Here are some recent studies done on the effects of colloidal gold in humans.
This is not our research and cannot be substantiated first hand.
Effect of Colloidal Metallic Gold on Cognitive
Functions: A Pilot Study
Guy E. Abraham, MD; Souhaila A. McReynolds; Joel S. Dill, PhD
Optimox Corporation, Torrance,
California
Abstract
In order to evaluate the effect of colloidal metallic gold on cognitive functions,
the revised Wechsler Intelligence scales battery of tests (WAIS-R) was administered to 5 subjects aged 15 to 45 years, before,
after 4 weeks on colloidal gold at 30 mg/day and again 1 to 3 months off the gold preparation. The WAIS-R total scores (I.Q)
were calculated by adding the sum of the verbal test scores to the sum of the performance scores. After 4 weeks on colloidal
gold, there was a 20% increase in I.Q scores with mean + SE of 112.8 + 2.3 pre gold and 137 + 3.8, post gold (p <0.005).
Both the performance and verbal test scores contributed equally to this increase in I.Q scores. The effect of the colloidal
gold persisted in 3 subjects after 1 to 2 month off gold, where as in 2 subjects who took the tests 3 months after stopping
the gold , I.Q scores were down to baseline levels.
Introduction
It is generally accepted that intelligence
or cognitive functioning is the sum of many mental capacities. For this reason, tests that were developed to measure intelligence
quotient (I.Q) comprised a series of subtests evaluating the several dimensions of intelligence. Of the several I.Q tests
available, educators have found that the Full Scale I.Q score of the Wechsler intelligence scales (WIS) battery, which is
calculated from the sum of the individual scores of 11 tests, (6 verbal and 5 performance tests) is an excellent predictor
of academic achievement.1 The revised version of this I.Q test (WAIS-R) has been used extensively to assess the effect of
deficiencies and supplementation of specific nutrients2,3 and the effects of sex, race, age and education4-7 on mental performance.
Gold
is a precious metal which belongs to the transition group I in the periodic table and exists in nature in two basic forms:
metallic gold and gold salts. Metallic gold is non-toxic, used extensively in dentistry and is widely available in colloidal
form as a nutritional supplement for human consumption. One of us (GEA) has observed a significant subjective improvement
of mental performance in 21 adult subjects after ingestion of a preparation of colloidal metallic gold (Aurasol®) for 3 to
9 months at a daily dosage of 15 mg of gold (unpublished). In order to use an objective and more standardized approach in
evaluating the effect of colloidal gold on mental performance, the WAIS-R battery of tests7 was performed on 5 subjects (4
females, 1 male) age 15-45 years, before, during and after the ingestion of the same colloidal gold preparation at 30 mg/day.
The results suggest that colloidal gold at 30 mg/day improved significantly the I.Q scores after only one month of administration.
Materials
and Methods
Aqueous dispersion of colloidal metallic gold was prepared by a modification of the citrate reduction
method of Frens. The concentration of gold in this preparation (Aurasol® ) was 30 mg per ounce of fluid.Five subjects were
recruited for this study ( 4 females and 1 male) with ages ranging from 15 to 45 years. The subjects were evaluated using
the WAIS-R procedure.7 Verbal scores, performance scores and total scores (I.Q) for each subject were calculated. The WAIS-R
battery was performed on each subject before gold administration, after ingesting 30 mg of colloidal gold daily for one month,
and again after being off the gold preparation for 1 to 3 months. The statistical significance of the data was assessed by
Student's paired t test.9
Results
The group of tests called verbal are non-learning and therefore is
not influenced significantly by repetition. The performance tests can be learned with repetition and this should be taken
into consideration when evaluating the results displayed in Table I. The mean scores + standard error (SE) were respectively
for pre- and post-gold administration: verbal 61.4 + 2.4 and 75.4 + 4.5 (p<0.005); performance 51.4 + 0.83 and 61.6 + 1.9
(p<0.01); total scores (IQ) 112.8 + 2.3 and 137 + 3.8 (p<0.005). Since both the verbal (non-learning and performance
(learning) scores contributed equally to the increased values observed in the total IQ scores following colloidal gold, the
positive effect of colloidal gold cannot be attributed solely to learning the correct responses on the second test due to
repetition.
