Immune Reactive Conditions: The
mercury connection to inflammatory and immune reactive conditions (asthma,
eczema, lupus, Scleroderma, celiac, chron’s, allergies,etc.)
I.
Increasing Incidence of Inflammatory, Immune Reactive Conditions
The incidence of allergic and immune reactive
conditions such as allergies, asthma, eczema, lupus, psoriasis, etc. have been
increasing rapidly in the United States over the last decade(1-4). The prevalence of asthma doubled over the
last decade(4) to approximately 31 million, 11.5% of the total
population(2). At least 50 million have
allergies(19%)(3), and the largest increase has been in infants(1-4), with
approximately 10 % of infants- approximately 15 million in the U.S. with
systemic eczema(1). Approximately 12% have had chronic sinusitis(3c). Many
studies have found exposure to mercury and other heavy metals to be common
causes of such conditions as will be shown in this paper.
II.
Oral Metal Exposures from Dental Materials and Oral Effects
The largest source of exposure to the metals that
will be shown to commonly cause inflammatory, immune reactive conditions is
from dental metals. Having dissimilar metals in the teeth, e.g.-
amalgam(mercury,copper,tin,silver), gold alloys(gold,palladium), nickel or stainless steel crowns(nickel,cobalt) causes galvanic electrical currents, and
much higher mercury vapor levels in oral
air and metal levels in oral tissues. (101-110). Government agencies and
medical studies have found that the largest source of mercury exposure in most
people is from dental amalgam fillings(122-130). For those with amalgam dental
fillings, exposure from fillings amounts to from 50 to 90 percent of exposure,
with the average being about 75 % of total exposure (123,125‑130).
Mercury is an unusual metal commonly a liquid at room temperature and
vaporizing to a gas from its liquid or solid states. The studies found that mercury amalgams are
unstable due to mercury's vaporization and galvanic action(101-110), leaking
mercury vapor continuously into the lungs and saliva at levels exceeding
government health standards(110,122,124,126).
Dental amalgam is also a major source of methyl mercury exposure for
many since oral and intestinal mercury is methylized
by oral bacteria and other methyl donars(121,130).
The other most common sources of mercury exposure are methyl mercury from fish
or mercury thimerosal from vaccines, which is a major source of exposure mostly
for infants or those frequently receiving flu shots(113).
The amount
of mercury released into saliva has been found by large studies to be about 1.5
to 1.9 micrograms per liter for each additional amalgam filling (116),
resulting in an increase of about 1 microgram per liter in urine(125) and even
higher levels excreted in feces(128). Average mercury levels in gum tissue near
amalgam fillings are over 100 ppm, and are the result
of flow of mercury into the mucous membrane because of galvanic currents with
the mucous membrane serving as cathode and amalgam metals as
anode(101,104,105,114). Concentrations of mercury in oral mucosa for a
population of patients with 6 or more amalgam fillings taken during oral
surgery were 20 times the level of controls(114). Amalgam also releases significant amounts of
silver, tin, and copper which also have toxic effects, with organic tin
compounds formed in the body being even more neurotoxic than organic mercury.
Mercury and other
metals accumulate in the oral cavity in fibroblasts, macrophages, and
multinuclear giant cells of connective tissue, in blood vessel walls, along
nerve sheath fibres, in basement-membranes of mucosal
epithelium, striated muscle fibres, along collagen
bundles and elastic tissue, in acini of salivary
glands, and in tooth roots and jaw bones(104,105). Such mercury including that
in the commonly formed amalgam tattoos moves to other parts of the body over
time in significant amounts and more rapidly than the other metals. Macrophages
remove mercury by phagocytosis and the mercury moves
to other parts of the body through the blood and along nerves. Oral galvanism, where electric currents caused by
mixed metals in the mouth take the metals into the gums and oral mucosa,
results in accumulating mercury and other dental metals at the base of teeth
with large amalgam fillings or metal crowns over amalgam base(101-111). Such metals are documented to cause local and
systemic lesions and health effects such as inflamed tissues, metal mouth,
discomfort, tooth pain, gingivitis, and oral lichen planus(102-107,111,15,16,39-43). Most usually improve from these conditions
after removal of amalgam fillings and/or the amalgam tattoos by
surgery(102,106,107,109,73b,126,127,15,16,39-43). The high levels of accumulated mercury also
are dispersed to other parts of the body. Some
studies have also found persons with chronic exposure to electromagnetic
fields(EMF) to have higher levels of mercury exposure and excretion(117,118).
Such fields are known to induce current in metals and would increase the
effects of galvanism..
III. Mechanisms by Which Mercury and Heavy Metals
Cause Chronic Inflammatory Conditions
Metals like mercury bind to
SH-groups(sulfhydryl) in sulfur compounds like amino
acids
and
proteins, changing the structure of the compound that it is attached to. This often results in suppression of the
immune system and in the immune systems T-cells not recognizing them as
appropriate nutrients and attacking them(78,18) with chronic exposure resulting
in autoimmunity. Such binding and
autoimmune damage has also been documented in collagen(18). Metals by binding to SH radicals in proteins
and other such groups can cause autoimmunity by modifying proteins which via
T-cells activate B-cells that target the altered proteins inducing autoimmunity
as well as causing aberrant MHC II expression on altered target
cells(81de).
