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1.
Radiologia (Engl Ed) ; 65(6): 531-545, 2023.
Article En | MEDLINE | ID: mdl-38049252

Placenta accreta spectrum (PAS) disorders (with increasing order of the depth of invasion: accreta, increta, percreta) are quite challenging for the purpose of diagnosis and treatment. Pathological examination or imaging evaluation are not very dependable when considered as stand-alone diagnostic tools. On the other hand, timely diagnosis is of great importance, as maternal and fetal mortality drastically increases if patient goes through the third phase of delivery in a not well-suited facility. A multidisciplinary approach for diagnosis (incorporating clinical, imaging, and pathological evaluation) is mandatory, particularly in complicated cases. For imaging evaluation, the diagnostic modality of choice in most scenarios is ultrasound (US) exam; patients are referred for MRI when US is equivocal, inconclusive, or not visualizing placenta properly. Herewith, we review the reported US and MRI features of PAS disorders (mainly focusing on MRI), going over the normal placental imaging and imaging pitfalls in each section, and lastly, covering the imaging findings of PAS disorders in the first trimester and cesarean section pregnancy (CSP).


Placenta Accreta , Pregnancy , Humans , Female , Placenta Accreta/diagnostic imaging , Placenta Accreta/pathology , Placenta/pathology , Cesarean Section , Magnetic Resonance Imaging/methods
2.
Radiología (Madr., Ed. impr.) ; 65(6): 531-545, Nov-Dic. 2023. ilus, tab
Article Es | IBECS | ID: ibc-227357

Los trastornos del espectro de placenta acreta (EPA) (en orden ascendente en función de la profundidad de la invasión: acreta, increta y percreta) plantean un desafío diagnóstico y de tratamiento. El examen patológico o la evaluación por técnicas de diagnóstico por imagen no son muy fiables si se consideran como herramientas diagnósticas independientes. Sin embargo, un diagnóstico temprano es de gran importancia, ya que la mortalidad materna y fetal aumentan de forma drástica si la paciente se encuentra en unas instalaciones inadecuadas en la tercera fase del parto. Es imperativo adoptar un enfoque multidisciplinario para el diagnóstico (que incorpore la evaluación clínica, por imagen e histopatológica), en particular en los casos con complicaciones. Para la evaluación mediante imagen, la modalidad diagnóstica de preferencia en la mayoría de los escenarios es la exploración mediante ecografía; las pacientes son derivadas para la resonancia magnética (RM) cuando los resultados de la ecografía son ambiguos, no concluyentes o no permiten una visualización adecuada de la placenta. Este artículo repasa las características ecográficas y de RM de los trastornos del EPA (centrándonos principalmente en la RM), examinamos las imágenes placentarias normales y los puntos débiles de las técnicas de diagnóstico por imagen en cada sección. Por último, comentamos los hallazgos de imagen de los trastornos del EPA en el primer trimestre. Por ultimo comentaremos los hallazgos de imagen de los trastornos del EPA en el primer trimestre y en la cicatriz de cesárea anterior.(AU)


Placenta accreta spectrum (PAS) disorders (with increasing order of the depth of invasion: accreta, increta, percreta) are quite challenging for the purpose of diagnosis and treatment. Pathological examination or imaging evaluation are not very dependable when considered as stand-alone diagnostic tools. On the other hand, timely diagnosis is of great importance, as maternal and fetal mortality drastically increases if patient goes through the third phase of delivery in a not well-suited facility. A multidisciplinary approach for diagnosis (incorporating clinical, imaging, and pathological evaluation) is mandatory, particularly in complicated cases. For imaging evaluation, the diagnostic modality of choice in most scenarios is ultrasound (US) exam; patients are referred for MRI when US is equivocal, inconclusive, or not visualizing placenta properly. Herewith, we review the reported US and MRI features of PAS disorders (mainly focusing on MRI), going over the normal placental imaging and imaging pitfalls in each section, and lastly, covering the imaging findings of PAS disorders in the first trimester and cesarean section pregnancy (CSP).(AU)


Humans , Female , Placenta Accreta/diagnostic imaging , Pregnancy Complications , Pregnancy, Ectopic , Magnetic Resonance Spectroscopy , Diagnostic Imaging/methods , Placenta Accreta/drug therapy , Placenta Accreta/therapy , Radiology , Pregnancy
4.
Clin Exp Immunol ; 195(3): 395-406, 2019 03.
Article En | MEDLINE | ID: mdl-30368774