It is of interest to note that in two subjects (#1 and #2) who repeated the battery 3 months after stopping
colloidal gold, the total IQ scores were close to baseline pre-gold levels whereas, in 2 subjects who performed the test 1
month after stopping the gold, (#3 and #5) and in one subject (#4) who did so after 2 months off colloidal gold, the total
IQ scores were still elevated above baseline, suggesting that the effect of the gold on mental performance has a carry-over
of one to two months after stopping the use of this preparation.
Discussion
The WIS battery of tests
is an excellent predictor of scholastic performance.1 In fact, according to Lezak,10 the average scores on a WIS battery provide
just about as much information as do average scores on a school report card. We have observed a significant increase (20%)
of the mean IQ scores in 5 subjects aged 15 to 45 years after only one month on oral colloidal metallic gold at 30 mg/day.
This effect persisted for up to 2 months following discontinuation of the gold preparation. To our knowledge, this is the
first study evaluating the effect of colloidal gold on mental performance. Possible mechanisms of action of the colloidal
gold preparation are only speculative at this time. However, the potential applications of a non-toxic colloidal metal with
marked and rapid positive effect on mental performance are without question of great practical value, not only in scholastic
performance but also in the workplace.
The encouraging results of this pilot study warrant further evaluation of colloidal
metallic gold in a larger number of subjects of different age groups. Testing various amounts of gold would assist in quantifying
the response of the IQ tests in term of cumulative amount of gold ingested in order to investigate a possible dose-response
relationship. Using the smallest amount of colloidal gold that results in a desirable effect on mental performance and scholastic
achievement would keep the cost of such a program as low as possible.
References
- Lezak, M.D., In: Neuropsychological Assessment. New York, Oxford University Press; 1995:690.
- Goodwin, J.S., Goodwin, J.M., Garry, P.J. Association between nutritional status and cognitive
functioning in a healthy elderly population. J Amer. Med. Assoc., 1983; 249:2917-2921.
- Southon, S., Wright, A.J., Finglas, P.M., Bailey, A.L., et. al. Dietary intake and micronutrient
status of adolescents: effect of vitamin and trace element supplementation on indices of status and performance in tests of
verbal and non-verbal intelligence. Br. J. Nutr., 1994; 71:897-918.
- Kaufman, A.S., McLean, J.E., Reynolds, C.R. Sex, race, residence, region, and education differences
on the 11 WAIS-R subtests. J. Clin. Psychology, 1988; 44:231-248.
- Kaufman, A.S., McLean, J., Reynolds, C. Analysis of WAIS-R factor patterns sex and race. J. Clin.
Psychology, 1991; 47:548-557.
- Kaufman, A.S., Reynolds, C.R., McLean, J.E. Age and WAIS-R intelligence in a national sample of
adults in the 20 to 74 year age range: A cross-sectional analysis with educational level controlled. Intelligence, 1989; 13:235-253.
- Kaufman, A.S. Assessing adolescent and adult intelligence. Boston, Allyn and Bacon Inc.; 1990.
- Abraham, G.E., Himmel, P.B. Management of Rheumatoid Arthritis: Rationale for the Use of Colloidal
Metallic Gold. In Press, J. Nutr. Med., 1997.
- Huntsberger, D.V., Leaverton, P.E., In: Statistical Inference in the Biomedical Sciences. Boston,
Allyn and Bacon Inc.; 1970:135.
- Lezak, M.D., In: Neuropsychological Assessement. New York, Oxford University Press;1995:691.
Colloidal Gold in the Treatment of Rheumatoid Arthritis (RA)
Peter B. Himmel, Jorge D. Flechas,
Guy E. Abraham
Gold salts (aurothiolates) once the primary therapy for active RA has in recent years declined in
its use because of apparent lack of long term efficacy, toxic side effects, and delayed onset of action. One of us (GEA) postulated
that the active ingredient in aurothiolates is colloidal gold generated by in vivo disproportionation with subsequent clustering
of monoatomic gold, and that the side effects were due to the aurothiolates themselves and the trivalent cationic gold generated
from the disproportionation. If this postulate is valid one would expect colloidal gold to have therapeutic effects in RA
and devoid of side effects.
