Date: 9 Jun 2000 02:00:09 -0000

There are 26 messages in this issue.

Topics in this digest:

1. USSW: Guide to Blood Tests for Arthritis Patients

2. USSW: Breast Implants And Connective Tissue Disease

3. USSW: AUGMENTATION MAMMOPLASTY AND CONNECTIVE TISSUE DISEASE

4. USSW: Antiglycolpid Antibodies In Symptomatic Women with Silicone Breast Implants

5. USSW: Antibody To Silicone And Native Macromolecules In Women With Silicone Breast Implants

6. USSW: Adjuvant Breast Disease

7. USSW: A Comparison Of The Capsules Around Smooth And Textured Silicone Prostheses

8. USSW: 1992 BREAST IMPLANT AND AUTOIMMUNE DISEASE STUDY

9. USSW: Breast Implant Testing Information

10. USSW: Clinical Characteristics of 343 Patients With Breast Implants

11. USSW: Histologic features of breast capsules reflect surface configuration and composition of silicone bag implants

12. USSW: Immune disorders are characterized by development of autoantibodies

13. USSW: Light Microscopy Techniques For The Demonstration of Silicone Gel

14. USSW: Mechanical Testing of Silicone Breast Implant Shells

15. USSW: The Role Of Immune System On Capsular Contracture Formation

16. Re: Older Documents from USSW

17. USSW: Quick Facts About Civil Litigation

18. USSW: Histologic Features Of Breast Capsules

19. USSW: Local Increase In Hyaluronic Acid and Interleukin 2

20. USSW: Immune Reactions in Breast Implant Patients

21. USSW: SWAN-Epidemiology of Silicone-Related Disease

22. USSW/JAMA: Self-reported Breast Implants and Connective-Tissue Diseases

23. Please use older documents from USSW

25. USSW: July 1995/statement of James E. Jenkins-DC VP

26. USSW: SUPPRESSED NATURAL KILLER CELL ACTIVITY

Message: 1

This FAQ/Guide to blood tests was written by Dr. Chris Tacker (Department of Geosciences, University of Tulsa) with assistance from his mother, Madge Chamness (Associate Professor in Department of Clinical Laboratory Science, School of Allied Health Sciences, East Carolina University).

1 General blood tests

a. CBC- Complete blood count

b. Basic chemistry panel

II. Specialized blood tests

a. Rheumatoid factor test for RA

b. HLA typing

c. Sedimentation rate

III. What to do with this information

I. General blood tests. Routine medical testing will probably include examination of blood cells, analyisis of blood chemistry,and urinalysis. These "screening" tests give a lot of general information about your state of health and may indicate the need for more specific tests.

They should be part of a complete physical every 2-5 years, depending on your age.

Ia. CBC- Complete blood count. This test is a Complete Blood Count of red blood cells, white blood cells and platelets. The information relates to anemia (low red cell count).

(1) WBC- White cell count. Normally around 5,000-10,000. People of African descent may have normal values in the 4,000 range. Increased values suggest inflammation or infection. Exercise, cold and stress (among others) will temporarily elevate the white cell count.

(2) RBC- Red cell count. Normal values vary with sex, with male values around 5-6 million per microliter. Female values are in the 3.6-5.6 million per microliter range.

(3) Hgb- Hemoglobin. Measures the iron-containing protein that carries oxygen. Male values 13-18 g/dl, females 12-16 g/dl.

(4) Hct- Hematocrit. Measures the % of the total blood volume that is red cells. Male values 40-55%, Female values 36-48%. In general, the RBC times 3=Hgb,, Hgb times 3= Hct, so if you have one value, you can estimate the others. Decreased values indicate anemia.

(5) MCV, MCH, MCHC. The red cell indices are values derived from the RBC, Hgb and Hct and give an indication of the size and hemoglobin content of individual red cells. If you are anemic, these indices give a clue about probable causes (iron deficiency, folate deficiency, etc.).

(6) Platelet count. Platelets makes the initial plug in the formation of a clot. Normal values are in the range of 150,000- 400,000. Many drugs decrease the platelet count or affect platelet function.

(7) Differential. The % and absolute number of each type of white cells. In order of decreasing frequency in adults, Neutrophils- (segmented and banded) Increased in bacterial infections and acute inflammation. Lymphocytes- Increased in viral infections. Monocytes- Increased in chronic infections. Eosinophils- Increased in allergies. Basophils- Only 1 or 2/100 white cells, not increased usually. Comment about anemia- In cases of chronic inflammation, the body starts to sequester iron, and the red cell values fall off to a medium-low value and stablizes. People usually adapt to the lower hemoglobin values, but usually do have a normocytic/normochromic anemia when a CBC is done.

Ib. Basic Chemistry Panel This is a series of tests that is run to evaluate overall health of the patient. It normally includes heart risk indicators (cholesterol, etc), diabetes indicators (glucose), kidney function test, liver function tests and a thyroid screening. Abnormal values indicate more testing to pinpoint the problem specifically.

II. Specialized blood tests. These are tests that are run for a more detailed examination of patient health, especially during diagnosis and treatment of chronic disease.

IIa. Test for Reumatoid Factor. This test looks for an antibody to immunoglobulin, in effect, an antibody to an antibody, because immunoglobulins are the proteins that serve as antibodies. It is a test for rheumatoid arthritis. The problem is that it is *not* definitive. The test is positive in about 70% or so of RA's. False positives occur in a number of other disorders and normal people often have RF at low levels. Higher levels correlate with more severe disease. If it is not 100% certain, then a reasonable question is

"Why do it?". It is performed as another clue for the doctor trying to make a diagnosis, and not used as a "make-or-break" piece of data. One of the online doctors on the Usenet made the point "You diagnose the patient, not the test", meaning the blood tests are used as part of evaluating the patient's entire condition. IIb. HLA typing. Most people are familiar with blood typing for transfusions or for donating blood to the Red Cross. White blood cells (lymphocytes) may be typed as well for HLA (Human Leukocyte Antigen). Presence of the HLA-27b seems to indicate a predisposition to athritis. It is not definitive, and it is not a great predictor of what is.going to happen 10 years on. This test is necessary for transplants, so it is common in medical centers, but the results are still somewhat technician dependent- i.e. it takes a trained and skilled Med. Tech. to do it, rather than someone who just runs a black box.

IIc. Sedimentation rate. Sed rate is the measurement of how fast red cells settle through a sample of your blood that has been treated with an anticoagulant. The sample is put in a calibrated, straight-sided pipette and the rate at which red cells fall is measured after an hour. Results are reported in millimeters per hour. The results depend a little bit on the actual method used, but normal is about 0-10 mm/hour. This is a test for the changes in proteins in the blood plasma. (This test will be familiar to Geologists and/or other scientists as a viscosity measurement via the "falling sphere" method.) During an acute flare, sed rate will rise as the body adds all sorts of things to the blood. Problems: Sed rate is non-specific. It will also go up if you have any other infection or inflammation, such as a strep throat or a sprained ankle. Anemia will also change the test results, as fewer red cells are present to be measured.

III. What to do with this information. The best way to use this information is to keep track of it yourself. Get a xerox of your test results. Many people have spreadsheet programs these days, which are excellent for this sort of data management, graphing and display. It is especially good if you have to change doctors. Example: If you track your cholesterol over several years you may notice a slow increase. The doctor would say that it is still within normal values, but it would be a good idea to get his input on getting those values back down *before* things get too bad. Be pro-active for yourself! Ask questions about any test values that aren't within normal limits.

Message: 2

Abstract: Breast Implants And Connective Tissue Disease: A Meta-Analysis Of Epidemiology Studies.

Authors: Perkins,Klein,Clark and Cook. Epidemiology Division-Dow Corning Corp.

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

Abstract: Case reports have raised questions about an increased risk of connective tissue diseases (CTD) among women with breast implants.

This meta-analysis investigated a possible association based on epidemiology studies reported through October,1994. The literature search included Medline, Toxline, Current Contents Search, dissertations, professional society meetings, and study references. A prior inclusion criteria stipulated that studies be printed in English and provide a relative risk (RR) estimate for the possible association between breast implants and CTDs either individually or in general. From the reviews of more than 2,600 abstracts, manuscripts, and dissertations, 12 studies met the inclusion criteria (six cohort studies, 5 case-control studies, and 1 other design). Some selected patients from clinical practices while others were population-based. Outcomes of interest included: CTD in general (n=6), scleroderms (SSc) (n=4), rheumatoid arthritis (RA)(n=1). Two additional studies were found but lacked sufficient detail for inclusion,i.e.,cell totals for the 2x2 table. The meta-analysis RR for CTD in general based on all 12 studies was 0.76(95% CI: 0.55, 1.04; heterogencity p-value=0.07). Combining the 11 case-control and cohort studies,the meta-analysis RR was 1.11 for CTD in general(95% CI: 0.74, 1.66; heterogeneity p-value=0.65). For the 3 case-control studies of SSc, the meta-analysis RR was 1.04(95% confidence interval(CI):0.58, 1.81; heterogencity p-value=0.72). Irrespective of which studies were aggregated in the meta-analysis, there was no significant increased risk for SSc,RA,or CTD in general. Conclusions from this study are consistent with the most recent review by the British Medical Devices Agency that found no scientific evidence to date of an increased risk of connective tissue disease associated with silicone gel breast implants.

