Melinda Barrow 10
FN200. Defendant's Exhibit 1293. Dr. Zeigler testified that he is not an expert in silicone disease, disease causation, or immunology, has not examined tissue or blood of women or animals that have had silicone gel breast implants, and is not a veterinarian or a medical doctor. He has not done NMR work on tissue or blood of women who had silicone gel breast implants.
FN201. Dr. Zeigler stated that NMR uses radio waves that are subject to noise. Dr. Garrido's work reflected that the signals relied on were not the required "twice the noise level," rendering Dr. Garrido's test meaningless and his data unreliable. Later in his testimony, Dr. Zeigler noted that in Dr. Peter Macdonald's draft report, Dr. Macdonald had taken the position that Dr. Garrido's work was on the edge of detection but was done in a scientifically valid manner and with accurate reasoning.
*21 Further, Dr. Zeigler testified, one of the degradation products which Dr. Garrido claimed to have found, selenium ion, was a reactive intermediate never observed unequivocally in a laboratory and which scientists for more than fifty years had been unable to make because of its instability. Dr. Zeigler testified that this product could not be observed by NMR in the aqueous environment of the body even if it could be formed. However, Dr. Zeigler admitted that Dow Corning had funded part of Dr. Macdonald's work to attempt to replicate Dr. Garrido's research, that the two men used different NMR machines, and that Dr. Zeigler did not know if such machines were of different sensitivities or calibrations. Nevertheless, Dr. Zeigler adhered to his criticism of Dr. Garrido's results as being incapable of duplication. [FN202]
FN202. As reflected in a report criticizing Dr. Macdonald's work about which Dr. Zeigler was questioned, "the absence of evidence is not evidence of absence." In other words, failure to prove silicone migrated into the blood stream does not mean such migration does not occur. Dr. Zeigler also spoke of a report in which the author stated that he did not believe either that Dr. Garrido had shown that he had seen the signal or that Dr. Macdonald had proven that Dr. Garrido had not.
Similarly, Dr. McCarty was critical of Dr. Garrido's report, stating that he disagreed with Dr. Garrido's position in his 1994 peer-reviewed article that NMR offers powerful evidence that silicone and other silicon compounds are found in the blood of all women with silicone gel breast implants, regardless of whether the elastomer is ruptured or intact, although the concentration is lower if the shell is intact.
After reviewing the evidence and observing the testimony and demeanor of the witnesses, the Court finds that the greater weight of the credible evidence supports the finding that the silicone gel from the silicone gel breast implants in Plaintiff migrated away from the surface of the breast implant elastomer and beyond the breast capsule which formed around each such implant. Particles from the silicone gel can be seen in Plaintiff's breast tissue beyond the capsule which surrounded the implant on slides containing such tissue extracted during her explant operation, and silicone particles remained in Plaintiff's extracted breast tissue after the explant. The preponderance of the evidence also supports the finding that particles from the silicone gel traveled away from the elastomer surface and breast tissue to Plaintiff's axillary lymph nodes. The gel bleed caused Plaintiff's tissues to become inflamed while the implants remained in her body in a chronic foreign body reaction. The foreign body reaction continued although with less severity after explant due to the particles from the silicone gel which remained in Plaintiff's tissues.
4. Systemic Silicone Disease
In addition to the evidence of foreign body reaction to the particles of silicone gel which bled through the breast implant elastomer and migrated into Plaintiff's tissues, there was extensive testimony concerning what, if any, other symptoms or diseases could be related to this phenomenon.
