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Find video protocols related to scientific articles indexed in Pubmed.
Microaneurysm formation rate as a predictive marker for progression to clinically significant macular edema in nonproliferative diabetic retinopathy.
Retina (Philadelphia, Pa.)
PUBLISHED: 04-17-2014
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To evaluate the predictive value of microaneurysm (MA) formation rate concerning the development of clinically significant macular edema (CSME) in patients with mild-to-moderate nonproliferative diabetic retinopathy as evaluated by an automated analysis of central field fundus 30° photographs.
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Adaptive designs with arbitrary dependence structure.
Biom J
PUBLISHED: 01-08-2014
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Adaptive designs were originally developed for independent and uniformly distributed p-values. There are trial settings where independence is not satisfied or where it may not be possible to check whether it is satisfied. In these cases, the test statistics and p-values of each stage may be dependent. Since the probability of a type I error for a fixed adaptive design depends on the true dependence structure between the p-values of the stages, control of the type I error rate might be endangered if the dependence structure is not taken into account adequately. In this paper, we address the problem of controlling the type I error rate in two-stage adaptive designs if any dependence structure between the test statistics of the stages is admitted (worst case scenario). For this purpose, we pursue a copula approach to adaptive designs. For two-stage adaptive designs without futility stop, we derive the probability of a type I error in the worst case, that is for the most adverse dependence structure between the p-values of the stages. Explicit analytical considerations are performed for the class of inverse normal designs. A comparison with the significance level for independent and uniformly distributed p-values is performed. For inverse normal designs without futility stop and equally weighted stages, it turns out that correcting for the worst case is too conservative as compared to a simple Bonferroni design.
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No significant difference in the prognostic value of the 5th and 7th editions of AJCC staging for differentiated thyroid cancer.
Clin. Endocrinol. (Oxf)
PUBLISHED: 01-02-2014
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The seventh edition of the American Joint Committee on Cancer (AJCC) has more detailed staging categories for differentiated thyroid cancer (DTC) than the fifth edition. The aim was to compare potential alterations in the disease-specific (DSS), event-free (EFS) and overall survival (OS), after reclassification from the fifth to the seventh edition.
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Epigenetic repression of the dopamine receptor D4 in pediatric tumors of the central nervous system.
J. Neurooncol.
PUBLISHED: 06-06-2013
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Epigenetic alterations are common events in cancer. Using a genome wide methylation screen (Restriction Landmark Genomic Scanning-RLGS) we identified the gene for the dopamine receptor D4 (DRD4) as tumor-specific methylated. As DRD4 is involved in early brain development and may thus be involved in developmentally dependent tumors of the CNS in children epigenetic deregulation of DRD4 and its functional consequences were analyzed in vitro. CpG methylation of DRD4 was detected in 18/24 medulloblastomas, 23/29 ependymomas, 6/6 high-grade gliomas, 7/10 CNS PNET and 8/8 cell lines by qCOBRA and bisulfite sequencing. Real-time RT-PCR demonstrated a significantly inferior expression of DRD4 in primary tumors compared to cell lines and non-malignant control tissues. Epigenetic deregulation of DRD4 was analyzed in reexpression experiments and restoration of DRD4 was observed in medulloblastoma (MB) cells treated with 5-Aza-CdR. Reexpression was not accompanied by demethylation of the DRD4 promoter but by a significant decrease of H3K27me3 and of bound enhancer of zeste homologue 2 (EZH2). Knockdown of EZH2 demonstrated DRD4 as a direct target for inhibition by EZH2. Stimulation of reexpressed DRD4 resulted in an activation of ERK1/2. Our analyses thus disclose that DRD4 is epigenetically repressed in CNS tumors of childhood. DRD4 is a direct target of EZH2 in MB cell lines. EZH2 appears to dominate over aberrant DNA methylation in the epigenetic inhibition of DRD4, which eventually leads to inhibition of a DRD4-mediated stimulation of the ERK1/2 kinase pathway.
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Cardiopulmonary resuscitation guidance improves medical students adherence to guidelines in simulated cardiac arrest: a randomised cross-over study.
Eur J Anaesthesiol
PUBLISHED: 05-25-2013
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The 2010 Resuscitation Guidelines require high-quality chest compression and rapid defibrillation for patients with ventricular fibrillation with rhythm analysis and defibrillation repeated every 2?min. A lack of adherence to the guidelines by medical students was observed during simulated resuscitation training.
