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2.
Antibiotics (Basel) ; 11(10)2022 Sep 21.
Article in English | MEDLINE | ID: mdl-36289943

ABSTRACT

Aims: This study evaluates the value of a new graphic representation of cell count data of synovial fluid in the diagnosis of acute periprosthetic joint infection (PJI). Methods: A total of 75 patients with revisions of 48 primary total knee and 27 hip arthroplasties within the first six weeks after surgery were analyzed with cultivation of the synovial fluid and determination of its cell count as well as microbiological and histological analyses of the periprosthetic tissue obtained during the revision surgery using the ICM classification. The synovial fluid was additionally analyzed for graphic representation of the measured cells using LMNE-matrices. Results: A total of 38 patients (50.7%) had an infection. The following types of LMNE matrices could be differentiated: the indeterminate type (IV) in 14.7%, the infection type (II) in 5.3%, the hematoma type (V) in 33.3%, and the mixed type (VI; infection and hematoma) in 46.7%. Differentiation of LMNE types into infection (types II and VI) and non-infection (types IV and V) resulted in a sensitivity of 100%, a specificity of 97.3%, and a positive likelihood ratio of 37.0. The cell count measurement showed a sensitivity of 78.9%, a specificity of 89.2%, and a positive likelihood ratio of 7.3 at a cut-off of 10,000 cells. The percentage of polymorphonuclear leukocytes showed a sensitivity of 34.2%, a specificity of 100%, and a positive likelihood ratio of >200 at a cut-off of 90%. Conclusion: The graphic representation of the cell count analysis of synovial aspirates is a new and helpful method for differentiating between genuine early periprosthetic infections and postoperative hemarthrosis.

3.
Antibiotics (Basel) ; 10(4)2021 Mar 24.
Article in English | MEDLINE | ID: mdl-33804988

ABSTRACT

AIM: This study was designed to answer the question whether a graphical representation increase the diagnostic value of automated leucocyte counting of the synovial fluid in the diagnosis of periprosthetic joint infections (PJI). MATERIAL AND METHODS: Synovial aspirates from 322 patients (162 women, 160 men) with revisions of 192 total knee and 130 hip arthroplasties were analysed with microbiological cultivation, determination of cell counts and assay of the biomarker alpha-defensin (170 cases). In addition, microbiological and histological analysis of the periprosthetic tissue obtained during the revision surgery was carried out using the ICM classification and the histological classification of Morawietz and Krenn. The synovial aspirates were additionally analysed to produce dot plot representations (LMNE matrices) of the cells and particles in the aspirates using the hematology analyser ABX Pentra XL 80. RESULTS: 112 patients (34.8%) had an infection according to the ICM criteria. When analysing the graphical LMNE matrices from synovia cell counting, four types could be differentiated: the type "wear particles" (I) in 28.3%, the type "infection" (II) in 24.8%, the "combined" type (III) in 15.5% and "indeterminate" type (IV) in 31.4%. There was a significant correlation between the graphical LMNE-types and the histological types of Morawietz and Krenn (p < 0.001 and Cramer test V value of 0.529). The addition of the LMNE-Matrix assessment increased the diagnostic value of the cell count and the cut-off value of the WBC count could be set lower by adding the LMNE-Matrix to the diagnostic procedure. CONCLUSION: The graphical representation of the cell count analysis of synovial aspirates is a new and helpful method for differentiating between real periprosthetic infections with an increased leukocyte count and false positive data resulting from wear particles. This new approach helps to increase the diagnostic value of cell count analysis in the diagnosis of PJI.

4.
JPGN Rep ; 1(2): e025, 2020 Nov.
Article in English | MEDLINE | ID: mdl-37206597

ABSTRACT

The infant was born at a gestational age of 28 + 2 weeks as second twin to a 26-year-old woman, G1/P0, due to eclampsia. The patient developed well and was on full oral feeds when he started to develop nonbilious vomiting at 5 weeks. He was diagnosed with pyloric hypertrophy and underwent pylorotomy, but the condition did not improve and the patient was referred to our hospital. Here, esophagogastroduodenoscopy showed severely inflamed esophageal and gastric mucosa which was found to be due to cytomegaly virus (CMV) infection and a nonpassable pylorus. The patient underwent pyloroplasty revealing a fibrous pyloric ring. Histology showed giant cells suggestive of CMV infection which was confirmed by polymerase chain reaction. He was started on valganciclovir and discharged 4 weeks later on full enteral feeds. To our knowledge, this is the first case of gastric outlet obstruction due to CMV infection in a premature infant.

