Corrosie van polymeren

Uit de bibliotheek van ex-president Bill Clinton: >> Silicone and matrix macromolecules. New research opportunities for old diseases from analysis of potential mechanisms of breast implant toxity. Bones, groans and silicone (lupus-2012-AE. Brawer) >>

Twenty years have elapsed since contentiousness and confusion began to dominate the issue of silicone gel-filled breast implants. In early 1992 the world literature on this topic could be summed up in one sentence: silicone gel-filled breast implants, when inserted into a live human being, had the capacity to make the recipient ill. The literature did not specifically state what the illness was, nor did it deduce with certainty that there even was such an illness. Subsequently there transpired a grievous and fundamental error in reasoning: siliconeinduced disease was defined in the courtroom before it was adequately studied in the examination room. Stated more simply, plaintiff and defense lawyers went to the rheumatology textbook, listed the criteria for classical connective tissue diseases (lupus, etc.), and forged a global class action settlement stating that if anyone became ill with such a disorder they would be compensated. A few other categories were defined for the stragglers, namely ‘atypical connective tissue disease’ and ‘atypical neurological disease’, whose criteria were also based on a preconceived idea of how the women were supposed to become ill. The stage was now set for chaos, which ensued shortly thereafter as a result of three events: (1) instead of 40,000 women showing up at the front door as expected, over 400,000 showed up; (2) there was a timetable to get all of the women examined (by August of 1994); and (3) the legal definition of silicone toxicity became adopted as the medical definition. Examinations of breast implant recipients were invariably geared toward gathering just enough information to place women on a legal compensable grid. Stated another way, the disorder was studied for what it was supposed to be rather than for what it was. By failing to consider multiple potential mechanisms of disease causation, data bases were artificially truncated and only a fraction of the women’s ailments were recorded. A further leap of faith transpired when it was assumed that

the inflammation manifested in the local breast milieu would invariably precipitate and be responsible for the systemic phenomena. Sooner or later, along the way, the immunologists would bail everyone out by coming up with the proper diagnostic tests. This aberrant and contrived methodology permeated the thought processes of nearly all investigators, yielding the dubious distinction 4 years later of having over 200,000 women examined and very little useful data (with the exception of the escalating reports of device rupture). Once the illness was defined by attorneys, it was a simple matter for implant manufacturers to fund studies to show that the fictitious illness did not exist. This proved very effective in the public arena via a simple slight-of-hand illusion: if a sick breast implant recipient does not have ‘A’ (something in the textbook), then she does not have ‘B’

(something new), i.e. she has nothing. This served to heighten the vociferous efforts of the breast implant recipients themselves, because now they felt victimized twice: once by a faulty product that made them ill, and second by clever manipulation of misleading data. Little did they realize that media coverage would come back to haunt them whereby women were blamed for inventing the illness after hearing about it. Sympathetic investigators were besieged by an army of company researchers who conducted critical and scathing reviews of the theories and premises of siliconeinduced immune activation. The trashing of immunotoxic mechanisms paralleled the vacuum created by the lack of careful and meticulous bedside observations, rendering disease verification elusive. Plaintiff’s lawyers began reeling from a succession of adverse jury verdicts and were left wondering why their ‘science’ was not yielding better results. Numerous erudite scientific panels also deduced that not enough data was present to reach any definite conclusion on causation.

Correspondence to: Arthur E. Brawer, M.D., Director of Arthritis & Connective Tissue disease Section, Monmouth Medical Center, 170 Morris Avenue, Suite B, Long Branch, NJ 07740, USA. Email: Received 6 March 2012; accepted 1 May 2012 The Author(s), 2012. Reprints and permissions: 10.1177/0961203312449493

Downloaded from at HINARI on September 18, 2012Many critics at the time debunked not only silicone toxicity but also Gulf War Syndrome (the latter was eventually proven to be a real and debilitating illness).

Other errors and omissions transpired during the 1990s that further hampered the processes of disease identification and epidemiological comparisons to textbook entities. These included the gross failure to consistently record detailed and accurate chronology of disease development, as well as the lack of photographic documentation of clinical features. The latter would have easily demonstrated what all proponents of silicone toxicity already knew, namely the monotonous, repetitive and redundant presentation of identical skin rashes and multiple other phenomena following implantation. In a similar vein, persistence and/or subsidence of these phenomena following explanation were poorly recorded. After all, how could one analyze data that was never taken down in the first place? Compounding all of this was the lack of appropriate long-term follow-up in large part because many implant recipients became partially or totally disabled, lost their health insurance, could not afford to revisit their doctor, or became separated or divorced. The original silicone gel-filled breast implants were slow delivery systems due to the phenomenon of gel bleed through an intact envelope or shell. This microdispersion began on day one of implantation, but has also been readily demonstrated to occur from the new generation of cohesive gel devices produced in the USA by Mentor and Allergan. Implant rupture causes macrodispersion, which can make the recipient disfigured and gravely ill in a manner comparable to individuals who have received multiple silicone injections. During the 1990s the rupture rate was noted to be 5% per year. The shell, or envelope, holding the contents of silicone gel is solid silicone, and is manufactured by adding silica (coal miner’s dust) to a viscous polymer of silicone gel to produce a rubber elastomer. Hydrolases released by macrophages can readily release the bound silica, which is one mechanism producing rupture. If the fibrocollagenous capsule that had formed around the implant was still intact, a patronizing reassurance was given to patients that they had ‘rupture with containment’. Little thought was given to the fact that electron microscopy of capsular collagen fibrils clearly showed no impediment to continued silicone migration into the body.

