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Wittenberg, Germany

Lohmann C.H.,Otto Von Guericke University of Magdeburg | Meyer H.,Otto Von Guericke University of Magdeburg | Nuechtern J.V.,University of Hamburg | Singh G.,National University of Singapore | And 4 more authors.
Journal of Bone and Joint Surgery - Series A | Year: 2013

Background: Tissue responses to periprosthetic metal wear debris are complex and poorly understood. There are two predominant tissue responses: a nonspecific macrophage-mediated granulomatous response and lymphocyte-dominated response, which has immunological memory and is mediated by T cells. Delayed hypersensitivitytype responses may accelerate aseptic loosening of arthroplasty implants. We hypothesized that the metal content of periprosthetic tissue but not of serum would be predictive of the type of tissue response to metal wear debris. Methods: We examined twenty-eight total hip arthroplasty implant retrievals from twenty-seven patients who had undergone revision arthroplasty at one institution. Indications for revision were pain and/or osteolysis; one patient had recurrent dislocations. Tissue samples were analyzed microscopically and the metal (Co, Cr, and Ni) content was determined. Explanted prosthetic components were examined for linear wear. Intraoperatively, periprosthetic metallosis was observed in twelve cases and formation of a bursa (pseudotumor) was observed in thirteen. The acetabular cup was loose in eleven cases, the femoral stem was loose in five, and both components were loose in five. Results: The metal (Co, Cr, and Ni) content of the periprosthetic tissue ranged from 1.4 to 4604.0 mg/g. Histologically, macrophages containing metal particles as well as diffuse and perivascular lymphocytic infiltration were observed. Fibrin exudation was also visible. Tissues that displayed a predominantly lymphocytic response had a mean metal content of 222.2 ± 52.9 mg/g, whereas those that displayed a macrophage-dominated response had a metal content of 3.0 ± 0.9 mg/g; this difference was significant (p = 0.001). The mean serum metal content did not differ significantly between the two subgroups (60.7 ± 13.4 compared with 43.7 ± 3.8 mg/L, p = 0.105). Conclusions: An association between periprosthetic tissue metal content and hypersensitivity appears likely but needs to be validated with larger-scale retrieval studies. Clinical Relevance: This study contributes to the understanding of tissue responses to metal wear debris after joint replacement and the factors that are predictive of a type-IV lymphocyte-dominated hypersensitivity reaction. Copyright © 2013 By The Journal of Bone and Joint Surgery, Incorporated. Source

Hermann H.P.,Evangelisches Krankenhaus
Deutsche Medizinische Wochenschrift | Year: 2011

History and admission findings: A 49-year-old man with loss of performance, ventricular ectopy and left bundle branch block was referred for diagnostic workup. He had dysmorphic skeletal features with shortening and muscular atrophy of arm and leg and syndactylia. Investigations: Echocardiography revealed peculiar hypertrabeculation of left ventricular myocardium which was confirmed by cardiac magnetic resonance imaging. Therefore a diagnosis of non-compaction cardiomyopathy was made. Holter monitoring showed non-sustained ventricular tachycardia, coronary heart disease was excluded by coronary angiography. Treatment aund course: The patient received optimal heart failure drug therapy. Because of malignant ventricular ectopy a biventricular ICD system (CRT-D system) was implanted. Signs and symptoms of heart failure have been stable for four years (NYHA-class II). Repeated sustained ventricular tachycardia were terminated by ICD overstimulation. A history of inadequate ICD shocks was due to incompliance of the patient regarding beta blocker use. Conclusion: Non-compaction cardiomyopathy is a rare but characteristic cause of heart failure which is associated with potential malignant arryhthmias. Diagnosis is based on echocardiographic workup with typical features. However, because of its low prevalence and awareness deficits in the medical community, non-compaction cardiomyopathy probably is diagnosed too late and not frequently enough. © Georg Thieme Verlag KG Stuttgart. Source

The population with end stage renal disease (ESRD) is becoming increasingly older and more frail with a high burden of comorbidities, resulting in increasingly more complex therapy decisions. From an ethical perspective the four principles by Beauchamp and Childress have to be considered: dialysis is only justified when patient autonomy, nonmaleficence, beneficence and justice are guaranteed. With respect to beneficence, the quality of life is becoming more important than a mere prolongation of life expectancy. A change in paradigm is noticeable: dialysis is to be offered to patients who are likely to benefit, otherwise conservative management should be considered, thus turning dialysis withdrawal and dialysis withholding into appropriate options. Advance care planning and shared decision-making allow early and ongoing involvement of the patient, supporting patient autonomy and beneficence. This communicative and processual approach requires an appropriate time frame and special communication skills as well as conflict management. In the case of conservative management in ESRD best supportive care at the end of life ensures fulfillment of the individual patient needs, symptom control and palliative care. © 2016 Springer-Verlag Berlin Heidelberg Source