Dr. Gary Solomon, a practicing rheumatologist who is board certified in internal medicine and rheumatology, testified concerning his experience studying women with breast implants and Atypical Connective Tissue Disease ("ACTD") which he also denominated Systemic Silicone Related Disorder ("SSRD"). [FN203] He described the various symposiums and scholarly study groups in which he has participated and which have noted strong evidence to support the relationship between silicone exposure and Atypical Connective Tissue Disorder. [FN204] While contending that epidemiology, which is used in evaluating classical diseases, [FN205] is of little help in evaluating ACTD, an atypical disease, he also emphasized that rheumatic diseases, such as rheumatoid arthritis which later became known as lupus, are difficult to define and classify since they usually evolve, since disease criteria used for clinical research change over time, and since classical diseases can have atypical presentations and/or not all patients have the same presentation of symptoms. [FN206] In this regard, Dr. Solomon noted that just as not all persons exposed to environmental factors get sick, not all women with silicone gel breast implants become ill. Nor do all women with breast implants form a capsule, and those who do may take from one to eight or more years before a capsule is formed. [FN207] Up to five percent of the population with silicone breast implants may have antibodies stimulated by silicone as an adjuvant in the blood and not show manifestation of the disease, and further ACTD can exist in women and men not exposed to silicone. For these reasons, Solomon advocates the use of biomarkers to determine those persons whose immune systems are activated consistently over a long period of time. Thus, he contends, the presence of auto-antibodies may not mean a person has a systemic or other disease, but it does mean that there is stimulation of the antibody-forming apparatus and the adjuvant effect may be present. Silicone, he noted, is an adjuvant which stimulates an antibody-making apparatus, and silicone can act as an adjuvant in the absence of a specific antigen. [FN208]
FN203. Dr. Solomon's curriculum vitae is Plaintiff's Exhibit 1.47. Dr. Solomon was qualified to testify as an expert in rheumatology and internal medicine with emphasis on the relationship, if any, between silicone exposure and Atypical Connective Tissue Disease. Dr. Solomon also variously called this disorder Atypical Connective Tissue Disorder ("ACTD") and Silicon Undifferentiated Connective Tissue Disorder "UCTD") to distinguish it from Connective Tissue Disorder ("CTD"). He described the latter as inflammation in the tissues below the skin and outside the organs. However, Dr. Solomon admitted on cross-examination that he and his peers in the rheumatology community had not been able to develop a generally accepted definition of ACTD despite many efforts to do so. Dr. Solomon testified that Human Adjuvant Disease is the same disorder which he calls SSRD, ACTD, or UCTD.
FN204. In this regard, he testified the following as support for his conclusion that silicone gel breast implants can cause SSRD in implanted women: (1) there is historical precedent for the concept, i.e., the Japanese hypothesis many years ago in which direct injection of silicone led to injury and death and the fact that other environmentally induced rheumatic disorders exist; (2) the concept has biologic plausibility, i.e., that silicosis disease has similar characteristics to Atypical Connective Tissue Disease and the activation of macrophages, cytokine generation, the production of autoantibodies, and the activation of B-cells making the adjuvant leads to the conclusion that silicone serves the role of activating the antibodies as an adjuvant in a non-specific way; and (3) the consistency of clinical observations of systemic disease found in women with silicone breast implants, i.e., profound fatigue, joint pains, flu- like myalgia, arthralgia, sicca, pain in the upper and sometimes lower chest, often with fever, chills, night sweats, hair loss, vascular abnormalities, rashes, lung problems, gastrointestinal problems, balance problems, cognitive impairment, and sometimes clusterings of symptoms. Of these symptoms, Dr. Solomon feels that fatigue, myalgia, arthralgia, sicca, and cognitive impairment are core to systemic disease criteria, but there is no requisite number of factors which a patient must have for one to conclude that the patient has ACTD.
FN205. Dr. Solomon described classical diseases as ones that have been known for a long time and tend to have more objective and quantitative symptoms with typical laboratory abnormalities linked to the disease, often representing underlying genetic factors of the host. He noted that there may be atypical presentations of the disease that have no specific, unique laboratory analysis linked to the disease.
FN206. In this regard, Dr. Solomon noted that in the 1960s when Japanese women were injected with silicone, not all responded. While some had an extreme response resulting in mastectomy, the most common result was scleroderma. Some women had multiple autoimmune disorders, and many women were ill but did not have classical disorders. The Japanese coined the term Human Adjuvant Disease for this disorder, and studies of the Japanese experience were published in the United States in the 1970s and 1980s.