Thorough understanding of the complex pathophysiology of osteoarthritis (OA) is necessary in order to open new avenues for treatment. The aim of this study was to characterize the CD4+ T cell population and evaluate their activation and polarization status in OA joints. Fifty-five patients with end-stage knee OA (Kellgren-Lawrence grades III-IV) who underwent surgery for total knee arthroplasty (TKA) were enrolled into this study. Matched samples of synovial membrane (SM), synovial fluid (SF) and peripheral blood (PB) were analysed for CD3+ CD4+ CD8- T cell subsets [T helper type 1 (Th1), Th2, Th17, regulatory T cells] and activation status (CD25, CD69, CD45RO, CD45RA, CD62L) by flow cytometry. Subset-specific cytokines were analysed by cytometric bead array (CBA). SM and SF samples showed a distinct infiltration pattern of CD4+ T cells. In comparison to PB, a higher amount of joint-derived T cells was polarized into CD3+ CD4+ CD8- T cell subsets, with the most significant increase for proinflammatory Th1 cells in SF. CBA analysis revealed significantly increased immunomodulating cytokines [interferon (IFN)-γ, interleukin (IL)-2 and IL-10] in SF compared to PB. Whereas in PB only a small proportion of CD4+ T cells were activated, the majority of joint-derived CD4+ T cells can be characterized as activated effector memory cells (CD69+ CD45RO+ CD62L- ). End-stage OA knees are characterized by an increased CD4+ T cell polarization towards activated Th1 cells and cytokine secretion compared to PB. This local inflammation may contribute to disease aggravation and eventually perpetuate the disease process.


Knee Joint/immunology , Osteoarthritis, Knee/immunology , Synovial Fluid/immunology , Synovial Membrane/immunology , Th1 Cells/physiology , Adult , Aged , Aged, 80 and over , Cell Polarity , Cytokines/analysis , Female , Humans , Lymphocyte Activation , Male , Middle Aged
5.
Schmerz ; 33(1): 4-12, 2019 Feb.
Article De | MEDLINE | ID: mdl-30560495

Osteoarthritis (OA) is one of the major causes of chronic pain. Although OA has long been considered a non-inflammatory "wear and tear" disease leading to loss of articular cartilage, recent findings provide convincing evidence that inflammatory mechanisms play a pivotal role in the pathophysiology of OA. In OA mononuclear cells (e. g. T­cells and macrophages) infiltrate the synovial membrane and the levels of pro-inflammatory cytokines in peripheral blood and synovial fluid samples are elevated. Increased release of inflammatory mediators including interleukin (IL) IL-1ß, IL-6, IL-8, IL-15 und tumor necrosis factor alpha (TNF­α) induces the expression of proteolytic enzymes such as matrix metalloproteinases resulting in cartilage breakdown. Molecular and cellular interactions between the immune and nervous system are also involved in the development of OA-related pain. Inflammatory mediators including IL-6 und TNF­α lead to peripheral sensitization of joint nociceptors and growth factors (e. g. NGF) trigger the expression of TRPV1 channels in primary afferents. Moreover, neuropeptides reduce the threshold of nociceptors of OA joints. The current review highlights the role of inflammatory mechanisms in OA-induced joint pain considering clinical signs of inflammation and major inflammatory pathways.


Cartilage, Articular , Osteoarthritis , Cytokines , Humans , Inflammation , Synovial Membrane
6.
Environ Pollut ; 242(Pt B): 1467-1475, 2018 Nov.
Article En | MEDLINE | ID: mdl-30142562

Toxocariasis is a neglected tropical disease of humans. Although many studies have indicated or shown that environmental contamination with Toxocara species eggs is a major risk factor for toxocariasis in humans, there has been no comprehensive analysis of published data or information. Here, we conducted the first systematic review and meta-analysis of current literature to assess the global prevalence of Toxocara eggs in public places (including beaches, parks and playgrounds). We conducted searches of the PubMed, Embase, Scopus and Science Direct databases for relevant studies published until 20 April 2018, and assessed the prevalence rates of Toxocara eggs in public places. We used the random effects model to calculate pooled prevalence estimates, with 95% confidence intervals (CIs), and analysed data in relation to WHO geographical regions. Subgroup analysis and meta-regressions regarding the geographical and environmental variables were also performed. Of 2384 publications identified, 109 studies that tested 42,797 soil samples in 40 countries were included in the meta-analysis. The pooled global prevalence of Toxocara eggs in public places was 21% (95% CI, 16-27%; 13,895/42,797). The estimated prevalence rates in the different WHO regions ranged from 13% to 35%: Western Pacific (35%; 95% CI, 15-58%), Africa (27%; 95% CI, 11-47%), South America (25%; 95% CI, 13-33%), South-East Asia (21%; 95% CI, 3-49%), Middle East and North Africa (18%; 95% CI, 11-24%), Europe (18%; 95% CI, 14-22%), and North and Central Americas (13%; 95% CI, 8-23%). A high prevalence was significantly associated with high geographical longitude (P = 0.04), low latitude (P = 0.02) and high relative environmental humidity (P = 0.04). This meta-analysis of data from published records indicates that public places are often heavily contaminated with eggs of Toxocara. This finding calls for measures to reduce the potential risk of infection and disease in humans.