Sabbatini P.,Sloan Kettering Cancer Center | Sehouli J.,Charite Campus Virchow Klinikum | Meier W.,Evangelisches Krankenhaus | Wimberger P.,Universitaetsklinikum Essen
Journal of Clinical Oncology | Year: 2013

Purpose To determine whether abagovomab maintenance therapy prolongs recurrence-free (RFS) and overall survival (OS) in patients with ovarian cancer in first clinical remission. Patients and Methods Patients with International Federation of Gynecology and Obstetrics stage III to IV ovarian cancer in complete clinical remission after primary surgery and platinum- and taxane-based chemotherapy were randomly assigned at a ratio of 2:1 in a phase III, double-blind, placebo-controlled, multicenter study. Abagovomab 2 mg or placebo was administered as 1-mL suspension once every 2 weeks for 6 weeks (induction phase) and then once every 4 weeks (maintenance phase) until recurrence or up to 21 months after random assignment of the last patient. The primary end point was RFS; secondary end points were OS and immunologic response. Results Characteristics of the 888 patients included: mean age, 56.3 years; Eastern Cooperative Oncology Group performance status, ≤ 1 in > 99% of patients; serous papillary subtype, 81.5%; stage III, 85.9%; and cancer antigen 125 ≤ 35U/mL after third cycle, 80.9%. Mean exposure to study treatment (± standard deviation) was 449.7 ± 333.08 days. Hazard ratio (HR) of RFS for the treatment group using tumor size categorization (≤ 1 cm, > 1 cm) was 1.099 (95% CI, 0.919 to 1.315; P = .301). HR of OS using tumor size categorization (≤ 1 cm, > 1 cm) was 1.150 (95% CI, 0.872 to 1.518; P = .322). The most frequently reported type of adverse event was an injection site reaction in 445 patients (50.2%), followed by injection site erythema and fatigue in 227 (25.6%) and 212 patients (23.9%), respectively. By the final visit, median anti-anti-idiotypic antibody level was 493,000.0 ng/mL, indicating a robust response. Conclusion Abagovomab administered as repeated monthly injections is safe and induces a measurable immune response. Administration as maintenance therapy for patients with ovarian cancer in first remission does not prolong RFS or OS. © 2013 by American Society of Clinical Oncology. Source

Strecker J.-K.,University of Munster | Minnerup J.,University of Munster | Schutte-Nutgen K.,University of Munster | Gess B.,University of Munster | And 2 more authors.
Stroke | Year: 2013

Background and Purpose - Stroke-induced blood-brain barrier (BBB)-disruption can contribute to further progression of cerebral damage. There is rising evidence for a strong involvement of chemokines in postischemic BBB-breakdown. In a previous study, we showed that monocyte chemoattractant protein-1 (MCP-1)-deficiency results in a markedly reduced inflammatory reaction with decreased levels of interleukin-6, interleukin-1β, and granulocyte colony-stimulating factor after experimental stroke. With MCP-1 as one of the key players in stroke-induced inflammation, in this study, we investigated the influence of MCP-1 on poststroke BBB-disruption as well as transcription/ translation of BBB-related genes/proteins after cerebral ischemia. Methods - Sixteen wild-type and 16 MCP-1-/- mice were subjected to 30 minutes of middle cerebral artery occlusion. By injecting high molecular-tracer, we compared the degree of BBB-disruption after middle cerebral artery occlusion. Real-time polymerase chain reactions and Western blot technique were used to compare tight-junction gene expression, protein secretion, and BBB-leakage. Results - Here, we report that MCP-1-deficiency results in a reduced BBB-leakage and a diminished expression of BBB-related genes occludin, zonula occludens-1, and zonula occludens-2. Real-time polymerase chain reactions and Western blot analysis revealed elevated claudin-5-levels in MCP-1-/- animals. MCP-1-deficiency resulted in reduced infarct sizes and an increased vascular accumulation of fluorescein-isothiocyanate-albumin. Conclusions - The results of the study provide further insights into the molecular mechanisms of BBB-opening and may help to better understand the mechanisms of infarct development after cerebral ischemia. © 2013 American Heart Association, Inc. Source

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