MERLIN vs. 3M/MCGHAN: The Concept of a New Disease Caused by Silicone is Biologically Plausible as Silicone is NOT Inert

[Guest guest]

MERLIN vs. 3M/MCGHAN

PLAINTIFFS' EXHIBIT LIST FOR DAUBERT HEARING

THE CONCEPT OF A NEW DISEASE CAUSED BY SILICONE IS

BIOLOGICALLY PLAUSIBLE AS SILICONE IS NOT INERT.

1. Investigation at Dow Corning into use of silicones

as pesticides: in 1968, found that Dow Corning 360

fluid both attracted and killed cockroaches; also

repelled mites and mealy bugs; killed and repelled

aphids.

(Plaintiffs' Exhibit 705)

2. Dow Corning Report, 'Histopathological Findings In

Animals of Various Species from Experiments Conducted

by D. Rees " , 4/22/68.

(Plaintiffs' Exhibit 548)

Silicone injected into various animals produced organ

damage including chronic inflammation of liver,

kidneys and occasional pancreas and gonad

abnormalities seen in mice; similar but less prevalent

organ damage in rats; and liver abnormalities and

chronic kidney inflammation in guinea pigs.

Additionally, holes in cytoplasm of cells commonly

observed in all species.

3. Dow Corning Research: Immunological Enhancing

Activities of Organosilicon Compounds and

non-functional fluids, 10/2/74.

(Plaintiffs' Exhibit 120)

Study carried out to determine if certain silicone

oils could act as adjuvants in experimental animals.

An adjuvant is a chemical that will enhance or prolong

the immune response when given mixed with a foreign

protein (antigen). Study concluded that nine of the

forty-nine adjuvants tested showe6 adjuvant activity

similar to that of known adjuvant (CFA).

CONCLUSION: Silicone oils can act as adjuvants to

enhance the antibody response to a standard antigen in

experimental animals.

ANIMAL STUDIES SHOW SILICONE INDUCES BIOLOGICAL AND

CHEMICAL CHANGES AND IS SYSTEMICALLY DISTRIBUTED

4. " Summary of Histopathological Findings in

Primates " , 3/21/67 Dow Corning Document. (Plaintiffs'

Exhibit 774)

Twelve monkeys injected with silicone fluids in both

breasts and left cheek. Animals sacrificed at two

years after first injection; findings included holes

in cells (vacyated cells) in lungs, cheeks and

breasts; abnormal adrenal glands and chronic kidney

inflammation.

These tests signal potential immunological impact of

long term presence of polysiloxane in primate fluids

in primates.

5. Structure-Activity Relationships of Oral

Organosiloxanes on the Male Reproductive System. by

D.R. , S.J. Gorzinsid, and J.E. LeBeau.

Toxicology and Applied Pharmacology. 21, 55-67 (1972).

(Plaintiffs' Exhibit 545)

Oral organosiloxanes depressed male reproductive

function in the mouse, rat and rabbit.

6. Local & Systemic Effects of Dimethylpolysiloxane

Fluid In Mice. by N.Ben-Hur, M.D., BaBantyne,

Jr., Ph.D., Rees, M.D. and @g Seidman, M.D.

Plastic & Reconstructive Surgery. Aprfl 1967.

pp.423-426. (Plaintiffs' Exhibit 544)

Mice and rats injected subcutaneously with silicone

fluid; on autopsy, silicone found in the vital organs

and lymph nodes. Phagocytes ingested silicone fluid

and caused granuloma-like lesions; silicone also

engulfed by wandering histiocytes and transported to

lymph nodes and throughout the reticuloendothelial

system to liver, spleen and other organs.

7. Changes In the Lung Following Injections of

Silicone Gel. by Marcus Castro Ferreira, M.D., Victor

Spina, M.D. and Kyoshi Iriya, M.D. British Journal of

Plastic & Reconstructive Surgery. pp.173-176. 1975.

(Plaintiffs' Exhibit 546)

Injections of silicone gel in 38 MI. rats produced

findings of silicone gels in lungs on autopsy, the

result of phagocytosis of the silicone by macrophages,

carried to the lungs in blood stream or through

lymphatics. Authors conclude that silicone gel behaves

like silicone fluid and is not so inert as solid

silicone as was previously supposed.

8. Dow Corning Corp Research Dept Report# 3977.

Authors: ph LeBeau & Stanley J. Gorzinski DMPS

fluid (Dow Corning 360 Medical Fluid) distribution and

disposition in rats following subcutaneous injection.

(Plaintiffs' Exhibit 687)

Dow Corning 360 medical grade silicone administered to

rats. With assistance from radioactive labeling,

silicone fluid found in expired air, urine and feces

as well as in times and organs. Migration of silicone

through lymphatic system confirmed.

9. Dow Corning Report # 3323 Project # 464 by Ruth M.

Lacefield, et al. Biological Distributions of DMPS.

(Plaintiffs' Exhibit 688)

Radioactive labeled medical grade 360 fluid traced to

determine biological distribution in test animal;

silicone found in brain, blood, bile, internal organs.

10. 2, 6-cis-Diphenylhexamethyl - cyclotetrasiloxane

Chemistry Analytical Chemistry, Biological Effects and

Excretion. By , Don R. Aborg, Bertfl. Editors

ACTA, Pharmacological et To;dcologir-al. Vol. 36,

Supp-III, 1975. (Plaintiffs' Exlubit 553)

2, 6-cis being evaluated as an estrogen by Dow, noted

to produce changes in male genital organs of rabbits

and dogs.

11. Structure Activity Relationships of

Organosiloxanes and the Female Reproductive System. by

F. Hayden & Sue A. Barlow. To7dcology and

Applied Pharmacology. Vol.21, 1972 pp.68-79.

(Plaintiffs' Exhibit 689)

2, 6-cis is biologically active in the female rat and

produced estrogen-like effect.

12. Investigation of the Toxicologic Properties of a

Phenylmethylcyclosiloxane by R.J. Palazzolo et al.

Toxicology and Applied Pharmacology. Vol.21, 1972.

pp.15-28. (Plaintiffs' Exhibit 691)

Experiments by oral ingestion and by skin applications

on various species showed silicone material to be

biologically active by mouth in monkeys leading to

testicular atrophy and decrease or absence of seminal

fluid.

13. Peritoneal Response To Silicone Fluid. A

Histologic Study. Brody, Gerald L., M.D. and Frey,

F., M.D. Arch Surg. Vol. 96, February 1968,

PP 237-241. (Plaintiffs' Exhibit 586)

Injection of silicone fluid into rats produced

histiocytic granulomas. Fact that granulomas exist

and that silicone is transported to draining lymph

nodes indicates that silicone is not inert.

