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PubMed1991

A review of ethical issues in AIDS research.

Much of the past research in AIDS concentrated in the epidemiology, virology, immunology and pathogenesis of human immunodeficiency virus (HIV) infection. However, current research activities incorporates aspects intended to modify human behaviour with a view to slowing down the spread. But a more comprehensive control of the AIDS epidemic can only be affected when a vaccine and, or effective anti HIV drugs are developed. Perspectives into AIDS research will therefore involve more vaccine and drug trials. How will these studies be conducted? To date there is no satisfactory animal model for HIV, and although chimpanzees have shown a promising role as animal models, this role which is not very good for the chimpanzees, is not entirely satisfactory for humans because of the long-incubation period and natural history of AIDS. Human subjects must therefore bear the burden of this research. Unlike in the past when ethical considerations in AIDS research in Africa and other developing countries were less stringent, these newer aspects, initiate more appropriate ethical issues to be instituted. It is also appropriate, to recognize contribution of human subjects in developing countries which should determine the pricing policy for AIDS drugs and vaccines in future.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Chronic Lyme borreliosis at the root of multiple sclerosis--is a cure with antibiotics attainable?

Apart from its devastating impact on individuals and their families, multiple sclerosis (MS) creates a huge economic burden for society by mainly afflicting young adults in their most productive years. Although effective strategies for symptom management and disease modifying therapies have evolved, there exists no curative treatment yet. Worldwide, MS prevalence parallels the distribution of the Lyme disease pathogen Borrelia (B.) burgdorferi, and in America and Europe, the birth excesses of those individuals who later in life develop MS exactly mirror the seasonal distributions of Borrelia transmitting Ixodes ticks. In addition to known acute infections, no other disease exhibits equally marked epidemiological clusters by season and locality, nurturing the hope that prevention might ultimately be attainable. As minocycline, tinidazole and hydroxychloroquine are reportedly capable of destroying both the spirochaetal and cystic L-form of B. burgdorferi found in MS brains, there emerges also new hope for those already afflicted. The immunomodulating anti-inflammatory potential of minocycline and hydroxychloroquine may furthermore reduce the Jarisch Herxheimer reaction triggered by decaying Borrelia at treatment initiation. Even in those cases unrelated to B. burgdorferi, minocycline is known for its beneficial effect on several factors considered to be detrimental in MS. Patients receiving a combination of these pharmaceuticals are thus expected to be cured or to have a longer period of remission compared to untreated controls. Although the goal of this rational, cost-effective and potentially curative treatment seems simple enough, the importance of a scientifically sound approach cannot be overemphasised. A randomised, prospective, double blinded trial is necessary in patients from B. burgdorferi endemic areas with established MS and/or Borrelia L-forms in their cerebrospinal fluid, and to yield reasonable significance within due time, the groups must be large enough and preferably taken together in a multi-centre study.

Animals↗
PubMed1994

Epidemiological aspects of attempted suicide--a case-control study in Gent, Belgium.

In order to study the distribution of attempted suicide among the population of Gent, exploratory and analytical case-control studies were carried out. The strength of the association between attempted suicide and marital and employment status was calculated taking into account the confounding and/or effect-modifying roles of age, gender, and the living situation. Unmarried individuals who were not living alone were at increased risk of attempted suicide compared to (cohabiting) married individuals. Young and middle-aged unemployed males and middle-aged unemployed females had significantly increased risks compared to employed individuals. In addition to a causal interpretation of the demonstrated associations, the roles of chance, reverse causality, and confounding or bias were considered. Selection and information biases may have accounted for the observed associations. For instance, in previous monitoring studies on attempted suicide, surprisingly little attention has been paid to the reliability of the information collected. The question of how one can reliably assess patients who may provide unreliable information remains unanswered. However, several findings support a role of causality in explaining the associations. The present studies therefore provide additional evidence for a detrimental affect of certain socio-demographic or -economic conditions on the occurrence of attempted suicide.

Adolescent↗
PubMed2003

Risks associated with the microbiological quality of bodies of fresh and marine water used for recreational purposes: summary estimates based on published epidemiological studies.

