Dennis H. Smith

An outcome analysis of 100 women after explantation of silicone gel breast implants.

A prospective outcome analysis was conducted on 100 consecutive women who requested explanation of their silicone gel breast implants from January 6, 1992 (the moratorium), through 1995. Eighteen patients were referred by rheumatologists with a diagnosis of autoimmune or rheumatic disease. Six had autoimmune disease (systemic lupus, 2 patients; rheumatoid arthritis, 2 patients; multiple sclerosis, 1 patient; and Raynauds disease, 1 patient). Twelve had rheumatic disease (fibromyalgia, 10 patients; inflammatory arthritis, 2 patients). All of these 18 patients had developed symptoms of their disease after they had received implants. All 100 patients were extensively evaluated pre- and postoperatively by interviews, clinical assessment, and by assay of the following laboratory tests: rheumatoid factor, ESR, ANA, and anti-Ro/SSA, -La/SSP, -Sm, -RNP, -double-stranded deoxyribonucleic acid, -Scl-70, -centromere, and -cardiolipin. Patients were also evaluated by a questionnaire that was sent at a mean time of 2.7 years postexplantation (range, 1–5 years), which had a 75% response rate. Reasons for implants were augmentation, 75%; lifting, 11%; reconstruction, 12%; and congenital aplasia, 2%. The mean age at first implant was 28.9 years (range, 13–55 years) and at explantation was 41.5 years (range, 25–65 years). The mean duration of implantation was 12.0 years (range, 1–27 years). Thirty-six percent of the patients had undergone at least one closed capsulotomy and 54% at least one open capsulotomy. The main reasons for explantation were suspected silicone-related health problems, 76%; suspected rupture, 59%; breast firmness, 36%; breast pain, 36%; and musculoskeletal pain, 23%. Before explantation 75% of the questionnaire respondees had lost some sensitivity in their nipples following their breast augmentation. In 36% of those 75 patients, that loss was almost complete. Loss of sensitivity was related to capsular contracture and to pain (p < 0.05). Following explantation there was significant improvement in nipple sensitivity in 38% of breasts in the 75 respondees. A total of 186 implants were removed. Fifty-seven percent had failed by rupturing or leaking. Only 3.2% demonstrated extravasation extracapsularly. Twenty-five percent of the capsules were calcified, demonstrating visible plaques of calcification on their inner surface. Forty-two percent were colonized by bacteria. The prevalence of class III–IV capsular contracture was 61% and it was related to implant location, duration in situ, and capsular calcification (p < 0.05), but not to capsular colonization or implant integrity (p > 0.05). Only 43 of the 100 patients elected to have saline implants inserted. Of the others, 56% felt that the shell of the saline implant could be associated with medical problems. The others felt that breast size was of minor importance to them at this time. There were few complications from the explantation procedure. Two “masses” were discovered—one was an occult carcinoma, the other a galactocele. There was one wound infection, which responded to antibiotics. Three patients developed decreased sensitivity and 3 developed increased breast pain. From the patient questionnaires, in those women who did not have saline implants inserted, 15% felt that their breast appearance was improved after explantation, 36% were “pleased,” 33% were disappointed, and 13% felt “mutilated.” In women who did have saline implants inserted, 18% felt that their breast appearance was now improved, 60% were “pleased,” and 14% were disappointed, mainly because of wrinkling. At a mean time of 2.7 years (range, 1–5 years) after explantation, 45% of the 75 questionnaire respondees felt that their implants had caused permanent health problems and 56% felt that they had not been given adequate informed consent by their original surgeon (particularly regarding implant rupture and a possible relationship to medical disease). Nineteen patients had breast fed after implantation (only 1 patient felt that her implants had adversely affected her child), 28% had attended an implant support group, 24% had undergone professional psychological support, and 43% were involved in litigation against implant manufacturers. Of the 75 respondees, those who had no proved rheumatic or autoimmune disease responded most favorably to explantation. In those patients, more than 80% related “major improvement” in their symptoms and more than 93% related significantly improved psychological well-being. In patients with fibromyalgia or inflammatory arthritis, most experienced an initial, almost euphoric improvement in symptoms during the first few months after explantation. However, their symptoms subsequently recurred over the following 6 to 12 months. Ultimately, 11 of these 12 patients related no change or further deterioration from their preexplantation status. One patient related “slight” improvement. In all 6 patients with autoimmune disease, there was no improvement in clinical or laboratory findings after explantation.

