Message: 1

Date: Wed, 7 Jun 2000 22:51:37 -0600

Subject: Older Documents from USSW

When I first came on the net in Jan. 1996, the USSW site was the main site for information and studies. It was maintained by Walt Monger who died almost two years ago. Some of you have been concerned about the loss of the information on his site.

I have many of those documents ready to be emailed out to the list. I just wanted to warn you they were coming. If anyone already has them and does not want to keep them, they are all identified as USSW in the subject line. They may be of interest to newer ladies on the list who did not have access to them.

Pam

3. USSW: DOW CORNING MDX 4-4011 Medical Fluid & Dept of Health, Education & Welfare FDA

4. USSW: What Dow Corning Won't Tell You

5. USSW: Silicone Toxicity and Immune Dysfunction Syndrome

6. USSW: Doctors Studies of Silicone

7. USSW: Dystrophy of the Arm

10. USSW:Silicone Breast Implants and Autoimmunity: Causation

11. USSW:Aspergillus Colonization Associated With Bilateral Silicone Mammary Implants

12. USSW: WOMEN'S EXPERIENCES WITH BREAST IMPLANTS

13 USSW: The Litigation Explosion: The Big Lie

14. USSW: The Consumer Attorneys of California: Truth Corner

15. USSW: Suing and Being Sued - When to Opt Out of a Class Action

16. USSW: Internal Memo From Dow Corning, 1976

18. USSW: Serious Adverse Affects

19 USSW: Multiple autoantibodies in patients with silicone breast implants

20. USSW: Effect Of Polydimethylsiloxane On Autoimmune Parameters

21. USSW: Silicone Gel Filled Breast Implants and Connective Tissue Disease

22. Re: Older Documents from USSW

23. USSW: elevated levels of blood silicone

24. USSW: DISQUISITION ON HUMAN ADJUVANT DISEASE

25. USSW: Congress at it again: Blaming Breast Implant Victim

26. USSW: Corning Pharmaceutical Services: Companies

27. USSW: Diagnostic And Clinical Criteria

Message: 3

DEPARTMENT OF HEALTH, EDUCATION AND WELFARE FOOD AND DRUG ADMINISTRATION

Name of Sponsor: DOW CORNING CORPORATION

Address: MIDLAND, MICHIGAN

Name of Investigational Drug:

DOW CORNING MDX 4-4011 Medical Fluid

100 CSTKS. to 12,500 CSTKS. Viscosity

(For tissue augmentation by injection except for mammary area)

June 8, 1965

Secretary of Health, Education and Welfare

Food and Drug Administration

For the Commissioner of Food and Drugs

Washington 25, D. C.

Dear Sir:

The sponsor, Dow Corning Corporation, submits this notice of claimed investigational exemption for a new drug under the provisions of section 505 (1) of the Federal Food, Drug and Cosmetic Act and Par. 130.3 of Title 21 of the Code of Federal Regulations.

Section 1. Name and Administration

DOW CORNING MDX 4-4011 Medical Fluid is the designation assigned to DOW CORNING <R> 360 Medical Fluid for purposes of identification and control of its use in tissue augmentation which is the subject of this new drug investigation. This fluid is identical to DOW CORNING 360 Medical Fluid and is the same as the commercial product which has been designated as DOW CORNING <R> 200 Fluid except that more rigid quality control procedures have been established for the medical grade product. The viscosities involved in the contemplated usage will include the standard range presently sold as DOW CORNING 360 Medical Fluid in viscosities of 100, 200, 350, 500, 1000, and 12,500 centistokes.

DOW CORNING MDX 4-4011 Medical Fluid is a dimethylpolysiloxane. References in the literature to "silicone" fluid usually are actually concerned with dimethylpolysiloxane because this was the earliest and most widely available fluid. On occasion, some writers have changed the prefix order and refer to the product as polydimethylsiloxane.

Dimethylpolysiloxanes are linear polymers containing the repeating polymeric unit CH3. When dimethylpolysiloxane of -Si-0 CH 3 a fluid consistency is being considered, unless designated in another manner, it is generally understood that the linear polymer is "end-blocked" with trimethylsiloxy units. The fluid in question is of this variety and the structure can be represented as: (CH 3)3S10 [(CH3)3S10]xSi(CH3)3 The viscosity is directly related to chain length (i.e., to the value of x in the above formula) and is controlled by the ratio of trimethylsiloxy units to dimethylsiloxy units in the product. The value of x is estimated to be approximately 85 for the 100 cs. fluid and 865 for the 12,500 cs. viscosity grade.

Administration will be by injection into the appropriate body area, the specific procedure to be at the discretion of the qualified investigator. Depending on the area of injection, the total quantity injected may vary from as little as 0.02 milliliters for treatment of a wrinkle to as much as 100 milliliters for the repair of facial hemiatrophy. In cases where the larger quantities of fluid are required, several separate injections may be made serially at appropriate intervals until the desired amount has been injected.

The use of a viscous fluid as an injectable tissue augmentation has several advantages over the use of surgically implanted materials. These are:

(1) more control of size and shape of implant

(2) can be done without or with a minimum of visible scar

(3) injected area will more readily conform to body contour

(4) less expensive

(5) provides a normal texture to deformed features.

This fluid injection technique should provide an easy and very effective means of improving facial hemiatrophy, acne scars, wrinkles and other disfigurements of the body. Hemiatrophy, in particular, is difficult to repair by the use of any prior techniques. With the use of DOW CORNING MDX 4-4011 Medical Fluid, it is expected that such tissue augmentations can be made without the use of major surgical procedures or general anesthesia.

We have the impression that the FDA may consider that the use in question is as a "drug". Although the sponsor has not considered that the described use falls strictly into the category of a "drug", the filing of this form is to insure full compliance with the law depending on clarification of the status.

There are no components in DOW CORNING MDX 4-4011 Medical Fluid other dimethylpolysiloxane as described in Section 1. It is emphasized that DOW CORNING MDX 4-4011 Medical Fluid consists of only dimethyl-polysiloxane and does not contain components such as lipids, olive oil or other materials which have been reported to have been compounded with silicone fluids for purposes of injection, particularly in the case of breast augmentation.

The composition of DOW CORNING MDX 4-4011 Medical Fluid is described in Section 1 and is the same as has been indicated for DOW CORNING 360 Medical Fluid. Variations that may be expected involve only the slight differences in average molecular weight encountered in any polymeric system from one batch to another. These variations are measured by the physical properties of this product which must fall within the ranges set below to be labeled DOW CORNING MDX 4-4011

Medical Fluid:

Test Method Requirements

Color APHA ASTM D1209-54 Less than 20

Viscosity ASTM D445 + - 5% of stated visc for all visc. except 12,500 cs. 12,500 cs. - + - 300 cs.

Specific Gravity at ASTM D1298 0.965 - 0.975 25 degrees C

Flash Point Open Cup ASTM D92 575 degrees F min. for 100 cs. 600 degrees F min. for other visc.

Refractive

Index at 25

degrees C ASTM D1218 1.401 - 1.405

Infrared Dow Corning

Analysis Quality Assurance

Method No.5

(Exhibit A) Match Standard

Acid Number Dow Corning

Quality Assurance

Method No. 7

(Exhibit B)

There are no other new drug substances in the product in question.

DOW CORNING MDX 4-4011 Medical Fluid is prepared by heating a mixture of distilled cyclic dimethylsiloxanes to about 120 degrees C for two to three hours with a source of end-blocking designated "Endblock A" in Dow Corning's plant, in the presence of a catalyst designated "Filtrol 20". The cyclics have the formula [(CH 3) 2 Si)] x where x is 3 to 6. "Endblock A" is a low molecular weight distillable copolymer having a viscosity of 2 to 3 cstks. and the formula (CH 3)2 SiO [(CH 3) 2 SiO] y Si(CH3) 3 where y is from about 3 to 6. Filtrol 20 is a sulfuric acid treated clay marketed by Filtrol Corp., 3250 East Washington Boulevard, Los Angeles, California.

This process is an "equilibration" mechanism in which the cyclics are opened up to form long chains and the trimethylsiloxy units are cleaved from the "Endblock A" to furnish the end-blocking units for those long chains, resulting in a statistical distribution such that the desired viscosity is obtained.

After equilibration, the catalyst is removed from the system by filtration. Volatiles are then removed by a continuous strip distillation at a pot temperature of 280 degrees C under a vacuum of 30 mm. of Hg. with a nitrogen purge. This is continued until the product (i.e., the distillation residue) has the designated minimum flash point.

A final filtration is carried out using a plate and frame filter press with canvas duck backed with kraft filter paper. Before filtering the following materials are slurried with 16,000 to 20,000 pounds of fluid to assist in the filtration:

5 lbs. sodium bicarbonate

6 lbs. Nuchar C

10 lbs. calcium hydride

25 lbs. of Hi-flow supercel

The product is to be controlled by means of the test methods shown in Section 3 above, and the specification set forth therein must be met before shipment. In addition to the above specifications, the product is inspected visually and compared with a standard using a strong light source to insure freedom from any contamination by particles of the catalyst or filter-aid.

The product will be packaged by Philadelphia Laboratories, Inc. in glass ampules containing 1cc. and 50 cc. of DOW CORNING MDX 4-4011 Medical Fluid. The packaged product is to be certified sterile by the packager. Copies of the packing information are attached as Exhibit C.

The use of DOW CORNING 360 Medical Fluid or of DOW CORNING MDX 4-4011 Medical Fluid is based on the well-known physiological inertness of silicones in general and dimethylpolysiloxanes in particular. The inert characteristics of such compounds have been documented previously in Dow Corning's Master File No. 126 and in NDA No. 9568.