5.
J Pathol Clin Res ; 4(1): 55-68, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29416877

ABSTRACT

Changes in glycosylation are salient features of cancer cells. Here, we report on the diagnostic and therapeutic properties of IDK1, an antibody against tumour associated, hypoglycosylated bone sialoprotein (hypo-BSP). The affinity of the rat monoclonal antibody IDK1 for hypo-BSP, as determined by microscale thermophoresis, was three orders of magnitude higher than for mature BSP, whereas the mouse monoclonal antibody used had similar affinity for both BSP forms. IDK1 showed no activity against the proliferation or migration of normal or cancer cells growing in vitro. In vivo, however, IDK1 caused dose-dependent regression of soft tissue and skeletal lesions in nude rats harbouring human MDA-MB-231 cells. At optimal dose, 80% of the treated rats showed complete remission of all tumour lesions. Analysis of BSP expression in vitro by fluorescence-activated cell sorting (FACS) and immunocytochemistry showed basal levels of this protein, which were visible only in a fraction of these cells. Cells of the metastatic cell lines MDA-MB-231 and PC-3 were more often positive for hypo-BSP. In addition, there was co-expression of both forms in some cells, but almost no co-localization; rather, hypo-BSP was present in the nucleus, and mature BSP was detected extra-cellularly. Normal osteoblasts and osteoclasts were negative for hypo-BSP. Breast cancer tissue, however, showed strong expression of mature BSP, which was present intra-cellularly as well as in vesicles outside cells. Hypo-BSP was present mainly in lesions from skeletal sites, thus explaining the antineoplastic activity of IDK1, which was high in lesions growing in the vicinity of the skeleton but low in lesions growing subcutaneously. Finally, hypo-BSP was detected in specimens from breast cancer patients, with a significantly greater intensity in skeletal metastases as compared to the respective primary cancers. In conclusion, IDK-1 is an antibody with diagnostic and therapeutic applications in skeletal metastases of breast cancer.

6.
Pigment Cell Melanoma Res ; 31(3): 437-441, 2018 05.
Article in English | MEDLINE | ID: mdl-29316280

ABSTRACT

Giant congenital melanocytic nevi may be symptomatically isolated or syndromic. Associations with capillary malformations are exceptional, and development of epidermal cysts has not been described. A 71-year-old patient with a giant congenital melanocytic nevus (CMN) of the lower back, buttocks, and thighs was asymptomatic except for unexpected hemorrhage during partial surgical excision years before. Blunt trauma at age 64 initiated recurrent, severe pain under the nevus; multiple large epidermal cysts then developed within it. Imaging and biopsy showed a large, non-pulsatile venous malformation intermingled with the deep nevus. A low-abundance, heterozygous BRAF c.1799T>A (p.V600E) mutation was present in both gluteal and occipital congenital nevi; additional mutations in NRAS, GNAQ, GNA11, HRAS, or PIK3CA were undetectable. This is the first demonstration of a recurrent BRAF mutation in multiple large congenital nevi from the same individual, confirming that this malformation can have multiple genetic origins. Early constitutive activation of BRAF can therefore cause unusual associations of giant nevi with vascular malformations, indicating that both pigment and endothelial cell physiology may be affected by mosaic RASopathies.


Subject(s)
Epidermal Cyst , Mutation , Nevus, Pigmented , Proto-Oncogene Proteins B-raf/genetics , Vascular Malformations , Aged , Epidermal Cyst/congenital , Epidermal Cyst/enzymology , Epidermal Cyst/pathology , Epidermal Cyst/surgery , Humans , Male , Nevus, Pigmented/congenital , Nevus, Pigmented/enzymology , Nevus, Pigmented/surgery , Vascular Malformations/enzymology , Vascular Malformations/genetics , Vascular Malformations/pathology
7.
Genes Cancer ; 9(5-6): 215-231, 2018 May.
Article in English | MEDLINE | ID: mdl-30603057

ABSTRACT

Liver is the main target of pancreatic ductal adenocarcinoma (PDAC) metastasis. Here, a rat model was used for analysing gene expression modulations during liver colonization. ASML PDAC cells were injected to isogenic rats and re-isolated at various stages of liver colonization for RNA isolation or re-cultivation. Microarrays were used for analysing mRNA and miRNA profiles of expres-sion. The results were partially confirmed by (q) RT-PCR and western blot. Selected genes were knocked down by siRNA transfection and the resulting cell behaviour was analysed. The ratio of up- and down regulated genes decreased from 20:1 (early stage) to 1.2:1 (terminal stage). Activation of cancer relevant gene categories varied between stages of liver colonization, with a nadir in the intermediate stage. The cells' environment triggered up to hundredfold changed expression for collagens, matrix metalloproteinases and chemokines. These modulations in mRNA expression were related to respective changes at miRNA levels. Gene expression knockdown of Mmp2 and Ccl20, which were highly modulated in vivo, was correlated with reduced prolif-eration and migration in vitro. Thus, target genes and temporal alterations in expression were identified, which can serve as basis for future therapeutic or diagnostic purposes.