Mercury and other toxic
metals cause release of inflammatory cytokines such as Tumor Necrosis
Factor-alpha(TNFa) and Interleukin-4 (47), which will
be documented to be factors in the chronic inflammatory conditions discussed here,
including asthma, lupus, rheumatoid arthritis, Scleroderma, celiac and chron’s disease, etc.
Studies have demonstrated that low concentrations of mercury(HgCl2,ie,
10(-9)-10(-15) M) significantly enhanced chemiluminescence,
as well as stimulated H2O2 production by polymorphonuclear
leukocytes(137). These studies clearly demonstrate the ability of extremely low
levels of HgCl2 not only to suppress various PMN leukocyte functions involved in host defense,
but also to stimulate reactive oxygen metabolism(137,95). In vivo, these HgCl2
effects would not only compromise host defense but also promote tissue injury
via the local production of reactive oxygen metabolites. This has been demonstrated increase effects
of factors in cardiovascular disease
and neurological disease. Melatonin,
vitamin E, and vitamin C have been found to counter these adverse effects(95a).
HgCl2 induces a protein
kinase C-dependent Ca2+ influx through L-type calcium
channels(65acd). The calcium/calcineurin-dependent
pathway and protein kinase C activation are both
implicated in HgCl2-induced IL-4 gene expression; and HgCl2 can activate directly protein kinase C, which is one of the main intracellular targets
for HgCl2. Inorganic mercury exposure
results in T cell polyclonal activation and the expansion of pathogenic autoreactive anti-class II Th2 cells . These cells
produce interleukin (IL)-4 and induce a B cell polyclonal activation that is
responsible for autoimmune disease. These effects of HgCl2
appear to be independent of antigen-specific recognition.
Na(+),K(+)-ATPase is a transmembrane protein
that transports sodium and potassium ions across cell membranes during an
activity cycle that uses the energy released by ATP hydrolysis. Mercury, nickel, aluminum, and other toxic metals are documented
to inhibit Na(+),K(+)-ATPase function at very low
levels of exposure(94,97,65). Studies have found that in asthma, lupus,
rheumatoid arthritis, Scleroderma, celiac/chron’s/IBS,
and eczema cases there was a reduction in serum magnesium and red blood
cell(RBC) membrane Na(+)-K+ ATPase activity and an
elevation in plasma serum digoxin (87-90,65).
The activity of some free-radical scavenging enzymes, concentration of
glutathione decreased significantly, while the concentration of serum lipid peroxidation products and nitric oxide increased. The inhibition of Na+-K+ ATPase
can contribute to increase in intracellular calcium and decrease in magnesium,
which can result in 1) defective neurotransmitter transport mechanism, 2)
neuronal degeneration and apoptosis, 3) mitochondrial dysfunction, 4) defective
golgi body function and protein processing
dysfunction. It is documented that
mercury and toxic metals are common causes of
these conditions (22,30,29,47-50,65,87-90,95,96,98,28,etc.) A study
found that 39% of a group of chron’s disease patients
tested were immune reactive to nickel (100).
Studies have also found mercury and
lead cause autoantibodies to neuronal proteins and neurofilaments, (18,79ag,80,82). The thymus gland plays a significant part in
the establishment of the immune system and lymphatic system from the 12th
week of gestation until puberty.
Inhibition of thymus function can thus affect proper development of the
immune and lymphatic systems. Lymphocyte
differentiation, maturation and peripheral functions are affected by the thymic protein hormone thymulin.
Mercury at very low concentrations has been seen to impair some lymphocytic functions causing subclinical
manifestations in exposed workers. Animal studies have shown mercury
significantly inhibits thymulin production at very
low micromolar levels of exposure(131). The metal allergens mercuric chloride and
nickel sulfate were found to stimulate DNA synthesis of both immature and
mature thymocytes at low levels of exposure, so
chronic exposure can have long term effects(132). Nickel in stainless steel braces and crowns
is a source of reactivity and autoimmunity along with gold and palladium in
crowns(32bc,16-18) Also, micromolar levels of
mercuric ions specifically blocked synthesis of ribosomal RNA, causing fibrillarin relocation from the nucleolus to the nucleoplasm in epithelial cells as a consequence of the blockade of ribosomal RNA
synthesis(133,81e). This appears to be a
factor in deregulation of basic cellular events and in autoimmunity caused by
mercury. There were specific
immunotoxic and biochemical alterations in lymphoid organs of mice treated at
the lower doses of mercury. The immunological defects were consistent with
altered T-cell function as evidenced by decreases in both T-cell mitogen and mixed leukocyte responses. Mercury caused increased immunoreactivity
for glial fibrillary
protein at 1 nanamole (0.2 ppb) concentration, and microglial response at
even lower levels(134). There was a particular
association between the T-cell defects and inhibition of thymic
pyruvate kinase, the
rate-limiting enzyme for glycolysis(135). Pyruvate and glycolysis problems are often seen in mercury toxic
children being treated for autism(136).
One mechanism of
mercury’s affect on contact sensitivities is the inhibition of glutathione S- transferase(92), which is a modulator of inflamation. Mercury also causes intestinal damage and
leaky gut, causing metabolic damage and increasing food sensitivities(93). Inorganic mercury was found to be a cause of
systemic eczema and digestive problems by a
Japanese study(15).