The current crisis developing simultaneously in many countries over the issue of silicone gel-filled breast implants has three components, all apparently linked to devices manufactured by Poly Implant Prothese (a company known as PIP): (1) an unusually high rate of rupture, (2) the substitution of substandard ‘industrial-grade’ silicone for conventional ‘medical-grade’ silicone and (3) the potential propensity to produce a rare form of cancer known as anaplastic large-cell lymphoma. With regard to rupture, it would not be surprising in the future to discover that devices from any manufacturer were readily failing at the rate of 5% per year. With regard to cancer, a discussion of that issue is beyond the scope of this editorial. The distinction between industrial-grade silicone and medical-grade silicone is a clever illusion propagated by manufacturers to allay fears over the latter. Although industrial silicone is a soup mixture of diverse organo-silicon components, all silicone molecules are capable of promoting intense inflammation, and all are subject to degradation in the body and thus are not chemically inert. Silicones are also not biologically inert, yet is anyone asking these implant recipients if they are ill? Knowledge of the normal integration of the element silicon in higher organisms is essential to understanding its role in causing biochemical aberrations when present in excess. Researchers need new tools to study the mechanisms by which excess silicon causes interference with the molecular basis of life (and, hence, disease), which may in turn unearth abnormalities that immunologists are fond of studying. In the end I suspect that an insight gleaned from these endeavors will inadvertently redefine inflammatory and immune responses, and could have major implications regarding the pathogenesis of lupus and other classical connective tissue diseases. What do plastic surgeons think of all of this? Not much. They have attributed problems with implants to poor operative technique, poor patient selection and lack of antibiotic use. Plastic surgeons have a great deal of data on local breast phenomena based on direct patient examinations.

Unfortunately, their attitudes regarding siliconeinduced systemic ailments have relied entirely on questionnaires and telephone interviews. We have known for decades that assessments of disease activity in lupus and other connective tissue diseases are reliable only when direct face-to-face contact is established. Why has here been a double standard with regard to silicone toxicity?

The moratorium on silicone gel-filled breast implants in the USA lasted from April of 1992 to December of 2006. During this interval cohesive gel devices were implanted in patients undergoing postmastectomy reconstruction who consented to be part of a research study. The Food and Drug Bones, groans, and silicone. AE Brawer

Lupus: Bones, groans and silicone

Downloaded from at HINARI on September 18, 2012

Administration only required 3 years of observational data, with no post-marketing surveillance after that. I now have six patients from the cohesive gel era who have developed a systemic illness comparable to my original cohort of 500 recipients seen in the 1990s. The latency period to disease onset in these six patients averages 3 ½ years, which explains why their medical records are virtually devoid of problems. It is therefore no surprise to me that a new epidemic may be emerging in multiple other countries since the United States lags behind the stampede to enhance one’s beauty by 10–15 years. And even if my prediction of a repeat debacle does indeed develop in the USA in the near future, will any medical association urge researchers to revisit this issue? In the latter half of the 1990s the American College of Rheumatology issued a position paper debunking silicone-induced disease. Plaintiff’s attorneys representing implant victims were not knights in shining armor either. They were not willing or able to remedy their mistakes because they needed to recoup their $100 million investment. The best way to do this, short of continuing to spend their way through 10 more years of proper research, was to use the rejection of untenable medical evidence to their benefit. This allowed them to bundle cases together dealing only with local breast phenomena (rupture, etc.), avoid costly court cases on systemic ailments, and avoid the perception of client abandonment. If you find yourself in a losing situation, go with the flow and use it to your advantage. The entire scenario also suited the judicial system well because it allowed gigantic and unmanageable court backlogs to be dispensed with. So what really happened? The lawyers created the science. The science they created served their purpose very poorly. They therefore had to abandon the science, and the best way to do this was to have national science panels do it for them. Will history repeat itself as newer implant recipients voice their concerns? Hopefully not, but this will depend in large part on giving ear to the clamor and guiding investigators to utilize prop. >>

