Appendix VIII
Potential Biological Consequences of Mercury Released From Dental Amalgam

Swedish Medical Research Council

CONTENTS

Preface

The questions

How is mercury released from dental amalgam?

Are there problems in determining small amounts of mercury in biological fluids and tissues?

Are there data demonstrating that mercury released from dental amalgam gives rise to, or contributes to, toxic systemic effects?

Are there data demonstrating that mercury released from dental amalgam may cause effects on the immune system in man?

Does silver amalgam cause systemic or local allergic reactions?

Will mercury released from dental amalgam give rise to teratological effects?

Are there data supporting that mental and psychosomatic disorders are potential side-effects of dental amalgam?

Have general or local side-effects been attributable to alternative restorative materials?

Is mercury in dental amalgam an environmental hygiene problem?

Do available data justify discontinuing the use of dental amalgam or recommending placement?

Conclusions

Scientific Panel

Moderators

Planning Committee

Speakers

 

PREFACE

Silver-containing amalgam is a common and efficacious dental material used to restore the function of posterior teeth. However, during the last decade the possibility of adverse effects on health resulting from exposure to dental amalgam has been raised and the issue has been discussed intensively both by the profession and the public.

The Swedish Medical Research Council has since 1989 given "ear-marked" grants to research on amalgam and other dental restorative materials.

During April 9-10, 1992, the Council held a State-of-the-Art Conference in Stockholm on the subject. The conference, entitled "Potential biological consequences of mercury released from dental amalgam," brought together scientists from various fields who, for two days, presented papers and discussed the subject in plenary sessions. On April 11 all the speakers were interviewed by a scientific panel appointed by the Swedish Medical Research Council.

The panel consisted of professor OD Bo Bergman, chairman, Umea Univesity, professor MD Harry Bostrom, Uppsala University, professor OD K. Sune Lawson, Karolinska Institute, Huddinge and professor Dr. Odont, director Harald Loe, National Institutes of Dental Research, Bethesda, Maryland, USA.

The panel weighed and analyzed the scientific evidence and responded to ten questions, which are presented in this document. The proceedings from the conference will be published separately.

Stockholm, June 1992
Tore Schersten
Secretary General
Swedish Medical Research Council

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THE QUESTIONS

  1. How is mercury released from dental amalgam?
  2. Are there problems in determining small amounts of mercury in biological fluids and tissues?
  3. Are there data demonstrating that mercury released from dental amalgam gives rise to, or contributes to, toxic systemic effects?
  4. Are there data demonstrating that mercury released from dental amalgam may cause effects on the immune system in man?
  5. Does silver amalgam cause systemic or local allergic reactions?
  6. Will mercury released from dental amalgam give rise to teratological effects?
  7. Are there data supporting that mental and psychosomatic disorders are potential side-effects of dental amalgam?
  8. Have general or local side-effects been attributable to alternative restorative materials?
  9. Is mercury in dental amalgam an environmental hygiene problem?
  10. Do available justify discontinuing the use of dental amalgam or recommending replacement?

The answers to these questions, and the conclusions of the conference are contained in this report to the Swedish Medical Research Council.

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Question 1: How is mercury released from dental amalgam?

Mercury is mainly released from dental amalgam in the form of elemental mercury (Hg°) vapour. This mercury vapour dissolves in the intra-oral air or in saliva and enters the organism via different routes. Mercuric ions (Hg2+) produced through electrochemical corrosion may also be released into saliva, bind to organic saliva components, and be swallowed. Fine powder particles of amalgam which might be introduced into oral mucosa during clinical operations can also undergo corrosion.

Finally, mercury can be released from amalgam particles which have been swallowed. Such pieces or particles may be dislodged during mechanical wear of amalgam fillings or produced during placement or replacement of amalgam fillings.