The current European standards for microbiological quality of bathing water (i.e., all running or still fresh waters or parts thereof and/or sea water [with the exception of water intended for therapeutic purposes and water used in swimming pools]) were issued in 1976 and are currently undergoing revision. In this article, the authors propose parameters for select microorganism indicators to assist in the establishment of public-health-based objectives for fresh and marine water quality. A type-II meta-analysis of the results of 18 published epidemiological studies was implemented in an attempt to characterize the relationship(s) between concentrations of bacterial indicators and rates of acute gastrointestinal diseases among bathers who had used fresh or marine water for recreational purposes. The authors fit multiple linear-regression models, which allowed for random effects across studies, to derive dose-response curves. Several confounders and effect modifiers were controlled for in the analyses. Risks were then estimated for a hypothetical individual who would bathe 20 times/yr in water that contained a given concentration of microorganisms. For fresh-water-associated highly credible gastrointestinal illnesses, a level of 10 fecal coliforms/100 ml water yielded an attributable risk of 0.2 cases/1,000 person-years; a risk of 2 cases/1,000 person-years was found for fecal streptococci. The corresponding yearly attributable risks were 1 and 13 cases/1,000 person-years, respectively, for 100 bacteria/100 ml fresh water. Risks associated with fecal coliforms were found to be lower in marine water than in fresh water. Irrespective of the type of water examined, total coliforms were related only weakly with acute digestive morbidity. Developers of future bathing-water standards should state the level of risk deemed acceptable for public health. The authors of this study maintain that levels of fecal coliforms and fecal streptococci should be used as criteria for infectious risk management associated with bodies of marine and fresh water used for recreational purposes.

Bathing Beaches↗
PubMed1997

Wartime civilian injuries: epidemiology and intervention strategies.

BACKGROUND: Trauma is the most important public health risk in wartime. Most preventive effort have addressed the political etiology of armed conflicts and the secondary effects of war (food, water, shelter, sanitation, and vector control). Little to no efforts have addressed the direct prevention and control of war trauma. METHODS: An extensive review of the literature, with compilation of the most important data. RESULTS: Civilians are the major wartime targets in recent wars, and account for most of the killed and wounded. The trend has been toward a greater proportion of injuries from powerful explosive devices such as artillery shells and mines. Lessons learned from Bosnia and Lebanon show that the most effective way to achieve successful surveillance and injury prevention is to enhance the local skills and resources. CONCLUSIONS: New approaches are needed to minimize trauma to civilians. Both political advocacy and local efforts (including modifying firearms and ammunition, bullet proof helmets for children, anti-sniper shields) are needed.

Blast Injuries↗
PubMed1997

Epidemiologic studies of ionizing radiation and cancer: past successes and future challenges.

The health effects of radiation have been a focus for research since early in the 20th century. As the century ends, extensive experimental and epidemiologic evidence has been accumulated that addresses the adverse consequences of radiation exposure; epidemiologic studies of radiation-exposed groups from the general population and specific occupational groups provide quantitative estimates of the cancer risks associated with exposure. This report provides a perspective on the extensive epidemiologic evidence on the health effects of ionizing radiation and on likely needs for further epidemiologic research on radiation and health. Epidemiologic studies have proved informative on the quantitative risks of radiation-caused cancer but we now face the challenges of more precisely characterizing risks at lower levels of exposure and also of assessing modifiers of the risks, including dose rate, genetic susceptibility, and other environmental exposures. This report considers investigative approaches, such as pooled analysis of multiple data sets, that can be used to address these complex questions and the limitations of these approaches for addressing societal concerns about the risks of radiation exposure.

Dose-Response Relationship, Radiation↗
PubMed2005

[Fetal nutrition and future health].

Fetal nutrition may permanently affect physiological properties of the new individual and hence the risk of future disease. Epidemiological studies indicate that fetal nutrition may significantly influence the risk of diabetes, cardiovascular disease, and cancer. Controlled animal studies show that even properties traditionally considered as exclusively genetic, like fur colour, may be modified by altered maternal nutrition. The expression "fetal programming" has been introduced to describe permanent effects of environmental conditions in fetal life. An important mechanism of fetal programming seems to be epigenetic regulation. One example of epigenetic regulation is methylation of the DNA base cytosine in promoter regions of some genes. DNA methylation will lead to decreased gene expression. Over the last two decades, marked changes in dietary habits and other life style features have taken place among young Norwegian women. This is particularly reflected in the increasing prevalence of obesity. Maternal weight and metabolic status is closely associated with the growth and development of the fetus. Thus, diet and physical activity become particularly important aspects of the health of young women.

Animals↗
PubMed1994

Has the Scandinavian solvent syndrome controversy been solved?