Implant failure and the immuno-incompetent fibro-inflammatory zone

Biomaterial implants are surrounded by an immuno-incompetent, fibro-inflammatory, integration-deficient zone within which stimulation of cellular immune responses results in superoxide radical and cytokine-mediated tissue damage with increased susceptibility to infection or aseptic loosening. Three important questions that pertain to surgical implants are (1) What are the mechanisms that cause abnormal inflammatory responses in the absence of infection and result in interface cellular disorganization and device failure? (2) What causes host defenses to be compromised to the extent that normal flora organisms like Staphylococcus epidermidis, with little or no virulence potential, can cause life-threatening infections at the implant--host interface? (3) What is the nature of surface regions of biomaterials that facilitate bacterial adherence? Pathogenic strains of S. epidermidis and Staphylococcus aureus have an affinity for biomaterial surfaces and are capable of initiating infection. Binding may be nonspecific and gluelike rather than a receptor-ligand event as for S. aureus and matrix proteins. This study indicates bacterial binding to sites of higher vanadium concentration at grain boundaries and mixed phases in titanium alloys. Repeated macrophage priming by biomaterial particulates results in the production of reactive oxygen intermediates, macrophage exhaustion, and adjacent tissue damage. A cytokine cascade is also initiated. A self-perpetuating enlarging immuno-incompetent fibro-inflammatory zone develops about implants, which features tissue cell damage, increased susceptibility to infection, and results in septic or aseptic failure of the implant. These effects are clearly exemplified by fibrosis about breast implants and osteolysis at the interface of total joint replacements. >>

Analysis of silicon in human tissues with special reference to silicone breast implants

The increase, in the last two decades, in the application of silicones (polysiloxanes) and inorganic silicon compounds in medicine and the food industry, has exposed the human body to extensive contacts with these substances. Most silicone breast implants contain a gel consisting of a crosslinked silicone elastomer swollen by silicone oil (PDMS). Diffusion of PDMS through the silicone elastomer envelope and rupture of the envelope with release of the gel contents both occur clinically. The amount and distribution of silicone compounds in various tissues are key issues in the assessment of health problems connected with silicone implants.

We have measured by GFAAS the Si content of tissues from normal and implant patients and the organic solvent extractable Si levels (assumed to be silicone), using careful control of sample collection and preparation. Whole blood levels were: implant patients mean 38.8 (SD 25.6) (μg/kg), controls mean 24.2 (SD 26.7) (μg/kg) in one study and subsequently 103.8 (SD 112.1) and 74.3 (SD 86.5) (μg/kg) in another study. Capsular tissue levels were: gel implants 25047 (SD 39313) (mg/kg of dry tissue), saline implants 20.0 (SD 27.3) (mg/kg of dry tissue) and controls 0.24 (SD 0.39) (mg/kg of dry tissue). Breast milk levels were: implant patients mean 58.7 (SD 33.8) (μg/kg), controls mean 51.1 (SD 31.0) (μg/kg); infant formula mean was 4.40 (mg/kg). Various precautions were undertaken to avoid Si contamination in this work, the most important being a) the use of a Class 100 laboratory for sample preparation and b) application of strict and elaborate washing procedure for specimen collection tools and laboratory plasticware.

This data demonstrated that to properly interpret the importance of these numbers for human health, a larger study of ”normal” levels of Si in human tissues should be undertaken and factors such as diet, water, race and geographical location should be considered. >>

Toxic hydrolysis product from a biodegradable foam implant

A commercially available mammary implant containing a soft polyester polyurethane foam shell has been examined for possible diamine hydrolysis products. Fourier Transform Infrared (FT-IR) analysis has shown ester and aromatic structures present in the intact foam shell Vigorous hydrolysis conditions using NaOH have produced a mixture with large amounts of toluene diamine (TDA) present as determined by Gas Chromatography-Mass Spectrometry (GC/MS), and GC/FT-IR. There are numerous clinical reports of the degradation of this implant shell after implantation with incorporation of fragments into phagocytic cells at the implantation site. Recent reports have discussed late pain and other allergic reactions to this implant. Release of the known toxic material, TDA, is consistent with these observations and strongly suggests that an alternative material be used in this application. >>

Wear and Degradation of Retrieved Ultrahigh Molecular Weight Polyethylene and Other Polymeric Implants

The statistics regarding the number of autopsies containing associated implants on the pathology service at the University Hospitals of Case Western Reserve University are presented. The objectives of the Pathology Department's retrieval and analysis program are presented, and the special methods used for analyzing the tissue and implant responses are described. Examples of wear and degradation of the polymeric components which have been analyzed are presented. Silicone rubber poppet occluders which demonstrate abrasive wear are discussed, and the tissue response to wear particles incorporated in the liver is documented. Silicone fluid in the fibrous capsule from a gelfilled breast prosthesis is analyzed. Analyses of degraded and worn ultrahigh molecular weight polyethylene (UHMWPE) joint components by thin-section optical microscopy, scanning electron microscopy, and xylene extraction techniques are presented. The principal wear mechanisms are abrasive wear and cracking between the incompletely sintered UHMWPE powder >>