DOW CORNING 360 Medical Fluid, 350 cstks. is the subject of IND 244 filed June 5, 1964, describing the use of this fluid for Instillation Into the Bladder. Another use is described in IND 369 for Medical Fluid 360, 1000 cstks. as an Oil Retention Enema. A third use is described for 100 cstks. DOW CORNING 360 Medical Fluid in IND 243 for the Immersion of Burn Victims. All of these 1571 Forms cite several references and contain exhibits indicating that silicone fluids are among the most inert of known fluids with no known indications of allergenic reactions, skin sensitization or conjunctivitis. Vol. 3, pages 457-462 (1953) also reports on results of intra-peritoneal injection of 0.2 cc. and 0.5 cc. of DOW CORNING 200 FLUID, 350 cstks. into 40 mice. At 3-8 weeks the mice were sacrificed and examined for evidence of the fluid and for histological studies. Three weeks after injection, the silicone fluid could still be found in the abdominal cavity. The authors reported that no silicone could be observed with certainty

in the animals sacrificed after 8 weeks. In the case of 4 of the mice, there appeared cysts about the size of a lentil either in the peritoneum or in the subcutaneous abdominal tissues. The cysts were reported to have had a gelatinous consistency and exuded fluid when opened. Histological examination of the cysts showed them to be a partially cohesive large-meshed net of tissue. The tissue surrounding the cysts showed round cells, detached mast-cells and polynuclear leucocytes. Of the 40 mice which had received injections of 18-21 cc./kg. of body weight, three were reported to have died from unknown causes.

The same authors also reported on injections of DOW CORNING 200 Fluid into 52 rats. No changes were observed by the investigators in the rats during the first 67 days with as much as 10 cc. injected. During the entire experimental period of 400 days, DOW CORNING 200 Fluid was found in the abdominal cavity. After 132 days, the fluid was reported to be a milky transudate. At this time whitish spots the size of a pinhead and thought to be silicone were found on the liver and spleen. In animals killed after the 400th day, the deposits on the spleen were greater in size than on the liver. From histological studies, the authors concluded that there were no specific changes on the organs.

The same type of deposit in connective tissue was observed as in the case of the mice. The tissue septs contained a cellular infiltrate, consisting of young and old connective tissue elements, round cells, epithelial cells and occasionally mast-cells and polynuclear leucocytes. No foreign body giant cells were observed.

A report published in Plastic and Reconstructive Surgery, Vol. 35, No. 2, February, 1965, by Dr. Thomas Rees and others of the Institute of Reconstructive Surgery, New York, University Medical Center and Department of Surgery, New York, University School of Medicine, (Exhibit 4) describes injection of one milliliter of 350 cstks. dimethylpolysiloxane fluid intra- and subdermally into the skin on the dorsum of 45 female Long-Evans rats. One-half milliliter of the same fluid was also injected into the dorsum of 10 Allimo mice. The animals were then sacrificed at intervals of 6 weeks, 3, 6, 9 and 12 months after injection. The injected skin was sectioned for microscopic examination.

Animals sacrificed 6 weeks following the injection showed a thinning of the dermis by disruption of the normal architecture of the dermis, subdermis and muscular layer. A mild inflammatory infiltrate of round cells was seen around vacuoles dispersed through the tissue. Three, six and nine month examinations demonstrated similar conditions, according to the authors, except that the round cell inflammatory infiltrate had subsided and disappeared in 6 months.

These results show that the injections were tolerated by the tissue with only minimal inflammation resulting. The only consistent findings reported were the disruption of the dermal and subdermal architecture, compression of the dermis and a minimal early inflammatory reaction which resolved in a short time.

In a paper presented at the Annual Meeting of the American Association of Plastic Surgeons in May, 1964, the same authors reported on the results of injecting extremely large amounts of dimethylpolysiloxane fluid each week subcutaneously into the flanks of 25 rats, 35 mice and 25 guinea pigs. This was in an attempt to develop toxic manifestations and to study the effect of massive amounts on the whole animal. Some rats received as much as 500 ml. as a total dose. No adverse effects were noted in general health. The injection areas appeared to contain the silicone oil as originally injected. The oil was surrounded by very thin and transluscent membranes representing the individual injections. It was noted that there was an absence of a thick scar tissue envelope and gross inflammatory response.

Tissue tolerance to silicone fluid has also been shown in work done by K. Prachuabmoh and B. Eiseman at the University of Kentucky Medical School and published in the Journal of the Medical Association of Thailand, Vol. 47, No. 1, 1964 (Exhibit 5). In this work from 15 to 40 milliliters of fluid of 500 and 1000 cstks. viscosity was injected into the thorax of 8 rabbits. Six dogs were also used where extensive parietal pleurectomies were performed. Either 10 or 20 milliliters of fluid was injected before closure. In 2 other dogs fluid was instilled after closure and in another it was instilled into the pericardial space through a right thoracotomy.

In the rabbits, no adhesions were noted by the authors. Microscopic examination revealed no leucocytic reaction. Approximately one-half of the silicone was observed by the investigators in the pleural space as a thick creamy fluid.

Six of the seven dogs with 20 milliliters of fluid were noted to be free of adhesions. Two dogs with 10 milliliters of fluid developed adhesions and all controls injected with saline developed strong adhesions. The conclusion was reached that the fluid significantly diminished experimentally produced post-operative thoracic adhesions.

An article by Ben-Hur and Neuman appearing in Israel Medical Journal, Vol. 22, January and February, 1963, No. 1 and 2, (Exhibit 6) reports work performed in the Department of Plastic and Maxillofacial Surgery of Hadassah University Hospital, Jerusalem. A local strain of one year old while mice were injected with DOW CORNING 200 Fluid of 20, 100 and 1000 centistokes viscosity. Of 36 mice injected, the fluid disappeared in 3; and in all others, the fluid was reported to be found in agglomeration of small cysts and inside one large cyst. Two of the 36 mice developed malignant tumors and these were believed by the authors to be of sweat gland origin.

No controls were reported in this work, thus the incidence of malignancy in this strain is not known. The fact that the tumors appeared in two to four weeks after injections has led other investigators to question whether the observed carcinomas were due to the silicone fluid or were spontaneous and in no way connected with the injected fluid.

The work of Ben-Hur and Neumann was repeated by Dr. Golberg and others in England and reported in a letter to the Lancet, July 11, 1964 (Exhibit 7). These workers found the fluid enclosed in one or two large cysts or in numerous small cysts but no evidence of tumor formation. This same report appeared in British Industrial Biological Research Associates Bulletin, Vol. 3, No. 7, September, 1964.

Dr. Ben-Hur continued his investigation and reported in a letter dated February 24, 1965, to the Dow Corning Center for Aid to Medical Research as follows:

"We chose one-months old male mice, in order to exclude two factors: (a) The spontaneous appearances of adeno-carcinoma of the breast; (b) Other growths which are not liable to appear at such a tender age. Three groups of 20 mice each were tested with three different viscosities:

Dow Corning Medical Fluid 360 (formerly 200 fluid):

1. Viscosity 1,000: Lot No. F 0011

2. Viscosity 20: Lot No. H 0018

3. Viscosity 100: Lot No. H 007

One mouse of each group was sacrificed weekly and studied for macroscopic and microscopic changes. There were no gross or microscopic inflammatory reaction and no mortality due to the injections.

The injected area was the site of a soft mass mobile under skin, the consistency of the higher viscosity injection having a hard rubbery feeling. The injected mass tended to move to the depended areas. Microscopically no foreign body reaction was noted and the envelope consisted of endothelial cells, probably of fibroblastic origin. The cysts were found subcutaneously as within the back muscles.

In one animal injected with solution of 100 viscosity, ten weeks post-injection, we found an area of foamy clear cytoplasm, probably macrophage which resembled a lipoid granuloma or paraffinoma. In this case, we wondered whether this was not a "silicoma", a reaction to silicone fluid.

This experiment lasted 20 weeks, during which time we did not find a similar histological picture to the one described above."

Work reported to the sponsor by Dr. Franklin Ashley (Exhibit 8)carried out at the U.C.L.A. Center for the Health Sciences on a larger number of rats, two Rhesus monkeys and ten Japanese apes involving subcutaneous and intramuscular injection of DOW CORNING 360 Medical Fluid, 350 cstks. showed no abnormalities in any of the animals except the local increase in soft tissue bulk in the areas of injection.

Biopsy specimens and tissue taken at autopsy on rats were reported to show no abnormalities, no evidence of tumor formation or granuloma. No evidence of organ change was reported.

A paper "Tissue Reactions to Injected Silicone Liquids - A Report of Three Cases" by Winer, L.H.; Sternberg, Thomas H.; Lehman, Robert; and Ashley, Franklin L., published in Archives of Dermatology, Vol. 90, No. 6, pages 588-593, December, 1964, (Exhibit 8A) describes tissue reactions observed by the authors in three humans injected with liquid silicones, one with an unknown material and the other two with a mixture with a base fluid reported to be DOW CORNING 360 Medical Fluid.

The same type of reaction was also noted according to this report in excised tissue from an ape said to have been injected subcutaneously with ten milliliters of DOW CORNING 360 Medical Fluid in eight different locations.

There is some disagreement in the data between this observation and that presented by Ashley (Exhibit 8) on ten apes in which no evidence of tumor formation or granuloma were observed.

In view of the evidence presented by Ashley and other investigators the possibility that the fluid used by Winer was contaminated prior to injection or contained an additive must be considered. The fluorescence observed by Winer in the histological sections under polarized light suggests strongly of contamination since DOW CORNING 360 Fluid observed in the sponsor's laboratory does not exhibit the fluorescence and the bright shining, silvery, luminous crystals and bodies observed by Winer. This could be expected of some of the mixtures that have been employed for soft tissue augmentation.

Although not directly related to tissue augmentation, but of interest in showing the general physiological inertness of silicones, is a paper entitled "The Use of Liquid Silicone in Retinal Detachment Surgery" published in the Archives of Ophthalmology, Vol. 68, page 590, 1963, by Paul A. Cibis, M.D., Bernard Becker, B. Edward Okun, M.D. and Samuel Keenan, M.D. In this work, DOW CORNING 200 Fluid, having a viscosity of 1000 cstks., was used to replace 0.2 to 0.8 milliliters of the vitreous in one eye of each of 8 rabbits. A second controlled experiment involved the replacement of 100 microliters of one anterior chamber aqueous humor in 18 with DOW CORNING 200 Fluid having a viscosity of either 200 or 100 centistokes.