Soil Pollutants/isolation & purification , Soil/parasitology , Toxocara/isolation & purification , Animals , Environmental Microbiology , Environmental Monitoring , Parasite Egg Count
7.
Clin Exp Immunol ; 180(1): 143-54, 2015 Apr.
Article En | MEDLINE | ID: mdl-25393692

It is still controversial which cell types are responsible for synovial inflammation in osteoarthritic (OA) joints. The aim of this study was to quantify the mononuclear cell populations and their cytokines in patients with different knee OA subtypes. Synovial membrane (SM), synovial fluid (SF) and peripheral blood (PB) were harvested from patients with unicompartmental (UC) and bicompartmental (BC) knee OA. Frequencies of mononuclear cells were assessed by flow cytometry in PB and SM. Naive SF samples were analysed for a broad variety of cytokines by multiplex analysis. SM of both groups displayed a distinct mononuclear cell infiltration, with CD14(+) macrophages being the major cell population, followed by CD4(+) T cells and only small numbers of CD8(+) T, CD19(+) B and CD16(+) CD56(+) natural killer (NK) cells. Between the two groups, SM of BC OA showed significantly higher amounts of mononuclear cells (135·7 ± 180 versus 805 ± 675 cells/mg, P = 0·0009) and higher CD4(+) T cell presence (3·4 ± 4·6 versus 9·1 ± 7·5%, P = 0·0267). SF of BC OA displayed significantly higher concentrations for a number of proinflammatory cytokines [CXCL1, eotaxin, interferon (IFN)-γ, interleukin (IL)-7, IL-8, IL-9, IL-12]. UC and BC OA show significant differences in their synovial inflammatory pattern. Whereas in UC OA CD14(+) macrophages are the predominant cell population, BC OA has a higher inflammatory profile and seems to be driven by CD14(+) macrophages and CD4(+) T cells. Inclusion of clinical information into the analysis of cellular and molecular results is pivotal in understanding the pathophysiology of OA.


Cytokines , Knee Joint , Leukocytes, Mononuclear , Osteoarthritis, Knee , Synovial Fluid , Aged , Aged, 80 and over , Antigens, CD/immunology , Antigens, CD/metabolism , Cytokines/immunology , Cytokines/metabolism , Female , Humans , Knee Joint/immunology , Knee Joint/metabolism , Knee Joint/pathology , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/pathology , Male , Middle Aged , Osteoarthritis, Knee/immunology , Osteoarthritis, Knee/metabolism , Osteoarthritis, Knee/pathology , Synovial Fluid/immunology , Synovial Fluid/metabolism
8.
Oncology ; 86(3): 177-84, 2014.
Article En | MEDLINE | ID: mdl-24751899

OBJECTIVE: To determine whether preoperative parameters correlate with the postoperative functional outcome in para- and tetraplegic patients with lung, kidney, breast and prostate cancer and metastatic spinal cord compression (MSCC). METHODS: Information on 43 patients undergoing decompressive surgery and rehabilitation for MSCC was reviewed, including primary tumor, age, pre- and postoperative ambulation status, mobility subcategory of the Spinal Cord Injury Measure (mSCIM) and the Tokuhashi score. Differences between groups were analyzed by the nonparametric χ(2) test, and correlation coefficients (Spearman's rho) were computed. RESULTS: Preoperative ambulation (p < 0.001), the American Spinal Injury Association Impairment Scale (p < 0.001) and the type of operation (p = 0.02) influenced the postoperative functional outcome. Any positive change in the mSCIM was influenced by preoperative ambulation (p < 0.001). Patients with breast carcinoma showed significantly more positive changes in the mSCIM compared with other tumors (p = 0.002). No correlation was found between the treatment categories of the Tokuhashi score and the preoperative ambulatory status (p = 0.13) or the change in ambulation status (p = 0.29). CONCLUSION: The postoperative functional outcome of MSCC patients shows a linear association between the categories of the Tokuhashi score and the change in ambulation status. We recommend surgical decompression even in a palliative situation (Tokuhashi score 0-8) with the aim of optimizing the short-term rehabilitation outcome.