This article discusses the "Scandinavian solvent syndrome" and reviews epidemiologic studies on occupational solvent exposure and two related outcomes. High cumulative exposure to organic solvents in the 1960-1970s was related to early retirement from neuropsychiatric disorders, but solvent exposure alone was an unlikely cause of more severe dementia conditions. Heavy alcohol consumption seemed to modify the effect on solvent-related brain disorders strongly, but no reports exist of alcohol consumption as a confounding factor. Many cross-sectional and experimental studies support functional impairment from high solvent exposure. The mists and myths around the "Scandinavian solvent syndrome" can now be cleared up: it was not a uniform syndrome, it might be reversible in many cases, it is not confined to the Scandinavian countries, the risk of more severe dementia is substantial for combined high solvent exposure and excessive alcohol consumption, and many solvent-exposed workers receive early retirement due to solvent-related neuropsychiatric disorders.

Air Pollutants, Occupational↗
PubMed2002

Modifiable risk factors for colon cancer.

Although many mechanisms remain unclear, a large body of evidence indicates that several dietary and lifestyle factors are likely to have a major influence on the risk of colon cancer. Physical inactivity, excess body weight, and a central deposition of adiposity are consistent risk factors. Overconsumption of energy is likely to be one of the major contributors to the high rates of colon cancer in Western countries. Beyond their influence on energy balance, the independent role of specific macronutrients remain controversial. Red meat, processed meats, and perhaps refined carbohydrates contribute to risk. Recent evidence indicate that chronic hyperinsulinemia may increase risk of colon cancer. As insulin resistance and subsequent hyperinsulinemia is induced by excess energy intake and some aspects of the Western diet (e.g., saturated fats and refined carbohydrates), insulin may be a focus of factors influencing colon cancer risk. Recent evidence also points to a role of IGF-1, but our understanding of modifiable factors that influence levels of these is poor at present. Of note is that hyperinsulinemia increases free IGF-1 exposure [25]. High alcohol consumption, probably in combination with a diet low in some micronutrients such as folate and methionine, and smoking early in life are likely to increase risk of colon cancer. Recent epidemiologic studies have tended not to support a strong influence of fiber; instead, some micronutrients or phytochemicals in fiber-rich foods may be important. Folate is one such nutrient that has received attention lately and is being studied in randomized intervention trials. Agents with chemopreventive properties, such as aspirin and postmenopausal estrogens, have potential adverse effects so a careful consideration of the risk-benefit ratio is required before general recommendations can be made. Other NSAIDs with a potential for reduced toxicity, such as celecoxib, are currently being evaluated for efficacy and toxicity. The overwhelming evidence indicates that primary prevention of colon cancer is feasible. At least 70% of colon cancers may be preventable by moderate changes in diet and lifestyle [197]. Secondary prevention, through screening by sigmoidoscopy and colonoscopy, is also critically important to prevent mortality from colon cancer; however, many of the diet and lifestyle risk factors for colon cancers are the same for cardiovascular disease and for some other cancers, so focusing on the modifiable risk factors for colon cancer is likely to have many additional benefits beyond this cancer.

Clinical Trials as Topic↗
PubMed1998

Prevalence of occupational asthma among automobile and furniture painters in the center of Eskisehir (Turkey): the effects of atopy and smoking habits on occupational asthma.

BACKGROUND: Occupational asthma (OA) is a respiratory disorder characterized by airway hyperreactivity caused by agents present in the workplace. For determination of the prevalence of OA among car and furniture painters exposed to isocyanate in the center of Eskisehir, Turkey, a clinical and epidemiologic prospective study in three phases was done, incorporating 312 (89.4%) of the painters. METHODS: Of these subjects, 190 (61%) were furniture painters and 122 (39%) automobile painters. In the first phase of the study, a modified questionnaire and pulmonary function test (PFT) were done. During the second phase, peak expiratory flow rate (PEFR) was monitored in 52 subjects whose complaints were confirmed and who agreed to a month of such monitoring. In the third phase, nonspecific bronchial provocation tests (NSBPT) with histamine were done on 23 of the PEFR-monitored workers. RESULTS: Finally, through questionnaire, typical history, PFT, PEFR monitoring, and NSBPT, 30 workers (9.6%) were diagnosed as having OA. Smoking habits and atopy in the OA-diagnosed workers were found to be statistically significantly high in comparison to the other workers. CONCLUSIONS: It was concluded that OA is a common disorder among automobile and furniture painters, and smoking habits and atopy were seen to have a significant effect on OA occurrence.

Adolescent↗
PubMed1993

Does contraception modify the risk of endometriosis?