Vapour

Inside an amalgam filling, mercury diffuses towards the surface of the filling where a concentration gradient of mercury prevails. This concentration gradient is the apparent source of mercury. It can be distributed by various processes in the oral cavity such as the chewing of chewing-gum or tooth-brushing, resulting in an increasing mercury release rate, and it can also be passivated resulting in a decreased release rate. The diffusion process inside the amalgam filling, however, cannot be influenced by any variable other than temperature. Since the temperature in the oral cavity is relatively constant over time, this cannot appreciably change the diffusion process. Thus, the degree of diffusion of mercury within the amalgam fillings is the factor determining the rate of mercury release. The release of mercury vapour from amalgam fillings has been measured using a variety of methods. Based on such data the daily uptake, or daily dose has been calculated considering varying mouth to nose breathing ratios. Published results indicate that most of the mercury vapour released from amalgam fillings is mixed/dissolved in saliva and swallowed, while part of the mercury vapour is inhaled and exhaled respectively. The lungs absorb 80% of the inhaled mercury vapour.

Electrochemical corrosion

No reliable in vivo data exist on the degree of electrochemical corrosion of amalgam fillings. Indeed it has been questioned whether electrochemical corrosion of mercury from amalgams in the oral cavity even occurs. Theoretical data on charge transfer-potential measurements suggest that initially the metals zinc (in the zinc-containing amalgams) and tin are the corroding metals. As these metals dissolve, mainly the mercury-rich and the silver-rich phases remain, a situation which should further the release of mercury. Furthermore, in situations where the amalgam fillings are in contact with other metallic restorations electrochemical corrosion of mercury may occur, thereby producing mercuric ions (Hg2+). Mercuric ions in saliva will not remain as ions, but will chemically bind to saliva components, and be swallowed together with the saliva. Approximately 5-10 percent of the mercury from mercuric mercury salts ingested is absorbed, the remainder being excreted in the feces.

Particulate matter

The amount of mercury available from swallowed amalgam particles varies widely. Besides particles which are swallowed during clinical operations most of the particles are dislodged from incompletely condensed fillings and from amalgam surfaces undermined by heavy corrosion. Subjects with bruxism may release bigger and greater amounts of amalgam particles, varying to some degree with the extent and duration of the bruxism. The absorption of metallic mercury in the gastrointestinal tract is very small.

Studies in rats have shown that less than 0.01 percent is absorbed this way.

Considering all known forms mercury uptake and routes of absorption a patient with an average number of amalgam surfaces, 20-30, will have a daily uptake of no more than 10 µg mercury from these amalgams.

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Question 2: Are there problems in determining small amounts of mercury in biological fluids and tissues?

Since the amounts of mercury vapour are small and the concentrations of mercury in body fluids and tissues are low and despite the fact that a number of reproducible and sensitive methods are available, the determination of mercury in tissues and fluids is associated with great difficulty. It is, therefore, of great importance that sampling methods and laboratory procedures be meticulously controlled to avoid contamination of mercury from air, water and other sources, as well as preventing mercury from adhering to sampling equipment, vessel walls, glassware, etc. which may jeopardize the assay.

The analytical procedures should be scrutinized and monitored continuously and internal and inter laboratory control programs should be maintained. Such programs do exist, and new laboratories are urged to adopt them.

Measurement of mercury content of body fluids is generally easier to standardize than measurement of mercury in the various tissues of the body. Also, it should be emphasized that assessments based on mercury content in hair from the scalp or the pubic region are of questionable validity, because values derived from such analyses do not reflect the amount of mercury released from dental amalgam.

A critical review of the methods and procedures used to determine the mercury content of tissues and organs in some human studies—even in many that are often cited—suggests that the results are ambiguous, inaccurate and sometimes false. For these reasons the conclusions drawn from such studies are severely impaired and at times completely useless.

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Question 3. Are there data demonstrating that mercury released from dental amalgam gives rise to, or contributes to, toxic systemic effects?

Although mercury is known to be a weak allergen and allergic reactions may occur (see Question 5) no evidence exists of systemic toxic effects from mercury released from dental amalgam.

In Swedish clinical studies, including large numbers of individuals claiming to suffer from various somatic symptoms and diseases caused by amalgam, the patients were subject to detailed medical and dental examinations and follow-up for several years. None of these studies support the view that the complaints of the patients studied were related to the presence or the number of amalgam fillings.