The intravitreous injection of silicone liquids was well tolerated in all animals except for one instance caused by an error in injection technique. The retina of the injected eye appeared indistinguishable from the control eye. The scleras remained white and the anterior chamber free of cells and flare and the optical media was clear. None of the animals in this series developed glaucoma.

The anterior chambers were likewise without any unusual effects in most animals. No significant differences in pressure or optical activity were noted in the injected eyes and the control eyes or before and after injection in the same eye.

A paper by Dr. M. F. Armaly published in the Archives of Ophthalmology, Vol. 68, pages 390-395, September, 1962, (Exhibit 9) reports work similar to that above with 18 rabbits, 45 cats and 3 owl monkeys. DOW CORNING 200 Fluid (the commercial version similar to DOW CORNING 360 Medical Fluid) ranging in viscosity from 100 to 13,000 cstks. was used in the experiments which involved a 15-month follow-up study. The author concluded that there was complete tolerance of the intraocularly implanted silicone fluid.

On the basis of these animal studies and other reports showing the chemical and physical inertness and lack of foreign body reaction of most silicones when implanted, several investigators started some clinical studies on the use of DOW CORNING 360 Medical Fluid on their own initiative without recommendation of the sponsor.

Typical clinical results were reported by Drs. Ashley, Rees, et al. in a paper (Exhibit 10) presented at the American Society of Plastic and Reconstructive Surgeons in October, 1964.

DOW CORNING MDX 4-4011 Medical Fluid has not been marketed for any use either inside or outside the United States. As noted in Section 1 above, this is a designation for DOW CORNING 360 Medical Fluid for the purpose of this investigation. Both DOW CORNING 200 Fluid and DOW CORNING 360 Medical Fluid, which is merely DOW CORNING 200 Fluid that has been subjected to a greater degree of quality control, have been sold for hundreds of different industrial uses, as well as various medical laboratory uses, which are absolutely not "drug" uses. Since Dow Corning has no way to check upon the nature of the uses to which DOW CORNING 200 Fluid or DOW CORNING 360 Medical Fluid have been put, these products may have been used for similar purposes without Dow Corning's knowledge by various investigators throughout the world.

There are numerous publications, some of which have been cited above, which show the general physiological inertness of dimethylpolysiloxanes in various situations, but it is assumed that the requirement for bibliography is not intended to extend into all areas of use by independent investigators. The most pertinent of the publications have been mentioned in Section 6a. above.

These and other significant references are listed in the bibliography attached as Exhibit 10a.

Dow Corning does not have any informational material which can be supplied to the investigators other than that which has been abstracted above and which has appeared or will appear in the published literature.

For the convenience of the investigators, we intend to supply the following items:

Bulletin: 14-003, DOW CORNING 360 Medical Fluid, Dow Corning Corporation, May, 1963.

"Toxicological Studies on Certain Commercial Silicones" by V. K. Rowe, H. C. Spencer and S. L. Bass, The Journal of Industrial Hygiene and Toxicology, Vol. 30, No. 6, pp. 332- 352 (Exhibit 1).

"Toxicity of Certain Silicone Fluids", Dow Corning Center for Aid to Medical Research.

"An Injection Technique for the Treatment of Facial Hemiatrophy", Ashley, et al. (Exhibit 8)

Bibliography, Dow Corning Center for Aid to Medical Research (Exhibit 10a)

A copy of the precautions which are typical of those mentioned by doctors who have worked with DOW CORNING 360 Medical Fluid will be sent to each investigator in addition to the publications listed above (Exhibit 11).

The sponsor is currently having additional long term animal work done by the Food and Drug Research Laboratories, Inc. on various silicones including DOW CORNING 360 Medical Fluid. This will include feeding experiments with C 14 tagged DOW CORNING 360 Medical Fluid, 50 cstks.and injection work with 350 cstks. material, some of which will be tagged. Dogs will be used for the injection work and dogs and rabbits for the feeding procedures. Any useful knowledge gained from this work will be communicated to the investigators involved with this IND.

The labels on ampuls of DOW CORNING MDX 4-4011 Medical Fluid to be shipped for the use of this investigation will state:

MDX 4-4011 1 cc. (50 cc.)

Sterile Dimethyl Polysiloxane Fluid

Caution: New Drug. Limited by Federal Law to Investigational Use Only.

Lot AA 5695

Dow Corning Corporation

Medicinal Products Division

Midland, Michigan, U.S.A.

Note: Medicinal Products Division is in error and will be corrected to read: Medical Products Division on future labels. The viscosity of Lot AA 5695 is 350 cs. Future labels will include the viscosity grade.

Dow Corning Corporation will not represent that the safety or usefulness of the product has been established for the purposes to be investigated.

Suggested protocol and record sheets will also be forwarded to each investigator (Exhibit 12).

It is believed that a medical degree and wide experience in the medical specialties involved will render an investigator suitable to evaluate the safety of the product and the system for the purposes to be investigated.

Thomas Rees, M.D., F.A.C.S. Assistant Professor Plastic Surgery New York University Medical School University Hospital 560 First Avenue New York, New York

Franklin L. Ashley, M.D. Associate Professor of Surgery Chief, Division of Plastic Surgery University of California Medical Center Los Angeles, California

Reed O. Dingman, M.D. The University of Michigan University Hospital Department of Surgery Ann Arbor, Michigan

Milton T. Edgerton, M.D. Professor of Plastic Surgery The Johns Hopkins Hospital Baltimore, Maryland 21205

Dicran Goulian, Jr., M.D. Clinical Assistant Professor of Surgery (Plastic) The New York Hospital-Cornell Medical Center Department of Surgery 525 East 68th Street New York, New York 10021

Norman Orentreich, M.D. Orentreich Research Corporation 909 Fifth Avenue New York 21, New York 

The curriculum vitae of these investigators is included as Exhibit D.

The names of other investigators will be added and submitted to the FDA upon their completion of Forms 1572 or 1573 and their agreements to follow the protocol which has been set up by a voluntary committee of medical consultants assembled by Dow Corning to guide the investigational use of DOW CORNING MDX 4-4011 Medical Fluid as an injectable.

No shipment of DOW CORNING MDX 4-4011 Medical Fluid will be made until the completed and signed forms have been received from the investigator.

Mr. F. L. Dennett, Assistant Director of the Dow Corning Center for Aid to Medical Research will be charged with assembling the data from the various investigators for study by the advisory committee which has been established to evaluate the progress of the investigation and to assess the value and safety of the product. The names of this advisory committee are listed below:

Franklin L. Ashley, M.D. Associate Professor of Surgery Chief, Division of Plastic Surgery University of California Medical Center Los Angeles, California

Ralph Blocksma, M.D. Butterworth Hospital Grand Rapids 3, Michigan

Reed O. Dingman, M.D. The University of Michigan University Hospital Department of Surgery Ann Arbor, Michigan

Milton T. Edgerton, M.D. Professor of Plastic Surgery The Johns Hopkins Hospital Baltimore, Maryland 21205

Dicran Goulian, Jr., M.D. Clinical Assistant Professor of Surgery (Plastic) The New York Hospital-Cornell Medical Center Department of Surgery 525 East 68th Street New York, New York 10021

Francis L. Lederer, M.D. Professor of Otolaryngology and Head of Department University of Illinois

College of Medicine 1852 West Polk Street Chicago 12, Illinois

Joseph E. Murray, M.D. Peter Bent Brigham Hospital 721 Huntington Avenue Boston 14, Massachusetts

Norman Orentreich, M.D. Orentreich Research Corporation 909 Fifth Avenue New York 21, New York

Thomas D. Rees, M.D., F.A.C.S. Assistant Professor Plastic Surgery New York University Medical School University Hospital 560 First Avenue New York, New York

Since considerable animal data is available on DOW CORNING 200 Fluid and DOW CORNING 360 Medical Fluid in the viscosity range proposed for this IND, as well as on other silicones of similar chemical nature, and because some independent clinical work has already been reported in the literature, it seems advisable to proceed with phase 2 covering initial trials on a limited number of patients.

It is our intention that the initial investigators listed in Section 9 will proceed with the investigation essentially as outlined in the protocol attached as Exhibit 12.

In his FD-1572 form, one investigator has indicated that he anticipates restoring contour on approximately 2 patients per month who have had surgery for head and neck cancer. He also intends to treat about 6 children per year who have very extensive congenital anomalies of the face and skull which can be greatly helped by liquid implants where growth will require a series of augmentation over years.

The other five expect to use both male and female patients between ages of 15 and 65 who are in general good health. All investigators will limit the maximum amount injected to approximately 100 ml. None working under this IND will use this fluid for mammary augmentation.

This work is planned for a separate investigation at some future date.

Forms for maintaining records will be supplied to the investigators as indicated in Exhibit 12. The maximum number of patients per investigator will be limited to about 100 for the first year of the program. If it seems advisable, the number of patients may be expanded and additional qualified investigators added.

Dow Corning will notify the Food and Drug Administration if the investigation is discontinued along with the reasons for the decision.

Dow Corning will notify each investigator if a new drug application is approved or if the investigation is discontinued.

DOW CORNING 360 Medical Fluid has been and will continue to be sold for purposes other than this investigation.

DOW CORNING MDX 4-4011 Medical Fluid will normally be donated for this investigational use. The sponsor may wish to consider sale of the fluid to the investigators or their financial backers as the investigation progresses to defray the considerable expense of packaging since its use will be involved as a service to the patients involved and the investigators will be receiving remuneration for their work.