Message: 3

Arthritis and Rheumatism

FROM ARTHRITIS AND RHEUMATISM VOL. 32 PG. 578 1989

"AUGMENTATION MAMMOPLASTY AND CONNECTIVE TISSUE DISEASE"

BY : CAROL M. BLACK, SALVOTORE LUPOLI, WENDY STEVENS, CATHERINE REID, CHRISTOPHER M. WARD, WEST MIDDLESEX UNIVERSITY HOSPITAL, ISLEWORTH, MIDDLESEX, TW7 6AF, UK

ALTHOUGH RETROSPECTIVE STUDIES HAVE RECORDED CONNECTIVE TISSUE DISEASES (CTD) IN PATIENTS WHO HAVE UNDERGONE AUGMENTATION MAMMOPLASTY, NO PROSPECTIVE STUDY HAS BEEN ATTEMPTED.

WE REPORT HERE THE PRELIMINARY FINDINGS OF SUCH A STUDY IN 30 FEMALES WHO UNDERWENT MAMMOPLASTY USING A THICK WALL HIGH BLEED SILICONE GEL PROSTHESIS.

PRIOR TO SURGERY THE GROUP SHOWED NO EVIDENCE OF A CTD AND BLOOD WAS DRAWN FOR HLA TYPING, AUTOANTIBODY SCREEN TYPE III PROCOLLAGEN PEPTIDES (P-3-NP) AND COLLAGEN ANTIBODIES. 26 OF THE 30 FEMALES WERE AVAILABLE FOR ONE-YEAR FOLLOW-UP, AND TO DATE 10 HAVE COMPLETED A TWO-YEAR REVIEW.

THE PATIENTS WERE ASSESSED CLINICALLY FOR CAPSULAR CONTRACTURES AND FOR EVIDENCE OF A CTD. CAPSULAR CONTRACTURE WAS EXCESSIVE IN 18 (BAKER'S CLASS 3 AND 4) AND MILD IN 8 (CLASS 1 AND 2) BUT NO PATIENT DEVELOPED A SYSTEMIC RHEUMATIC DISEASE. NO PRE- OR POST-OPERATIVE SERA HAD ANTIBODIES TO dsDNA OR SOLUBLE CELLULAR ANTIGENS. FIVE PATIENTS GAVE A POSITIVE FLUORESCENCE TEST, IN 3 THIS WAS PRESENT PRE- AND POST-OPERATIVELY. THE P-3-NP LEVELS WERE SIGNIFICANTLY RAISED AT ONE YEAR (p < 0.001) AND REMAINED RAISED IN 10 PATIENTS TESTED AFTER 2 YEARS. COLLAGEN ANTIBODIES (TYPE I, II, III, BOTH NATIVE AND DENATURED) WERE NOT STATISTICALLY DIFFERENT AT ONE YEAR, BUT IN THE 10 PATIENTS AVAILABLE FOR 2-YEAR FOLLOW-UP THEIR TITRES WERE SIGNIFICANTLY REDUCED. WE CONCLUDE THAT NO PATIENT HAS DEVELOPED A CTD BUT THAT THERE IS A LOCAL FIBROUS REACTION WITH ENCAPSULATION REFLECTED IN THE LEVELS OF P-3-NP AND COLLAGEN ANTIBODIES.FURTHER FOLLOW-UP WILL TAKE PLACE AT 5 YEARS.

Message: 4

Abstract: Antiglycolpid Antibodies In Symptomatic Women With Silicone Breast Implants.

Authors: Kemple-Portland,Or. Alan Pestronk- St.Louis

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

Abstract: A syndrome of joint pain, fatigue and sicca symptoms is widely recognized in women with silicone breast implants.Many of thes patients complain of paresthesias,cognitive impairment and other neurologic symptoms.

Antiglycolipid antibodies(AGL Abs)have been associated with a group of uncommon lower motor neuron and peripheral neuropathies. An association between these antibodies and neurologic disease has been suggested in women with SBI's. We have studied a group of 283 symptomatic women with SBIs to determine the prevalence of AGL Abs and the extent to which these antibodies correlated with neurologic symptoms, clinical illness, and other autoantibodies.

Antibodies against glycolipid antigens (GM1,asialo GM1,MAG and sulfatide)were quantitated using a standardized ELISA. Controls included 52 patients with fibromyalgia and 44 normal volunteers.

Results are as follows;SBI Patients-56/283-% of sera with abnormal antibodies, N Volunteers 5%(2/44) FM patients 9%(5/52).The majority of abnormal sera were polyreactive;e.g.,multiple antigens(55/62 SBI; 5/5 FM;2/2 normals).IgM and IgG reactivity were equally common and did not overlap.In the SBI group with abnormal AGL results, 84% complained of significant paresthesias compared with % of the AGL negative grup(P<.01). Six patients were felt to have significant neurologic disease and all of these had abnormal test results with average titers somewhat higher but no difference in pattern. Of patients with AGL antibodies, 78% had abnormal ANAs compared with 61% of those without AGL antibodies.

Conclusions: 1) Antiganglioside antibodies are significantly increased among this population of symptomatic women with SBIs. 2) Positive AGL antibodies correlate with paresthesias. 3)Patients with significant neurologic illness tend to have more abnormal results.

Message: 5

Abstract: Antibody To Silicone And Native Macromolecules In Women With Silicone Breast Implants.

Authors: Vojdani, Brautbar, Campbell

Source: Immunopharmacol Immunotoxicol Nov.1994; 16(4):497-523

Abstract: Silicone implants have been associated with the development of multiple organ system abnormalities, including rheumatic disorders, nervous system, pulmonary dysfunction associated with autoantibodies and abnormalities of cellular immunity. In this regards a number of case reports are series of articles have been described.

We hypothesized that an immune reaction to silicone breast implants would include the host reactivity against silicone and the macromolecules within the microenvironment of the implant, and these autoantibodies may react with other tissue antigens far from the site of the implant.

To test this hypothesis 520 symptomatic women with silicone implants which have developed silicone related immunological disorders and have typically complained of breast pain, myalgia-arthralgia,fatigue, or generalized pain, were examined by their physician.

Blood samples were obtained and examined for the presence of silicone antibodies, myelin basic protein and human serum albumin antibodies. These samples were then compared to 520 matched controls without implants. At least at the level of two standard deviation silicone specific antibodies, IgG, IgA, IgM, IgE and IgG+IgA+IgM antibodies were detected above the mean of normal controls.

When these antibodies were classified based on the specialty of the examining physician, the % of patients with silicone antibodies were varied; general practice 51.6, rheumatology 58.7, and plastic surgery 83.3, which may relate to the severeness of the disease. Being that a large % of patients demonstrated very high levels of myelin basic protein antibodies, possible cross reactive antibodies were sought. However, absorption of highly positive sera for silicone antibodies with MBP did not change the levels of silicone antibodies. On the other hand, silicone -HSA was able to reduce the antibody values significantly. This reduction in antibody levels by silicone is the best indication for the specificity of these antibodies. Moreover when data for silicone antibodies and MBP antibodies was analyzed in patients some with high and others with medium or low levels of silicone antibodies, MBP antibodies did not correspond to the silicone antibodylevels. Similarly human serum albumin antibodies which was significantly higher in patients with silicone implants did not correlate with levels of silicone antibodies.

These results indicate that immune reaction to silicone and different tissue antigens do occur and they are initiated through different mechanisms.

And since predominant antibody class against silicone, mbP and HSA was IgM, clonal activation of IgM is possible which certainly warrants further investigation.

Message: 6

Adjuvant Breast Disease: An Evaluation of 100 Symptomatic Women with Breast Implants or Silicone Fluid Injections

Britta Ostermeyer Shoaib, Bernard M Patten and Dick S Calkins (Received for publication on December 7. 1993)

We evaluated 100 referred women with breast implants (n = 97) or silicone fluid injections (n = 3) into breasts who developed various symptoms. All reported symptoms occurred at a median latency period of 6 years (range 0-24 years) after implantation or injection of silicone. Commonest symptoms were weakness (95%), fatigability (95%), myalgia (90%), morning stiffness (89%), arthralgia (81%), memory loss (81%), sensory loss (77%), headache (73%) and dry eyes and dry mouth (72%).

