Mapping the amide I absorption in single bacteria and mammalian cells with resonant infrared nanospectroscopy.

Infrared (IR) nanospectroscopy performed in conjunction with atomic force microscopy (AFM) is a novel, label-free spectroscopic technique that meets the increasing request for nano-imaging tools with chemical specificity in the field of life sciences. In the novel resonant version of AFM-IR, a mid-IR wavelength-tunable quantum cascade laser illuminates the sample below an AFM tip working in contact mode, and the repetition rate of the mid-IR pulses matches the cantilever mechanical resonance frequency. The AFM-IR signal is the amplitude of the cantilever oscillations driven by the thermal expansion of the sample after absorption of mid-IR radiation. Using purposely nanofabricated polymer samples, here we demonstrate that the AFM-IR signal increases linearly with the sample thickness t for t > 50 nm, as expected from the thermal expansion model of the sample volume below the AFM tip. We then show the capability of the apparatus to derive information on the protein distribution in single cells through mapping of the AFM-IR signal related to the amide-I mid-IR absorption band at 1660 cm(-1). In Escherichia Coli bacteria we see how the topography changes, observed when the cell hosts a protein over-expression plasmid, are correlated with the amide I signal intensity. In human HeLa cells we obtain evidence that the protein distribution in the cytoplasm and in the nucleus is uneven, with a lateral resolution better than 100 nm.

Mid-infrared spectroscopy beyond the diffraction limit via direct measurement of the photothermal effect.

An atomic force microscope equipped with temperature sensitive probes was used to measure locally the photothermal effect induced by IR light absorption. This novel instrument opens a pathway to correlated topographical, chemical composition, and thermal mapping with nanoscale resolution. Proof of principle demonstration is provided on polymers and plasmonic samples.

Resonance enhanced AFM-IR: a new powerful way to characterize blooming on polymers used in medical devices.

In this paper we demonstrated the application of resonance enhanced AFM-IR to the study of the medical device surfaces. Surface state is one of the most important parameter on the biocompatibility of an implantable medical device. By using this new technique, it was possible to obtain with high resolution topographic and chemical maps and to identify the chemical nature of very thin deposit observed on the surface. This was illustrated with the case of lubricant exudation on polyurethane used in the making of implantable catheters.

High-sensitivity nanometer-scale infrared spectroscopy using a contact mode microcantilever with an internal resonator paddle.

Infrared (IR) spectroscopy is one of the most widely used techniques for identifying and characterizing materials, but is diffraction limited to a spatial resolution of no smaller than several micrometers. This paper reports IR spectroscopy with 100 nm spatial resolution, using a tunable laser whose absorption in an organic layer is measured via atomic force microscopy. Wavelength-dependent absorption in the sample results in local thermomechanical deformation, which is sensed using the sharp tip of a resonant atomic force microscope cantilever. We introduce a cantilever and system design capable of 100 nm spatial resolution and a 6 x sensitivity improvement over previous approaches.

Self-reported symptoms among Danish women following cosmetic breast implant surgery.

The aim of this study was to examine self-reported symptomatology and to identify distinctive characteristics among women with silicone breast implants (SBI). Using the Danish hospital and population registers we identified three groups of women with a hospital diagnosis of muscular rheumatism (a nonspecific soft-tissue diagnostic code) who had previously undergone SBI surgery (n = 28), breast reduction surgery (n = 29) or no breast surgery (n = 27); and three groups of women without a diagnosis of muscular rheumatism who had undergone SBI surgery (n = 21), breast reduction surgery (n = 27) or no breast surgery (n = 56). All study subjects completed a self-administered questionnaire focusing on sociodemographic factors, lifestyle habits, somatic symptoms and psychological symptoms. Women with SBI and women with breast reduction with no previous diagnosis of muscular rheumatism had similar patterns of reporting for most symptoms and characteristics. They reported significantly more somatic symptoms and psychological distress, including somatisation, obsessive-compulsiveness and depression, than women with no breast surgery. No significant differences in self-reported symptomatology and characteristics were observed among the three groups of women with a previous diagnosis of muscular rheumatism. Overall, women with prior muscular rheumatism reported more symptoms than those without. We concluded that self-reported somatic symptoms among women with SBI were similar to those of controls. Women with cosmetic breast surgery appear to have distinctive psychological characteristics. Our study emphasises the importance of taking the psychological profile and previous history of rheumatic diseases into account when examining women with SBI.

Capsular contracture after cosmetic breast implant surgery in Denmark.