FN207. He also noted that in some women with bilateral silicone gel breast implants, a capsule may form around one breast implant but not the other.
FN208. Dr. Soloman described the means by which silicone activates the autoimmune system due to gel bleed which causes a macrophage reaction. The macrophage ingests the silicone particles and secretes chemicals which cause tissue to form and also cause release of cytokines and activation of T-cells. The release of the cytokines is a biological mechanism which he feels proves that some, but not all, women have symptoms of ATCD. Further, he opined that there is a 51% probability that the production of cytokines is in response to the silicone gel breast implant. Dr. Solomon noted that the silicone gel molecules which have migrated to the capsular tissue can enter the blood of the host. However, unlike the chemicals manufactured by the macrophage which are measurable in the autoimmune reaction, the molecules of silicone in the blood cannot always be measured. He noted various studies involving the autoimmune response of the body to silicone, such as Plaintiff's Exhibit 1.23 T (describing how T-cells respond specifically to silica and silicone gel); Plaintiff's Exhibit 1.23 Q (studying the means by which silicone exposure causes release of cytokines); and Plaintiff's Exhibits 1.23R & S. He noted that Dr. Garrido, using NMR spectrocity in a study, was able to follow silica containing chemicals in the body after exposure to silicone gel. Dr. Solomon testified that the tissue formed around a breast implant has many layers in which there is an ongoing, specific immune response occurring. Instead of being an area of containment, the tissue looks like a lymph node in which a specific, not random, T-cell response occurs in women with silicone gel breast implants. He explained that most of the studies of this matter are preliminary and that the field is in its infancy. However, he testified that there was ample material available to manufacturers of silicone gel breast implants in 1986 to apprise them of the fact that these devices bled gel, that such gel bleed activated macrophages, generated cytokines, T- cells, and B-cells, and led to chronic disease. He stated that these points were known and discussed with plastic surgeons at least by 1977 at the Ann Arbor meeting which Lynch attended. E.g., Plaintiff's Exhibits 1 .23 YY & 1.23 XX. See supra note 171.
*22 Dr. Solomon testified that he has examined approximately 1350 women with silicone gel breast implants. Some of them developed what is called "local disease" such as pain, encapsulation, armpit lymph node swelling, inflammation of the nerve endings, inflammation of the shoulder, and a clustering of symptoms. He found that local disease always preceded systemic disease in these patients, and that while women with encapsulation tended to be the ones who got ill, not all of them did.
Dr. Solomon was critical of the 1995 position of the American College of Rheumatology [FN209] which issued an opinion that there was no linkage between silicone gel breast implants and systemic disease. He described that position as hasty, done without the review of its membership, and subject to criticism because of conflict of interest. He noted that the position of that body at present has changed; it now states that the data is not fully developed and that the matter needs further study and development of criteria. He also criticized epidemiological studies [FN210] that concluded there was no relationship between silicone gel breast implants and systemic disease on the grounds that such studies looked at classic disease, not ATCD disorders, they used inadequate sample size, they were not based on direct examination of the patient, the time factor of three to four years used was inadequate, [FN211] the studies did not use biomarkers which are a standard part of modern medical research, and the researchers failed to disclose their bias and conflicts of interest generated when funding for a study was sponsored by one side of the litigation involving such implants or when processes of litigation were used to terminate the study before it could be completed. [FN212]
FN209. Plaintiff's Exhibit 1.23 RR.
FN210. E.g., Plaintiff's Exhibit 1.23 UU.
