[A case of human adjuvant disease with clinical features of Guillain-Barré syndrome].

A 69-year-old female developed subacute diplopia, right peripheral facial nerve palsy, bilateral upper and lower extremities dysesthesia and weakness 50 years after silicone injection for breast augmentation. Motor conduction study revealed prolonged distal latency and reduced amplitude in the median, ulnar, and peroneal nerves. Sensory conduction velocities were reduced in the median and ulnar nerves, and sensory potential in the sural nerve could not be recorded. While intravenous immunoglobulin therapy was ineffective, explantation of silicone breast implants improved her neurological symptoms. Histopathological study of axillary lymph node revealed foreign body granulomas and macrophages phagocyting silicone. The patient was diagnosed with human adjuvant disease presenting clinical features of Guillain-Barré syndrome. Human adjuvant disease should be considered in the patients with implants like silicone and neurological symptoms.

Mesotherapy: Safety profile and management of complications.

BACKGROUND: Mesotherapy is a procedure that involves the injection of active substances into the dermis and subcutaneous tissue in order to treat several local medical and cosmetic conditions. Despite being considered as a relatively safe method, a series of adverse reactions can occur due to its wide application and lack of standardization processes. OBJECTIVES: The aim of this paper is to summarize all the mesotherapy-related complications published so far, and to provide an insight into their management. PATIENT/METHODS: Articles derived from the databases, PubMed, EMBASE, and SCOPUS, and published between 1992 and 2018, were analyzed for this review. The study was conducted according to the PRISMA guidelines. RESULTS: In this literature, there is a number of case series and isolated case reports describing various side effects of different severities. The therapeutic management of these complications is-in most cases-individualized. CONCLUSIONS: Larger systematic studies are needed in order to adequately evaluate the safety profile of mesotherapy, and in order to determine standardized therapy parameters, so as to minimize the risk of potential adverse reactions.

Improved Multicellular Response, Biomimetic Mineralization, Angiogenesis, and Reduced Foreign Body Response of Modified Polydioxanone Scaffolds for Skeletal Tissue Regeneration.

The potential of electrospun polydioxanone (PDX) mats as scaffolds for skeletal tissue regeneration was significantly enhanced through improvement of the cell-mediated biomimetic mineralization and multicellular response. This was achieved by blending PDX ( i) with poly(hydroxybutyrate- co-valerate) (PHBV) in the presence of hydroxyapatite (HA) and ( ii) with aloe vera (AV) extract containing a mixture of acemannan/glucomannan. In an exhaustive study, the behavior of the most relevant cell lines involved in the skeletal tissue healing cascade, i.e. fibroblasts, macrophages, endothelial cells and preosteoblasts, on the scaffolds was investigated. The scaffolds were shown to be nontoxic, to exhibit insignificant inflammatory responses in macrophages, and to be degradable by macrophage-secreted enzymes. As a result of different phase separation in PDX/PHBV/HA and PDX/AV blend mats, cells interacted differentially. Presumably due to varying tension states of cell-matrix interactions, thinner microtubules and significantly more cell adhesion sites and filopodia were formed on PDX/AV compared to PDX/PHBV/HA. While PDX/PHBV/HA supported micrometer-sized spherical particles, nanosized rod-like HA was observed to nucleate and grow on PDX/AV fibers, allowing the mineralized PDX/AV scaffold to retain its porosity over a longer time for cellular infiltration. Finally, PDX/AV exhibited better in vivo biocompatibility compared to PDX/PHBV/HA, as indicated by the reduced fibrous capsule thickness and enhanced blood vessel formation. Overall, PDX/AV blend mats showed a significantly enhanced potential for skeletal tissue regeneration compared to the already promising PDX/PHBV/HA blends.

Dexamethasone Reduces the Foreign Body Reaction to Intraneural Electrode Implants in the Peripheral Nerve of the Rat.