14. Biocompatibility of Silicone Implants. by Heggers,

P. Ph.D., etal., Reprinted ls of Plastic

Surgery. Vol. 11, No. 1, July 1983, PP 37.

(Plaintiffs' Exhibit 592)

Silicone is capable of eliciting a cellular immune

response. This may indicate that silicone acts like

an incomplete antigen.

THE IMMUNE RESPONSE TO SILICONE: FROM THE ANIMAL MODEL

TO THE HUMAN

15. The Adjuvant Effect Of Silicone-Gel On Antibody

Formation In Rats. by Naim, 0. Lanzafame,

J. Oss, Carl J. The University of Rochester School of

Medicine and Dentistry, Rochester, New York.

(Plainiffs' Exhibit 604)

Silicone gel is a potent, immunological adjuvant and

may also be able to mediate an auto-immune reaction.

16. The Effect of Silicone Gel on the Immune Response.

by Naim, 0. Lanzafame, J. Oss, Car] J.

Journal of Biomaterials Science accepted 2/10/94.

Silicone gel is capable of eliciting auto-antibodies

in the series of animal experiments; silicone gel from

McGhan commercial breast implant behaves both as a

potent humoral adjuvant and relatively weak

cellular-mediated immunity adjuvant. Silicone gel

also capable of inducing auto-antibodies in the rat.

THE IMMUNE RESPONSE IN HUMANS FROM SILICONE

17. Antibodies To Silicone Elastomers and Reactions To

Ventriculoperitoneal Shunts. Goldblum, Randall M.

P., et al., The Lancet, Vol. 340: August 29,

1992. PP 510-513. (Plantiffs' Exhibit 595)

Severe immune reactions seen in patients with silicone

elastomer (shunts).

18. " Antinuclear Autoantibodies In Women with Silicone

Breast Implants " . 11/28/92, Press RI et al. Lancet

340: pp.1304-1307.

Antinuclear Autoantibodies (ANAS) found in women with

silicone breast implants; some of the ANAs similar to

those found in idiopathic auto-immune disorders but

some other putative antigens could not be identified

and may represent novel auto-antibody/autoantigen

systems.

19. " A Clinical and Immunologic Evaluation of Women

with SBI and Symptoms of Rheumatic Disease " . 6/15/1993

Bridges A.B et al. ls Int. Med. 118 (12):

929-936.

Physical exams and lab work conducted on 156 women

with silicone breast implants and rheumatic disease

complaints; controls for lab studies were 12 women

with silicone implants and no rheumatic symptoms and

174 with fibromyalgia without silicone implants.

Findings suggest that most women with SBI and

rheumatic disease symptoms do not have classical

connective tissue diseases; however possibility that

atypical auto-immune illness, may be associated with

silicone exposure in small number of women exists.

20. Immunopathologic Effects of Silicone Breast

Implants. Suzanne S. Teuber, M.D., H. Yoshida,

Ph.D. and Gershwin, M.D. Western Journal of

Medicine, Vol.162, No.5, May 1995. pp.418-425.

(Plaintiffs' Exhibit 516)

This review of studies on silicone and immunity

concluded that silicones are neither biologically nor

chemically inert and that there is clinical and

theoretical reason for concern.

AUTHORS COMMENT ON IACK OF POWER SUFFICIENT FOR

STUDIES TO BE CONSIDERED DEFINITIVE OF ENGLERT

SCLERODERMA STUDY FROM AUSTRALIA AND MAYO CLINIC

STUDY.

21. Immunological Reactions to Silicone Implants: Risk

and Management. F. Spiera, et al. Clinic

Immunother 1 (6) 1994, pp.406-411. (Plaintiffs'

Exhibit 517)

Scleroderma-like illnesses are markedly

over-represented in women with silicone implants and

identifiable connective tissue disease, mimicking the

earlier reported Japanese experience with injectable

silicones. Although authors clinically recommend to

their patients removal of implants if symptomatic,

some patients with scleroderma-like illness may have a

progression of disease and even death despite

explantation perhaps due to migration of silicone

distantly in the host and the consequent inability to

remove the substance entirely. Exposure may thus

initiate a self-perpetuating disease process no longer

requiring the presence of the initial silicone

stimulus.

22. " Surface Dependent Antigens Identified by High

Binding Affinity of Serum Antibodies in a

Subpopulation of Patients with Breast Prosthesis " .

12/93 Kossovsky, Nir et al. Journal of Applied

Biomaterials 4 (33): pp.1-(Plaintiffs' Exhibit 538)

Silicones found to function as human adjuvants by

denaturing native macromolecules. Hypothesis tested

by two assays of sera from three groups: 249 with SBI,

47 non-implanted age-matched healthy women; 39

non-implanted women with various known rheumatological

diseases. Conclusion is that silicone may function as

an adjuvant by inducing changes in the confirmation of

native molecules.

23. Silicon and Silicones Theoretical and Clinical

Implications of Breast Implants. by H. Yoshida

et al. in Regulatory Toxicology and Pharmacology.

Vol.17, 1993, pp.3-18.

Authors review the element silicon, the chemistry of

silicone, the immunogenicity of silicone, and the know

biological functions of silicone to demonstrate how

silicone might promote auto-immune disease in

pre-disposed individuals. Review of case reports of

27 people with immunological reactions as well as

literature on silicone exposures in animal studies

leads authors to conclude that silicone can generate

inflammatory and immune responses despite its long

standing and incorrect representation as a chemically

and biologically inert substance.

SOLID, SCIENTIFICALLY VALID LABORATORY DATA

DEMONSTRATE THE DISEASE

24. Autoantibodies In Patients with Silicone Breast

Implants. by Alan J. Bridges. Seminars in Arthritis &

Rheumatism, Vol.24, No.1, Supp.1, Aug. 1994, pp.54-60.

(Plaintiffs' Exhibit 488)

Review of literature as well as 1992 American College

of Rheumatology abstracts from annual meeting show

differences in the clinical and serological features

of patients with connective tissue disease associated

with silicone implants compared with patients with

idiopathic connective tissue disease.

A DEFINITIVE EPIDEMIOLOGICAL STUDY TO DETECT

REIATIONSHIP BETWEEN SILICONE IMPLANTS AND CONNECTIVE

TISSUE DISEASE MAY NEVER BE ABLE TO BE PERFORMED

BECAUSE OF THE LONG LATENCY PERIOD AND THE RARUY OF

CONNECTIVE TISSUE DISEASES. THUS, A STUDY OF CLINICAL

AND SEROLOGICAL FEATURES OF PATIENTS WITH IMPLANTS WHO

DEVELOPED DISEASE BECOMES PARTICULARLY IMPORTANT.

