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  • 1
    Language: English
    In: Journal of neurology, March 2006, Vol.253(3), pp.349-56
    Description: Motor dysfunction is an important clinical finding in patients with liver cirrhosis and mild forms of hepatic encephalopathy. The mechanisms and clinical appearance of motor impairment in patients with liver cirrhosis are not completely understood. We studied fine motor control in forty four patients with advanced liver cirrhosis (excluding those with hepatic encephalopathy grade II) and 48 healthy controls using a kinematic analysis of standardized handwriting tests. We analysed parameters of velocity, the ability to coordinate and the level of automatisation of handwriting movements. Furthermore, we studied the association between impairment of handwriting and clinical neuro-psychiatric symptoms. As compared with control subjects, patients showed a statistically significant reduction of movement peak velocity in all handwriting tasks as well as a substantial increase of number of velocity inversions per stroke. Using a z-score based assessment we found impairment of handwriting in fourteen out of forty four patients (31.8 %). The deterioration of handwriting was associated with clinical symptoms of motor dysfunction, such as bradykinesia, adiadochokinesia, dysmetria of upper extremities and gait ataxia. This is the first study that quantitatively investigates impairment of handwriting in patients with liver cirrhosis. Our findings suggest the application of kinematic analysis of handwriting for diagnostics of motor dysfunction in patients with mild forms of hepatic encephalopathy.
    Keywords: Handwriting ; Liver Cirrhosis -- Complications ; Movement Disorders -- Etiology ; Psychomotor Performance -- Physiology
    ISSN: 0340-5354
    E-ISSN: 14321459
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  • 2
    Language: English
    In: Chest, October 2012, Vol.142(4), pp.1020-1026
    Description: We previously identified amplification of the fibroblast growth factor receptor 1 gene ( ) as a potential therapeutic target for small-molecule inhibitor therapy in squamous cell lung cancer (L-SCC). Currently, clinical phase I trials are underway to examine whether patients with -amplified L-SCC benefit from a targeted therapy approach using small-molecule inhibitors. Because most patients with lung cancer present with metastatic disease, we investigated whether lymph node metastases in L-SCC share the amplification status of their corresponding primary tumor. The study cohort consisted of 72 patients with L-SCC, 39 with regional lymph node metastases. Tissue microarrays were constructed from formalin-fixed, paraffin-embedded tissue of the primary tumors and, where present, of the corresponding lymph node metastasis. A biotin-labeled target probe spanning the locus (8p11.22-23) was used to determine the amplification status by fluorescence in situ hybridization. amplification was detected in 16% (12 of 72) of all primary L-SCCs. In metastatic tumors, 18% (seven of 39) of the lymph node metastases displayed amplification with an exact correlation of amplification status between tumor and metastatic tissue. amplification is a common genetic event occurring at a frequency of 16% in L-SCCs. Moreover, lymph node metastases derived from -amplified L-SCCs also exhibit amplification. Therefore, we suggest that the amplification is a clonal event in tumor progression. Beyond this biologically relevant observation, the findings carry potential therapeutic implications in that small-molecule inhibitors may be applicable to the treatment of a subset of patients with metastatic L-SCC.
    Keywords: Medicine
    ISSN: 0012-3692
    E-ISSN: 1931-3543
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  • 3
    In: Rheumatology, 2017, Vol. 56(3), pp.451-456
    Description: Objectives. To evaluate the effect of autologous stem cell transplantation (aSCTrans) on antibody (Ab) reactivity towards topo I in patients with SSc, and to see whether it may correlate with clinical outcome after aSCTrans. Methods. Eighteen anti-topo/Scl70–positive patients with SSc in whom non-myeloablative aSCTrans had been performed were analysed. Seven patients showed good response without relapse for several years (group 1), eight primarily responded but later relapsed and three did not respond (group 2). A total of 74 sera were analysed at different time points and tested by ELISA against full length ( fl ) topo I, truncated ( tr ) topo I and a previously identified immunodominant epitope covering amino acid 489–573. Results. Eighty-three percent had IgG Abs to topo fl and topo tr . Ab reactivity significantly decreased after aSCTrans, but remained positive in 10 of the 11 patients followed for up to 24 months. The decrease did not correlate with the clinical outcome after aSCTrans. Fifty-six percent of the patients reacted with topo489–573, and reactivity was nearly confined to group 2. There was no correlation between Ab reactivity towards topo fl or topo489–573 and the modified Rodnan Skin Score before aSCTrans or its decrease after aSCTrans. Conclusions. Although aSCTrans is a good treatment option in patients with progressive SSc, it does not abrogate Ab reactivity towards topo I. The presence of anti-topo489–573 Abs before aSCTrans may indicate a less favourable course after aSCTrans.