Sincerely yours,

DOW CORNING CORPORATION

F. L. Dennett 6/8/65

Assistant Director

Dow Corning Center for Aid to Medical Research

Message: 4

1. They have paid millions to cover up the hazards of silicone.

2. They knew from the 50s that silicone is dangerous.

3. They knew silicone gel attracted and killed cockroaches.

4. They knew it crossed the placenta and caused hormonal changes.

5. They knew it shrank the testicles of mice.

6. They knew it was biologically active in the body and was NOT inert.

7. They bought science by paying for rigged studies.

8. They paid for the Mayo and Harvard studies.

9. Harvard and Mayo studies were done by their paid consultants and experts.

10. The contributed $7 million to the hospital where studies were done.

11.They controlled science by buying editors or medical journals.

12. Peter Schur, Editor of Arthritis and Rheumatism,made $300 an hour on Dow's payroll.

13. Dow conspired with plastic surgeons to try to cover up the risks.

14. Plastic surgeons and Dow inflated the number of women with implant to 2 million.

15. 2 million,inflated numbers,deliberately made the risks look smaller.

16.Implantscontain silica,benzene,formaldehyde,vinyl chloride,aluminum,platinum.

17. Silicone migrates to all organs of the body and the brain.

18. Silicone breaks down to crystalline silica in the body.

19. The mixture of chemicals are toxic and even create a chemotherapy drug in the implants.

20. Implants become contaminated with body fluids.

21. Some implants contain fungus not normally seen in humans.

22. Dow Corning falsified documents.

Message: 5

CAUSE

There are several forms of the chemical in breast implants that can cause a problem in the human organism. Silicon (Si) is the basic element and probably causes immune system changes. Silica or SiO2 (chemical formula) is the form it is mined from the earth. Silicone gel is a synthetic material containing 38% silicon. The silica is 45% silicon.

There is slow leakage ("bleeding") of the silicone gel from the implants through the semi-permeable membrane envelope and also into and through the capsule that surrounds the implants. This is picked up by the microphages (scavenger cells) of our immune system and is broken down inside these cells which travel all over the body. The gel breaks down inside these cells, which travel all over the body. The gel breaks down into Silica and Silicon which causes an immune system dysregulation. Thus, there are antibodies produced against the silicon and also against the silicon and protein complex (organ systems) so that you get autoimmune illness.

As well, there is also damage that is not related to the immune system, because the silicone gel causes oxidants (damaging molecules) to be produced that directly damage our cell walls, DNA, and enzyme systems. All of this adds up to slowly-developing chronic debilitating illness affecting every organ system of the body.

There are so many possible symptoms that the patient may experience. I shall only mention the major ones here. Almost any symptom can be related to this syndrome, either directly or indirectly.

Peripheral Neuropathy (weakness, tingling, numbness, etc.)

Central Neurotoxic Neuropathy (cognitive difficulties, memory problems, hyperactivity,attention deficits)

Cervical and axillary enlarged or painful lymph nodes

Fibromyalgia (multiple tender areas)

Myositis (painful inflamed muscles)

Fatigue

Night sweats

Hair loss

Abdominal pain

Pulmonary hypersensitivity (shortness of breath, etc.)

Emotional instability

Joint and tendon pain

Multiple Chemical Sensitivities

Food and inhalant sensitivities

1. In-depth history (including details of implant problems)

2. Physical examination

3. Studies to rule out other conditions such as Lyme disease, multiple sclerosis, etc.

4. Various laboratory studies: Immune studies (Complex) T-Cell Silicone Immune Study Fungal or Bacteriological Studies (if indicated) Biochemical profile Skin testing (if needed)

5. Address each organ system damage individually depending on patient's complaints

Brain: PET, SPECT, BEAM, EMG, etc.

Pulmonary: PFT

Rheumatological: Snyovial Fluid

Breast: MRI, Xeromammography

GI: Digestive studies, pancreatic malfunction

Immunological: Chemical Antibodies, Silicone

Antibodies, T-Lymphocyte subpopulation,

Activated Lymphocytes, Lymphocyte Immune

Function, Natural Killer Cells and Activity,

Immune Complexes, Complement Levels, ANA,

Autoantibody Analysis (Myelin, Striated

Muscle, Thyroid, Skin Antibody,

Collagen Antibody), Skin Testing (chemicals, foods, etc.).

Damage to the immune system leads to various autoimmune situations. Direct damage from free radical oxidant molecules leads to diffuse organ system damaging effects

1. Diet: Organic, High alkaline, semi-vegetarian, moderately high protein

2. Exercise: Moderate low-impact (daily)

3. Intravenous nutritional therapy: Detoxification Antioxidant

4. Nutritional supplementation (oral)

5. Immunotherapy Chemicals Foods Silicon Inhalants

6. Environmental and chemical controls

7. Immune modulation Transfer factor DHEA Immune stimulants: Thymus, herbals, etc. Intravenous Gamma Globulin

For more information on this topic, please read Silicone Immune Toxicity Syndrome. 1995 Stephen B. Edelson, M.D., F.A.A.F.P., A.A.E.M.

This information is provided for educational purposes. Any medical procedures, dietary changes, or nutritional supplements discussed herein should only be undertaken on the advice of a qualified physician

Stephen B. Edelson, M.D., F.A.A.F.P., F.A.A.E.M.

Environmental and Preventive Health Center of Atlanta

3833 Roswell Road, Suite 110

Atlanta, GA 30342

(404)841-0088

FAX: (404) 841-6416

Message: 6

Dr. Nalm-Was one of the first to show that silicone is a potent adjuvant, presented a study on arthritis induced in rats. The silicone gel taken from a commercial breast implant is capable of mediating a collagen(protein in connective tissue)induced arthritis in the rats. In his study, the silicone that was mixed with another adjuvant(to hasten or increase the role)caused arthritis in 80% of the rats, however the gel by itself did not cause arthritis.

The National Cancer Institute and others have studied cytotoxicity (poison to cells),and membrane and DNA damaging effects of siloxanes on cells. Although the terms are very technical, the study says that many siloxanes produce lethal effects on cells and make plasma membranes permeable. The results also point to mutations in rat embryo fibroblast cells-from which connective tissue develops. Again, we see indications of problems in the second generation from implants. These doctors were using some of the D4 component used in our implants.

Dr. Smalley presented a study showing the manufacturers long touted"fumed silica" used both as a filler in the gel and in all envelopes, including saline implants, is no different in antigenic stimulation in the body than crystalline silica. There is No Safe Silica! Dr. Shanklin has studied more that 350 biopsy specimens. They indicate a wide range of reaction, including hypemature scar, lymphocytic infiltration, granulomatosis(formation of tumors),and infiltration into plasmacyte and eosinophil cells. He says that tissue samples show the principal foreign matter to be silicone and crystalline silica. Silicone shows up on dark field microscopy, but polarizing microscopy is essential for identification of the silica. Again, He shows that silicone does not break down to silica and the fumed silica in implants doesn't remain fumed! He says that tissue evidence indicates that exposure to silicone implants sets into motion a significant and long-lasting disease with many immunopathic findings.

Genetic predisposition has frequently been questioned as a possible reason why some women react to silicone and others may not. Some St. Louis physicians reported that symptomatic patients with implants share important genetic characteristics that our asymptomatic counterparts may not have. They suggest that HLA-DR53(a gene type)may be a marker of women who are predisposed to develop an immune-mediated reaction to some component of the implants. Wouldn't it have been nice to know this years ago?

Message: 7

Abstract:

Silicone Breast Implant-Associated Scarring Dystrophy of the Arm.

Authors:

Teuber,Ito,Anderson, Gershwin Division of Rheumatology,Allergy,and Clinical Immunology,University of Calif.-Davis

Source: Arch Dermatol Jan.1995-Vol.131,Pgs.54-56

Abstract: Backgroud: Breast implants have been known to rupture after trauma or closed capsulotomy with spread of the gel down the arm or abdominal wall. Nodular foreign-doby granulomatous reactions have been reported in these cases. We report the unique occurrence of significant overlying scarring and ulceration following silicone gel migration down the affected arm.

Observations: A 47 yr.old woman experienced rupture of her right silicone gel implant with migration of the silicone down her arm 10 yrs.before our examination. Skin changes with atrophic hidebound scarring and ulceration slowly progressed over the last 7yrs. Radiographs and magnetic resonance imaging scans demonstrated material consistent with silicone in the soft tissues.

Conslusions: Silicone is not an inert substance and can rarely result in devastating local tissue destruction where migration has occurred. The possibility of significant silicone gel migration should be considered during evaluation of patients with ruptured implants.

Message: 10

Brautbar,Campbell,Vojdani

University of Southrn California, School of Medicine,LA

J Biomater Sci Polym Ed 1995;7(2):133-45

Abstract: In vivo and in vitro studies,case reports and population studies show that:

(1) Silicone is immunogenic.

(2) Silicone is biodegradable and transported via the reticuloendothelial system to distant location;

(3) Silicone brast implants leak and in turn silicone migrates outside the breast tissue;

(4) Case reports and population studies document an autoimmune reaction and immunological dysfunction in patients with silicone breast implants;

(5) These immunological abnormalities and symptoms are reversible upon removal of the breast implants (in 50-70% of cases). The criteria to establish medical causation are defined, and based on those criteria it is concluded that silicone breast implants cause immunological disease.

Note: Concerning silicone being transported via the reticuloendothelial system.

From Tabers:

The reticuloendothelial system - Term applied to those cells scattered throughout the body which have the power to ingest (phagocytose) particulate matter (bacteria,colloidal particles). Includes macrophages(histiocytes, clasmatocytes,or resting wandering cells) of loose connective tissue; reticular cells of lymphatic organs and myeloid tissues; Kupffer cells of the liver; cells lining blood sinuses of spleen, bone marrow, adrenal cortex, and hypophysis; microglia of central nervous system; adventitial cells about blood vessels; and dust cells of the lungs. The above

types are called fixed reticuloendothelium cells. Under certain conditions, esp. inflammatory stimuli, fixed cells may become wandering reticuloendothelium calls,i.e., they become actively motile.

Monocytes of the blood also are included in this group. Reticuloendothelium cells function in elimination of worn out cells, esp. red blood cells; in repair of injured tissue; and in defense mechanisms, both local and general of the body.