Many studies including
patch tests and immune reactivity tests have been carried out to assess the level
of mercury sensitivity in different populations. They have found that there is a significant portion of
the population that are reactive and sensitive to mercury and such have
significant effects. In a group of
medical students tested by patch test, 13 % were sensitive to mercury(20). The mercury sensitized students were found to
have more than average number of amalgam fillings, higher hair mercury than
non-sensitized students, and more allergic reactions to other things such as
cosmetics, soaps, shampoos, etc. Many
other studies have found similar levels of sensitization in recent years, with
those populations with higher exposures such as those with many fillings or
dental staff tending to have higher levels of sensitization(17-19) and more adverse
health effects. In a group of 8 with
contact eczema patch tested for mercury in Spain, all were positive for
mercurochrome, six to inorganic mercury, and some to thimerosal(21). This study like several others noted the
danger in patch tests for mercury as 2 of the patients suffered anaphylactic
shock after the patch test due to the extreme immune reactivity of some to
mercury.
Allergic contact eczema
is the most frequent occupational disease (1,91), and
the most common cause of contact eczema is exposure to metals(1, 5-14). The metals most commonly causing allergic
immune reactivity are nickel, mercury, chromium, cobalt, and palladium(5-13,18,
60,91). The highest level of
sensitization is to Infants, who are most reactive to thimerosal, a form of
mercury that has been used as a preservative in vaccines and eye
drops(14).
Antigen specific LST-test was performed on a large
number of patients with atopic eczema(33), using
T-cells of peripheral blood. 87% showed LST positive reactions to Hg, 87% to
Ni, 38% to Au and 40% to Pd They
removed LST positive dental metals from the oral cavities of patients.
Improvement of symptoms was obtained in 82% (160/196) of the patients within
1-10 months. Similar results have been
obtained at other clinics(34-38).***
Dental staff have been found to have significantly
higher prevalence of eye problems, conjunctivitis, atopic
dermatitis, and contact urticaria(91c). Finnish dental staff have the highest occupational
risk of contact dermatitis with 71% affected over time(91b)
with plastics, rubber, and mercury the most common causes of
sensitization. Korean dental technicians
have a high incidence of contact dermatitis, with dental metals the most common
sensitizers. Over 25% had contact dermatitis with over 10% sensitive to 5
metals, chromium, mercury, nickel, cobalt, and palladium(91a). 16.3% were immune reactive to mercury.
In asthma allergen
related T-lymphocytes cause release of inflammatory mediators from mast cells, esinophils, and lymphocytes, along with inflammatory cytokins such as Interleulin-4(Il-4), TNF-alpha, histamine,
and increased IgE(49i). It has also been documented that the majority
of cases have decreased serum magnesium levels, decreased NA+K+ATPase
levels, and increased digoxin levels(an inhibitor of NA+K+ATPase)(49d).
Mercury exposure has been documented to cause an increase in inflammatory
cytokines such as TNF-alpha and IL-4(47,49b,49e,65a,81abc). TNFA-alpha has been found to increase the
Ca(2+) sensitivity of agonist-stimulated phosphorylation
and contractility in airway smooth muscle (ASM) and increase airway
hyper-responsiveness(49a). TNFa levels have also been found to be significantly
correlated to levels of the inflammatory cytokines Il-4, Il-8, Il-13 released
from histamine-containing basophils which results in
histamine releases and increased IgE levels, as well
as airway reactivity, and asthmatic
attacks(49acfkl). The release of these inflammatory
cytokines has also been shown to be a factor in mercury’s inducement of autoimmunity
that is involved in the development of airway inflammation(49g).
Asthmatic patients are
especially susceptible to air pollution. Upon contact with an allergen, sensitized mast
cells release highly active proinflammatory
mediators. Allergen-mediated mast cell activation is an important mechanism in
the pathogenesis of atopic asthma. Epidemiologic
studies found a positive correlation between severity of symptoms among
asthmatic patients and the level of particulate matter (PM) in the air. Among
the constituents of PM are metals and transition metals. A Polish study(49b) observed that several
metal and transition metal ions activated mast cells and enhanced
allergen-mediated mast cell activation.
Metal and transition
metal ions also induced significant secretion of interleukin (IL)-4 and
increased antigen-mediated IL-4 secretion in mast cells. These effects of metal
and transition metal ions on mast cells were observed at concentrations that do
not result in direct cytotoxicity.