    Keywords: Systemic Sclerosis ; Autologous Stem Cell Transplantation ; Anti - Topoisomerase I Antibodies ; Immunodominant Epitope
    ISSN: 1462-0324
    E-ISSN: 1462-0332
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  • 4
    In: Rheumatology, 2014, Vol. 53(5), pp.919-922
    Description: Objective. The aim of this study was to find a new and less cardiotoxic conditioning regimen for high-dose chemotherapy and autologous stem cell transplantation (aSCT) in patients with severe SSc and pre-existing cardiac involvement. Methods. Six patients with cardiac involvement were treated for SSc with a conditioning regimen including reduced-dose CYC plus the non-cardiotoxic alkylant thiotepa. All patients received an implantable cardioverter defibrillator (ICD) before aSCT. The response at months 6 and 12 was measured according to reduction of the modified Rodnan skin score (mRSS). CT histography was used to monitor pulmonary manifestations, as were echocardiography, N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin for the cardiac involvement. Cardiac events were defined as death or hospitalisation due to heart failure or appropriate discharge of the ICD. Results. Between December 2008 and May 2012, four male and two female patients with a median age of 41 years received aSCT. The median mRSS significantly decreased from 26.5 to 18 and 17.5 at month 6 and 12, respectively. The total lung volume also significantly improved. Within the median follow-up of 1.6 years (range 1–3.8) two patients experienced a relapse of SSc, which results in a progression-free survival rate of 66.6%. Three patients experienced ICD discharge. Conclusion. For patients with SSc and cardiac involvement, the use of thiotepa and reduced-dose CYC is feasible and effective. The rate of ICD discharge underlines the need for protection in these endangered patients. This preliminary experience allowed us to use this regimen for our currently recruiting prospective trial (NCT01895244).
    Keywords: Systemic Sclerosis ; Stem Cell Transplantation ; Treatment ; Cyclophosphamide ; Ct Histography ; Thiotepa ; Heart
    ISSN: 1462-0324
    E-ISSN: 1462-0332
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  • 5
    In: BJU International, February 2012, Vol.109(4), pp.634-638
    Description: To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1464-410X.2011.10392.x Keywords: renal cell carcinoma (RCC); XPA-210; proliferation; oncocytoma; biomarker; thymidine kinase 1 Abstract: What's known on the subject? and What does the study add? The exposed proliferation antigen 210 (XPA-210) of the proliferation marker thymidine kinase 1 (TK1) showed higher expression levels in metastatic renal cell carcinoma. The current study used a new XPA-210 antibody to clarify the role of TK1 tissue expression in the largest reported cohort of different renal cell carcinoma types and oncocytomas. OBJECTIVE To determine the clinical role of the exposed proliferation antigen 210 (XPA-210) of the proliferation marker thymidine kinase 1 (TK1) in a large cohort of different renal cell carcinoma (RCC) types, oncocytomas and normal renal tissues samples, as TK1 is reported to be of clinical significance in several cancer entities and is suggested as a prognostic serum biomarker for RCC. PATIENTS AND METHODS Expressions of XPA-210 were determined immunohistochemically in 40 clear cell RCCs (ccRCC), 25 papillary RCCs (papRCC), 17 chromophobe RCC (chRCC), 27 oncocytomas and 64 normal renal parenchyma paraffin-embedded specimens. Immunohistochemistry was performed with a monoclonal anti-XPA-210 antibody. Staining was measured by the percentage of positive cells. Expression was compared between subgroups and correlated with respective clinical data using one-way analysis of variance with post hoc Tukey-Kramer analyses. RESULTS XPA-210 staining in the RCC subgroup was significantly different from the oncocytomas (mean [ sem] 4.1 [0.4] vs 2.2 [0.4]; P = 0.004) and from normal renal tissue (1.0 [0.1]; P 〈 0.001], whereas oncocytomas did not differ from normal renal parenchyma staining (P = 0.18). Subdivided into RCC groups, only ccRCC (mean [ sem] 5.1 [0.6]; P 〈 0.001) and papRCC (4.4 [0.6]; P 〈 0.001) varied from normal renal parenchyma, whereas chRCC (1.4 [0.3]; P = 0.99) did not. RCC XPA-210 staining was significantly associated with higher tumour stage (T = 3, P = 0.002) and grade (G = 3, P = 0.001). CONCLUSIONS The malignant character of RCC is reflected by higher XPA-210 expression as compared with oncocytomas and normal kidney. The ccRCC and papRCC subgroups had higher XPA-210 levels. XPA-210 could be considered a potential marker for the assessment of the proliferative activity in primary RCC. Author Affiliation: (1)Departments of Urology (*)Pathology, Eberhard-Karls University, Tuebingen, Germany ([dagger])Alere North America, Inc., San Diego, CA, USA Article History: Accepted for publication 16 March 2011 Article note: Christian Schwentner, Department of Urology, Eberhard-Karls University Tuebingen, Hoppe-Seyler Strasse 3, 72076 Tuebingen, Germany. e-mail: Christian.schwentner@med.uni-tuebingen.de
    Keywords: Renal Cell Carcinoma Rcc ; Xpa‐210 ; Proliferation ; Oncocytoma ; Biomarker ; Thymidine Kinase 1
    ISSN: 1464-4096
    E-ISSN: 1464-410X