Intraneural electrodes must be in intimate contact with nerve fibers to have a proper function, but this interface is compromised due to the foreign body reaction (FBR). The FBR is characterized by a first inflammatory phase followed by a second anti-inflammatory and fibrotic phase, which results in the formation of a tissue capsule around the implant, causing physical separation between the active sites of the electrode and the nerve fibers. We have tested systemically several anti-inflammatory drugs such as dexamethasone (subcutaneous), ibuprofen and maraviroc (oral) to reduce macrophage activation, as well as clodronate liposomes (intraperitoneal) to reduce monocyte/macrophage infiltration, and sildenafil (oral) as an antifibrotic drug to reduce collagen deposition in an FBR model with longitudinal Parylene C intraneural implants in the rat sciatic nerve. Treatment with dexamethasone, ibuprofen, or clodronate significantly reduced the inflammatory reaction in the nerve in comparison to the saline group after 2 weeks of the implant, whereas sildenafil and maraviroc had no effect on infiltration of macrophages in the nerve. However, only dexamethasone was able to significantly reduce the matrix deposition around the implant. Similar positive results were obtained with dexamethasone in the case of polyimide-based intraneural implants, another polymer substrate for the electrode. These results indicate that inflammation triggers the FBR in peripheral nerves, and that anti-inflammatory treatment with dexamethasone may have beneficial effects on lengthening intraneural interface functionality. Anat Rec, 301:1722-1733, 2018. © 2018 Wiley Periodicals, Inc.

Preventive role of superoxide dismutase on radiation-induced periprosthetic capsule development.

BACKGROUND: Capsule fibrosis is the most important and annoying complication of breast implant surgery. Radiotherapy (RT) used in the local treatment of breast cancer has an increasing effect on the existing fibrous capsule; this is called radiation-induced fibrosis (RIF). In this randomized controlled experimental study, we aim to investigate the reduction effect of superoxide dismutase (SOD) on RIF. METHODS: Sprague-Dawley rats were randomized into four groups, all of which were subjected to implant surgery. No additional procedures were done for the control group. The other groups were the SOD group, the RT + SOD group, and the RT group. The capsules were evaluated histopathologically. RESULTS: Although SOD reduced surgery-induced capsule formation, it neither prevented nor reduced significantly RIF. CONCLUSIONS: In an experimental model that resembled breast cancer treatment, we concluded that SOD cannot reduce RIF but is effective in reducing capsular fibrosis around the silicone after implant surgery.

In vivo characterization of a new type of biodegradable starch microsphere for transarterial embolization.

Transarterial embolization is an established minimally invasive treatment for solid tumors. Unintended inflammation, foreign body reactions and ischemia-triggered neoangiogenesis are clinical drawbacks of permanent embolic materials. The aim of the current study was to characterize a new type of biodegradable starch microsphere with regard to angiographic and histopathological features such as patterns of acute arterial occlusion as well as induction of tissue necrosis, microsphere biodegradation, and inflammation and foreign body reactions during follow-up. Key characteristics of both biodegradable prototypes (L1 and L2; prototype groups) were as follows: microspheres are biodegradable by serum α-amylase, produced from chemically crosslinked potato starch to different extents, in a diameter range of ∼300-800 µm, differing in size distribution and featuring a microsphere deformation of ∼1%. In vivo transarterial embolization with L1 and L2, while applying clinical standard techniques, was performed and compared with clinically established permanent microspheres (Embosphere®500-700 and Embosphere®700-900; control groups). Twenty-four pig kidneys were embolized with the different embolic materials by following the study protocol, and there were no technical failures or complications. Parenchymal necrosis with interstitial calcification was observed in all kidneys independent of the type of embolic material used. Compared with the permanent embolic materials, biodegradable microspheres showed complete (L1) or partial (L2) biodegradation within one week after transarterial embolization, and induced a comparable (L1) or a lower (L2) degree of arterial wall necrosis and a lower degree of inflammation and foreign body reactions. In conclusion, the presented new type of biodegradable microsphere is promising, and could be further evaluated in terms of clinical translation.

Evaluation of Soft Tissue Reaction to Corundum Ceramic Implants Infiltrated with Colloidal Silver.