Applications of artificial intelligence for chemical inference—XXI: Chemical studies of marine invertebrates—XVII. The computer-assisted identification of [+]-palustrol in the marine organism Cespitularia sp., aff. subviridis☆☆☆

Abstract In order to demonstrate the power utility of the interactive computer program CONGEN, 5 an example describing its use in the identification of the tricyclic sesquiterpene alcohol, [+]-palustrol, in extracts of a marine Xeniid ( Cespitularia sp., aff subviridis ) is provided. The rotation of [+]-palustrol further supports the remarkable antipodal relationiship between sesquiterpenes from marine Coelenterates and their corresponding terrestrial forms. 6

Capsular calcification associated with silicone breast implants : Incidence, determinants, and characterization

Capsular calcification was present clinically in 64 of 404 silicone gel breast implant capsules (15.8%) analyzed from 1981 to 1996. It presented as white-gray plaques on the inner surface of capsules in 62 of 64 capsules, and as massive heterotopic ossification in 2 capsules. Chi-squared analysis confirmed that calcification was related to the generation of the implant (i.e., year of manufacture;p<0.001). All 28 first-generation implants (1963-1972, with Dacron patches) were clinically intact and all demonstrated extensive calcification. Their mean duration in situ was 17.6 years (range, 14-28 years). Thirty-four of the 348 second-generation implants (9.8%; 1973-1987) were associated with capsular calcification. Their mean duration in situ was 16.0 years (range, 13-22 years). Because all first-generation implants demonstrated calcification, they were compared with the second-generation implants that had been in place for the same duration (>14 years). Only 42% of these 81 secondgeneration implants demonstrated calcification, compared with 100% of the first-generation implants (p<0.001). Thus, thicker first-generation implants with Dacron patches are more likely to calcify and the effect is not entirely due to their longevity. None of the 28 third-generation implants (1987-1991) demonstrated calcification. Their mean duration in situ was 4.2 years (range, 2-7 years). For second-generation implants, calcification was related to duration in situ (p<0.001). None of the 294 implants in place for less than 11 years were associated with significant clinical calcification. The percentages of capsules with calcification were 13 to 14 years, 33%; 15 to 16 years, 45%; and 17 to 22 years, 57%. Calcification with second-generation implants was not associated with patches on the envelopes. Of the 34 second-generation implants with calcification, only two had patches (composed of silicone, not Dacron). Among secondgeneration implants, calcification was related to implant integrity. Of implants in place for more than 12 years, 52.5% of those implants that were ruptured showed calcification, but only 10.0% of intact implants demonstrated calcification (p<0.001). Seventeen of the 64 calcified capsules were examined histologically. In all of these specimens, calcification existed in two forms: globular aggregates on the surface of the capsule (adjacent to the implant) and actual bone formation within the fibrous tissue of the capsule. All calcified capsules demonstrated both globular aggregates and true bone formation regardless of the implant generation, duration in situ, or integrity. Ultrastructural analysis was performed on four capsules from 2 women who had received first-generation Dow Coming gel implants 24 and 28 years previously, and on 2 capsules from one woman who had received Heyer-Schulte gel implants 21 years previously. These capsules were analyzed according to distribution, density, mineral nature, crystal phases, and elements within crystals by electron microscopy, energy-dispersive X-ray spectrometry, and electron diffraction. These analyses confirmed two types of calcification, each with hydroxyapatite crystals. In areas of heterotopic bone, crystals 40 × 10 nm were deposited in an orderly fashion on collagen fibers. In contrast, in areas of globular aggregates, spherulitic aggregates of much larger crystals were present, without any relationship to the collagen. Titanium was demonstrated in capsules of first-generation implants at areas of attachment of the Dacron patches. The calcification associated with saline implants revealed only one form of crystal: agglomerates, which were adherent to the elastomeric shell of the implants. A hypothesis is presented to explain the differences in calcification deposition properties between silicone gel-filled and saline-filled breast implants.

The dendral project: recent advances in computer- assisted structure elucidation

Abstract Recent advances in the DENDRAL Project on computer-assisted approaches to structure elucidation are reviewed. Important developments include: (1) novel approaches to constrained generation of constitutional isomers to obtain structural candidates for an unknown; (2) the first solution to the problem of exhaustive generation of configurational stereoisomers and the implementation of a program for constrained generation of such stereoisomers; (3) the refinement of methods for predicting mass spectra of molecular structures and for using such predicted spectra to determine the relative plausibilities of different hypothesized structures for an unknown; (4) the development of experimental approaches for the interpretation and prediction of 13 C-n.m.r. spectra. Future extensions allowing the representation and use of conformational stereochemical information, and potential applications of such extensions are discussed.

Managing the Combinatorial Explosion

Computer software designed to deal with the large amounts of data generated by chemical and biological research programs is described. The software includes methods for representation of the structural components of combinatorial libraries, enumeration of structures and structure-based searches, and comparisons within combinatorial libraries.

Applications of artificial intelligence for chemical inference—X : Intsum. A data interpretation and summary program applied to the collected mass spectra of estrogenic steroids☆☆☆

Abstract A method for systematic interpretation and summary of evidence found for all possible mass spectral fragmentations of a molecule or set of related molecules is described. The method is embodied in a computer program (INTSUM) which interprets, in terms of fragmentation processes, mass spectral data collected on known compounds. Utilizing high resolution mass spectra from 47 estrogenic steroids, the method is verified and new findings are discussed. Finally, the method is used to explore the fragmentations of equilenins and several acetate and benzoate ester derivatives.