Corrosion and degradation of implants materials

Degenerative mineralization in the fibrous capsule of silicone breast implants

The formation of a fibrous capsule made of long collagen fibers surrounding breast implants represents an unavoidable phenomenon as the patient's reaction to the presence of a foreign body. Depending upon the size and shape of the implants and the chemicals percolating through the shell, this fibrous capsule is continuously remodeled. The compaction of the foreign debris in the vicinity of the silicone shell is followed by the loss of cellular activity, shrinkage and necrosis. Calcification is the ultimate step. These phenomena were illustrated in the analysis of 18 explanted breast prostheses after 20 or more years of implantation. The degenerative mineralization was shown in scanning electron microscopy and light microscopy. The minerals proved to be bone-like hydroxyapatite by X-ray diffraction and Solid State NMR analysis. Whatever the characteristics of any sophisticated new model of breast implant, phenomenon of mineralization might be minimized but it is very unlikely that it would be totally eliminated. >>

Biocompatibility and Fatigue Properties of Polystyrene−Polyisobutylene−Polystyrene, an Emerging Thermoplastic Elastomeric Biomaterial

Biomaterials and Functional Polymers Laboratory, Polymer Institute, Szczecin University of Technology, Pulaskiego 10, 70-322 Szczecin, Poland, General and Hand Surgery Clinic, Pomeranian Medical University, Unii Lubelskiej 1, Szczecin, Poland, Department of Polymer Science, The University of Akron, Akron, Ohio 44325, and Department of Polymer & Engineering, University of Bayreuth, Universitätsstr. 30, 95440 Bayreuth, Germany >>

Biodegradation evaluation of polyether and polyester-urethanes with oxidative and hydrolytic enzymes

Enzyme-induced liberation of components from seven different radiolabeled polyurethanes was monitored by radiolabel counting of the incubation solutions and product isolation by high performance liquid chromatography (HPLC). The polyurethanes were selected to reflect variations in the hard-segment chemistry, soft-segment chemistry, soft-segment chemistry, and polyurethane hydrophilicity resulting from combinations of hydrophobic/hydrophilic soft segments. All materials were characterized using electron spectroscopy for chemical analysis, differential scanning calorimetry, size exclusion chromatography, and Fourier transform infrared spectroscopy. The material surfaces were examined both before and after incubation with enzyme and control solutions using scanning electron microscopy. Biodegradation assays were carried out at 37°C using cholesterol esterase (CE) and horseradish peroxidase (HRP) under optimal pH conditions for each enzyme. The hydrolytic enzyme (CE) was effective in releasing degradation products that contained hard-segment components from some of the polyurethanes. HPLC analysis of products for a polyesterurethane synthesized with toluene diisocyanate (TDI) suggested that the bulk of the incorporated radiolabeled TDI was still covalently bonded within the cleaved chain segments of the original polymer and was not released as pure toluene diamine (TDA). The data suggest that urethane linkages in the soft-segment domains of phase separated polyetherurea-urethanes may be more prone to cleavage by CE than are the urea/urethane groups in the hard-segment domains. This could be related to the nature of the hard-segment domain structures. The oxidative enzyme (HRP) was not able to induce liberation of radiolabeled segments from either the polyether or polyester-based polyurethanes. © 1994 John Wiley & Sons, Inc. >>

The mechanisms of oxidative degradation of biomedical polymers by free radicals

Degradation is an essential factor in polymer biocompatibility. The physiological environment of the human body can be aggressive to polymers. Most implanted polymers suffer degradation and the kinetics and mechanisms of the processes can be significantly affected by various biologically active species, especially enzymes, lipids, peroxides, free radicals, and phagocytic cells. Iron enhances the toxicity of oxygen free radicals. Superoxide and hydrogen peroxide can interact to form the very toxic hydroxyl radical in the presence of iron. The data have shown that the hydroxyl radical is likely to be one of the main causes of polymer degradation in implantable devices. © 1994 John Wiley & Sons, Inc. >>

Poly-L-lactide surfaces subjected to long-term cell cultures: cell proliferation and polymer degradation