25. Multiple Autoantibodies In Patients with Silicone

Breast Implants, E. Bar-Meir, S.S. Teuber, et al.

Journal of Autoimmunity, 8, 1995, pp.267-277.

(Plaintiffs' Exhibit 509)

Sera from 250 patients tested blindly (116 women with

SBI and 134 controls) to analyze twenty

auto-antibodies. Chief complaints of implanted

patient group included polyarthralgias, fatigue,

myalgias, morning stiffness and decreased memory.

Statistically significant greater frequency of

auto-antibodies in women with implants for fifteen of

the twenty auto-antigens. The association of auto-

antibodies in implants suggests an adjuvant action of

silicon/silicone by products.

26. Detection of Lymphocyte Simulation by Silicon

Dioxide, by L. Smalley, R. Shanklin,

F. Hall and V. s in International

Journal of Occupational Medicine and Toxicology Vol.

4, No.1, pp.63-70. (Plaintiffs' Exhibit 594)

In the continuing work investigating the immune

response to silicone, the authors adapted standard

mitogen testing which demonstrated cell-mediated

immune responses of T-lymphocytes to purified silicon

dioxide or silica in the implanted patients.

These test were run on 50 symptomatic patients with

SBI and 50 normal age matched female controls without

implants or symptoms. T-lymphocytes were harvested

from each group. This test method distinguishes the

immune disorders found in mammary implant patients due

to sensitization to silicon dioxide (silica) from

other altered immune disorders unrelated to implants.

27. Quantitative Aspects of Cellular Responses to

Silicone by R. Shanklin and L. Smalley,

International Journal of Occupational Medicine and

Toxicology Vol. 4, No.1, 1995 pp.99-111. (Plaintiffs'

Exhibit 762)

A study of pathology slides from 100 consecutive but

random patient consultations and mammary capsular

tissue surrounding which had surrounded SBI. Cellular

responses occur in women with mammary, as seen in

histopathological examination. Lymphocytic response

with resulting formation of granulomas and

macrophages.

28. Immunologic Markers In Silicone Breast Implant

Recipients, by Smalley, F. Hall, R.

Shanklin and NCchael s in International Journal

of Occupational Medicine and Toxicology Vol. 4, No. 1,

1995 pp.147-153. (Plaintiffs' Exhibit 763)

The presence of various autoantibodies and the

significant number of symptomatic implantation is

taken as evidence for a range Atypical Immune

responsiveness consistent with a primary cellular

immune response. The name - silicone associated

disease - is understood as an inclusive term fota new

form of autoimmunity caused by an alien material

(silicones and related substances) which mimic known

and better defined autoimmune diseases.

29. Immunologic Stimulation of T-lymphocytes by Silica

After Use of Silicone Implants. by L. Smalley,

R. Shanklin, Mazy F. Hall, V. s

and Aram Hanissian. The FASEB Journal, Vol. 9,

Mar.1995, pp.424-427. (Plaintiffs' Exhibit 504)

Standard lymphocyte stimulation test performed on 70

implant patients, 76 normal controls without implants

or symptoms, and 18 patients with classic rheumatic

disorders without a history of SBI. Lymphocytes

harvested from all groups. Results show implant

patients with increased stimulation index compared to

controls in those with rheumatic disorders. Follow-up

study with 220 normal controls, no SBI, 942 implants

with symptoms, and 34 implant patients without

symptoms.

CONCLUSION: Silicone Implant patients respond

immunologically to the silicone dioxide (silica)

contained in mammary prostheses.

30. Affidavit of R. Shanklin, M.D.

(Plaintiffs' Exhibit 764)

Dr. Shanklin, a Board Certified pathologist, discusses

the six independent reports by six independent labs,

each documenting silcone/silica memory T Lymphocytes.

31. Curriculum Vitae of R. Shanklin, M.D.

(Plaintiffs' Exhibit 765)

32. Affidavit of Donard S. Dwyer, Ph.D. (Plaintiffs'

Exhibit 766)

Dr. Dwyer, former Director of Immunology at Procept

(owned by Bristol-Myers Squibb), managed the research

program on T-cell receptors funded by Bristol- Myers

Squibb, a former manufacturer of silicone breast

implants. The Smalley/Shanklin laboratory data was

evaluated by Dr. Dwyer and found to be based on the

standard and acceptable method for measuring T-cell

proliferation which has been reproduced and is

consistent in the Procept laboratory.

Thus, the conclusions that patients with SBI have a

T-cell mediated Immune response to silicon dioxide

(silica) is justified.

33. Curriculum Vitae Donard S. Dwyer, Ph.d.

((Plaintiffs' Exhibit 767)

34. Antinuclear Antibodies in Breast Implant Patients

are Exposure-Duration Dependent But Not Age Dependent.

Ira Lewy, M.D., FACP; Ezraffson, Ph.D.

Departments of Medicine, Baylor College of Medicine

and University of Texas Health Science Center of

Houston, Houston, TX. Immunology of Silicones

Workshop. March 13-14, 1995. National Institute of

Health, M.D. (Plaintiffs' Exhibit 495)

35. Autoantibodies In Sera from Patients with

L-Tryptophan-Associated Eosinophilia-Myalgia Syndrome.

by Leed D. Kaufman, Varga, J. Gomez-Reino,

Jimenez, and Iran N. Targoff, Clinical

Immunology and Immunopathology, Vol.76, No.2, August,

pp.115-119, 1995.(Plaintiffs' Exhibit 508)

Study found unique auto-antibodies in sera from

patients with EMS (Eosinophilia-Myalgia Syndrome)

associated with exposure of L-Tryptophan. These auto

antibodies were clearly distinct from the

aut-antibodies commonly recognized in systemic

auto-immune conditions.

36. Silicone Breast Implants: Immunotoxic and

Epidemiologic Issues. by H. Yoshida, Shanna

Swan, Suzanne Teuber and M. Gershwin, Life

Sciences Vol. 56, No. 16, pp.1299-1310, 1995.

(Plaintiffs' Exhibit 695)

Discussion of adverse immune effects from silicone

from literature analysis including local responses in

animals, systemic responses in animals, inflammatory

responses in humans and autoimmune disease in humans.

Discussion of limitations of epidemiological studies

of silicone related diseases to date, including Mayo

Clinic Study, Wells and Englert.