Decompression, Surgical/methods , Paraplegia/physiopathology , Quadriplegia/physiopathology , Spinal Cord Compression/diagnosis , Spinal Cord Compression/surgery , Spinal Neoplasms/secondary , Adult , Aged , Aged, 80 and over , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Paraplegia/etiology , Postoperative Period , Prognosis , Quadriplegia/etiology , Recovery of Function , Severity of Illness Index , Spinal Cord Compression/etiology , Treatment Outcome
9.
J. investig. allergol. clin. immunol ; 23(7): 455-461, nov.-dic. 2013. tab
Article En | IBECS | ID: ibc-117660

Background: Allergic rhinitis is a complex polygenic disorder of the upper respiratory tract. Given that proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin (IL) 1 seem to play a role in the development of allergic rhinitis, we evaluated the associations between various single-nucleotide polymorphisms (SNPs) of the TNF and IL1 genes in a case-control study. Methods: The study population comprised 98 patients with allergic rhinitis. Genotyping was performed using polymerase chain reaction with sequence-specific primers for 2 TNFA promoter variants (rs1800629 and rs361525), 1 variant in the promoter region of IL1A (rs1800587), 2 SNPs in the IL1B gene (rs16944 and rs1143634), 1 variant in the IL1 receptor (rs2234650), and 1 in IL1RA (rs315952). Results: Patients who were homozygous for the T allele of rs16944 in IL1B had an 8.1-fold greater risk of allergic rhinitis than those with the C allele. In TNFA, a significant relationship was also detected between rs1800629 and rs361525 and allergic rhinitis. Except for rs1800587 in IL1A and rs315952 in IL1RA, significant differences were found between the patient and control groups for all other SNPs. Conclusions: We found that allelic variants in the TNFA and IL1 genes were not only associated with the risk of developing allergic rhinitis, but also affected disease course and severity (AU)


Antecedentes: La rinitis alérgica es una alteración poligénica compleja de las vías respiratorias. El TNF y la familia de la IL-1, como citoquinas proinflamatorias, parecen jugar un papel en el desarrollo de la rinitis alérgica. En este estudio de casos y controles, se evalúan las posibles asociaciones de diferentes polimorfismos de nucleótidos simples (SNPs) de los genes que regulan TNF- α e IL1. Métodos: Se estudiaron 19 pacientes con rinitis alérgica, los cuales fueron genotipados mediante PCR para primeras especie-específicos, para dos variantes del promotor del TNF- α (rs1800629 y rs361525), uno en el receptor de IL1 (rs2234650), dos SNPs en el gen de IL1ß (rs16944 y rs1143634), uno en el receptor de IL1 receptor (rs2234650) y IL1RA (rs315952). Resultados: En cuanto a los resultados obtenidos, los pacientes homicigotos para el alelo T de rs16944 en IL1ß mostraron un riesgo 8.1 veces mayor de tener rinitis alérgica que los que presentaban el alelo C. Con respecto al TNF- α, se observó una relación significativa entre los dos SNPs rs1800629 y rs361525 con la presentación de una rinitis alérgica. Excepto rs1800587, en IL1 α, y rs315952 en IL1RA, encuentran una diferencia significativa entre el grupo control y el de pacientes para el resto de los SNPs. Algunos SNPs se asociaron con el curso y con la gravedad de la enfermedad. Conclusiones: En conclusión, encontramos variantes genéticas de TNF-α y IL1 que se asocian con el riesgo de desarrollar una rinitis alérgica, y que también afectan al curso y gravedad de la enfermedad (AU)


Humans , Rhinitis, Allergic, Perennial/immunology , Polymorphism, Single Nucleotide/immunology , Tumor Necrosis Factors/immunology , Interleukin-1/immunology , Genotyping Techniques/methods , Genetic Predisposition to Disease , Chemokines/immunology
10.
Orthopade ; 42(8): 643-50, 2013 Aug.
Article De | MEDLINE | ID: mdl-23877660

The use of metal implants has become increasingly more frequent in all fields of medicine throughout the past decades. Numerous studies have demonstrated that metal ions released from these implants can be detected in body fluids remote from the implants. Although diseases directly linked to the release of these ions seem to be rare, the general public is unsettled. In this study we aimed to analyze the impact of molybdenum(V), cobalt(II), chromium(III) and nickel(II) ions on cell surface markers (CD25, CD38, CD69, CD95) and viability (7-AAD/AnnexinV) of human CD4+ T-lymphocytes in vitro. Cobalt(II) ions at a concentration of 1000 µg/l led to a significant suppression of lymphocyte activation markers while nickel(II), chromium(III) and molybdenum(V) did not show any significant impact on these lymphocyte activation markers. Cell viability was significantly reduced by all metal ions, whereas cobalt(II) led to the highest increase of apoptotic cells and was the only metal ion to significantly increase the necrosis rate. While the pathophysiological significance of these findings remains unclear, they are in favour of further research in this field.


