Robert R. LeVier

Occurrence and Activity of Myofibroblasts in Human Capsular Tissue Surrounding Mammary Implants

Capsular tissue obtained from a series of 16 patients with silicone mammary implants was exposed in vitro to smooth-muscle stimulants and relaxants. Capsule relaxation was produced in 75 percent of the patients. The most active antagonists were papaverine and veratrine. Capsule contracture was produced in 69 percent of the patients. The most active agonists were histamine and epinephrine. Myofibroblasts were identified in several capsules. These data support the hypothesis that the myofibroblasts is a probable cause of capsular contracture.

Positive identification of silicone in human mammary capsular tissue.

A specific quantitative assay was developed to determine silicone concentrations in contracted mammary capsular tissue. The concentrations of silicone in tissues from 14 patients with gel-filled implants varied from 15 to 9800 micrograms polydimethylsiloxane per gram of tissue. This silicone is probably a high-molecular-weight polymer that has diffused through the implant envelope. Samples from a patient with saline-filled implants contained no silicone. The concentration of silicone was not related to capsule age. The polymer in these tissues appeared to be unaltered, in that no evidence of metabolic products was found.

Distribution of silicon in the adult rat and rhesus monkey.

The distribution of silicon in tissues of the rat and rhesus monkey was determined using a colorimetric method specifically designed for biological materials. Soft-tissue silicon levels in both species varied from 1 to 33 mug silicon/g dry weight (ppm) excepting the primate lung and lymph nodes, which averaged 942 ppm and 101 ppm, respectively. This distribution may reflect flow-through of silicon in the form of particulates and water-soluble silicate contaminates in the environment and food effectively masking tissue or organ-specific silicon of functional significance. The silicon content of the whole rat femur was 38 ppm as determined by emission spectroscopy, whereas the monkey femur shaft was 43 ppm and the femur head containing the epiphysis was 456 ppm. This silicon may be functionally involved in the calcification process as suggested by others. The silicon content of rat liver subcellular fractions was also determined. The supernatant, nuclei/debris, and mitochondrial portions contained 0.6-1.0 mug silicon/g liver equivalents, whereas the microsomal fraction contained only 0.2 mug silicon/g liver equivalents.

The Pharmacology of Silanes and Siloxanes

A wide spectrum of biological action is to be found among the myriad molecular structures resulting from more than a century of organosilicon chemistry. Deflatulent, hormonal, analgesic, anti-microbial, and anticonvulsant properties exhibited by silicon compounds ranging in molecular size from simple monomers to high polymers are discussed. These selected pharmacons are drawn from throughout the range of common silicon structures and are illustrative of the breadth of biological action which may be attained.

Analysis of Some Organosilicon Compounds in Biological Materal

The analytical chemical experience gained in the analysis in biological material of the compound 2,6-cis-diphenylhexamethyl-cyclotetrasiloxane (KABI 1774, CisobitanR) and the products formed following its biotransformation is discussed. Quantitative analysis was performed with the highly selective technique of gas chromatography- mass spectrometry (GC-MS), enabling the determination of concentrations down to 0.1 µg/ml of serum. The extraction of this rather lipophilic compound from serum samples into organic solvents was very slow, and to achieve quantitative extraction a homogeneous extraction technique using heptane containing methanol followed by the addition of water was developed. Contamination problems due to the volatility of the organosilicon compound are discussed. Mass fragmentography and mass chromatography were used to unequivocally identify five products formed following the biotransformation of 2,6-cis (in rat, monkey and man), i.e., dimethylsilanediol, methylphenylsilanediol, trimethylphenylsiloxanediol and phenol, all identified as their trimethylsilyl derivatives. The M.S. data were compared to those obtained from similarly derivatized authentic samples. In these studies radioactively labelled substrate was used as an aid for coarse separation of the metabolites and stable isotope labelling was an aid in confirming the source of dimethyl-silanediol as various amounts of this compound appeared in the blanks. Possible metabolic and chemical routes leading to the formation of the breakdown products are briefly discussed.