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Background: In 2007 an article was published describing the first forays into the practice of episcleral tattooing. Currently only a handful of people worldwide have undergone this procedure, whereby a needle is used to inject dye under the bulbar conjunctiva. To date there have been no previous reports of the risks and complications of this emerging practice in the medical literature. We present a case involving a complication that arose in one of the few people in Britain to have undergone episcleral tattooing for cosmetic purposes., Case Presentation: A 43-year-old Caucasian man presented to the eye casualty clinic with red, lumpy conjunctivae bilaterally, having undergone episcleral tattooing 7 weeks previously. On examination there were 3 distinct areas of conjunctival swelling in each eye, representing a total of 6 injection sites. No other gross abnormalities were identified. The clinical picture remained unchanged 6 months on, apart from a degree of fading of the conjunctival dye. He will remain under our care to ensure that any further complications such as granulomatous inflammation are managed and documented., Conclusion: Episcleral tattooing is carried out by individuals with no medical training. The short-term complications reported so far include: headaches, severe photophobia, persistent foreign body sensation, and migration of ink staining. More serious short-term risks such as infection, globe penetration, and peri-ocular haemorrhage could occur. For now we can only speculate as to the long-term consequences, but these may include carcinogenic change or granulomatous inflammation. We feel that the potential risks of the procedure should be communicated more widely to those body modification practitioners undertaking it. This practice could result in more serious presentations to acute eye services in the future.

Purpose: To report the adverse effects of topical tosufloxacin in two patients with corneal deposits in compromised cornea., Case Report: Tosufloxacin was administered topically to a 13-month-old girl after penetrating keratoplasty in the left eye. Three days posttransplantation, corneal precipitations appeared and thereafter continuously increased. An 80-year-old woman, who maintained postoperative multiple topical medications including tosufloxacin, presented dense white deposits in the left eye a month postoperation. In both cases, the deposits showed a granular pattern and were limited to areas of large epithelial defects. After discontinuation of tosufloxacin, the deposits slowly decreased and completely disappeared in a few weeks. In the former case, corneal re-epithelialization was significantly disturbed and resulted in anterior stromal opacity, whereas visual acuity and visualization of the retina were severely interfered in the latter case., Conclusions: Tosufloxacin can precipitate especially on compromised corneal surfaces. Therefore, topical tosufloxacin should be avoided in patients who are at risk of losing corneal surface integrity.

This study evaluated different dosage forms of aluminum adjuvant in generating allergic rhinitis animal models. Forty female BALB/c mice were assigned to four groups, including three dosage forms of aluminum adjuvant [powder, gel, and hydrosolvent of aluminum hydroxide, Al(OH)3] mixed with ovalbumin to simulate the symptoms of allergic rhinitis and one control group. Although the aluminum adjuvants were in different dosage forms, the content was 5 mg after conversion in all groups. The fourth group was given normal saline instead as a control. Mice of the powder group displayed typical symptoms of allergic rhinitis. We also found discrete eosinophils in the nasal mucosa of mice from the hydrosolvent group; however, no eosinophils were found in the gel group. These two groups both displayed cytotoxic symptoms and foreign body granuloma. Aluminum adjuvant used in producing animal models can induce foreign body granuloma and other untoward reactions, which are associated with the dosage level and form.