Diseases of the reticuloendothelial system include lymphosarcoma, reticulum cell sarcoma, Hodgkin's disease, follicular lymphoma, mycosis, fungoides, Gaucher's disease and Niemann-Pick's disease.

Niemann-Pick's Disease - A disturbance of lipoid metabolism characterized by enlargement of liver and spleen, anemia, lymphadenopathy, and progressive mental and physical deterioration. A hereditary disease, its onset is in early infancy with death usually before the third year. Typical cells, having a foamy appearance and filled with a lipoid believed to be sphingomyelin, can be found in bone marrow, spleen, or lymph nodes and aids in establishing the diagnosis.

Gaucher's Disease - A rare chronic congenital disorder of lipid metabolism. Fatty substances called glycosphingolipids accumulate in the reticuloendothelial cells. Associated with enlarged spleen, increased skin pigmentation, and bone lesions.

Mycosis - Any disease induced by a fungus.

Message: 11

Authors: Walton, Bunkis

Source: Plast.Reconstr.Surg. Feb.1983 - 71(2):260-1

Abstract: A case of Aspergillus niger fungal colonization associated with bilateral inflatable silicone mammary implants is reported. Painful fibrous capsular contractures without clinical evidence of infection or inflammation characterized the presenting symptoms. Operative findings included a cheesy-white exudate that surrounded the implants and turbid fluid within the implants.

All specimens yielded a heavy growth of Aspergillus niger. Special stains of the fibrous capsules were negative for fungal invasion.

The etiology and pathogenesis of Aspergillus colonization in this patient are postulated.

Message: 12

The issue of silicone gel breast implants has recently received much media attention. However, I do not believe an appreciation of its full complexity and the implications to women's health will occur until women themselves share their experiences.

If you are a woman personally touched by this issue, you are invited to participate in a research study aimed at exploring women's experiences with breast implants. Further details and questionnaires in business reply envelopes are available at the registration table from:

Dr. Mary Lou Logothetis Associate Professor of Parent-Child Nursing and Women's Health College of Nursing Valparaiso University Valparaiso, IN 46383 (219) 464-5480

Age Occupation

Highest level of education completed

Date of initial implant surgery

Type of surgery augmentation reconstruction

Type of implant

Manufacturer

Date/s of subsequent surgery/s (please describe type/s)

The following questions are meant to elicit your personal experience with breast implants and are purposely very broad. Please feel free to omit from or add to them in any manner that best helps you share that experience. You may respond in the space provided or use other sheets of paper as you like. I welcome your response regardless of its length .

1. What circumstances led to your breast implant surgery?

2. Do you feel you made a free and informed decision about your implant surgery?

What did you believe to be its benefits and risks?

3. What health problems have you had that you attribute to your breast implants?

How did your physicians respond to your implant problems?

How did your husband/significant other respond?

4. Have you considered implant removal? Why or why not?

Have you considered reconstruction such as the flap surgery that uses you own tissue? Why or why not?

5. Have you considered legal action? Why or why not?

6. What do you think can/should be done to resolve the controversy about breast implants?

7. What prompted you to contact the Command Trust Network support group?

What has participation in the network and association with its members provided for you?

8. What personal feelings and/or emotions have your experiences with implants aroused in you?

9. What do your breasts mean to you?

10. What message would you choose to transmit to a young daughter about her breasts?

Message: 13

By David S. Casey, Jr.

David S. Casey, Jr., CAOC Vice President, is with Casey, Gerry, Reed & Schenk in San Diego. CA

Recently, the governor of California attacked the civil justice system denouncing the ever increasing explosion of lawsuits. The San Diego Union in an editorial stated that over 2,200 lawsuits would be filed a day this year and that over 800,000 would be filed during the entire year and that with such massive filings, tort reform is clearly needed. The press and the public condemn the litigation explosion. It has been said that if you repeat a lie often enough, it becomes the truth. The appearance of reality, although not real, becomes real. That is exactly what is happening in California with litigation.

In the recent release of the judicial council findings for 1994, there were two startling facts that debunk the entire myth of the litigation explosion.

First, in the fiscal year 1992 to 1993, there were 88,000 lawsuits filed in the entire state of California involving tort issues for personal injury or property damage. This is almost one tenth of the figure being popularly used in the press. In addition, from 1988 until 1993, there has been a decline of over 43 percent in the lawsuits filed involving personal injury torts and property damage in the State of California.

Lets look at the overall picture presented on lawsuits in California by the Judicial Council.

In the fiscal year 1992/1993 there were a total of 684,070 civil actions filed. Of these, family law matters represented 162,974. Probate and guardianship matters added another 56,193 and eminent domain matters 1,200. As mentioned, personal injury actions totalled 88,346 which was comprised of 53,839 matters involving motor vehicle accidents and 34,507 other personal injury type cases. The remaining civil cases filed fall into general civil filings involving real estate, contract disputes and others which accounted for 107,377.

This area includes petitions for adoption, change of name, establishing the fact of birth or death, writs of review, mandate and prohibition, petitions for conciliation. The largest number of all these petitions or actions filed under the Reciprocal Enforcement of Support Act. The only area of litigation that has been truly climbing in California have been civil actions filed for reimbursement of child support. This category, other civil petitions, has grown in the fiscal year 1988/1989 from 163,255 filings to 267,980 filings in 1992/1993.

The true litigation explosion has been in the area of seeking reimbursement for child support. In the press or the public there would be very little criticism of the district attorney or others filing actions for reimbursement of child support. Nonetheless, all of these figures are added together in one figure to depict a litigation explosion and then are used as an argument for changes in the tort system.

In addition, not reflected in these statistics is the population growth of over 5 million which has occurred in the last 7 years. If these statistics were adjusted for population growth, the decline in litigation in the personal injury area would be even more dramatic.

It is our responsibility as members of the legal profession to educate the public and press on the true facts of what is occurring in the civil litigation system. There are groups whose sole purpose would be to abolish the civil justice system and replace it with administrative procedures. Their goals would be to do away with the role of juries and judges in the civil justice system. These groups will grab anecdotal cases and publicize them to show that the civil justice system does not work. These groups will take statistics and distort them to lead the public and press to form the wrong conclusion. In talking with lawyers and judges in the community, I was impressed that not only is the public misled by the "litigation explosion myth" but many of us in the legal profession are as well. It is time for each of us to begin to speak up, not only to the press, but to our legislators so we dont see the destruction of common law formulated over hundreds of years.

Message: 14

NOT FOR COMMERCIAL USE WITHOUT THE PERMISSION OF THE AUTHOR

The Consumer Attorneys of California: Truth Corner - For Media Only:

"CONTRARY TO POPULAR BELIEF, PERSONAL INJURY, PRISONER SUITS AREN'T JAMMING THE FEDERAL DOCKET." That is the conclusion of a National Law Journal special report that appeared in the respected publication this week.

NLJ editors said, "Using a data base developed by staff reporter Marianne Lavelle, the NLJ's Washington bureau examined 11,940 civil cases that the federal judiciary itself has deemed judicial emergencies for having lasted three years."

Concluded the report: "Although some politicians have demonized personal-injury and prisoner suits for burdening the nation's judicial system, business disputes predominate among the most intractable cases in the federal courts."

Why is this NLJ special report significant? As many California journalists and politicians know, the so-called tort reform activity in the Golden State is tied to a national campaign to restructure our civil justice system.

Those pushing for tort reform contend that courts are clogged because of consumers and their personal injury lawyers.

Not so on the federal level, according to the NLJ report (and not so in California courts, according to other credible sources). Said the report: "Personal injury and products liability cases make up the second-largest chunk of the backlog. But when mass torts, such as the numerous suits involving the Dalkon Shield intrauterine device and the 1988 Pan Am disaster over Lockerbie, Scotland, are counted as single cases in order to reflect the way they are managed, torts drop dramatically as a proportion of the backlog."

The report quoted federal courts scholar Linda Mullenix, of the University of Texas School of Law, who said: "There's a political agenda, one other than a concern for the courts' time, in the attacks on tort suits, civil rights suits, environmental cases," she added. "Different segments of the bar and public just don't like those lawsuits. But in terms of creating a crisis or dilemma for the federal courts, it just isn't true and historically hasn't been true."

(NOTE: For a paste-up copy of the NLJ article, contact Bob Forsyth at (916) 442-6902).

Copyright 1995, 1996

Message: 15

Why would someone not want to be included in a class action lawsuit, which is known as opting out?

The only good reason to opt out of a class action settlement is if the legal deadline for filing your claim has not expired, and you have a good faith belief that you could recover significantly greater damages by pursuing your own lawsuit, *and* you are willing to undertake the often considerable expense, time and mental stress that pursuing that belief *may* entail.

To use an example, let's consider the recent breast implant settlement. If you had a breast implant that went horribly wrong and have sustained substantial damages (such as medical bills and chronic pain and suffering), then you may very well receive substantially greater damages (as indeed some women have done) by "opting out" of the class settlement and pursuing your own lawsuit. On the other hand, if there were no apparent problems with the operation, then you may have difficulty in retaining an attorney to represent you on a contingency fee basis since your damages may be relatively minimal. It just may not be worth your time and effort (or that of an attorney) to pursue your own claims.

Similarly, in securities lawsuits, if your losses were not very significant, then it may not be worth the cost and bother to file a separate action, and you may be well advised to accept the settlement. Even if you only recover a portion of your actual losses, it may be cheaper in the long run. However, only an experienced attorney who knows your particular situation would be in a position to properly advise you if "opting out" was the right choice for you.

Robert A. Merring 369 San Miguel Drive, Suite 30 Newport Beach, CA 92660

Materials Copyright CourtTV 1995. All Rights Reserved. Disclaimer: Nothing in this site is intended to constitute legal advice"

Message: 16

January 15, 1976

Subject: Comment on Mammary Prosthesis Quality and Request for more information on the Scottsdale Breast Symposium

From: Tom Talcott

"The general tone of Art's report on the Phoenix Breast Symposium was one of disappointment that we are not #1 in the market place. Disappointment that two of our units broke during augmentation surgery for the TV tape demonstration."

