Antipolymer antibodies, silicone breast implants, and fibromyalgia.
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Biomedical subjects
Publications and source records attributed to N S Hardt.
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BACKGROUND: Surgical implantation of silicone breast prostheses has been conducted and considered safe for over 30 years. Some implant recipients, however, complain of a group of symptoms similar to those observed in connective tissue disorders, rheumatoid arthritis, systemic lupus erythematosus, or polymyositis. To date, immunologic sequelae have not been confirmed and remain controversial. OBJECTIVE: To examine an autoimmune-like basis for the "silicone associated disease" reported by some women with silicone breast prostheses. METHODS: Proliferative responses of peripheral blood mononuclear cells against a panel of control and connective tissue proteins and to compounds common to silicone prostheses were measured in 26 women who received silicone breast implants (with implants in place an average of 166.4 [standard deviation (SD) 58.3] months), and 23 age-matched and sex-matched healthy controls. RESULTS: The frequency and intensity of cellular immune responses against collagen I, collagen III, fibrinogen, and fibronectin were significantly increased in silicone breast implant recipients versus controls. In implant subjects, the highest frequency of immune reactivity was directed against collagen I (11/26, 42%) with collagen III being the most immunostimulatory self-antigen with a mean stimulation index (SI) of 8.2 [95% confidence interval (95% CI) 3.2]. In addition, 10/26 (39%) of the implant recipients responded to more than one of the connective tissue antigens versus 0/23 (0%, P = .0007) healthy controls. Immunologic reactivities to other antigens, including silicone-based compounds, were remarkably similar. CONCLUSIONS: The identification of self-reactivity towards these connective tissue antigens may provide important information for attempts at associating silicone breast implants with disease.
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A method to measure gel bleed from intact silicone gel-filled breast implants was developed. This nondestructive technique permits accurate and reproducible serial measurements of silicone bleed from smooth wall breast implants (n=10) under simulated physiologic conditions in vitro. Gel bleed rates from new low bleed gel-filled implants and intact explants (unbarriered, low bleed, double lumen) were determined. These results demonstrate the reliability of this method to quantify silicone gel bleed and may permit a meaningful comparison of bleed rates from implants in the future.
Citing evidence that breast implant-related capsules resolve uneventfully, surgeons have elected to leave the capsules in place when implants are removed because capsulectomy adds both morbidity and expense to the procedure. However, recent clinical and histopathologic evidence suggests that uneventful resolution is not always the case, and several potential problems may arise from retained capsules after removal of the implant. Retained implant capsules may result in a spiculated mass suspicious for carcinoma, dense calcifications that obscure neighboring breast tissue on subsequent imaging studies, and cystic masses due to persistent serous effusion, expansile hematoma, or encapsulated silicone filled cysts. Furthermore, retained capsules are a reservoir of implant-related foreign material in the case of silicone gel-filled implants and textured implants promoting tissue ingrowth. To avoid complications from retained capsules, total capsulectomy or postoperative surveillance should be offered to patients.
A new method for diagnosis of ruptured silicone gel-filled implants was developed. The method uses a recently described technique for insertion of a catheter into an implant capsule. This allows irrigation with saline and recovery of cells for cytopathologic diagnosis. Cytopathologic diagnosis was both sensitive (94 percent) and specific (95 percent) in the detection of intracellular foreign material accompanying ruptured implants. The intracellular material has been positively identified as silicone. This laboratory study included 42 samples obtained at three time intervals on 5 rabbits, each of which had one "ruptured" and one intact implant for a total of 10 implants.