8.
Clin Orthop Relat Res ; 471(3): 956-64, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22806261

ABSTRACT

BACKGROUND: The role of the synovial biopsy in the preoperative diagnosis of a periprosthetic joint infection (PJI) of the hip has not been clearly defined. QUESTIONS/PURPOSES: We asked whether the value of a biopsy for a PJI is greater than that of aspiration and C-reactive protein (CRP). METHODS: Before revision in 100 hip endoprostheses, we obtained CRP values, aspirated the joint, and obtained five synovial biopsy samples for bacteriologic analysis and five for histologic analysis. Microbiologic and histologic analyses of the periprosthetic tissue during revision surgery were used to verify the results of the preoperative diagnostic methods. The minimum followup was 24 months (median 32; range, 24-47 months). RESULTS: Forty-five of the 100 prostheses were identified as infected. The biopsy, with a combination of the bacteriologic and histologic examinations, showed the greatest diagnostic value of all the diagnostic procedures and led to a sensitivity of 82% (95% CI, ± 11%), specificity of 98% (95% CI, ± 4%), positive predictive value of 97% (95% CI, ± 5%), negative predictive value of 87% (95% CI, ± 8.3%), and accuracy of 91%. CONCLUSIONS: The biopsy technique has a greater value than aspiration and CRP in the diagnosis of PJI of the hip (Masri et al. J Arthroplasty 22:72-78, 2007). In patients with a negative aspirate, but increased CRP or clinical signs of infection, we regard biopsy to be preferable to just repeating the aspiration. LEVEL OF EVIDENCE: Level II prognostic study. See Guidelines for Authors for a complete description of levels of evidence.


Subject(s)
Arthroplasty, Replacement, Hip/adverse effects , Biopsy , Hip Joint/surgery , Hip Prosthesis/adverse effects , Prosthesis-Related Infections/diagnosis , Synovectomy , Adult , Aged , Aged, 80 and over , Arthroplasty, Replacement, Hip/instrumentation , Bacteriological Techniques , Biomarkers/blood , Biopsy/methods , Biopsy, Needle , C-Reactive Protein/analysis , Female , Hip Joint/microbiology , Hip Joint/pathology , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Prosthesis-Related Infections/microbiology , Prosthesis-Related Infections/pathology , Prosthesis-Related Infections/surgery , Reoperation , Sensitivity and Specificity , Synovial Membrane/microbiology , Synovial Membrane/pathology
9.
Arch Orthop Trauma Surg ; 131(10): 1459-66, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21594572

ABSTRACT

BACKGROUND: Adipogenous tissue derived stem cells (ASC) are available in abundance in the human body and can differentiate in the presence of lineage-specific induction factors, for example, in myogenic, adipogenic, chondrogenic and osteogenic cells. The aim of this study was to evaluate the impact of osteogenic induced ASC's (O-ASC) on revascularization and cellular repopulation of avital cortical bone employing a vascularized bovine scaffold. METHODS: An inguinal arterio-venous bundle was dissected in the groin of female white New Zealand rabbits (n = 6) and placed centrally inside an O-ASC seeded scaffold via a central drill hole. In the same surgical session this construct was placed into a segment of avital cortical bone allograft from a donor rabbit. Unseeded scaffolds that were implanted and treated in the same fashion served as controls (n = 6). In order to prevent external revascularization, all constructs were wrapped in silicon foil and finally implanted in the rabbits' groin. Three months later, the constructs were explanted and investigated for vascularization of (a) the scaffold (b) the surrounding bone allograft. Histological stainings to determine cell growth, cellular repopulation of the scaffold and the cortical bone matrix, as well as inflammatory parameters were carried out. RESULTS: O-ASC seeded scaffolds showed a significant increase in new vessel formation in the scaffold as well as in the bone allograft compared to unseeded scaffolds. Furthermore, new vital osteocytes as a sign of cellular repopulation inside the bone allograft were found only in the treatment group. Vital chondrocytes were only found in the O-ASC seeded scaffolds as well. CONCLUSION: The presence of O-ASC significantly induce neo-vascularization and osteocytic repopulation of previously avital bone allograft as opposed to unseeded scaffolds in a rabbit model. Hence, this model might be of relevant value for future bone tissue engineering research and for re-vitalizing marginally nourished bone such as in avascular bone necrosis.