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Autonomic Dysfunction in Patients with Arrhythmogenic Right Ventricular Cardiomyopathy: Biochemical Evidence of Altered Signaling Pathways.
Pacing Clin Electrophysiol
PUBLISHED: 01-20-2013
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Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden cardiac death especially in times of increased sympathetic tone, for example, during sports, which have been confirmed by nuclear imaging studies. However, the underlying biochemical pathways remain to be delineated. Therefore, we investigated the expression levels of proteins of the signaling cascade in patients with ARVC.
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Connexin expression patterns in arrhythmogenic right ventricular cardiomyopathy.
Am. J. Cardiol.
PUBLISHED: 01-12-2013
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Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inheritable myocardial disease accounting for ventricular tachycardia and sudden death in the young and arising from areas of fibrofatty replacement of predominantly right ventricular myocardium. That some patients manifest life-threatening ventricular tachycardia in the absence of substantial myocardial replacement suggests that gap junction remodeling might be acting synergistically to ventricular remodeling to promote arrhythmogenesis. Hence, we sought to verify gap junction composition and distribution by analyzing the expression and occurrence of specific gap junction proteins (connexins [Cxs]) in patients with ARVC. Right ventricular endomyocardial biopsy specimens were taken from 16 patients with definite ARVC (age 48 ± 16 years) and analyzed for Cx40, Cx43, and Cx45 messenger ribonucleic acid expression (relative to glyceraldehyde-3-phosphate-dehydrogenase messenger ribonucleic acid expression). The results were compared to those obtained from nondiseased donor hearts (n = 6; age 32 ± 11 years). The patients with ARVC showed a significant reduction in the messenger ribonucleic acid expression of Cx40 (p <0.0001) and Cx45 (p <0.0001) compared to that of the controls. The expression of Cx43 was similar in patients with ARVC and controls (p = 0.098). Mutations in plakophilin-2 were identified in 7 of 16 patients (25%). The Cx expression levels were comparable between the mutation carriers and noncarriers (p = NS). In conclusion, ARVC features alterations in the expression of Cxs and their distribution at cardiac intercalated discs. Apart from the deposition of extracellular matrix, the potential loss of gap junctions and shift in the composition of gap junctional Cxs in the ventricular conduction system might further contribute to the development of ventricular arrhythmias in patients with ARVC.
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Anti-Escherichia coli asparaginase antibody levels determine the activity of second-line treatment with pegylated E coli asparaginase: a retrospective analysis within the ALL-BFM trials.
Blood
PUBLISHED: 09-22-2011
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Hypersensitivity reactions limit the use of the antileukemic enzyme asparaginase (ASE). We evaluated Ab levels against Escherichia coli ASE and ASE activity in 1221 serum samples from 329 patients with acute lymphoblastic leukemia who had received ASE treatment according to the ALL-BFM 2000 or the ALL-REZ BFM 2002 protocol for primary or relapsed disease. ASE activity during first-line treatment with native E coli ASE and second-line treatment with pegylated E coli ASE was inversely related to anti-E coli ASE Ab levels (P < .0001; Spearman rank order correlation). An effect on ASE activity during second-line treatment with pegylated E coli ASE was, however, only observed when anti-E coli ASE Ab levels were high (> 200 AU/mL). In the presence of moderate or intermediate Ab levels (6.25-200 AU/mL) the switch from native to pegylated E coli ASE resulted in a significant increase of ASE activity above the threshold of 100 U/L (P < .05). Erwinia chrysanthemi ASE activity was not correlated with anti-E coli ASE Ab levels. Erwinia ASE was found to be the best ASE alternative if Ab levels against E coli ASE exceed 200 AU/mL. This retrospective analysis is the first to describe the relationship between the level of anti-E coli ASE Abs and serum activity of pegylated E coli ASE used second-line after native E coli ASE.
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Cardiac sympathetic dysfunction in genotyped patients with arrhythmogenic right ventricular cardiomyopathy and risk of recurrent ventricular tachyarrhythmias.