Genetic characteristics
have been found that affect the susceptibility
Many clinics and
studies involving thousands of patients have found that patients with allergic
reactive conditions such as oral lichen planus,
eczema, chronic allergies etc. usually recover or have significant improvements
after amalgam replacement. Of a group of
86 patients with CFS symptoms, 78% reported significant health improvements
after replacement of amalgam fillings within a relatively short period, and MELISA
test found significant reduction in lymphocyte reactivity compared to pre
removal tests(17). The improvement in symptoms and lymphocyte reactivity imply
that most of the Hg-induced lymphocyte reactivity is allergenic in nature. Patients with other systemic neurological
or immune symptoms such as arthritis, myalgia, OLP,
MCS, MS, etc. also often recover after amalgam replacement(15-18). Cases of documented clinical cases with
recovery after amalgam replacement include:
eczema and contact dermatitis(22,33,34,52-54,16b,99), psoriasis(33-36, 99), asthma(50,52,72,99),
lupus(16b,27,33,70,71,31,18),allergies(22,31,32,43,48,49,52,53,66-74,99), chronic multiple chemical sensitivities
(32,52,70,71,73,75-77,17,31),
Oral lichen planus (15,16,39-43),
CFS (17,31,33,52-54,66,70,71,75,84,85)
and muscular/joint pain/fibromyalgia
(17,31,53,72,84) MS(16b,31,99) ***
As an example of experience of those with allergic conditions
after amalgam replacement, a German study(52) followed a large group of
patients. Over 50% followed indicated they experienced significant improvement
after amalgam replacement for 5 chronic conditions followed: asthma, chronic bronchitis,
polymyosis, eczema, contact allergy and food allergy. The study showed that skin allergy(patch)
test apparently is not a reliable indicator of those with mercury related
health problems. Patch test was positive in only 13.1 % of patients, whereas
more than 50% of patients had significant health improvement for most
conditions followed.***
References
(1) National Institute of
Arthritis and Musculoskeletal and Skin Diseases, (U.S.), National Institutes of
Health, April, 2003; www.niams.nih.gov/hi/topics/dermatitis/index.html#link_b
& Rudikoff D and Lebwohl
M. "Atopic dermatitis." Lancet
351(9117): 1715-21. 1998.
(2)
U.S. Centers for Disease Control. National Center for Health Statistics, Asthma Prevalence, Health Care Use
and Mortality, 2000-2001,
www.cdc.gov/nchs/products/pubs/pubd/hestats/asthma/asthma.htm
(3) American Academy of Allergy, Asthma and Immunology (AAAAI). The Allergy Report:
Science Based Findings
on the Diagnosis & Treatment of
Allergic Disorders, 1996-2001;
www.niaid.nih.gov/factsheets/allergystat.htm
& (b) The International Study of Asthma
and Allergies in Childhood (ISAAC) Steering Committee. "Worldwide
variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis,
and atopic eczema: ISAAC." Lancet 351:
1225-32. 1998.
&(c)
U.S. Centers for Disease Control. Fast Stats A-Z, Vital and Health Statistics, Series
10, no. 200, Table 57. 1996. Web:
www.cdc.gov/nchs/data/series/sr_10/sr10_200.pdf.
&
(d) U.S. CDC, National Center for Chronic Disease Prevention and Health
Promotion, Lupus Fact Sheet,
www.cdc.gov/od/oc/media/pressrel/fs020503.htm
(4)
Stephen Redd, Chief, Air Pollution and Respiratory
Health Branch, National Center for Environmental Health, Centers for Disease Control and Prevention
(CDC), Asthma in the United States: Burden and Current
Theories, Environmental Health
Perspectives Supplements Volume 110, Number 4, August 2002.
(5) Romaguera
C, Vilaplana J.
Contact dermatitis in children: 6 years experience. Contact Dermatitis
1998; 39(6): 277-80.
(6) Xue
C, He Z, Zhang H, Li S. Study on the
contact allergen in patients with dermatitis and eczema. Wei Sheng Yen Chiu 1997, 26(5): 296-8.
(7) Nakada T,
Higo N, Iijima M, Nakayama H, Maibach
HI. Contact
Dermatitis.
1997 May;36(5):237-9.;
(8) Brasch J, Geier J, Schnuch A. Differentiated contact allergy lists serve
in quality improvement. Hautarzt 1998; 49(3): 184-91;
(9) Schafer T, Bohler
E, et al, Epidemiology of contact allergy in adults. Allergy. 2001 Dec;56(12):1192-6.
(10) Meding
B, Jarvholm B.
Hand eczema in Swedish adults and children - J Invest Dermatol
2002 Apr;118(4):719-23;
(11) Guo YL,
Wang BJ, Lee JY, Chou SY. Occupational hand dermatoses of
hairdressers in Tainan City. Occup Environ Med.
1994 Oct;51(10):689-92
(12) Sun CC. Allergic contact dermatitis
of the face from contact with nickel and ammoniated mercury. Contact Dermatitis 1987, 17(5):306-9; &
[Allergic contact dermatitis][Article in Polish] Pol Merkur Lekarski.
2003 Jun;14(84):605-8. Gliński W;
(13) Lindemayr H, Drobil M, .[Eczema of the lower
leg and contact allergy] [German] Hautarzt. 1985
36(4): 227-31.
(14) Patrizi
A, Rizzoli L, Vincenzi C, Trevisi
P, Tosti A. Sensitization to thimerosal in atopic
children. Contact Dermatitis,
1999, 40(2): 94-7.
& Manzini
BM, Ferdani G, Simonetti V,
Donini M, Sedernari S. Contact sensitization in children. Pediatr Dermatol 1998; 15(1): 12-17.
& Forstrom L, Hannuksela M, Kousa M, Lehmuskallio E. Merthiolate
hypersensitivity and vaccination. Contact Dermatitis.
1980 Jun;6(4):241-5.
& Audicana MT, Munoz D, del Pozo MD, Fernandez E, Gastaminza
G, Fernandez de Corres L. Allergic contact dermatitis from mercury
antiseptics and derivatives: study protocol of tolerance to intramuscular injections
of thimerosal. Am J Contact Dermat. 2002
Mar;13(1):3-9.;
(15)
Koizumi A et al, Mercury poisoning as cause of smelter disease. Lancet 1994;
343(8910): 1411-2.
