article on study for implants

[Guest guest]

HOME SUPPORT GREATLINKS QUACK LIBEL VICTORY DEFAMATION CASE

PUBLIÇATIONS DAILY NEWS

CITIZEN PETITION

November 18, 2003

Dockets Management Branch

Food and Drug Administration

Department of Health and Human Services, Rm 1061

5630 Fishers Lane

Rockville, MD. 20852

FAX 301/827-6870

Re: Silicone Gel-filled Breast Implants

The undersigned submits this petition under 21 C.F.R. 10.35 to

request

that the Commissioner of the Food and Drug Administration (FDA) delay

approval of any and all Premarket Applications ( " PMAs " ) for silicone

gel-filled breast implants (SGFBIs) until additional valid long-term

scientific data is collected. We request that in accordance to 21

C.F.R. 14.7, the Commissioner expedite the review of this petition

and

make a reasonable effort to render a decision before the action

concerned in the petition is finalized. In addition to the conditions

agreed upon by Inamed, we request that the following conditions be

met:

A. Action Requested

1. We request that the FDA require long-term research (age-matched to

core study participants in a control group) regarding symptoms

including, but not limited to, the following: muscle, joint,

neurological (including depression), muscle pain, joint pain, morning

stiffness, fatigue, and generalized pain. This study should be funded

by Inamed but conducted and reviewed by an independent third party.

The third party must be independent of plastic surgeons as well as

all

companies manufacturing breast implants.

2. We request that platinum (including valence) testing and

measurements be conducted in connective tissue (scar capsule tissue)

and explants in a retrieval study. Included in this platinum study

would be chemical and metal sensitization studies of women who have

reported leaking or ruptured implants where platinum has been used as

the catalyst in the manufacturing process.

3. We request that the FDA require a breast-milk study using

appropriate measurements of low molecular weight silicone,

particulate

debris, heavy metals, and cytokine levels to determine safety of

breast milk from implanted mothers versus controls. This study should

be funded by Inamed but conducted and reviewed by an independent

third

party.

4. We request in-vivo and in-vitro testing for biological responses

to

silicone elastomer particles, less than 10 micrometers in size. This

testing is needed to determine a cellular response to particulate

debris in a retrieval study, which should include monocyte,

macrophage

and fibroblast responses.

5. We request that blood be drawn on an annual basis from all women

in

the Inamed core study. This blood should be tested for natural killer

cell counts and for inflammatory and anti-inflammatory cytokine

levels. This blood should then be stored for future research.

6. We request that the expected serviceable life of the implant while

in the human body be determined and stated in the informed consent

along with the expected shelf life.

B. Statement of Grounds

• The General and Plastic Surgery Devices Panel of the Medical

Devices

Advisory Committee voted 9-6 to approve Inamed's SGFBIs, with

conditions. This panel included four plastic surgeons – one with a

stated conflict of interest – and two breast surgeons. While plastic

surgeons should be included on the panel for their expertise, they

should be excluded from voting, as they or their colleagues will

financially benefit if the device is approved.

• One member of the panel stated she decided to vote for approval

after she heard Inamed's summation, proposal of conditions for

approval, and commitment to follow-up. Unfortunately, the best

predictor of future behavior is past behavior. In Inamed's " Adjunct "

study of reconstruction patients barely half stayed in the study for

one year and even fewer (27%) stayed for three years. The revision

patients were even less likely to stay in the study. Less than half

(44%) stayed in the study for one year and only one in five (20%)

stayed for three years. Inamed had only a 57% rate of follow-up for

reconstruction patients after approval of their saline-filled breast

implants was obtained. Their follow-up for augmentation patients was

only 62%. Neither is high enough to assure adequate follow-up at ten

years, as the FDA has required. Manufacturers have shown time and

again that they have no incentive or motivation on follow-up.

• Some members of the panel voiced " shock " that only one, two and

three years of data were provided for consideration. Inamed stated on

October 14, 2003 that the implants under review had been used for ten

years in the U.S. and for twenty-five years in Europe. Even after

this amount of time Inamed still has not been able to provide studies

showing long-term implant safety. This is a red flag and raises

questions of caution and concern.

• In 1992, the FDA announced its decision to allow SGFBIs on the

market only under controlled clinical studies for reconstruction

after

mastectomy, correction of congenital deformities, or replacement of

ruptured SGFBIs due to medical or surgical reasons. Until these

clinical studies could be submitted and reviewed, the FDA authorized

temporary and limited distribution of silicone gel-filled implants

for

reconstructive patients on an urgent need basis, with a very detailed

informed consent form.