J. Nucl. Med.
PUBLISHED: 09-09-2011
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Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) typically present with ventricular tachyarrhythmias preferentially triggered by an elevated sympathetic tone. Previous studies demonstrated an impairment of the presynaptic catecholamine reuptake as assessed by (123)I-labeled norepinephrine analog on metaiodobenzylguanidine ((123)I-MIBG) SPECT. Mutations in the gene encoding for plakophilin-2 (PKP-2) are the most common cause of autosomal dominant ARVC (ARVC-9). In this study, we investigated the potential role of adrenergic dysfunction on the arrhythmia profile in patients with ARVC and correlated these findings with the causative genotype.
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Microvascular dysfunction in nonfailing arrhythmogenic right ventricular cardiomyopathy.
Eur. J. Nucl. Med. Mol. Imaging
PUBLISHED: 08-05-2011
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Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a nonischaemic cardiomyopathy and leading cause of sudden death in the young. It has been shown that microvascular dysfunction reflected by an impaired myocardial blood flow (MBF) response to stress is present in patients with other forms of nonischaemic cardiomyopathy, e.g. dilated cardiomyopathy, and that the reduced MBF may be related to a poor prognosis. Therefore, we quantified MBF, coronary flow reserve and coronary vascular resistance in patients with nonfailing ARVC using H(2)(15)O and PET.
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Sex-related differences of patient-controlled epidural analgesia for postoperative pain.
Pain
PUBLISHED: 06-14-2011
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Gender differences in pain modulation are evident but data are rare with regard to perioperative regional analgesia. The aim of the present analysis was to assess gender-related differences in pain ratings, analgesic consumption, and adverse events in a large group of patients treated with patient-controlled epidural analgesia (PCEA) after major surgery. Data from 14,988 adult patients (6506 women; 8482 men) receiving a PCEA between January 1998 and December 2009 were examined. Demographic data and postoperative measurements assessed by the Acute Pain Service, including total PCEA consumption, pain scores, and complications, were analyzed by using PASW Statistics (18.0; SPSS Inc, Chicago, IL, USA). Beyond standard descriptive analyses, gender-related differences were investigated using a stepwise multivariate analysis of variances. Postoperative pain scores during rest and movement were almost equal between men and women. However, women showed lower total PCEA consumption consistently throughout the 5-day observation period (relative reduction by 1.7%-10.2% compared to men; P=0.00). Total PCEA consumption did not interact with surgical site (abdomen, thorax, extremity) (P=0.379) or age (<50, 50-75, >75 years; P=0.330), but was influenced by body mass index (P=0.017) and vomiting (P=0.011). Furthermore, motor blockade was greater in females compared to males (P=0.000). In patients treated with PCEA, gender differences in numeric rating scale scores exist but are not clinically relevant. However, reduced total PCEA consumption in women might be a consequence of an increased incidence of motor blockade and vomiting; the latter point towards an opioid-free PCEA solution in female patients at high risk for vomiting.
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Usefulness of semi-automatic volumetry compared to established linear measurements in predicting lymph node metastases in MSCT.
Acta Radiol
PUBLISHED: 04-06-2011
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Volumetry of lymph nodes potentially better reflect asymmetric size alterations independently of lymph node orientation in comparison to metric parameters (e.g. long-axis diameter).
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Impaired cardiac sympathetic innervation in symptomatic patients with long QT syndrome.
Eur. J. Nucl. Med. Mol. Imaging
PUBLISHED: 03-18-2011
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Increased sympathetic activation is a key modifier for arrhythmogenesis in patients with long QT syndrome (LQTS), a congenital channelopathy. Therefore, we investigated cardiac sympathetic function using 123I-metaiodobenzylguanidine (MIBG) single photon emission computed tomography (SPECT) in a cohort of symptomatic LQTS patients and correlated these findings with the underlying genotype.
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Five-year single-center study of asparaginase therapy within the ALL-BFM 2000 trial.
Pediatr Blood Cancer
PUBLISHED: 02-18-2011
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Therapeutic drug monitoring (TDM) of asparaginase (ASNase), a fundamental element of acute lymphoblastic leukemia treatment, was integrated in the ALL-BFM 2000 protocol on a voluntary basis.
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Combined immunochemotherapy in selected patients with metastatic renal cell carcinoma: HLA class II genotype can help to predict response to therapy.