Laboratory results revealed abnormal levels of serum immunoglobulins or complement in 57% and autoantibodies in 78%. Sural nerve biopsy was abnormal in 80% with the major finding of loss of myelinated fibers in 79%. Biceps muscle biopsy was abnormal in 58% with the major finding of neurogenic atrophy in 27%. Ninety-six patients underwent implant removal; 60% of the patients were found to have one or both implants ruptured with silicone spilled into tissue. At time of removal, a pectoralis major muscle biopsy was taken which was abnormal in 89% with the major finding of neurogenic atrophy in 55%. Biopsy of implant capsule was abnormal in 94% showing foreign body giant cells containing retractile material consistent with silicone in 69% whether or not the elastomer shell was ruptured. Silicone can cause a systemic autoimmune disease with a variety of symptoms probably due to a global activation of the immune system. Since our patients had objective laboratory and histologic findings together with a high rate of mechanical implant failure, further investigations are necessary. (Keio J Med 43 (2): 79-87, June 1, 994)

Health professionals, federal officials and patients have raised numerous questions about the safety and efficacy of breast implants because they have been associated with a number of local and systemic complications such as capsular contracture, implant rupture and gel migration, gel bleeding, granuloma formation, lymphadenopathy, infection, interference with tumor detection and rheumatologic and systemic autoimmune diseases.(1-25)Dow Corning Corporation, who has been the biggest implant manufacturer until it quit the implant business in 1992, announced on March 19, 1993, that their silicone-gel had been found to be a strong irritant of the immune system.(26)Since approximately one million women in the United States have already received silicone breast implants,(27)the topic is of concern to the medical community as well as to the public.

We have now (December 1993) evaluated around 1500 women who developed an autoimmune disease associated with breast implants. The purpose of this study was to find out whether women with breast implants or silicone fluid injections and symptoms have objective and histologic findings.

The patients are the first 100 consecutively presenting women with silicone breast implants or silicone fluid injections who were referred to our service for evaluation of their symptoms between 1985 and July, 1992. All patients developed the symptoms reported here after receiving silicone breast implants or silicone fluid injection.

Each patient received an evaluation consisting of history and physical examination including breast examination and neurological examination. We sent a questionnaire inquiring about the patient's implant history and the patient's symptoms to each patient. Every patient was seen in consultation by an outside plastic surgeon or by a plastic surgeon at Baylor College of Medicine. All patients underwent quantitative measurements of immunoglobulin IgG, IgM, IgA and complement C3 and C4 by immune precipitation using rate-nephelometry, but results were only available in 76 patients. Ninety-three patients were tested for antinuclear antibodies (ANA) by indirect immunofluorescence, 92 patients for antimyelin associated glycoprotein antibodies (anti-GM1) by ELISA, 90 patients for rheumatoid factor (RF) by Latex agglutination, 88 for antiganglioside Ml antibodies (anti-GM1) by ELISA(28) and 79 patients for antisulfatide antibodies by ELISA.

Eighty-four patients received an MRI of the brain, 28 patients underwent a spinal tap with analysis of cells, protein, glucose and electrophoresis, 93 patients underwent EMG and studies of nerve conduction velocity, 20 patients had visual evoked responses measured, 32 patients had a xeromammogram of the breast, 40 patients had an ultrasound examination of the breast and 45 patients had an MRI of the breast. Sixty-six patients underwent a biopsy of the left sural nerve and 93 patients underwent a biopsy of the left biceps muscle. Ninety-six patients underwent removal of the implants and the surrounding implant capsule (open capsulectomy). At timeof implant removal, 90 patients had a biopsy of the implant capsule and 71 patients had a biopsy of the pectoralis major muscle taken. Frozen sections of muscle tissue were processed for staining using NADH-tetrazolium reductase, myofibrillar ATPase at pH 9.4 and modified Gomori's trichrome. Frozen sections of nerve biopsy tissue were stained with H&amp;E, modified Gomori's trichrome and crystal violet. Formalin sections of the implant capsule were stained with H&amp;E.

A Kaplan-Meier(29)estimated survival curve of discovered time to implant rupture was plotted without regard to type of implant to characterize the time to implant failure.

The median age of the patients at the time of first implantation of silicone breast implants or silicone fluid injections was 32 years (range 19-52 years). The median age of onset of clinical symptoms was 38 years (range 23-57 years). The median latency period between insertion of silicone implants or injection of silicone fluid and development of clinical symptoms was 6 years (range 0-24 years). Sixty-eight patients had received silicone breast implants (n = 65) or silicone fluid injections (n = 3) for cosmetic purpose. Thirty-two patients had received silicone breast implants for reconstruction of the breast after mastectomy for either fibrocystic disease (n=28) or breast cancer (n=4). Fifty-six patients had received silicone-gel filled breast implants, 20 patients had silicone-gel filled breast implants coated with polyurethane, 17 patients had double-lumen silicone breast implants and 4 patients had saline filled silicone breast implants. Three patients had silicone fluid injections into breast. Two of these later received silicone-gel breast implants. Forty-one patients had received more than one pair of breast implants due to local complications of the initial breast implants.

Message: 7

Abstract: A Comparison Of The Capsules Around Smooth And Textured

Silicone Prostheses Used For Breast Reconstruction. A Light And Electron Microscopic Study.

Authors: Wickman, Johansson, Olenius, Forslind Department of Plastic and Reconstructive Surgery, Karolinska Hospital, Stockholm,Sweden

Source: Scan J. Plast Reconstr Surg.Hand Surg. 1993, Vol.27

Abstract: A total of 18 women who had undergone modified radical mastectomy and tissue expansion for breast reconstruction were studied.

When the expanders were replaced, 9 patients had received smooth, gel-filled permanent prostheses and 9 had received textured, gel-filled permanent prostheses. For medical reason, e. g. capsular contraction, incorrecly placed or size implant, an additional operation was performed, and then biopsy specimens from the capsules around the prostheses were taken and subsequently examined with the aid of the light and transmission electron microscope (TEM). A histologist was able to classify blindly 11 capsules out of 13 which were investigated by light microscopy in the correct groups and several differences between the capsules were found.

Capsules around the smooth implants had a clear line of separation between the inner surface and the prosthesis, and formed a single collageneous layer. They were sparse in fibroblasts, which were long and thin. Capsules around textured implants consisted of two layers, the outer being compact with long, slender fibroblasts, and the inner one looking rugged with wavy bundles of collagen often splitting from each other, and with shorter and more rounded fibroblasts. The overall thickness seemed greater compared to the capsules around the smooth prosheses, which, on the other hand, showed a greater variation in thickness.

To analyze collagen fibril diameters, sample sections were photographed at magnification 22,000 x in the TEM. The fibril diameters were measured with an interactive image analysis system (IBAS). The mean diameter of the collagen fibrils was 47.2 nm in the capsules around the smooth prostheses and 51.7 nm in the capsules around the textured prostheses.

Message: 8

A new study strengthens the link between silicone gel breast implants and autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and a skin-hardening disorder known as scleroderma.

Scientists led by Eng M. Tan of Scripps Research Institute in La Jolla, Calif., have found so-called antinuclear antibodies in the blood of 23 women who developed autoimmune disease after receiving breast implants made of silicone gel. Tan and his colleagues report in the Nov. 28 LANCET that those women with the highest levels of such antibodies had the worst symptoms. Moreover, women whose implants had ruptured or leaked silicone experienced symptoms more than five years sooner than women whose implants had remained intact, they say.

Physicians currently use elevated levels of specific anti-nuclear antibodies - so named because they attack proteins within cell nuclei -to diagnose various autoimmune disorders. Tan and his colleagues suggest that exposure to silicone can cause autoimmune diseases. However, they caution that their data do not allow them to rule out the possibility that such exposure simply hastens the onset of symptoms among women already developing an autoimmune disease.

Copyright 1992 by Science News. Text may not be copied without the express written permission of Science News. Monastersky, Richard, Breast implants and autoimmune disease., Vol. 142, Science News, 12-12-1992, pp. 414.<P>

Message: 9

Originally Composed 03/29/92

Today (Monday March 29, 1992), I caught all but the first 5 minutes of the Jenny Jones' follow up show to the one she did a few weeks ago about silicone breast implants. I realize that few of us have the implants but many of us are concerned about the health of friends or relatives that have them. Barbara Bertrand - 76304,2752

Here is a summary of the info and recommendations I heard:

Dr Edward Truppman PhD

* President of the American Society of Aesthetic Plastic Surgery

Supports

1 A registry of breast implants and all medical implants.

2 Further research.($10 million has been allocated by Dow Corning for 24 + studies to be conducted by the American Society of Plastic andReconstructive Surgeons to research auto-immune disorders, ruptures, mammography, capsular contracture, etc.)

3 Returning to your operating physician in order to facilitate gathering post-operative information for the doctors, yourself and others.

Remove implants only if there is a problem.

If a problem is mistakenly self-ascribed to the implants - upon removal the symptoms will likely abate or disappear due to a lessening of concern.

All of us, but especially diabetics, have silicone in our bodies from disposable syringes with silicone lubricants (note: also hairspray)

If silicone is in the lymphatic system "there is until now no evidence of problems or disease" (HIS words) from this.

