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Clinical scientists from eight European countries and China gathered in the ancient Chinese capital of Xi'an on April 26-28, 2001 to discuss collaboration on a modern approach to gastric cancer prevention. Participants at the First Sino-European Workshop on Immunogenetics and Pathogenesis of Gastric Cancer presented their most up-to-date research results on topics ranging from epidemiology and immune mechanisms to Helicobacter pylori and vaccine development. Researchers then formed groups with their Chinese or European counterparts to plan future research endeavors which will benefit Chinese and European populations alike. After 3 years of organization between the Institute of Digestive Diseases of the Fourth Medical University in Xi'an, China and the Laboratory of Immunogenetics, VU University Medical Center in Amsterdam, the first workshop came into being under the joint sponsorship of the Commission of the European Union, National Natural Science Foundation of China and the Institute of Digestive Diseases, Xi'an, China. As gastric cancer is the most prevalent malignant tumor in China, the workshop was of special significance to the Chinese researchers and to the Chinese population in general. During the workshop, presentations on the epidemiology of gastric cancer showed that this disease is in fact common the world over: it is the second most common cancer next to lung cancer and about 1 million new cases were diagnosed in 2000. Three-quarters of the cases of gastric cancer occur in Asia, and approximately 80% of these cases are in China and Japan. Genetic factors and environmental factors such as diet and H. pylori infection play a role in gastric carcinogenesis. As a recognized cause of gastric cancer, H. pylori was the subject of various presentations ranging from immunological studies, molecular analysis of strains and pathogenesis to vaccine development. Specific areas of discussion included bacterial-epithelial interactions in H. pylori infection, epidemiology in China, global distribution of vacA and cagA genotypes, new evidence for host factors, nonsteroidal antiinflammatory drugs and H. pylori as independent risk factor for gastric cancer, new diagnostic techniques for H. pylori using serum levels of pepsinogen I, and autoimmune processes in corpus atrophy. Vaccine development using a variety of strategies against H. pylori was the subject of an entire session of talks. Oral immunization with urease with Escherichia coli heat labile enterotoxin was shown to be safe and immunogenic in humans as a mucosal adjuvant. Results of a study using attenuated Salmonella typhimurium as a vehicle for DNA-mediated immunization in mice were also presented. A final presentation discussed an ongoing trial comparing strain variability in the vacA and cagA gene sequences and disease expression between H. pylori infection in Europe and China. Researchers also discussed the role of IL1 gene family and TNF gene polymorphisms in gastric pathology and various immune mechanisms involved in gastric cancer, such as down-regulation of NF kappa B, IL-1 and IL-1RA, cyclooxygenase signalling, and identification of MGAg antibodies. An interactive discussion followed each presentation and ideas and suggestions were provided. According to specialty, the presenters were then assigned to groups of four or five to make plans for joint research projects. A number of international and Chinese observers were present, including representatives from the European Commission, the World Health Organization and the Chinese National Center for Biotechnology Development, and offered input on the financial feasibility of such projects.
UNLABELLED: The aim of the study was to develop a simple, inexpensive, reproducible ethidium bromide (EB)-agar based method that is independent of any specialized instrumentation, for the demonstration of efflux pump activity, which is responsible for antibiotic resistance of bacteria. MATERIALS AND METHODS: A series of agar plates containing varying concentrations of EB were swabbed with strains of Escherichia coli or Staphylococcus aureus, which differed with respect to efflux pump activity. The plates were incubated at different temperatures and time periods and the measurements of fluorescence were used to evaluate the efflux activity of each culture. RESULTS: This simple assay allowed us to identify the efflux of EB in different bacteria following an overnight incubation. The minimal concentration of EB that produced fluorescence was significantly greater at 37 degrees C than at 4 degrees C, suggesting the presence of an energy-dependent pump. The method was shown to simultaneously identify strains of a mixed culture that differed from each other with respect to the activity of their efflux pumps. CONCLUSION: The method, in conjunction with the use of antibiotic-containing disks, provides an additional advantage for the easy identification and selection of colonies that differ with respect to antibiotic susceptibility and degree of efflux pump activity. Because the method is very reproducible it may form the basis for interlaboratory standardization of efflux pump activity of multi-drug resistant (MDR) clinical isolates.
