disease. Despite this biologic plausibility and supporting evidence from epidemiologic studies, data from confirmatory clinical trials are lacking. Because of this, recommendations for hormone replacement therapy should be made on an individual basis.

Animals↗

PubMed1987

Fiber, stool bulk, and bile acid output: implications for colon cancer risk.

Dietary fiber has direct effects on stool bulk and bile acid output that may be of relevance in the etiology of colon cancer. Most types of fiber increase the total volume of stool and reduce the concentration of specific substances, including bile acids, that are in contact with the bowel wall. However, fibers differ in their effect on stool bulk, with wheat fiber being a more effective stool bulking agent than fruit and vegetable fibers. In addition, the extent to which a specific fiber reduces bile acid concentration will be modified by its concomitant effects on total fecal sterol excretion. Whereas wheat bran reduces fecal bile acid concentration, pectin, lignin, and oat bran do not. These three fibers significantly increase total bile acid output. Bile acids act as promoters of colonic tumors in mutagenesis assay systems and in various animal models. Human epidemiological studies show a relationship between various dietary variables, including fat and fiber intake, fecal concentration of bile acids, and colon cancer risk.

Animals↗

PubMed2001

Inhalation toxicology of urban ambient particulate matter: acute cardiovascular effects in rats.

Wistar rats were exposed for 4 hours by nose-only inhalation to clean air, resuspended Ottawa ambient particles (EHC-93*, 48 mg/m3), the water-leached particles (EHC-93L, 49 mg/m3), diesel soot (5 mg/m3), or carbon black (5 mg/m3). Continuous data for physiologic endpoints (heart rate, blood pressure, body temperature, animal's activity) were captured by telemetry before and after exposure. Blood was sampled from jugular cannulas 1 to 3 days before exposure and at 2 and 24 hours after exposure, and by heart puncture on termination at 32 hours (histology group) or 48 hours (telemetry group) after exposure. Lung injury was assessed by 3H-thymidine autoradiography after the rats were killed. We measured endothelins (plasma ET-1, big ET-1, ET-2, ET-3) to assess the vasopressor components; nitric oxide (NO)-related metabolites (blood nitrate, nitrite, nitrosyl compounds, and plasma 3-nitrotyrosine) to assess the vasodilator components; and catecholamines (epinephrine, norepinephrine, L-DOPA, dopamine) and oxidative stressors (m- and o-tyrosine) for additional insight into possible stress components. Lung cell labeling was uniformly low in all treatment groups, which indicates an absence of acute lung injury. Inhalation of EHC-93 caused statistically significant elevations (P < 0.05) of blood pressure on day 2 after exposure, plasma ET-1 at 32 hours after exposure, and ET-3 at 2, 32, and 48 hours after exposure. In contrast, the modified EHC-93L particles, from which soluble components had been extracted, did not affect blood pressure. The EHC-93L particles caused early elevation (P < 0.05) of the plasma levels of ET-1, ET-2, and ET-3 at 2 hours after exposure, but the endothelins returned to basal levels 32 hours after exposure. Exposure to diesel soot, but not carbon black, caused an elevation (P < 0.05) of plasma ET-3 at 36 hours after exposure; blood pressure was not affected by diesel soot. Our results indicate that inhalation of the urban particles EHC-93 can affect blood levels of ET-1 and ET-3 and cause a vasopressor response in Wistar rats without causing acute lung injury. Furthermore, the potency of the particles to influence hemodynamic changes appears to be modified by removing polar organic compounds and soluble elements. Because the pathophysiologic significance of elevated endothelins has been clinically established in humans, our observations suggest a novel mechanism by which inhaled particles may cause cardiovascular effects. These findings in rats contribute to the weight of evidence in favor of a biologically plausible epidemiologic association between ambient particulate matter and cardiovascular morbidity and mortality in human populations.

Administration, Inhalation↗

PubMed1975

[Radioimmunologic determination of hepatitis antigen and its clinical implications].