37. Repeated Exposure to Silicone Gel Can Induce

Delayed Hypersensitivity. P. Narini, M.D., et

al. Plastic & Reconstructive Surgery, Vol.96, No.2.

August 1995. pp.371-380. (Plaintiffs' Exhibit 519)

Study performed to investigate a possible

cell-mediated immune response to silicone gel.

Authors demonstrated an antigen-specific

lymphocyte-mediated response in the animals primed

only with silicone gel. A delayed type

hypersensitivity to silicone gel was induced.

38. Antinuclear Antibodies and Breast Implants. Henry

Claman, M.D. and Alastair D. on, Ph.D. The

Western Journal of Medicine. Vol. 160, No.3. March

1994. pp.225-228. (Plaintiffs' Exhibit 513)

Antinuclear antibodies tested in the sera of four

groups of women. Four groups studied:

Group 0 = 19 women without SBI, healthy;

Group I = 38 women with SBI, healthy and pleased with

implants;

Group II = 82 women with SBI with various symptoms but

no definite diagnosis of autoimmune connective tissue

disease;

Group III= 11 women with SBI with overt connective

tissue diseases.

Results: no positive ANA tests in Group 0.

Significant positive ANA tests in higher than expected

frequency (18%) of Group I women, healthy women with

SBI.

Many women have a variety of complaints and also have

positive ANA tests (26%).

In women with breast implants with later connective

tissue disease, scleroderma was far more prevalent

than rheumatoid arthritis or SLE.

39. Self-Reported Signs & Symptoms In Breast Implant

Patients with Novel Antibodies to Silicone Surface

Associated Antigens [anti-SSAA(x)]. Nir Kossovsky,

Journal of Applied Biomaterials, Vol.6, 1995,

pp.153-160. (Plaintiffs' Exhibit 520)

Previous sera studies that had shown statistically

significant levels of antibodies to Silicone Surface

Association Antigens were correlated to symptoms by

clinical survey sent to sera positive SBI women.

Results showed statistically significant differences

in 3 symptoms of anti-SSAA positive patients.

40. Immune Functional Abnormalities In Patients With

Chemical Abnormalities and Silicone Breast Implants.

by , W., M.D. Vojdani, Aristo, Ph.D.,

Brautbar, Nachman, M.D. (Plaintiffs' Exhibit 587)

Forty patients with SBI and forty healthy sex and

age-matched controls selected for study including

physical examination, history and laboratory tests.

Many immunological abnormalities are found in

individuals with SBI; conclusion is mechanism of fime

injury causing auto-immune diseases or syndromes.

41. A Pathophysiological Examination of the Biophysics

and Bioreactivity of Silicone Breast Implants. by Nir

Kossovsky and Stassi. Seminars in Arthritis &

Rheumatism, Vol.24, No.1, Supp.1, Aug. 1994, pp.18-21.

(Plaintiffs' Exhibit 573)

Biological responses to implanted silicone are

initiated by surface adsorption of native proteins to

the implant. Proteins then undergo conformational

changes and denature on complexing silicone.

Bioreactivity is thus surface dependant and affected

by characteristics such as surface area, shape, charge

in chemistry. Biological response occurs with possible

immunological activation.

42. Silicone Toxicology, by Busch. Seminars in

Arthritis & Rheumatism, Vol.24, No.1, Supp.1, Aug.

1994, pp.11-17. (Plaintiffs' Exhibit 572)

Silicone is not inert; silicone and/or the multiple

chemical contaminants within elicit foreign body

reactions associated with granulomatous inflammation

and fibrosis and have potential for significant

toxicity in the implanted recipient.

43. Abstracts and Presentations from the Workshop on

Immunologies of Silicones Sponsored by National

Institute for Health, NCI and DCBDC held March 13,

1995. (Plaintiffs' Exhibit 772)

44. Silicone-Specific Blood Lymphocyte Response in

Women with Silicone Breast Implants, by Emmanuel A.

Ojo-Amaize, Victor Conte, Hun-Chi Lin, Brocker,

Milcon Agopian and . COIN. Giagn Lab.

Immunol. Nov. 1994, pp. 689-695. Vol. 1, No.6.

(Plaintiffs' Exhibit 621)

Blinded cross-sectional study with 99 women, 44 with

SBI. SBI group divided into asymptomatic, symptomatic

and implanted women and symptomatic explanted women.

Control was 55 healthy volunteer women without SBI.

Conclusion: Silicon specific T-cell responses observed

in twice as many symptomatic as asymptomatic women

exposed to SBI, sugggesting cell mediated

immunogenicity plays a role In the development of

abnormal immune reactions associated with silicone.

This provides a new apparently specific screening

blood test.

45. Human Immune Response to Polydimethylsilaxe

(silicone): Screening Studies in a Breast Implant

Population. Wolf, Lappe, and Ezrailson.

Vol. 7, Oct. 1993, FASBE Journal, pp. 1265-1268.

(Plaintiffs' Exhibit 622)

THE BIOLOGICAL PIAUSIBILITY OF A SILICONE ASSOCIATED

DISORDER: SILICA EXPOSURE AND AUTO-IMMUNE DISEASES

46. Portions of Lot History from 3M Implants - Lot #

S04-19747 implanted in Mildred Merlin showing silica

as component material.

47. Report from the Instructional Course of the Int'l

Society of Aesthetic Plastic Surgery, Uppsala, Sweden,

March 16-18, 1993. in Memorandum from Curt Sahlgren,

3M Sweden to: Bruno Lowinger, 3M Europe. March 18,

1983. (Plaintiffs' Exhibit 483)

3M acknowledges that recent investigations have shown

that gel bleed from an intact implant leaves

" ...particles of elemental silica and organic silicone

within the systemic organism of the body with not yet

known adverse effects. "

48. Adjuvant Effects of Amorphous Silica on the Immune

Response to Various Antigens in Guinea Pigs., by D.

Mancino and N. Bevilacqua Int. ARchs. Allergy appl.

Immun. S31 97-103 (1977). (Plaintiffs' Exhibit 480)

Amorphous silica is able to enhance the humoral immune

response to various antigens, widely differing in

molecular weight.

Silica has been shown to influence the immune response

with either depressive or stimulators effects

depending on the type and amount of substance used.

49. Pathological Effects of Inhaledled Amorphous

Silicas in Animals, by H. Groth, M.D., Choudari

Kommieni, D.V.M., Ph.D., J. Moorman, Lloyd E.