(16) V.D.M.Stejskal et al, “Mercury-specific Lymphocytes: an
indication of mercury allergy in man”, J. Of Clinical Immunology, 1996, Vol 16(1);31-40. www.melisa.org; & (b)Prochazkova J, Sterzl I, Kucerova H, Bartova J, Stejskal VD; The beneficial effect of amalgam replacement on health in
patients with autoimmunity. Neuro Endocrinol Lett.
2004 Jun;25(3):211-8.
www.melisa.org
(17) Stejskal VDM, Danersund A, Lindvall A, Hudecek R, Nordman V, Yaqob A et al. Metal-
specific memory lymphocytes: biomarkers of sensitivity in man. Neuroendocrinology
Letters, 1999; 20: 289-98. http://www.melisa.org/chronic-fatigue-syndrome.php
(18) Jenny Stejskal,
Vera Stejskal. The role of metals in autoimmune
diseases and the link to neuroendocrinology Neuroendocrinology
Letters, 20:345‑358, 1999.
(19) Valentine-Thon E, Schiwara HW, Validity of MELISA for metal sensitivity
testing; Neuroendocrinol Lett,
2003, Feb-Apr, 24(1-2): 57-64.
(20) Mori T, Hirai T, Tomiyama T, Iida K, Miyakoshi S, Sato K, Kusaka Y, Yanagihara M, Ueda K,
Mercury sensitization induced by environmental exposure. Nippon Eiseigaku Zasshi 1998 Jan;52(4):661‑6 .
(21) Galindo PA, Feo F, Fernadez F. Mercurochrome allergy: immediate and delayed hypersensity.
Allergy 1997; 52(11): 1138-41.
(22) Redhe O, Pleva J. Recovery from asthma and
allergies after removal of dental amalgam fillings. Int J of Risk & Safety in Medicine 1994; 4:229-236.
(28)
(a)P.E. Bigazzi, “Autoimmunity and Heavy Metals”,
Lupus, 1994; 3: 449-453;
&(b) Pollard KM, Pearson Dl, Hultman
P. Lupus-prone mice as
model to study xenobiotic-induced autoimmunity. Envriron Health Perspect 1999; 107(Suppl 5):
729-735;
& (c)Nielsen JB; Hultman P.
Experimental studies on genetically determined susceptibility to mercury‑induced autoimmune response. Ren Fail 1999 May‑Jul;21(3‑4):343‑8;
&
(d)Hultman P, Enestrom S,
Mercury induced antinuclear antibodies in mice,
Clinical and Exper Immunology, 1988, 71(2):
269-274;
(29) (a)C.Gordon et al,
“Abnormal sulphur oxidation in systemic lupus erythrmatosus(SLE)”, Lancet, 1992,339:8784,25-6;
&
(b)P.Emory et al, “Poor sulphoxidation
in patients with rheumatoid arthitis”, Ann Rheum Dis, 1992,
51:3,318-20; & (c)P.Emory et al, Br J Rheumotol, 1992, 31:7,449-51;
&(d)
Wilkinson LJ, Waring RH. Cysteine dioxygenase:
modulation of expression in human cell lines by cytokines and control of sulphate production. Toxicol In Vitro. 2002 Aug;16(4):481-3;
(30)(a)S.A.
McFadden, “Xenobiotic metabolism and adverse
environmental response: sulfur-dependent detox
pathways”,Toxicology, 1996, 111(1-3):43-65; &
(b)Markovich et
al, "Heavy metals (Hg,Cd) inhibit the activity of the liver and kidney sulfate
transporter Sat‑1", Toxicol Appl Pharmacol, 1999,154(2):181‑7;
&(c)
Alberti A, Pirrone P, Elia M, Waring RH, Romano C. Sulphation deficit in “low-functioning” autistic children. Biol Psychiatry 1999, 46(3):420-4;
& (d)Quig
D, Doctors Data Lab,"Cysteine metabolism
and metal toxicity", Altern Med Rev, 1998;3:4,
p262‑270,
& (e) J.de Ceaurriz et al,
Role of gamma‑glutamyltraspeptidase (GGC) and extracellular glutathione in dissipation of inorganic mercury",J Appl
Toxicol,1994, 14(3): 201‑;
(31)
Huggins HA, Levy,TE, Uniformed Consent: the hidden
dangers in dental care, 1999, Hampton Roads Publishing Company Inc;
& (c)
Huggins, HA, Solving the MS Mystery:
Help, hope and recovery, 2002;
(32)Barnett JH,
Discoid lupus erythematosus exacerbated by
contact dermatitis. Cutis 1990
Nov;46(5):430‑2 (nickel & lupus); & (b) Schultz
JC, Connelly E, Glesne L, Warshaw
EM. Cutaneous and oral eruption from oral exposure to nickel in dental braces. Dermatitis. 2004
Sep;15(3):154-7; & Genelhu MC, Marigo M et al;
Characterization of nickel-induced allergic contact stomatitis
associated with fixed orthodontic appliances, Am J Orthod
Dentofacial Orthop. 2005
Sep;128(3):378-81; &(c) Marcusson JA,
Contact allergies to nickel sulfate, gold sodium thiosulfate
and palladium chloride in patients claiming side-effects from dental alloy
components, Contact Dermatitis, 1996
May, 34:5, 320-3
(33) P.Dallmann,”kon nen durch Quecksilber entstehen? PeDa_Eigenverisg,
1995; & Perioral
dermatitis after dental filling in a 12-year-old girl: involvement of
cholinergic system in skin neuroinflammation? ScientificWorldJournal. 2008 Feb 6;8:157-63, Guarneri F, Marini H.