Long episodes of regular, prolonged, abundant menstrual flows are generally agreed to increase the risk of endometriosis. Since oral oestrogen-progestogen combinations reduce and intra-uterine contraceptive devices increase menstrual flow, an effect on the risk of development of endometriosis in women utilizing these forms of contraception could be expected. Analysis of the most recent epidemiological observations shows no consensus on a possible relationship between use of cyclic oral contraceptives and endometriosis, with an increase, a decrease, and no effect on the risk of developing the disease all being reported. A lower relative risk of endometriosis in previous users of the intrauterine contraceptive device was only found in two series, most of the other data suggesting a rise in risk or no effect. Further studies on the relationship between type of contraception and endometriosis are needed to demonstrate whether the risk of development of the disease could be influenced, and whether well tolerated, relatively inexpensive, long-term treatment might be available for symptomatic patients not desiring offspring.

Contraceptives, Oral↗
PubMed2005

Hepatocellular carcinoma as a complex polygenic disease. Interpretive analysis of recent developments on genetic predisposition.

The different frequency of hepatocellular carcinoma (HCC) in humans at risk suggests a polygenic predisposition. However, detection of genetic variants is difficult in genetically heterogeneous human population. Studies on mouse and rat models identified 7 hepatocarcinogenesis susceptibility (Hcs) and 2 resistance (Hcr) loci in mice, and 7 Hcs and 9 Hcr loci in rats, controlling multiplicity and size of neoplastic liver lesions. Six liver neoplastic nodule remodeling (Lnnr) loci control number and volume of re-differentiating lesions in rat. A Hcs locus, with high phenotypic effects, and various epistatic gene-gene interactions were identified in rats, suggesting a genetic model of predisposition to hepatocarcinogenesis with different subset of low-penetrance genes, at play in different subsets of population, and a major locus. This model is in keeping with human HCC epidemiology. Several putative modifier genes in rodents, deregulated in HCC, are located in chromosomal segments syntenic to sites of chromosomal aberrations in humans, suggesting possible location of predisposing loci. Resistance to HCC is associated with lower genomic instability and downregulation of cell cycle key genes in preneoplastic and neoplastic lesions. p16(INK4A) upregulation occurs in susceptible and resistant rat lesions. p16(INK4A)-induced growth restraint was circumvented by Hsp90/Cdc37 chaperons and E2f4 nuclear export by Crm1 in susceptible, but not in resistant rats and human HCCs with better prognosis. Thus, protective mechanisms seem to be modulated by HCC modifiers, and differences in their efficiency influence the susceptibility to hepatocarcinogenesis and probably the prognosis of human HCC.

Animals↗
PubMedDate not supplied

Routine serologic testing for hepatitis C virus infection should be instituted among dialysis patients.

Since the cloning of hepatitis C virus (HCV), a number of serologic and virologic tests for detecting infections with this virus have been made available for clinical practice. This led to the recognition of HCV as a major health hazard in hemodialysis (HD) centers. Yet the nephrology community has not been offered explicit recommendations about routine serologic testing for HCV of dialysis patients and consequently has remained unclear and divided about the utility of this testing. This review presents evidence in support of instituting routine serologic testing for HCV among dialysis patients. It concludes that because of the peculiar features of HCV infection in HD patients, serologic testing for HCV is the only means for unequivocal diagnosis of hepatitis C and an irreplaceable instrument for monitoring the incidence and the prevalence of the infection in this population. Serologic surveillance for HCV infection is crucial for identifying the association of new cases of HCV infection with potential risk factors for HCV transmission, particularly nosocomial, that can be modified in a way to prevent further dissemination of the virus. Data collected from routine serologic testing for HCV will undoubtedly improve our understanding of the epidemiology of HCV in the dialysis population and will provide a strong foundation for developing preventive measures and infection control strategies that are highly effective in controlling HCV infection. Routine serologic testing for HCV is also of direct benefit to the individual patient since establishing the HCV serologic status of each patient is important for optimizing patient care.

Alanine Transaminase↗
PubMed2005

High-risk human papillomavirus detection and related risk factors among pregnant and nonpregnant women in Mexico.