Subject(s)
Adipocytes/physiology , Adipose Tissue/cytology , Bone Transplantation/methods , Osteogenesis/physiology , Stem Cells/physiology , Tissue Scaffolds , Animals , Biomarkers/metabolism , Cattle , Female , Immunohistochemistry , Neovascularization, Physiologic , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Rabbits , Statistics, Nonparametric , Transplantation, Homologous , Vascular Endothelial Growth Factor A/metabolism
10.
J Vasc Interv Radiol ; 21(8): 1262-70, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20656224

ABSTRACT

PURPOSE: Paclitaxel is an antiproliferative agent in drug-eluting stents with largely unknown tissue interaction. Toxicity might result from overdosage and/or accumulation. Part 1 of this two-step study investigated how paclitaxel uptake depends on dose density, coronary drug transfer kinetics, and elution efficacy. MATERIALS AND METHODS: With cobalt chromium stents and Polyzene-F nanoscale coating, low, intermediate, and high paclitaxel dose densities (25 microg, 50 microg, and 150 microg per stent) were investigated in porcine right coronary arteries (RCAs). Coronary and myocardial tissue concentration measurements and determination of on-stent paclitaxel and plasma concentrations were performed at 2, 8, 24, and 72 hours. RESULTS: For all stents, uptake was similar at all time intervals (paclitaxel RCA concentration range, 1,610-33,300 ng). Low- and intermediate-dose stents showed similar RCA concentrations, but those for high-dose stents were three times greater. Residual on-stent paclitaxel concentration was not time-dependent, at 33.3% on low-, 30.6% on intermediate-, and 17.4% on high-dose stents. Paclitaxel was measurable in only the plasma immediately after stent placement, with a linear dose relationship and a timely regression: measurements in high-dose stents were 0.0454-0.656 ng/mL at 1 minute and 0.0329-0.0879 ng/mL at 5 minutes. Untreated control samples of the left coronary artery showed a linear dose-dependent concentration (12.6 ng/g, 21.2 ng/g, and 85.2 ng/g). CONCLUSIONS: Overall coronary paclitaxel uptake is fairly independent from the baseline overall dose density and, hence, depends on immediate binding mechanisms of the arterial wall. This is supported by the fact that, regardless of the applied dose density, the kinetics of paclitaxel uptake did not follow an exposure time pattern.


Subject(s)
Angioplasty, Balloon, Coronary/instrumentation , Cardiovascular Agents/pharmacokinetics , Coated Materials, Biocompatible , Coronary Vessels/metabolism , Drug-Eluting Stents , Inflammation/metabolism , Paclitaxel/pharmacokinetics , Angioplasty, Balloon, Coronary/adverse effects , Animals , Biological Availability , Cardiovascular Agents/administration & dosage , Cardiovascular Agents/blood , Cardiovascular Agents/toxicity , Chromium Alloys , Coronary Vessels/drug effects , Coronary Vessels/pathology , Dose-Response Relationship, Drug , Female , Inflammation/chemically induced , Inflammation/pathology , Models, Animal , Myocardium/metabolism , Paclitaxel/administration & dosage , Paclitaxel/blood , Paclitaxel/toxicity , Polymers , Prosthesis Design , Swine , Swine, Miniature , Tissue Distribution
11.
J Bone Miner Res ; 25(4): 706-15, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19821765

ABSTRACT

The bone matrix is composed mostly of collagen, but the initial and continuous presence of fibronectin was found to be crucial for collagen matrix integrity in vitro. It has been assumed that osteoblasts produce the fibronectin required for bone matrix formation. Using transgenic mice, we conditionally deleted fibronectin in the osteoblasts and in the liver using the cre-loxP system. We also used mice with mutated fibronectin and conditionally deleted beta(1)-integrin in osteoblasts to identify the receptor involved in fibronectin effects on osteoblasts. Conditional deletion of fibronectin in the differentiating osteoblasts [using the 2.3 kb collagen-alpha1(I) promoter] failed to show a decrease in fibronectin amount in the bone matrix despite evidence of successful deletion. Using these mice we established that osteoblast-derived fibronectin solely affects osteoblast function. This effect was not mediated by integrins that bind to the RGD motif. Conditional deletion of fibronectin in the liver showed a marked decrease in fibronectin content in the matrix associated with decreased mineral-to-matrix ratio and changed biomechanical properties but had no effect on osteoblasts or osteoclasts. In conclusion, osteoblast fibronectin affects osteoblasts function. This does not seem to be mediated by the RGD motif on fibronectin. In contrast, liver-derived fibronectin affects bone matrix properties without affecting osteoblast or osteoclast function. A novel role for liver-derived circulating fibronectin thus was defined and delineated from that of locally produced fibronectin.


