Foreign Body Granuloma Formation Research Articles

β-Tricalcium phosphate promotes cell proliferation, osteogenesis and bone regeneration in intrabony defects in dogs

Objective This study investigates the effect of the new synthetic bone grafting material, high pure-phase β-tricalcium phosphate (Cerasorb ® M, granule size 500–1000 μm), on the osteogenesis process and proliferation marker in bone marrow stromal cells (BMSCs) and its regenerative effect in the periodontal intrabony defects in dogs. Design The effect of Cerasorb ® M (20 and 40 mg ml −1 for 1 and 2 weeks) on the proliferation rate of BMSCs was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2 H-tetrazolium bromide (MTT) assay on the proliferating cell nuclear antigen (PCNA) by immunoblotting and on alkaline phosphatase level by colourimetric assay. The regenerative effect of Cerasorb ® M in the periodontal intrabony defects in dogs was investigated by histological and immunohistochemical analysis after 3 and 6 months of grafting. Results Incubation of BMSCs with Cerasorb ® M for 2 weeks led to significant increase in cell proliferation rate, which was associated with increased PCNA. Cerasorb ® M significantly increased the production of alkaline phosphatase as a marker for the osteogenic stromal lineage and for differentiation and bone formation in BMSCs after 2 weeks. In the histological features and immunohistochemical analysis of PCNA of the intrabony defects in dogs augmented with Cerasorb ® M, osteoid tissue with a plate-like structure and cellular mesenchymal proliferation besides osteoid islands joined by bridges were observed after 3 months. Six months after the implantation, the Cerasorb ® M granules were replaced by abundant new plate-like bone besides PCNA-enriched, small, oval-shaped mononuclear cells and multinucleated-giant cells that were attached to newly formed bones. No remains of the Cerasorb ® M granules could be seen after 3 and 6 months with the newly formed plate-like bones and no histological sign of inflammatory reaction or formation of foreign-body granulomas. Conclusion Cerasorb ® M may induce cell proliferation via induction of PCNA that may induce early osteogenesis and bone formation. Cerasorb ® M regenerated the bone completely in intrabony defects and that this regeneration was highly associated with PCNA expression in different cell lineage.

Evaluation of the safety of aluminium adjuvant in the preparation of allergic rhinitis animal model

To evaluate the effect and safety of the formulation and dosage of aluminium adjuvant, Al(OH)(3), in the preparation of allergic rhinitis animal model. Sixty health BALB/c mice were divided randomly into 6 groups. Al(OH)(3) powder (5 mg) was used in one group, Al(OH)(3) colloid gel of different concentration (0.5 - 5 mg) was used in four groups, and normal saline was used in the control group. Ovalbumin injection and nasal topical challenge were used in the 5 testing groups to induce allergic rhinitis in mice. Normal saline was used in the control group. Typical allergic rhinitis symptoms including frequent nasal scratching, and edema of peri-nasal mucosa were found in mice of the 5 mg Al(OH)(3) powder group. Eosinophils accumulation, goblet cells hyperplasia and hypersecretion were found in the mucosa of lateral nasal wall and inferior nasal turbinate. Neither obvious allergic rhinitis symptom, nor eosinophils accumulation in nasal mucosa was observed in the Al(OH)(3) colloid gel groups. Hemorrhagic ascites and lots of white nodules (foreign body granuloma) formation were found in the liver, spleen, and kidney of all mice of the 5 mg Al(OH)(3) colloid gel group. Five out of 10 mice of the 2 mg Al(OH)(3) colloid gel group exhibited above signs but of lower grade. Despite dispersed fine white sediment in the liver and mesentery, no obvious ascites was found in mice of the 1 mg and 0.5 mg Al(OH)(3) colloid gel groups. Al(OH)(3) powder, 5 mg, is effective and safe in the preparation of allergic rhinitis animal model. Al(OH)(3) colloid gel of different concentration (0.5 - 5 mg) may cause side effects such as foreign body granuloma.