BACKGROUND: Corundum ceramic is a biomaterial used as a bone graft substitute. Silver is a well known antiseptic substance with many practical, clinical applications. OBJECTIVES: The aim of this study was to estimate soft tissue (in vivo) reaction to a new kind of ceramic implants. In our experiment, we examined the soft tissue reaction after implantation of corundum ceramic infiltrated with colloidal silver in the back muscles of 18 Wistar rats. The use of colloidal silver as a coating for the implant was designed to protect it against colonization by bacteria and the formation of bacterial biofilm. MATERIAL AND METHODS: In our study, based on the experimental method, we performed implantation operations on 18 Wistar rats. We implanted 18 modified ceramic implants and, as a control group, 18 unmodified implants. As a follow up, we observed the animals operated upon, and did postoperative, autopsy and histopathological examinations 14, 30, 90 and 180 days after implantation. RESULTS: We didn't observe any pathological reactions and significant differences between the soft tissue reaction to the modified implants and the control group. CONCLUSIONS: Lack of pathological reaction to the modified implants in the living organism is the proof of their biocompatibility. This is, of course, the first step on the long path to introduce a new kind of biocompatible ceramic implant with antiseptic cottage. Our experiment has an only introductory character and we plan to perform other, more specific, tests of this new kind of implant.

A histological analysis of human median and ulnar nerves following implantation of Utah slanted electrode arrays.

For decades, epineurial electrodes have been used in clinical therapies involving the stimulation of peripheral nerves. However, next generation peripheral nerve interfaces for applications such as neuroprosthetics would benefit from an increased ability to selectively stimulate and record from nerve tissue. This increased selectivity may require the use of more invasive devices, such as the Utah Slanted Electrode Array (USEA). Previous research with USEAs has described the histological response to the implantation of these devices in cats and rats; however, no such data has been presented in humans. Therefore, we describe here the degree of penetration and foreign body reaction to USEAs after a four-week implantation period in human median and ulnar nerves. We found that current array designs penetrate a relatively small percentage of the available endoneurial tissue in these large nerves. When electrode tips were located within the endoneurial tissue, labels for axons and myelin were found in close proximity to electrodes. Consistent with other reports, we found activated macrophages attached to explanted devices, as well as within the tissue surrounding the implantation site. Despite this inflammatory response, devices were able to successfully record single- or multi-unit action potentials and elicit sensory percepts. However, modifying device design to allow for greater nerve penetration, as well as mitigating the inflammatory response to such devices, would likely increase device performance and should be investigated in future research.

Local delivery of mutant CCL2 protein-reduced orthopaedic implant wear particle-induced osteolysis and inflammation in vivo.

Total joint replacement (TJR) has been widely used as a standard treatment for late-stage arthritis. One challenge for long-term efficacy of TJR is the generation of ultra-high molecular weight polyethylene wear particles from the implant surface that activates an inflammatory cascade which may lead to bone loss, prosthetic loosening and eventual failure of the procedure. Here, we investigate the efficacy of local administration of mutant CCL2 proteins, such as 7ND, on reducing wear particle-induced inflammation and osteolysis in vivo using a mouse calvarial model. Mice were treated with local injection of 7ND or phosphate buffered saline (PBS) every other day for up to 14 days. Wear particle-induced osteolysis and the effects of 7ND treatment were evaluated using micro-CT, histology, and immunofluorescence staining. Compared with the PBS control, 7ND treatment significantly decreased wear particle-induced osteolysis, which led to a higher bone volume fraction and bone mineral density. Furthermore, immunofluorescence staining showed 7ND treatment decreased the number of recruited inflammatory cells and osteoclasts. Together, our results support the feasibility of local delivery of 7ND for mitigating wear particle-induced inflammation and osteolysis, which may offer a promising strategy for extending the life time of TJRs.

Illicit injections in bodybuilders: a clinicopathological study of 11 cases in 9 patients with a spectrum of histological reaction patterns.