Subject(s)
Bone Matrix/metabolism , Fibronectins/blood , Osteoblasts/metabolism , Animals , Bone Density , Cell Differentiation , Collagen/metabolism , Extracellular Matrix/metabolism , Female , Fibronectins/genetics , Fibronectins/metabolism , Integrin beta1/metabolism , Liver/metabolism , Male , Mice , Mice, Transgenic
12.
Histochem Cell Biol ; 133(1): 69-83, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19830446

ABSTRACT

Protein p0071 is a member of the p120-subfamily of armadillo proteins and is well known as a junctional plaque component involved in cell-cell adhesion, especially in adherens junctions. By systematic immunohistochemical analysis of mouse and human kidney tissues, p0071 was prominently detected in distinct kidney tubules. Upon double-labeling immunolocalization experiments with segment-specific markers, p0071 was predominantly localized in distal straight and convoluted tubules and to a lesser extent in proximal tubules, in the ascending thin limb of loop of Henle and in the collecting ducts. In capillaries of the kidney, p0071 co-localized with VE-cadherin an endothelium-specific cadherin. Protein p0071 was also detected in both, renal cell carcinomas derived from distal tubules and in maturing nephrons of early mouse developmental stages. Immunoblotting of total extracts of cultured cells of renal origin showed that p0071 was detected in all human and murine cells analyzed. Upon immunolocalization, p0071 was observed in adherens junctions but also in distinct cytoplasmic structures at the cell periphery of cultured cells. Possible structural and functional roles of p0071 are suggested by its preferential occurrence in distinct tubule segments, and its potential use as a cytodiagnostic cell type marker in renal pathology is discussed.


Subject(s)
Adherens Junctions/metabolism , Armadillo Domain Proteins/biosynthesis , Kidney Tubules, Distal/metabolism , Adherens Junctions/ultrastructure , Armadillo Domain Proteins/chemistry , Armadillo Domain Proteins/metabolism , Cells, Cultured , Cloning, Molecular , Humans , Kidney Tubules, Distal/ultrastructure , Microscopy, Fluorescence
13.
J Vasc Interv Radiol ; 20(12): 1597-607, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19944985

ABSTRACT

PURPOSE: To determine the arterial distribution pattern of the embolic agent Embozene within the porcine kidney and compare it with those of other spherical embolic agents. MATERIALS AND METHODS: Embozene, Embosphere, Bead Block, and Contour SE in size classes of 100-300 microm, 500-700 microm, and 700-900 microm and Embozene and Embosphere in the size class of 40-120 microm were used for total arterial occlusion in minipig kidneys. Organs were evaluated microscopically regarding vascular distribution of the different embolic agents and particle sizes. RESULTS: The following variations of arterial distribution were identified. In the 40-120-microm size class, Embosphere particles penetrated significantly deeper compared with Embozene (P = .04). In the 100-300-microm size class, Bead Block showed a significantly deeper distribution as microscopy identified particles in arteries much smaller than their nominal size. In the 500-700-microm size class, Embosphere and Contour SE showed a deeper distribution. The most uniform arterial distribution was observed in the 700-900 microm size class,. However, few Embosphere and Contour SE particles were found in arcuate arteries, also indicating a distal distribution. CONCLUSIONS: Throughout the four most-used size classes, from very small (40-120 microm) to large (700-900 microm), the distribution characteristics of the four tested materials vary substantially. Particularly, small Embosphere particles and small Bead Block particles showed a more distal distribution, as did medium-sized Embosphere and Contour SE particles. In the largest investigated size class, the distribution was more uniform. In general, the Embozene particles are very uniform in size, and they seem to reach vessels closely corresponding to their nominal size.