• The FDA denied applications for using SGFBIs for augmentation but

planned that the manufacturers would later conduct clinical trials

that would include a limited number of augmentation patients (the

core

studies).

• On July 24, 1992, the FDA approved Mentor Corporation's Stage 2,

Adjunct Study protocol for silicone gel-filled implants for

reconstruction and revision only. A memo (attached as Exhibit A)

dated 9/25/92 from St. 's Regional Health Center, Springfield,

Missouri to the Institutional Review Committee (IRC) members

regarding

the " Mentor Adjunct Study of Silicone Gel Breast Implants " makes the

following statements:

" Our subcommittee had a number of concerns about

the design of this study and the consent form. The protocol did

not appear to us to be a `research study' in any familiar sense of

that

term.

a) There is no accrual goal. The study is simply open for five years

to any women who qualify. Participants are to be followed for five

years.

There are few exclusion criteria.

c) Inclusion criteria are very subjective and general.

The consent form omitted a good deal of information that we believed

should be revealed. In one section we found an outright error (when

compared to information given in the protocol itself). Tobias Meeker

called Dr. Grant Bagley of the FDA…Dr. Bagley represented `the

clinical point of view' for the FDA team…A National Advisory

Commission (NAC) was formed to review the status of silicone breast

implants. The NAC recommended that a PMA should be required for

marketing of silicone gel- filled breast implants. But the NAC also

states that these devices should continue to be widely available to

persons in unusual circumstances who would have medical need for

them. To this end, the commission recommended that there be a limited

core study that would be quite controlled and an adjunct study that

would make the devices widely available (since not everyone with

medical need – due to location or whatever

– would be able to qualify for a traditional clinical trial.)

The Mentor `study' is designed to serve this latter purposes. Dr.

Bagley

said of this protocol: `It is an administrative device to continue

to make these

devices widely available to those who have such need that the lack of

established safety can be over- looked if there is a good informed

consent

process and the oversight of an IRC…One of the surgeons who hopes

to do these procedures met with us… His understanding that

this protocol was designed `to give the illusion of a study' so that

the devices could remain on the market…We feel that we are being

asked to

rubber-stamp a political solution to this highly politicized

issue. This `study' will recklessly put many women at risk. Asking

IRCs to behave in this manner violates their mandate and calls into

question their integrity. It appears to us that the FDA has lost

its objectivity. "

• On 11/4/92, Tobias Meeker, Director, Ethics Program at St. 's

sent a letter ( Exhibit to Kessler, M.D., Director,

FDA expressing his concerns regarding Mentor's adjunct study. He

reiterates many of his grave concerns expressed in the above memo

including the following:

" A woman could simply report to a surgeon that she didn't

like the appearance of her breasts due to say – ptosis – and

medically

`qualify' to have reconstruction with silicone gel…We realize that

many plastic

surgeons have firm convictions that the silicone poses no health

risk.

We respect their convictions, but point out that strong convictions

do not

constitute scientific evidence…FDA has concluded that women who

desire breast

augmentation are at higher risk than patients with breast cancer who

have had a mastectomy

Unlike patients who have undergone mastectomy, they still

have breast tissue and the presence of an implant complicates the

use of

mammography for the detection of breast cancer. In the end, it comes

down to

this: In our opinion the risk-benefit ratio does not at this time

favor the

unrestricted use of silicone breast implants in healthy women. The

design of the

Mentor adjunct study belies the concerns you (Dr. Kessler)

expressed. This

study makes these devices widely available to women who have not had

mastectomies. If women are to be offered these implants outside of

scientifically valid studies, we believe this offer should be

restricted to the present

`urgent need' population…To assume that a good consent process (with

IRC

oversight) will protect subjects from unjustified risks strikes us

as a faulty

assumption. This im plant is a product with unproven safety and

demonstrated

(but unproven) risks. Further, we are concerned that misrepresenting

this

`administrative device' as a legitimate scientific study misleads

potential

recipients, making it more difficult for them to assess risk. "