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A comparison of testing methods for constituents of Ginkgo biloba was performed as part of the process for determining which of the many available analytical methods was most appropriate for inclusion in the American Herbal Pharmacopoeia (AHP). Three primary methods were reviewed: those adopted by the European Pharmacopoeia, the National Science Foundation-Institute for Nutraceutical Advancement (NSF-INA) and the United States Pharmacopeia. Methods were compared by evaluating sample preparation and hydrolysis, precision and methods of total flavonol glycoside calculation by two independent laboratories. The AHP adopted the method of NSF-INA for inclusion in the AHP monograph owing to observed superiority of this method in terms of precision, glycoside calculation, ease of sample preparation and chromatographic parameters.
Professor Cesare Maltoni, a renowned leader in the research of the hazards of carcinogens in the workplace, died on January 22, 2001 at the age of 70. Born in Faenza (Ravenna), Italy on November 17, 1930, he received his M.D. degree from the University of Bologna in 1954-1955. He was Director of the Institute of Oncology of Bologna (1964 to 1997), Director of the Bologna Centre for the Prevention and Detection of Tumours and Oncological Research (1966 to 1989), and Scientific Director, European Foundation of Oncology and Environmental Sciences "B. Ramazzini" from 1993 until he died. Maltoni conducted long-term carcinogenic studies on some 200 agents. He was the first to demonstrate that vinyl chloride is a carcinogen that produces, among other tumors, angiosarcoma of the liver. He was the first to show that benzene is a powerful multipotential carcinogen. Maltoni authored more than 700 original scientific publications, books, and proceedings. He was editor and coeditor of many journals. Among his many awards were the Stokinger Award, American Conference of Governmental Industrial Hygienists (ACGIH), Kansas City, 1995; International Award "B. Ramazzini" of the Collegium Ramazzini, Washington, 1995; International I.J. Selikoff Memorial Award, Washington, 1995; and the Sigillum Magnum of the University of Bologna, 1997. Many fellow Ramazzinians and his coworkers wish to be considered part of the group of, as he once wrote, his "always family friends" and to remember happy moments when we were together. A man of great stature and many contributions, Cesare Maltoni will never be forgotten.
The National Toxicology Program rodent cancer bioassay program design evolved from that of the National Cancer Institute in the 1970s. Groups of 50 or more mice are assigned to control or treatment groups. Test substances are given at three dose levels by intubation, dietary or drinking water consumption, or dermal or inhalation exposure. Dosing starts at age 5-6 weeks and lasts for 2 years, when surviving animals receive a complete histopathologic examination. Statistical approaches accommodate survival differences and no longer require differentiation between fatal and incidental tumors. Photocarcinogenicity studies, employing SKH-1 hairless mice, evaluate onset of skin papillomas and incidences at 1 year. Top doses are chosen to expose animals to a minimally toxic challenge and lower doses to operate within the linear range of kinetics. This dosing allows comparison of results across studies. Bioassay and ancillary studies successfully identify tumor-causing agents in rodents, provide information on dose-response, and characterize other chemical-related toxicities. NTP and Ramazzini Foundation bioassay designs differ in several aspects, but bioassays at both institutions provide chemical-specific information for predicting human carcinogens, thus providing for protection of public health. Bioassays constitute an essential information reference set for new assay development and further investigations into mechanisms of action. The scientific community and the public owe a huge debt of gratitude to Dr. Cesare Maltoni of the European Foundation of Oncology and Environmental Sciences and to Dr. David P. Rall of the National Institute of Environmental Health Sciences for their foresight and wisdom in creating and nurturing these bioassay programs.
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Tamoxifen was submitted to carcinogenicity bioassays on Sprague-Dawley rats (of the colony used at the Cancer Research Center in the Castle of Bentivoglio of the European Ramazzini Foundation of Oncology and Environmental Sciences) at the dose of 3.3 mg/kg b.w., by stomach tube, in three experiments. In the first experiment the drug was administered once daily, 6 days a week to male and female rats, 8 weeks old at start for their life span. In the second experiment, the drug was administered to female rats, 12 weeks old at start, once daily for 8 consecutive days every 8 weeks for their life span. In the third experiment the drug was administered to female rats, 56 weeks old at start, 6 times weekly for 40 weeks; and then the animals were kept alive for their life span. In the first experiment, a mild increase in hepatocarcinomas with low grading was detected. In the first and second experiments, a borderline increase in uterine malignancies was found. No carcinogenic effect was observed in the third experiment. In the three experiments, tamoxifen showed a strong, long-lasting chemopreventive effect on mammary benign tumors and cancers. The presented data also indicate that tamoxifen treatment reduces the incidence of other tumors: pituitary adenomas, adrenal pheochromocytomas, islet cell pancreatic tumors, Leydig cell testicular tumors, and polyps of the uterus.
