Scanning electron microscope fractography of induced fatigue-damaged saline breast implants.

Breast implant strength and durability is presently an important topic in biomaterials science. Research studies are being conducted to determine the mechanisms and rates of failure in order to assess the in vivo performance of breast implants. Fatigue life is a measure of breast implant durability since fatigue failure is a potential in vivo failure mechanism. This study describes the characterization of the fracture surface morphology of breast implant shell regions that have failed due to cyclic fatigue. Saline breast implants were fatigue tested to failure using a laboratory apparatus in which flat plates cyclically compressed the implants. The implants were unimplanted control devices of both textured and smooth saline implants. The failure surfaces of the fatigued shells were examined using scanning electron microscopy (SEM). The morphological features of the failure surfaces are described for implants with short and long fatigue lifetimes. The details of both the inside and outside surfaces of the shell at the failure location are described. Two different modes of failure were observed in both the textured and smooth shells. These modes depend on the magnitude of the cyclic load and corresponding number of fatigue cycles at failure. The first mode is a tear in the shell of about 18 mm in length, and the second mode is a pinhole approximately 1 mm in diameter. Details of the surface morphology for these two types of failure modes and shell thickness data are presented herein. There was no significant change in the crosslink density of the shell as a result of fatigue.

Variability in the properties of silicone gel breast implants.

Several generations of silicone gel breast implants have been produced by implant manufacturers. The primary material usually viewed as the base material in the manufacture of implants is polydimethylsiloxane. Polymeric reactions are notorious for their variability and nonuniformity. The elastomer used in different types of implants can have vastly different properties. Furthermore, the material properties associated with a particular type of implant can vary considerably from one lot to the next. Considering the various designs, styles, and manufacturing techniques associated with silicone gel implants, knowledge of the original properties of the implants before implantation is important in determining the effects of aging in vivo. This study was conducted to investigate differences in key mechanical and chemical properties of silicone gel breast implant materials. The two types of implants chosen for analysis were Silastic I and Silastic II control implants. Material property data were determined for both types of controls and significant differences were found in their values. Lot-to-lot variability was also investigated and found to be significant.

The transport of octamethylcyclotetrasiloxane (D4) and polydimethylsiloxane (PDMS) in lightly cross-linked silicone rubber.

The transport of octamethylcyclotetrasiloxane (D4), one of the major constituents of silicone fluids and rubbers, and low viscosity polydimethylsiloxane oil into a silica filled cross-linked silicone elastomeric rubber was measured as a function of temperature, cross-link density of the rubber, and concentration of the D4 in methanol solution. A small amount of material, approximately 3 wt%, is extracted from the rubber with hexane. The extraction process has a large effect upon D4 solubility in the rubber, increasing from approximately 160 to 180 wt% after extraction. The heats of solution for both penetrants into the rubber are essentially zero and the activation energies for diffusion are small, approximately 8 and 15 kJ molt(-1) for D4 and PDMS, respectively. The diffusion process is Fickian and the diffusion coefficient of D4 into silicone/silica rubbers is essentially independent of concentration over the concentration investigated, i.e. from 1 to 100 vol% D4 in methanol. The permeability, i.e. the product of the diffusion coefficient and the solubility, decreases rapidly for D4 concentrations less than 50 vol% (0.1 mol fraction). This suggests that the permeation of D4 out of any encapsulation device, such as a silicone breast implant, is linearly dependent upon the concentration of D4 in the prosthesis. Swelling is isotropic and was measured by dimensional changes in rectangular samples and correlates well with the volume of D4 sorbed.

Effects of environmental antiandrogens on reproductive development in experimental animals.