Stettler, Ph.D., D. Wagner. Presented at ASTM

International Symposium on Health Effects of Synthetic

Silica Particulates, Torremolinos, Spain 6 November

1979. (Plaintiffs' Exhibit 479)

Exposure by inhalation to monkeys of amorphous, fumed

silica produced findings of large quantities of silica

in macrophages in lungs and tracheal lymph nodes of

monkeys and early nodular fibrosis in the lungs of

monkeys.

50. The Biological Action of Degussa Submicron

Amorphous Silica Dust (Dow Corning Silica).

Inhalation Studies on Rats. by Gerrit Schepers, M.D.,

D.Sc., M. Durkan, M.E., B. Delahant;

Francis T. Creedon AMA ARCH. of IND. Health. Vol.16.

Aug. 1957. pp.125-146. (Plaintiffs' Exhibit 484)

Inhalation studies on rats exposed to amorphous silica

dust from Dow Corning silica died from pulmonary

vascular obstruction coupled with pulmonary

insufficiency and emphysema.

51. Myoflbroblasts and Free Silicon Around Breast

Implants. by Ross Rudolph, MD Jerrold Abraham, M.D.,

Vecchione, M.D., Guber, M.D. and Marilyn

Woodward. Plastic And Reconstructive Surgery.

Vol.62. No.2. Aug. 1978. pp.185-196. (Plaintiffs'

Exhibit 485)

Breast tissue and capsules (scar tissue) explanted

from women during explantation surgery revealed

presence of the element silicon via scanning electron

microscopic technique. Such a technique cannot

identify silica. Such a technique must be developed

because silica in tissue can cause silicosis, a

fibrotic disease.

52. The Association of Progressive Systemic Sclerosis

(Scleroderma) with Coal Miner's Pneumoconiosis & other

Forms of Silicosis. Gerald Rodnan, M.D. et al.

ls of Internal Medicine. Vol. 66, No.2 February

1967, pp.323- 334. (Plaintiffs' Exhibit 602)

Silica exposure is a hazard of coal mining; the

authors describe an association of progressive

systemic sclerosis (scleroderma) within coal miners or

in other occupations marked by heavy exposure to

silica dust

53. Health Effects of Synthetic Silica Particulates.

A Symposium sponsored by ASTM Committee E-34 on

Occupational Health and Safety and the Industrial

Health Foundation Benalmadena-Costa (Torremolinos),

Spain 5-6 No. 1979. ASTM STP 732. D.D. DUNNOM, Ed.,

American Society for Testing and Materials, 1981,

pp.82-93. (Plaintiffs' Exhibit 478)

Chapter by Burrell " Immunological Aspects of

Silica " .

54. Effects of a Crystalline Silica on Antibody

Production to T-Dependent and T-Independent Antigens

In Balb/c mice. by D. Mancino, M.L. Viotte, M.

Minucci. Int. ARchs Allergy appl. Immun. 73:10-13

(1984). (Plaintiffs' Exhibit 481)

55. Adjuvant Effects of Silica (Tridymite) on Antibody

Production, by Benvenuto Pernis and Florenzo Paronetto

(Introduced by Hans Popper). Dept of Experimental

Pathology, Institute of Industrial Medicine,

University of Milan, Italy. Received 12 April, 1962.

PSEBM, 1962, v.110. (Plaintiffs' Exhibit 482)

56. Endothelial Metaplasia of the Alveolar Capillaries

In Experimental Silicosis of Rats. by Mochimura H.,

Kawanami O., Kudoh S., Niitani H. Japanese Journal of

Thoracic Diseases. 33(3):268-74, 1995 Mar.

(Plaintiffs' Exhibit 672)

Silicosis induced in rats by administration of silica

particles.

57. Mortality Study of Gold Miners Exposed to Silica

and Nonasbestiform Amphibole Minerals: An Update with

14 More Years of Follow-up. by Steenland K, and Brown

D. American Journal of Industrial Medicine. 27(2):

217-29, 1995 Feb. (Plaintiffs' Exhibit 673)

Follow-up study of over 3,000 gold miners reveals

significant excesses of arthritis, muscular skeletal

diseases including systemic lupus and sclerosis and

skin conditions including scleroderma and lupus, all

diseases of auto-immune origin which have been

associated with silica exposure.

58. Silicosis in Brazilian pit diggers: relationship

between dust exposure and radiologic findings. by

Holanda NM, Holanda NM, s MP., Felismino PH.,

and Pinheiro VG. American Journal of Industrial

Medicine. 27(3):367-78, 1995 Mar. (Plaintiffs' Exhibit

674)

59. Detection of anti-topoisomerase I antibodies using

a full length human topoisomerase I recombinant

protein purified from baculovirus _expression system.

by Whyte J., Earnshaw WC., Champoux JJ., LH.,

L., Hall ND., and McHugh NJ. Clinical &

Experimental Immunology. 100(2):214-8, 1995 May.

(Plaintiffs' Exhibit 675)

60. Occupational silicosis-Ohio, 1989-1994 [published

erratum appears in MMWR Morb Mortal Wkly Rept 1995

Apr 28;44(16):325]. by Anonymous. Morbidity &

Mortality Weekly Report. 44(4):61-4, 1995 Feb.3.

(Plaintiffs' Exhibit 676)

61. Shedding of Silicone Particulates From Inflated

Breast Implants. by Vargas, M.D. Plastic &

Reconstructive Surgery. Vol.34, No.2. pp.252-253.

Aug. 1979. (Plaintiffs' Exhibit 486)

Explantation of a saline implant showed collections of

" sand " on the surface; on infrared spectroscopy,

demonstrated the silicon-carbon bond.

62. Silica Exposure In Auto-Immune Disease. by

Steenland, , Ph.d. and Goldsmith, , MSPH,

Ph.d. American Journal of Industrial Medicine

28:603-608 (1995). (Plainfiffi' Exhibit 489)

Authors summarize the evidence of association of

silica exposure to a variety of auto-immune diseases

including systemic sclerosis, rheumatoid arthritis,

lupus and chronic renal disease. Authors posit the

link between silicone exposure and auto-immune

disease, and whether silicone breast implants have

same causal relationship with auto-immune disease.

63. Silica-Induced Scleroderma, Haustein, Ziegler,

Hurrmann. Panel of the American Academy of

Dermatology., 1990; 22:444-8 (Plaintiffs' Exhibit

507).