Subject(s)
Embolization, Therapeutic/methods , Kidney/blood supply , Polymers/administration & dosage , Renal Artery , Acrylic Resins/administration & dosage , Animals , Gelatin/administration & dosage , Hydrogel, Polyethylene Glycol Dimethacrylate/administration & dosage , Injections, Intra-Arterial , Models, Animal , Organophosphorus Compounds/administration & dosage , Particle Size , Polyvinyl Alcohol/administration & dosage , Radiography , Renal Artery/anatomy & histology , Renal Artery/diagnostic imaging , Swine , Swine, Miniature
14.
J Vasc Interv Radiol ; 20(12): 1608-16, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19944986

ABSTRACT

PURPOSE: In part 1 of the present study, the authors demonstrated that coronary paclitaxel uptake from drug eluting stents (DESs) was not dependent on exposure time and dose. In this second part, the effect of the different paclitaxel dose densities on long-term biologic behavior was evaluated. MATERIALS AND METHODS: In 40 minipigs, (with 4- and 12-week follow-up), identical stents with the same three paclitaxel dose densities as in part 1 were implanted in the right coronary artery. Minipigs implanted with Polyzene-F nanocoated stents served as the control group. Quantitative angiography measuring average luminal diameter (from three in-stent reference points), minimal luminal diameter (from the point of maximum in-stent stenosis), average late loss, maximum late loss, and binary stenosis rate was performed, as was microscopy to determine neointimal thickening, injury score, and inflammation. RESULTS: All three DESs were associated with a high average late loss, binary stenosis rate, and neointimal thickening, without significant differences. Drug-free stents had significantly less late in-stent stenosis: there was an average late loss of 0.3 mm +/- 0.3 in drug-free stents versus 0.8 mm +/- 0.2 in intermediate-dose stents and 1.5 mm +/- 0.6 in high-dose stents (P = .04). DES-associated inflammation was high in all DESs and six times higher as in the drug-free stents (Kornowski scores of 0.2 +/- 0.1 in drug-free stents, 1.3 +/- 0.9 in low-dose stents, 1.7 +/- 0.8 in intermediate-dose stents, and 1.3 +/- 1.0 in high-dose stents; P = .04). It worsened with time in all DESs, as did late in-stent stenosis. CONCLUSIONS: The extensive and long-term retention of paclitaxel even in a low-dose formulation, at least according to the present labeling of DESs, might be associated with negative long-term results with regard to inflammation and late in-stent stenosis.


Subject(s)
Angioplasty, Balloon, Coronary/instrumentation , Cardiovascular Agents/toxicity , Coated Materials, Biocompatible , Coronary Restenosis/chemically induced , Coronary Vessels/drug effects , Drug-Eluting Stents , Inflammation/chemically induced , Paclitaxel/toxicity , Angioplasty, Balloon, Coronary/adverse effects , Animals , Cardiovascular Agents/administration & dosage , Coronary Angiography , Coronary Restenosis/diagnostic imaging , Coronary Restenosis/pathology , Coronary Vessels/pathology , Dose-Response Relationship, Drug , Female , Inflammation/diagnostic imaging , Inflammation/pathology , Models, Animal , Paclitaxel/administration & dosage , Prosthesis Design , Prosthesis Failure , Swine , Swine, Miniature , Time Factors
16.
J Vasc Interv Radiol ; 20(7): 927-35, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19497761

ABSTRACT

PURPOSE: To compare outcomes with a thermoplastic polyurethane (TPU)-covered self-expanding nitinol stent-graft (TPU graft) with those of a bare self-expanding nitinol stent in a porcine model. MATERIALS AND METHODS: Fourteen TPU grafts and 14 commercially available bare nitinol stents were implanted, one each, in the iliac arteries of 14 minipigs. Follow-up was performed at 1 week (six animals), 4 weeks (four animals), and 12 weeks (four animals). The primary study endpoint was in-stent stenosis assessed with quantitative angiography and microscopy. Secondary endpoints were injury, inflammation, and endothelialization. RESULTS: After 1 week, the maximum percentage luminal loss was significantly greater in TPU grafts (average, 16.2%; range, 0.0%-35.8%) than in bare nitinol stents (8.2%; 0.0%-17.3%) (P = .04). Three of the four TPU grafts were occluded after 4 weeks, and all four TPU grafts were occluded after 12 weeks. Binary stenosis was seen in three of four bare nitinol stents after both 4 and 12 weeks. At 4-week follow-up, the average percentage luminal loss was significantly greater in TPU grafts (85.2%; 40.8%-100%) than in bare nitinol stents (49.5%; 37.9%-62.4%) (P = .003). The difference in neointimal height and percentage average stenosis between TPU grafts (1,028.7 microm and 68.4%) and bare nitinol stents (1,033.6 microm [918.0-1,118.40 microm] and 68.1% [60.44%-71.99%]) was not statistically significant. After 12 weeks, the average percentage luminal loss was 100% in TPU grafts due to occlusion of all stent-grafts and 24.9% (8.0%-63.9%) in bare nitinol stents (P = .011). CONCLUSIONS: TPU grafts failed to provide improved patency compared with the bare nitinol stents because of excessive neointimal growth and subsequent occlusion. In addition, the bare nitinol stents showed considerable in-stent stenosis at angiography and microscopy.