The AA. carrie out an analysis of the results obtained by means of the radioimmunologic method and concludes as follows: 1) Au-positive acute hepatitis represent the more largely diffused form among adult people; 2) from a clinical point of view, it seems appropriate to modify definitions of A and B hepatitis, of infectious hepatitis or serum hepatitis, classifying this disease as follows: a) hepatitis with positive antigenemy; b) hepatitis with negative antigenemy; and this independently from the anamnestic and epidemiologic elements. In the second part of this report, the AA., after introducing some considerations on the effects of the therapy by means of steroids, illustrate the data concerning a study carried out on a group of Au-positive and Au-negative subjects, subdivided into treated and non treated patients. From these analysis, even if a statistical survey has not been made, no elements are noticed, able to differentiate the behaviour of the two groups of hepatitis studied, in comparison with the therapy by means of steroids. One single Au-negative case, within a certain period of time, after the therapy with steroids, showed the presence of a positivity of immunologic phenomena only by the radioimmunoassay.

Adolescent↗

PubMed1976

[Thrombogenic and atherogenic effects of dietary fats].

1. Epidemiologic studies have shown that CHD (arterial thrombosis) and venous thrombosis were closely associated with dietary saturated fat intake. 2. In vitro and in vivo studies are unanimous in that long chain saturated fatty acids, mostly-stearic acid, are thrombogenic, while linoleic acid has protective effects. 3. Stearic acid appears to modify the fatty acid composition of platelet phospholipids resulting in an increase in the aggregating and clotting capacities of platelets. 4. In coronary patients or in subjects eating saturated fats, similar modifications in platelet behaviour can be observed related to changes in platelet phospholipids. Those results appear to confirm the hypothesis that certain dietary saturated fats, in addition to induce hyperlipemia and atherosclerosis, predispose to thrombosis mostly through blood platelets.

Adult↗

PubMed2001

Modifying the natural history of atherosclerosis: the SECURE trial.

Experimental and epidemiological evidence suggests that activation of the reninangiotensin-aldosterone system and oxidative modification of low density lipoprotein cholesterol both play important roles in atherosclerosis. A substudy of the HOPE (Heart Outcomes Prevention Evaluation) trial, the SECURE trial (Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and vitamin E), evaluated the effects of long-term treatment with the angiotensin-converting enzyme (ACE) inhibitor, ramipril, and with vitamin E on atherosclerosis progression in high risk patients. A total of 732 patients were enrolled into the study. These patients were 55 years or older, had vascular disease or diabetes with at least one other cardiovascular risk factor, but did not have heart failure or low ejection fraction. Patients were randomly assigned according to a three-by-two factorial design to receive placebo, ramipril 2.5 mg/day or ramipril 10 mg/day and placebo or vitamin E 400 IU/day. Progression of atherosclerosis was evaluated by B-mode carotid ultrasonography. The primary outcome evaluated was the annualised progression slope of the mean maximum carotid intimal-medial thickness (IMT) across 12 pre-selected carotid arterial segments. The average follow-up was 4.5 years. The progression slope of the mean maximum IMT was 0.0217 +/- 0.04 mm/year in the placebo group, 0.018 +/- 0.44 mm/year in the ramipril 2.5 mg/day group and 0.0137 +/- 0.04 in the ramipril 10 mg/day group (P = 0.33 for the overall effect of ramipril and P = 0.028 for the comparison between patients receiving ramipril placebo and ramipril 10 mg/day). The reduction in atherosclerotic progression observed with ramipril remained significant after adjusting for systolic and diastolic blood pressure changes (P = 0.043) and after multivariate adjustment (P = 0.046). Administration of vitamin E 400 IU/day had no impact on atherosclerosis progression. The SECURE study is the first demonstration, in human subjects, of an effect of ACE inhibition on atherosclerotic progression. This benefit cannot be explained by the lowering of blood pressure alone. Vitamin E 400 IU/day had a neutral effect on the ultrasound measurements of atherosclerosis progression in the SECURE trial.

Aged↗

PubMed2000

Predictors of time to remission from depression in primary care patients: do some people benefit more from positive life change than others?

The authors examined the role of personality, social support, and coping strategies and their interaction with positive life change (PLC) in influencing time to remission from depression in 86 depressed primary care patients (69% women, mean age = 36.6 years), who were followed for 3.5 years. Diagnostic information was obtained by the Present State Examination (J. K. Wing, J. Cooper, & N. Sartorius, 1974), and life change by the Life Events and Difficulties Schedule (G. W. Brown & T. O. Harris, 1978). The association of PLC and other predictors with the time to remission was studied by means of Cox regression. PLC reduced time to remission in women, but not in men. Other predictors that expedited remission were low severity of premorbid difficulties, high self-esteem, and a tension-reducing coping style. Neuroticism modified the effect of PLC in that the remission forward bringing effect of PLC was stronger for highly neurotic people. The results suggests that women and psychologically vulnerable persons benefit most from PLC.