FN211. Dr. Solomon testified that a latency period of 10 to 15 years was necessary to make such studies reliable. Since 1985 to 1986 were peak years for breast implants, a 10-year latency period would mean that these illnesses were becoming manifest at the present time. However, Dr. Solomon noted that there is no criteria for the length of the time lag between the implant and the appearance of local symptoms on the one hand and the subsequent development of systemic symptoms. The lack of criteria for latency is why Dr. Solomon testified he argued that local injury or disease must precede systemic disease for a diagnosis of ATCD.
FN212. In this regard, Dr. Solomon was referencing the 1991 Harvard study that was abruptly abandoned because its findings subjected the researchers to unwanted involvement in the breast implant litigation occurring throughout the country.
From his experience Dr. Solomon believes that a proper epidemiological study can be done to develop the criteria and scientifically test for systemic disease, although he concedes that no such proper study has been completed at the present time. He further concedes that to have a controlled epidemiological study, there must be a case definition and a disease criteria, which he is still trying to articulate. [FN213] In his opinion, the silicone breast implant manufactured by MEC was capable of inducing an illness and immune abnormality in some, but not all, women. The silicone gel from such implant's bleed travels to other places in the body and is taken up by macrophagia which induce an immune reaction which can, but does not always, cause local and systemic illness.
FN213. See Plaintiff's Exhibit 1.23 QQ.
In contrast to the testimony of Dr. Solomon, Defendant presented the testimony of Drs. Caldwell and Kotzin. [FN214] Dr. Jacques Caldwell [FN215] testified that, from his experience in treating approximately 100 women with silicone gel breast implants and from talking to colleagues and reading medical literature, there is no such thing as silicone-associated disease and no relationship between such medical devices and systemic disease. While silicone gel breast implants can be associated with local complications, they are safe, he opined. Further, he testified that Plaintiff has no physical, organic disease or tissue damage, no disease caused by silicone, and no evidence of any systemic disease.
FN214. Dr. Williams also testified that he is current and has kept up with the medical literature on this matter since 1991 and that the vast majority of epidemiological studies say there is no health risk associated with silicone gel breast implants.
FN215. Dr. Caldwell, an expert witness for Defendant in internal medicine, rheumatology, immunology, and allergies, whose curriculum vitae is Defendant's Exhibit 1137, examined Plaintiff for MEC and prepared a report. Dr. Caldwell spends approximately 80% to 85% of his professional time seeing patients with arthritis and the remaining time seeing patients with other immunological diseases. He spends about 20 hours each week doing research. Approximately 60% of his patients are women. He testified that after a television show with Connie Chung frightened people about silicone gel breast implants, the number of his patients with such devices increased to about 100, of which he felt one or two had autoimmune disease. He testified that he did not believe then and now still does not believe that autoimmune disease is related to these devices. He testified further that he has reviewed three to four breast implant cases for MEC, has examined plaintiffs and testified at two trials, and has earned less than $15,000 for such services.
*23 Dr. Kotzin testified that the complaints and symptoms of Plaintiff are similar to the majority of the rheumatology patients he sees in his practice, including patients who do not have breast implants. [FN216] While not an epidemiologist, Dr. Kotzin stated that he has designed epidemiological studies and teaches how to understand such studies as they relate to CTD. [FN217] He stated that there have been fifteen to twenty epidemiological studies done since 1992 on whether women with silicone gel breast implants develop a defined CTD, and these show that women with silicone gel breast implants do not have an increased risk of getting a defined CTD. None of these studies have resulted in a relative risk factor of 2.0 or more, meaning the results of these studies are not statistically significant sufficient to denote that silicone gel breast implants are the cause of these problems. [FN218] In dealing with undefined CTD, the problem is compounded, according to Dr. Kotzin, because those claiming that silicone gel breast implants cause a silicone-associated CTD use different names for the disease, and the disease has not been defined yet to enable study. [FN219] Dr. Kotzin testified that these studies show that there is no increased risk from a breast implant of developing a currently defined CTD such as scleroderma, lupus, or rheumatoid arthritis, and that Plaintiff does not have a defined CTD. Further, no valid epidemiological study has been done which shows that silicone gel breast implants cause an undefined CTD. [FN220]
FN216. Dr. Kotzin referred to a list of common complaints of patients whom he sees, Defendant's Exhibit 1294, and stated that these appear in patients with and without CTD; some patients have a few and some have all of these symptoms, and most do not have silicone gel breast implants.