Subject(s)
Blood Vessel Prosthesis/adverse effects , Disease Models, Animal , Graft Occlusion, Vascular/etiology , Iliac Artery/surgery , Polyurethanes/adverse effects , Stents/adverse effects , Alloys/adverse effects , Alloys/chemistry , Animals , Coated Materials, Biocompatible/chemistry , Equipment Design , Equipment Failure Analysis , Graft Occlusion, Vascular/diagnosis , Hot Temperature , Humans , Iliac Artery/diagnostic imaging , Iliac Artery/pathology , Plastics/adverse effects , Plastics/chemistry , Polyurethanes/chemistry , Porosity , Radiography , Swine
17.
J Vasc Interv Radiol ; 20(7): 936-45, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19555888

ABSTRACT

PURPOSE: To evaluate the immunohistochemical inflammatory reaction after porcine renal embolization with the new spherical embolic agent Embozene and to compare it with other spherical embolic agents. MATERIALS AND METHODS: After superselective porcine renal embolization (40 pigs) with different sizes of embolic agents (Embozene, Embosphere, Bead Block, Contour SE), tissue arrays were obtained (size ranges, 40-120 microm, 100-300 microm, 500-700 microm, 700-900 microm). After immunostaining for CD subtyping (CD45 and CD68) and cytokines (C-reactive protein [CRP] and interleukin-1 beta), a semiquantitative immunoreactivity score was calculated for each marker: intensity of staining was scored between 0 (negative) and 3 (intensive) and extent of staining between 0 and 4 (>80%), indicating the percentage of positive staining. The intensity score (0-3) was multiplied by the extent of staining score (0-4), resulting in a semiquantitative immunoreactivity score (0-12). RESULTS: Analysis of cellular expression profiles (ie, CD45, CD68) revealed a significantly higher inflammatory score 4 weeks after embolization with Embosphere 100-300 microm particles than after embolization with Embozene, Bead Block, and Contour SE. After 12 weeks, the Embosphere 100-300 microm score decreased. Analysis of CRP expression showed similar results, with a significantly higher score 4 weeks after embolization with Embosphere 100-300 microm. In the size class used most frequently for uterine artery emboliation (500-700 microm), all scores were low (<2.5) and there was no significant difference among particle types. CONCLUSIONS: Pronounced immunomarker expression was seen 4 weeks after embolization with small Embosphere particles. However, in general, modern spherical embolic agents cause a fairly low level of inflammatory reaction. In the present experimental setting, which is highly sensitive for specific tissue-to-agent reactivity, Embozene presented with low inflammatory results.


Subject(s)
Acrylic Resins/adverse effects , Disease Models, Animal , Gelatin/adverse effects , Hemostatics/adverse effects , Nephritis/chemically induced , Nephritis/pathology , Uterine Artery Embolization/adverse effects , Animals , Humans , Kidney/drug effects , Kidney/pathology , Swine , Swine, Miniature
18.
Cardiovasc Intervent Radiol ; 32(2): 303-12, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19139955

ABSTRACT

We sought to describe and compare material specific inflammatory and foreign body reactions after porcine liver embolization with spherical embolic agents. In 40 animals, superselective liver embolization was performed with four different spherical embolic agents of various sizes: 40-120 microm (Embozene, Embosphere), and 100-300 microm, 500-700 microm, and 700-900 microm (Embozene, Embosphere, Bead Block, and Contour SE, respectively). After 4 or 12 weeks, inflammatory reactions were evaluated microscopically according to the Banff 97 classification. For investigation of foreign body reactions, a newly designed giant cell score was applied. Banff 97 and giant cell scores closely correlated. At 4 weeks, small Embosphere particles (100-300 microm) had a significantly higher Banff 97 score than Embozene, Bead Block, and Contour SE of the corresponding size. After 12 weeks, the calculated differences were not statistically significant. Comparison between the 4-week results and the 12-week results revealed a statistically higher Banff 97 score for Embosphere 100-300 microm after 4 weeks than after 12 weeks (P = 0.02). The overall foreign body reaction was pronounced after embolization with smaller particles, especially in small Embosphere particles. Giant cell numbers with Embosphere 100-300 microm were statistically higher compared with the other materials of corresponding size (P < 0.0001). Inflammatory and giant cell reactions after embolization procedures depend on the embolic material. The overall inflammatory reaction was low. However, marked inflammation was associated with small Embosphere particles at 4 weeks, a finding that might be caused by the allogeneic overcoat. Correspondingly, giant cells indicating a foreign body reaction were more frequently associated with small particle sizes, especially after embolization with small Embosphere particles.