CLINICAL EVIDENCE OF A SILICONE RELATED SYSTEMIC

DISEASE: CASE REPORTS AND CASE SERIES PUBLISHED IN

MEDICAL AND PEER-REVIEWED JOURNALS

64. Silicone in the Liver. Possible Late Effects. By

J. Hunt, M.J.G. Farthing, L.R.I. Baker, P.R. Crocker,

D.A. Levison. Gut. 1989, 30, 239-242. (Plaintiffs'

Exhibit 540)

Silicone identified in liver of two patients that had

abnormal liver function and liver scarring. 'nese

patients had been on dialysis prior to renal

transplant and siliconized blood pump insert had

liberated silicone into liver.

65. Migration and Chemical Modification of Silicone In

Women w/Breast Prostheses. by Lencio Garrido, MRM

Vol.31, 1994, pp.328-330. (Plaintiffs' Exhibit 692)

NMR (Nuclearmacnetic resonance) spectroscopy performed

on women with SBI and 3 without implants revealed

silicone and other silicon compounds in both blood and

liver of implanted women, whether or not implants were

clinically ruptured; however total concentration was

lower when implants appear to be intact.

66. Migration and Accumulation of Silicone In the

Liver of Women with Silicone Gel-Filled Breast

Implants. Bettina Pfleiderer & Leonicio Garrido.

Magnetic Resonance in Medicine Jan. 1995 33(l):

pp.8-17 (Plainfiffi' Exhibit 664)

Authors formed NMR spectroscopy in liver of human

volunteers with implants and results clearly reveal

presence of silicone in the liver. Prior work by same

authors on rat model demonstrated a considerable

amount of free silicone migrates from gel-filled

implants and that silicone is not chemically inert but

undergoes chemical degradation.

CONCLUSION: Migration of free material from silicone

implants to local and distant sites occurs through

lymphatic or hematogenous pathway.

67. Rheumatic Disease Among 1167 Women Reporting Local

Implant and Systemic Problems After Breast Implant

Surgery. Ann , R.N.P., Ph.D., et al.

Journal of Women's Health, Vol.3, No.3, 1994.

pp.165-177. (Plaintiffs' Exhibit 518)

National Cancer Institute (NCI) investigators

contacted 1,167 women who had had breast implant

surgery and who had reported local implant or systemic

problems to the FDA. Out of the 820 women

interviewed, statistically significant associations

that were found included breast implant type with

scleroderma, breast implant manufacturer with systemic

lupus.

68. Siliconosis: A Spectrum of Illness, by

Borenstein. Seminars in Arthritis & Rheumatism,

Vol.24, No.1, Supp.1, Aug. 1994, pp.1-7. (Plaintiffs'

Exhibit 632)

This, and ensuing papers published in Seminars in

Arthritis and Rheumatism, emanated from a symposium

held in 1992 at Washington University Medical

Center. Information reported at the symposium

presented initial data supporting the notion that

patients with exposure to silicone gel are

experiencing a new illness, previously described as

" human adjuvant disease " or chronic silicone

arthropathy. Symposium presenters used terms such as

siliconosis or silicone implant syndrome.

Conclusion: Siliconosis is a musculoskeletal pain

syndrome characterized by overwhelming fatigue,

arthraigias and myalgias. Additionally, alopecia,

fever, sleep disturbances, Sjogren's-like Syndrome,

lymphadenopathy and arthritis have also been

identified.

69. Clinical Findings In Symptomatic Women with

Silicone Breast Implants. by B. Vasey, Deborah

L. Havice, S. Boranegra, Mitchel J. Seleznick,

H. Bridgeford, Pindaro ex-Osuna, and

R. Espinoza. Seminars in Arthritis & Rheumatism,

Vol.24, No.1, Supp.1, Aug. 1994, pp.22-28.

(Plaintiffs' Exhibit 633)

Fifty women seen in clinic between 1977 and 1991 with

SBI were followed. The most common clinical findings

included chronic fatigue, muscle pain, joint pain,

joint swelling and lymphadenopathy. 33 women underwent

explantation: 24 of them improved clinically, 8 did

not change and one worsened. Authors believe that

this case series supports the relationship between SBI

and rheumatic disease signs and symptoms.

70. A Clinical and Laboratory Profile of Symptomatic

Women with Silicone Breast Implants. by .

Seminars in Arthritis & Rheumatism, Vol.24, No.1,

Supp.1, Aug. 1994, pp. 29-37. (Plaintiffs' Exhibit

634)

276 patients with SBI evaluated to describe frequency

of various symptoms in symptomatic patients.

Conclusion: siliconosis Is a novel systemic disease

with symptoms of chronic fatigue, cognitive

disfunction, sicca syndrome and arthralgia occurring

in women with longstanding implants who have

antecedent local pathology in the form of capsular

contracture and/or implant ruptue.

71. Epidemiology of Silicone Related Disease. by

Shanna Swan. Seminars in Arthritis & Rheumatism,

Vol.24, No.1, Supp.1, Aug. 1994, pp.38-43.

(Plaintiffs' Exhibit 635)

Author discusses problems inherent in epidemiology of

silicone related diseases, especially due to atypical

nature of the disease, which complicates disease

definition and renders study of classic disease

unlikely to check risks of silicone exposure. The

report addresses the most important study design

issues -- disease and exposure definitions, bias,

confounding and power -- in the context of studies of

silicone related disorder.

72. A Profile of Symptomatic Patients with Silicone

Breast Implants; A Sjogren's-like Syndr-ome. by Bruce

Freundlich, Atman, et al. Seminars in

Arthritis & Rheumatism, Vol.24, No.1, Supp.1, Aug.

1994, pp. 44-53. (Plaintiffs' Exhibit 636)

Prospective non-controlled study on first fifty

consecutive women with SBI at the Graduate Hospital of

Rheumatology revealed the most prominent complaints to

be fatigue, generalized stiffness, poor sleep and

arthalgias. Other problems included Raynaud's

phenomenon, alopecia, adenopathy, night sweats and

frequent soar throats. Fifty percent of the women

complained of dry eyes and dry mouth. Positive ANA or

rheumatoid factors in 38% of patients.

Conclusion: Findings indicate the presence of a unique

syndrome associated with silicone breast implants

characterized by musculoskeletal pain and auto-immune

features.

73. Scleroderma After Silicone Augmentation

Mammoplasty, by Spiera, H., JAMA 260: 236-238, 198838

(Plaintiffs' Exhibit 773)

Case-control study showed a much higher incidence of

prior silicone implantation in scleroderma patients

when compared with patients with rheumatoid arthritis.