Short term cell cultures are usually grown in contact with biomaterials to assess cytocompatibility. Depending on the rate of material degradation or corrosion, the time of culture can be a key-point in the method which, if too short, may not show any effect of the released material on the cells. A long term culture was therefore carried out with L929 fibroblast cells in contact with PLLA/PDLA samples for up to eight months. The degradation was measured in terms of shear-strength properties, intrinsic viscosity of the material and its cristallinity. The effect of the material on the cells was evaluated by measuring the growth rate of the cells. A significant decrease in the shear strength of the material was measured after three months. The rate of modification of the intrinsic viscosity was regular and decreased progressively throughout the culture period. Differential scanning calorimetry showed that the samples were initially essentially amorphous and that contact with the cell culture and its medium did not change its crystallinity level. The growth rate of the cells was not modified by the presence of the material when compared to the control. This study showed this material to be cytocompatible for a long period of time, even after detection of modifications of its physico-chemical properties. >>

Silicon and matrix macromolecules: new research opportunities for old diseases from analysis of potential mechanisms of breast implant toxicity

Brawer AE

An understanding of the normal and essential integration of the element silicon in biosystems, as well as knowledge of its fundamental chemistry, are crucial to understanding its role in health and disease. Modern organosilicon chemistry, based in part on the artificial silicon-carbon bond, coincided with the emergence of the biomaterials and bioengineering fields fifty years ago, and was thought to be a fortunate coincidence according to conventional wisdom that high-molecular-weight polymeric siloxanes were chemically and biologically inert. These concepts have been challenged by reports of silicone migration and degradation following insertion of gel-filled breast implants, claims of a novel systemic illness appearing in many breast implant recipients, and investigations implicating varied and permeating immunotoxic mechanisms of disease causation by breast devices. The present study develops additional potential pathogenetic ideas based on alterations of cell biochemistry by silicon-containing compounds, and offers correlation of the patients' diverse clinical features with plausable disruption of basic biological processes. This in turn raises new questions concerning everyday environmental exposure, has broad implications for multiple other diseases, can provide alternative directions for future investigative research, and may contribute to the ongoing redefinition of immune dysfunction and inflammation. >>

Carbonate hydroxylapatite, hopeite and parascholzite in fibrous capsules surrounding silicone breast implants

Catherine Rolland ande Robert GuidoinLaboratoire de Chirurgie Expdrimentale, Universitd Laval, Sainte-Foy, Qudbec GIK 7P4 Robert Ledoux Departement de Gdologie, University Laval, Sainte-Foy, Qudbec GIK 7P4 Amina Zerguina and Paul-Emile RoyDepartement de Pathologie, Universitl Lwal, Sainte'Foy, Quebec GIK 7P4


The presence of mineral matter was observed in 13..590 of the capsular tissues of 262 mammary prostheses recovered after surgical excision. Three distinct mineral phases were identified: carbonate-hydroxylapatite, para- scholzite and hopeite. The most abundant is carbonate-

hydroxylapatite Ca5(POa,CO:):(OH), a well-known physiological and pathological mineral. Parascholzite, CaZn2(POa)2,2H2O' and hopeite' Zn3@O)2.4H2O, have not previously been reported in human tissues. The subs- titution of CO3 for POa in hydroxylapatite (Type B) is documented by infrared absorption spectroscopy. Statis- tical analysis of the data reveals links between the presence of the phosphate minerals on the one hand and the pros- theses having polyester (Dacron@) fixation patches, the implant integrity, and the time elapsed since implantation. Keywords: carbonate-hydroxylapatite, parascholzite, hopeite, breast implant, fibrous capsulas, biominerais; infrared absorption spectroscopy.

Souvrannr Nous avons ddcouvert des accumulations de matibre min6rale dans 13.590 des capsules fibreusa de 252 prothbes mammaires regues aprbs ex6r0se chirurgicale. Trois pha- ses mindrales ont &e identifides: hydroxylapatite carbona- t6e 0a plus r€pandue), Ca5(PO4,CO3)3(OH), biomin€ral physiologique et pathologique bien connu, parascholzite CaZn2@o)2./H2o et hop€ite Zns@o)2'4H2o. Ces deux phosphates de zinc.nfavaient pas 6td signal6s ant6rieure- ment dans les tissus biologrques humains. Les spectres d'absorption infrarouge etayent la substitution du CO3 au POa dans l'hydroxylapatite de type B. L'analyse statisti- que d6montre un lien entre la pr€sence des phases min6ra- les et les prothbses ayant des sites de fixation en polyester (Dacrono), I'integrite de I'implant, et la durde du s6jour des prothbses chez les patientes.

Mots-cl4s: hydroxylapatite carbonat6e, parascholzite, hop€ite, prothese mammaire, capsule fibreuse, biomi- n6raux, spectroscopie d'absorption infrarouge.