The authors investigated the association between the occurrence of capsular contracture and implant and patient characteristics. All women with breast implants from 1977 to 1997 were identified from the files of two private plastic surgery clinics in Denmark. Information on implant and patient characteristics, surgical procedure, and complications was obtained through medical records and self-administered questionnaires. Of 754 women (1,572 implants), average age at implantation was 32 years. Implant types were silicone double lumen, textured, 31.2%; silicone single lumen, textured, 27.8%; silicone single lumen, smooth, 24.5%; silicone double lumen, smooth, 0.8%; and other or missing, 15.7%. Placement was submuscular for more than 90% of implants. Capsular contracture occurred in 7.9% of implanted breasts, on an average of 621 days postoperatively, with 51.6% being bilateral. Overall, 66.1% of capsular contractures were recorded within the first 12 months postoperatively, and 79.0% were recorded within 24 months. Double-lumen implants were associated with a significantly (p < 0.01) reduced occurrence of capsular contracture. In summary, capsular contracture typically occurs within the first 2 years of implantation. Host factors may be important because more than half the capsular contractures in the current study were bilateral. Occurrence of capsular contracture did not appear to be associated with implant surface or placement, occurrence of local complications, or patient characteristics, although these findings should be interpreted cautiously.

Rheumatic manifestations in danish women with silicone breast implants.

The aim of this study was to investigate whether women with silicone breast implants (SBI) present with a unique rheumatic symptomatology. We assessed the profile of rheumatic disease in six groups of women identified through Danish hospital and population registers, three groups of women with a prior hospital diagnosis of muscular rheumatism (a non-specific diagnostic code) who had previously undergone SBI surgery (n = 28), breast reduction surgery (n = 29) or no breast surgery (n = 27); and three groups of women without a diagnosis of muscular rheumatism who had undergone SBI surgery (n = 21), breast reduction surgery (n = 27) or no breast sugery (n = 56). All women in the study population (n = 188) underwent a thorough clinical examination, blood tests and a personal interview. In all study groups soft-tissue rheumatism and degenerative diseases were the most frequent diagnoses. Women with a prior diagnosis of muscular rheumatism but no prior breast surgery had a significantly higher prevalence of soft-tissue rheumatism than those with breast implant or reduction surgery. No significant differences in the frequencies of rheumatic diseases were observed among the three groups of women without previous muscular rheumatism. No specific pattern of inflammatory rheumatic disorders or soft-tissue complaints was identified among the women with SBI, and blood tests for autoimmunity revealed no unique pattern. Overall, women with earlier rheumatism had significantly increased frequencies of rheumatic conditions than did those without. We found no evidence of a rheumatic symptomatology unique to women with silicone breast implants. Our study emphasises the need for consideration of prior rheumatic disease when evaluating rheumatic manifestations in women with SBI.

Prevalence of silicone breast implant rupture among Danish women.

The durability of silicone gel-filled breast implants is of concern, but there are few epidemiological studies on this issue. To date, most of the relevant findings are derived from studies of explantation, which suffer from bias by including women with symptoms or concerns about their implants. As part of a long-term magnetic resonance imaging study of the incidence of rupture, this study involved 271 women with 533 cosmetic breast implants who were randomly selected from among women who underwent cosmetic breast implantation from 1973 through 1997 at one public and three private plastic-surgery clinics in Denmark. The prevalence of rupture was determined from the first magnetic resonance screening. The images were evaluated by four independent readers, using a standardized, validated form. The outcomes under study were rupture, possible rupture, and intact implant. Ruptures were categorized as intracapsular or extracapsular. Overall, 26 percent of implants in 36 percent of the women examined were found to be ruptured, and an additional 6 percent were possibly ruptured. Of the ruptured implants, 22 percent were extracapsular. In multiple regression analyses, age of implant was significantly associated with rupture among second- and third-generation implants, with a 12-fold increased prevalence odds ratio for rupture of implants that were between 16 and 20 years of age, compared with implants between 3 and 5 years of age. Surgitek implants (Medical Engineering Corporation, Racine, Wis.) had a significantly increased prevalence odds ratio of 2.6 for rupture, compared with the reference implants. No significant association was found with the position (subglandular or submuscular) or the type of implant (single- or double-lumen). Extracapsular ruptures were significantly associated with a history of closed capsulotomy (p = 0.001). In the future, the authors plan to examine the women in their cohort with a second magnetic resonance imaging scan to establish the incidence of rupture, a parameter unknown to date in the literature, and to further characterize those factors associated with the actual risk of rupture.