Even the number of case reports published in scientific journals dealing with individual patients suffering from various symptoms ascribed to toxic effects of amalgam, and who claimed relief after removal of the amalgam fillings, is very small. This fact is especially important in view of the many millions of patients all over the world who have had their teeth restored with amalgam.

Kidney dysfunction following severe industrial occupational exposure to mercury has led to speculation of a similar role for mercury from dental amalgam. It should be noted that the exposure to mercury in these industrial workers was extremely high compared with the levels produced by vapour from amalgam fillings. There are currently no scientific data to support the hypothesis that mercury from dental amalgam causes disturbance of kidney functions in humans. Moreover despite the great interest devoted to clinical research on kidney function in recent decades, no observations on the existence of a relationship between mercury from amalgam and kidney function have been made.

Neurological diseases such as multiple sclerosis and amyotrophic lateral sclerosis have also been alleged to be caused by mercury released form dental amalgam. However, it must be emphasized that there is no evidence for the existence of such relationship.

Epidemiological studies in Sweden have not revealed that amalgam fillings are a risk factor for cardiovascular disease, diabetes mellitus, cancer, or early death.

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Question 4: Are there data demonstrating that mercury released from dental amalgam may cause effects on the immune system in man?

Mercury compounds, as it happens, require conjugation to a carrier to be able to induce a specific immune response. Intravenous injections with mercury chloride (HgCl2) have been found to polyclonally activate T and B cells in vivo as evidenced by increased proliferation and polyclonal antibody synthesis including a variety of auto antibodies. These effects have been induced by mercury in doses as low as 50-100 µg /100 g body weight given at various times. However, mercury chloride can only induce polyclonal T-cell activation in a very restricted number of rat and mouse strains. Mercury chloride appears to be unique among known polyclonal T-cell activators in its requirement for certain genes in the MHC region.

The interest has been focused on certain auto antibody specificity's such as anti-DNA antibodies, antibodies against glomerular basement membrane and immune complex mediated glomerulonephritis. However, in contrast to other known polyclonal B-cell activators, HgC12 induces disease. Most likely, the immune complexes and the antiglomerular basement antibodies are responsible for the development of certain kidney disorders such a proteinuria and nephrosis, but no renal failure develops. These auto immune manifestations require the presence of T-cells, and only occur in certain animal strains, Brown Norway rats and A. SW mice are the most susceptible to disease induction by mercury. It has been shown that the susceptibility genes were localized to the MHC region. also, in humans many auto immune diseases are under HLA-control, but no HLA-controlled specific reactivity to mercury has been found. The mechanism by which mercury can induce auto immunity is not known.

There are few studies on the effect of mercury on the immune system in humans. Mercury has been used therapeutically in various disorders and there are reports on mercury-induced membranous glomerulopathy and glomerulonephritis. These might be due to immunological reactions. Immunological reactions to mercury have been found in man and skin testing has been the most common method to evaluate hyperactivity to mercury in exposed individuals. Severe allergic reactions have been observed in people exposed to mercury ointments and mercury vapour. Some workers exposed to metallic mercury have developed nephritic syndrome and the disease has had immunological components, such as deposits of immunoglobulin and complement in the glomeruli.

Studies on possible immunological effects of mercury in silver-amalgam are few. In one study it was found that dental students showed a higher incidence of positive skin tests to mercury with longer exposure time. In another report, dental students were shown to have a higher frequency of certain sub populations of blood T cells, which has been used as a sigh of "immunoactivation." However, there is no link to specific reactivity to mercury, rather non-specific, possibly inflammatory reactions are involved. Finally, skin tests have also been performed in a study in patients with lichenoid oral mucosal lesions and in patients with burning mouth syndrome without lichenoid lesions. In one report reactions to mercury were found in one third of the patients with lichenoid lesions, but not in patients in the other two thirds. However, another study on patients with similar symptoms used biopsies from affected areas in contact with amalgam and in areas not in contact with amalgam and failed to find any differences with regard to lymphocyte sub populations or signs of immune activation.