Methods:
10 patients (6 female, 4 male; average age 50 +/- 3.16 (SE)
with long standing erosive RA ( 9 of 10 seropositive) were given an oral dose of 30 to 60 mg a day of colloidal gold (Aurasol-tm)
for a period of 1 month. Clinical exams were performed weekly and laboratory studies done on weeks 1, 2, 4. Gold toxicity
was evaluated by questioning the patient as to pruritus, rashes, oral ulcers, metallic taste, GI disturbance. The blood was
checked for a drop in WBC, Hb, platelet count, BUN, creatinine or eosinophil elevation; and urine for proteinuria. Efficacy
was evaluated by an 86 Joint Count Index scoring for joint tenderness and swelling: AM stiffness; the Modified Health Assessment
Questionnaire (MHAQII) by T. Pincus and an ESR.
Results:
Statistically significant improvement were found
on each weekly exam for joint tenderness and swelling beginning with the first week 58.8 to 18.2 (p<0.01) for tenderness;
42.5 to 15.9 (p<0.01) for swelling. Joint swelling reduced further to a value of 13.0 (p<0.001) by week 4. Patients
fatigue decreased from 5.32 to 3.35 (p<0.05) over the month and a feeling of satisfaction in ones ability to do activities
was apparent after 1 week, 3.1 to 2.5 (p<0.01) and persisted. No laboratory tests indicative of gold toxicity were noted.
One patient reported 2 chancre sores which cleared while on therapy, 8 of 10 patients responded to colloidal gold.
Conclusion:
In
this pilot study colloidal gold (Aurasol-tm) was found to be rapid acting (within one week) by reducing joint tenderness and
swelling, without side effects, improved ones feeling of satisfaction in the ability to perform activities and reduce fatigue
in 8 out of 10 patients with long standing erosive RA. The study will continue for one year. More definitive controlled trials
should now be undertaken with colloidal gold.
Note:
The study has now completed its eighth month
with all ten of the original patients still enrolled. The patients continue to do well with no significant side effects noted.
This data is being compiled to be submitted for publication.
Management of Rheumatoid Arthritis:
Rationale for
the Use of Colloidal Metallic Gold
Guy E. Abraham MD FACN1 and Peter B. Himmel MD2
1Optimox Corporation, Torrance,
CA, USA and 2 Himmel Health, Wakefield, RI, USA
In Press - J. Nutr. Med., Vol. 7 - Dec. 1997
- Abstract
- Introduction
- Materials and Methods
- Results
- Discussion
- References
Abstract
Gold salts of monovalent gold (AU I) with a gold-sulfur ligand (aurothiolates) are the only form of gold currently
in use for the management of Rheumatoid Arthritis (RA). Aurothiolates have limited success and are associated with a high
incidence of side effects. Metallic gold (AUo) is non-toxic and used extensively in dentistry. Monoatomic metallic gold is
generated in vivo from AUI salts, during oxydation to AU III. Monoatomic gold tends to form clusters of colloid particles.
It is postulated that the active ingredient in aurotherapy is AUo and the side effects are caused by AU III. To test this
postulate, 10 RA patients with long standing erosive bone disease not responding to previous treatment, were recruited from
a private practice. Clinical and laboratory evaluation were performed prior to oral administration of 30 mg of colloidal metallic
gold daily, and thereafter weekly for 4 weeks and monthly for an additional 5 months. There was no clinical or laboratory
evidence of toxicity in any of the patients.
The effects of the colloidal gold on tenderness and swelling of joints
were rapid and dramatic, with a significant decrease in both parameters after the first week, which persisted during the study
period. The mean scores for tenderness and swelling were respectively for the pre-and post- 1 week = 58.8 and 18.2 (p<0.01);
and 42.5 and 15.9 (p<0.01).