Biocompatible Materials/pharmacology , Lymphocytes/drug effects , Lymphocytes/physiology , Metals/pharmacology , Aged , Apoptosis/drug effects , Cell Survival/drug effects , Cells, Cultured , Female , Humans , Ions/pharmacology , Lymphocytes/cytology , Male
11.
Cell Prolif ; 46(4): 396-407, 2013 Aug.
Article En | MEDLINE | ID: mdl-23869761

OBJECTIVES: Although clinical applications using mesenchymal stromal cells (MSCs) are becoming more frequent, procedures for their in vitro culture are far from standardized. Growth factors such as FGF-2 are frequently added during expansion to improve population growth and differentiation characteristics. However, up to now its influence on surface marker distribution of MSCs has been close to unknown. The purpose of this study was therefore to analyse effects of FGF-2 supplementation on pre-selection of MSC subpopulations. MATERIALS AND METHODS: Mesenchymal stromal cells were harvested from bone marrow of six patients and expanded in alpha-MEM or DMEM-LG. Starting in passage 2, 10 ng/ml FGF-2 was administered and non-supplemented media were used as controls. Growth indices were calculated from P0 to P4. After P4, fluorescence cytometry for common MSC surface markers was performed and standard chondrogenic, adipogenic and osteogenic differentiation protocols were applied. RESULTS: Cell population growth indices were higher for those in FGF-2 supplemented media. Significant differences in surface marker distribution were observed for CD13, CD14, CD49, CD90, CD340 and STRO-1 depending on respective culture conditions. FGF-2 suppressed CD146 expression in both alpha-MEM and DMEM-LG. No differences in adipogenic and osteogenic differentiation potential could be observed, while FGF-2 significantly improved chondrogenic differentiation in DMEM-LG. CONCLUSIONS: While holding the benefit of improving MSC chondrogenic differentiation potential, FGF-2 pre-selects certain MSC subtypes. Our data clearly show that expansion culture conditions have a significant effect on distribution of a number of MSC surface markers.


Biomarkers/metabolism , Fibroblast Growth Factor 2/pharmacology , Mesenchymal Stem Cells/drug effects , Osteogenesis/drug effects , Adipogenesis/drug effects , Adult , Cell Differentiation/drug effects , Cells, Cultured , Female , Fibroblast Growth Factor 2/metabolism , Humans , Male , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism
12.
Orthopade ; 42(8): 622-8, 2013 Aug.
Article De | MEDLINE | ID: mdl-23842780

Increased wear leads to elevated systemic and local metal ion concentrations for patients treated with metal-on-metal bearings. The local metal ion content in the close environment of the joint replacement (e.g. joint aspirate or tissue) is several times higher compared to the systemic metal content (e.g. in blood or serum). As a result of increased metal ion levels, local and systemic effects, such as osteolysis, pseudotumors, sensitization or in rare cases toxicity may occur. Although the definition of a specific threshold to define clinical problems is difficult due to a lack of sensitivity, the systemic metal concentration is frequently measured clinically. Currently a threshold for cobalt and chromium between 4 µg/l and 7 µg/l is under debate. Very high levels (≥ 20 µg/l) or a steady increase over time should be a warning sign; however, metal ion levels should not be interpreted as a single diagnostic tool but rather in the entire context of the clinical, radiological and cross-sectional imaging, metal artefact reduction sequence (MARS) magnetic resonance imaging (MRI), ultrasound and computed tomography (CT) findings.


Hypersensitivity/etiology , Hypersensitivity/metabolism , Joints/chemistry , Joints/drug effects , Metal-on-Metal Joint Prostheses/adverse effects , Metals/adverse effects , Metals/chemistry , Humans , Ions/adverse effects , Ions/chemistry , Particle Size
13.
Clin Exp Immunol ; 173(3): 454-62, 2013 Sep.
Article En | MEDLINE | ID: mdl-23607395