(34) Kohdera T, Koh N, Koh R. Antigen-specific lympocyte stimulation
test on patients with psoriasis vulgaris. XVI
International Congress of Allergology and Clinical
Immunology, Oct 1997, Cancoon, Mexico;
& Ionescu G. Schwermetallbelastung bei atopischer
Dermatitis und Psoriasis. Biol Med 1996; 2:65-68
(35)Britschgi M, Pichler WJ. Acute generalized exanthematous
pustulosis, a clue to neutrophil-mediated
inflammatory processes orchestrated by T cells.
Curr Opin Allergy Clin
Immunol. 2002 Aug;2(4):325-31.
& Wehner‑Caroli
J; Scherwitz C; Schweinsberg
F; Fierlbeck
G. Exacerbation of pustular psoriasis in mercury poisoning. Hautarzt 1994
Oct;45(10):708‑10
(36) Yiannias JA; Winkelmann RK; Connolly SM. Contact sensitivities in palmar plantar pustulosis (acropustulosis).
Contact Dermatitis 1998 Sep;39(3):108‑11;
& Roujeau JC, Bioulac-Sage P, Bourseau C, Guillaume JC, Bernard P, Lok
C, Plantin P, Claudy A, Delavierre C, Vaillant L, et al.
Acute generalized exanthematous pustulosis.
Analysis of 63 cases.
Arch Dermatol. 1991
Sep;127(9):1333-8; & Acute generalized exanthematous pustulosis, a clue
to neutrophil-mediated inflammatory processes
orchestrated by T cells. Curr Opin Allergy Clin Immunol. 2002 Aug;2(4):325-31, Britschgi M, Pichler WJ.
(37) Lindvall A, Lindh U, Danersund A, Metal Profiles in 25 Patients with Long-Term
Illness. Presented at Eurotox 93
Congress & Lindh,
U. Nucl Instr and Meth B30:404. 1988 & Hallgren,
R; Feltelius, N; Lindh,
U.J. Rheumatol. 15:308. 1988?
(39)
Wong L, Freeman S. Oral
lichenoid lesions (OLL) and mercury in amalgam
fillings. Contact
Dermatitis. 2003 Feb;48(2):74-9.
(40) Ostman PO, Anneroth G, Skoglund A. Amalgam-associated oral lichenoid reactions. Clinical and histologic changes after removal of amalgam fillings. Oral Surg
Oral Med Oral Pathol Oral Radiol
Endod. 1996 Apr;81(4):459-65.
(41) Skoglund A. Value of epicutaneous
patch testing in patients with oral, mucosal lesions
of lichenoid character. Scand J Dent Res. 1994 Aug;102(4):216-22.
(42) Koch P, Bahmer
FA.. Oral lesions and symptoms related
to metals used in dental restorations: a clinical, allergological,
and histologic study.
J Am Acad Dermatol.
1999 Sep;41(3 Pt 1):422-30.
(43)
Ibbotson SH, Speight EL, Macleod RI, Smart ER, Lawrence CM. , “The relevance of amalgam replacement on
oral lichenoid reactions”, British Journal of
Dermatology, 134(3):420-3, 1996.
(47) (a)Noda M, Wataha
JC, Lockwood PE, Volkmann KR, Kaga M, Sano H. Sublethal, 2-week
exposures of dental material
components alter TNF-alpha secretion of THP-1 monocytes
Dent Mater. 2003;19(2):101-5; &(b)
Kim SH, Johnson VJ, Sharma RP. Mercury inhibits nitric oxide production
but activates proinflammatory cytokine expression in murine
macrophage: differential modulation of NF- kappaB and
p38 MAPK signaling pathways. Nitric Oxide. 2002
Aug;7(1):67-74;
& (c) Dastych J, Metcalfe DD et
al, Murine mast cells exposed to
mercuric chloride
release granule-associated N-acetyl-beta-D-hexosaminidase
and secrete IL-4 and TNF-alpha. J Allergy Clin
Immunol.
1999, 103(6):1108-14;
&(e) Hide I.
[Mechanism of production and release of tumor necrosis factor implicated
in inflammatory diseases] Nippon Yakurigaku Zasshi.
2003 Mar;121(3):163-73;
& (f)Chen L, Nordlind
K, Liden S, Sticherling M., Increased expression of keratinocyte
interleukin-8 in human contact eczematous reactions to heavy metals.
APMIS. 1996 Jul-Aug;104(7-8):509-14.