• We believe the same agreement was made with McGhan (now Inamed

Corporation). Many plastic surgeons have built their own outpatient

surgical facilities to circumvent the concerns expressed by the

Institutional Review Committee in the above memo and letter. We

request, as consumers, a more detailed explanation of the FDA's

design

and approval of the AR-90 and adjunct study to determine long term

risk in light of the above memo and letter. We request, as consumers,

to know why we do not have ten or more years of data from a well

designed clinical study to determine long term risk for

reconstruction

and revision patients. According to Inamed's documents, their 5-year

adjunct study for reconstruction patients started on 11/25/97 and

ended 8/22/02 with a follow-up compliance of 27% at 3 years. We

request, as consumers, to know why the follow-up of the adjunct study

by Inamed had such low compliance rates to thereby, render the data

useless. Consumers can only have true informed consent when they know

the risks they can expect and are willing to accept. Two or three

years of data are inadequate to determine risk for a device that will

be implanted and not removed until suspected of being ruptured.

• When silicone gel-filled devices are implanted into young woman of

childbearing age, they can possibly pass chemicals such as

low-molecular weight silicone, degradation particles, and ionized

platinum to children born after implantation either through the

placental barrier or in breast-milk. Research by Holten et al., 1995

documents a case report (attached as Exhibit C) in which silicone

accumulated in the lactiferous ductal system of the breast with the

underlying prostheses being intact. It demonstrated the disconcerting

potential of silicone to migrate through tissue planes that were not

disrupted. Inamed currently states on their website regarding

breast-feeding and children " A woman with breast implants who has

questions about risks while pregnant or breast feeding should consult

her physician. " Until the proper testing is conducted on breast-milk

from implanted women and the long-term clinical studies are

completed,

it is impossible for a physician to advise a pregnant woman with

implants on risks.

• Some members of the panel expressed " alarm " that all symptoms

including muscle, joint, neurological, muscle pain, joint pain,

morning stiffness, fatigue, and generalized pain increased after only

two years of implantation. The panel did not have a control group of

age-matched women (other plastic surgery patients without any type of

implant) and in the general population to determine the significance

of this data. Therefore before these devices are approved, we request

a study control group to be evaluated yearly. We request that this

study be funded by Inamed but conducted and reviewed by an

independent

third party. Depression should be added to this list of symptoms in

light of three studies indicating a three-fold increased rate of

suicide by breast implanted women – Brinton et al., 2001 (Exhibit D),

Koot et al., 2003 (Exhibit E), and Pukkala et al., 2003 (Exhibit F).

• At the hearings the FDA admitted the issue regarding systemic

disease and mixed connective tissue disease in implanted patients has

still not been resolved.

• In U. S. patent number 6,251,137 (Exhibit G) filed 6/26/01 by

McGhan

(now Inamed) it states: " Silicone filled implants typically comprise

about 10-20% cross-linked silicone which forms an interconnected

`sponge' in the implant with the remainder of the filler material

being low molecular weight silicone oil…adverse medical consequences

have recently become associated with the use of silicone gel filled

implants because it has been discovered that the silicone oil can

migrate through the implant shell and the silicone oil is not

biocompatible with other human tissues " . This information presents

grave unknown safety risks.

• In 1999, research from Teuber, et al., (Exhibit H)

states: " Silicone

gel once it leaves the implant is not biologically inert and in some

persons can elicit profound pathogenic responses…an unexplained

change

in the chemical composition of the implanted silicone gel, rendering

it more fluid-like, may have increased its propensity to migrate

locally. Unfortunately, little research has been performed on

biodegradation of silicone in the body, although there is evidence

that this may occur…the implants and extractable gel/fluid were sent

to the manufacturer (McGhan Medical Corporation, Santa Barbara, CA,

USA) for analysis, but no information is available on the results of

the analysis to determine if the ratio of polymer chain length had

shifted…the relentless inflammatory response against widespread

silicone has already resulted in the near total loss of function of

the hand…no doubt can remain that silicone can induce severe,

devastating local inflammation. " Breast implant manufacturers have

known since 1978 about potential migration of silicone gel when

research reported by Capozzi et al., (Exhibit I) documented that thin

gel had migrated through subcutaneous planes as far as the groin from

a ruptured breast implant.

• Inamed reported 30 days after implantation, 0.06% of radio labeled

gel left the implant site. At the hearing, one of the members of the

panel made the observation that Inamed reported in their retrieval

collections none of the implants lost more than 5 grams of material.