There is increasing evidence that inflammation in the synovium plays a major role in the progression of osteoarthritis (OA). However, the immunogenic properties of mesenchymal stromal cells (MSCs), which are considered to regulate immunity in various diseases, remain largely unknown in OA. The purpose of this study was to determine the influence of MSCs from OA patients on regulatory T cells (Tregs ) in an allogeneic co-culture model. Bone marrow (BM) and synovial membrane (SM) were harvested from hip joints of OA patients and co-cultured with lymphocytes enriched in CD4(+) CD25(+) CD127(-) regulatory T cells (Treg (+) LC) from healthy donors. Treg proportions and MSC markers were assessed by flow cytometry. Cytokine levels were assessed after 2 and 5 days of co-cultivation. Additionally, Treg (+) LC cultures were analysed in the presence of interleukin (IL)-6 and MSC-supernatant complemented medium. B-MSCs and S-MSCs were able to retain the Treg proportion compared to lymphocyte monocultures. T cell-MSC co-cultures showed a significant increase of IL-6 compared to MSC cultures. S-MSCs produced higher amounts of IL-6 compared to B-MSCs, both in single and T cell co-cultures. The effect of retaining the Treg percentage could be reproduced partially by IL-6 addition to the medium, but could only be observed fully when using MSC culture supernatants. Our data demonstrate that retaining the Treg phenotype in MSC-T cell co-cultures can be mediated by MSC derived from OA patients. IL-6 plays an important role in mediating these processes. To our knowledge, this study is the first describing the interaction of MSCs from OA patients and Tregs in an allogeneic co-culture model.


Mesenchymal Stem Cells/immunology , Osteoarthritis/immunology , T-Lymphocytes, Regulatory/immunology , Adult , Aged , Aged, 80 and over , Biomarkers/metabolism , Bone Marrow Cells/immunology , Bone Marrow Cells/metabolism , Coculture Techniques , Female , Forkhead Transcription Factors/metabolism , Humans , Interleukin-6/biosynthesis , Interleukin-7 Receptor alpha Subunit/metabolism , Male , Mesenchymal Stem Cells/metabolism , Middle Aged , Osteoarthritis/metabolism , Synovial Membrane/cytology , Synovial Membrane/immunology , T-Lymphocytes, Regulatory/metabolism , Young Adult
14.
J Periodontal Res ; 48(4): 533-9, 2013 Aug.
Article En | MEDLINE | ID: mdl-23317308

BACKGROUND AND OBJECTIVE: Genetic backgrounds play a key role in susceptibility to and protection against a spectrum of periodontal diseases. Like other infectious diseases, the human leukocyte antigen (HLA) have been found to be associated with periodontitis. This study aimed to investigate differences in allele and haplotype frequencies of HLA class II antigens in a sample of Iranian patients with aggressive periodontitis compared with a healthy control group. MATERIAL AND METHODS: Fifty unrelated patients with aggressive periodontitis and 130 healthy volunteers were enrolled in this study. HLA genotyping for HLA-DRB, HLA-DQA1 and HLA-DQB1 was performed using the PCR with sequence-specific primers. Allele and haplotype frequencies were compared across groups. RESULTS: The frequencies of HLA-DQA1*03:01, HLA-DQB1*03:02 and HLA-DQB1*03:05 alleles, as well as that of the HLA-DRB1*04:01 allele, were significantly higher in patients with aggressive periodontitis compared with control subjects (p = 0.01, p = 0.04, p = 0.05 and p = 0.04, respectively). In contrast, the frequency of the HLA-DQB1*0603 allele was significantly lower in patients with aggressive periodontitis compared with control subjects (p = 0.006; odds ratio = 0.20). With regard to haplotype association, a significantly higher frequency of two haplotypes - HLA-DRB1*04:01/HLA-DQA1*03:01/HLA-DQB1*03:02 and HLA-DRB1*16:01/HLA-DQA1*01:03/HLA-DQB1*05:01 - was observed in patients with aggressive periodontitis compared with healthy controls (p = 0.01, odds ratio = 2.56 and p = 0.05, odds ratio = 5.38, respectively). CONCLUSION: These results provide additional evidence that class II HLA polymorphisms, particularly in the DQ locus, are associated with protection against and susceptibility to aggressive periodontitis.


Aggressive Periodontitis/immunology , Gene Frequency/genetics , HLA-DQ alpha-Chains/genetics , HLA-DQ beta-Chains/genetics , HLA-DR beta-Chains/genetics , Haplotypes/genetics , Adult , Aggressive Periodontitis/genetics , Case-Control Studies , Dental Plaque Index , Female , Genetic Predisposition to Disease/genetics , Genotype , Humans , Iran , Male , Periodontal Attachment Loss/genetics , Periodontal Attachment Loss/immunology , Polymorphism, Genetic/genetics
15.
J Investig Allergol Clin Immunol ; 23(7): 455-61, 2013.
Article En | MEDLINE | ID: mdl-24654309