Alternatives to implants

Flap procedure (expensive & painfull mastectomy reconstruction

technique)

Autologous fat transfer from tummy tissue or buttocks (with large scars and some underlying muscle taken) - 10 year old procedure NOT to be performed on those who smoke, are diabetic or overweight. He gave a typical $6000-8000 surgeons fee.

* Associate Professor of Medicine and Surgery at Johns Hopkins University

* one of the first to sound an alarm on silicone breast implants

* chairman of the first FDA panel on silicone breast implants

* consultant on latest panel on silicone breast implants

We need an FDA mandated Universal registry of implanted medical devices by type and lot number.

Of 12 breast implant manufacturers 9 are gone (and Dow Corning has stopped making them) and there have been 60 to 70 different variations of the breast implants.

New implants include peanut oil & see-thru (as regards mammographic x-rays).

Implant Rupture Rates - 0.4 % - Manufacturers Figure - 6-8 % - FDA Figure

Dr. Pierre Blaise (SP?) of Canada (on patients at time of removal because of capsular contracture or size adjustment) determined the following rupture rates (which Dr. Anderson said demonstrated the deterioration of the shell strength such that the oldest implants could rupture with a mammogram or even a firm hug):

- 5-7 years - Very few broke

- 7 + years - Increase in rupture rate

- 12+ years - 13 of 14 ruptured

- Capsular contraction is an indication of leakage. (note: all implants are said to have a slight slow-bleed leak thru the shell, and milder capsular contraction will take place in the body's reaction to the silicone shell).

- Implant Rupture Symptoms

- Searing breast pain

- Chest wall complaints

- Shoulder-arm syndrome (muscle spasm and reflex nerve action)

- Fibro mialagia (general muscle stiffness)

(Note: Dr. Anderson said "this DOES NOT indicate lupus or sceleroderma but is hellishly difficult to treat.")

Dr. Anderson, also commented on the FDA hearing testimony of Dr. John Sargeant, Chief of Medicine at St. Thomas Hospital in Nashville, who said about silicone gel implant ruptures as related to rhumatic disease (rhumatoid arthritus, lupus, sceleroderma, etc.) and mammograms, there is "not enough there to continue the moratorium."

Dr. Anderson stated that "it is also evident that he could not rule out that, although it [the breast implant] did not cause lupus it might make the lupus activate or [make it] worse".

- Tests For Augmented Breasts

- Recommended yearly Displacement Method Compression mammograms AND Ultrasound testing. (see below)

- Use Displacement Method Mammography rather than the Compression method for breast cancer detection, as the latter misses at least 50 % of silicone implant ruptures.

- For rupture detection use the "zero mammogram" from the Xerox Corp.

- Ultrasound is useful for supplementing mammograms in cases of silent rupture, bulges or herniated implants indicating threat of rupture.

- For those with polyurethane covered implants, a Urine test for TDA (TutolueneDiamine Acetate) breakdown products. Here are some additional addresses and phone numbers:

The Command Trust Network

256 S. Linden Drive

Beverly Hills, CA 90212

(Lists of doctors, tests, etc.)

International Breast Implant Registry 1-800-892-9211 (Fee - Will update you on your implant, optional participation in studies)

The Plastic Surgery Patient Relations Network hotline 1-800-635-0635 (for when you have a problem with your physician. They will give you referrals to locate an ASPRS Board Certified plastic surgeon.)

Dow Corning's Implant Information Center 1-800-442-5442 Will pay up to $1200 to women who need but can't afford surgery to remove implants - a procedure the company says can cost $1000 to $5000.

Important deadlines and dates in the global breast implant settlement:

-- June 17: Deadline for implant recipients to comment, object or decline settlement.

-- Aug. 18: Fairness hearing before U.S. District Sam Pointer in Birmingham, Ala.

-- Sept. 16: Deadline for women claiming implant-related diseases to submit medical records for first round of payments.

-- Dec. 1: Deadline to remain eligible for money for medical evaluations, implant removal and other injuries not covered by disease compensation.

The toll-free information hot line for breast implant recipients is 1-800-887-6828.

12/06/93

HOUSTON -- A private laboratory says it has developed a blood test that could provide a simpler way for women to find out if their silicone breast implants have ruptured. Some scientists, however, say researchers first must determine if silicone implants really are harmful. And one researcher dismisses the test completely.

Emerald Biomedical Sciences Inc. says the test measures antibodies created by the bodyin reaction to silicone, the substance used in devices implanted in more than 1 million American women.

"What we're finding is women with ruptures or leakage have significantly higher antibody levels," said Richard Furlin, president of the company based in The Woodlands, north of Houston. Furlin said the lab is seeking approval from the Food and Drug Administration to market the test. He said it could be used instead of surgery or expensive nonsurgical tests such as magnetic resonance imaging to determine if implants have ruptured or are leaking. He also said it might aid researchers in discovering whether a link exists between implants and disease. Emerald said a study of its blood test shows women with known ruptures had higher levels of the antibody. Women with implants that were intact had slightly higher antibody levels than control subjects, Furlin said.

One researcher disputes whether an antibody test would be accurate.

"We know that most of the women who have breast implants have anti-silicone antibodies in their body," said Dr. Bernard Patten, associate professor of neurology at Baylor College of Medicine in Houston. "We find that the women uniformly have higher elevations ... but the level of antibodies doesn't correlate with their disease or with other complications," said Patten, who is researching breast implant complications.

Results of Emerald's study were published this fall in the FASEB journal, the publication of the Federation of American Societies for Experimental Biology. Susan Cruzan, an FDA spokeswoman, said it is against agency policy to comment on pending cases.

One group questions the usefulness of such a test, even if accurate. "It's difficult to say, even if the antibodies are found, what the next step would be," said Laura Kopulos Asplund, spokeswoman for the American Society of Plastic and Reconstructive Surgeons, based in Chicago. Ms. Asplund said that without proof that silicone or the antibodies cause any health problems, the test might only serve to unnecessarily alarm women.

Message: 10

Abstract: Clinical Characteristics of 343 Patients With Breast Implants.

Authors: Davis, Campagna, Perrillo, Criswell UCSF-San Francisco, CA. 94143

Presented at Amer.College of Rheum. Oct. 24th, 1995 Poster Discussion Group

Abstract: Current epidemiologic studies have failed to identify an association between defined rheumatic illness and silicone breast implants (SBI), however a case definition for a novel disease entity was not available for these studies.

We examined the medical records of all women with breast implants presenting to 2 board-certified rheumatologists (N=343). The majority of patients were either physician or self-referred.

The most frequent diagnosis was atypical connective tissue disease ( a term defined for evaluation of SBI patients), and representing a constellation of signs and symptoms. 68% of the women had implantation for cosmetic reasons, and 96% had exposure to silicone through silicone gel, double lumen, or polyurethane implants.

The mean age of the women at evaluation was 47 yrs, and the mean latency period between implantation and first systemic symptom was 6 years.

The most common symptoms reported were:

arthralgia (91%), chronic fatigue (85%)

dry eyes (69%) numbness and tingling (69% and 66%),

stiffness (68%) dry mouth (67%)

rash (63%) and joint swelling (37%)

In addition, 65% of the patients reported cognitive dysfunction (most commonly short-term memory loss (53%), and difficulty with calculations (33%), concentration (16%), directions (9%), and word finding (8%).

The most common physical findings were:

arthritis (76%), trigger points (76%),

dry oral mucosa and conjunctiva (66% and 22%),

enlargement of parotid, thyroid, or submandibular glands (59%),

hypoesthesia (50%), lymphadenopathy (46%),

livedo reticularis (28%), photosensitive rash (20%).

There was documented evidence of rupture in 158 patients, primarily by surgical report or pathology, MRI, mammography or ultrasound. Among 222 patients who had their implants removed, 52 patients (23%) reported improvement in their symptoms. We compared the frequency of cognitive dysfunction (CD) and overall level of disability between patients whose implants had and had not ruptured and found significantly worse overall disability (but no significant differnence in CD) among those with rupture. Although these 343 women represent a select group of patients (i.e. they were referred to a rheumatologist), the constellation of signs and symptoms observed among symptomatic women may help in the development of a case definition for subsequent eipidemiologic studies.

Message: 11

DATABASE: MEDLINE ® 1986-Present (Copyright 1995)

SOURCE: National Library of Medicine

Periodical: American journal of clinical pathology.

Title: Histologic features of breast capsules reflect surface configuration and composition of silicone bag implants [see comments]

Name: Kasper CS

Subject: ADULT

Aged.

Breast pathology.

FEMALE

Foreign Bodies Pathology

Foreign-Body Reaction Etiology gels

HUMAN

Middle age.

Silicones.