"During our task force assignment to get the new products to market, a large number of people spent a lot of time discussing envelope quality. We ended up saying the envelopes were "good enough" while looking at gross thin spots and flaws in the form of significant bubbles. The allowable flaws are written into our current specifications."

"Plant engineering or other effort to make uniform and flaw free envelopes would still be usefull. It is unfortunate that the thinner dispersion, four dip method proved by Bartolo and Vallender in early 1974 appeared too expensive to plant personnel to even try, although a much higher acceptance rate would be obtained. I sincerely hope this experience will convince us to support programs for "high quality" rather than "just enough quality" in the future.

Message: 17

Authors: Edworthy, Martin, Barr, Skris Department of Medicine Univ.of Calgary

Source: American College of Rheumatology Sept.1995 Vol.38, No.9

Abstract: In the province of Alberta, Canada 9,240 women underwent breast augmentation procedures and 7,400 women received non-implant cosmatic surgery between 1978-1986. A prospective population-based, cohort study with a matched comparison group of women with other cosmetic surgery was undertaken.

Physical exam was comprised of 2 parts: a semi-blinded interview and exam with a specialized nurse, which included a detailed breast exam, followed by a blinded physician exam which included assessment for systemic rheumatic diseases. These 2 exams allowed correlations of systemic diseases with local effects to be investigated.

For implant recipents, local skin reactions were catalogued during the nurse exam and in addition the Baker's Classification was applied. Contractures were noted in 56.8% of silicone implant patients and 40.5% of saline implant patients. Baker's classification, a method of describing the severity of changes demonstrated more severe changes in the silicone group than the saline. Changes in overlying cutaneous tissues were more pronounced in silicone than saline patients. However, no significant antibody levels or patterns were associated with these local findings.

Systemic rheumatic conditions affecting skin such as scleroderma and lupus, were not significantly associated with the local changes noted. Although local immunological mechanisms may play a role, there is no evidence for systemic immunological changes associated with breast contractures. However,the high prevalence of skin changes in this population-based study indicates that this problem requires closer examination.

Message: 18

MEDWATCH

THE FDA MEDICAL PRODUCTS REPORTING PROGRAM

WHAT IS A SERIOUS ADVERSE EVENT?

An adverse event is any undesirable experience associated with the use of a medical product in a patient. The event is SERIOUS and should be reported when the patient outcome is:

* DEATH

Report if the patient's death is suspected as being a direct outcome of the adverse event.

* LIFE-THREATENING

Report if the patient was at substantial risk of dying at the time of the adverse event or it is suspected that the use or continued use of the product would result in the patient's death.

Examples: Pacemaker failure; gastrointestinal hemorrhage; bone marrow suppression; infusion pump failure which permits uncontrolled free flow resulting in excessive drug dosing.

* HOSPITALIZATION (INITIAL OR PROLONGED)

Report if admission to the hospital or prolongation of a hospital stay results because of the adverse event.

Examples: Anaphylaxis; pseudomembranaus colitis; or bleeding, causing or prolonging hospitalization.

* DISABILITY

Report if the adverse event resulted in a significant, persistent, or permanent change, impairment, damage or disruption in the patient's body function/structure, physical activities or quality of life.

Examples: Cerebrovascular accident due to drug-induced hypercoagulability; ototoxicity; peripheral neuropathy.

* CONGENIALITY Anomaly

Report if there are suspicions that exposure to a medical product prior to conception or during pregnancy resulted in an adverse outcome in the child.

* REQUIRES INTERVENTION TO PREVENT PERMANENT IMPAIRMENT OR DAMAGE

Report if you suspect that the use of a medical product may result in a condition which required medical or surgical intervention to preclude permanent impairment or damage to a patient.

Examples: Acetaminophen overdose-induced hepatotoxicty requiring treatment with acetylcysteine to prevent permanent damage; burns from radiation equipment requiring drug therapy; breakage of a screw requiring replacement of hardware to prevent malunion of a fractured long bone.

Message: 19

Author: Bar-Meir, Teuber, Lin, Alosacie, Goddare, Terybery, Barka, Shen, Peter, Blank

Diverse immunologic abnormalities have been described in women who received silicone breast implants. However, most studies have focused on either a limited number of patients or a small panel of autoantibodies. We report the analysis of 20 autoantibodies in 116 women with implants and 134 controls. The partients ranged from 26-66 yrs. old, with a mean of 45.7 yrs., with a range of 4-30, the chief complaints of the 116 patients included polyarthralgias, fatigue, myalgias, morning stiffness, and decreased memory.

All 250 sera were tested blindly using a panel of 20 autoantigens including SS-A, SS-B, RNP, cardiolipin (CL), collagen types I,II and IV, phosphatidylserine (PS), myeloperoxidase (MPO), sulfatides (sulf),thyroglobulin (TG), gangliosides (GDIa;GM2), proteinase-3 (PR3), Jo-1, Sm, HPRPP-ribosomal phosphate, histone (H2AH2B), Scl-70 and glomerular basement membrane (NC-1). Values from individual patients were considered positive only when greater than 3 SD above the control mean. There was a statistically significant greater frequency of autoantibodies in women with implants for 15 of the 20 autoantigens; these were particularly striking for anti-H2AH2 B, HPRPP, SS-A SS-B, Scl-70, CL, PS, GM2, and NC-1. Many patients harbored several autoantibodies; 20 had four autoantibodies; 8 had 6 autoantibodies. The association of autoantibodies and implants suggests an adjuvant action of silicon/silicone by products.

Message: 20

Authors: Osborn,Moore,McMurtry University of St.Louis

Source: American College of Rheumatology Sept.1995 Vol.38, No.9

B6-1pr.mice develope and autoimmune disease characterized by lymphadenopathy, antinuclear antibodies, and early mortality.

We injected 20 six week old B6-1pr mice with sterile polydimethylsiloxane

(Si) containing 5% D4(cyclotetradimethylsiloxane) and 20 six week old B6-1pr mice with 0.2 cc of sterile saline (Sa) subcutaneously in the dorsal area between the scapula. Animals were monitored at 0,1 mo.,3 mo.,6 mo., and 12 mo. for antinuclear antibodies, rheumatoid factor, lymph node enlargement,a nd death. P values by CHI2 were all greater than 1.05 at each age for both ANA and RF. Cervical and axillary lymph node weight in mg/gram body weight was 7+2 in both Si and Sa treated groups.Mortality at 48 weeks as 10/20 in the Si injected mice and 11/20 in the Sa treated mice. In conclusion there was no statistically significant difference in autoimmune parameters in C57Bi-b6 1pr mice injected with silicone or saline.

Message: 21

Authors: Spiera,Gibofsky,Spiera. Hospital for Special Surgery Cornell Univ.Medical College

Source: J.Rheumatol Feb.1994 Vol.21 - Pgs.239-245

Abstract: Objective. To review the literature examining the association of silicone gel filled implants and connective tissue disease.

Methods: Computerized literature searches and manual review of bibliographies.

Results: Numerous concerns have arisen regarding the safety of silicone gel filled breast implants. The structure of these prostheses is reviewed. Silicones are not biologically inert. Injectable as well as implantable silicones have proven capable of eliciting inflammatory and fibroproliferative responses. Silicone leakage from silicone gel filled implants is well documented as is distant migration of silicone in the host. In the past decade,over 60 cases of connective tissue disease following mammoplasty with silicone gel filled implants have been reported.

About half of these patients developed scleroderma or scleroderma-like illnesses. This reported overrepresentation of scleroderma compared to other rheumatic diseases mimics the Japanese experience with injectable silicones. Possible biological rationale for the association is presented.

Conclusion: The physical and biological properties of silicone gel filled implants and their behavior in vivo is compatible with the hypothesis that they may contribute to the development of connective tissue disease. The association seems most likely with

scleroderma; however, there is yet inadequate epidemiological data to definitively establish causality.

Message: 22

I used to get the USSW newspaper when it was run by Shirley Goodner and I do miss it even now. Still, I would love to get this mailed to me also, for I send up/down lines to those not yet hooked into net.

Pat Wingate

641 S. Jones Ave.

Rock Hill, S.C.29730-5840 Thank you ever so much! Love & Light! Weedlet

At 10:51 PM 6/7/00 -0600, you wrote:

When I first came on the net in Jan. 1996, the USSW site was the main site for information and studies. It was maintained by Walt Monger who died almost two years ago. Some of you have been concerned about the loss of the information on his site.

I have many of those documents ready to be emailed out to the list. I just wanted to warn you they were coming. If anyone already has them and does not want to keep them, they are all identified as USSW in the subject line. They may be of interest to newer ladies on the list who did not have access to them.

Pam

Message: 23

Abstract: Do patients with silicone-gel breast implants have elevated levels of blood silicone compared with control patients?

Author: Peters, Smith, Lugoski, McHugh, Baines Wellesley Hospital, university of Toronto, Ontario, Canada

Journal: Am. Plast Surg.

Date: April 1995, Vol 34, Pgs. 343-347

Abstract: Whole blood silicon levels in 30 patients with silicon-gel implants (inserted between 1973-1991) were compared with those of 24 health, age-matched, female patients without breast implants using atomic absorption spectrometry with a graphite furnace.

The blood silicon levels in the implant patients were significantly higher than those of controls (median 33.45 vs 17.05 ng/ml; p=0.005). Of the 30 patients with implants, 15 had received their implants between 1973 and 1985, and 15 had received implants

between 1986 and 1991. Implants made between 1973 and 1985 have been shown to be weaker and to have higher silicone "bleed" levels than those made from 1986 onward. However, there were no significant differencs in the blood silicone levels between these 2 groups of patients.