Subject(s)
Acrylic Resins , Embolization, Therapeutic/instrumentation , Foreign-Body Reaction/chemically induced , Gelatin , Liver , Animals , Inflammation , Models, Animal , Particle Size , Statistics, Nonparametric , Swine
19.
Clin Infect Dis ; 47(11): 1403-9, 2008 Dec 01.
Article in English | MEDLINE | ID: mdl-18937579

ABSTRACT

BACKGROUND: The value of microbiological culture to diagnose late periprosthetic infection is limited, especially because standard methods may fail to detect biofilm-forming sessile or other fastidious bacteria. There is no agreement on the appropriate cultivation period, although this period is a crucial factor. This study was designed to assess the duration of culture that is necessary for reliable detection. PATIENTS AND METHODS: Ten periprosthetic tissue specimens each were obtained during revision from 284 patients with suspected late hip or knee arthroplasty infection. Five samples were examined by microbiological culture over a 14-day period, and 5 were subjected to histologic analysis. To define infection, a pre-established algorithm was used; this included detection of indistinguishable organisms in >/=2 tissue samples or growth in 1 tissue sample and a positive result of histologic analysis (>5 neutrophils in at least 10 high-power fields). The time to detection of organisms was monitored. RESULTS: Infection was diagnosed in 110 patients. After 7 days (the longest incubation period most frequently reported), the detection rate via culture was merely 73.6%. Organisms indicating infection were found for up to 13 days. "Early"-detected species (mostly staphylococci) emerged predominantly during the first week, whereas "late"-detected agents (mostly Propionibacterium species) were detected mainly during the second week. In both populations, an unequivocal correlation between the number of culture-positive tissue samples and positive results of histologic analysis was noted, which corroborated the evidence that true infections were detected over the entire cultivation period. CONCLUSIONS: Prolonged microbiological culture for 2 weeks is promising because it yields signs of periprosthetic infection in a significant proportion of patients that would otherwise remain unidentified.


Subject(s)
Arthritis/diagnosis , Bacterial Infections/diagnosis , Bacteriological Techniques , Hip/microbiology , Knee/microbiology , Prosthesis-Related Infections/diagnosis , Aged , Arthritis/microbiology , Arthritis/pathology , Bacteria/isolation & purification , Bacterial Infections/microbiology , Bacterial Infections/pathology , Female , Hip/pathology , Humans , Knee/pathology , Male , Prosthesis-Related Infections/microbiology , Prosthesis-Related Infections/pathology , Statistics as Topic , Time Factors
20.
J Surg Orthop Adv ; 17(3): 153-8, 2008.
Article in English | MEDLINE | ID: mdl-18851799

ABSTRACT

Semitendinosus and gracilis tendons taken from 25 cadaveric knees were investigated using light and electron microscopy, immunohistochemistry, and morphometry. Thickness of the collagen fibrils, fibril/interstitium ratio, density of blood vessels, density of fibroblasts, and distribution of the collagen fibrils (types I, III, and V collagen and elastic fibers) were analyzed. It was hypothesized that the difference in biomechanical stability between the gracilis and semitendinosus tendons could be reflected by different morphologic features. The results of this study showed that the gracilis tendon, in comparison with the semitendinosus tendon, provides a significantly higher fibril/interstitium ratio and a higher density of collagen III fibers. Conversely, the semitendinosus tendon provides a higher density of blood vessels and collagen I fibers. No differences regarding the density of fibroblasts, thickness of collagen fibrils, and elastic and type V collagen fibers were found. In conclusion, the gracilis tendon graft can provide approximately 15% more collagen than the semitendinosus tendon graft with the same thickness. This fact can play an important role for better biomechanical stability of the gracilis tendon.


Subject(s)
Tendons/ultrastructure , Adult , Biomechanical Phenomena , Collagen Type I/metabolism , Female , Humans , Immunohistochemistry , Male , Middle Aged , Tendons/metabolism , Tendons/physiology , Young Adult
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