Computer-assisted structure manipulation : Studies in the biosynthesis of natural products

Abstract A computer program (“REACT”) that simulates chemical reactions by manipulating representations of structures has been utilized to study biochemical reactions. Biosynthetically plausible sterol side chains were generated and the number of plausible isomeric sterols were calculated. Possible label distributions in structures resulting from the biochemical conversion of a humulene precursor to some known fungal metabolites were followed by studying different biochemical pathways.

The DENDRAL project: computational aids to natural products structure elucidation

We discuss the use of several computer programs designed to aid chemists in structure elucidation. These programs are highly interactive in that a chemist works together with a program to derive structural candidates for an unknown, to evaluate the candidates using spectroscopic data, and to explore relationships between structure and biological activity. An example is carried through the discussion to illustrate our methods.

Calcification properties of saline-filled breast implants.

Three patients requested explantation of their salinefilled breast implants. Bilateral calcification had occurred in all six implants. Four of the implants were manufactured by McGhan Corporation (Santa Barbara, Calif.), and two, by the Simaplast Company (Toulon, France). All implants had been inserted in the subglandular plane and had been in place for 7 to 23 years. At the time of explantation, patients were 32, 34, and 44 years old. Calcification on the surface of the implants and capsules was analyzed. Implant surface calcification was clinically evident on all six implants, appearing as ivory‐colored, tenaciously adherent deposits, only on the anterior surface of the implant. Capsular calcification, which was observed only microscopically, was characterized by poorly organized, irregularly shaped, calcified agglomerates; this calcification also occurred only on the anterior surface of the capsule, adjacent to the area of calcification on the implant. Ultrastructural analysis of scrapings from the implant surface showed large, electron‐dense aggregates of crystals, with individual crystals measuring approximately 40 × 10 × 10 nm. In contrast, capsular calcification was characterized by two patterns of deposition, spherulitic aggregates of needle‐shaped crystals and areas of metaplastic bone. The individual crystals were approximately 40 × 10 × 10 nm. Energy‐dispersive x‐ray spectroscopy of specimens from the areas of calcification on the implant and capsule surfaces demonstrated calcium and phosphorus. Electron diffraction of crystals from the implant and capsule surfaces demonstrated the D‐spacings characteristic of calcium apatite. There were many differences between the calcification properties of these six saline implants and those of silicone gel implants. For example, mineralization has not been observed on the surface of gel implants, but in these saline implants it occurred primarily on the implant surface. Also, capsular calcification has been observed clinically in gel implants across the surface of the capsule (except at the site of attachment of a Dacron patch), but in this study it was observed only microscopically and was located on the anterior surface of the capsule, adjacent to the area of calcification on the implant. In addition, crystals 100 times larger than those observed on the six saline implant capsules have been observed on the surface of gel implant capsules. A model is presented to explain the mechanism of calcification associated with breast implants and to explain the observed differences between saline‐filled and gel‐filled implants. (Plast. Reconstr. Surg. 107: 356, 2001.)

Silicon assays in women with and without silicone gel breast implants--a review.

During the past 5 years, as the failure properties of silicone gel breast implants have emerged, there has been considerable interest in measuring the levels of silicone and silicon in blood, serum, breast milk, and body tissues. Assays have been done in control patients without implant exposure, and in patients with silicone gel implants in an attempt to predict implant failure. Nuclear magnetic resonance measurements of silicone compounds have not been helpful because of their low sensitivity of detection. However, all compounds containing the element silicon, which includes silicone, have been measured accurately. Modern techniques, such as electrothermal atomic absorption spectrometry, direct-current plasma emission spectrometry, and inductively coupled plasma emission spectroscopy have allowed precise measurement of silicon in body fluids and tissues. Using these techniques, recent studies have demonstrated consistent levels of silicon in the blood and plasma of control women without exposure to implants. In one study, plasma silicon was shown to be 140 +/- 10 ng per milliliter. In four other studies, serum silicon levels in control patients were the following: mean, 130 +/- 70 ng per milliliter; mean, 170 +/- 100 ng per milliliter; median, 100 ng per milliliter (range, 30-209 ng per milliliter); and 10 to 250 ng per milliliter. Three independent studies have shown that women with silicone gel implants have higher blood and serum silicon levels than control subjects, but their values were still within the range of control subjects. One study has shown that the mean silicon level in breast milk was not significantly different between 15 implant patients and 34 control patients. The measurement of silicon in control breast tissue has shown consistent results in three different studies, with most tests varying from <0.2 to 2.2 microg per gram dry weight. Three studies have shown that capsules from women with silicone gel breast implants had markedly elevated silicon levels compared with control breast tissue. Median silicon levels varied from 9,980 to 14,390 microg per gram dry weight. There was no significant difference in capsule silicon level between intact and ruptured implants or associated with implant duration in situ or year of implantation. Four studies have shown that capsules from saline implants had elevated levels of silicon compared with control tissue, but their silicon levels were much lower than those of gel implants. The median levels of silicon in the capsules of these studies were as follows: 7.7, 71.5, 198, and 1,100 microg per gram dry weight. Based on current knowledge, because of the large variability among patients, the use of silicon measurements in blood, serum, breast milk, or implant capsule tissue has no clinical role for the effective monitoring of implant leakage in women with silicone gel breast implants.