FN217. Dr. Kotzin testified at length about the scientific method, the use of placebo control, double blinding, and randomization in designing epidemiological studies, the use of a cohort or a large population of people in which some had exposure to the phenomenon and some did not, the use of relative risk analysis or the measure of the increased risk in the study group compared to the control group, and the necessity to determine if the relative risk falls within a 95% confidence interval and thus is statistically significant, as computed by a statistician, in order to determine whether the results of the study are not occasioned by chance alone. While Dr. Kotzin explained that the relative risk has to be over 2.0 for the association between the exposure and the disease to be more probable than not, he admitted on cross-examination that relative risk applies to a population, not to an individual, and it is not appropriate to disregard a relative risk of less than 2.0 on all occasions. Dr. Kotzin also explained the Bradford-Hill criteria as being a reasonable enumeration of factors to be considered for determining the causation of an exposure which results in illness as follows: (1) the strength of the association or how far above 1.0 is the relative risk; (2) the consistency of the association or its reproducibility; (3) the specificity of the signs and symptoms or whether they are unusual and distinctive; (4) the dose response; (5) the temporality; and (6) the biologic plausibility of the theory of causation. According to Dr. Kotzin, the more of these criteria which are satisfied, the more likely the exposure causes the disease, although all criteria do not have to be present for a theory of causation to be valid, and some diseases have more than one cause. In this regard Dr. Kotzin cautioned against use of a case report or a case series to establish an association between a cause and effect because of the danger of selection bias, conceptual bias, referral bias, or over-reporting of the symptoms. He did acknowledge that some of the epidemiological studies on which he relied for his opinions, such as the Harvard Nurses Study, may have suffered from the defect of underestimating the true incidence of disease by excluding women with mild or atypical cases of CTD, by excluding certain symptoms from the criteria, such as fatigue over three months in duration or unexplained skin rashes, and by excluding women who did not fulfill the criteria early enough in the disease. He admitted inadequate sample size and failure to look for a constellation of symptoms as well as other defects in other studies on which he relied such as the Mayo Clinic Study. He also admitted that the studies, such as the Mayo Clinic Study and the Harvard Nurses Study, on which he relied for his opinion that there is no disease associated with silicone, had been funded in whole or in part by manufacturers of silicone gel breast implants for litigation. While contending that Dr. Solomon's work was defective for referral bias, or being based on patients referred to him incident to litigation, Dr. Kotzin denied that funding of a scientific study by a breast implant manufacturer would have any effect on the outcome of the study. He concluded that study results could be affected by using one-sided or two-sided (tailed) hypotheses, for instance a onesided test could look only at whether silicone gel breast implants increase the incidence of the symptoms of CTD while a two-tailed test would look at that question plus the question of whether such devices prevent the disease. Whether the study was one or two- tailed is important because it determines the way relative risk will be spread. In a two-tailed study, the risk is spread between two hypotheses, while in a one-tailed study, all risk is allocated to one hypothesis. He acknowledged that implant manufacturers had requested two-tailed studies in research they sponsored, such as the Henneken's study sponsored by Dow Corning which found a relative risk of 1.24 for CTD in women with silicone gel breast implants. If the data in this study had been analyzed using a one-tailed test, the level of statistical significance or "P value" would change how the risk was allocated. Further, he stated that epidemiological studies can have different results. Sometimes a false negative can occur because the study is too small, the exposure is too low or short, the follow-up is too short or incomplete, or there is improper allowance for the latency period.