Impact of Proinflammatory Cytokine Knockout on Mesh Integration

Placement of mesh is involved in 75–80% of hernia operations. It is known that an exaggerated foreign body reaction leads to clinical complications. To further improve patients outcome using biotechnological agents targeted against tumor necrosis factor-α (TNF-α) or interleukin-6 (IL-6), a study was conducted investigating the impact of cytokine knockout on mesh integration. Sixty mice were used: C57BL/6 wild type control, C57BL/6-IL-6 interleukin-6 knockout, C57BL/6-Tnfrsf1a knockout of TNF-α receptor 1, and C57BL/6-Tnfrsf1b knockout of TNF-α receptor 2. Standard polypropylene mesh was implanted subcutaneously for 7, 21, and 90 days. The inflammatory and connective tissue formation was characterized by diameter of inner cellular infiltrate and outer fibrous capsule of the foreign body granuloma, and by quantity (collagen/protein ratio) and quality (collagen type I/III ratio) of collagen formation. Microscopic investigation of the mesh/host-tissue interface showed typical formation of foreign body granulomas. Ninety days after implantation none of the knockout strains showed significant differences compared to the control group investigating amount of inflammatory and connective tissue formation. Analyzing the quantity of filamentary collagen deposition the C57BL/6-IL-6 group showed significant lowered values compared to the control group 90 days after implantation. In all groups collagen type I/III ratio increased over time as an indicator for maturation of the surrounding collagen formation. However, no difference was found comparing strains at the end of the observation period. The results support the notion that wound healing is affected by cytokine deficiency. However, a desirable reduced amount of inflammatory tissue formation as well as an increased collagen type I/III ratio due to cytokine knockout could not be observed.

Foreign body granuloma formation secondary to a vocal fold silicone injection : A case report

Foreign body granuloma formation secondary to a vocal fold silicone injection : A case report

Brain abscess and granuloma formation as late complications of retained ventricular catheter

This report presents a rare complication of ventriculoperitoneal shunt, delayed development of brain abscess and foreign body granuloma formation adjacent to the intraventricular catheter. Both the complications occurring in the same patient is unusual.

Scrotal calcinosis due to resorption of cyst walls: a case report

IntroductionScrotal calcinosis is a rare benign entity defined as the presence of multiple calcified nodules within the scrotal skin. There are controversies about the origin of this entity. In fact, it is still debatable whether scrotal calcinosis is an idiopathic growth or dystrophic calcification of dartoic muscles. It is also unclear whether scrotal calcinosis originates from inflammation of epidermal cysts affected by mild to moderate inflammation of mononuclear cells, from foreign body granuloma formation followed by resorption of cyst walls or from eccrine epithelial cysts.Case presentationWe report a 41-year-old male Turkish patient presenting with a 10-year history of scrotal tumours increasing slowly in size and number. Histopathologically, there was no epithelial lining around the calcified nodules, but there was fibrosis adjacent to atrophic stratified squamous epithelium.ConclusionResults of histopathological examinations suggested that scrotal calcinosis might have been due to resorption of cyst walls. Surgery remains the key for this problem. In cases of non-massive scrotal calcinosis, like the case presented here, excision of the nodules from the affected part of the scrotal wall and repairing the defect with horizontal stitches offer good cosmetic results without relapse.

Porcine pericardium as glaucoma implant tube coverage: an experimental study

To evaluate the inflammatory response associated with the use of processed porcine pericardium and glycerin-preserved homologous sclera as silicone glaucoma drainage device coverage in a rabbit experimental model. Eight New Zealand white rabbits' eyes received an equal-sized glycerin-preserved homologous scleral patch or a double-layered processed porcine pericardium that was sutured to the bare sclera covering a silicone tube. Conjunctival hyperemia was graded using the double-blind method during the immediate postoperative period and during the first, third, and seventh postoperative weeks. After the seventh week, the enucleated eyes were histopathologically examined. They were also evaluated for signs of patch graft melting, tube erosion and chemosis. There was no occurrence of graft melting or tube exposure, although porcine pericardium was associated with greater inflammation through clinical observation. Light microscopy revealed marked inflammation surrounding the porcine pericardium with foreign body granuloma formation. On the other hand, the sclera group presented milder inflammation with foreign body granulomas only around the sutures. Porcine pericardium is associated with significant inflammation when used as tube coverage in a rabbit model, at both histopathologic and clinical levels, when compared to glycerin-preserved homologous sclera during the seven-week follow-up period.