(48)
(a)A.F.Zamm, “Removal of dental mercury: often an
effective treatment for very sensitive patients”, J Orthomolecular Med, 1990, 5(53):138-142. (22 patients);
&
(b)Dr. T. Rau, Paracelsus Alergy Clinic, Lustmuhle, Switzerland,
Allergies: Causes, Clarification, Treatment; Explore, 8(4),1996,
www.explorepub.com/articles/bio‑therapy.html ;
&
(c) Dr. B. Shelton, Director, The
Allergy Center, Phoenix, Arizona,
www.hamptonroadspub.com/main/books/excerpts/elements2.html;
& (d) E. Cutler, Winning the War against Asthma & Allergies,
Delmar Learning; 1st edition (July 9, 1997)
(49) (a) Hunter I, Cobban
HJ, et al; Tumor necrosis factor-alpha-induced activation of RhoA in airway
smooth muscle cells: role in the
Ca2+ sensitization of myosin light chain20 phosphorylation. Mol Pharmacol. 2003
Mar;63(3):714- 21;
&
(b) Walczak-Drzewiecka A, Wyczolkowska J, Dastych J. Environmentally Relevant Metal and Transition Metal Ions
Enhance Fc Epsilon RI-Mediated Mast Cell
Activation. Environ Health Perspect. 2003
May;111(5):708-13;
& (c)
Halasz A, Cserhati
E, Kosa L, Cseh K. Relationship between the tumor necrosis factor system and the serum interleukin-4, interleukin-5, interleukin-8, eosinophil cationic protein, and immunoglobulin E levels in the
bronchial hyperreactivity
of adults and their children Allergy
Asthma Proc. 2003
Mar-Apr;24(2):111-8;
&(d) Kurup RK, Kurup PA.
Hypothalamic digoxin, cerebral chemical
dominance, and pathogenesis of pulmonary diseases
Int J Neurosci. 2003
Feb;113(2):235-58;
&(e)Wu Z, Turner DR, Oliveira DB.
IL-4 gene expression up-regulated by mercury in rat mast cells: a role
of oxidant stress in IL-4 transcription.
Int Immunol. 2001
Mar;13(3):297-304;
&
(f) Strenzke N, Gibbs BF, et al, Mercuric chloride enhances immunoglobulin E-dependent mediator
release from human basophils. Toxicol Appl Pharmacol. 2001 Aug 1; 174(3):257-63;
&(g) Gillespie KM, Mathieson
PW, et al, Interleukin-4 gene expression
in mercury-induced
autoimmunity. Scand J Immunol. 1995 Mar;41(3):268-72;
&
(h)Beghe B, Holloway J, et
al. Polymorphisms in the interleukin-4 and interleukin-4
receptor alpha chain genes confer susceptibility to asthma and atopy in a Caucasian
population. Clin
Exp Allergy. 2003 Aug;33(8):1111-1117;
&(i)
Fireman P. Understanding
asthma pathophysiology. Allergy
Asthma Proc. 2003 Mar-Apr;24(2):79-83;
&(j) P.W. Mathieson,
“Mercury: god of TH2 cells”,1995, Clinical Exp Immunol.,102(2):229-30.
&(k) Halasz A, Cserhati E, Cseh K. [Role of the TNF system in the pathomechanism of bronchial asthma] [Article in Hungarian] Orv Hetil. 2002 Mar
17;143(11):553-7;
&
(l) Gorrie MJ, Qasim FJ,
Whittle CJ, Gillespie KM, Szeto CC, Nicoletti F, Bolton EM, Bradley JA, Mathieson
PW. Exogenous type-1 cytokines modulate
mercury-induced hyper-IgE in the rat. Clin Exp Immunol. 2000 Jul;121(1):17-22.
(50)
(a)Katsunuma et al, “Anaphylaxis improvement after
removal of amalgam fillings”, Annals of Allergy, 1990, 64(5):472-75; & (b)Yoshida S, Mikami H, Nakagawa H, Amayasu
H. Amalgam allergy associatiated with
exacerbation of aspirin-intolerant asthma. Clin Exp Allergy
1999; 29(10): 1412-4; & (c) M.Drouet et al,
“Is mercury a
respiratory tract allergen?”, Allerg Immunol(Paris),1990;
22(3):81.
(52) B.A.Weber, “The Marburg Amalgam Study”, Arzt
und Umwelt, Apr, 1995; (266 cases)
& (b)
B.A. Weber, “Amalgam and
Allergy”, Institute for Naturopathic Medicine, 1994; &
http://home,t‑online.de/home/Institut_f._Naturheilverfahren/patinf.htm" (see abstract)
(53) S.Zinecker, “Amalgam: Quecksilberdamfe
bis ins Gehirn”, der Kassenarzt, 1992,
32(4):23; “Praxiproblem
Amalgam”, Der
Allgermeinarzt, 1995,17(11):1215-1221. (1800
patients)
(54) A.Tosti et al, “Contact stomatitis”,
Semin Cutan Med Surg, 1997, 16(4):314-9;
(65) (a)Badou
A et al, “HgCl2-induced IL-4 gene expression in T cells involves a protein kinase C-dependent calcium influx through L-type calcium channels”J Biol Chem. 1997 Dec
19;272(51):32411-8,
&
(b) D.B.Veprintsev, 1996, Russian Academy of Sciences, Pb2+ and Hg2+ binding to alpha‑lactalbumin”.Biochem Mol Biol Int 1996 ;
39(6): 1255‑65;
&(c)
Rajanna B et al, “Modulation of protein kinase C by
heavy metals”, Toxicol Lett,
1995, 81(2-3):197-203;
&
(d) A. Szucs et al, Effects of inorganic mercury and methylmercury on the ionic currents of cultured rat hippocampal neurons. Cell Mol Neurobiol,
1997,17(3): 273-8;
(66)Melchart D, Wuhr E, Weidenhammer W, Kremers L. A multicenter survey of amalgam fillings
and subjective complaints in
non-selected patients in the dental practice. Eur J Oral Sci 1998; 106:770-77 (6,744 patients in 34 clinics)
(67)Ziff, M.F., “Documented Clinical Side Effects to Dental Amalgams”,
ADV. Dent. Res.,1992;
1(6):131-134; & S.Ziff,Dentistry
without Mercury, 8th Edition, 1996,
Bio-Probe, Inc., ISBN 0-941011-04-6;
(68) Daunderer M, Handbuch der Amalgamvergiftung, Ecomed Verlag, Landsberg 1998, ISBN 3‑609‑71750‑5
(in German); & “Improvement of Nerve
and Immunological Damages after Amalgam Removal”, Amer. J. Of Probiotic Dentistry
and Medicine, Jan 1991; & Toxicologische erfahrungen am menchen; Quecksilber in der umwelf- hearing zum amalgamproblem”,Niedersachsiscles
Umweltministerium, 1991; & “Amalgam”, Ecomed-Verlag, Landsberg, 1995; & “Amalgamtest”,
Forum Prakt.Allgen.Arzt, 1990, 29(8): 213-4; & “Besserung von Nerven- und Immunschaden nach Amalgamsanierung”,Dtsch.Aschr.