In summary, there are no data to support the idea that the mercury from amalgam fillings is responsible for auto immune disease or kidney lesions in man, or that mercury from amalgam fillings negatively affects the immune system.

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Question 5: Does silver amalgam cause systemic or local allergic reactions?

Systemic reactions to mercury from amalgam, such as urticaria and asthma, seem to be extremely rare, this is also true for delayed type IV-reactions. Contact dermatitis caused by amalgam fillings has been reported in the scientific literature in less than 100 patients. Other constituents of the amalgam than mercury may also be responsible for these reactions. Hypersensitivity demonstrated by patch tests might be derived from other sources of mercury, such as preservatives in vaccines, drugs and cinnabar in tattoos.

The incidence of local allergic reactions also appears to be low. Lichenoid oral mucosal lesions in contact with amalgam fillings do occur, and skin tests of such patients with various test antigens have, in some cases, shown hyperactivity to mercury compounds. On the other hand, studies of lichenoid lesions or normal mucosa in contact with amalgam fillings have revealed no differences in lymphocyte reactivity or in the availability of specific rnarkers in lymphocytes. When such lichenoid reactions occur, they can be eliminated by the removal of the restoration.

In summary, very few patients appear to be at risk of developing systemic or local allergic reactions in response to the placement of amalgam fillings.

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Question 6: Will mercury released from dental amalgam give rise to teratological effects?

A Polish study has claimed that a significant positive correlation exists between the mercury concentration in the hair of female dental personnel with occupational exposure to mercury and their history of reproductive failures. Information obtained from the main author in 1991 revealed that the hair was assessed for mercury in 1985-86, but that the five children with spina bifida were born in 1968, 1972, 1977, 1980 and 1982. It must be emphasized that the hair samples only represent the mercury levels at the time of assessment and cannot be representative of pregnancies prior to that time. Both the methods of establishing the amount of mercury in the bodies of these women and the design of the study suggest that the results are highly questionable.

Other studies on female dental personnel have not revealed any difference in the rates of birth defects or spontaneous abortion. Adverse effects, such as decreased libido and fertility in men and menstrual disturbances and spontaneous abortions in women have been reported in industrial workers exposed to metallic mercury vapour. However, this occupational exposure was extremely high compared to that from amalgam fillings, and the results are irrelevant.

Since elemental mercury passes through the placenta, it has been inferred that mercury vapour released from dental amalgam is a potential hazard to the fetus. The concentration of a teratogen at the target tissue is determined not only by the dose and the rate of placental transfer, but also by other factors such as distribution within the mother, affinity to the fetal liver and blood, the hematocrit value and the passage through the ductus venosus. These factors might explain the toxicological mechanisms and species differences, and must be considered if the results of animal experiments are to be extrapolated to human conditions. It should also be emphasized that although measurable amounts of mercury may be incorporated in certain fetal organs, this is not evidence of a toxicological or teratological effect per se.

As an indication of human fetal exposure, the mercury concentration in cord blood and maternal blood gives a fetal to mother-ratio (F/M ratio) slightly over or close to one as 14 studies have revealed. The observation that in sheep the F/M ratio of blood-Ha in late gestation exceeded one and was in fact as high as four, has attracted a great deal of attention, but this might indicate a species peculiarity in handling elemental mercury. It has been shown that in the guinea pig elemental mercury is readily oxidized and accumulated in the fetal liver, and consequently little is distributed to other fetal organs. Also, postnatally this mercury, temporarily trapped in the fetal liver, helps to reduce exposure and avoid concentration peaks in other, more vulnerable, organs such as the brain.

Organic and inorganic mercury concentrations in human fetal brain and liver have been determined. In the brain the total mercury concentration in five fetuses ranged from 7.1-65.0 ng/g, but inorganic mercury was detected in only one. In four fetuses the total mercury concentration in the liver ranged from 26.1-89.8 ng/g and the inorganic fraction ranged from 27.2-59.9%. Pregnant women derive organic mercury from the diet. Those with amalgam restorations may, in addition, take in metallic mercury vapour from the fillings.