Connective tissue disease and other rheumatic conditions following cosmetic breast implantation in Denmark.

OBJECTIVE: To examine the occurrence of connective tissue diseases (CTDs) as well as ill-defined and other rheumatic conditions among Danish women with cosmetic silicone breast implants. PATIENTS AND METHODS: A total of 2761 women with breast implants and 8807 control subjects were identified from plastic surgery private clinics and from public hospital plastic surgery departments. Women operated on at plastic surgery private clinics were identified through the files of each clinic, while women operated on at public hospitals were identified using the nationwide Danish National Registry of Patients. The control group consisted of women who underwent cosmetic surgery other than breast implantation or who only had a consultation. All women were followed up from January 1, 1977, through December 31, 1996, through the Danish National Registry of Patients for the occurrence of CTD as well as ill-defined and other rheumatic conditions. For the study period January 1, 1977, through December 31, 1994, the Danish National Registry of Patients contains information on hospitalization only, whereas data on outpatient visits are included from 1995 on, thus improving the sensitivity of the data. The implant and control groups were compared with the Danish population rates for CTD and ill-defined and other rheumatic conditions, and a direct comparison between the implant and control groups was also performed. RESULTS: When compared with rates from the general population, no excess of definite CTD was observed in the implant cohorts. For ill-defined and other rheumatic conditions, statistically significant excesses of unspecified rheumatism were observed in both the implant and control cohorts when compared with national rates. A direct comparison between the implant and control cohorts found no material differences between the groups. CONCLUSIONS: The findings of this study support previous investigations and independent review panel conclusions that an association between silicone breast implants and definite CTDs is unlikely. The observation of an excess of unspecified rheumatism among women with implants and among control women suggests that women undergoing cosmetic plastic surgery have hospitalization rates for this condition in excess of those from the general population.

Connective tissue disease after hip and knee implant surgery.

OBJECTIVE: To increase the knowledge of the long-term effects of artificial hip and knee joint implants. METHODS: The study groups consisted of 24,636 patients with osteoarthritis who underwent hip implant surgery and 5,221 who received knee implants during 1977-89. The post-implant rate of hospitalization for connective tissue disease (CTD) was compared with the rate in the general population of Denmark and with that among osteoarthritis patients without implant surgery. RESULTS: The rates of hospitalization for CTD were higher than the background level among both hip and knee implant patients with osteoarthritis, whereas the comparison with non-implanted osteoarthritis patients revealed that the hospitalization rate for CTD was reduced after hip implant surgery, but increased after knee implant surgery. CONCLUSION: Since the materials used in hip and knee implants in Denmark are not substantially different, these results are unlikely to reflect an implant effect but rather the selection criteria of referral for implant surgery.

Neurological disease among women with silicone breast implants in Denmark.

OBJECTIVES: To investigate the risk of neurological disease among women with cosmetic breast implants. MATERIAL AND METHODS: We identified 1,653 women who had undergone breast implant surgery at private clinics in Denmark and a comparison cohort of 1,736 women who underwent other types of cosmetic surgery at the same clinics. Ratios of observed-to-expected numbers of hospitalizations for neurological disease in the private implant and comparison cohorts were calculated, separately and combined with data from updated public hospital cohorts. RESULTS: The occurrence of neurological disease in the private clinic implant cohort was comparable to that in the general population. A similar risk pattern was observed in the private clinic comparison cohort. When data for these private clinic cohorts were combined with updated data for public hospital cohorts, excess risks for neurological disorders were seen in both implant and comparison cohorts, reaching statistical significance only in the comparison cohort. CONCLUSION: Our findings indicate no causal association between silicone breast implants and neurological disease.

Cancer occurrence after cosmetic breast implantation in Denmark.