Adult↗

PubMedDate not supplied

Epidemiology of genital herpes - recent advances.

Genital herpes is a common, distressing infection which, due to increasing incidence world-wide, has become a prominent public health issue over recent years, even throughout the decade of human immunodeficiency virus (HIV). Since the late 1970's, the prevalence of herpes simplex virus type 2 (HSV-2) infection has increased by approximately 30 percent in the US. The number of sufferers world-wide is currently estimated at approximately 86 million people. New serological methods based on the detection of type-specific antibodies to herpes simplex virus (HSV) glycoproteins have clarified issues concerning the true incidence of genital herpes, the modifying effect of prior HSV-1 infections, the changing proportions of HSV-1 genital herpes, and the importance of asymptomatic shedding. Patients' ignorance of their diagnosis along with the occurrence of atypical symptomatology and asymptomatic viral shedding of HSV all contribute to the transmission of genital herpes. Genital ulcer disease, of which genital herpes is the most common cause in developed countries, is an important risk factor in the acquisition and transmission of human immunodeficiency virus (HIV) infection and has contributed to the spread of this disorder. Risk factors for genital herpes HSV-2 are strongly related to lifetime number of sexual partners, number of years of sexual activity, male homosexuality, black race, female gender and a history of previous sexually transmitted diseases (STD). Understanding the epidemiology of genital herpes is of great importance in limiting the spread of this STD. In this review, we summarise current knowledge related to the epidemiology of genital herpes.

Age Factors↗

PubMed1992

Epidemic and demographic interaction in the spread of potentially fatal diseases in growing populations.

The spread of a potentially fatal infectious disease is considered in a host population that would increase exponentially in the absence of the disease. Taking into account how the effective contact rate C(N) depends on the population size N, the model demonstrates that demographic and epidemiological conclusions depend crucially on the properties of the contact function C. Conditions are given for the following scenarios to occur: (i) the disease spreads at a lower rate than the populations grows and does not modify the population growth rate: (ii) the disease initially spreads at a faster rate than the population grows and lowers the population growth rate in the long run and the following three subscenarios are possible: (iia) the population still grows exponentially, but at a slower rate; (iib) population growth is limited, but the population size does not decay; (iic) population increase is converted into population decrease.

Animals↗

PubMed1999

The relative effectiveness of exposure to 131I at low doses.

There is much interest in estimating the thyroid cancer risks to children exposed to low doses of (131)I from nuclear fallout. Direct epidemiological studies of individuals exposed as children to low doses of (131)I have insufficient power to yield useful risk estimates. Consequently, extrapolation from risk estimates for acute exposure to kilovoltage x rays are used to generate (131)I risk estimates. There are two distinct effects that might need to be considered in modifying the x-ray generated risk estimates: first, the differing quality of the radiations and, second, the lower overall dose rates for (131)I exposure. We suggest that it is helpful to split the overall correction factor into its component parts-radiation quality and radiation dose rate-and consider them separately, in that a good deal is known separately about each. There is good radiobiological evidence that electrons emitted in (131)I decays are less biologically effective than kilovoltage x rays, and the microdosimetric/radiobiological analyses described here suggest that the low-dose relative effectiveness is around 0.6 compared to kilovoltage x rays. Use of different endpoints suggests that this estimate is quite robust, and it agrees well with available animal data. Any correction factor for dose-rate effects is likely to be close to unity.

Beta Particles↗

PubMed2004

Ambient carbon monoxide may influence heart rate variability in subjects with coronary artery disease.

OBJECTIVE: Days of high ambient carbon dioxide (CO) have been associated with increased hospital admissions for cardiac disease. This study was conducted to determine if daily concentrations of CO and fine particulates (PM2.5) are associated with daily changes in heart rate variability. METHODS: Each of 36 adults with coronary artery disease had personal exposure to PM2.5 and CO measured along with heart rate variability for one 24-hour period each week for up to 10 weeks. RESULTS: Among those not taking beta-receptor blockers, there was a positive association between the standard deviation of the R-to-R intervals and CO (P = 0.02). No effect was found for PM2.5. CONCLUSIONS: Urban exposure to CO may exert a biologic effect on the heart, which may be modified by medications.

Adrenergic beta-Antagonists↗