J. Immunother.
PUBLISHED: 02-10-2011
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A number of new agents have been approved for systemic therapy of metastatic renal cell carcinoma (mRCC) recently. Thereby, prognostic factors may aid in predicting the effectiveness of various treatment modalities in individual cases. Aim of this study was to determine the value of human leukocyte antigen (HLA) class II characteristics in predicting response of mRCC to combined immunochemotherapy (ICT). A retrospective study of 29 patients with mRCC treated with ICT was performed: 17 patients (group A) with long-term remission and 12 (group B) with progressive disease after ICT. DNA was used for high resolution typing of HLA-DRB1, -DRB3, -DRB4, -DRB5, -DQA1, and -DQB1. Statistical evaluation started with Classification and Regression Trees analysis. The assignment of single alleles to the groups was then aggregated to create a classification on a patients basis. Finally, the accuracy of this test algorithm was evaluated. HLA-DRB1 (DRB1*0301*0401*0402*0407*1101*1501=progression) was the strongest discriminator between the 2 groups. The test algorithm defined all patients with at least one of these DRB1 alleles to be progressive after ICT. Thus, 12 of 12 patients of group B could have been identified as progressive (sensitivity=100%). However, only 10 of 17 patients of group A would have been identified as responding (specificity=58%). Thus, the test had a positive and negative predictive value of 63% and 100%, respectively. Approximately 5% to 10% of all patients with mRCC are able to benefit from ICT with long-term remission. HLA class II characteristics may aid in identifying this small subgroup of patients with mRCC.
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Safety of endomyocardial biopsy in patients with arrhythmogenic right ventricular cardiomyopathy: a study analyzing 161 diagnostic procedures.
JACC Cardiovasc Interv
PUBLISHED: 02-08-2011
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The aim of the present study was to assess the feasibility and safety of target-directed sampling of right ventricular (RV) endomyocardial biopsies (EMB) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC).
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Carboplatin dosing in children: calculation by different formulae.
Onkologie
PUBLISHED: 01-17-2011
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Carboplatin dosing in children is based on renal function and there exists a wealth of formulae available for calculating the body surface area (BSA), the glomerular filtration rate (GFR), and the carboplatin dose.
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Nutritional manipulation of primate retinas, V: effects of lutein, zeaxanthin, and n-3 fatty acids on retinal sensitivity to blue-light-induced damage.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 01-01-2011
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Blue-light photooxidative damage has been implicated in the etiology of age-related macular degeneration (AMD). The macular pigment xanthophylls lutein (L) and zeaxanthin (Z) and n-3 fatty acids may reduce this damage and lower the risk of AMD. This study investigated the effects of the lifelong absence of xanthophylls followed by L or Z supplementation, combined with the effects of n-3 fatty acid deficiency, on acute blue-light photochemical damage.
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Measurement accuracy and reproducibility of semiautomated metric and volumetric lymph node analysis in MDCT.
AJR Am J Roentgenol
PUBLISHED: 09-23-2010
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The purpose of this study was to assess the measurement accuracy and reproducibility of semiautomated metric and volumetric lymph node analysis in MDCT.
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Clinical trials and rare diseases.
Adv. Exp. Med. Biol.
PUBLISHED: 09-09-2010
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Whenever possible, standard methodological approaches should be applied in the design and analysis of a clinical trial that warrant adequate informative value. However, there are circumstances when the number of experimental subjects is unavoidably small. In such circumstances it is justified to consider abandoning standard statistical methodology in place of alternative approaches. Performing a small clinical trial however it should be pointed out, that a such trial can never be as meaningful and provide as much evidence as a larger trial. In the present text, basic concepts are presented, that apply to small clinical trials in general. Moreover, several specific methodological approaches are presented, that either enhance the efficiency of standard statistical procedures or evolve from the idea of abandoning classical paradigms in the design and analysis of clinical trials. Within the scope of the former approach, (Bayesian) adaptive randomisation, group sequential (adaptive) designs, repeated measurement designs for longitudinal data, and meta-analyses are illustrated and discussed. The latter approach comprises alternative strategies such as (non-randomised) risk-based allocation designs, statistical prediction designs, ranking and selection designs, as well as the application of Bayesian statistics.
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Prediction of lymph node manifestations in malignant lymphoma: significant role of volumetric compared with established metric lymph node analysis in multislice computed tomography.
J Comput Assist Tomogr
PUBLISHED: 07-27-2010
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Comparison of 2-dimensional and semiautomated 3-dimensional (3D) measurements to distinguish between benign and malignant lymph nodes in patients with malignant lymphoma.
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Hypothyroidism after head-and-neck radiotherapy in children and adolescents: preliminary results of the "Registry for the Evaluation of Side Effects After Radiotherapy in Childhood and Adolescence" (RiSK).