The member of the panel stated: " In orthopedics, a half a gram

would cause osteolysis in the same time period, so 5 grams is

actually

a `whopping' amount of material. " He further stated: " If you had 5

grams distributed kind of uniformly rather than in a lump, it

possibly

could be missed in visual observation by the explanting surgeon. " In

orthopedics and joint replacement, the most biologically active

particles are ones that cannot be seen visually. Since 1995 the scope

of wear-related problems in orthopedics has expanded to include not

only the local effects of debris but also systemic distribution and

effects, as reported in the book " Implant Wear: in Total Joint

Replacement " . According to the authors, both implants and the wear

debris they generate are thought to release chemically active metal

ions. The inflammatory response to metallic and polymeric debris in

lymph nodes has been found to include immune activation of

macrophages

and associated production of cytokines. Before approval of this

device, consumers need to know how much gel can be predicted to leave

the implant site after ten or more years of implantation or after

rupture. Sam Arepalli, PhD., FDA Chemist, stated that even with a

barrier layer you could not completely eliminate bleed of the gel

from

an implant. There is presently no way to remove the gel, particle

debris, and platinum after it has spread to all parts of the body.

• One of the members of the panel expressed his concern that there

seemed to be a disconnect between Inamed's testing showing how

difficult it was to rupture a new implant and what actually happens

in

the body. This disconnect could be explained by 1998 research by

, et al, (Exhibit J) which found: " Ninety-eight percent of

implants and other previously implanted silicone devices were found

to

have evidence of lipid infiltration…We conclude that lipids

infiltrate

the outer silicone shell and may be a factor related to breast

implant

aging and rupture due to progressive mechanical weakening of the

outer

silicone shell. " This disconnect might also be explained by the 1995

research by Tang, et al., (Exhibit K) which made the following

conclusion: " Chronic inflammatory processes, in many cases in

response to fragments of implanted biomaterials, may cause implant

failure…In some instances, material-mediated inflammatory responses

may even cause degradation of the material itself (via oxidative

products released by implant-associated inflammatory cells). " Before

approval is given, Inamed should be required to conduct testing on

explanted devices to determine if lipid infiltrates have weakened the

shell strength, if chronic inflammatory processes have caused

degradation of the material, or determine a logical explanation of

rupture rates.

• We, as consumers, do not detect any real progress and request the

FDA to inform us on the status of the research as recommended by the

Institute Of Medicine (IOM) after a review of the safety of silicone

breast implants in 1999. The IOM made the following recommendations:

1. " Reliable techniques for the measuring of silicone concentration

in

body fluids and tissues are needed to provide established, agreed-

upon

values and ranges of silicone concentrations in body fluids and

tissues with or without exposure to silicone from an implanted

medical

device. Such developments could improve the study of silicones and

silicone distribution in humans, could help with regulatory

requirements, and might in some circumstances resolve questions by

providing quantitative data on the presence or absence of silicones.

2. Ongoing surveillance or recipients of silicone breast implants

should be carried out for representative groups of women, including

long-term outcomes and local complications, with attention to, or

definition of the following:

• Implant physical and chemical characteristics,

• Tracking identified individual implants,

• Using appropriate, standardized, and validated technologies for

detecting and defining outcomes,

• Carrying out associated toxicology studies by standards consistent

with accepted toxicological standards for other devices; and

• Ensuring representative samples, appropriate controls and

randomization in any specific studies, as required by good

experimental design.

3. The development of a national model of informed consent for women

undergoing

breast implantation should be encouraged, and the continuing

effectiveness of such

a model should be monitored "

• The FDA guidance document (Exhibit L) makes the following

statement:

" …for the metal used as the catalyst in the curing reaction, you

should provide the valence state and the amount of residue of the

catalyst. " We request an explanation as to why the valence state of

the platinum catalyst at the time of manufacture was not provided by

Inamed. Dow notified the EPA (Exhibit M) on 12/27/96 of substantial

risk to their 3-8015 Intermediate Platinum #2 used as a catalyst in

making breast implants. This notification was the result of skin

sensitization studies. Please advise if Inamed uses Dow 3-8015

Intermediate Platinum #2 as a catalyst in making the breast implants

under current review. If not, please explain in detail the catalyst

used and the safety data provided, as no published research is

available.