The practice of self-injection of anabolic steroids (AS) in bodybuilders is common. AS are not the only materials used by bodybuilders for muscle augmentation or image enhancement. Other materials, for example, plant oils, silicon, Vaseline, and paraffin are also injected either in a pure form or mixed with AS. Muscle bulking is the main aim. However, bodybuilders undergo illicit injections for cosmetic, therapeutic, and sexual purposes. Even though the practice of unsupervised injection is probably common in the sports community, site-specific complications are underreported in the medical literature and mostly limited to case reports. Complications can be clinically and pathologically challenging because some can be confused with nonneoplastic and, more important, with neoplastic lesions. Bodybuilders are reluctant to disclose information because of stigma and legal issues. This study attempts to correlate the clinical manifestations and histomorphological features of different injected materials used for different purposes by bodybuilders in our region. A series of 11 cases out of 9 male bodybuilders was studied. A variety of clinical presentations and histological tissue reactions was identified, with some overlapping features between some cases. We identified 5 basic tissue reaction patterns depending on the injected materials, site, and duration of injection. Certain histological features provide useful hints in the absence of prior knowledge of injection history. However, in other cases, a retrospective enquiry by clinicians is warranted to avoid pitfalls. The medical and sports community should be aware of these injection-site complications. Bodybuilders should be discouraged from this practice by implementing appropriate educational and legislative measures.

How has the introduction of new bearing surfaces altered the biological reactions to byproducts of wear and modularity?

BACKGROUND: Biological responses to wear debris were largely elucidated in studies focused on conventional ultrahigh-molecular-weight polyethylene (UHMWPE) and some investigations of polymethymethacrylate cement and orthopaedic metals. However, newer bearing couples, in particular metal-on-metal but also ceramic-on-ceramic bearings, may induce different biological reactions. QUESTIONS/PURPOSES: Does wear debris from the newer bearing surfaces result in different biological responses compared with the known responses observed with conventional metal-on-UHMWPE bearings? METHODS: A Medline search of articles published after 1996 supplemented by a hand search of reference lists of included studies and relevant conference proceedings was conducted to identify the biological responses to orthopaedic wear debris with a focus on biological responses to wear generated from metal-on-highly crosslinked polyethylene, metal-on-metal, ceramic-on-ceramic, and ceramic-on-polyethylene bearings. Articles were selected using criteria designed to identify reports of wear debris particles and biological responses contributing to prosthesis failure. Case reports and articles focused on either clinical outcomes or tribology were excluded. A total of 83 papers met the criteria and were reviewed in detail. RESULTS: Biological response to conventional UHMWPE is regulated by the innate immune response. It is clear that the physical properties of debris (size, shape, surface topography) influence biological responses in addition to the chemical composition of the biomaterials. Highly crosslinked UHMWPE particles have the potential to alter, rather than eliminate, the biological response to conventional UHMWPE. Metal wear debris can generate elevated plasma levels of cobalt and chromium ions. These entities can provoke responses that extend to the elicitation of an acquired immune response. Wear generated from ceramic devices is significantly reduced in volume and may provide the impression of an "inert" response, but clinically relevant biological reactions do occur, including granulomatous responses in periprosthetic tissues. CONCLUSIONS: The material composition of the device, the physical form of the debris, and disease pathophysiology contribute to complex interactions that determine the outcome to all wear debris. Metal debris does appear to increase the complexity of the biological response with the addition of immunological responses (and possibly direct cellular cytotoxicity) to the inflammatory reaction provoked by wear debris in some patients. However, the introduction of highly crosslinked polyethylene and ceramic bearing surfaces shows promising signs of reducing key biological mechanisms in osteolysis.

The periprosthetic capsule and connective tissue diseases: a piece in the puzzle of autoimmune/autoinflammatory syndrome induced by adjuvants.