During revision of a conventional polyethylene joint replacement, surgeons usually remove the source of osteolysis (polyethylene) but cannot always remove all of the polyethylene granuloma tissues. We developed a human/rat xenograft model to investigate the effects of polyethylene granuloma tissues on bone healing. Human osteoarthritic and periprosthetic tissues collected during primary and revision hip arthroplasty surgeries were transplanted into the distal femora of athymic nude rats. After 3 weeks in vivo, there was a significant difference in the bone volume fraction (Vf ) between empty, primary, and revision defects (p = 0.02), with a lower Vf in defects with revision granuloma tissues compared to defects with primary osteoarthritic tissues. Polyethylene granuloma tissues in trabecular bone defects inhibited bone healing. Therefore, debridement around a metal-on-polyethylene hip replacement may shorten the time it takes to achieve secondary stability around a revision hip replacement., (© 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background: Cutaneous granulomas after a soft filler injection represent one of the worst scenarios for both patient and injector., Objectives: To present clinical and histopathological features of granulomatous nodular reactions induced by a new alginate-based dermal filler (Novabel(®)), and put it in context of the process of injectable soft tissue fillers approval and promotion in the EU., Methods: A case series of four patients injected with Novabel(®) for volume restoration of the face and hands, who developed severe foreign body reactions., Results: Four patients injected with Novabel(®) into tear troughs and/or dorsa of hands developed severe granulomatous reactions within months after injections. As we injected with the new filler into a total of 10 patients, a high incidence of 40% of the disfiguring adverse effect was observed. The inadequate response of manufacturer to our reporting the side-effects along with the available data on registration process of dermal fillers confirmed that the area is not well-regulated., Conclusions: The status of dermal fillers as class III medical devices, and the process of their approval and marketing in the EU need to be seriously reconsidered to avoid unnecessary and serious adverse reactions., (© 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.)

Mesh biocompatibility is basically determined by the foreign body reaction (FBR). In contrast to physiological wound healing and scar formation, the FBR at the host-tissue/biomaterial interface is present for the lifetime of the medical device. The cellular interactions at the mesh/tissue interface proceed over time ending up in a chronic inflammatory process. The time course of the FBR has been studied extensively and consists of three crucial steps that are protein absorption, cell recruitment and, finally, fibrotic encapsulation and extracellular matrix formation. Each of these steps involves a complex cascade of immune modulators including soluble mediators and various cell types. Recent research has focused on the cellular and molecular interactions of the distinct phases of the FBR offering a new basis for therapeutical strategies. The highly dynamic process of the FBR is considerably influenced by the biomaterial composition. Modifications of the type of polymer, the material weight, the filament structure and the pore size are realized and have substantial effects on the in vivo biocompatibility. Moreover, modern mesh technology aims to utilize the available implants as carrier systems for bioactive drugs. Studies in animal models account for the efficiency of these drugs that aim to reduce mesh-related infections or to minimize FBR by influencing inflammation or extracellular matrix remodelling. A thorough understanding of the molecular mechanisms of FBR provides a sophisticated background for the development of new biomaterials at least as carrier systems for bioactive reagents to reduce inflammation and to improve clinical outcome.

Recurrent trigeminal neuralgia after microvascular decompression (MVD) may be due to insufficient decompression, dislocation of the implant to pad the neurovascular contact, or the development of granuloma. Here, we report on our experience with Teflon granuloma including its treatment and histopathological examination. In a series of 200 patients with trigeminal neuralgia MVD was performed with Teflon felt according to Jannetta's technique. In three patients with recurrent facial pain Teflon granuloma was found to be the cause for recurrence. In each instance, the granuloma was removed for histopathological examination. Mean age at the first procedure was 62.3 years and at the second procedure 66.3 years. Recurrence of pain occurred between 1 and 8.5 years after the first procedure. MRI scans demonstrated local gadolineum enhancement in the cerebellopontine angle, and CT scans showed local calcification. Intraoperatively dense fibrous tissue was found at the site of the Teflon granuloma. Histopathological examination revealed foreign body granuloma with multinuclear giant cells, collagen-rich hyalinized scar tissue, focal hemosiderin depositions, and microcalcifications. The Teflon granuloma was completely removed, and a new Teflon felt was used for re-decompression. Patients were free of pain after the second procedure at a mean of 40.3 months of follow-up. Teflon granuloma is a rare cause for recurrent facial pain after MVD. Small bleeding into the Teflon felt at surgery might trigger its development. A feasible treatment option is surgical re-exploration, nerve preserving removal of the granuloma, and repeat MVD.