By 24 weeks of gold administration, the mean scores were 10 times lower than pre-treatment
levels being respectively 5.4 and 3.3 for tenderness and swelling. As a group, there were significant improvement of functional
status after 24 weeks of gold therapy: 3 patients were in clinical remission and one patients status improved from totally
disabled to full-time work. Evaluated individually, 9 of 10 patients improved markedly after 24 weeks of colloidal gold at
30 mg/day. Cytokines interleukin-6 (IL-6) and Tumor necrosis factor (TNFa) were significantly suppressed by the colloidal
gold with pre- and post-24 week mean values of 270 and 104 (p<0.05) for IL-6; and 207 and 74 (p<0.05) for TNFa. The
results of this open trial in 10 patients with long standing erosive RA not responding to previous treatment support the postulate
that colloidal gold is indeed the active ingredient in aurothiolate therapy, and that the side effects are mainly due to the
trivalent gold (AU III) generated by oxydation of AU I. Colloidal metallic gold could become an effective and safte alternative
to the aurothiolates in the management of RA patients. Keywords: rheumatoid arthritis, colloidal metallic gold.
Introduction
Aurothiolates have been used in the treatment of rheumatoid arthritis (RA) since their introduction by Forestier in
1929 (1). In a follow-up publication, Forestier reported that the only forms of gold effective in the management of RA were
organic compounds containing monovalent cathionic gold (AU I) covently bound to a sulfur moiety (aurothiolates), and given
by weekly intramuscular injection to achieve a total cummulative dose of 2.5 to 3 gm (2). He stated that colloidal gold was
ineffective, but did not mention the dosage, the form of colloidal gold, whether metallic or cathionic, neither the method
of administration. Several subsequent reports by various investigators have confirmed the short term efficacy of the parenteral
forms of aurothiolates in RA (3), but in more recently published clinical studies with the parenteral aurothiolates, several
side effects were reported: Pulmonary damage (4-7), myelotoxicity, leukopenia, thrombocytopenia, and anemia (8-12). In a recent
longitudinal study of 822 RA patients receiving parenteral aurothiolate therapy over a 5 year period (13), no statistical
improvement was observed in two outcome variables evaluated: functional assessment and number of painful joints. In an attempt
to minimize the side effects of injectable gold complexes, an oral preparation was introduced in 1976 (14). However, this
preparation caused diarrhea/loose stools in 50% of the patients, was less effective than the parenteral forms of aurothiolates
and produce the same side effects as the injectable forms of gold salts although to a lesser extent.
Since chemical
complexes of monovalent gold readily disproportionate in solution with formation of metallic monoatomic gold and trivalent
gold according to the reaction: 3AU+® 2AUo + AU +++ (15), it would be expected that monovalent gold organocomplexes, such
as the aurothiolates if administered orally or parenterally, would disproportionate in vivo with formation of metallic monoatomic
gold and trivalent gold (AU III). In vivo clustering of metallic gold atoms would eventually form colloidal particles of gold.
One of us (GEA) postulated that the active ingredient in aurothiolate therapy is colloidal metallic gold generated by in vivo
disproportionation with subsequent clustering of monoatomic metallic gold to form colloidal gold; and that the side effects
were due mainly to the trivalent gold (AU III) generated from disproportionation (Fig 1). If this postulate is valid, one
would expect colloidal metallic gold to have therapeutic effects in RA and devoid of side effects. Metallic gold is non-toxic,
used extensively in dentistry and is widely available in colloidal form as a nutritional supplement for human consumption.
The above postulate was tested in 10 patients with long standing erosive RA with minimal to no response to previous treatment.
The results obtained support the postulate that colloidal metallic gold is indeed the active ingredient in aurothiolate therapy
and offer a more effective and safer alternative to aurothiolate therapy in R.A. patients.