Most studies on cancer incidence after breast implantation have focused on breast cancer, while the risk of cancers at other sites has been less well investigated. We examined cancer incidence among 1,653 women who underwent cosmetic breast implant surgery at private clinics of plastic surgery in Denmark and 1,736 women attending the same clinics for other reasons during the period 1973-1995. Furthermore, we updated previously reported results among 1,114 women who received implants for cosmetic indications at public hospitals. All women were followed for cancer through the Danish Cancer Registry. In comparison with the general female population, the overall standardized incidence ratio (SIR) for cancer among women who received implants in private clinics was 1.65 [95% confidence interval (CI) = 1.17-2.27]. This elevated SIR reflected increased incidence ratios for almost all major cancer sites; however, only for non-melanoma skin cancer was there an excess of more than 2 cases. No significant excess of cancer was observed among women who received implants in public hospitals (SIR = 1.10, 95% CI = 0.76-1.52) or among women attending the private clinics for other problems (SIR = 1.10, 95% CI = 0.78-1.52). The SIRs for breast cancer after breast implantation were 1.1 (95% CI = 0.5-2.2) among private clinic patients and 0.9 (95% CI = 0.4-1.7) among public hospital patients. The overall findings of these 2 implant cohorts and results from other investigations suggest that cancer risk is probably not increased among women receiving cosmetic breast implants. The inconsistent results for private clinics and public hospitals are likely related to selection bias and confounding among the private clinic patients, but our data did not permit exploration of these possibilities. Further research into the determinants of these inconsistencies is warranted.

Health outcomes in offspring of mothers with breast implants.

OBJECTIVE: To examine the occurrence of esophageal disorders, connective tissue diseases, and congenital malformations in children of mothers with breast implants. METHODS: Nationwide register-based follow-up study of all offspring born during 1977 to 1992 to a cohort of 1135 women with breast implants for cosmetic reasons and to a comparison cohort of 7071 women who underwent breast reduction surgery. Cause-specific hospi-talization rates among offspring, relative to those of the general population, were calculated from the Danish National Registry of Patients. RESULTS: Among the 939 children of mothers with breast implants, higher rates of esophageal disorders were observed, but the excess was similar for those born before versus after the implant surgery. Higher than expected hospitalization rates for these conditions were also observed among 3906 children of women who underwent breast reduction surgery. No significant increases in connective tissue diseases or congenital malformations were observed in either the breast implant or breast reduction cohorts. CONCLUSIONS: This first epidemiologic cohort study provides no evidence that silicone breast implants affect risks of esophageal or other disorders in children of the implantees. Rather, the observed risk pattern suggests that a lower threshold exists among both groups of women who have undergone cosmetic breast surgery in seeking professional medical care for problems normally solved outside the hospital.

Neurologic disease among women with breast implants.

OBJECTIVE: To investigate the risk of neurologic disease among women with silicone breast implants. BACKGROUND: Since 1992, several case series reported an association between silicone breast implants and neurologic diseases. METHODS: Between 1977 and 1992, 1,135 women received cosmetic silicone breast implants, and 7,071 women had breast reduction surgery, as identified by the Danish National Register of Patients (NRP). NRP files provided information on numbers and types of subsequent neurologic disorders at hospital discharge, which were compared with expected numbers, calculated on the basis of national hospital discharge rates. RESULTS: In the two study cohorts, hospital discharge rates for neurologic diseases were raised by some 60% to 70% compared with Danish women in general. Among women with silicone breast implants, 13 subsequently developed a neurologic disorder compared with 7.7 expected; whereas in the comparison group, 63 observed versus 39.1 expected disorders were recorded. These results indicate that relative to the comparison cohort, women with implants had no excessive levels of definite neurologic disease. Furthermore, medical record reviews revealed that the majority of women with implants discharged with a neurologic diagnosis had either symptoms before implant surgery or neurologic symptoms secondary to degenerative diseases. CONCLUSIONS: Our findings do not support the hypothesis of silicone-induced neurologic disease. The reasons for the elevated rates of neurologic disease in both the exposed and comparison cohorts remain unclear, but may reflect selection processes associated with these women seeking medical care more often than the general population.

Breast implants and cancer risk in Denmark.

Although millions of women worldwide have received breast implants for cosmetic or medical reasons, possible late effects (in particular cancer) have not been well studied. To provide quantitative information on cancer occurrence among women undergoing breast implant surgery, 1,135 women treated for cosmetic reasons in Denmark were evaluated. Patients were identified using the nationwide Hospital Discharge Registry with linkage to the nationwide Danish Cancer Registry to determine subsequent cancer incidence. The average age of the women at implant surgery was 31 years, and the average follow-up was 8.4 years, up to a maximum of 17 years. Overall, 27 cancers developed after implant surgery compared with 24.7 expected based on incidence rates from the general population (standardized incidence ratio [SIR] = 1.1; 95% CI: 0.7-1.6). Eight breast cancers were observed vs. 7.8 expected (SIR = 1.0; 95% CI: 0.4-2.0). No evidence was found to link breast implants with increased cancer risk in the decade after surgery. While the results are encouraging, longer follow-up into later life will be necessary to assess fully any possible adverse effects.