Imprint: United States : 1994 Nov

Note: CAS Registry 0 (Gels)

CAS Registry 0 (Silicones)

JOURNAL ARTICLE

Comment in: Am J Clin Pathol 1994 Nov;102(5):565-6

Abstract:

The fibrous capsules that develop around silicone gel breast implants may become excessively thickened and result in painful hardened breasts. This article examines the microscopic anatomy of 80 periprosthetic breast capsules removed during a 2-year period (1990-1992), and describes the histopathologic characteristics of capsules adjacent to themore recently modified implant types.

Capsules were examined by routine light microscopy, with and without polarization. Several distinctive histologic patterns were recognized, and these unique patterns could be correlated with the implant type used. All capsules were lined by a cellular membrane resembling synovium. Capsules adjacent to smooth-surfaced implants were lined by an intact histiocytic membrane of uniform thickness. In contrast, the membrane adjacent to textured implants varied in thickness, and was disrupted along its length. In addition, the inner surface of capsules adjacent to textured implants was conspicuously festooned with small (.25 to .5 mm) knob-like projections that were not seen in capsules adjacent to smooth-surfaced implants. A variety of foreign materials also were observed either within or adjacent to the capsules, and included droplets of liquid silicone, irregular solid fragments of the bag envelope, geometric crystalline fragments of polyurethane, and talc. Thus, the microanatomic features of periprosthetic breast capsules reflect the composition and surface configuration of the corresponding silicone bag type.

Message: 12

Abstract: Autoantibodies In Patients With Silicone Implants.

Authors: Bridges Department of medicine,University of Wisconsin Madison.

Source: Semin Arthritis Rheum. Aug.1994 Volume:

Abstract: Immune disorders are characterized by development of autoantibodies.

Autoantibodies, particularly antinuclear antibodies,are detected in the majority of patients with connective tissue diseases such as systemic lupus erythematosus and scleroderma. Recent reports have described persons with silicone implants who have developed scleroderma and systemic lupus erythematosus. Since autoantibodies are suspected to play an important role in the pathogenesis of the connective tissue disease, the nature of the autoantibodies produced in patients with silicone-associated rheumatic disease is important to understand.

A review of the English literature and abstracts from the 1992 American College of Rheumatology meeting showed that immunofluorescent testing for antinuclear antibody was positive in a wide range (70 of 68 patients with silicone implants.)

When examining only those patients with silicone implant and clinical evidence of connective tissue disease, the proportion of patients with a positive immunofluorescent test was less than commonly found in a series of patients with idiopathic connective

tissue disease. Sensitive testing by Western blot technique revealed autoantibodies in 10f patients with silicone implants and negative immunofluorescent test results.

Patients with silicone implants and scleroderma-like illness were characterized by anticentromere and anti-PM-Scl antibodies,whereas patients with silicone implants and SLE or undifferentiated connective tissue disease were characterized by antibodies to small nuclear ribonucleoproteins, specifically B'/B polypeptide. In addition, antibodies to a high molecular weight protein have been discovered by Western Blot in more than 50f persons with silicone implants.

Differences in autoantibody production between patients with silicone-associated rheumatic disease and patients with idiopathic rheumatic disease may be a distinguishing feature.

Further characterization of these autoantibodies is needed.

Message: 13

Abstract: Light Microscopy Techniques For The Demonstration of Silicone Gel.

Authors: Raso, Greene, Vesely, Willingham

Department of Pathology and Laboratory Medicine

Medical University of South Carolina

Source: Arch Pathol Lab Med

Oct.1994 - Vol 118, Pgs. 984-987

Abstract: Because of the difficulty in identifying silicone gel in histologic and cytologic specimens by means of conventional light microscopy, we investigated alternative light microscopy techniques, as well as specimen staining and preparation. Specimens from 6 periprosthetic capsules, one silicone granuloma specimen, and one synovial biopsy specimen obtained from a women with silicone breast implants were cut cut at 4-,10-,20-, and 30-microns sections, stained with a variety of common stains, and correlated with electron probe microanalysis. In addition, a commercial silicone gel and silicone gel extracted from a previously implanted silicone breast prosthesis were smeared and examined unstained or stained with Papanicolaou and Diff Quik. Silicone was noted to be refractile, nonpolarizable, and nonstainable. Thicker sections prevented silicone "dropout" during processing and increased the contrast between stained tissue and unstained silicone (negative staining). The relative ease of silicone identification was greatly increased with non-Koehler, phase contrast, and darkfield microscopy. Staining the mounting media of ematoxylin-eosin-stained sections with a nonparticulate commercial ink allowed enhanced negative staining detection of silicone gel.

Message: 14

Breast implants have been used for over 30 years, but the dependence of their strength on time in the body has only recently been studied. In a 1995 report by deCamara, Lockwood, and Grebner, the tensile strength of breast implant shells was shown to be negatively correlated with time in the body. The purposes of this thesis are (1) to repeat the tensile testing procedure used by Phillips et al. on additional implant shells, (2) to determine if other mechanical properties, such as strain, energy, or toughness, correlate better with implantation time than stress does, (3) to measure the tensile strength across fold flaws, and (4) to investigate possible variations in mechanical properties among the shell regions.

Fifty-seven used implant shells, with implantation times ranging from 1.1 to 20.2 years, were inspected. The distribution of condition was 27 shells intact, 7 leaking, and 23 ruptured. Forty of these 57 used shells and 5 unused shells were cut into specimens and tested according to ASTM standards. (Unused shells were never implanted in a patient.) A total of 573 specimens were prepared and tested satisfactorily; 514 were from used shells and 59 were from unused shells. Test results of specimens cut from the same shell were averaged together. The average, standard deviation, and variance of force, stress, strain, energy, and toughness were reported for each shell. Fold flaws were observed on 22 of the 57 inspected used shells, 18 of the 40 tested used shells, and 25 of the 514 specimens from used shells.

A very strong correlation was observed between shell condition and implantation time. Maximum stress correlated strongly with implantation time and weakly with condition. Maximum strain correlated stronger with both condition and implantation time than

stress did. Energy and toughness values from the high-performance shells were much greater than values from the older standard-performance shells. Fold flaws per se do not appear to affect the tensile strength of shell material, but intersections and terminations of fold flaws are often sites for pinholes that may lead to leakage and rupture. Thickness and tensile strength were similar among shell regions.

The strong correlations between maximum strain, which is easily measured, and both implant condition and implantation time suggest that maximum strain can be used as a convenient and representative measure of implant durability.

Message: 15

Abstract: Silicone Breast Implants:The Role Of Immune System On Capsular Contracture Formation.

Authors: Granchi,Cavedagna,Ciapetti,Stea,Schiavon,Giuliani, Pizzoferrato. Laboratory for Biocompatibility Research on Implant

Materials. Bologna,Italy.

Source: J.Biomed Mter Res. Feb.1995

Abstract: We evaluated the role of the immune system in the pathogenesis of the periprosthetic capsular contracture, the most frequently occurring complication following the implant of silicone prostheses. Peripheral blood samples from 22 patients with silicone-gel-filled implants were examined. In all cases a capsule was felt by palpation, and it was classified according to the Baker scale. 10 patient (group1 )had a Baker 2 contracture, and 12 (group 2) had severe contracture rated 3 and 4. The cells positive to antigens CD3, CD4, CD8, HLA-DR,CD19, DC25, CD57, CD16, and CD14, and the cytotoxic activity of the lymphocytes on target cells K562 were assessed by cytofluorimetric analysis. At time 0 there were no statistically significant differences between patients and normal subjects, nor between the 2 groups. At 48h,the group2 patients had a number/mm3 of cells CD57+significantly higher than both group 1 and control group(P<.05). In group 1 patients, the cytotoxic activity was similar to that of normal subjects, whereas in group 2 it was significantly increased, in respect to both the controls(P<.05) and group 1(P<.001). In all groups, the contact of the lymphocytes with the silicone extract did not modify either the antigen expression or the lymphocyte functional activity. On the basis of these results we hypothesize the involvement of the immune system in the formation of the capsular contractue around the prosthesis.

Message: 16

Please Post

Hi Pam,

We are so grateful you are doing this. We agree, it should be very beneficial to the younger women who are just recently discovering this travesty. For anyone who does not have a computer, or can't print these out, we will be happy to send them a complete copy of all these document, for a minimal $10 donation to cover cost of printing & mailing. All donations to the National Silicone Implant Foundation (NSIF) is tax deductible!

Many thanks to you, Pam,

Martha Murdock, Director

Karen Lawrence, President

National Silicone Implant Foundation

Dallas Headquarters

-----Original Message-----

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

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Message: 17

With Governor Wilson putting tort reform at the top of his agenda, some highprofile rhetoric about litigation issues will probably be in the headlines in the months ahead. The following checklist is provided so that members will have facts ready to refute incorrect and irresponsible claims.

The 1994 Annual Report of the Judicial Council shows that since the peak year of 1987 personal injury and wrongful death filings in the Superior Court have dropped to all time lows. Case filings plummeted from 137,379 cases in 1987 to 88,346 cases in 1993, even though during the same period our states population grew from 27.8 million to 31.5 million. On a per capita basis filings of personal injury and wrongful death cases have dropped 43 percent in six years.