Chemicals that act as androgen receptor (AR) agonists and antagonists or inhibit fetal steroidogenesis can induce reproductive malformations in humans and laboratory animals. Several environmental chemicals disrupt development in rats and/or rabbits at fetal concentrations at, or near, exposure levels seen in some segments of the human population. In rats, fetal tissues concentrations of 10-20 p.p.m. of the DDT metabolite, p,p'-DDE, are correlated with reproductive abnormalities in male offspring. These concentrations are similar to those measured in first-trimester human fetal tissues in the late 1960s. The pesticides vinclozolin, procymidone, linuron and DDT are AR antagonists. They reduce male rat anogenital distance, and induce areolas at relatively low dosages. Hypospadias, agenesis of the sex accessory tissues and retained nipples are seen in the middle dosages, while undescended testes and epididymal agenesis are seen in the highest doses. Phthalate esters (PE) inhibit testosterone synthesis during fetal life, but do not appear to be AR antagonists. Prenatal administration of a single low dose of dioxin (50-1,000 ng TCDD/kg) alters the differentiation of androgen-dependent tissues at p.p.t. concentrations, but the mechanism of action likely involves interaction with a hormone-like nuclear transcription factor, the hormone-like receptor AhR, rather than AR. p,p'-DDT and p,p'-DDE, vinclozolin and di-n-butyl phthalate affect reproductive function in rabbits when administered during prenatal and/or neonatal life. Cryptorchidism and carcinoma in situ-like (CIS) testicular lesions were seen in male rabbits treated during development with p,p'-DDT or p,p'-DDE. Extrapolation of effects from rodents to humans would be enhanced if future studies incorporate determination of tissue concentrations of the active metabolites. Knowledge of the tissue concentrations of the active toxicants also would provide an important link to in-vitro studies, which provide more useful mechanistic information when they are executed at relevant concentrations.

Scanning electron microscopy characterization of surgical instrument damage to breast implants.

In this article, mechanisms of breast-implant failure caused by surgical instruments commonly used to perform implantation, breast biopsies, needle localization procedures, cyst aspirations, and explantation are described. Failure was artificially induced in breast-implant shells using various types of surgical instruments, including scalpels, suture needles, hypodermic needles, hemostats, and Adson forceps. Field-emission scanning electron microscopy (SEM) was used to document the morphology of the failure sites produced by these instruments. Micrographs were used to categorize failure according to a specific type of surgical instrument. SEM micrographs were also obtained on explants that failed in situ, and the morphology of the corresponding failure sites was examined. The study was designed to document a range of failure mechanisms associated with gel-filled, saline-filled, double-lumen (saline-gel), and soybean oil-filled implants. The results of the study also demonstrate that SEM can often be used to determine the cause of breast-implant failure.

Practical methods for detecting mendacity: a case study.

This study demonstrates the concurrence of the use of objective verbal and nonverbal signs and lying. President Clinton's Grand jury Testimony of August 17, 1998, was examined for the presence of 23 clinically practical signs of dissimulation selected from 64 peer-reviewed articles and 20 books on mendacity. A segment of his testimony that was subsequently found to be false was compared with a control period during the same testimony (internal control). A fund-raising speech to a sympathetic crowd served as a second control (external control). The frequencies of the 23 signs in the mendacious speech were compared with their frequencies during the control periods, and the differences were analyzed for statistical significance. No clinical examination was performed nor diagnosis assigned. During the mendacious speech, the subject markedly increased the frequency of 20 out of 23 signs compared with their frequency during the fund-raising control speech (p < .0005). He increased the frequency of 19 signs compared with their frequency during the control period of the same testimony (p < .003). The 23 signs may be useful as indicators of the veracity of videotaped and scripted testimony. If these findings are confirmed through further testing, they could, with practice, be used by psychiatrists conducting interviews.

Characterization of the period of sensitivity of fetal male sexual development to vinclozolin.

Vinclozolin is a fungicide whose metabolites are androgen receptor (AR) antagonists. Previous work in our laboratory showed that perinatal administration of vinclozolin to rats results in malformations of the external genitalia, permanent nipples, reduced anogenital distance (AGD), and reduced seminal vesicle, ventral prostate, and epididymal weights. The objectives of this study were to determine the most sensitive period of fetal development to antiandrogenic effects of vinclozolin and to identify a dosing regime that would induce malformations in all of the male offspring. Pregnant rats were dosed with 400 mg vinclozolin/kg/day on either GD 12-13, GD 14-15, GD 16-17, GD 18-19, or GD 20-21, or with corn oil (2.5 ml/kg) from GD 12 through GD 21 (Experiment 1). All 2-day periods in which significant effects were produced were included in an extended dosing period, GD 14 through GD 19, in which pregnant rats were dosed with 200 or 400 mg vinclozolin/kg (Experiment 2). In Experiment 1, significant effects of vinclozolin were observed in rats dosed on gestation days (GD) 14-15, GD 16-17, and GD 18-19, while the most significant effects were observed in rats treated on GD 16-17. These effects include reduced AGD; presence of areolas, nipples, and malformations of the phallus; and reduced levator ani/bulbocavernosus weight. In contrast, ventral prostate weight was reduced only in the GD 18-19 group. The expanded dosing regime (Experiment 2) increased the percentage of male offspring with genital malformations (> 92%), and retained nipples (100%), further reduced the weight of the ventral prostate, and reduced the weight of the seminal vesicles. In addition, malformations were more severe and included vaginal pouch and ectopic/undescended testes. The latter was induced only in the 400 mg/kg group. These data indicate that the reproductive system of the fetal male rat is most sensitive to antiandrogenic effects of vinclozolin on GD 16 and 17, although effects are more severe and 100 % of male offspring are affected with administration of vinclozolin from GD 14 through GD 19.