Message: 24

BERNARD M. PATTEN and BRITTA OSTERMEYER SHOAIB

Classical rhetoric distinguishes five topics under which any issue may be addressed: definition, comparison, relationship, circumstance, and testimony. I propose to examine Human Adjuvant Disease (HAD) in light of these topics.

Human Adjuvant Disease (HAD) is an autoimmune condition associated with foreign materials in contact with the human body. Its existence must be inferred because the manufacturer's package insert says it may occur [1]; numerous medical articles on the subject exist [2-11]; there have been improvements post-explant of foreign materials that have been implanted [12-14]; and in animals, immune stimulation activity of' foreign materials has been demonstrated especially epoxyresins, oleoanilides (the cause of Spanish Oil syndrome), vinyl chlorides, chlorinated hydrocarbons and octamethylpolycyclicsiloxane (D4) and silica.

HAD means the disease produced by the immune stimulation caused by the effect of' foreign material(s). Therefore, this definition excludes all naturally occurring disorders merely worsened by the immune stimulation of the foreign material. Such disorders should be classified as "worsened by adjuvant activity of." For example system lupus that is believed to be worsened by adjuvant activity of' polyurethane and free siloxane in tissue should be classified as system lupus worsened by those adjuvants-and not as HAD.

Most cases of HAD would be expected to exhibit the following characteristics, as adapted and modified from Miyoshi's original description [21]:

1. Foreign material or materials in the body at some time prior to the development of the autoimmune disease;

2. Local reaction to the implanted material with any one or all of these things: encapsulation, pain, tenderness, heat, swelling, redness;

3. Some signs and symptoms generally associated with known autoimmune

conditions, including but not necessarily restricted to aches and pains in muscles and joints, stiffness, weakness, and easy fatigue; 4. At least one circulating autodirected antibody at some time after installation of the foreign material. Such antibodies must be detected in amounts elevated above normal (Only university - based or certified commercial laboratories can be reasonably and reliably used to fulfill this characteristic's requirement);

5. No other condition or disease explains the patient's illness, including infection, malignancy, or naturally occurring autoimmune disease. If, for instance, the patient meets the accepted criteria of the American Rheumatism Association for diagnosis of lupus or rheumatoid arthritis, HAD is excluded. The exclusion of typical diseases makes sense, because HAD usually produces atypical autoimmune disease;

6. Evidence is found for local immunological activation. This commonly consists of foreign body giant cells, but can be simply a chronic inflammation with plasma cells, some lymphocytes, but mainly lots of macrophages marginated on or near the foreign material or surrounding the foreign material;

7. Improvement follows explanation when most if not all the foreign material is removed. Time to improvement depends on the age of the patient, the duration of illness, the severity of the autoimmunity, and many other influences and conditions not fully understood. In general, significant clinical and laboratory improvement in HAD occurs within two years of explantation. If improvement fails to occur within this time frame, HAD probably was not the cause of the patient's condition.

These empiric defining criteria, like the criteria for rheumatic diseases in general [22], derive from a dynamic area of research which at present has an incomplete concept of the disease and an imperfect diagnostic technology. In the years ahead, improved knowledge and techniques will likely change refine and more accurately describe these characteristics. Meanwhile, the seven divisions offer a standard against which individual cases or groups of patients can be identified, measured, and compared.

Similarities and differences among cases define HAD and help distinguish it from other conditions. Degree also indicates the type of illness and cause.

Most HAD patients can be identified by the pattern distribution of abnormalities in their cases and their similarity to others who have had comparable problems. The usual patient has had foreign material installed within body tissues, followed sometime later by the development of local difficulties around the site of implantation and, after that, systemic signs and symptoms of reaction to the material. Local complications include pain, aching, heat, contracture, and tenderness around the foreign material. Prominent systemic symptoms include morning stiffness, aches and pains in muscles and joints, gel phenomena, memory loss for recent events, dry eyes, weakness and easy fatigue of skeletal muscle, regional lymphadenopathy, and skin rash. Signs include local heat, redness, induration, and irregularity around the implant, and generalized weakness, glove and stocking sensory loss, and evidence of other peripheral or central nervous system dysfunction or both. This pattern distribution of local complications near the foreign material associated constitutes a combination unique to HAD. Future studies may show it the sine qua non of this disease, a stereotype of abnormalities usually not seen in conditions other than HAD.

Incidentally, HAD does not occur exclusively in women. It happens in men in cases associated with ruptured pectoralis and testicular implants. Laboratory reports show a variety of abnormalities not unique to HAD but occurring in other autoimmune conditions. All of the abnormalities probably reflect diffuse rather than focal activation of the immune system. The ANA, rheumatoid factors, positive antibodies against human antigens, the antibodies against the major ganglioside in the central nervous system, anti-GM, antibodies, myelin associated glycoprotein antibodies (anti-MAG), antisulfatide, and anti-beta-tubulin antibodies do not mean the patient has lupus or rheumatoid arthritis or the other relatively specific diseases associated with those positive blood tests, and certainly do Hot mean those diseases are present in the absence of

clinical disease. They are immune markers suggesting immune system activation by the foreign material.

Other tests show what organ systems are adversely affected by the immune activation and by how much. So, when indicated, MRI, SPECT scan, EMG, and so forth can help define the extent of' damage already present in an individual patient and can help organize the approach to treatment.

Patients with HAD differ from other patients in a variety of ways, including the obvious presence of foreign material in their bodies and also in the multiplicity of signs and symptoms. They usually have at least 20 complaints and commonly circle over 50 percent of the lists of common symptoms of disease [23, 24]. Other patients who do not have HAD have a much more circumscribed list of complaints. The large number of complaints in HAD makes sense if one considers the disease is likely due to a diffuse activation of the immune system and not a circumscribed focal activation of one part of the immune system. If the immune system is diffusely and globally activated, then there should be diffuse and global complaints referable to virtually every level of the nervous system, to the muscles and nerves, connective tissue, blood vessels, and skin.

As the severity of local problems increases, the systemic problems do too, especially if the implant has ruptured or if the immunogenic foreign material directly contacts the immune system by regional or systemic spread. In our series of implanted patients who had systemic disease, the proven rupture rate was 60 percent at explantation [23, 24], a number higher than the estimate of 1.5 percent by the manufacturer and the 15 to 20 percent mentioned by the FDA. Some foreign materials, such as polyurethane, seem to cause more immune activation and produce more skin rashes and other adverse systemic effects sooner than other materials.

The presence of different time courses and clinical degrees of affliction associated with different foreign materials strongly suggests that the foreign material plays an etiological role and may actually cause the disease. For instance, the time course of vinyl chloride disease differs from that of toxic Spanish Oil syndrome. With silicone gel implants, six years usually elapse from the time of implantation to development of first systemic symptoms; silicone implants surrounded by polyurethane have a shorter latency. Taken together, the similarity of disease among patients exposed to the same agent, the differences that the induced disease bears to other naturally occurring diseases, and the fact that degrees of adversity depend on degrees of exposure, as well as the time-linked nature of theexposure to the subsequent development of the disease, all argue that the agents named actually cause the condition.

The topic of relationship divides into three parts: cause and effect, antecedent and consequent, and contraries and contradictories.

To assign a cause and make it stick requires four elements. The cause must be sufficient to produce the effect; it must be the most likely among several possible causes; conditions must not inhibit the cause from exerting its effect; and the cause must invariably produce the effect. In the muddy waters of statecraft, real-life situations, the legal arena, and medicine "invariably" has given way to "more likely than not" or with a reasonable degree of medical certainty."

In HAD, all four elements apply to foreign materials that are associated with local complications, such as the rupture of an implant and spill of free silicone into tissue. The rupture of the implant alone is sufficient to produce the spill of silicone into tissue and to provoke a local inflammatory reaction. Systemic complications require no small degree of circumspection, and cases must be considered individually. It is not enough to show that the disease followed implantation. Dry streets get wet after rain and then dry; when rain recurs, they get wet again. This does not mean dry streets cause rain. Medicine abounds with post hoc propter hoc errors. There was a time when malaria was considered caused by swampy land that had bad air. Although we now know that malaria is induced from circumstances more complicated than that, yet when Roman engineers drained the swamps around the Tiber 2,000 years ago, they abolished malaria in that section of Italy. These things considered, most people will associate a ruptured implant with the systemic disease that follows, because most individual cases have strong evidence for unique activation of the immune system.

This less rigorous form of' cause and effect argument generally applies to implants and can be reduced to a rephrased syllogism: (1) Foreign materials produce local and systemic reactions; (2) an implant is a foreign material; therefore, (3) an implant causes local and systemic reactions. Whether the implant has in fact done so in an individual case depends on the individual evidence adduced.

Contraries and contradictions offer an avenue of proof, since two contraries cannot be both true simultaneously: either the implant causes local complications or it doesn't. To prove that implants cause local complications, it is necessary simply to demonstrate one case of a local complication. Since numerous cases of local complications are on record-not to mention the numerous types of local complications-the proof of contraries is more than abundantly fulfilled.

One can make the same argument for the causation of systemic complications. Either implants cause systemic complications or they don't. If the implant doesn't cause autoimmune disease, then why does manufacturer Dow Corning state under section 17, paragraph 3, of the package insert that "if an immune response is suspected and the response persists, removal of the prosthesis is recommended along with the surrounding capsule tissue. Such patients should not be re-implanted" [II? Are they suggesting operations for no purpose? Would they endanger the lives of the implanted patients for no valid reason? If implants and foreign materials cannot cause immune reactions, then why are there numerous published papers that say they do? Why are there animal studies that show foreign materials are immunogenic? Clearly the reasoning of contraries proves that implants cause systemic problems. Whether they have done so in an individual case must be determined on the basis of the evidence presented.

The general heading of circumstance comprises two main lines of discourse: the possible and the impossible, and the past fact and future fact.

The possible and impossible come in five Aristotelian flavors, most of which apply to the matter at hand. Their application is simple.

First, if one pair of similar items is possible, then the other is possible also. Silicone directly injected into tissue causes local and systemic reactions; therefore, silicone indirectly injected into tissue after a silicone implant ruptures causes local and systemic complications.