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 07-26-2010
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The "Registry for the Evaluation of Side Effects After Radiotherapy in Childhood and Adolescence" (RiSK) has been established to prospectively characterize dose-volume effects of radiation in terms of side effects. The aim of this analysis was to characterize the function of the thyroid gland after radiotherapy to the head-and-neck region in children and adolescents.
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Randomized comparison of safety and pharmacokinetics of caspofungin, liposomal amphotericin B, and the combination of both in allogeneic hematopoietic stem cell recipients.
Antimicrob. Agents Chemother.
PUBLISHED: 07-26-2010
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The combination of liposomal amphotericin B (LAMB) and caspofungin (CAS) holds promise to improve the outcome of opportunistic invasive mycoses with poor prognosis. Little is known, however, about the safety and pharmacokinetics of the combination in patients at high risk for these infections. The safety and pharmacokinetics of the combination of LAMB and CAS were investigated in a risk-stratified, randomized, multicenter phase II clinical trial in 55 adult allogeneic hematopoietic stem cell recipients (aHSCT) with granulocytopenia and refractory fever. The patients received either CAS (50 mg/day; day 1, 70 mg), LAMB (3 mg/kg of body weight/day), or the combination of both (CASLAMB) until defervescence and granulocyte recovery. Safety, development of invasive fungal infections, and survival were assessed through day 14 after the end of therapy. Pharmacokinetic sampling and analysis were performed on days 1 and 4. All three regimens were well tolerated. Premature study drug discontinuations due to grade III/IV adverse events occurred in 1/18, 2/20, and 0/17 patients randomized to CAS, LAMB, and CASLAMB, respectively. Adverse events not leading to study drug discontinuation were frequent but similar across cohorts, except for a higher frequency of hypokalemia with CASLAMB (P < 0.05). Drug exposures were similar for patients receiving combination therapy and those randomized to monotherapy. There was no apparent difference in the occurrence of proven/probable invasive fungal infections and survival through day 14 after the end of therapy. CASLAMB combination therapy in immunocompromised aHSCT patients was as safe as monotherapy with CAS or LAMB and had similar plasma pharmacokinetics, lending support to further investigations of the combination in the management of patients with invasive opportunistic mycoses.
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Primary tumour size is a prognostic parameter in patients suffering from differentiated thyroid carcinoma with extrathyroidal growth: results of the MSDS trial.
Eur. J. Endocrinol.
PUBLISHED: 07-21-2010
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The Multicentre Study Differentiated Thyroid Cancer (MSDS) collective represents a well-defined group of patients with thyroid carcinomas with extrathyroidal extension. The aim of the present study was to evaluate the relationship of the primary tumour size with clinicopathological features as well as the outcome of patients with minimum and extensive extrathyroidal growth (pT3b- and pT4a-tumours; UICC 2002/2003, 6th ed).
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Therapeutic drug monitoring of methotrexate in cerebrospinal fluid after systemic high-dose infusion in children: can the burden of intrathecal methotrexate be reduced?
Ther Drug Monit
PUBLISHED: 06-24-2010
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The use of intrathecal (IT) methotrexate (MTX) in combination with systemic high-dose (HD) MTX is an established procedure for central nervous system prophylaxis in patients with acute lymphoblastic leukemia, but the evidence for the necessity of this combination is not convincing. The MTX concentration in the cerebrospinal fluid (CSF) was evaluated in 138 samples from children with acute lymphoblastic leukemia and non-Hodgkin lymphoma. CSF samples were obtained by lumbar puncture 12-24 hours after starting the HD MTX infusion (5 g/m2 over 24 hours) and immediately before the IT administration of MTX. Serum MTX concentrations at the end of infusion were assessed by routine therapeutic drug monitoring. Cytotoxic MTX concentrations of 1 microM or greater were detected in 81.2% of CSF samples. CSF MTX concentrations were significantly lower in samples from patients younger than 7 years. The correlation between MTX concentrations in the serum and the CSF was moderate (r = 0.451) and became stronger with increasing age. The median CSF MTX concentrations per cycle were comparable (1.40, 1.25, 1.39, 1.38 microM for cycles 1-4, respectively). The predictive value and the accuracy of the CSF MTX concentration measured during the first cycle of HD MTX in respect to concentrations in the following cycles were high (94.4% and 85.7%, respectively) suggesting that the CSF MTX concentration during the first HD MTX infusion is a useful predictor for sufficient CSF MTX concentrations in the following HD MTX cycles. Our results confirm previously published data on MTX accumulation in the CSF after 5 g/m2 MTX over 24 hours in an independent cohort monitored in a real-life setting. Based on the common opinion that 1 microM represents the minimal antileukemic MTX concentration, current data warrant reevaluation of the necessity of routine IT MTX following HD MTX. Our findings offer a perspective on reducing the burden of IT MTX in children on consolidation therapy by CSF MTX drug monitoring.