Internal mammary prostheses are amongst the most frequently used implantable devices after su- tures, dental materials and arterial prostheses (Blais 1988). More than 10,000 marnmary prostheses are implanted each year in Quebec; 140,000 Canadian and more than 1,000,000 American women bear them. These prostheses are inserted for cosmetic rea- sons in 8090 of the cases and as post-mastectomy reconstruction in the rest (Rolland et al. 1989). Although short-term results seem rather good, re- operation rates cal be very high; one woman out of three is a potential candidate for reoperation within ten years after implantation @andal 197). The prin- cipal reason for reoperation is the development of a fibrous tissue, usually called "fibrous capsule", all around the prosthesis (Fig. l). This capsule cor- responds to a normal response of the body in reac- tion to the foreign material implanted (Elbaz & Ohana 1982). When the capsule stays soft and thin, its presence is not a problem for the patient. In many cases, the capsule becomes thick and very contractile, the breast turns hard and painful, and reoperation is then necessary to deliver the prosthesis from this closed fibrous tissue. The other possible causes of reoperation are

1) the tear of the shell prosthesis, leading to silicone leakage,

2) the moving of the im- plant, resulting in deformation of the breast, and

3) the deposition of mineral matter, most commonly located on the internal surface of the capsular tis- sue, i.e., in contact with the shell prosthesis. In an effort to prevent these evolutive complications, we have identified patients who require this type of sur- gery, and we have assessed and quantified the physical properties of the prostheses that may undergo changes since implantation (Rolland, et al. 1989). I1 is necessary to study the pathological minerals and identify those parameters that have a sigaificant correlation with the presence of these minerals.


The 262 mammary prostheses, some of them accompanied by their capsules, were provided by

medical centres in the Quebec City area. The prostheses were explanted because of comptcations following implantation. All of them were composed of a silicone envelope made of polydimethylsiloxane filled with a gel of the same material. Tables I and,2 give the numbers of patients, prostheses, capsules, medical files consulted and the number of prosthe- ses depending on the manufacturer. Ideally, after surgrcal excision, the prostheses and capsules were rinsed with physiological saline solution and fixed in 1090 fernalins solution without buffer or in 2% eilutaraldehyde solution with a phosphate buffer. Before our investigation of the minsp4ls deposited, the organic matter was removed by immersion in suc- cessive baths of sodium hypochloride (2090) and the materials rinsed with distilled water. The frequencies, sizes, and physical properties of the deposits of mineral matter were determined by visual inspection ofthe fibrous capsules. The speci fic gravity was determined with a Berman balance. Microscope slides of individual grains reduced to 30 pm were observed under a Zeiss polarizing micros- cope. A Philips EM300 transmission electron micros- cope was used in order to examine thin sections of the capsular tissues. The samples were embedded in Epon 812 and stained with uranyl acetate and lead citrate. Some carbon-covered specimens were examined by means of a JEOL JSM 35CF scanning electron microscope equipped with a Princeton Gamma Tech PGT System 4 multichannel energy-dispersion spectrometer.

A 114.6-mm Gandolfi camera was used to record X-ray-diffraction lines. The samples were exposed

during twelve hpurs. A copper target (Cul(n radiation, )r 1.5418 A) and a nickel filter were used with a Philips PWlOlO generator operated at 40 kV and 20 mA. The infrared absorption spectra of pressed specimens into KBr (200 mg of KBr for 2 mg specimen) were recorded with a Beckman spectrophotometer (4000 to 400 crf).

Three statistical tests were used to analyze the data: the Kruskal-Wallis and the Wilcoxon rank-sum tests for continuous variables not normally distributed, and the Chi-square test, with Yate's correction, on discrete variables (Walpole 1982). All tests were based on a 0.05 level of significance.

Rrsurrs The macroscopic examination revealed that mineral deposition had occurred in 2l of 155 fibrous capsules (13.590). The volume of the deposits and the size of particles per unit area varied. Three of the capsules showed little mineral matter, nine were moderately affected, and in another nine cases mineral matter was found to cover the intire surface @ig.

2). Generally, the deposits occur on the internal faces of the capsules, at the capsule-prosthesis interface. Two specimens exhibit mineral matter within the fibrous tissue, and one specimen shows little globular groups of radiating crystals deposited on the internal and external surfaces of the capsule. Macroscopic examination of the mineral crusts showed three types of deposits: (l) isolated white or beige tabular deposits were pre$ent in 19 ofthe 155 capsule specimens. Deposits found at the capsule- prosthesis interface are very thin (from a few tenths of a mm to I mm), with maximum lenglh of 10 mm. On a few specimens, crystal facets with dihedral angles were observed (Fig. 3); (2) whitish equigra- nular aggregates, up to 4 mm in diameter. This deve- lopment occurred throughout the fibrous tissue of