Effect of surgical insertion on the local shell properties of SILASTIC II silicone gel breast implants.

The reasons for the failure of silicone gel breast implants are unclear. One potential failure mechanism is the weakening of the implant shell during its insertion into the breast. Such local weakening could eventually lead to implant failure. We recently reported on the effect of implant surgery on the overall mechanical properties of SILASTIC II gel-filled implants. In the earlier study, the mechanical properties of 34 Dow Corning SILASTIC II gel-filled breast implants from the same manufacturing lot were measured. Twenty of the thirty four implants were not implanted but were evaluated to establish a baseline of control data. The other fourteen lot-matched implants were inserted into a subglandular pocket through an inframammary incision in a cadaver breast and then removed. The experimental augmentation scenario was designed to represent actual breast implantation as closely as possible. The mechanical properties of the anterior and posterior sides of the control implants (not implanted) and explants (implanted in a cadaver) were measured and compared to determine whether differences existed between the explant and control groups. We found that the implantation surgery process did slightly reduce the average tensile strength. Although not as statistically significant, other mechanical properties such as breaking energy and moduli were less for the explants than the controls. The reduction was a relatively small percentage in the context of overall shell properties. Elongation and tear resistance were unaffected. Our findings suggested that the surgical act of implanting a breast implant has a small but detectable weakening effect on the average tensile strength, breaking energy and moduli of the elastomeric shell of the device. The present study is an extension of the previous investigation. Here we have analyzed the explant shell region where the surgeon's fingers forced the implant through the incision. Our results indicate that the implant shell can be locally damaged due to the implantation process.

Gestational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) severely alters reproductive function of female hamster offspring.

Low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), administered as a single dose to the dam during gestation, alter development of the fetal rodent reproductive system. In male rat and hamster offspring, dosing with TCDD during gestation reduces epididymal and ejaculated sperm counts and delays puberty. In female rats, in utero TCDD-exposure results in reduced ovarian weight and fecundity, and induces cleft phallus and a persistent thread of tissue across the vaginal orifice. Here, we demonstrate that 2-microgram TCDD/kg, administered as a single oral dose prior to sexual differentiation, alters reproductive function in female hamster offspring, a species relatively resistant to the lethal effects of TCDD. In the current study, pregnant hamsters (P0 generation) were dosed orally with vehicle (corn oil) or 2 micrograms TCDD/kg on gestational day (GD) 11.5. P0 maternal viability, body weight, fertility, and F1 litter size did not differ between control and treated groups. In the F1 generation, body weights were permanently reduced by about 30%, vaginal opening was delayed (p < 0.0001), and vaginal estrous cycles were altered by TCDD treatment. In contrast, most treated female offspring displayed regular 4-day behavioral estrous cycles, indicating that in utero TCDD treatment did not markedly disrupt hypothalamic-pituitary-gonadal hormonal cyclicity. Although both control and TCDD-treated F1 females mated successfully with a control male (estrous cyclicity was abolished by mating), 20% of the F1 treated females did not become not pregnant (no implants). In addition, 38% of pregnant F1 females from the TCDD group died near-term, and the numbers of implants in pregnant animals (treated 5.1 versus 11.3) and pups born live (2.7 treated vs. 8.7 control) were reduced by TCDD-treatment. In the F2, survival through weaning was drastically reduced (15% treated vs. 78% for control) by TCDD treatment of P0 dams. F1 female hamster offspring exposed in utero to TCDD displayed external urogenital malformations, with most females having complete clefting of the phallus, an effect previously reported in the rat. Unlike rats exposed to TCDD (0.2-1.0 microgram/kg) on GD 15 or GD 8, hamster offspring did not display vaginal threads. These results demonstrate that in utero administration of TCDD adversely affects growth, reproductive function, and anatomy in female hamster offspring given a dosage level nearly four orders of magnitude below the dosage level toxic to the adult animal. Adverse effects of TCDD persisted through two generations (F1 and F2), even though the F1 was only indirectly exposed during gestation and lactation.