• Recent German research by Flassbeck, et al, 2003 (Exhibit N)

" Determination of Siloxanes, Silicon, and Platinum in Tissues of

Women

with Silicone Gel-filled Implants " demonstrates that for the first

time in published research, platinum leaks from intact prostheses and

accumulates in a lipid-rich medium analogous to fat tissue or fibrous

tissue in humans. Further this research clearly demonstrates elevated

levels of the siloxanes D4-D6 in fatty tissue of a woman with a

" bleeding " implant. The data from this work clearly show that the use

of elemental silicon as an indicator of migration from breast

implants

to the surrounding tissue is not appropriate. In the FDA's letter

(Exhibit O) dated 3/30/01 in response to my petition (Docket Number

00P-16-7/CP-1 Exhibit P) it quoted from the IOM's review of the

potential toxicity of silicon and stated: " …there is ample evidence

that infants breast-fed by mothers with silicone breast implants

receive no higher silicon intakes than infants breast-fed by mothers

without breast implants. Infants receiving cow's milk or commercial

infant formula feedings are likely to have higher silicon intakes

than

breast-fed infants. " The independent research by Flassbeck

demonstrates that the Dow funded, Semple, et al., 1998 (Exhibit Q)

study of elemental silicon is not an appropriate measurement to

determine safety of breast-milk from implanted mothers.

• In the FDA's letter to CANDO dated 3/30/01 it stated: " The supplier

of the platinum catalyst used to manufacture breast implants, and

scientist who have studied the chemistry of these catalyst, have

recently assured the FDA that chloroplatinic acid is consumed during

the formation of these catalysts and is not present in the materials

used to produce the implants. " Inamed's data of metal analysis found

the following: Shell Pt (3.3 PPM), Patch Pt (2.6 PPM), and Gel (4

PPM). With the Flassbeck research (2003) data showing platinum

accumulating in human tissues, with the Maharaj research data showing

significant platinum found in connective tissue of implanted women,

and with the data presented to the FDA (Exhibit R) from Ernest

Lykissa, Ph.D. suggestive that ionic platinum in various oxidation

states may be present in explanted devices, it becomes imperative

that

the FDA require Inamed to quantify the amount of platinum and the

valence state in explants, fluids, and tissues in a retrieval study.

Platinum is listed as a suspected respitory, neurological, immune,

and

organ toxicant. Chloroplatinic acid is one of the most

hypersensitizing agents known to man. Before approval is given for

implantation of young women of childbearing age, Inamed and the FDA

should determine if the platinum used in breast implants reverts back

to its original form, at any time, after implantation.

• Naidu, et al., (Exhibit S) in 1996 research concluded that an acute

in vivo inflammatory response to silicone elastomer particulate

debris

is particle-type specific and that silicone elastomer particles are

acutely inflammatory. Because of concern over well documented

" particle disease or chronic inflammatory syndrome " the following

questions need to be answered before approval is given:

1. How does silicone elastomer and gel age and degrade inside the

body?

2. How does the chemical composition of the shell or gel change

during

any stage of the degradation process?

3. What size and how many elastomer particles can be generated inside

the body in five or ten years?

4. Does absorption of silicone fluid and body fats by the elastomer

shell weaken and accelerate degradation and breakdown of the

elastomer

shell?

5. Can these particles further physically degrade into smaller and

more reactive particles inside the body?

6. Can monocytes, macrophages and fibroblasts become activated,

inside

the body, when they ingest silicone elastomer particles and/or

silicone fluid or gel droplets from silicone gel-filled breast

implant

and their shells?

7. Can macrophages synthesize and release inflammatory and

anti-inflammatory cytokines, inside the body, after they ingest

silicone elastomer from the implant shell?

• The FDA stated that the finding of excesses of cancer including

lung

(or respiratory), cervical, vulvar, and leukemia in implanted women

have been reported in more than one study. Inamed currently states on

their website under cancer risks " At this time, there is no

scientific

evidence that women with silicone breast implants are more

susceptible

to cancer than other women. " We believe this is inaccurate and

misleading.

• Inamed reported a diagnosed rupture rate of 4.7% for breast cancer

reconstruction patients, 2.2% for revision patients, and 1% for

augmentation patients. The FDA assumed the rupture rate was higher

than reported, since most of the data was based on the first MRI

screening at 1 year and only 29% of the core group had an MRI.

Augmentation and revision patients may lose all of their natural

breast tissue if silicone from ruptured implants has to be scraped

out

of the tissues as reported by Rose Ferrelli (Exhibit T) at

the

hearings. This presents an unacceptable outcome with high patient

dissatisfaction.