Breast prostheses have been criticized for being responsible for triggering systemic autoimmune disease. The presence of breast implants causes a natural foreign body reaction characterized by the infiltration of macrophages and T-cells. Using PubMed, Medline and eMedicine, we performed a systematic literature review on the stages of periprosthetic capsule formation and cells involved in order to understand which immunological pathways could be responsible for giving rise to, and the development of, connective tissue disease such as systemic sclerosis. We focused on the relationship between tissue growth factor-ß, interleukin (IL)-1, IL-6 and T helper 17 or T regulatory cells, as well as on their effects on the different steps of capsular tissue formation. A disturbance in the modulation of these key cytokines may be responsible, in susceptible individuals, for a perpetuation of the inflammatory reaction which can locally lead to capsular contracture and at the systemic level may contribute to triggering autoimmune diseases.

Surgical Results and Microscopic Analysis of the Tissue Reaction following Implantation and Explantation of an Intraocular Implant for Epiretinal Stimulation in Minipigs.

AIMS: For the purpose of visual rehabilitation of subjects with photoreceptor degeneration, an implantable microelectronic device for epiretinal stimulation was developed. Our study aimed to show whether implantation and explantation could be conducted safely and to investigate tissue compatibility. METHODS: The device was implanted in 5 Göttinger minipigs. Four weeks later, the implant was surgical- ly removed. Histopathological examination that followed aimed at detecting inflammatory or proliferative changes. Stains used were hematoxylin and eosin, leukocyte common antigen, CD68 and glial fibrillary acidic protein. A grinding technique was used to visualize the retinal tissue in conjunction with the retinal tacks. RESULTS: The implantation of the devices was successful in all cases. The explantation was complicated by intraoperative hemorrhages. Complete explantation could only be achieved after modifying the implantation strategy. Histopathology revealed a mild degree of cystic disaggregation of the retina. Immunohistochemically, an increased glial fibrillary acidic protein expression of Müller cells was found, which shows a moderate glial cell activation. Inflammatory cells were absent. Using the grinding technique, tissue adjacent to the retinal tacks showed a mild gliosis. DISCUSSION: The viability of implantation and explantation of the implant in minipigs has been shown. The absence of immunoreactive cells or a considerable glial reaction suggest that the device may be considered safe and suitable for further implantation in humans.

[Reticulated teleangiectatic erythema after implantation of medical devices. An increasingly occurring phenomenon?]. / Retikuläre teleangiektatische Erytheme nach Implantation von elektrischen medizinischen Geräten. Ein an Häufigkeit zunehmendes Phänomen?

Reticulated telangiectatic erythema (RTE) is a rare skin reaction to extraneous materials. We present three cases in which asymptomatic persistent erythemas developed in the area of implantation after medical devices were inserted. Topical and systemic treatment did not improve the skin changes. Patch testing including applied materials showed negative results in all cases. Histological investigation of punch biopsy specimens showed moderate dilatated vessels and a slight lymphocytic infiltrate. Due to our findings and in synopsis with the clinical impression we diagnosed RTE. As RTE is asymptomatic in most cases, the devices need not be removed.

Effects of folk medicinal plant extract Ankaferd Blood Stopper on early bone healing.

OBJECTIVE: Several haemostatic agents are available for clinical use. Ankaferd Blood Stopper (ABS), a mixture of five medicinal plant extracts, has been used historically as a haemostatic agent. The aim of this in vivo study was to investigate the effects of ABS on early bone healing using a rat tibia defect model. MATERIAL AND METHODS: Sixteen male Wistar rats were randomized into two groups of 8 animals each. After deep anesthesia with ketamine, bone defects (3 mm diameter and 2 mm deep) were created in the right and left tibiae of all animals and either treated with 1 cc of ABS (Group 1) or left untreated (Group 2; control). Surgical areas were closed primarily. The animals were sacrificed on the 7th postoperative day and bone samples were collected from the tibias. The samples were examined histopathologically for infection, necrosis, fibrosis, new bone formation and foreign body reaction. The histomorphometric results were analyzed statistically by the chi square test, with the level of significance set at p<0.05. RESULTS: Significant differences were found in both groups in terms of inflammation, necrosis and new bone formation (p=0.001, p=0.0001, p=0.001). No foreign body reaction was observed in the experimental group. ABS application decreased fibrosis in the experimental group, but there were no statistically significant differences from the control group. CONCLUSIONS: Histopathologically, it was observed that the application of ABS decreased the occurrence of inflammation and necrosis, while increasing new bone formation in early bone healing period. Further in vitro and in vivo studies are necessary for evaluating the benefits and possible adverse effects of the application of this herbal product on wound healing.