The present article analyzes the relation between technological changes and the advance of science, as well as the attitude of individuals in relation to science nowadays. According to researches carried out by the National Science Foundation in the United States, a large number of Americans and Europeans accept the benefits of science and technology, but have complex attitudes in relation to this topic. Contemporary cultures display this contradiction in many different ways. An evidence of this ambiguity is the prevailing image of scientists in popular culture: that of the mad scientist. Interpreting science and technology to a large and diversified audience is the main mission for most science centres. The changes that take place in society demand new approaches in the relationship with visitors. The present article analyzes the economic and intellectual sustainability of science centres and the continuously reinvented ways through which each one of them tires to shape its relationship with the community and with its identity as a science centre in the twenty-first century.
Used well, science provides effective ways of identifying potential risks, protecting citizens, and using resources wisely. It enables government decisions to be based on evidence and provides a foundation for a rule-based framework that supports global trade. To ensure that the best available science becomes a key input in the decisions made by EU institutions, this abridged version of a working paper produced for the European Policy Centre, a leading, independent think tank, considers how science is currently used in the policy and decision-making processes of the EU, what the limitations of scientific evidence are, and how a risk assessment process based on scientific 'good practices' can be advantageous. Finally, the paper makes recommendations on how to improve the use of science by EU institutions.
Europe is a patchwork of various medical cultures and financial resources. Variations abound with respect to financing, accessibility to public health systems, health expenditures, drug registration and reimbursement, the prescription of drugs, and clinical applications, as well as the perception of osteoporosis itself. However, there are possibilities for the harmonization of medical services among the various countries within Europe. The European Agency for the Evaluation of Medicinal Products (EAEMP) is attending to the centralized or decentralized procedures for the registration of drugs. The Group for the Respect of Ethics and Excellence in Science (GREES) is investigating guidelines for drug registration as well as gathering and making available medical references. The European Foundation for Osteoporosis and Bone Diseases (EFFO) is increasing awareness of the prevalence of the disease and the need for prevention and treatment. Finally, the International Federation of Societies on Skeletal Diseases (IFSSD) is coordinating epidemiologic, clinical, and social research. There is a need for increased awareness of osteoporosis throughout Europe. Health authorities are in need of cost/benefit reports leading to the registration and reimbursement of agents. Primary care physicians need information about osteoporosis and need to become involved in the diagnosis and science of the disease. Awareness needs to be generated among specialists; they need to be educated in the latest techniques for diagnosis and treatment. Finally, the general population needs to become aware of osteoporosis and to be encouraged to participate in the prevention and treatment of this disease. Current screening and detection in Europe is being done by densitometry. However, other techniques on the horizon include ultrasound and biochemical markers. Primary prevention, i.e., maximizing peak bone mass, includes examining the genetics of osteoporosis to determine the high-risk population and promoting reasonable physical exercise and dietary/life-style habits (e.g., increased calcium and avoidance of tobacco). Secondary prevention includes the identification of high-risk groups through risk factors, biochemical markers, and densitometry and adherence to the World Health Organization definition of osteopenia-osteoporosis (adapted to financial concerns by GREES guidelines). Other therapies include hormone replacement agents (although there are risks for cancer and concerns about durability), calcium and other inhibitors of bone resorption, physical activity, and vitamin D prophylaxis in the elderly. Treatment of established or severe osteoporosis includes drugs upon availability (inhibitors of bone resorption and stimulators of bone formation), surgery, and experimental approaches.