C. Conclusion

For the above stated reasons, the Commissioner should delay the

approval of any and all PMA's for SGFBIs until rupture rates and

long-term risk has been ascertained and the conditions stated above

have been met.

D. Environmental Impact

This petition qualifies for categorical exemption under 21 C.F.R.

25.15, 25.30-32 from the preparation of an environmental assessment.

E. Economic Impact

A statement of the economic effect of the petition will be submitted

if deemed necessary by the Commissioner.

F. Certification

The undersigned certifies that, to the best knowledge and belief of

the undersigned, this petition includes all information and views on

which the petition relies, and that it includes representative data

and information known to the petitioner that are unfavorable to the

petition.

Keeling, President

Chemically Associated Neurological Disorders

P. O. Box 682633

Houston, Texas 77268-2633

281/444-0662

281/444-5468 FAX

keeling.m@...

Exhibits

Exhibit A:

Memo from St. 's Regional Health Center, Springfield, Missouri to

the Institutional Review Committee (IRC) members regarding

the " Mentor

Adjunct Study of Silicone Gel Breast Implants " .

Exhibit B:

Letter dated 11-4-92 to Kessler, M.D. Director, FDA from Tobias

Meeker, Director, Ethics Program at St. 's Regional Health

Center,

Springfield, Missouri

Exhibit C:

Holten, IW, Barnett, RA. Intraductal Migration of Silicone from

Intact Gel Breast Prostheses. Plast Reconstr Surg 1995 Mar; 95 (3):

563-6 PMID 7870784

Exhibit D:

Brinton, LA, Lubin, JH, Burich, MC, Colton, T, Hoover, RN. Mortality

among Augmentation Mammoplasty Patients. Epidemiology 2001;12:

321-326

Exhibit E:

Koot, VCM, Peeters, PHM, Granath, DE, Nyren, O. Total and cause

specific mortality among Swedish women with cosmetic breast implants:

prospective study. BMJ 2993; 326: 527-8

Exhibit F:

Pukkala, E, Kulmala, I, Hovi, SL, Hemminki, E, Keskimaki, I,

Lipworth,

L, Buice, JD, McLaughlin, JK. Causes of Death Among Finnish Women

with

Cosmetic Breast Implants, 1971-2001. Ann Plast Surg 2003;51: 339-342

Exhibit G:

U. S. Patent number 6,251,137 filed 6/26/01 by McGhan (now Inamed

Corporation)

Exhibit H:

Teuber, SS, Reilly, DA, Howell, L, Oide, C, Gershwin, ME. Severe

Migratory Granulomatous Reactions to Silicone Gel in 3 Patients. J

Rheumatol 1999;26: 699-704

Exhibit I:

Capozzi, A, Dubou, R, Pennisi, VR. Distant Migration of Silicone Gel

from a Ruptured Breast Implant. Plast Reconstr Surg 1978 Aug; 62 (2)

302-3 PMID 353852

Exhibit J:

, WP Jr, JB jr, Rohrich RJ. Lipid Infiltrations as a

Possible Biologic Cause of Silicone Gel Breast Implant Aging. Plast

Reconstr Surg 1998 Jan; 101 (1): 64-8 PMID 9427917

Exhibit K:

Tang, L, Eaton, JW. Inflammatory Responses to Biomaterials. Am J.

Clin Pathol 1995 Apr; 103-4 PMID 7726145

Exhibit L:

Guidance for Saline, Silicone Gel, and Alternative Breast Implants;

Guidance for Industry and FDA.

Exhibit M:

Dow Corning letter dated 12/27/96 to U. S. Environmental Protection

Agency. Dow Corning letter to FDA dated 1/28/97 in compliance with

the Toxic Substances and Control Act. Agenda for Dow Corning/ FDA

meeting 3/18/97. Dow Corning Mammary Implant Material Formulation

(includes chloroplatinic acid 3-8015 INT PLATNM2).

Exhibit N:

Flassbeck, D, Pfleiderer, B, Klemens, P, Heumann, KG, Eltze, E,

Hirner, AV. Determination of siloxanes, silicon, and platinum in

tissues of women with silicone gel-filled implants. Anal Bioanal Chem

2003;375: 356-362

Exhibit O:

FDA letter dated 3/30/01 in response to Chemically Associated

Neurological Disorders (CANDO) petition Docket Number OOP-1607/CP-1

filed 11/7/00

Exhibit P:

CANDO petition Docket Number OOP-1607/CP-1 filed 11/7/00

Exhibit Q:

Semple, JL, Lugowski, SJ, Baines, CJ, , DC, McHugh, A. Breast

Milk Contamination and Silicone Implants: Preliminary Results Using

Silicon as a Proxy Measurement for Silicone. Plast Reconstr Surg

1998;102: 528-532

Exhibit R:

Lykissa, E. Speciation of Platinum in Whole Blood Samples Compared to

Speciation of Platinum Released From Subject's Implant. Platinum in

Samples of Women with Silicone Gel-filled or Silicone Saline Implants

and Their Children.