Influence of mesh materials on the integrity of the vas deferens following Lichtenstein hernioplasty: an experimental model

The utilization of mesh reinforcement of the inguinal area with polypropylene mesh has increased drastically over the last decade. Infertility due to obstructive azoospermia is a rare but serious complication following inguinal hernia repair, especially in young patients. The aim of this study was to evaluate the effect of different mesh structures on integrity of the vas deferens. Twenty male Chinchilla rabbits were used. The spermatic cord was dissected free and a Lichtenstein repair was performed with a low-weight polypropylene mesh (UltraPro) and a heavy-weight polypropylene mesh (Prolene) on the contralateral side. A vasography was performed after six months in order to investigate obstructions of the vas deferens. Light microscopy of the mesh host tissue interface was also performed and the foreign body reaction analyzed. Spermatogenesis was evaluated using the Johnsen score. Vasography revealed relevant obstructions (>75% of lumen diameter) located at the mesh margins (50% of Prolene and 22.2% of UltraPro mesh samples). Microscopic investigation of the mesh-host tissue interface showed typical formation of foreign body granulomas. The diameters of the foreign body granulomas were significantly reduced in the UltraPro mesh group (41.7 +/- 5.5 microm) compared to the Prolene mesh group (48.7 +/- 7.7 microm). Upon investigating the percentages of apoptotic (TUNEL) and proliferating (Ki67) cells, no significant differences were found. Following Prolene mesh implantation, a mean Johnsen score of 9.1 +/- 1.2 was estimated, which was not significantly different from the UltraPro mesh samples (8.9 +/- 1.4, P > 0.05). If a mesh material is needed for inguinal hernia repair in young patients, the use of modern low-weight large porous and elastic samples appears to have a beneficial effect on integrity of the vas deferens.

Foreign body granuloma formation secondary to silicone injection

Injectable silicone has been used extensively over the last 40 years for soft tissue augmentation. Although considered biologically inert, this material has been implicated in a variety of adverse reactions including granulomas, disfiguring nodules, and lymphedema, sometimes with latent periods of decades. Often these complications are a result of the use of industrial grade products injected by unlicensed or unskilled practitioners. Here we report a case of foreign body granuloma in the thigh secondary to silicone injection in the buttocks. Initially the patient did not disclose a cosmetic contouring procedure administered by a nonprofessional nine months earlier, making diagnosis difficult. We remind clinicians to include foreign body granulomas in the differential diagnosis of apparent cellulitis and to question patients about the use of injectable fillers.

HIV-associated lipodystrophy: a review of underlying mechanisms and therapeutic options

Lipodystrophy (LD) is a common adverse effect of HIV treatment with highly active antiretroviral therapy, which comprises morphological and metabolic changes. The underlying mechanisms for LD are thought to be due to mitochondrial toxicity and insulin resistance, which results from derangements in levels of adipose tissue-derived proteins (adipocytokines) that are actively involved in energy homeostasis. Several management strategies for combating this syndrome are available, but they all have limitations. They include: switching from thymidine analogues to tenofovir or abacavir in lipoatrophy, or switching from protease inhibitors associated with hyperlipidaemia to a protease-sparing option; injection into the face with either biodegradable fillers such as poly-L-lactic acid and hyaluronic acid (a temporary measure requiring re-treatment) or permanent fillers such as bio-alcamid (with the risk of foreign body reaction or granuloma formation); and structured treatment interruption with the risk of loss of virological control and disease progression. There is therefore a need to explore alternative therapeutic options. Some new approaches including adipocytokines, uridine supplementation, glitazones, growth hormone (or growth hormone-releasing hormone analogues), metformin and statins (used alone or in combination) merit further investigation.