1993 civil filings for personal injuries resulting from motor vehicle accidents dropped 24 percent in just one year. (1994 Annual Report of the Judicial Council.)

Products liability amount to only about 4 percent of tort cases filed in state courts nationwide, about 40,000 cases. (Brian J. Ostrum et al., State Court Caseload Statistics: Annual Report 1992, at 16.)

Over 21,000 deaths and 28 million injuries nationwide are reported annually arising from consumer products. (Consumer Product Safety Commission, November 8, 1994.)

During the past 25 years, there have been only about 355 punitive damage verdicts nationwide in all products liability cases. Yet, the risk of punitive damages is a major force in inducing investment in safety and deterring unsafe behavior. (Michael Rustad, Demystifying Punitive Damages in Products Liability Cases: A Survey of a Quarter of a Century of Trial Verdicts 2627 (Roscoe Pound Foundation 1992).)

Punitive damage awards in medical malpractice cases are rare: only 265 between 1963 and 1993 nationwide. Most involve egregious behavior such as sexual assault or deliberate injury. (Thomas Koenig and Michael Rustad, His and Her Tort Reform: Gender Injustice in Disguise 85 (1994).)

California already has the tough "clear and convincing" standard for proving punitive damages that is proposed in the Contract with America. Between 1981 and 1987, before the clear and convincing standard, only 6.4 percent of successful civil verdicts included punitive damages awards. (Myth and Reality in Punitive Damages, S. Daniels, 75 Minn. Law Review 1 (1990).)

One of the largest property casualty insurers in the United States said that "any abuses of the contingent fee system are best addressed through marketplace solutions (full disclosure to potential clients of the hours likely to be spent on a case, probability of success, probable recovery, and alternative fee arrangements) and when necessary, reduction of excessive fees by the courts. We do not support regulating fees." (Judith W. Pendall, Vice President of Aetna Insurance Company, Letter to the Editor, N.Y. TIMES, Mar. 11, 1994.)

Clients know that contingent fees are their keys to the courthouse. No limits on fees or requirements for disclosure have ever been proposed by "reformers" for fees incurred by the defense.

No-fault does not reduce auto premiums. Indeed, states with no-fault systems that limit compensation for pain and suffering saw their liability rates increase an average of 30.9 percent between 1989-92, an average of over 10 percent per year. Contrast that to non no-fault states that saw an average increase of just over 7 percent per year. (National Association of Insurance Commissioners, State Average Expenditures &amp; Premiums for Personal Automobile Insurance in 1992 (December 1993).)

Between 1989 and 1992, the six states that saw the greatest increase in auto liability premiums were all states that have some form of no-fault insurance: Hawaii, Texas, Michigan, Massachusetts, Kentucy and Delaware. (Ibid.)

While the average liability premium for other states grew 20 percent since 1989, California's has dropped .02 percent. (Ibid.)

The economic cost of preventable death and injury in the United States is more than $399 billion annually. That figure does not take into account anguish and suffering. (National Safety Council, Accident Facts 2 (1993).)

Proponents of socalled "tort reform" are found in large corporations, the insurance industry, and the medical industry.

Americans live in the safest country in the world. They can protect their homes, their workplaces, and their environment through the civil justice system, which allows people to change unacceptable conduct for the better.

_______________

Portions of this article are reprinted with permission of the Advocate (February 1995). &#169; The Association of Trial Lawyers of America. Copyright 1995, 1996

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Message: 18

Abstract: Histologic Features Of Breast Capsules Reflect Surface Configuration And Composition Of Silicone Bag Implants.

Author: Kasper-Baylor Univ.Medical Center

Source: Am J. Clin. Pathol Nov.1994 Vol.102-Pgs. 655-659

Abstract: The fibrous capsules that develop around silicone gel breast implants may become excessively thickened and result in painful hardened breasts. This article examines the microscopic anatomy of 80 periprosthetic breast capsules removed during a 2-yr. period(1990-1992), and describes the histopathologic characteristics of capsules adjacent to the more recently modified implant types. Capsules were examined by routine light microscopy,with and without polarization. Several distinctive histologic patterns were recognized, and these unique patterns could be correlated with the implant type used. All capsules were lined by a cellular membrane resembling synovium. Capsules adjacent to smooth-surfaced implants were lined by an intact histiocytic membrane of uniform thickness. In contrast, the membrane adjacent to textured implants varied in thickness, and was disrupted along its length. In addition, the inner surface of capsules adjacent to textured implants was conspicuously festooned with small(.25-.5mm) knob-like projections that were not seen in capsules adjacent to smooth-surfaced implants. A variety of foreign materials also were observed either within or adjacent to the capsules, and included droplets of liquid silicone, irregular solid fragments of the bag envelope, geometric crystalline fragments of polyurethane, and talc. Thus, the microanatomic features of periprosthetic breast capsules reflect the composition and surface configuration of the corresponding silicone bag type.

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Message: 19

Abstract: Local Increase In Hyaluronic Acid and Interleukin 2 In The Capsules Surrounding Silicone Breast Implants.

Authors: Wells, Daniels, Gunasekaran Department of Internal Medicine, University of South Florida, College of Medicine, Tampa

Journal: Ann.Plast.Surg. - July 1994,Vol.33,Pgs.1-5

Abstract: Connective tissue disease-like illness has been associated with silicone breast implants. however, no data are currently available on the immunopathology of the capsule surrounding the breast implants. Sera from women with breast implants were collected and assayed for interleukin-6 (IL-6),IL-2, and hyaluronic acid. Capsular biopsies were stained with a probe for HYA or with monoclonal antibodies specific for human macrophages (CD68), T cells (CD4), IL-6, and IL-2. Control specimens consisted of breast biopsies from women undergoing reduction mammoplasty. Our results revealed an increased local amount of hyaluronic acid in the capsule of patients with breast implants compared with control breast tissue. 

The HYA was localized extracellularly in areas containing fibrosis and cellular infiltrates. The infiltrating cells were determined to be primarily macrophages and T cells. No IL-6 was localized in any of the tissue sections. In contrast, large amounts of IL-2 were found in regions of infiltrating lymphocytes. No significant increase in IL-6, IL-2, or hyaluronic acid was found in the sera. The role of hyaluronic acid and cytokines in the inflammatory response in the capsules of silicone breast implants is discussed.

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Message: 20

EVIDENCE OF IMMUNE REACTIONS IN BREAST IMPLANT PATIENTS

Despite the recent study published in the June 1994 issue of the New England Journal of Medicine suggesting that breast implants do not cause classical immune disease, research conducted by SBI Laboratories demonstrates that silicone breast implants can cause a non-classical, atypical autoimmune disease that would not be detected with standard rheumatologic tests.

"Because silicone syndrome is a new disease, it requires a new test to make its proper diagnosis," said Nir Kossovsky, M.D., silicone researcher and developer of a new test, the Detecsil Silicone Sensitivity Test. SBI Laboratories is offering the Detecsil test to help detect immune reactions in breast implant patients that cannot be found through standard tests such as those cited in the Mayo Clinic study.

SBI Laboratories has teamed with rheumatologists and other researchers who are studying the effects of silicone on a wide variety of people exposed to silicone in its gel, oil and particle formulations. In a recent sampling of more than 160 women with silicone breast implants, this research confirmed a high correlation between exposure to silicone and the presence of increased antibodies to collagen I, a protein that comprises up to 90 percent of skin, bone and tendon. This increase in antibodies may indicate an autoimmune reaction.

The Detecsil Silicone Sensitivity Test is based on the fact that silicone behaves like a vaccine, preparing the body against a "silicone invasion." According to Kossovsky, silicone is a tacky substance that sticks to the body's own molecules and in the process deforms the molecules, causing them to look like foreigners to the body's own immune system. The body may then engage in biological "friendly fire" against its own tissues, sometimes with deadly effect.

This phenomenon is further described by Kossovsky in the July 1994 issue of the American Medical Association's Archives of Pathology and Laboratory Medicine.

Based on 14 years of research on silicone surface reactions, Kossovsky says the process that occurs when native body molecules are exposed to silicone may account for non-specific symptoms experienced by many women with breast implants and explain why standard rheumatologic tests cannot make a proper diagnosis.<P>The Detecsil Silicone Sensitivity Test provides medical researchers with a highly accurate analysis of whether an individual has an immune response to silicone, and the degree of the response, as well as whether antibodies have been stimulated against native body molecules, including collagen I and III (bone, skin and tendon), fibrinogen (blood clotting protein), fibronectin (connective tissue), myelin (nerves), insulin and silicone.

According to SBI Laboratories President Beth Brandegee, "Detecsil is a highly accurate and reliable test that will help characterize silicone immunities and will determine the presence of silicone immune responses and possibly silicone-induced disease."