FN218. In this regard, Dr. Kotzin testified that there is a conceptual bias, or a hypothesis which leads to an incorrect conclusion, among many persons interested in this issue, to the effect that in women with silicone gel breast implants everything that develops is because of these devices. There was lengthy testimony given on direct and cross-examination analyzing the various studies on which Dr. Kotzin based his opinions, including reference to various types of biases of the researchers or the populations studied.
FN219. Dr. Kotzin referenced various names for the silicone associated disease such as Human Adjuvant Disease and Systemic Silicone Related Disease. See supra note 203.
FN220. Dr. Kotzin noted that while some doctors have tried to develop criteria for such disease, the study is at the observation and hypothesis formation stage, and the criteria is in the process of being defined so the study can be done. He noted that the way the criteria is defined currently will foreclose a valid study because it includes having a silicone gel breast implant and local complications. Thus, the criteria cannot be used to determine if there is an increase of symptoms in these women when compared with women without such devices.
Dr. Kotzin testified the symptoms presented, such as fatigue, pain, cognitive complaints, dry eyes, and dry mouth, are not unique to women with silicone gel breast implants, and these symptoms are those most commonly seen in rheumatology patients without silicone gel breast implants who do not have CTD. [FN221] Next, Dr. Kotzin noted that epidemiological studies have been uniform in their failure to demonstrate an increased risk of developing a CTD or a number of different signs or symptoms of a CTD in women with silicone gel breast implants. The constellation of signs and symptoms of systemic disease are not specific to women with silicone gel breast implants. In other words, there is no specificity of association between having silicone gel breast implants and systemic symptoms. [FN222] Further, there is no biomarker or laboratory test that is distinctive or reflects a particular disease process that is distinctive in its association with silicone gel breast implants, [FN223] and there is no dose response correlation between silicone gel breast implants and systemic illness. [FN224] As to latency or the time from exposure to silicone gel breast implants to the development of the disease process, the case reports and case series cannot define an association, so the latency period cannot be determined. Finally, Dr. Kotzin discounted the biologic plausibility of such implants causing systemic disease, stating those who drew this conclusion did not do so based on epidemiologic studies but instead did so based upon theory or hypothesis. He opined that no biologically reasonable mechanism explains the development of systemic symptoms in women with silicone gel breast implants.
FN221. In this regard, Dr. Kotzin testified that he had reviewed Plaintiff's records, and using differential diagnosis, he stated, it cannot be determined that her symptoms are caused by her silicone gel breast implants because they occur in the general population which does not have silicone gel breast implants. Differential diagnosis, or the process of determining if there is an underlying illness(es) to explain the patient's symptoms, often will not lead to a defined illness as a cause. He enumerated the steps in differential diagnosis as first obtaining a history of and listening to the patient, next conducting a physical examination of the patient, then reviewing the medical records of the patient, ordering appropriate laboratory studies, and reviewing all the information obtained to arrive at a list of illnesses that may explain the patient's symptoms and signs. Dr. Kotzin was critical of those who contend that silicone gel breast implants are a cause of symptoms because they cannot explain such symptoms using differential diagnosis.
FN222. As noted earlier, Dr. Kotzin described this factor in terms of an analysis of how unique or distinctive the symptoms of the population with exposure to silicone gel breast implants are compared to those without the exposure to such devices.
FN223. With reference to Dr. Solomon's testimony, Dr. Kotzin testified that the low titer antinuclear antibodies ("ANA") are not biomarkers for women with silicone gel breast implants because low titer ANAs are normal in women with or without silicone gel breast implants. Further, Plaintiff's ANA test showed no reactivity.
FN224. Dose response involves giving a higher dose of the material, or giving a dose over a longer period of time, and correlating it to any increase in frequency or development of the disease. Dr. Kotzin testified that there is no study to suggest that persons with a ruptured silicone gel breast implant were correlated with systemic illness when compared with persons with intact implants. However, he has not studied the relation between fumed amorphous silica and crystalline silica, although he has read papers comparing the properties of both in animals, which studies find that animals with high doses of fumed amorphous silica suffered adverse effects.