74. Case Report- Scleroderma, Primary Bilary Cirrhosis

and Sjogren's Syndrome After Cosmetic Breast

Augmentation with Silicone Injections: A Case Report

of Possible Human Adjuvant Disease. Y. Okano et al.

l of the Rheumatic Diseases, 43, pp.520-522, 1984

(Plaintiffs' Exhibit 599)

A 52 year old women developed scleroderma, liver

disease and sjogren's syndrome after cosmetic

injections with silicone.

75. Silicone Implants and Rheumatic Diseases. by

S. Sergent, et al. Textbook of Rheumatology, Update 4.

1993 pp.1-12. (Plaintiffs' Exhibit 623) This chapter

in 's Rheumatology discusses silicon, silica and

silicones as well as the diseases associated with

these materials.

That silicone is toxic in both animals and man is well

proven, according to author. Author discusses local

reactions to silicone implants, lymphadenopathy and

granuloma formation and silicone implant related

synovitis, the immune reaction in humans to silicone,

and the musculoskeletal and rheumatic diseases

associated with silicone.

76. Causal Inference In Syndromes Associated with

Silicone Breast Implants: Psychogenic and

Environmental Factors, by Marc Lappe, International

Journal of Occupational Medicine and Toxicology, Vol

4, No.1 1995. pp.165-175. (Plaintiffs' Exhibit 768)

Author discusses three hypotheses that could explain

the occurrence of illness in silicone gel implanted

women and rules out all but the causal hypothesis that

silicone is responsible for bonafide systemic,

immunological illnesses in some breast implant

patients.

77. Silicone-Reactive Disorder, a New Auto-immune

Disease Caused by Immunostimulation and Supemntigens,

by M.A. Lappe, Medical Hypotheses (1993) 41, 348-352.

(Plaintiffs' Exhibit 769)

Silicone related illness is a unique disease complex

best described as " silicone-reactive disorder. The

author supports his theory with five lines of

evidence: 1) silicone breast implant components

include immunostimulating substances including

amorphous fumed silica; 2) silica-stimulated

macrophages can induce auto-immune disease; 3)

silicone has been shown to provoke antibody production

in concert with certain antigens; 4) autoimmune

reactions following exposure to superantigens have

been associated with a wide range of bacteria; 5) some

of these bacteria are found in the silent infections

that have been reported in breast implant recipients.

CLINICAL METHODOLOGY OF DIAGNOSING A DISEASE AND ITS

CAUSE

78. Cecil Textbook of Medicine, 18th Edition, Edited

by Wyngarrden and Lloyd , 1988 W.B.

Saunders Co. (Plaintiffs' Exhibit 770)

Clinical tests to reach a diagnosis include medical

history, chronological events and symptoms to test

diagnostic hypotheses, physical examination and

laboratory studies. Physician must gather data and

interpret data in order to reach diagnosis.

79. Preliminary Criteria for Silicone Related Disease

(SSRD), Berkeley Delphic Panel 10/22/95, Consensus

Statement on Systemic Silicone Related Disease.

(Plaintiffs' Exhibit 771)

PRIOR TESTIMONY REGARDING METHODOLOGY IN DIAGNOSIS OF

NEW SILICONE RELATED DISORDER AND ITS CAUSE.

81. Testimony of N. Gershwin, M.D., Thiess v. 3M.

(Circuit Court State of Oregon, No. 9401-00139), June

8, 1995

page 789/14 - 790/3

page 790/10 - 795/17

page 796/5 - 811/20

page 813/25 - 830/2

Dr. Gershwin, Board Certified in Internal Medicine,

Rheumatology and Immunology, a Professor at U.C.

for the past twenty years, formerly of NIH, Editor in

Chief of Clinic Reviews in Allergy and Immunology, has

six to eight articles relating to silicone exposure

and disease in peer-reviewed journals, testified in

this case against 3M that there is a new, unique

disease in which women have a constellation of

symptoms that are not ordinarily seen in other

circumstances, but which experience has occurred in

the past from other exposures such as drugs or

environmental agents such as silica.

Dr. Gershwin has assembled a bibliography listing over

600 articles about silicone gel and autoimmune

disease.

82. CV of Dr. N. Gershwin

83. Excerpts from Trial Testimony of Espinoza,

M.D. from case of Toole v. Baxter Healthcare,

Tried before the Honorable Sam C. Pointer, U.S.

District Court Northern District of Alabama, January

1995

pp. 1891-1922

Dr. Espinoza, a Board Certified Rheumatologist and

Professor of Medicine, Chief of Rheumatology, LSU

School of Medicine at New Orleans, Board Certified in

Internal Medicine, Rheumatology, and Diagnostic

Immunology and Laboratory Rheumatology, with 8

published Peer-Reviewed articles relating to the

effects of silicone breast implants on women,

testified that in the Department of Rheumatology at

the LSU Medical School, Dr. Espinoza supervises 5

faculty members, 6 research fellows, 1 clinical fellow

in rheumatology, as well as other technicians. There,

approximately 3,000 women with silicone breast

implants have been seen and evaluated and treated,

since 1984.

At LSU College of Medicine, the rheumatology

department has confirmed that anti-nuclear antibodies

system (ANA) is positive in over 50% of women with

silicone breast implants, as compared with less that

20% of women in the general population who will show a

positive ANA.

The conclusion of Dr. Espinoza is that the typical

symptom complex that women with silicone breast

implants consists of painful muscles, painful joints,

debilitating fatigue. In symptomatic women, these

symptoms are present in approximately 80-85% of the

symptomatic patient population.

Other symptoms that are common to women with SBI are

skin rashes, telangiectasias which are dilatations of

the capillary vessels, commonly seen in patients with

connective tissue disease, atypical synovitis, nerve

entrapment, and Raynaud's phenomenon.

84. Excerpts of testimony from 2 doctors in the case

of Toole v. Baxter before Judge Pointer. (USDC

Northern District of Alabama, Southern Div. Cv94-P-13,

5595 - Dr. Gloria Gastone, Dr. Kirwin

Schneider.

Gloria Gastone:

page 1702/14 - 1702/21

page 1707/6 - 170917

page 1714/18 - 1714/25

page 1722/16 - 1724/21

Kerwin Schneider

page 1386/9 - 1388/3

page 1390/9 - 1391/10

page 1395/1 - 1399/24

page 1412/18 - 1422/15

page 1451/7 - 1453/3

85. Affidavits From Physicians Attesting to Silicone

Related Disease identified, Diagnosed and Treated in

Their Patient Population

Bethea, M.D.

Lenore Brancato, M.D.

Nachman Brautbar, M.D.

E. Burns, M.D.

J.D. Doll, M.D.