Focal Uptake of Tc-99m MDP in a Gossypiboma

A 51-year-old Korean woman with a history of breast cancer underwent screening bone scintigraphy, which revealed minimal soft tissue uptake of Tc-99m methylene diphosphonate (MDP) in the right lower quadrant. CT and plain films confirmed that the uptake was due to a retained surgical sponge or gossypiboma. The incidence of gossypibomas has been reported at high as 1 in 1000 to 15,000 intra-abdominal operations. The natural progression of an aseptic gossypiboma is a foreign body reaction and granuloma formation. This inflammatory granulomatous reaction is the most likely cause of the extraosseous accumulation of Tc-99m MDP. This entity should be added to the already extensive list of etiologies of extraosseous MDP accumulation.

Alternative macrophage activation in periprosthetic osteolysis

Several disorders characterized by macrophages accumulating non-disposable (or hard to dispose of) material or formation of multinucleated giant cell containing granulomas have been linked to elicitation of an alternative macrophage activation phenotype. Gene profiling efforts have shown that alternative macrophage activation can exist in numerous forms, each specific for the particular biological niche in which the macrophage finds itself, accentuating the plasticity of this cell type. Periprosthetic osteolysis is characterized by macrophage phagocytosis of particles of wear debris and formation of foreign body granulomas, suggesting the hypothesis that it may represent a new member of this group of diseases characterized by alternative macrophage activation. Gene profiling has provided strong supportive evidence for this hypothesis, revealing that periprosthetic tissues of osteolysis patients show the presence of a pronounced alternative macrophage activation pathway, with the classical pro-inflammatory activation pathway being less evident. These findings have important implications for our understanding of periprosthetic osteolysis and how to approach future investigations into this disease.

Migration of aluminum silicate from the oral cavity to the submandibular region, with foreign body granuloma formation: report of a case

We present the first case of foreign body granuloma in the cervical (submandibular) region as a result of migration of noninjected aluminium silicate particles from the oral mucosa. This migration can be explained by macrophage phagocytosis and transport through the local lymphatic network and surgical disruption of fascial layers. The appearance of foreign body granulomas in distant sites may appear several weeks after the local event in a specific disposition according with the migration route. This entity must be born in mind in differential diagnosis of multiple nodules, pigmentation, or persistent swelling in the cervical-orofacial region.

Control of Pseudomonas aeruginosa Skin Infections in Mice Is Mast Cell-Dependent

Mast cells (MCs) have recently been shown to be essential for the elicitation of efficient immune responses in murine sepsis. To explore whether MCs also contribute to the control of bacterial skin infections, we studied skin lesions induced by Pseudomonas aeruginosa (PA) in genetically MC-deficient Kit(W)/Kit(W-v) mice, normal Kit(+/+) mice, and MC-reconstituted Kit(W)/Kit(W-v) mice. PA injections resulted in strikingly (>2-fold) larger skin lesions in Kit(W)/Kit(W-v) mice than in Kit(+/+) mice, which exhibited pronounced MC degranulation at infection sites. In addition, neutrophil recruitment following PA injections and bacterial clearance from sites of infection was significantly impaired in Kit(W)/Kit(W-v) mice compared with Kit(+/+) mice. Notably, the adoptive transfer of MCs to the skin of Kit(W)/Kit(W-v) mice before PA infection resulted in normal neutrophil accumulation as well as skin lesions comparable with those in Kit(+/+) mice in both bacterial burden and size. These findings demonstrate for the first time that activated MCs are crucial for the induction of protective innate immune responses to bacterial skin infections.

Adverse reactions to polylactic acid injections in the periorbital area

Correction of aging changes and contour deformities has been addressed largely by tissue augmentation agents whose volume is injected into tissues to achieve the required result. Polylactic acid (PLA) is an agent that is injected with the aim of enhancing the host's own collagen deposition. We describe the development of multiple nodules and one case of a foreign-body granuloma formation following the administration of PLA to the face for correction of rhytides and contour deformities. Methods Four case presentations, including clinical history, injection protocol, histopathology, individual treatment, and their outcomes, are discussed with pertinent literature review. Four patients who received injections of PLA developed nodules that were clinically similar in size, shape, and consistency. Histopathologic examination revealed the presence of a foreign-body granulomatous inflammatory reaction in one of the patients. Cosmetic treatment with PLA may be complicated by disfiguring nodules that may mask a granulomatous reaction. PLA-induced nodules and foreign-body granulomas have proven difficult to treat. Therefore, PLA should only be injected in the infraorbital area by experienced injectors who have had appropriate training. In addition to this, PLA should be injected in a "depot" method below the muscle at a significantly diluted volume. Due to the complications encountered after the use of PLA, we feel that a cautionary warning regarding the use of PLA in this area may be prudent regardless of the abovementioned precautions.