Ftc. 2. Capsular lissue entirely covered with carbonate-hydroxylapatite deposits adhering to its surface on the internal side in contact with the prosthesis. Time elapsed since implantation of the prosthesis: 17 years. 30 pm were observed under a Zeiss polarizing microscope. A Philips EM300 transmission electron microscope was used in order to examine thin sections of the capsular tissues. The samples were embedded in Epon 812 and stained with uranyl acetate and lead

citrate. Some carbon-covered specimens were examined by means of a JEOL JSM 35CF scanning electron microscope equipped with a Princeton Gamma Tech PGT System 4 multichannel energy-dispersion spectrometer. A 114.6-mm Gandolfi camera was used to record X-ray-diffraction lines. The samples were exposed during twelve hpurs. A copper target (Cul(n radiation, )r 1.5418 A) and a nickel filter were used with a Philips PWlOlO generator operated at 40 kV and 20 mA. The infrared absorption spectra of pressed specimens into KBr (200 mg of KBr for 2 mg specimen) were recorded with a Beckman spectrophotometer (4000 to 400 crf).Three statistical tests were used to analyze the data: the Kruskal-Wallis and the Wilcoxon rank-sum tests for continuous variables not normally distributed, and the Chi-square test, with Yate's correction, on discrete variables (Walpole 1982). All tests were based on a 0.05 level of significance.

The macroscopic examination revealed that mineral deposition had occurred in 2l of 155 fibrous capsules (13.590). The volume of the deposits and the size of particles per unit area varied. Three of the capsules showed little mineral matter, nine were moderately affected, and in another nine cases miner- al matter was found to cover the intire surface @ig.

2). Generally, the deposits occur on the internal faces of the capsules, at the capsule-prosthesis interface. Two specimens exhibit mineral matter within the fibrous tissue, and one specimen shows little globular groups of radiating crystals deposited on the internal and external surfaces of the capsule. Macroscopic examination of the mineral crusts showed three types of deposits: (l) isolated white or beige tabular deposits were pre$ent in 19 ofthe 155 capsule specimens. Deposits found at the capsule-prosthesis interface are very thin (from a few tenths of a mm to I mm), with maximum lenglh of 10 mm. On a few specimens, crystal facets with dihedral angles were observed (Fig. 3); (2) whitish equigra- nular aggregates, up to 4 mm in diameter. This development occurred throughout the fibrous tissue of


Frc. 3. Thin, tabular carbonate-hydroxylapatite showing crystal facets at the prosthesis interface of capsular tissue. Time elapsed since implantation of the prosthesis: 16 years. two capsule specimens; (3) globular groups of radra- ting crystals, which grew on both surfaces of ano- ther capsule. The largest diameter of the clusters is I mm (Fig. 4). The mean specific gravity of five examples of tabular deposits is 2.80, and the specific gravities ofther two cases of equigranular deposits are, respectively,

2.46 and 3.22. Transmission electron microscopy The microscopic examination showed the presence of very small acicular crystals growing on the edge of vacuoles identified as silicone vacuoles by Zerguini (1989). The earliest crystals seemed to have grown with their longest axis perpendicular to the edge of the vacuoles (Fig. 5). At a later stage, the minerals became denser, and crystal forms were not recognizable. Finally, other crystals with encrusted facets were observed to make up the margins of the large mineralized areas. Sconning electron microscopy and microanalysis The tabular deposits (19 specimens) showed cha- racteristic X-ray peaks corresponding to phosphorus and cdcium, whereas in the case of massive deposits, microanalysis identified phosphorus, calcium, and zinc in one specimen and phosphorus and zinc in the other. The elobulax groups ofradiating crystals gave chaxacteristic X-ray peaks of phosphorus, zinc, and calcium. Observations by scanning electron microscope showed a collection of thin lamellar crystals placed in a radial arrangement (Fig. 6). The euhedral crystals and the deposits found on both sur- faces of the capsule suggest that Cxoups of radiating crystals could be artifacts. However, the capsules were conseryed in glutaraldehyde solution with phosphate buffer in which the Zn ion was absent, and no other contamination was likely. X-ray diffractometry X-ray diffraction confumed the identification of carbonate-hydroxylapatite, Ca5(PO4,CO3)OH, in 19 tabular specimens. The presence of (COr)2- ions in the hydroxylapatite was indicated by a 300 re- flection shifted to a higher angle (32.98' ?.0) anda 002 reflection shifted to a lower anele Q5.84" 20) than for hydroxylapatite without carbpnate (LeGeros et al. 1969). The main d values'(in A), in order of decreasing intensity, are: 2.81, 2.7 8, 2.7 2, 3.45, l.U,

1.94, 2.63, 2.26, 1.7 3, 3.07.

Cell-dimension calculations based on hexagonal symmetry gave a9,410, c 6.892 A. These cell dimensions are consistent with those found in literature (LeGeros et al, 1969). Two granular specimens from two different capsules yielded reflection values corresponding to those of parascholzite, CaZn @Oa)z.2HzO, a mineral described for the first time by Sturman et al, (1981). The unit cell of this phase very closely corresponds to the monoclinic qubcell of scholzite. The strongest reflections d (in A) are 8.57,2.80,4,15,3,40,2.77,

2.26, 4.52,2.59.