Detecsil is available for research use at $350 for each six-assay battery. A comprehensive analysis is provided to the researcher within 10 days of sample receipt. SBI Laboratories are located at 1401 Forbes Avenue, Suite 237, Pittsburgh, Pennsylvania 15219. For more information, call the silicone information line at (800) 766-6646.

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Message: 21

Abstract: Epidemiology of Silicone-Related Disease.

Author: Swan Department of Epidemiology,School of Public Health,

University of Cal.at Berkeley.

Source: Semin Arthritis Rheum. Aug.1994 Vol.24 - Pgs.38-43

Abstract: The epidemiology of silicone-related disease (SRD) is complicated by the variety of disease end points that have been associated with silicone exposure and the atypical nature of these diseases in silicone-exposed women. Current research reviewed here suggests that SRD may constitute a new disease entity, thus complicating disease definition and rendering studies of classic disease unlikely to detect risks of silicone exposure. This report addresses the most important study design issues (disease and exposure definitions, bias, confounding, and power) in the context of studies of SRD. The variety of silicones used complicates the definition of exposure for all studies, and for some populations simply determining who was implanted will be difficult. For any of these studies, inadequate patient follow-up is likely to underestimate disease risk. Studies of SRD are also complicated by confounding. That is, race, and other variables also related to rheumatoid and autoimmune disease. The absence of an appropriate control group also plaques published studies of silicone-related disease. Finally, inadequate sample size, resulting in studies of low statistical power, is a critical problem for rare diseases such as SRD. These points are illustrated using two published studies and 5 studies in progress.

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Message: 22

Self-reported Breast Implants and Connective-Tissue Diseases in Female Health Professionals

A Retrospective Cohort Study

Charles H. Hennekens, MD Dr PH; I-Man Lee, MBS, ScD, Nancy R. Cook, ScD. Patricia R. Heber; Ph.D.: Elizabeth W. Karlson, Md; Fran LaMott; JoAnn E. Manson, MD. DrPH; Julie E. Buring, ScD

Objective--To evaluate the association of breast implants with connective-tissue diseases.

Design and Participants--Retrospective cohort study of 395 543 female health professionals who completed mailed questionnaires for potential participation in the Women's Health Study. A total of 10,380 women reported breast implants and 11,805 reported connective-tissue diseases between 1962 and 1991. Cox proportional hazards regression models were used in analysis.

Results--Compared with women who did not report breast implants, the relative risk (RR) of the combined end point of any connective-tissue disease among those who reported breast implants

was 1.24 (95% confidence interval, 1.08 to 1.41, P=.0015). With respect to the individual diseases, the finding for other connective-tissue diseases (including mixed) was statistically significant (P=.017), the findings for rheumatoid arthritis, Sjogren's syndrome, dermatomyositis or polymyositis, or scleroderma were of borderline statistical significance (.05&lt;P&lt;.10), and the finding for systemic lupus erythematosus was not statistically significant (P=.44). There were no clear trends in RR with increasing duration of breast implants.

Conclusion--These self-reported data from female health professionals are compatible with prior reports from other cohort studies that excluded a large hazard, but do suggest small increased risks of connective-tissue diseases among women with breast implants. The very large sample size makes chance an unlikely explanation for the results but bias due to differential over reporting of connective-tissue diseases or selective participation by affected women with breast implants remains a plausible alternative explanation. The Major contribution of this and other observational analytic studies has been to exclude large risks of connective-tissue diseases following breast implants.

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Message: 23

For those of you who didn't know Walt, it is OK to use the documents I am sending out that came from the USSW site. Walt's site doesn't exist anymore and his partner was not able to keep it up. She lived over a thousand miles away and Walt's site had been on the server of one of his friends. Even if the documents go through here, they are not personal information and can be shared.

As I clean up more documents, I will send them out. I am almost finished with the first disk of them.

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Message: 25

STATE OF MICHIGAN

IN THE CIRCUIT COURT FOR THE COUNTY OF WAYNE

DOW CORNING CORPORATION, et al.,

Pealigned Plaintiffs, Case No.: 93-325789 CK

Hon. Robert J. Columbo, Jr.

vs.

HARTFORD ACCIDENT AND

INDEMNITY COMPANY, et al.,

Realigned Defendants.

AFFIDAVIT OF JAMES E. JENKINS

STATE OF MICHIGAN

COUNTY OF BAY

James E. Jenkins, being of full age and duly sworn, deposes and says:

1. I am Dow Corning Corporation's Vice-President, Secretary and General Counsel and have been General Counsel of Dow Corning since 1982. In my capacity as General Counsel, I am the chief legal officer of Dow Corning. I am an attorney and a member of the Michigan and Illinois Bars. I have personal knowledge of the facts set forth in this affidavit, and if called to testify in this matter, I could competently and truthfully testify concerning these facts.
2. In April, 1992, I attended an "Outside Counsel seminar" held at the Dallas/Fort Worth Hilton Hotel for Dow Corning's silicone breast implant defense counsel that was hosted by Dow Corning. At the seminar, I explained certain aspects of Dow Corning's generic defense efforts. Specifically, I explained that Dow Corning would be dedicating Greg Thiess and at least five other Dow Corning in-house lawyers to defend against silicone breast implant claims and that I would also be working on defending against breast implant claims. At the seminar, certain Dow Corning employees, including Dr. Robert LeViar, Paul Klykton, and Dr. Ralph Cook gave precaution on clinical, non-clinical, and epidemiological studies related to breast implants that Dow Corning and other entities were funding. It was explained that these studies were intended to be a centerpiece of Dow Corning's generic defense efforts.
3. In order to defend against silicone breast implant claims, Dow Corning funded or contributed funding to a number of internal and external studies which were intended to provide the epidemiological data necessary to defend against allegations of breast implant plaintiffs that their breast implants caused certain diseases. Many of the breast implant plaintiffs based their allegations on questions raised in the Food and Drug Administration pre market approval process for breast implants and subsequent inquiries. The studies also had the purpose of confirming with more recent studies matters brought into question during the criminal investigation brought by the Assistant U.S. Attorney, Baltimore, MD.

4.While one of Dow Corning's main purposes in funding internal and external scientific studies was to respond to the concerns to women who had breast implants, another major purpose of funding the studies, especially those recently funded, was to respond to allegations of breast implant plaintiffs. Each external scientific study that Dow Corning funded was only after consulting with legal counsel to determine its impact on the breast implant litigation.

5. Dow Corning withdrew from the breast implant business in 1992 and has no intention of re-entering that business. Dow Corning is seeking to recover from its insurers only those scientific research costs that Dow Corning incurred after Dow Corning withdrew from the silicone breast implant business. This research provides only of minimal benefit to Dow Corning in terms of research and development or product marketing largely because Dow Corning intends to never sell breast implant products again.

James E. Jenkins

Sworn to before me this ___ day of July, 1995.

Notary Public

My Commission Expires:

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Message: 26

SUPPRESSED NATURAL KILLER CELL ACTIVITY IN PATIENTS WITH SILICONE IMPLANTS: REVERSAL UPON EXPLANTATION BY:

ANDREW W, CAMPBELL, M.D., Clinical assistant professor, University of Texas Health Science Center, Medical Director, Center For Immune, Environmental and Toxic Disorders, Houston, Texas. NACHMAN BRAUTBAR, M.D., clinical Professor of Medicine, University of Southern California School of Medicine, Medical Director, Center for International Occupational and Toxicological Medicine, Los Angeles, California. ARISTO VOJDANI, PH.D., Associate Professor of Medicine, Drew University School of Medicine and Science, Department of Medicine and Dermatology, Director, Immunosciences Lab, Inc., Los Angeles, California. PUBLISHED, TOXICOLOGY AND INDUSTRIAL HEALTH 10: 3 MAY - JUNE 1994 Address all correspondence to:

Andrew W. Campbell, M.D.

14441 Memorial Drive, Suite 6

Houston, Texas 77079

Reprinted with the permission of Andrew W. Campbell, M.D.

SUPPRESSED NATURAL KILLER CELL ACTIVITY IN PATIENTS WITH SILICONE EXPLANTATION - ABSTRACT

We have previously shown that natural killer cell activity is significantly suppressed in patients with silicone breast implants. These patients were symptomatic and the suppression of natural killer cell activity was associated with additional significant immunological abnormalities. (1) Our studies have recently been confirmed by Srnith et al., (2) who described natural killer cell activity suppression following exposure to silicone gel. and reversal upon removal of the gel.

This study has been designed to evaluate the natural killer cell activities in symptomatic women with silicone breast implants after implantation and after the explantation of the implants. Each patient served as its own control. Our findings show a marked significant increase in previously suppressed natural killer cell activity. These findings are compatible with the recent studies in experimental animals, showing that administration of silicone reduces natural killer cell activity. and that this is reversible upon removal of silicone.