The fungicide procymidone alters sexual differentiation in the male rat by acting as an androgen-receptor antagonist in vivo and in vitro.

Procymidone is a dicarboximide fungicide structurally related to the well-characterized fungicide vinclozolin. Vinclozolin metabolites bind to mammalian androgen receptors (AR) and act as AR antagonists, inhibiting androgen-dependent gene expression in vivo and in vitro by inhibiting AR-binding to DNA. The current study was designed to determine if procymidone acted as an AR antagonist in vitro and to describe the dosage levels of procymidone that alter sexual differentiation in vivo. In vitro, procymidone inhibited androgen from binding the human AR (hAR) in COS (monkey kidney) cells transfected with hAR at 3.16 microM. In vitro, procymidone acted as an androgen antagonist, inhibiting dihydrotestosterone (DHT)-induced transcriptional activation at 0.2 microM in CV-1 cells (cotransfected with the hAR and a MMTV-luciferase reporter gene). In vivo, maternal procymidone exposure at 0, 25, 50, 100, or 200 mg kg-1 day-1 during gestation and early lactation (gestational day 14 to postnatal day 3) altered reproductive development of male offspring at all dosage levels tested. Male offspring exhibited shortened anogenital distance (at 25 mg kg-1 day-1 and above), permanent nipples, reduced weight of several androgen-dependent tissues (levator ani and bulbocavernosus muscles, prostate, seminal vesicles, Cowper's gland and glans penis), and malformations (hypospadias, cleft phallus, exposed os penis, vaginal pouch, hydronephrosis, occasional hydroureter, epididymal granulomas, and ectopic, undescended testes). In addition, perinatal procymidone treatment had a marked effect on the histology of the lateral and ventral prostatic and seminal vesicular tissues of the offspring (at 50 mg kg-1 day-1 and above). These effects consisted of fibrosis, cellular infiltration, and epithelial hyperplasia. This constellation of effects is similar to that produced by perinatal exposure to vinclozolin. However, procymidone appears to be slightly less potent in inducing malformations than vinclozolin by a factor of about two. In summary, the antiandrogenic activity of procymidone was demonstrated in vivo and in vitro in cell lines transfected with hAR. Since the role of androgens in mammalian sexual differentiation is highly conserved, it is likely that humans would be adversely affected by procymidone in a predictable manner if the human fetus was exposed to sufficient levels during critical stages of intrauterine and neonatal life.

Effect of gonadotropins on the ability of 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) to inhibit germinal vesicle breakdown in bovine oocytes.

The transcriptional inhibitor, 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), prevents germinal vesicle breakdown (GVBD) in bovine oocytes only in the presence of gonadotropins. The objectives of this study were to examine the ability of gonadotropins to facilitate transcriptional inhibition of GVBD in bovine oocytes and to examine the effect of gonadotropins on transcriptional inhibition of cumulus expansion. Cumulus-oocyte complexes (COC) from 2 to 7 mm follicles were cultured in TCM-199 with 1 microg/ml estradiol, 50 microg/ml gentamicin and hormonal treatments for 20 to 24 h at 39 degrees C in 5% CO2 in air. After culture, COC were assessed for degree of cumulus expansion and oocytes were then denuded, fixed and stained to determine stage of meiosis. In the presence of LH and FSH the proportion of oocytes arrested at germinal vesicle (GV) stage was significantly increased with DRB treatment (58 vs 3% GV for LH/FSH + DRB vs LH/FSH-DRB; P < 0.001). However, maximal inhibition of GVBD by treatment with DRB could also be achieved in the presence of FSH alone (60% GV for FSH + DRB). The ability of DRB to block GVBD was significantly reduced in the presence of LH alone (20 to 28% GV for LH + DRB; P < 0.05 vs FSH + DRB), and treatment with DRB did not block GVBD in the presence of hCG (6.8 to 13.3% GV for hCG + DRB; P < 0.001 vs FSH + DRB). Inhibition of cumulus expansion by treatment with DRB occurred in the presence of either FSH or LH. Based on these results, it is suggested that DRB prevents GVBD in cultured bovine COC by interfering with a transcriptional event mediated primarily by FSH.

Surgical treatment of persistent exit-site infections.