Exhibit S:

Naidu, SH, Beredjiklain, P, Adler, L, Bord, FW Jr, Baker, DG. In Vivo

Inflammatory Response to Silicone Elastomer Particulate Debris. J

Hand Surg (Am) 1996 May; 21 (3): 496-500 PMID 8724486

Exhibit T:

Statement at 10/14/03 FDA hearing by Rose Ferrelli

Other References

Maharaj, SVM, Platinum Concentration in Silicone Breast Implant

Material and Corresponding Connective Tissue by Inductively Coupled

Plasma-mass Spectrometry.

2003., pers. comm..

, TM, Goodman, SB (eds). Implant Wear: In Total Joint

Replacement. American Academy of Orthopaedic Surgeons, Rosemont, Il.

2000

Ojo-Amaize, EA, Lawless, OJ, , JB. Elevated Concentrations of

Interleukin-1beta and Interleukin-1 Receptor Antagonist in Plasma of

Women with Silicone Breast Implants. Clinical and Diagnostic

Laboratory Immunology 1996; 3: 257-259

Empl, M, Renaud, S, Erne, B, Fuhr, P, Straube, A, Schaeren-Wiemers,

N,

Steck, AJ. TNF-alpha Expression in Painful and Nonpainful

Neuropathies. Neurology 2001 May 22; 56 (10): 1371-7 PMID 11376190

Deprez, M, Lubke, U, Verlaet, M, Debrus, S, Delvenne, P, , JJ.

Detection of Cytokines in Human Sural Nerve Biopsies; an

Immunohistochemical and Molecular

Study. Acta Neuropathol (Berl) 2001 Apr; 101 (4): 393-404 PMID

11355311

Lindenlaub, T, Sommer, C. Cytokines in Sural Nerve Biopsies from

Inflammatory and Non-inflammatory Neuropathies. Acta Neuropathol

(Berl) 2003 Jun; 105 (6): 593-602 PMID 12734666

The following organizations support this petition:

Toxic Discovery Network - Missouri

United Silicone Survivors of the World – Houston Chapter

The Breast Implant Information Exchange - Illinois

Silicone Solutions Outreach - Louisiana

United Silicone Survivors of the World – New Mexico Chapter

National Silicone Implant Foundation - Texas

United Silicone Survivors of the World – Florida Chapter

Implant Veterans of Toxic Exposure - Idaho

Coalition of Silicone Survivors - Colorado

Silicone, Saline Information Support System – Nevada

Cen-Tex Silicone Implant Support – Texas

Toxic2KIDS - Missouri

Members of Saline Support Internet Support Groups ()

In The Know – California

United Silicone Survivors of the World – Ohio Chapter

Children Afflicted by Toxic Substances – New York

Command Trust - California

Humantics Foundation for Women

United Silicone Survivors of the World – Oregon Chapter

FastCounter by bCentral

---------------------------------------------------------------------

-----------

HOME SUPPORT GREATLINKS QUACK LIBEL VICTORY DEFAMATION CASE

PUBLIÇATIONS DAILY NEWS

[Guest guest]

Isn't this amazing? . . . Here we are over two years

later, still needing the same things done - and

NOTHING has changed!

So much for our tax dollars at work!

Rogene

--- loverofmysoul60 <loverofmysoul60@...>

wrote:

>

> CITIZEN PETITION

> November 18, 2003

>

>

> Dockets Management Branch

> Food and Drug Administration

> Department of Health and Human Services, Rm 1061

> 5630 Fishers Lane

> Rockville, MD. 20852

> FAX 301/827-6870

>

> Re: Silicone Gel-filled Breast Implants

>

>

> The undersigned submits this petition under 21

> C.F.R. 10.35 to

> request

> that the Commissioner of the Food and Drug

> Administration (FDA) delay

> approval of any and all Premarket Applications

> ( " PMAs " ) for silicone

snip . . .