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  • 6
    Language: English
    In: PLoS ONE, 01 January 2013, Vol.8(11), p.e80454
    Description: BACKGROUND: Myostatin is a muscle derived factor that functions as a negative regulator of skeletal muscle growth. Induction of myostatin expression was observed in rodent models of muscle wasting and in cachectic patients with cancer or pulmonary disease. Therefore, there is an increasing interest to use serum myostatin as a biomarker. METHODS: We established an immunoradiometric sandwich assay (IRMA), which uses a commercially available chicken polyclonal, affinity purified antibody directed against human myostatin prodomain. We determined the serum concentrations of myostatin prodomain in 249 healthy individuals as well as 169 patients with heart failure, 53 patients with cancer and 44 patients with chronic pulmonary disease. RESULTS: The IRMA had a detection limit of 0.7ng/ml, an intraassay imprecision of ≤14.1% and an interassay imprecision of ≤ 18.9%. The specificity of our assay was demonstrated by size exclusion chromatography, detection of myostatin by Western-blotting and a SMAD-dependent transcriptional-reporter assay in the signal-rich serum fractions, as well as lack of interference by unspecific substances like albumin, hemoglobin or lipids. Myostatin prodomain was stable at room temperature and resistant to freeze-thaw cycles. Apparently healthy individuals over the age of 55 had a median myostatin prodomain serum concentration of 3.9ng/ml (25(th)-75(th) percentiles, 2-7ng/ml) and we could not detect increased levels in patients with stable chronic heart failure or cancer related weight loss. In contrast, we found strongly elevated concentrations of myostatin prodomain (median 26.9ng/ml, 25(th)-75(th) percentiles, 7-100ng/ml) in the serum of underweight patients with chronic pulmonary disease. CONCLUSIONS: We established a highly specific IRMA for the quantification of myostatin prodomain concentration in human serum. Our assay could be useful to study myostatin as a biomarker for example in patients with chronic pulmonary disease, as we detected highly elevated myostatin prodomain serum levels in underweight individuals of this group.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 7
    Language: English
    In: The Journal of infectious diseases, 01 March 2011, Vol.203(5), pp.595-601
    Description: Recently, a IL28B (rs 12979860) gene polymorphism was identified as a predictor for response to hepatitis C virus-specific treatment in human immunodeficiency virus (HIV)-uninfected and -infected patients with chronic hepatitis C. In an analysis of HIV-infected patients with acute hepatitis C, we found that the IL28B genotype was associated with serum levels of hepatitis C virus RNA, g-GT, and CD4 cell count. In contrast to HIV-infected patients with chronic hepatitis C, the IL28B genotype was not significantly associated with treatment response rates in patients with acute hepatitis C. Thus, effects of the IL28B single-nucleotide polymorphism may differ in HIV-infected patients with chronic and acute hepatitis C.
    Keywords: Polymorphism, Single Nucleotide ; HIV Infections -- Complications ; Hepatitis C -- Genetics ; Interleukins -- Genetics
    ISSN: 00221899
    E-ISSN: 1537-6613
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  • 8
    Language: English
    In: The Journal of rheumatology, February 2012, Vol.39(2), pp.269-75
    Description: Autologous stem cell transplantation (aSCT) for systemic sclerosis (SSc) has been shown to be effective in recent reports. This aggressive approach and the disease itself are associated with a high mortality. We report our experiences in 26 consecutive patients. Between 1997 and 2009, 26 patients were scheduled for aSCT. Our standard transplant regimen consists of cyclophosphamide (CYC) and granulocyte colony-stimulating factor (GCSF) for mobilization and CYC plus antithymocyte globulin for conditioning before the retransfusion of CD34 selected stem cells. The major outcome variable was the response to treatment [reduction of modified Rodnan skin score (mRSS) by 25%] at Month 6. Secondary endpoints were the transplant-related mortality and the progression-free survival. Significant skin and lung function improvement of the mRSS was achieved in 78.3% of patients at Month 6. The overall response rate was 91%, as some patients improved even after Month 6. Three patients died between mobilization and conditioning treatment, 2 due to severe disease progression and 1 whose death was considered treatment-related (i.e., GCSF or CYC toxicity). Depending on definitions, transplant-related mortality was 4% and treatment-related mortality 11%. Seven patients experienced a relapse during the 4.4 years of followup. The progression-free survival was 74%. Four patients died during followup and the most frequent causes of death were pulmonary and cardiac complications of SSc. aSCT led to significant improvement in most patients with SSc. The procedure requires further optimization; hence we are modifying our screening and treatment strategy. To minimize infectious complications, CYC for mobilization and GCSF were reduced. We intensified our screening for cardiac involvement and modified our conditioning regimen in case of cardiac involvement.