Materials and Methods
A. Colloidal metallic gold:
Aqueous dispersions of colloidal gold (Aurasol®) were prepared by one of us
(GEA) at a final concentration of 1000 mg/L, (1000 PPM) by the citrate method of Maclagan (16) and Frens (17), with several
proprietary modifications. The sizes of the colloid particles were less than 20 nm in several batches, confirmed by quantitative
recovery after passing through a 20 nm filter. Accelerated shelf-life studies proved the stability of the aqueous dispersion
for up to 2 years at ambient temperature. The following metals were measured in the aqueous colloidal gold dispersion and
were undectable at 0.5 PPM (<0.5 mg/L): Antimony, arsenic, barium, beryllium, cadmium, chromium, cobalt, copper, lead,
mercury, molybdenum, nickel, selenium, silver, thallium, vanadium, and zinc. Lead levels were measured again in a more sensitive
assay and were undetectable at 50 PPB (<0.05 mg/L). Sterilization was achieved by microfiltration through 100 nm pore size
and sodium benzoate was used as anti-microbial preservative.
B. R.A. Patients:
In order to minimize the placebo
effect, the 10 worse cases (9 of 10 seropositive) with long standing (7-40 years duration) erosive RA with minimal to no response
to previous treatment, were recruited from the private practice of one of us (PBH). Nine of 10 patients received previously
aurothiolate therapy without effect and 5 of the 9 experienced side effects of skin rash, stomatitis and proteinuria. The
clinical data on these patients are displayed in Table I. Six of the ten patients were totally work-disabled. After informed
consent was obtained, the patients underwent complete clinical and laboratory evaluations before and weekly afterward for
4 weeks and monthly for an additional 5 months of oral colloidal gold administration. The inflammatory cytokines, tumor necrosis
factor a (TNFa) and interleukin-6 (IL-6) were evaluated prior to and 24 weeks following gold administration (Immunoscience
Lab, Beverly Hills, CA). Paired data analysis was used for the evaluation of response to colloidal gold (18).
Performance
parameters were assessed by the method of Pincus, et. al., (19). The severity of swelling and tenderness was assessed for
86 joints, based on the quantitation of Lansbury (20), and the classification described in the Dictionary of the Rheumatic
Diseases (21). The American Rhematology Association (ARA) functional class by Steinbrocker, et al., (22) was used to evaluate
functional status: Class I: Complete functional capacity with ability to carry on all usual duties without handicaps; Class
II: Functional capacity adequate to conduct normal activities despite handicap or discomfort or limited mobility of one or
more joints; Class III: Functional capacity adequate to perform only few or none of the duties of usual occupation or or self
care; Class IV: Largely or wholly incapacited with patient bed ridden or confined to wheel chair, permitting little or no
self care.
Since preliminary data by one of us (GEA) suggested that amounts up to 15 mg/day of colloidal gold was without
clinical effect in RA, patients 1 through 5 received 30 mg/day for the first week and 60 mg/day for the second week, whereas
patients 6 through 10 received 60mg/day for the first week and 30 mg/day for the second week. Except for one patient, no significant
difference was found between these two amounts on the clinical parameters evaluated. The patients were therefore continued
on the trial at 30 mg/day for a duration of 24 weeks.
Results
The effects of the colloidal gold (Aurasol®) on tenderness and swelling of joints were rapid and dramatic, with a
significant decrease in both parameters after the first week, which persisted during the study period. The mean scores for
tenderness and swelling were respectively for the pre- and post- 1 week = 58.8 and 18.2 (p<0.01); and 42.5 and 15.9 (p<0.01).
By 24 weeks of gold administration, the mean scores were 10 times lower than pre-treatment levels being respectively 5.4 and
3.3 for tenderness and swelling. Duration of AM joint stiffness (in hours) showed a decreasing trend that reached statistical
significance with pre-and post 24 week mean scores of 2.8 and 0.4 respectively (p<0.01).
The mean body weight after
24 weeks on colloidal gold was not significantly different from the pre-treatment mean value. As a group, there were significant
changes in ARA functional class, and physician's estimate of disease activity. Pre- and post- 24 week mean values were 2.9
and 2.3 (P<0.05) for ARA functional class; and 3.1 and 1.5 (P<0.01) for physician's estimate of disease activity. After
24 weeks on colloidal gold, 3 patients (#5, #6, #7) were in clinical remission. Work status improved in 3 patients (#3, #5,
#6), with the most impressive results in patient #6, who changed from totally disabled to full time work, and ARA class IV
to class I. The inflammatory cytokines IL-6 and TNFa were significantly suppressed by the colloidal gold with pre- and post-24
week mean values of 270 and 104 (p<0.05) for IL-6; and 207 and 74 (p<0.05) for TNFa.