Finally, in one of the two capsular tissues containing parascholzite, one grain provided dvalues cor- responding to hopeite Zry@O)r.4HrO. The most intense reflections (d in A) from this specimen are

2.86, 8.52,9.16, 4.56, 3.39, 4.41,2.n, 1,94,2,66,

The unit-cell dimensions of this orthorhombic mineral calculated froru the d values are a 10.601,

18.330, and c 5.020 A.

Infrared absorption spect roscopy Infrared absorption spectroscopy conoborated the identification of the three phosphate minerals and indicated, in addition to HrO, the presence of structural CO3. Nadal er al. (1970) and Bonel (1972) described two types of carbonate-apatite, named type

A and type B, depending on the location ofthe carbonate ions in the structure. In type A, the vibra- tion bands of the carbonate are at 1534-1465 arl;d 884 cm-I, and the carbonate ion sites are in chan- nels along the six-fold screw a:(es, replacing the OH anions. In type B, carbonate vibration bands are at 1455-1430 and 864 cm-l, and the carbonate groups substitute for phosphate groups in the framework. Eleven of our specimens yielded spectra representing type-B carbonate-hydroxylapatite. Frequencies and assignments for these absorption spectra are given in Table 3.

The infrared absorption spectrum of the hopeite phase described by Hill & Jones (1976) showed four

bands characteristic of phosphate, but in our samples, the second lattice vibration band is missing, probably because of the low resolution of our spectrometer. The spectrum of parascholzite was interpreted and compared with that ofhopeite. Frequencies and band assignments for these two spectra are given in Table 4. Three more specimens yielded spectra consistent with a mixture of carbonate-hydroxylapatite and parascholzite.The comparison of three spectra (Fig. 7) clearly

demonstrates the presence of a characteristic band at 950 cm-!, related to zinc cation in the structures of different phosphates. In spectrum l, the carbonale-hydroxylapatite contains only calcium and no zinc; there is no band at 950 cm-l. In spectrum 2, the parascholzite, which contains zinc and calcium ions, shows a medium band at 950 qn-t; the intensity of this band is stronger in the hopeite spectnrm. Infrared absorption spectroscopy has a great potential in detecting the presence of zinc in phosphates and could be an indicator of its relative quantity. The advantages of this method are the small quantity of material required (2 mg), easy sam- ple preparation and rapidity. Stotistical analysis. The Kruskal-/ellis test shows that the occlurence of deposits of mineral matter does not depend on the age of the patients at their first implantation. The Wilcoxon test demonstrates a close relation between the presence of deposits and time elapsed since implantation (h : 13.33; critical region X?c = 3.84).

The Chi-square test, with Yate's correction, was used in order to test the relations between the pre sence of mineral deposits and the following: brand of the prostheses, physical breakdown of the pros- theses and Dacron@ fixation patches. The occurrence of mineral deposits was closely related to the broken prostheses (1J": 5.61) and also to the presence of Dacron@ fixation patches at the surface of the prostheses (a2r";29.39) (critical region f: 3.84), but no correlation was observed between the ocsurrence of minerals and the brand of the implants.


Whereas carbonate-hydrorylapatite is frequently identified as the major constituent of normally cal-

cified tissues like bones and teeth and is also present in human pathological minera'lizatiel as cardiovascular deposits (LeGeros & LeGeros 1984, Roy et al. 1983) and breast prostheses (Nicoletis & Wodarczyk 1983), this is the first report of two zinc phosphates associated with the fibrous reaction of silicone breast implants. Parascholzite is a mineral first described from a Bavarian pegrnatite (Sturman et al. l98l), and hopeite is a secondary mineral in zinc-bearing ore deposits (Nriagu 1984, Hill & Jones l9Q. Both parascholzite and hopeite have not previously been found in humans, either in normal or pathological mineralizations. The unusual presence of zinc as a major constituent of these mineralizations associated with fibrous capsules raises the question of its origin. X-ray-fluorescence analysis of the silicone gel and shell failed to demonstrate the presence ofzinc as a constituent ofthe prosthesis, and no anomalous high zinc-diet on the parts of the patients is known.The moust plausible source of zinc is the RTV ( room temperature vulcanization) glue that is used in the final sealing of the outer envelope. ( M.Popple, pers comm). The possiblility of changes in zinc metabolism caused by surgery could also have some effects (Cornelisse 1980)


Blais, P. (1988): The polyurethane breast implant: a basis for caution. Transpl. Impl. Today 5' 28-29. Rest van de referenties slecht leesbaar....