BACKGROUND: Allergic rhinitis is a complex polygenic disorder of the upper respiratory tract. Given that proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin (IL) 1 seem to play a role in the development of allergic rhinitis, we evaluated the associations between various single-nucleotide polymorphisms (SNPs) of the TNF and IL1 genes in a case-control study. METHODS: The study population comprised 98 patients with allergic rhinitis. Genotyping was performed using polymerase chain reaction with sequence-specific primers for 2 TNFA promoter variants (rs1800629 and rs361525), 1 variant in the promoter region of IL1A (rs1800587), 2 SNPs in the IL1B gene (rs16944 and rs1 143634), 1 variant in the IL1 receptor (rs2234650), and 1 in IL1RA (rs315952). RESULTS: Patients who were homozygous for the T allele of rs16944 in IL1B had an 8.1-fold greater risk of allergic rhinitis than those with the C allele. In TNFA, a significant relationship was also detected between rs1800629 and rs361525 and allergic rhinitis. Except for rs1800587 in IL1A and rs315952 in IL1RA, significant differences were found between the patient and control groups for all other SNPs. CONCLUSIONS: We found that allelic variants in the TNFA and IL1 genes were not only associated with the risk of developing allergic rhinitis, but also affected disease course and severity.


Interleukin-1/genetics , Polymorphism, Single Nucleotide , Rhinitis, Allergic, Perennial/genetics , Tumor Necrosis Factor-alpha/genetics , Adolescent , Child , Child, Preschool , Female , Genotype , Haplotypes , Humans , Male , Rhinitis, Allergic
16.
Eur Cell Mater ; 23: 320-32, 2012 May 04.
Article En | MEDLINE | ID: mdl-22562232

Aggrecanases from the ADAMTS (A Disintegrin And Metalloproteinase with ThromboSpondin motifs) family are important therapeutic targets due to their essential role in aggrecan depletion in arthritic diseases. Whether their function is also important for matrix rearrangements during chondrogenesis and thus, cartilage regeneration, is however so far unknown. The aim of this study was to analyse the expression and function of ADAMTS with aggrecanase activity during chondrogenic differentiation of human mesenchymal stem cells (MSCs). Chondrogenic differentiation was induced in bone marrow-derived MSC pellets and expression of COL2A1, aggrecan, ADAMTS1, 4, 5, 9, 16 and furin was followed by quantitative RT-PCR. Formation of the NITEGE (ADAMTS-cleaved) and DIPEN (MMP-cleaved) aggrecan neoepitopes was detected by immunohistochemistry. While the expression of ADAMTS4, 9, 16 and furin was up-regulated during chondrogenesis, ADAMTS1 and 5 were down-regulated. Despite this regulation of ADAMTS, no formation of NITEGE neoepitopes occurred in MSC pellets, indicating no ADAMTS-induced cleavage of aggrecan. In contrast, MMP-induced cleavage of aggrecan appeared at 14 d after induction of chondrogenesis. Submission of differentiated MSC pellets to IL1ß treatment for 3 d resulted in strong upregulation of ADAMTS1, 4 and 5, rapid proteoglycan depletion, and stimulation of ADAMTS-induced but not MMP-induced cleavage of aggrecan. Thus, there is no evidence for ADAMTS-induced aggrecan cleavage during chondrogenesis, but proteoglycan turnover is rapidly inducible under inflammatory signals. Therapeutic aggrecanase inhibition for treatment of arthritic disease may thus not impede regenerative self-healing pathways based on chondrogenesis of local progenitor cells in the joint.


ADAM Proteins/metabolism , Aggrecans/metabolism , Chondrogenesis , Endopeptidases/metabolism , Mesenchymal Stem Cells/metabolism , ADAM Proteins/genetics , ADAMTS Proteins , ADAMTS1 Protein , ADAMTS4 Protein , ADAMTS5 Protein , ADAMTS9 Protein , Adolescent , Adult , Aged , Aged, 80 and over , Aggrecans/genetics , Amino Acid Sequence , Cells, Cultured , Child , Endopeptidases/genetics , Epitopes/metabolism , Gene Expression Regulation/drug effects , Humans , Immunohistochemistry , Interleukin-1beta/pharmacology , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Middle Aged , Procollagen N-Endopeptidase/genetics , Procollagen N-Endopeptidase/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Young Adult
17.
Z Orthop Unfall ; 149(2): 131-34, 2011 Apr.
Article De | MEDLINE | ID: mdl-21847794