There was no clinical
or laboratory evidence of toxicity in the patients. Specifically no change was observed in subsets of white blood cells and
platelets in the RA patients, supporting the absence of cytotoxicity from colloidal gold. There was no significant change
in hemoglobin, hematocrit, liver function tests, BUN, serum creatinine and urinalysis in the RA patients and the levels of
these parameters remained within normal limits during the study period. Clinically, there were no reports or signs of skin
rashes, stomatitis, gastrointestinal disturbances, vasomotor reactions, myalgias, arthralgias, pruritus, headache or metallic
taste. Evaluated individually, 9 of 10 patients improved markedly after 24 weeks of colloidal gold at 30 mg/day.
Discussion
In studies performed in vitro (23) and in vivo (24), administered metallic colloidal gold particles are ultimately
sequestered within lysosomes of phagocytes, visible under electron microscopy (EM). After administration of aurothiolates
to RA patients, gold particles visible under EM selectively accumulate in the lysosomes of synovial cells and macrophages
(25). It is believed that stabilization of lysosomes by these gold particles plays a role in their therapeutic actions (26).
Electron probe x-ray analysis of lysosomes revealed that the form of gold present in lysosomes obtained from patients receiving
aurothiolates is devoid of sulfur atoms and therefore cannot be in the form of aurothiolates (26). Since disproportionation
of aurothiolates generate monoatomic metallic gold with a diameter of 0.28 nm, a size below the resolution of EM, the only
way the gold particles in the lysosomes could be visible under EM is by clustering of metallic monoatomic gold to form colloidal
gold particles. These results are consistent with the postulate that the gold in lysosomes is in the form of colloid particles
of metallic gold. Therefore, the argument that colloidal metallic gold is the active ingredient from aurotherapy seems very
plausible.
The results of this open trial in 10 patients with long standing erosive RA not responding to previous treatment
support the postulate that colloidal gold is indeed the active ingredient in aurothiolate therapy, and that the side effects
are mainly due to the trivalent gold (AU III) generated by in vivo disproportionation. Common sense would favor the active
ingredient in its pure state over a precursor that generates both the active form and another form causing side effects. The
most prevalent side effects of aurotherapy are skin rash and diarrhea. Trivalent gold cause contact dermatitis and skin rash
(27). The diarrheogenic action of aurothiolates can be explained by their ability to stimulate intestinal secretion in vitro,
an effect shared by trivalent gold (28). Aurothiolates cause adverse immune reactions in up to one third of RA patients (29-31).
Some of these side effects can be reproduced in susceptible mouse strains following long-term exposure to the aurothiolates:
increased serum levels of IgM, IgG and IgE formation, of IgG antinuclear antibodies, and granular IgG deposits along the glomerular
basement membrane (32-34). T-lymphocytes from susceptible mice fail to be sensitized to the aurothiolates but mount a secondary
response to Au (III) salts, suggesting the adverse immune reactions to the aurothiolates are elicited by T cell sensitization
to Au (III) formed in vivo through oxidation of Au (I) (35).
A placebo effect in these RA patients is very unlikely
since their favorable clinical response was associated with the concurrent suppression of the inflammatory cytokines TNFa
and IL-6. The powerfull anti-inflammatory properties of colloidal gold while devoid of cytotoxicity and side effects could
make it usefull in other inflammatory and immune complexes diseases. Tissue levels of colloidal gold in the therapeutic ranges
could be achieved rapidly with increased dosages without the risks of complications reported for the aurothiolates. Colloidal
metallic gold could become an effective and safe alternative to the aurothiolates in the management of R.A. patients.