[Silicone breast implants and breast cancer]. / Silikonebrystproteser og brystkraeft.

Sarcomas have been shown to develop next to foreign body implants, silicone included, in animal experiments. However, this carcinogenesis is not believed to have any human relevance. A review of the existing epidemiological studies suggests that women with silicone breast implants have a reduced risk for developing breast cancer. However, the presence of breast implants does obscure mammographic visualization as well as palpation of mammary tissue. This has led to the assumption that breast cancer detection could be compromised in women with breast implants. In the few studies that have dealt with this issue, women with breast implants were diagnosed with the same stage of disease as women without implants. However, the percentage of false negative mammographies was increased in one study. In conclusion, there is currently no evidence of an association between breast implants and cancer or postponed breast cancer detection.

The loci of mineral in turkey leg tendon as seen by atomic force microscope and electron microscopy.

Transmission electron micrographs of fully mineralized turkey leg tendon in cross-section show the ultrastructure to be more complex than has been previously described. The mineral is divided into two regions. Needlelike-appearing crystallites fill the extrafibrillar volume whereas only platelike crystallites are found within the fibrils. When the specimen is tilted through a large angle, some of the needlelike-appearing crystallites are replaced by platelets, suggesting that the needlelike crystallites are platelets viewed on edge. If so, these platelets have their broad face roughly parallel to the fibril surface and thereby the fibril axis, where the intrafibrillar platelets are steeply inclined to the fibril axis. The projection of the intrafibrillar platelets is perpendicular to the fibril axis. The extrafibrillar volume is at least 60% of the total, the fibrils occupying 40%. More of the mineral appears to be extrafibrillar than within the fibrils. Micrographs of the mineralized tendon in thickness show both needlelike-appearing and platelet crystallites. Stereoscopic views show that the needlelike-appearing crystallites do not have a preferred orientation. From the two-dimensional Fourier transform of a selected area of the cross-sectional image, the platelike crystallites have an average dimension of 58 nm. The needlelike-appearing crystallites have an average thickness of 7 nm. The maximum length is at least 90 nm. Atomic force microscopy (AFM) of unstained, unmineralized turkey leg tendon shows collagen fibrils very much like shadow replicas of collagen in electron micrographs. AFM images of the mineralized tendon show only an occasional fibril. Mineral crystallites are not visible. Because the collagen is within the fibrils, the extrafibrillar mineral must be embedded in noncollagenous organic matter. When the tissue is demineralized, the collagen fibrils are exposed. The structure as revealed by the two modalities is a composite material in which each component is itself a composite. Determination of the properties of the mineralized tendon from the properties of its elements is more difficult than considering the tendon to be just mineral-filled collagen.

Silicone mammary implants and connective tissue disease.

The American Food and Drug Administration recently restricted the use of silicone gel-filled mammary implants for breast augmentations and reconstructions because a number of case reports had suggested that there was an association between silicone and connective tissue disease. We have found 36 such case reports published since 1982. Systemic sclerosis is the most common reported diagnosis (n = 15). Implants were removed from 15 patients, in nine of whom symptoms improved. The mechanism behind the postulated relationship is obscure, and most authors focused on an auto-immune-like response to silicone, which acts directly as a hapten or as an adjuvant. We found no conclusive evidence to implicate silicone mammary implants in connective tissue diseases. We do, however, recommend removal of implants from patients with severe connective tissue diseases. Patients with symptoms or active connective tissue disease should not be considered for silicone implants.

[Silicone breast implants and connective tissue disease]. / Silikone-brystimplantater og bindevaevssygdomme.

The American Food and Drug Administration (FDA) recently introduced a temporary stop for silicone breast prosthesis implants. The reason is a suspected connection between silicone implants and the development of autoimmune disease. The present authors have reviewed the 32 cases of connective tissue disease which have hitherto been reported in the literature, of these 13 were cases of systemic sclerodermia. On the basis of approximately 2 million silicone prosthesis implants which were introduced in USA alone during the past 20 years, approximately 200 cases of systemic sclerodermia would be anticipated. Nevertheless, the fact that several patients had spontaneous remission of their chronic disease after removal of the silicone implant speaks in favour of a possible connection. It is concluded that on account of the limited number of cases of connective tissue disease which have been reported in patients with silicone implants, insufficient evidence is present to stop implantation of these. Implantation of prostheses filled with saline are recommended for patients with connective tissue disease.