    Keywords: Hematopoietic Stem Cell Transplantation -- Methods ; Scleroderma, Systemic -- Surgery
    ISSN: 0315-162X
    E-ISSN: 14992752
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  • 9
    Language: English
    In: Annals of Hematology, 2016, Vol.95(6), pp.973-983
    Description: Myelofibrosis (MF) is a rare disease responsible for an increasing ineffective hematopoesis by a progressive fibrosing process in the bone marrow. The only curative treatment option is allogeneic hematopoietic cell transplantation (HCT). In this single-center analysis, we evaluated retrospectively 54 consecutive patients suffering from primary or secondary MF which underwent HCT from 1997 to 2014 after either myeloablative (MAC, n  = 19) or reduced-intensity conditioning (RIC, n  = 35). Overall survival (OS) and disease-free survival (DFS) after 3 years was 54/53 % for RIC versus 63/58 % for MAC ( p  = 0.8/0.97). Cumulative incidence of relapse was 34 % after RIC and 8 % after MAC ( p  = 0.16). Three-year non-relapse mortality (NRM) was 15 % after RIC and 34 % after MAC ( p  = 0.29). We found that RIC was associated with a lower incidence of acute graft versus host disease (GvHD; II–IV 26 vs. 0 %, p  = 0.004). Evaluation of prognostic relevance of the Dynamic International Prognostic Scoring System (DIPSS) score showed a significant better OS in patient with risk score ≤3 versus 〉3 (after 3 years, 71 vs. 39 %, p  = 0.008). While similar OS and DFS were observed with MAC or RIC, the use of RIC resulted in lower incidence of acute GvHD. RIC regimens may be therefore the preferred conditioning approach for allogeneic HCT in patients with MF.
    Keywords: Reduced intensity conditioning ; Myeloablative conditioning ; Hematopoietic cell transplantation ; Myelofibrosis
    ISSN: 0939-5555
    E-ISSN: 1432-0584
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  • 10
    Language: English
    In: The Journal of Allergy and Clinical Immunology, September 2017, Vol.140(3), pp.845-853.e3
    Description: Atopic dermatitis (AD) is a chronic relapsing skin disease prevalent in 1% to 3% of adults in Western industrialized countries. We sought to investigate the effectiveness of educational training in an outpatient setting on coping with the disease, quality of life, symptoms, and severity in adults with AD. In this German prospective, randomized controlled multicenter study, adult patients with moderate-to-severe AD were educated by referring to a comprehensive 12-hour training manual consented by a multiprofessional study group from different centers (Arbeitsgemeinschaft Neurodermitisschulung für Erwachsene [ARNE]). Patients were randomly allocated to the intervention or waiting control groups. Study visits were performed at baseline and after 1 year (1 year of follow-up). Primary outcomes were defined as a decrease in (1) “catastrophizing cognitions” with respect to itching (Juckreiz-Kognitions-Fragebogen questionnaire), (2) “social anxiety” (Marburger Hautfragebogen questionnaire), (3) subjective burden by symptoms of the disease (Skindex-29 questionnaire), and (4) improvement of disease signs and symptoms assessed by using the SCORAD index at 1 year of follow-up. Data were analyzed on an intention-to-treat basis. At 1 year of follow-up, patients from the intervention group (n = 168) showed a significantly better improvement compared with the waiting group (n = 147) in the following defined primary study outcomes: coping behavior with respect to itching (  〈 .001), quality of life assessed by using the Skindex-29 questionnaire (  〈 .001), and the SCORAD index (  〈 .001). This is the first randomized, controlled multicenter study on patient education in adult AD. The ARNE training program shows significant beneficial effects on a variety of psychosocial parameters, as well as AD severity.
    Keywords: Atopic Dermatitis ; Adulthood ; Patient Education ; Multi-Professional ; Psychosocial ; Disease Severity ; Quality of Life ; Coping ; Medicine
    ISSN: 0091-6749
    E-ISSN: 1097-6825
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