Since
colloidal metallic gold catalyzes electron-transfer in oxydation reduction reactions (36), one possible mechanism of action
of colloidal gold could be in potentiating the suppressive effect of antioxydants on free radical formation. The mechanisms
of action of colloidal gold however remain speculative at this time, and we are currently investigating such mechanisms in
animal models. Acknowlegement: The authors wish to thank Ralf Albrecht for usefull discussions, and Pat Kellum for skillfull
secretarial assistance.
References
- Forestier, J: La Chrysotherapie dans les Rhumatismes Chroniques, Bull. et Mem. Soc. Med. des Hop.
de Paris, 1929; 44: 323-329.
- Forestier, J: Rheumatoid Arthritis and its Treatment by Gold Salts, J. Lab. Clin. Med., 1935;
20: 827-840.
- Empire Rheumatism Council: Gold Therapy in Rheumatoid Arthritis. Final Report of a Multicenter
Controlled Trial. Ann. Rheum. Dis., 1961; 20: 315-324.
- Geddes, DM, Brostoff, J: Pulmonary Fibrosis Associated with Hypersensitivity to Gold Salts, BMJ,
1976; 1: 1444.
- Gould, PW, McCormack, PL, Palmer, DG: Pulmonary Damage Associated with Sodium Aurothiomalate Therapy,
J. Rheumatol., 1977; 3: 181-182.
- Scott, DL, Bradby, GV, Aitman, TJ, et. al.: Relationship of Gold and Penicillamine Therapy to
Diffuse Intestinal Lung Disease, Ann. Rheum. Dis., 1981; 40: 136-141.
- Belleli, A, Boiardi, L, Turniad, B, Brigari, C: Diffuse Intestinal Lung Disease Associated with
Hypersensitivity to Gold Salt, Clin. Exp. Rheumatol., 1985; 3: 181-182.
- Kay, AGL: Myelotoxicity of Gold, Br. Med. J., 1976; I: 1266-1268.
- Coblyn, JS, Weinblatt, M, Holdsworth, D, Glass, D: Gold Induced Thrombocytopaenia; A Clinical
and Immunogenetic Study of Twenty-Three Patients, Ann. Intern. Med., 1981; 95: 178-181.
- Adachi, JD, Benson, WG, Kassam, Y: Gold Induced Thrombocytopaenia; 12 Cases and a Review of the
Literature, Semin. Arthritis. Rheum., 1987; 16: 287-293.
- Amos, RS, Bax, DE: Leucopaenia in Rheumatoid Arthritis: Relationship to Gold or SulphasalazineTherapy,
Br. J. Rheum., 1988; 27: 465-468.
- Madhok, R, Pullar, T, Capell, HA, Dawood, F, Sturrock, RD, Dick, HM: Chrysotherapy and Thrombocytopenia,
Ann. Rheum, Dis., 1985; 44: 589-591.
- Epstein, WV, Henke, CJ, Yelin, EH, Katz, PP: Effect of Parenterally Administered Gold Therapy
on the Course of Adult Rheumatoid Arthritis, Ann. Int. Med., 1991; 114: 437-444.
- Finkelstein, AE, Walz, DT, Batista, V, et. al.: Auranofin: New Oral Gold Compound for Treatment
of Rheumatoid Arthritis, Ann. Rheum. Dis., 1976; 35: 251-257.
- Pearson, RG: Hard and Soft Acids and Bases, J. of Amer. Chemical Society, 1963; 85: 3533- 3539.
- Maclagan, NF: The Preparation and use of Colloidal Gold Sols as Diagnostic Agents, J. Exp. Path.,
1947; 27: 369-377.
- Frens, G: Controlled Nucleation for the Regulation of the Particle Size in Monodisperse Gold Suspensions,
Nature Phy. Sci., 1973; 241: 20-22.
- Goldstein, A.: Biostatics: An Introductory Text. New York, The MacMillan Company, 1964; 61-62.
- Pincus, T, Summey, JA, Soraci, SA, Jr, Wallston, KA, Hummon, NP: Assessment of patient satisfaction
in activities of daily living using a modified Stanford health assessment questionnaire., Arthritis Rheum., 1983; 26: 1346-1353.