Bruce Freundlich, M.D.

ph Markenson, M.D.

Lige Rushing, M.D.

, M.D.

, M.D.

Sumner, M.D.

Affidavits from other physicians have been promised

but have not yet been forwarded to this office for

inclusion in this Exhibit List.

86. Curriculum Vitae Shanna Helen Swan, Ph.D.

87. Curriculum Vitae of Arthur Brawer, M.D.

88. CV Mark Lappe, Ph.D.

89. CV F. Goldsmith, M.S.Ph., Ph.D.

90. Affidavit of , M.D.

91. Affidavit and Curriculum Vitae of

Wallis, M.D.

THE EPIDEMIOLOGY TO DATE.

92. Letters to the Editor, Arthritis and Rheumatism,

Vol.38, No.5, May 1995, pp. 719-726., by Spiera

in respect to the -Gueffeo study. (Plainfiffi'

Exhibit 600)

93. Letters to the Editor, Vol. 333, No. 21, England

Journal of Medicine, pp. 1423-1424. Nov. 23, 1995.

These letters and correspondence concern some of the

limitations and problems perceived by other physicians

practicing in the field of medicine, rheumatology and

internal medicine, concerning the Harvard Study.

94. Affidavit of R. , General Counsel to

Dow Corning, sworn to on July 10, 1995 in support of

Dow Corning Motion for Summary Judgment against

Insurance r to pay, as defense costs, the Dow

Corning funding of Medical Research and Epidemiology.

95. Portions of the proceedings on the record before

Honorable J. Columbo, Jr., August 11, 1995,

State of Michigan, Circuit Court for the County of

Wayne. Case No. 93-325-788CK. Dow Corning

Corporation v. Hartford Accident Indemny Co., granting

Dow Corning's Motion for Summary Judgment on

Transamerica's duty to pay all Dow Corning's costs for

medical research as defense cost in defense of claims

for systemic illness and autoimmune disease caused by

silicone breast implants.

96. Letter, Plastic Surgery Educational Foundation

(PFES) 8/5/92 to Dr. Sherine - PSEF wiU fund

90% of costs of Mayo Clinic Study.

97. Portions of Testimony of R. Barrett Noone, M.D.,

Vol. 2, Sept. 1994.

Re: All PSEF Funding for Epidemiology came from SBI

Manufacturers.

98. Letter to the Editor, New England Journal of

Medicine, July 8, 1994 from Plaintiffs Steering

Committee for MDL-926 concerning and enclosing 1994

research funding to PSEF by manufacturers for

" epidemiology research " .

99. Dow Corning Bankruptcy Schedule dated 6/30/95

showing all funding for external mammary research

studies by Dow Corning.

100. Excerpts from Deposition of Graham Colditz, Ph.D.

1/21/95 In Re: Silicone Breast Implant Product

Liability Litigation concerning regarding receipt of

Dow Corning money for Harvard Study.

Page 11115 - 11/25

Page 13/24 - 14/3

Page 17/10 - 17/18

Page 19/23 - 26/21

Page 49/8 - 50/14

Page 70/18 - 85/12

101. Excerpts of Deposition of H. Liang, M.D.

1/21/95 In Re: Silicone Breast Implants MDL-926

Page 15/6 - 15/20

23/9 - 24/1

36/23 - 38/4

41/20 - 56/13

64/15 - 69/4

81/12 - 86/21

126/16 - 132/3

141/24 - 142/13

153/19 - 158/10

181/8 - 188/7

102. Excerpts of Deposition Testimony of Pierre

Blais, Ph.D. 11/14/95 from the case of Merlin v. 3K

Vol.2, pps. 243-252.

Dr. Blais is of the opinion that the presence of

silica in the McGhan/Merlin implants was a defect

(silica is hydrophilic and absorbs lipids to some

degree as well as water) and there is no distinction

in fact between amorphous silica and the crystalline

silica, as amorphous is simply silica that is reduced

through a fine state of division although the

crystalline structure is the same as crystalline

silica.

Cite pages 261/19 - 268/8

In addition to platinum, used as a catalyst there are

other impurities and additives to the silicone gel.

The gel consists of only 80-909'o PUTE silicone and

the balance are additives, impurities and such things

as D4.

103. Excerpts from Deposition Testimony of Noel

Rose, M.D., Ph.d. September 16, 1995 and

September 17, 1995 - designated as defense expert

immunoligist in case of Merlin v. 3M.

page 37/21 - 40/11

page 43/9 - 43/21

page 45/6 - 55/2

page 71/2 - 72/14

page 75/4 - 75/16

page 84/18 - 85/1

page 95/14 - 96/21

page 115/19 - 116/1

page 122/12 - 123/1

page 127/21 - 128/11

page 129/18 - 130/18

page 170/8 - 171/6

VOL. II

page 185/17 - 186/5

page 208/14 - 209/14

page 219/4 - 219/8

page 227/7 - 227/17

page 234/14 - 238/8

page 241/3 - 241/13

page 245/2 - 249/2

page 254/18 - 255/2

page 261/14 - 262/1

page 266/11 - 267/18

page 268/19 - 269/1

page 283/13 - 284/7

104. A Rheumatologist's View of Silicone, by B.

Vasey, International Journal of Occupational Medicine

and Toxicology, Vol.4, No.1 1995, p.203-209.

105. The Epidemiology of Scleroderma: A

Population-based Case-Control Study, Principal

Investigator - Schottenfeld, M.D., University of

Michigan, School of Public Health

106. T-Cell Modified Immune Response... by Shanklin &

s

107. Connective Tissue Effects..., Abstract by

, Edworthy & _______

108. Immunological Aspects of Silica, by

Burrell, Health Effects of Synthetic Silica

Particulates, ASTM STP 732, American Society for

Testing of Materials, 1981, pp.82-93.

109. Mortality Study of Gold Miners Exposed to

Silica, by Steenland & Brown (See Exhibit 57.)

110. Silica-Associated Connective Tlssue A Study of

24 Cases, By Anne- Claude Koeger, M.D., Thierry Lang,

M.D., Didier Alcaix, M.D., Bernard on, M.D.,

Sylvie Rozenberg, M.D., Pascal Chaibi, M.D., Josiane

Arnaud, D.Pharm, Mayaud, M.D., Jean-

Camus, M.D. and Pierre Bourgeois, M.D., Medicine,

Vol.74, No.5, September 1995.

111. Photos made from slide presentation testimony of

Dr. Arthur Brawer at Merlin v. 3M Daubert Hearing USDC

District of Nevada CV N-95-696HDM on December 11,

1995.