Second, if a difficult thing is possible, then the easier thing is possible also. If you can recite the alphabet backwards, chances are likely you can recite it forwards as well. If the bleed of silicone causes a local inflammatory reaction, then a rupture of an implant will cause a local inflammatory reaction.

Third, if one problem-causing thing can do something, then two problem-causing things together can make things worse. If silicone causes a local inflammatory reaction, then silicone plus an additional foreign material like polyurethane (probably more irritant) must do so faster, and more severely.

Fourth, if a thing is possible without aggravating or complicated conditions, then it is definitely possible with the complications. An intact implant may elicit a surrounding inflammatory reaction; therefore, a ruptured implant may do so too.

Finally, if the parts are possible, so is the whole. Hence, if the implant has been

associated with Sjogren's syndrome, Raynaud's phenomena, scleroderma, memory loss, muscle weakness, and what have you in individual cases, then a patient who exhibits all of those afflictions can have a possible complication too.

Whether a thing has happened or not is useful in establishing precedent. When companies have settled cases that purport injuries due to implants for large amounts of money, a precedent is established; the same occurs when a jury awards a large amount of money for the same reasons. Past fact suggests that reasonable people studying a particular situation reached a reasonable conclusion, and projects that similar people acting under similar circumstances may reach similar conclusions in the future, establishing a similar or identical future fact. What can be said about past fact hews closely to common sense: two events closely associated (implant and some disease) in the past produce event X (compensation). It is likely the same associated events will also produce the same consequences in the future, and that other cases will be settled or large monetary awards made in compensation.

What is right or wrong about this cannot be determined by this line of argument, since past fact merely predicts future fact-not what is correct, just, or right. In a larger sense, one can invoke the physical laws of the universe to predict the production of future fact. The second law of thermodynamics, for example, has never been violated and therefore is considered a sound predictor of what will happen. It tells us that everything is breaking down, headed towards disintegration and disorder. Since the implant is part of the physical universe, it is governed by the second law and therefore it too must break down. And if it breaks down, it must cause those things known by past fact to be caused by mechanical implant failure-including spilling silicone into tissue, local inflammation, scar formation, pain and tenderness, heat, and, of course, deformation of the tissue in which that implant had been placed.

Testimony, the last major topic, encompasses six subheads: authority, testimonial, statistics, maxims, law, and precedent.

We tend to imagine some distant past where people unblinkingly accepted the dictates of Church or King, and therefore say that authority isn't what it used to be. We try to believe in this modern, scientific, democratic age that people look at things skeptically and tend not to accept anything unless proven by evidence and reason.

Unfortunately, this belief remains unjustified by the facts: a new age of human intelligence has not dawned. While many old authorities have been simply shunted aside, they have been replaced by new authorities because humans crave simple answers to complex problems. Appeal to authority-any authority, even the manufacturer of the package insert or the FDA itself-remains illogical, because an authority can be right or can be wrong.

What an authority says must be judged by the evidence and not by the position or reputation of the authority. Nevertheless, provided you cite authority that people accept, arguments citing authority carry considerable weight, especially if the authority cited is one of the new breed-such as the talk shows, the popular press, or public radio, or even better a famous movie star, television news personality, or public opinion surveyor. The new authorities are not disinterested. Instead, they have a financial stake in selling newspapers or getting people to listen to their broadcasts. Therefore, positions taken by modern authorities tend to be emotionally colored, sensational, and not based on a dispassionate analysis of evidence.

Plastic surgeons continue to complain about the rather poor press coverage of the breast implant situation and the overblown emphasis on side effects and the supposed faults of the manufacturers. They railed that there were no scientific studies proving that implants caused problems and even claimed the extreme and untenable position that there were no problems.

Message: 25

OPEN FORUM -- Blaming Breast Implant Victims

Mary Alexander

IN MARCH, the National Cancer Institute and the National Institute of Health prompted by a high incidence of cancer among women with breast implants, convened a symposium on "immunology of silicone." Experts at the conference concluded that exposure to silicone breast implants sets into motion significant and long-lasting diseases. When silicone gel leaks from a ruptured implant, it poisons the system, triggering immune responses that set the body against itself.

More than 20,000 women are demonstrably sick as a result of their ruptured implants.

On June 21, a 45-year-old woman, diagnosed with lupus, a connective-tissue disease, went to her plastic surgeon after learning that her breast implants had ruptured. A nurse by profession she had accepted the conventional wisdom that breast implants were safe when she had the surgery 12 years ago. For the last 10 years she has been suffering from the symptoms of silicone poisoning, which include dryness of the eyes, nose and mouth; headaches, numbness and tingling in the limbs; memory loss; nausea; and arthritic conditions. She is now unable to work and permanently disabled.

Her plastic surgeon said, "Haven't you read the papers? They're saying there's no connection between your disease and leaking silicone from breast implants." He then suggested that she should leave her ruptured implants in or get new ones.

Newspapers across the country were carrying a story about a magazine article of a study last year on breast implants. The study asserted that there was no link between silicone gel leaking from breast implants and connective-tissue disease in women. Since the study was partially conducted at Harvard Medical School, it was given wide coverage in the media and was believed, even by doctors.

But the study is seriously flawed. It used inappropriate scientific methodology. The researchers got their information from questionnaires; they never actually examined the women in the study. Even if they had, statistically the number of participants was too small and the time period was too short. Experts have determined that the latency period for silicone disease is about 8.5 years after implantation. Conclusions in the study about silicone poisoning were based on what are known as ``classic auto-immune diseases.'' Silicone poisoning is a new disease, with auto-immune symptoms that are ``atypical'' but just as serious. 

Other factors cast further doubt on the study. Two of its authors admitted under the threat of perjury that they were paid consultants of breast implant manufacturers, a clear conflict of interest. At least one of them knew Dow Corning, the world's largest silicone breast implant manufacturer had donated $5 million to one of the hospitals involved in the study. Yet doctors who support the Harvard study are implying that the women, though not exactly lying, are making things up. That mentality could lead to dangerous consequences by stopping continuing, long-term scientific research on silicone poisoning.

One such doctor is Shaun Ruddy, president of the American College of Rheumatology. "I would think that if there had not been the endless litigation," Ruddy said, "that it is unlikely that anyone would choose to study this issue further." What Ruddy ignores is that without the litigation, four decades of evidence hidden by Dow Corning would never have seen the light of day.

Internal documents show that Dow Corning knew back in 1954 that silicone gel could cause internal damage to test animals -- a fact the company stripped from its report to the Food and Drug Administration. A memorandum from one of their own engineers complained that they could not even film demonstration tapes of implant insertions without two of the salesmen to wipe leaked silicone gel off the implants before demonstrating them to plastic surgeons. Dow Corning salesmen were going into public rest rooms to dry off the implants on their way to sell them to doctors.

This is a sampling of the kind of information that Dow Corning deliberately withheld from the public and the medical community until they were finally sued. The fact is, Dow Corning (which went bankrupt because of the verdicts) and other manufacturers created breast implants, aggressively marketed them, deceived the public and now blame women for suffering the consequences.

Message: 26

Corning Pharmaceutical Services

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As a unique global resource, the Corning Pharmaceutical Services network of companies can handle all aspects of drug development from preclinical through clinical and periapproval studies, all the way to contract manufacturing, packaging and labeling.

Along with the financial stability of Corning, a Fortune 500 company, Corning Pharmaceutical Services offers the Corning commitment to quality, customer service, and innovation, as well as continuity of management and systems.

Whether your needs are for small, specialized protocols or large-scale, multinational clinical trials, Corning Pharmaceutical Services has the expertise and resources to successfully guide and execute your clinical drug development program from inception to completion.

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Message: 27

Abstract: Diagnostic And Clinical Criteria Distinguishing Silicone Related Disorders From Classical Rheumatic Diseases.

Authors: Tenenbaum,Rice,Rlymale,Sander,Wilson,Garry.

Tulane University School of Medicine New Orleans, LA.

Swan -Univ.of California,Berkeley

Gluck,Tesser,Weinrib,Stribrny, Bevan - AZ.

Rheumatology Center.

Cuellar and Espinoza-LSU-Medical Center

Source: American College of Rheumatology Sept.1995 Vol.38-No.9

Abstract: A proportion of women exposed to silicone breast implants (SBI) report symptoms consistent with classical autoimmune diseases,such as scleroderma, Sjogren's syndrome and systemic lupus erythematosus, as well as symptoms of atypical rheumatic and connective tissue diseases. In previous unblinded studies we found that the presence of anti-polymer antibodies (APA) distinguished healthy blood donors (9/100 seroreactive) from individuals with SBI who have experienced silicone related disorders (SRD) (363/667) seroreactive;p<0.0005). Non-SBI exposed individuals with classical rheumatic diseases did not have elevated APa reactivity (16/297) seroeactive). A blinded and controlled single center study was designed to assess the efficacy and improve an APA assay and other selected diagnostics that may objectively identify individuals with SRD.Detailed physician and patient questionnaires were obtained and will be used to associate specific clinical signs and symptoms with objectively distinguishable diagnostic patterns. participants included:

1. SBI exposed women with a variety of classical or atypical complications(subdivided on the basis of disease severity,N=97), 2. asymptomcatic SBI exposed women (n=19), 3. non-SBI exposed helathy women (n=23), and 4. non-SBI exposed women with classical autoimmune diseases (n=15).

Despite the small numbers of participants in this blinded study, diferences by objective quantitation techniques for APA seropositivity approached statistical significance when women with moderate or severe nonspecific autoimmune conditions or atypical connective tissue disease were compared to groups 2,3 or 4 described above (p=0.05, p<0.06 and p<0.02, respectively). In general, the percentage of women seropositive for APA increased with the severity of symptoms.

Some of the medical expenses for women in this study were paid for by the plantiff attorneys.

RFG has received research support from Baxter and Bristol-Myers Squibb. LRE and SHS have served as expert witnesses for plantiff attorneys in SBI litigation.