A 69-year-old man presented with subarachnoid hemorrhage due to a ruptured anterior communicating artery aneurysm. The aneurysm neck was clipped and a lumbar drainage tube was inserted for cerebrospinal fluid drainage. However, the tube was accidentally cut during removal and a fragment remained in the spinal canal. A subarachnoid, subcutaneous abscess appeared 7 days later, which was treated with antibiotics. He noted numbness of his left leg after 6 months, and gait disturbance manifested 3 months later. T(1)-weighted magnetic resonance (MR) imaging disclosed a well-enhanced extramedullary mass at the T9-10 intervertebral level, and T(2)-weighted MR imaging showed moderate edema around the peri-lesional spinal cord. The mass containing a drainage tube fragment was surgically removed. Histological examination confirmed granuloma due to chronic infection. This case suggests that retained tube fragments should be removed surgically, especially in the presence of infectious complications.

Femoral nerve palsy after THA is well known, but delayed palsy is rare. We describe a 58-year-old man who had progressive thigh pain, weakness, and numbness develop 13 years after cementless arthroplasty of his left hip. Plain radiographs showed substantial liner wear. MRI of the lumbar spine was unrevealing and EMG showed a peripheral neurogenic process involving the left femoral nerve. The large intrapelvic cystic mass was confirmed by an abdominopelvic CT scan. Percutaneous aspiration of the cyst was performed. Cultures of the fluid were negative and cytopathologic examination showed necrotic debris without malignant cells. Biopsy revealed necrosis and abundant foreign body granulation tissue with polarizable debris. During surgical removal of the cyst, a defect of the inner acetabular wall was noted. After subsequent revision arthroplasty with allograft bone, the patient's clinical symptoms improved and his EMG returned to normal.

Mycobacterium microti, a member of the Mycobacterium tuberculosis complex, causes tuberculosis in small rodents and occasionally in other mammals including man. Three adult male squirrel monkeys, two with a history of lethargy, weakness and stridor and one with paralysis of the hind legs, were presented for necropsy. One of the two lethargic animals showed multiple granulomas in the mesentery, mesenteric lymph nodes, lung, liver, kidneys and spleen, while the other showed granulomas only in the lung. The animal with paralysis of the legs had an abscess-like lesion in the skeletal muscle of the neck, granulomas in the mesenteric and mediastinal lymph nodes, and a fracture of the thirteenth thoracic vertebra with severe lesions of the spinal cord. Histologically the granulomas showed typical features of tuberculous granulomas, i.e., central necrosis surrounded by epithelioid cells, multinucleated giant cells, inflammatory cells and a border of connective tissue. Ziehl-Neelsen stain demonstrated sporadic acid-fast bacilli within the granulomas, these organisms being identified as M. microti by microbiological and molecular methods.

In this study the effects of compound B1, bis(3-aryl-3-oxo-propyl)methylamine hydrochloride, and an anti-inflammatory drug, indomethacin, were tested by carrageenan-induced paw edema and cotton pellet granuloma tests, for effects on acute and chronic phases of inflammation, respectively. Their effects on vascular permeability were also determined by hyaluronidase-induced capillary permeability test. Anti-inflammatory activity of B1 was compared with indomethacin. B1 decreased the carrageenan-induced paw edema by 49%, 35%, and 47% at 50, 100, and 200 mg kg(-1) doses, respectively, while this decrease was 82% by indomethacin at 20 mg kg(-1) dose. Antiproliferative effects in cotton pellet test of B1 at 50 mg kg(-1) and indomethacin at 20 mg kg(-1) doses were 44% and 43%, respectively. Indomethacin but not B1 inhibited the hyaluronidase-induced increase in capillary permeability. Our results suggest that B1 inhibits both acute and chronic phases of inflammation probably by an effect not mediated by prevention of increased capillary permeability. Especially, its anti-inflammatory activity against chronic phase of inflammation was comparable with that of indomethacin. Further detailed studies are needed to clarify the mechanism(s) of action responsible for the anti-inflammatory activity of B1.

A 45-year-old man received an injection of Restylane (cross-linked hyaluronic acid) to a mid-forehead furrow line in an attempt to reduce its prominence. The injection was uncomplicated and successful in reducing the line. Five months after the injection, he returned with an inflammatory reaction in the area of injection that resolved without treatment over a period of 3 weeks.