The aim of the "Youth Forum of the DGOU" during the Convention 2010 in Heidelberg was to place a statement concerning the professional politics in the field of Orthopaedic and Trauma Surgery. The Bologna Process realizes a standardization of the academic training within the European Union. For medicine this concept would raise the opportunity to opt out after three years with a bachelor degree applying for alternative occupations within the health care system. However, these alternative occupations are rarely defined and, in addition, the current structure of medical school in Germany provides the highest possible education for doctors in a direct and very well established way. Thus, reforming medical school in Germany into a Bachelor-master's system is an ambivalent approach, which considers a thorough reappraisal. There is currently no necessity for an speciality training in emergency medicine. The rapid and qualified treatment by the specific subspecialty provides a high standard of care for the patient. The high frequency exposure of the trauma and orthopaedic resident with emergency cases is an essential part of the current professional training.The "Junge Forum der DGOU" continues to understand the speciality training "Facharzt für Orthopädie und Unfallchirurgie" as the basic module of the profession. After that it should be possible to continuing subspecialty training and obtaining "spezielle Unfallchirurgie" bzw "spezielle orthopädische Chirurgie". After that further subspecialty training should be encouraged.


Curriculum , Education, Medical, Undergraduate/organization & administration , Orthopedics/education , Traumatology/education , Germany
19.
Z Orthop Unfall ; 149(1): 7-11, 2011 Jan.
Article De | MEDLINE | ID: mdl-21332044

The aim of the "Youth Forum of the DGOU" during the Convention 2010 in Heidelberg was to place a statement concerning the professional politics in the field of Orthopaedic and Trauma Surgery. The emigration of young German physicians, the occupational image of the Physician Assistant and the quality of the German residency programs in Orthopaedic and Trauma Surgery we discussed as main topics. The main reason for young German physicians to go abroad is, besides better work conditions and less bureaucracy, the better structured education during residency. Therefore the "Youth Forum" generally supports the concept of the "physician assistant" as "a relief from non-physician duties rather than discussing the delegation of true physician duties". The "Youth Forum" is looking forward to collaborating on the improvement of the ongoing education of residents. In this regard, Orthopaedic and Trauma Surgery needs to become more attractive for young academics. We also support a uniform and nationwide curriculum, which guarantees a structured education to improve the theoretic, practical and academic skills of the future specialist in orthopaedic and trauma surgery. Additional surveys and interviews among the current generation of residents are needed to further specify the potential goals of such a curriculum. We would like to discuss the future of our speciality with our colleagues. Therefore different communication platforms including our website http://www.jf-dgou.de have been created.


Curriculum , Internship and Residency/organization & administration , Orthopedics/education , Traumatology/education , Germany , Workforce
20.
Spinal Cord ; 49(6): 721-7, 2011 Jun.
Article En | MEDLINE | ID: mdl-21243001

STUDY DESIGN: Clinical cohort study. OBJECTIVE: To evaluate if the impact of the severity of the trauma as a possible confounding factor influences the neurological and functional recovery in paraplegia during the course of a 6-month follow-up period after injury. SETTING: Spinal Cord Injury Center, Heidelberg University Hospital, Germany. METHODS: A retrospective monocentric analysis, from 2002 to 2008, of the Heidelberg European Multicenter Study about spinal cord injury database was performed. We included 31 paraplegic patients (neurological level T1-T12) who were assigned either to a monotrauma (polytraumaschluessel (PTS) 1) or to a polytrauma (PTS≥2) group. The American Spinal Injury Association Impairment Scale, lower extremity motor score, pin prick, light touch and the spinal cord independence measure (SCIM) were obtained at five distinct time points after trauma. Data were analyzed using Mann-Whitney U-test (α<0.05). RESULTS: The changes in lower extremity motor score, pin prick and light touch showed no significant differences in both groups over the whole evaluation period. Polytraumatic paraplegics showed a significantly delayed increase of SCIM between 2 and 6 weeks compared with monotraumatic patients, followed by a quantitative increase in the subitems bladder management, bowel management, use of toilet and prevention of pressure sores between 3 and 6 months (P=0.031). The mean length of primary rehabilitation in the polytrauma group was 5.5 vs 3.6 months in monotrauma. CONCLUSIONS: The prognosis of polytraumatic paraplegics in terms of neurological recovery is not inferior to those with monotrauma. Multiple-injured patients need a prolonged hospital stay to reach the functional outcome of monotraumatic patients.


Multiple Trauma/epidemiology , Paraplegia/epidemiology , Spinal Cord Injuries/epidemiology , Adult , Cohort Studies , Female , Humans , Male , Middle Aged , Paraplegia/physiopathology , Paraplegia/rehabilitation , Retrospective Studies , Spinal Cord Injuries/physiopathology , Spinal Cord Injuries/rehabilitation , Treatment Outcome , Young Adult
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