Effects of folk medicinal plant extract Ankaferd Blood Stopper® on early bone healing

OBJECTIVE: Several haemostatic agents are available for clinical use. Ankaferd Blood Stopper® (ABS), a mixture of five medicinal plant extracts, has been used historically as a haemostatic agent. The aim of this in vivo study was to investigate the effects of ABS on early bone healing using a rat tibia defect model. MATERIAL AND METHODS: Sixteen male Wistar rats were randomized into two groups of 8 animals each. After deep anesthesia with ketamine, bone defects (3 mm diameter and 2 mm deep) were created in the right and left tibiae of all animals and either treated with 1 cc of ABS (Group 1) or left untreated (Group 2; control). Surgical areas were closed primarily. The animals were sacrificed on the 7th postoperative day and bone samples were collected from the tibias. The samples were examined histopathologically for infection, necrosis, fibrosis, new bone formation and foreign body reaction. The histomorphometric results were analyzed statistically by the chi square test, with the level of significance set at p<0.05. RESULTS: Significant differences were found in both groups in terms of inflammation, necrosis and new bone formation (p=0.001, p=0.0001, p=0.001). No foreign body reaction was observed in the experimental group. ABS application decreased fibrosis in the experimental group, but there were no statistically significant differences from the control group. CONCLUSIONS: Histopathologically, it was observed that the application of ABS decreased the occurrence of inflammation and necrosis, while increasing new bone formation in early bone healing period. Further in vitro and in vivo studies are necessary for evaluating the benefits and possible adverse effects of the application of this herbal product on wound healing.

The effect of liposome-delivered prednisolone on collagen density, myofibroblasts, and fibrous capsule thickness around silicone breast implants in rats.

Capsular contracture is a potential adverse effect of breast implants. An inflammatory reaction is most likely the origin of fibrosis around the implant. It is possible that some substances may act to prevent this inflammatory reaction. Thus, our goal was to evaluate the effectiveness of local depot prednisolone phosphate-liposomes (PPL) on fibrous capsule formation around textured silicone breast implants. Shell prostheses (2 mL) were implanted in the right (plus PPL group) and left (plus saline solution, saline group) subcutaneous dorsum of 18 rats. In another 18 rats, the implants were positioned in the left of the back without any drug instillation (control group). In the PPL group, the capsule thickness (microm) and density (%) of collagen were significantly (p<0.0001) lower compared with the control group on days 35 and 90 postsurgery. Furthermore, in the PPL group, a significant reduction in myofibroblast count was observed on day 90 postsurgery (p<0.0001). In conclusion, a single dose of depot liposome-delivered prednisolone was effective at impairing capsule formation around the silicone implant. The results suggest a strong local and weak systemic effect of PPL on the fibrous tissue around silicone implants. To our knowledge, no study has yet assessed the effect of PPL on silicone breast implants.

Late onset cervical myelopathy secondary to fibrous scar tissue formation around the spinal cord stimulation electrode.

STUDY DESIGN: Case report. OBJECTIVES: To report the late onset of cervical myelopathy secondary to fibrous scar tissue formation around an epidural electrode implanted for spinal cord stimulation (SCS). SETTING: Department of Orthopaedic Surgery, Hoshigaoka Koseinenkin Hospital, Osaka, Japan. METHOD AND RESULTS: A 49-year-old man who had an electrode implanted for SCS 5 years ago was referred to our department on 2 March 2005, complaining of difficulty using chopsticks and walking. A computed tomography scan with myelography revealed severe spinal cord compression around the epidural electrode. Surgical removal of the electrode was not effective. Removal of fibrous scar tissue during a second surgery significantly improved his neurological symptoms. CONCLUSION: Late onset cervical myelopathy secondary to fibrous scar tissue formation around the epidural electrode should be considered a possible event associated with SCS therapy.