Over 2 million silicone breast prostheses have been implanted since they were introduced in the 1960s. After implantation, a fibrovascular tissue reaction referred to as a "capsule" is observed. Many consider this capsule to be a static structure, an effective barrier to the egress of foreign material. However, reports documenting the presence of silicone within lymph nodes of patients with apparently unruptured implants indicate that silicone may be transported away from the breast-implant capsule. To characterize the cells making up the breast-implant capsule, 183 capsules from 103 ruptured or bleeding implants and 80 intact implants were studied. Gross and light microscopic studies were performed on all, and selected capsules were subjected to ultrastructural study and Fourier-transform infrared spectroscopy. Light microscopic examination of the capsule revealed an organized, layered structure with an associated network of endothelia-lined spaces. The capsules varied in cellularity, depending on the type and integrity of the implant. The superficial cell layer of all capsules had cytoplasmic processes directed toward the surface. These long cytoplasmic processes contained vacuoles ultrastructurally, indicating phagocytic and pinocytotic capability. These cells bore immunological markers of bone marrow derived macrophage-type cells. The extracellular matrix of the surface layer consisted of an amorphous fibrillar protein lacking the ultrastructural periodicity of mature collagen. No cell-to-cell junctions were observed. Deeper capsular layers were characterized by fibroblast-type cells in a collagen matrix. No capsules studied contained basement membrane or basal lamina between the stroma of the capsule and the surface cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Clinically useful methods to identify and document the presence of foreign material in tissues surrounding breast implants are needed. Fourier transform infrared microspectroscopy is an ideal technique for examining tissue for the presence of implantable biomaterials. Because the spectroscopy is microscopically guided, the pathologist is assured that the obtained spectrum is from the region of interest in a tissue section. Scanning electron microscopy yields elemental data but cannot be used to identify compounds. Because each compound has a unique spectrum by Fourier transform infrared microspectroscopy, the spectrum obtained enables identification of the various foreign materials observed by light microscopy in tissues surrounding breast implants. Histopathology from implant capsules demonstrating a silicone gel-filled implant, a saline-filled textured implant, a polyurethane foam-covered gel-filled implant, a Dacron fixation patch, and a paraffin injection granuloma are presented with corresponding Fourier transform infrared microspectroscopy spectra.
To evaluate the effect of sampling method and cytometric method on DNA ploidy results, a comparison study was performed on 20 whole prostate glands removed at prostatectomy. Fresh sampling was by sampling fine-needle aspiration (FNA). Paraffin sampling was by microdissection and re-embedding of 3 to 13 (average 6) 5-mm foci of microscopically proven tumor. Analysis was by flow cytometry and by image cytometry (microscopically guided). In tumor negative cases, flow and image cytometry of the FNA was diploid in each case, and flow cytometry of paraffin-embedded tissue was diploid in 5/6 cases. In tumor positive cases, non-diploid tumor was detected by image cytometry of the FNA in 70%, by flow cytometry of the FNA in 29%, and by flow cytometry of paraffin-extracted nuclei in 21%. The most effective combination was sampling fine-needle aspiration and image analysis.
Vulvar vestibular biopsy specimens from 31 women with clinical and pathologic findings of vulvar vestibulitis were studied using polymerase chain reaction (PCR) for the identification of human papilloma virus (HPV). The PCR technique specifically probed for HPV types 6, 11, 16, and 18. Of the 31 subjects, three were found to have HPV within the biopsy specimens; two had HPV type 11 and one had HPV 16. Five of the 31 cases had histopathologic features of koilocytosis consistent with HPV effect; three of these five were found to have HPV. The findings support the hypothesis that HPV types 6, 11, 16, and 18 are rarely associated with vulvar vestibulitis. The frequencies identified were similar to those seen with control patients. True koilocytosis is the most useful pathologic feature distinguishing HPV-related cases; it is rarely identified in typical vulvar vestibulitis. Nonspecific changes in the vestibular epithelium associated with glycogen effect should not be interpreted as koilocytosis.
Recent concern regarding breast implants has emphasized the special imaging needs of the approximately 2 million American women who currently have prosthetic breast implants, including silicone gel, silicone gel with a textured silicone coating, saline, biocompatible gel, polyurethane-coated, double-lumen, and tissue expanders. Both palpable and nonpalpable breast lesions can occur in patients with implants, and these lesions must be evaluated in the same manner as in patients without implants, which presents a challenge for the mammographer. Not only is the breast tissue of a patient with implants more difficult to image, but the patient may have complications from the implants. The major complications of their use involve hematoma in the early postoperative period, infection, capsule contracture, rupture, and silicone granulomas. Familiarity with the more common types of implants, the possible complications of their use, and concurrent breast disease may help improve diagnosis in these patients.
