Insulin-dependent (type 1) diabetes is a prototypic organ-specific autoimmune disease resulting from the selective destruction of insulin-secreting beta cells within pancreatic islets of Langerhans by an immune-mediated inflammation involving autoreactive CD4(+) and CD8(+) T lymphocytes which infiltrate pancreatic islets. Current treatment is substitutive, i.e. chronic use of exogenous insulin which, in spite of significant advances, is still associated with major constraints (multiple daily injections, risks of hypoglycaemia) and lack of effectiveness over the long term in preventing severe degenerative complications. Finding a cure for autoimmune diabetes by establishing effective immune-based therapies is a real medical health challenge, as the disease incidence increases steadily in industrialized countries. As the disease affects mainly children and young adults, any candidate immune therapy must therefore be safe and avoid a sustained depression of immune responses with the attendant problems of recurrent infection and drug toxicity. Thus, inducing or restoring immune tolerance to target autoantigens, controlling the pathogenic response while preserving the host reactivity to exogenous/unrelated antigens, appears to be the ideal approach. Our objective is to review the major progress accomplished over the last 20 years towards that aim. In addition, we would like to present another interesting possibility to access new preventive strategies based on the 'hygiene hypothesis', which proposes a causal link between the increasing incidence of autoimmune diseases, including diabetes, and the decrease of the infectious burden. The underlying rationale is to identify microbial-derived compounds mediating the protective activity of infections which could be developed therapeutically.
Cites: J Immunol. 2000 Jun 1;164(11):5683-810820244
This paper examines the effect of banning broadcast advertising of alcoholic beverages. The data used in this study are a pooled time series from 17 countries for the period 1970 to 1983. The empirical results show that countries with bans on spirits advertising have about 16% lower alcohol consumption than countries with no bans and that countries with bans on beer and wine advertising have about 11% lower alcohol consumption than countries with bans only on spirits advertising.
Comment In: J Health Econ. 1993 Jul;12(2):213-2810127781
AIMS: To test if there is relationship between alcohol consumption and pancreatitis mortality at the population level. DATA AND METHODS: Annual pancreatitis death rates for 1950-95 were converted into age-adjusted mortality rates per 100,000 inhabitants. Per capita alcohol consumption was measured by alcohol sales. The relationship was estimated with time-series analysis on data from 14 western countries. Several models were tested with different assumptions about risk function and lag structure. RESULTS: According to the assumed most appropriate model, a positive relationship was found in each country, and statistical significance was reached in all countries except from Finland, Italy and Canada. The magnitude of the association was fairly consistent across countries, with the alcohol effect parameters ranging between 0.05 and 0.14. However, Sweden and Norway deviated from this pattern with estimates between 0.30 and 0.40. CONCLUSIONS: Pancreatitis joins a wide range of causes of death where the mortality rate is influenced by per capita alcohol consumption, and more so in northern Europe. It is suggested that pancreatitis mortality is an important indicator of alcohol-related harm, not least because a large amount of morbidity is likely to be connected to the mortality rate.
In order to demonstrate how possible causal relationships are critically evaluated in epidemiologic research, literature on the association between alcohol and breast cancer is reviewed and discussed. A cause can be defined as a factor which, in combination with other factors, known and unknown, is sufficient to produce an effect. Since the hypothesis-generating study was published in 1977, a total of 34 positive and 16 negative studies have been published. Methodological problems, such as chance, bias and confounding, cannot be considered as plausible explanations for the above majority of positive findings. The question of causality was then evaluated using the guidelines developed by Bradford Hill in 1965. Among these, the strength of the association, consistency, temporality, biological gradient and biological plausibility, are the most important. In spite of the relatively weak association and somewhat inconsistent results, it is concluded that alcohol consumption should be considered as a cause of breast cancer. It is estimated that in Norway, between 24 and 180 cases of breast cancer may be attributed to alcohol consumption. Future research should focus on the question of effect-modification and on the possible implications of different patterns of alcohol consumption.
We evaluated the use of coronary angiography and clinical outcomes among patients who had heart failure and were enrolled in the Intravenous Novel Plasminogen Activator (NPA) for the Treatment of Infarcting Myocardium Early study, a large international trial of fibrinolytic therapy in ST-elevation myocardial infarction.
The ECO.SENS study is the first international survey to investigate the prevalence and susceptibility of pathogens causing community-acquired acute uncomplicated urinary tract infections (UTIs). Midstream urine samples were taken for culture and for testing for the presence of leucocytes from 4734 women not older than 65 years presenting with symptoms of acute UTI at 252 community health care centres in 17 countries. Recognized urinary tract pathogens were identified and the susceptibility to 12 antimicrobials determined. Pathogens were present in 3278 (69.2%) patients, Escherichia coli accounting for 77.0% of isolates. In E. coli, 42% of the isolates were resistant to one or more of the 12 antimicrobial drugs investigated. Resistance was most common to ampicillin (29.8%) and sulfamethoxazole (29.1%), followed by trimethoprim (14.8%), trimethoprim/sulfamethoxazole (14.1%) and nalidixic acid (5.4%). Resistance in E. coli to co-amoxiclav, mecillinam, cefadroxil, nitrofurantoin, fosfomycin, gentamicin and ciprofloxacin was
Few environmental health issues are as contentious as the question of whether exposure to electromagnetic fields (EMFs) from power lines increases cancer risk. Among the many actors in this controversy, epidemiologists have played the leading role in raising the question and motivating research. Epidemiologic studies of the effects of exposure to power-line EMFs include the investigation by Dr. Gilles Thériault and colleagues into incidence rates of cancer among electric-utility workers in Quebec, Ontario and France. With the development of personal dosimeters to measure exposure to electric, magnetic and pulsed EMFs, occupational studies in the 1990s have made an important methodologic advance. But, as Thériault explains, improvements in assessing exposure have not yet translated into clear and consistent findings.
Cites: Am J Epidemiol. 1988 Jul;128(1):21-383164167
Technological developments in percutaneous coronary interventions (PCI) allow the possibility for less invasive revascularization in an increasing number of patients with atherosclerotic coronary artery disease. Bare-metal stents (BMS) have considerably improved the efficacy of PCI in addition to greatly reducing restenosis. However, even with standard stents, restenosis has remained a significant limitation of this revascularization technique. The advent of drug-eluting stents (DES) has dramatically reduced in-stent restenosis and, as a result, the need for repeat revascularization. However, their potential thrombogenicity has raised concerns about their clinical utility and long-term safety. Indeed, there is a possible higher rate of late stent thrombosis (LST) with DES compared with BMS. Antiplatelet therapy has been shown to be efficient in preventing DES thrombosis. Nevertheless, in the future, significant improvement will occur to improve the safety and efficacy of this therapy. This article will summarize the pathophysiology and the epidemiology of stent thrombosis (ST). Definitions of definite, probable and possible ST will be described. Furthermore, clinical risk factors for ST will be clearly enumerated. Then, the various antiplatelet therapeutic strategies used to prevent ST will be taken in consideration. Finally, a summary of the major recommendations about antiplatelet therapy made by some of the most prestigious learned societies will be presented.