F. Biologische Zahnmedzin,
1990, 6(4):152-7. ( amalgam removal
& DMPS,over 3,000 cases)
(69) F.Berglund, Case
reports spanning 150 years on the adverse effects of dental amalgam, Bio-Probe, Inc.,Orlando,Fl,1995;ISBN
0-9410011-14-3(245 cured)
(70) M.Davis,editor, Defense Against Mystery Syndromes”, Chek Printing Co., March, 1994 (case histories)
(71) Sven Langworth et al,”Amalgamnews and Amalgamkadefonden,
1997 and Svenska Dogbladet,1997 (286 cases); &
F.Berglund,Bjerner/Helm,Klock,Ripa,Lindforss,Mornstad,Ostlin),
“Improved Health after Removal of dental amalgam
fillings”, Swedish Assoc. Of Dental Mercury Patients, 1998. (www.tf.nu)
(over 1000 cases) (Sweden Gov’t
maintains health records on all citizens) ; & Heavy Metal Bulletin,
No.3,1996 and No.1, 1999, p7,8;
& Klock B, Blomgren J, Ripa U, Andrup B, "Effekt av amalgamavlägsnande
på patienter som misstänker att de lider eller har lidit av
amalgamförgiftning", Tandläkartidn
81(23):1297-1302 (1989) .
(72) P.Engel, “Beobachtungen uber die gesundheit vor und nach amalgamentfernug”,Separatdruck aus
Schweiz. Monatsschr Zahnm. 1998, vol 108(8).(75 cases
amalgam removal) http://soho.globalpoint.ch/paul‑engel (89% sigificant improvement)
(73) Lichtenberg, HJ "Elimination of
symptoms by removal of dental amalgam from mercury poisoned patients", J Orthomol Med 8:145-148, 1993;
& Lichtenberg H, "Symptoms before and
after proper amalgam removal in relation to serum-globulin reaction to
metals", Journal of Orthomolecular Medicine,1996, 11(4): 195-203.
(74) F.Perger, Amalgamtherape, in Kompendiu
der Regulationspathologie
und Therapie, Sonntag-Verlag,
1990; & “Belastungen durch
toxische Schwermetalle”,
1993, 87(2): 157-63;
& K.H.Friese, ”Homoopathische Behandlung der Amalgamvergiftung”, Allg. Homoopathische Z, 241(5); 184-187, &Erfahrungsheikunde,
1996, (4): 251-253;
& “Amalgamvergiftung_moglicher”Der
Naturazt,1995,135(8):13-15;;
& M.Strassburg et al, “Generalized
allergic reaction from silver amalgam fillings”, Dtsche
Zahnarztliche Zeit, 22:3-9,
1967.
(75)Adolph
Coors Foundation, “Coors Amalgam Study: Effects of placement and removal of
amalgam fillings”, 1995. (www) & Internations
DAMS Newsletter, p17, Vol VII, Issue 2, Spring 1997.
(31 cases)
(76)G.Hall, V-TOX, Mercury levels excreted after Vit C IV as chelator‑ by
number of fillings Int
Symposium "Status Quo and Perspectives of Amalgam and Other Dental
Materials" European Academy, Ostzenhausen/Germany. April 29 ‑ May 1, 1994; &
Heavy Metal Bulletin, Apr 1996,Vol.3,Issue 1, p6-8 (200 cured or significantly improved)
(77) U.F.Malt et al, “Physical and mental problems attributed to
dental amalgam fillings”, Psychosomatic medicine, 1997, 59:32-41. (99 cured)
(78) Immunotoxic effects of
mercuric compounds on human lymphocytes and monocytes.
III. Alterations in B-cell function and viability; & Shenker BJ, Berthold P, Decker
S, Mayro J, Rooney C, Vitale L, Shapiro IM.
Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes. II. Alterations in cell viability. Immunopharmacol Immunotoxicol. 1992;14(3):555-77.
(79) (a)C.J.G.Robinson
et al, “Mercuric chloride induced anitnuclear
antibodies In mice”, Toxic Appl Pharmacology, 1986, 86:159-169.