Vascular endothelial growth factor (VEGF) is a potent growth factor that is indispensable for the development of blood vessels in the fetus and for wound healing in adults. VEGF likely plays a role in maintaining the blood vessels once they have been formed. It is not clear, however, whether a low tissue VEGF (caused either by disease or by systemic administration of VEGF antagonists) can cause abnormalities in preexisting blood vessels, especially of wound tissue that requires high local levels of VEGF for healing. The present study investigated the effect of VEGF antagonism on blood vessels of foreign-body granulomas (a model of wound-healing tissue). Granulomas were induced by implanting perforated polyvinyl tubes into the subcutaneous tissue of rats and allowed to develop for 14 days, at which time the implanted tubes were completely encapsulated by the subcutaneous tissue. The encapsulated granulomas consisted of 3 distinct histological layers, of which the middle layer was well perfused by a rich supply of microvessels. Morphologically, the granuloma remained "stable" after developing for 14 days. At 1 week, VEGF levels in the granuloma fluid, which is in equilibrium with the interstitial fluid, were 25 times higher than in the plasma. VEGF levels in the granuloma fluid continued to increase for up to 3 weeks, reflecting the high dependence of the wound tissue on ambient VEGF levels. After injection of the VEGF receptor antagonist in the fully formed granuloma, the preexisting blood vessels in the middle layer regressed and underwent apoptosis, accompanied by expansion of the extracellular matrix (predominately collagen I) into areas normally devoid of matrix. We conclude that wound tissue is sensitive to ambient VEGF levels, and that a low VEGF condition resulting from VEGF receptor antagonism can disrupt the healing of wound tissue.

Minute pieces of debris left in the surgical site can interfere with optimal wound healing. Even when these microbodies are not obvious without magnification, their presence can cause post-surgical complications including infections, amplified and prolonged inflammation, permanent tissue damage, exaggerated and reduced quality scarring, granulomas, adhesions, organ dysfunction, infertility, and other pathological consequences. This chapter reviews foreign debris-initiated, post-surgical complications; presents associated pathological mechanisms; identifies sources of debris contamination; describes foreign-microbody characteristics that can further amplify pathological responses; and presents recommendations for minimizing their presence.

In our study, the effects of the compound 3-benzoyl-1-methyl-4-phenyl-4-piperidinol hydrochloride (C1) and also an anti-inflammatory drug, indomethacin, tested by carrageenan-induced paw edema and cotton pellet granuloma tests, for their effects on acute and chronic phases of inflammation, respectively. Their effects on vascular permeability were also tested by hyaluronidase-induced capillary permeability. C1 decreased the carrageenan-induced paw edema 61.98, 80.84, and 90.32% at 50, 100, and 200mgkg(-1) doses, respectively, while this decrease was 89.93% by indomethacin at 20mgkg(-1) dose. Antiproliferative effects of C1 at 100mgkg(-1) and indomethacinin at 20mgkg(-1) doses were 46.1 and 43.1%, respectively, in cotton pellet test. C1 and indomethacin both significantly inhibited the hyaluronidase-induced increase in capillary permeability.

In the development of a cholesterol granuloma both cellular and vascular permeability factors have to be taken into consideration. It may arise as a special degradation product in a chronic cerebral infarct because of the partial insufficient activity of the macrophages. Consequently, the degradation of brain sphingolipids and other compounds does not follow the usual route of degradation and transportation by granular cells to the stage of neutral fat but the necrotic mass transforms into cholesterol esters. Cholesterol crystals produce an irritative effect to neighbouring tissues which may result in the formation of young fibroblasts with proliferative tendency in the vessel wall. Some of the fibroblasts take part in the proliferation of connective tissue, while the rest degenerate, producing more cholesterol or xanthomatous material. Inflammatory changes may also be associated with these lesions. The amount of cholesterol sometimes increases in the inner side of the thickening connective tissue layer. The final result may be an intracranial space occupying mass or it may end as a small cholesterol granuloma, as demonstrated in our incidental cases. By the time a granuloma has developed, the original vessel usually disappears completely, but sometimes remnants of vessels might prove the vascular origin. Other pathomechanisms should also be taken into consideration, such as a cholesterol embolus or anomalous vessel with a large cholesterol plaque in the wall. This also explains why trauma (hemorrhage, granulation), cholesterol embolus, inflammation, metabolic imbalance may predispose to the formation of a granuloma, as well as the hypercholesterolaemia. The nine cases demonstrate the significance of the intracranial granuloma from pathological, clinical and neurosurgical points of view. Such cases have not yet been reported in the national or international literature.