Histopathologic study of minced and injected expanded polytetrafluoroethylene (Gore-Tex) in quadriceps muscle of rats for injection laryngoplasty

Objective Gore-Tex has not yet been used as an injection material, and no animal study has been performed. The purpose of this study was to investigate the histopathological and volumetric changes of minced and injected expanded polytetrafluoroethylene (Gore-Tex) in the quadriceps muscle of rats to find out its possibility as an injection material in future injection laryngoplasty. Design A prospective study was performed in 13 Wistar rats. Methods The 50 ± 5 mg Gore-Tex vascular graft was minced until it was fine enough to pass through a 16G injection cannula. To create viscosity in order to avoid precipitation, minced Gore-Tex was mixed with sodium hyaluronate (SH) gel. 0.5 ml of this mixture was injected into the middle part of the right quadriceps muscle of each subject. Then, pure SH (0.5 ml) was injected into the middle part of the left quadriceps muscle of each subject. To compare the volumetric and histopathological changes of the injection area occupied by the materials over the time, two rats were sacrificed 1 day after the procedure, four rats after 1 month, four rats after 3 months and three rats after 6 months. Results In pure SH: SH was observed as an effusion in the muscle of one subject on the first day only. We did not detect SH in the muscle in the first, third and sixth months and, as a result, there was no augmentation. Inflammation and fibrosis was not detected in any of these applications of SH. In minced Gore-Tex + SH gel mixture: SH was again eliminated from the muscle in a very short period of time, but the remaining Gore-Tex created a 15.8% volumetric gain. Fibrosis and capsule formation began in the first month and, in the sixth month; we observed connective tissue surrounding the Gore-Tex material. Ingrowth of connective tissue into the Gore-Tex, though not present in the first month, occurred partially in the third and significantly in the sixth month. In addition, we observed foreign body granuloma formation after the third month. Conclusions Pure SH, though easily applicable, was immediately eliminated leaving no trace. In the relatively difficult applications of Gore-Tex mixed with SH, however, there was residual Gore-Tex present in all subjects throughout the study. Gore-Tex may be an applicable material for injection laryngoplasty.

Experimental Evaluation of Early and Long-Term Effects of Microparticle Embolization in Two Different Mini-Pig Models. Part I: Kidney

Using a pig model: (1) to evaluate the vascular distribution pattern, including the homogeneity and completeness of the intra-arterial microsphere distribution, of 40-120-microm trisacryl-gelatin microspheres (Embospheres) in acute whole-kidney embolization; (2) to evaluate the durability and biocompatibility of 40-120-microm trisacryl-gelatin microspheres (Embospheres) in chronic partial kidney embolization. Twenty-two animals were divided into four groups: group 1 (n = 4) underwent total arterial renal occlusion with immediate euthanasia. Groups 2-4 had chronic superselective and partial renal embolization with increasing follow-up times: group 2 (n = 2), 1 week; group 3 (n = 7), 4 weeks; and group 4 (n = 9), 14 weeks. Key endpoints in group 1 were homogeneity and completeness of acute embolizations. In groups 2-4 the key endpoints were durability of embolization and particle-related inflammation in chronic partial embolizations as assessed by quantitative angiography or histomorphometry. A numerical angiographic occlusion score (0.0 to 4.0, where 3.0 is optimal) was developed to assess and quantify the angiographic durability of superselective embolizations (groups 2-4). In group 1, a relatively homogeneous distribution of the particles from segmental arteries to the precapillary level was shown by histomorphometry. Some particles reached the glomerular vas afferens (10 microm diameter). In groups 2-4, a mild recanalization appeared during follow-up. The immediate average postembolization occlusion score of 3.18 +/- 0.73 was reduced to 1.44 +/- 0.73 (statistically significant). Microscopy revealed subtotal necrosis but no foreign body granuloma formation. The intra-arterial appearance of giant cells closely attaching to the surface of the embolic spheres inside the vessel lumen was noted. Vessel walls showed major ischemic reactions. Microspheres 40-120 microm in diameter might achieve total occlusion of the arterial kidney vasculature when injected centrally as a result of their fairly homogeneous distribution. Segmental renal infarction occurs after chronic partial embolization despite recanalizations during follow-up. Only mild specific intra-arterial foreign body reactions were found.