Since NK cells are important in the control of tumor cell growth we propose here that patients with reduced NK cell activity are at a higher risk of developing cancer. a notion recently described in experimental animals. (3 & 4) *Nachman Brautbar, M.D. to whom all communications should be addressed at: 2222 Ocean View Avenue, Los Angles. California 90057

NK cells are sensitive indicators of activation by biologic response modifiers, and their monitoring has been used to document alteration in the activity of circulating immune cells, Abnormalities in NK cell activities have also been described in Autoimmune Disorders. Most recently, NK cell activities have been shown to be affected in patients exposed to chemicals, and in patients with silicone breast implants.

Since the symptomatology of patients with silicone breast implants has been associated with multiple immunological abnormalities, including production of autoantibodies.(',',',') stimulation and suppression of T cells, (1) elevation of circulatory immune complexes, (1) and since the reversal of symptomology upon removal of the implants has been associated with reversal of the immunological abnormalities, (5 )it is logical to suggest that immunological marker, such as NK cell activity, will follow these patterns: Suppression as a result of exposure to silicone and reversal to normalization upon removal of the silicone. Indeed, our studies here support this notion and further support the concept of an immune response to silicone breast implants.

Forty women who underwent silicone breast implants and were evaluated for symptoms ranging from joint pain, muscle pain central nervous system symptomatology, skin rashes and myalgias (3) have been studied. Natural Killer cell activities were studied prior to the explantation and 3 to 15 months after explantation with an average of 8 months: +/- 1.2 S. E.

Separation of Human PBL Mononuclear cells from patients and controls were separated from the fresh whole blood by Ficoll-hypaque density gradient centrifugation (Litton Bionetics, Rockville, MD). The lymphocyte band at the interface was collected and cells pelleted by centrifugation, washed twice in RPMI- 1640 and suspended in complete medium, consisting of RPMI-1640 supplemented with 10)% human AB serum, 2mM glutamine, 25mM Hepes (pH 7.2), 50 units penicillin, and 50 units streptomycin per mi.

NK Cell Cytotoxicity Assay A modified (51)CR-release assay, as described previously, was employed. Briefly, 1X10(4) (51)Cr-labeled K562 target cells (New England Nuclear Corporation, Boston, MA) in 0. I mil CM were added per well in microliter plates. Effector cells were pipetted into quadruplicate wells to give effector:target cell ratios of 100: 1, 50: 1 and 25: 1. These cells were allowed to interact at 3 7degC for 4 hr in an atmosphere of 5% C02/95% air.

(51)Cr-release was determined by centrifuging the plates at 1000 x g for 5 min and harvesting 0.1 ml of the culture supernatant for counting gamma counter. Total release was determined by adding 100 ul of 1.0% Triton X-100 and spontaneous release by adding labeled target cells alone in CM.

The percent "Cr-release was determined by the experimental (R(e)), spontaneous (R(s)). and total (R(t)) release by the following formula: "Cr-release = (R(e)) - (R(s)) - x 100% (R(t))- (R(s))

Lytic units (LU) were calculated from effector titration curves, and (1)LU was defined as the number of effector cells required to achieve 20% lysis. LU/ 10(6) is the number of LU in 10(6) effector cells. For assay reproductability, recommended criteria were employed, Statistical analysis of significance utilized the paired + test and the difference of the means of the of the 2 groups studied.

Table I shows the individual values for natural killer cell activities prior to explantation and after explantation.

There was a marked and significant increase in natural killer cell activity after explantation. Natural killer cell activity was 27.00ñ3.0 (S.E.) Prior to explantation and 36.89+- 3,7 (S.E.) after explantation. The average age of implants was 9.5 years ñ 0.96. P value for the difference of the means between NK cell I and NK cell III was P<0.032.

Previous studies reported from our laboratory have shown a significant and marked reduction of natural killer cell activities in patients with silicone breast implants. (1) This reduction was attributed to direct effect by silicone through activation of cellular or humoral mechanisms secondary to an immune response to adjuvant effects of silicone.

The following functions have been ascribed to natural killer cells:

1) control of tumor cell growth

2) involvement in the control of microbial infections,

3) immunoregulatory properties

4) involvement in the development of graft versus host disease,

5) contributes to the development of some forms of diabetes, and

6) involvement in various gastrointestinal diseases. (7) Natural killer cells mediate a non-major histocompatibility complex with restricted killing against target cells, which are termed "NK susceptible. " This lytic activity can be observed against a variety of neoplastic and viral-infected cells in non-major histocompatibility complex restricted function. Inhibition of natural killer cell activity has been described using prostaglandin A and E glucocorticoids and prolactin as well as luteinizing hormone. Exposure of murine or human natural killer cells to agents such as anti-asialo-GNfl or Prostaglandins induce dose-response suppression. Other cellular mechanisms have been described in association with suppression of natural killer cells, including suppressor cells, which play a physiological role in regulation of NK cell activity in vivo. Most recently, exposure to orgarfic solvents has been shown to cause suppression of NK cell activity and stimulation of several autoantibodies. (8) Our findings here show that the suppressed activity of the natural killer cells is reversed and improved markedly upon removal of the silicone implants, indicating that the direct or indirect effect of the silicone breast implants, which caused suppression of natural killer cell activities, has been eliminated by removal of the silicone, the causative agent. This was not correlated with the length of implantation which ranged anywhere from 0.6 to 16 years with an average of 9.5 +- 0.96 years, nor was this correlated with the length of time period from the explantation.

Our studies here are in agreement with the studies reported recently by Smith et al., (2) which reported in rats implanted with silicone gel a marked reduction, in natural killer cell activity, and reversal of this suppression immediately following removal of the implants.

Our studies here demonstrate clearly that symptomatic patients with silicone breast implants significantly are associated with a marked reduction of natural killer cell activity, and that this reduction is improved upon removal of the silicone breast implants. The issue of cancer development in patients with silicone breast implants has not been addressed at the molecular level, nor has it been addressed at the clinical level.

Recent studies (9) have shown carcinogenicity of silicone in experimental animals. Indeed, these studies were followed by an editorial calling for epidemiological studies in patients with silicone breast implants to further evaluate the incidence of hematological malignancy.(10) These investigators did not measure natural killer cell activities in these studies, however, based on our clinical studies here, and on the experimental studies by Smith et al, (2) it is strongly suggested that one mechanism contributing to the carcinogenicity is the reduced activity or inhibition of natural killer cells. The actual mechanisms by which silicone inhibits NK cell activity is not clear. Additional studies at the molecular level are required to further understand the mechanism of suppression of NK cell activity by silicone.

Our studies described here indicate that silicone does inhibit the functions of natural killer cell activities and that this inhibition is reversible, however, may be associated with reduction of ability to control tumor cells, and in those patients who have chronic reduction of natural killer cell activity, may be associated with carcinogenicy. We propose clinical studies to find the incidence of cancers in patients with silicone breast implants.

1. Vojdani A, Campbell A, Brautbar N Immune Functional Impairment in Patients with Clinical Abnormalities and Silicone Breast Implants. Toxicology and Industrial Health 1992; 8;415-429.

2. Smith SD, Gerber DC, Butterworth LF, McCay JA, White KL, Munson AE. Natural Killer Cell Activity is Suppressed Following Exposure to Silicone Gel. Society of Toxicology. Dallas, 03/1994.

3. Kumagai Y, Shiokawa Y, Medsger TA, Jr., Rodnan GP. Clinical Spectrum of Connective Tissue Disease After Cosmetic Surgery. Arthritis and Rheumatism, 1984;2791:9-12,

4. Weiner SR, Clements PJ, Paulus HH. Connective Tissue Disease After Augmentation mammoplasty. Arthritis and Rheumatism, 1989; 23:23-24.

5. Kaiser W, Biesenbach G, Stubby U, Graffinger P, Zazgomik J. Human Adjuvant Disease: Remission of Silicone-Induced Disease After Explantation of Breast Augmentation. European Journal of Surgical Oncology 1990; 16:468-69.

6. Bridges AJ, Connelly C, Wong G, Bums DE, Vassey FB. A Clinical and Immunological Evaluation of Women with Silicone Breast Implants and Symptoms of Rheumatic Disease. Annals of Internal Medicine, 1993; 118:929-36.

7. Lewis, C.E. McGee, J.O.D. Editors. The Natural Killer Cell. Department of Pathology and Bacteriology, University of Oxford, IRL Press, Oxford University Press, 1992- Page 7.

8. VOJDANI A, Ghoneum M, Brautbar N. Immune Alteration Associated with no Exposure to Toxic Chemicals. Toxicology and Industrial Health. 1992; 8:231-246.

9. Potter, M., Morrison, S., Weiner, F., Zhang, K.K., Miller, F.W., Journal of National Cancer Institute, 1986-) (14) July 7/20/94.

10. Salmon; S.E., Kyle, RA.. Silicone gels, induction of plasma cell tumors, and genetic susceptibility in mice: A call for epidemiological investigation of women with silicone breast implants. Journal of National Cancer Institute. 86; 14, July 1994.