Persistent exit-site infections and tunnel infections (ESI/TI) are a cause for removal of Swan neck catheters (SNC). Previous studies report variable success in the treatment of these infections by surgical exposure and removal of the subcutaneous external cuff. We report our experience with this technique. All 5 patients with persistent ESI/TI were successfully treated with antibiotics and surgical intervention. All cultures grew Staphylococcus aureus. Average time to complete healing after surgical exposure was 39.4 days. Mean follow-up after complete healing was 164.8 days. There were no subsequent episodes of ESI/TI in these patients. None of the catheters subsequently malfunctioned or developed leaks. Persistent ESI/TI in Swan neck catheters can be successfully treated with surgical exposure and removal of the subcutaneous external cuff.

Chemical, physical and mechanical analysis of explanted breast implants.

The chemical and biomechanical properties of explanted implants whose time of implantation ranged from zero to 21 years were measured. The properties appear to decrease with time. However it is important to note that proper controls have yet to be tested. The consistency of the gel varied considerably with manufacturer and date of manufacture. The data will be correlated with control samples when they become available. The data are consistent with the hypothesis that in some instances, the gel does affect the cross-linking, i.e., strength, of the silicone rubber shell. At the present time only a limited number of samples have been tested in this on-going program. One of our major objectives, to determine the influence of the physiological environment of the human body on the durability of the silicone implant, has yet to be quantified.

Acid dialysate correction of metabolic alkalosis in renal failure.

Severe metabolic acidosis may occur during hemodialysis when the incorrect acid dialysis concentrate from a two-part bicarbonate dialysis system is used in an acetate dialysis machine. We deliberately applied this technique to correct severe metabolic alkalosis in a patient with chronic renal failure. Rapid correction of the metabolic alkalosis was achieved and the procedure was well tolerated.

Effects of feto-placental markers with plasma exchange in pregnancy.

To evaluate changes in feto-placental markers with plasma exchange in pregnancy, two patients at varying stages of pregnancy referred to a tertiary care hospital and requiring plasma exchange for intercurrent problems were evaluated. Alpha-fetoprotein, human chorionic gonadotropin, and free estriol were sequentially measured in the patients' plasma and in the fluid removed, thus permitting calculations of permeability rates and clearances. Despite markedly different molecular weights, all three feto-placental markers had similar permeabilities and clearances. While in both patients maternal levels of alpha-fetoprotein and human chorionic gonadotropin decreased rapidly with plasma separation and rebounded rapidly to baseline, free estriol responded differently and did not appear to decrease with therapy. Maternal levels of feto-placental markers only transiently changed with plasma exchange during pregnancy and rapidly returned to baseline with no apparent consequences to the pregnancy.

Acute plasma separation with hemodialysis equipment.

Although plasma separation has been reported to have a relatively small complication rate in large series of healthy outpatients, little attention has been directed to the evaluation of the safety and effectiveness of the therapy in acutely ill, hospitalized patients. The experience of using standard hemodialysis equipment and membrane plasma separators with 281 plasma separation treatments in 49 patients over the last 7 yr is reported and analyzed. The data reveal a 1.4% incidence of hypotension and a 0.4% incidence of hematuria in the 281 treatments--rates similar to those reported in outpatients. In addition, analysis of the diseases and patients treated over the 7 yr reported demonstrates a marked shift from immunological and hematological disorders towards neurological disorders. The data suggest that plasma separation may be easily and safely performed by any institution capable of performing acute hemodialysis.

Adequacy of dialysis in CAPD and cycler PD; the PET is enough.

Assessment of adequacy of dialysis has become a necessary part of all peritoneal dialysis programs; this task is particularly burdensome in home cycler patients. To test the hypothesis that the Peritoneal Equilibration Test (PET) reliably predicts clearance, as measured by classical clearance methodology, both CAPD and cycler patients underwent PET tests and clearance studies. In cycler patients, Dialysis to Plasma Ratios (D/P) for urea nitrogen (UN) and D/P for creatinine as determined by clearance methods correlated extremely well with those obtained by PET test. D/P creatinine also correlated well (clearance versus PET) in CAPD patients; D/P UN approached unity in all CAPD patients with dwell times of 4 hours or longer. In all cases, the PET prescription was highly accurate in predicting 24-hour clearance results. These results are useful in those patients in whom 24-hour home collections are inconvenient or impossible, especially in cycler patients.