BACKGROUND: Significant differences in human papillomavirus (HPV) prevalence between pregnant and nonpregnant women have been reported. Some studies suggest that physiological processes during pregnancy modify the host-immune response, increasing detectability of high-risk HPV infection as a result of viral reactivation. It remains uncertain, however, whether pregnancy has an effect on HPV DNA positivity as a result of a general lack of data and based on contradictory results found in previous epidemiologic studies. We conducted an epidemiologic study to identify differences in the prevalence of HPV infection between pregnant and nonpregnant women in Mexico. We also investigated the relationship of HPV DNA positivity with socioeconomic, gynecologic, and obstetric risk factors. METHODOLOGY: We screened pregnant and age-matched nonpregnant women for high-risk HPV infection. The study population was clients of the family medicine healthcare services of the Mexican Institute of Social Security in Cuernavaca, Morelos, Mexico. A total of 274 pregnant and 1060 nonpregnant study participants were screened for the presence of high-risk HPV DNA in self-collected specimens by the Hybrid Capture 2 test (HC2; Digene Corp., Gaithersburg, MD). RESULTS: High-risk HPV DNA was detected in 37.2% (95% confidence interval [CI], 31-43%) of pregnant women and in 14.2% (95% CI, 12-16%) of nonpregnant women. Combining both groups for the multivariate analysis, pregnancy was associated with an increased risk for HPV infection (odds ratio, 3.5; CI, 2.7-4.9). CONCLUSIONS: Our results are consistent with other studies reporting increased high-risk HPV detection rates among pregnant women. HPV-positive status in pregnant and nonpregnant women appears to be influenced by age. The decrease in HPV positivity by number of pregnancies in both currently pregnant and nonpregnant women is consistent with a possible effect of immune protection as a result of earlier HPV infections. Despite lack of information about a woman's history of sexual behavior, these data support the hypothesis that an alteration of immunologic responses during pregnancy may be associated with an increased risk of HPV acquisition or reactivation.

Adolescent↗
PubMed2003

Adenosine-dopamine interactions: development of a concept and some comments on therapeutic possibilities.

This brief review presents a personal perspective on the historical development of the current knowledge about the biologically important concept of functional antagonism between adenosine A2A and dopamine D2 receptors in caudate-putamen, accumbens, and tuberculum olfactorium. In the 1970s, studies of dopamine actions suggested an unexpected role of adenosine. Developments during the next decade substantiated this finding and demonstrated that a subform of adenosine A2 receptors was enriched in the basal ganglia. Cloning of adenosine receptors provided better tools for cellular localization and showed that A2A receptors are closely associated with D2 receptors. Distinct functional interactions at several levels were discovered, and there is now strong evidence that A2A receptors are tonically active and modified by dopamine acting at D2 receptors. Development of selective antagonists and knockout mice have highlighted the potential usefulness of A2A antagonists in decreasing symptoms and progression of Parkinson's disease-something that has also been vindicated by careful epidemiologic studies. There are issues of efficacy and potential side effects that need to be resolved, but the future looks bright.

Adenosine↗
PubMed1997

Can low-level 50/60 Hz electric and magnetic fields cause biological effects?

Some epidemiological studies have suggested that exposure to ambient, low-level 50/60 Hz electric and magnetic fields (EMFs) increases risk of disease. Whether this association has a causal basis depends in part on whether the electrical, chemical and mechanical "signals" induced within living cells by ambient EMFs are detectable in the complex milieu of voltages, currents and forces present within the living organism. Magnetic responsiveness has been found in some animals and bacteria; aquatic animals (e.g. sharks and rays) can sense weak electric fields. We outline the physics of several mechanisms by which EMFs may interact: (1) Energy transfer by acceleration of ions and charged proteins modifies cell membranes and receptor proteins; however, EMF energies are far below those typical of biomolecules in the cell. (2) Electric fields induced inside the body exert force on electric charges and electric moments; however, these forces are considerably smaller than typical biological forces. (3) The magnetic moments of ferromagnetic particles and free radical molecules interact with magnetic fields, but magnetic-moment sensory cells have not been found in humans, and modification of radical recombination rates by EMFs in a biological system is highly problematic. (4) Resonant interactions involve EMFs driving vibrational or orbital transitions in ion-biomolecule complexes; these mechanisms conflict with accepted physics, and many experimental tests have not found the predicted effects. (5) Temporal averaging or spatial summation can improve the ratio of "signal" to "noise" in any system, but this "mechanism" requires biological structures and neural processes having the necessary capabilities of EMF detection and temporal averaging that have not been found in humans. In summary, biological effects in humans due to extremely low-frequency EMFs of the order of those found in residential environments [< or = 2 microT (< or = 20 mG)] are implausible based on current understanding of physics and biology. Biological effects in humans at higher fields [> 10 microT (> 100 mG)] might reach plausibility as a result of time-averaging in combination with a magnetic-moment transduction mechanism; but even here, neither specialized EMF transduction structures nor appropriate averaging networks have been demonstrated. The bypothesis that the epidemiological associations observed between 50/60 Hz EMFs and disease reflect a causal relationship is not supported by what is known about mechanisms.

Animals↗
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↗