We present a method for controlling variability that may arise from inconsistencies in sample preparation for DNA content analysis of paraffin-embedded tissue. Human tonsil tissue obtained from routine surgical specimens was embedded in paraffin according to standard protocols. Fifty-micrometer sections were cut from the block and analyzed each day for 20 days to establish control ranges. One tonsil tissue section was processed in parallel with each run of clinical specimens. In this context, a run was defined as the simultaneous processing of 50-microns tissue sections for extraction of cell nuclei (dewaxing and rehydrating). If the tonsil G0/G1 peak coefficient of variation (CV) exceeded 2 SDs of the established mean, and optimum instrument performance and staining were verified, all samples prepared with the tonsil control were reprocessed. Instrument performance and staining were assessed by using the appropriate external controls. By using this rejection rule (12s), the frequency of sample reprocessing in our laboratory was approximately 6%. When the run was repeated and the tonsil control CV was within acceptable range, the G0/G1 peak CV of the corresponding clinical specimens improved 25% of the time. Because most investigators are willing to accept higher CVs for paraffin-embedded tissue than for fresh tissue, it is desirable to have a control to detect decreased peak resolution, resulting from errors in sample processing.
Management of children with hypercholesterolemia has proven to be a controversial issue. The appropriate approach is to test those at highest risk for premature coronary heart disease most likely to benefit from intervention. Recommendations are reviewed in the context of the National Cholesterol Education Program Expert Panel on Blood Cholesterol Levels in Children and Adolescents. An overview is provided of the problem of preventing coronary heart disease through childhood intervention.
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Fresh whole prostate glands were examined systematically in a water bath to look for four sonographic criteria for prostatic carcinoma: well-circumscribed hypoechoic regions, external asymmetry of the gland, increase in anterior-posterior diameter ratio, and irregularity of the prostatic capsule. Whole mount sections were examined to correlate the histopathologic and sonographic findings. Using hypoechogenicity alone, 26 of 43 glands harboring tumor were identified correctly. Using all four criteria, 40 of 43 glands harboring tumor were identified, a statistically significant improvement in sensitivity (P less than 0.05). Specificity of both methods was similar (P greater than 0.1). The three tumors that were missed measured 0.5 x 0.5 x 0.5 cm, 0.5 x 0.5 x 0.5 cm, and 0.3 x 0.4 x 0.9 cm, and were found at autopsy in patients who died of causes unrelated to the prostate. The authors conclude that systematic examination of the gland with attention to multiple criteria for abnormality can improve case finding in prostatic adenocarcinoma.
For more than two decades, Apgar scores have been used to predict developmental outcome in newborns. However, most studies have used full-term babies for their data base, and the predictive value of Apgar scores for low birthweight infants has remained unclear. This study was designed to provide a data base for premature infants, demonstrating to what degree Apgar scores predict developmental outcome. We tested Apgar scores alone and in combination with two other easily quantified variables, birthweight and gestational age, as predictors of risk for 256 infants weighing less than 1800 gm at birth. Although significant correlations existed between Apgar scores and Bayley Mental and Psychomotor Developmental Indices, multiple regression analyses demonstrated that these relationships were not significant independent of birthweight and gestational age. That is, after controlling for birthweight and gestational age, Apgar scores did not predict morbidity in low birthweight infants and should not be used to provide a developmental prognosis.
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While Apgar scores provide a valid prediction of mortality in term infants (primarily reflecting asphyxia), intervening variables in premature newborns complicate interpretation. Physiologic states normal to preterm infants (such as, decreased muscle tone) can depress scores but may not influence survival significantly. Therefore the relationship between Apgar scores and survival in term and preterm infants differs. Because of the paucity of studies on preterm infants, we tested Apgar scores, as well as birthweight and gestational age, as outcome predictors in 748 low-birthweight infants (500-1800 gm). Our purpose was to assess the relationship between 1- and 5-minute Apgar scores and survival, and to evaluate all combinations of the four variables as outcome predictors. Univariate analysis showed a significant relationship between each of the four variables and survival; however, no single variable accounted for more than 32% of the variance in outcome, thus no single factor could be invoked as the major determinant of survival. Logistic regression analyses demonstrated the interrelationships of the four variables to survival. While both Apgar scores were related to survival, independent of the effects of birthweight and gestational age, they were slightly less predictive than either of these variables alone. However, when 1- and 5-minute Apgar scores were combined with gestational age, the predictive value was slightly better than any of the four variables alone or in other possible combinations.