Granulation tissue formation is an example of new tissue development in an adult. Its rich vascular network has been thought to derive via angiogenic sprouting and extension of preexisting vessels from the surrounding tissue. The possibility that circulating cells of hematopoietic origin can differentiate into vascular endothelial cells (ECs) in areas of vascular remodeling has recently gained credibility. However, no quantitative data have placed the magnitude of this contribution into a physiological perspective. We have used hematopoietic chimeras to determine that 0.2% to 1.4% of ECs in vessels in control tissues derived from hematopoietic progenitors during the 4 months after irradiation and hematopoietic recovery. By contrast, 8.3% to 11.2% of ECs in vessels that developed in sponge-induced granulation tissue during 1 month derived from circulating hematopoietic progenitors. This recruitment of circulating progenitors to newly forming vessels would be difficult to observe in standard histological studies, but it is large enough to be encouraging for attempts to manipulate this contribution for therapeutic gain.

The use of bone anchors as a superior fixation for suburethral slings is becoming popular. We present a case report of pubic osteomyelitis and granuloma after bone anchor placement. A 71-year-old woman underwent placement of a vaginal wall sling using pubic bone anchors placed through a suprapubic incision. Recurrent swelling of the mons pubis required re-exploration and removal of the anchors from an infected pubic bone. When symptoms persisted over the following 10 months, the patient underwent repeat surgery and excision of a pubic bone granuloma. The use of bone anchors in suburethral sling surgery is associated with possible increase in patient morbidity, and no benefit to the patient has been shown.

Optimal hearing is one goal of otologic surgery. It is generally presumed that hearing thresholds after tympanoplasty-mastoidectomy surgery are determined by remaining anatomy. We assessed the effect of the disease process on hearing after surgery, and our data do not support this presumption. We studied the relationship between preoperative and postoperative hearing across tympanoplasties with differing anatomies in 124 patients without ossicular reconstruction with prostheses or bone. Our results indicate that poor hearing before surgery is associated with poor hearing after surgery, regardless of anatomy (type of tympanoplasty). This relationship holds for both the airbone gap and the speech-reception threshold. When considering ossicular reconstruction, the surgeon should remember that the disease process itself affects hearing in addition to the physical attributes of the ear. These results should be considered in preoperative counseling, as well as in the interpretation of the otologic literature.

A 40-year-old woman presented with acute obstructive lung disease. She was treated with steroids and achieved a good response. However, she had two previous pelvic operations with histological findings of uterine serosal caseating granulomas presenting in the latter operation. Antituberculosis (TB) prophylaxis was suggested due to the suspicion of TB reactivation under steroid management. Investigation for TB infection or exposure was negative while revision of the histological slides disclosed talc granulomas. Although talc granuloma is reported in starch powder gloves which should not contain talc, it is still very uncommon.

Intralaryngeal Teflon injection for correction of unilateral vocal cord paralysis is known to produce a foreign body giant cell reaction. In our practice, we have seen increasing numbers of patients who had developed dysphonia related to Teflon injection. This patient series was reviewed, as were the surgical technique to correct this condition, voice results, and acoustic analysis of a subset of the patient series. We conclude that dysphonia, secondary to Teflon injection, can be either from overinjection of Teflon or inappropriate injection, or from the proliferative granulomatous response of the larynx to the Teflon. Our technique of laser incision into the superior aspect of the Teflon implant, followed by vaporization and preservation of a margin of mucosa of the cord medially, resulted in improved voice in 8 of 11 patients treated in this manner. Acoustic and aerodynamic analyses reveal significant deficits in vocal function that may persist after procedures used to correct this condition.