Restriction of amalgam therapy during pregnancy has been advocated on the grounds that the insertion of removal of amalgams causes an acute peak exposure to mercury vapour. Available scientific data do not support such a restrictive policy.

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Question 7: Are there data supporting that mental and psychosomatic disorders are potential side-effects of dental amalgam ?

Available data suggested that in patients who perceive that they suffer from mercury intoxication, the symptoms are mostly of low or moderate grade, but severe enough for the patients to feel sick. Neurotic symptoms dominate with a mixture of anxiety, depression and asthenia. Probably these symptoms also explain the mandibular dysfunction's which increase the level of anxiety in vicious circles. Although in the general population there is a relationship between the number of amalgam surfaces and mercury levels in plasma and urine, the levels are far below those found in workers in the mercury industry, and also lower than those in dental personnel.

Studies have demonstrated that the mercury levels in plasma and urine are very similar in patients who believe they are mercury intoxicated and in control subjects with the same number of fillings. This does not support the hypothesis that the mental are caused by mercury. In fact, no relationship between the mercury levels and severity of mental symptoms has been established in scientific studies.

The focus on the amalgam problem may give these patients an immediate and transient relief from their anxiety and depression. However, such patients need a thorough medical, oral, psychological and social examination and counseling to address the core problems of their lives. The current health care system has not always been successful in managing these patients' problems.

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Question 8: Have general or local side-effects been attributable to alternative restorative materials?

Materials to replace dental amalgam are available, but there is no one material that can completely replace amalgam. Inlays, inlays and crowns in gold and ceramic can replace amalgam in larger posterior cavities or in medium-sized cavities on stress-bearing tooth surfaces. Smaller cavities in premolars and molars can now be restored with resin-based composite materials, glass ionomers or compacted gold.

Current evidence suggests that casting alloys, composite resins, glass ionomers and ceramics placed in teeth, release chemical components and degradation products, and that these substances are released from the restorations over time. These substances may be absorbed locally, inhaled or swallowed. The general systemic reactions will depend on the chemical composition of the materials or the degradation products, and their absorption and accumulation rates, as well as on several other factors. In any event, based on available data the incidence of general biological side-effects appears to be low. However, this paucity of information on systemic toxicity could be due to the lack of longitudinal dam on some of the newer materials.

Evidence suggests that non-amalgam restorative materials may induce local reactions in some individuals. Lichenoid lesions in the oral mucosa in contact with resin-based composites have been described, but these reactions usually disappear upon removal of the restoration.

Based on analyses of 16,000 treatments in 13,000 patients, the incidence rate of systemic or local toxic or allergic reactions to all restorative dental materials in current use has been estimated to be less than 1:1000, with the reactions being of minor severity.

In summary, virtually all non-amalgam materials used in tooth restorations contain constituents that could contribute to local reactions. However, there is no clear evidence that these substances are released in sufficient quantities and forms to produce general toxic effects or severe hypersensitivity reactions in humans.

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Question 9: Is mercury in dental amalgam an environmental hygiene problem ?

On a global basis approximately 10,000 tons of mercury are produced annually for anthropogenic use. It has been estimated that 3-4 percent is used in restorative dentistry. According to most recent statistics 1.7 tons of dental mercury is sold annually in Sweden. In dental practice approximately 50 percent of the freshly triturated amalgam is used to produce amalgam fillings, 10 percent is collected as primary surplus and the remaining 40 percent is discharged with the waste water or as solid waste. It should be noted, however, that these estimates are highly dependent on local clinic routines and may vary considerably.

Major chunks of amalgam produced during the fabrication of amalgam restorations are usually carefully collected and sold for reprocessing. Minor amalgam particles develop during the production of new fillings or amalgam dust is formed during the removal of old restorations.

Studies have found significantly lower levels of mercury in waste water when dental clinics were equipped with amalgam separating devices. Approved amalgam separators are now mandatory clinic equipment in a number of countries, including Sweden. Recent studies have shown that by practicing simple guidelines for the management of solid waste, including collecting extracted teeth with amalgam fillings and trituration capsules, most of this waste can be properly handled, and the amount of mercury from dental sources be significantly reduced.