- Lansbury, J: Quantitation of the activity of Rheumatoid Arthritis., 1956; 232: 300-310.
- American Rheumatism Association: Dictionary of Rheumatic Diseases, Volume I. Signs and Symptoms.
Contact Associates International Ltd., NY, NY, 1982; 75-76.
- Steinbrocker, O, Traeger, CH, Batterman, RC: Therapeutic Measurement in Rheumatoid Arthritis,
JAMA, 1949; 140: 659-662.
- Juurlink, BHJ, Devon, RM: Colloidal Gold as a Permanent Marker of Cells, Experientia, 1991; 47:
75-77.
- Danien, BJ, Sims, PA, Kruse-Elliott, KT, Homan, TS, Cashwell, RJ, et. al.: Use of Colloidal Gold
and Neutron Activation in Correlative Microscopic Labeling and Label Quantitation, Scanning Microscopy, 1995; 9: 773-780.
- Roberts, VB, Dore, JL, Jessop, JD, et. al.: Selective Concentration and Localization of Gold in
Macrophages of Synovial and Other Tissues During and After Chrysotherapy in Rheumatoid Patients, Ann. Rheum. Dis., 1976; 35:
477-486.
- Ghadially, FN, Oryschak, AF, Mitchell, DM: Ultrastructural Changes Produced in Rheumatoid Synovial
Membrane by Chrysotherapy, Ann. Rheum. Dis., 1976; 35: 67-72.
- Kligman, AM: The Identification of Contact Allergans by Human Assay. III. The Maximization Test:
A Procedure for Screening and Rating Contact Sensitizers. J. Invest. Derm., 1966; 47: 393-409.
- Hardcastle, J, Hardcastle, PT, Kelleher, DK: Effect of Auranofin on Ion Transport by Rat Small
Intestine, J. Pharm. Pharmacol., 1989; 41: 817-823.
- Lockie, LM, Smith, DM: Forty-seven Years Experience with Gold Therapy in 1019 Rheumatoid Arthritis
Patients, Semin Arthritis Rheum., 1985; 14: 238-246.
- Panayi, GS: New Ideas on the Pathogenesis of Rheumatoid Arthritis, Ann. Ital. Med. Int., 1990;
5: 1-4.
- Kavanaugh, AF, Lipsky, PE: Gold, Penicillamine, Antimalarials, and sulfasalazine. In: Gallin JT,
Goldstein IM, Snyderman, R (eds) Inflammation. Raven Press, New York, 1992; 1083-1101.
- Robinson, CJG, Balazs, T, Egorov, JK: Mercuric Chloride-Gold Sodium Thiomalate-and D-Penicillamine-Induced
Antinuclear Antibodies in Mice, Toxicol. Appl. Pharmacol., 1986; 86: 159-169.
- Pietsch, P, Vohr, BW, Degitz, K, Gleichmann, E: Immunological Alterations Inducible by Mercury
Compounds, II. HgCl3 and Gold Sodium Thiomalate Enhance Serum IgE and IgG Concentrations in
- Susceptible Mouse Strains, Int. Arch. Allergy Appl. Immunol., 1989; 90: 47-53.Schuhmann, D, Kubieka-Muranyi,
M, Mirtschewa, J, Gunther, J, Kind, P, Gleichmann, E: Adverse Immune Reactions to Gold. I. Chronic Treatment with an Au (I)
Drug Sensitizes Mouse T Cells not to Au (I), but to Au (III) and Induces Autoantibody Formation, J. Immunol., 1990; 145: 2132-2139.
- Goebel, C, Kubieka-Muranyi, M, Tonn, T, Gonzalez, J, Gleichmann, E: Phagocytes Render Chemicals
Immunogenic: Oxidation of Gold (I) to the T Cell-Sensitizing Gold (III) Metabolite Generated by Mononuclear Phagocytes, Arch.
Toxicol., 1995; 69: 450-459.
- Freund, PL, Spiro, M: Colloidal Catalysis: The Effect of Sol Size and Concentration, J. Phys.
Chem., 1985; 89: 1074-1077.
|