The potential of microscopic sterile sponge particles to induce foreign body reaction

The sterile sponges may lose a significant amount of lint during their routine use in surgery, which is usually neglected. We designed an experimental model to evaluate the potential of sterile sponges to lose lint and to induce foreign body reaction in surgically created wounds. In 15 Wistar rats, separate subcutaneous pockets were created. Left-sided pockets were temporarily packed with sterile sponges, while the right-sided pockets remained empty. All the pockets were then irrigated with sterile saline. The presence of microscopic sponge particles was evaluated in the irrigation materials. After 4 weeks, the presence of inflammation and foreign body reaction were evaluated histologically. Microscopic sponge remnants were present in 14 of 15 samples collected from the left sides. The presence of foreign body giant cells with ingested sponge particles and formation of well-defined foreign body granulomas were observed only in samples collected from the left sides. A statistically significant difference was observed between the two sides when the intensity of inflammation was graded (P= 0.012). Cotton sponges used in surgery are shown to have a potential of losing invisible microscopic particles that have a potential to induce foreign body reaction.

Lung disease 35 years after aspiration of activated charcoal in combination with pulmonary lymphangioleiomyomatosis

Activated charcoal provides effective treatment for most toxic ingestions. Accidental aspiration of activated charcoal is rare. Previously, there have been a few single cases reported on charcoal-related pulmonary complications. We describe an unusual case of pulmonary lesions 35 years after accidental aspiration of activated charcoal. The 38-year-old female patient presented with recurrent pneumothorax. A routinely performed chest roentgenogram revealed pulmonary lesions, highly suggestive to lymphangioleiomyomatosis (LAM). Histopathological investigation of the lung tissue demonstrated some features of LAM but showed prominent pneumoconiotic lesions with cystic tissue destruction. The pneumoconiotic reaction was characterized by prominent black deposits accompanied by foreign-body granuloma formation and minimal fibrosis. Scanning electron microscopic investigation of these deposits showed particles measuring up to 300 microm in greatest diameter. Energy-dispersive X-ray spectra of these particles revealed carbon-rich material, presumably charcoal. The aspiration event was confirmed by the clinical history. To our knowledge, this is the first report not only on a long-term follow-up after aspiration of activated charcoal but also on charcoal-related pulmonary lesions in combination with LAM.

Granuloma annulare – A genetic disorder that sustain an incomplete foreign-body granuloma reaction

Granuloma annulare (GA) is a common dermatosis characterized by an annular arrangement of erythematous papules, plaques, rarely nodules or patches. It is a type of non-infectious granuloma with unknown etiology. Hypothesis. The immune reaction always begins with the foreign-body granuloma formation. However, if during the process the antigen is recognized as too small the immune reaction stops the granuloma development. In the case of GA the dysfunctional control mechanism continues to sustain the granulomatous formation. Because the target does not exist anymore, the initiated process starts the "search" for a new target (circular spreading). Different histological and clinical presentations depends on which gene of the control mechanism is dysfunctional, while the distribution depends on the type of antigen and its distribution at the start of the immune reaction. The disappearance of GA after biopsy, that occurs in some cases, could be attributable to the specific defective gene involved (the biopsy can disrupt only some type of GA). So, new therapies for solitary GA formations could be directed to the disruption and creation of a new and healthy immune response from the point of disruption. A comparative analysis of the gene expression of GA and the foreign-body granuloma in the same patient, and GA among different patients could clarify which genes are involved in granulomatous formations. The cells affected by those genetic defects are probably histiocytes and lymphocytes (both always present in GA). Because of some similarity, necrobiosis lipoidica could also be a specific type of GA.