Very few data are available on the potential environmental effects of amalgam fillings from deceased and buried persons. The emission of mercury from Swedish crematoria has been estimated, but published data are sparse. Emission filters that effectively reduce the release of mercury from crematoria are available and may significantly decrease the release of mercury into the air.

With proper mercury hygiene measures, mercury emerging from dental amalgam does not per se represent an environmental hygiene problem.

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Question 10: Do available data justify discontinuing the use of dental amalgam or recommending replacement?

Silver amalgam has been used as dental restorative material for more than 150 years. Even today, with the advent of new synthetic non-metallic materials and novel, time-saving procedures, silver amalgam is the most widely used and cost-effective dental material in restorative dentistry.

Although minute amounts of mercury are released from amalgam restorations, these do not cause demonstrable adverse effects of significance to the general public. Published reports of systemic toxic effects documented to have been caused by mercury from dental amalgam, are not available in the scientific literature. Local allergic reactions are exceedingly rare, and when they occur, they can be eliminated by the substitution with another material. Available scientific evidence does not justify the discontinuation of the use of amalgam, nor does it endorse a clinical concept that recommends the removal and replacement of satisfactory amalgam fillings with other materials.

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CONCLUSIONS

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SCIENTIFIC PANEL

Bo Bergman, professor OD, Department of Prosthetic Dentistry, University of Umea, Umea, Sweden (Chairman)

Harry Bostrom, professor MD, Department of Medicine, University of Uppsala, Uppsala, Sweden

K. Sune Larsson, professor OD, Department of Odontological Toxicology, Karolinska Institute, Huddinge, Sweden

Harald Loe, professor Dr. Odont, Director, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland USA

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MODERATORS

Harry Bostrom, professor MD, Department of Medicine, University of Uppsala, Uppsala, Sweden

Harald Loe, professor Dr. Odont, Director, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland, USA

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PLANNING COMMITTEE

Bo Bergman, professor OD, Department of Prosthetic Dentistry, University of Umea, Umea, Sweden (Chairman)

Harry Bostrom, professor MD, Department of Medicine, University of Uppsala, Uppsala, Sweden

K Sune Larsson, professor OD, Department of Odontological Toxicology, Karolinska Institute, Huddinge, Sweden

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SPEAKERS

Dorthe Arenhold Bindslev, associate professor Ph.D., Department of Oral Pathology and Toxicology, Royal Dental College, Aarhus, Denmark

Calle Bengstssun, professor MD, Department of Primary Health Care, University of Goteborg, Gothenburg, Sweden

Maud Bergman, professor OD, Department of Dental Materials and Technology, University of Umea, Umea, Sweden

Thomas W. Clarkson, professor PhD. MD/hc, Director, Environmental Health Sciences Center, University of Rochester, Rochester, NY, USA

K. Sune Larsson, professor OD, Department of Odontological Toxicology, Karolinska Institute, Huddinge, Sweden

Ivar Mjor, professor Dr. Odont, Director, Scandinavian Institute of Dental Materials, Haslum, Norway

Goran Moller, professor MD, Department of Immunology, University of Stockholm, Stockholm Sweden

Jan-Otto Ottoson, professor MD, Department of Psychiatry, University of Goteborg, Gotenburg, Sweden

Eva Selin, associate professor Ph.D., Department of Physics, (Chalmers University of Technology, Gothenburg, Sweden

Staffan Skerfving, professor MD, Department of Occupational Medicine, University of Lund, Lund, Sweden

Per Skrabanek, professor Dr., Department of Community Health, University of Dublin, Dublin, Ireland

Murray J. Vimy, professor MD, Department of Medicine and Medical Physiology, University of Calgary, Calgary, Alberta, Canada

Per Olov Wester, professor MD, Department of Medicine, University of Umea, Umea, Sweden

THE SWEDISH MEDICAL RESEARCH COUNCIL

Swedish Medical Research Council
Box 6713
S-113 85 STOCKHOLM
Sweden

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