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With a background in biochemistry and radiation biology, I started to get involved in the control of chemicals area by battling the use of alkyl-mercury compounds in Swedish agriculture during the years 1964-1965 (C.-G. Rosén, H. Ackefors, and R. Nilsson, 1966, Seed dressing compounds based on organic mercury-economic aspects and health hazards, Svensk Kemisk Tidskrift 78, 8-19), and subsequently I acted as the sole technical advisor to the plaintiffs for the thalidomide children in Sweden for 4 years, ending in a 100 million US dollar (present value) settlement with the producers in 1969 (H. Sjöström and R. Nilsson, 1991, Thalidomide and the Power of the Drug Companies, Penguin, London, Feltrinelli, Milano, Iwanami Shoten, Tokyo Fisher Verlag, Berlin). I joined the Swedish EPA in 1974 and became head of the toxicological unit of the Products Control Division, where I was instrumental inter alia in pushing through regulations on reductions of lead in gasoline as well as the first general restrictions in world on the use of cadmium (R. Nilsson, 1989, Cadmium-an Analysis of Swedish Regulatory Experience, Report to the OECD Chemicals Group and Management Committee, January 1989). Since 1986 responsibility for control of chemicals was largely taken over from the Swedish EPA by the newly created National Chemicals Inspectorate (KEMI), an agency that employs me in the capacity of toxicologist. In between, I have been working for the OECD Chemicals Program as well as for WHO (IPCS) in various capacities and as a consultant in risk assessment for the US chemical industry under the Superfund Program. I was also associated with the Ministries of Environment of the governments of Iran and India. With respect to the latter, part of my recommendations were incorporated in the new Indian laws and regulations on chemicals that were issued subsequent to the Bhopal disaster (R. Nilsson, 1988, Procedures and Safeguards for Notification and Handling of Hazardous Chemicals in India, Report to WHO South-East Asia Region, SEA/EH/391, April 1988). As a consequence of a decreasing role for science in regulatory affairs, and a corresponding increasing influence from politics, for the past 8 years I have devoted myself mainly to research-oriented activities in my capacity as adjunct professor of molecular toxicology and risk assessment at the Stockholm University. In international collaboration, my projects have been supported by the Directorate General for Science, Research and Development of the Commission of the European Communities, the US Chemical Manufacturers' Association, the Coulston Foundation (Alamogordo, State of New Mexico), L'Oreal, Merck Co., and in the past to a limited extent also by my own agency, the National Swedish Chemicals Inspectorate. However, my position as member of the executive board for the International Society of Regulatory Toxicology and Pharmacology in the United States, which I held for 5 years, as well as my role as technical advisor in products liability litigation, reflects my continued interest in the "politics of chemical risk." In this context my critical comments with respect to the current regulatory policy for control of chemicals have caused considerable concern within the Swedish regulatory establishment (R. Nilsson, M. Tasheva, and B. Jaeger, 1993. Why different regulatory decisions when the scientific information base is similar? I. Human risk assessment, Regul. Toxicol. Pharmacol. 17, 292-332; R. Nilsson, 1994, Problems in the regulation of carcinogenic chemicals in an international perspective. III. Critical assessment of regulatory approaches. Rev. Int. Contam. Ambiental, México City, 10, 99-199; R. Nilsson, 1998, Integrating Sweden into the European Union: Problems concerning chemicals control. In The Politics of Chemical Risk-Scenarios for a Regulatory Future, R. Bal and Halffman, Eds, pp. 159-171, Kluwer Academic, Dordrecht).
Guillaume Jacob born in Castelnau-Montratier at the dawn of the XVIIIth century, physician of the School of Medicine of Montpellier was attracted by Spain during the reign of Philip V grand-son of Louis XIV. Nominated Professor of Anatomy at the Royal Society of Medicine of Sevilla, later Royal Academy, he worked during seventeen years to improve Spanish medical science: he informed himself in Paris of the discoveries of French scientists, obtained modern surgical instruments, books to enrich the library, laid the foundations of a botanical garden for medical plants and established links between the Royal Society of Sevilla and various European Royal Academies in order to allow exchanges.
Throughout past millennia, human beings have shared the common goal of improving health for longevity. However, different cultures around the world have developed their own approaches to achieve this goal. Various traditions have emerged, rendering distinct medical systems such as Ayurveda, Yoga, Chinese-Japanese medicine, shamanism, and Native American healing. Traditional medicine involves a holistic approach to the human body to integrate healing with culture, environment, and tradition. Modern allopathic medicine originated from Greco-Roman Medicine and Northern European traditions and is built on the science of anatomy, physiology, and biochemistry and the structure-function relationship between cells, tissues, and organs. This foundation focuses on diagnosis, treatment, and cure for acute illnesses via potent pharmaceutical drugs, surgery, radiation, and other treatment modalities. Within this past century, we have doubled the life-span of human beings. Genomic medicine, including stem cell research, cloning, and gene therapy, will increase our capability to treat even more diseases. In the new millennium, we face more chronic illnesses related to aging, environment, and lifestyle, such as cancer, diabetes. osteoporosis, and cardiovascular diseases. Thus, health care providers face the challenge of prospecting for health and disease prevention. Modern science and medical advancements provide the rationale for the integration of various traditional healing techniques, which have been termed Alternative and Complementary Medicine, to promote healing, health, and longevity. Advances in medicine must include the holistic approach of traditional medicine to face the current challenges in health care. Therefore, the New World of Medicine must fuse the antiquity of ancient healing with the innovations of modern medicine to increase life-expectancy and improve quality of life throughout the world.