Background: The CO2 laser is a common surgical modality in dermatology. To clarify conflicting reports on the histological healing properties of CO2 laser on incisional or ablative wounds, we have applied it in a miniature hairless porcine skin model at power settings similar to those used in clinical practice., Methods: Histological parameters of wound healing in skin incisions using the CO2 laser were compared with those using scalpel, hot scalpel, and electrosection, and in dermal ablation using CO2 laser, fraize, wire brush, and electrofulguration alone or with curettage., Results: In incisional wounds, tissue damage was most extensive in CO2 laser wounds, with delayed dermal healing and reepithelialization. In ablative wounds, CO2 laser caused a similar degree of tissue damage as did the electrosurgical modalities, and more damage than did fraize or wire brush. Reepithelialization was complete in CO2 laser, fraize, and wire brush wounds before electrosurgical wounds. Final histology of both incisional and ablative wounds at 6 weeks was similar with all surgical modalities., Conclusion: The CO2 laser and electrosurgery both produce greater focal tissue damage in incisional and ablative applications than the other modalities. Delayed epithelialization of the wound occurs with both modalities in incisional wounds but only with electrosurgery in ablative wounds. At 6 weeks, the appearance of the scar in all incisional and ablative modalities is similar grossly and histologically. Confirmation of these findings requires standardization of power density of the CO2 laser in incision and ablation.

Background: Within a large population of patients seropositive for human immunodeficiency virus type 1 (HIV-1), seven had biopsy specimens that showed foreign body reactions with histologic features different from those seen in non-HIV-1-positive patients., Objective: These cases were reviewed to determine whether there was a specific pattern of response to foreign bodies in HIV-1 infection and whether this pattern was related to the stage of disease., Methods: Biopsy specimens were reviewed to identify ruptured epidermal cysts. These were studied in routine hematoxylin-and-eosin-stained sections and with immunohistochemical stains to characterize the inflammatory infiltrate., Results: The lesions in HIV-1-infected patients contained abundant macrophages with evidence of decreased function and a lack of giant cells., Conclusion: These histologic features suggest an early functional deficit before there is a significant decrease in the number of T4 lymphocytes.

The pro-inflammatory activity of prolactin (PRL) was clearly demonstrated in our previous research on rat paw oedema. In the present study we report our results on the activity of PRL on other animal models of acute and chronic inflammation. Repeated administration of ovine PRL provoked a significant increase in the inflammatory parameters in experimental carrageenan pleurisy (leukocytes number and prostaglandin E2 concentration in the exudate). A pro-inflammatory effect was also present after a hyperprolactinaemia induced by pituitary gland graft. Moreover, the inflammatory response to polyester sponge implantation was significantly potentiated by oPRL, whereas the hormone was completely inactive on cotton pellet granuloma test. A possible involvement of prostaglandins in the pro-inflammatory activity of PRL is suggested.

To understand further the role of macrophages in the loosening of cemented arthroplasty, several in vitro effects of polymethyl methacrylate (PMMA) particle exposure in these cells were studied. The kinetics of arachidonic acid and derived inflammatory mediator release was characterized following macrophage exposure to either PMMA or control polystyrene particles. Temporal release of radiolabeled products by [14C]arachidonate-labeled cells was determined by sequential scintillation counting. Significant dose-dependent release of arachidonic acid mediators by macrophages was observed within half an hour of exposure to either PMMA or styrene particles. Unexposed control cells incubated in media alone did not release detectable amounts of radiolabeled products. The leakage of intracellular lactate dehydrogenase (LDH), a marker of cell injury, was detected spectrophotometrically 4 h following exposure to PMMA but not styrene. PMMA-induced LDH release was dose dependent. In contrast, polystyrene exposure failed to increase LDH release above unexposed control cells. These in vitro studies reveal that macrophages rapidly released arachidonic acid and derived inflammatory mediators in response to both PMMA and styrene particles. However, cells exposed to PMMA are lethally damaged, as reflected by the subsequent leakage of their intracellular LDH. We propose that a similar sequence of events may occur when macrophages encounter PMMA particles at the bone-cement interface. This is characteristic of a foreign body granulomatous response.