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Development of healthy childrens feet--nine-year results of a longitudinal investigation of plantar loading patterns.
Gait Posture
PUBLISHED: 04-27-2010
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The purpose of the present study was to provide normative data for foot loading patterns and foot form parameters in order to support decisions about the normal or abnormal development of the growing foot during childhood. In a longitudinal design, 36 healthy German children were followed over the course of nine years. The children had a mean age of 14.6 ± 1.8 months at the first appointment and 122.8 ± 2.0 months at the last appointment. The children participated in 17 measurement appointments every 3, 6 or 12 months. Dynamic foot loading was evaluated with plantar pressure measurements during walking and static footprints were taken to determine changes in foot form. During the investigation period an increase of peak pressures of the total foot by 190%, of the relative maximum force of the total foot by 20% and the foot length by 90% was observed. A decrease for the relative maximum force under the midfoot (63%) and for the arch index (49%) could also be demonstrated. Furthermore, body height showed a significant influence on foot length and midfoot width. Body weight had a significant influence on the static parameter midfoot width. Between genders, boys showed a significant wider midfoot and a smaller forefoot contact area as compared to girls. The established database can be used as comparative values for clinical decisions about the normal foot development.
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Multistation proprioceptive exercise program prevents ankle injuries in basketball.
Med Sci Sports Exerc
PUBLISHED: 04-14-2010
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To investigate the effectiveness of a multistation proprioceptive exercise program for the prevention of ankle injuries in basketball players using a prospective randomized controlled trial in combination with biomechanical tests of neuromuscular performance.
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Acute toxicity profile of radiotherapy in 690 children and adolescents: RiSK data.
Radiother Oncol
PUBLISHED: 03-16-2010
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The "Registry for the evaluation of side effects after radiation in childhood and adolescence" (risk) was introduced to characterize adverse effects of radiotherapy in childhood and adolescence prospectively. The aim of this analysis was to characterize the pattern of acute side effects.
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The Randomized Shortened Dental Arch study (RaSDA): design and protocol.
Trials
PUBLISHED: 02-19-2010
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Various treatment options for the prosthetic treatment of jaws where all molars are lost are under discussion. Besides the placement of implants, two main treatment types can be distinguished: replacement of the missing molars with removable dental prostheses and non-replacement of the molars, i.e. preservation of the shortened dental arch. Evidence is lacking regarding the long-term outcome and the clinical performance of these approaches. High treatment costs and the long time required for the treatment impede respective clinical trials.
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Therapeutic drug monitoring of asparaginase in the ALL-BFM 2000 protocol between 2000 and 2007.
Pediatr Blood Cancer
PUBLISHED: 01-29-2010
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On a voluntary basis therapeutic drug monitoring (TDM) was implemented in the ALL-BFM 2000 protocol for the three currently used asparaginase (ASNase) preparations (first line: native Escherichia coli ASNase; second line: pegylated ASNase and third line: Erwinia chrysanthemi ASNase).
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Metabolic rate analysis of healthy preterm and full-term infants during the first weeks of life.
Am. J. Clin. Nutr.
PUBLISHED: 10-07-2009
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Longitudinal data on resting energy expenditure (REE) in extremely immature infants and full-term neonates are scarce but are necessary to understand the energy requirements in neonatal nutrition during the first weeks of life.
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Single nucleotide polymorphism genomic arrays analysis of t(8;21) acute myeloid leukemia cells.
Haematologica
PUBLISHED: 09-08-2009
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Translocation of chromosomes 8 and 21, t(8;21), resulting in the AML1-ETO fusion gene, is associated with acute myeloid leukemia. We searched for additional genomic abnormalities in this acute myeloid leukemia subtype by performing single nucleotide polymorphism genomic arrays (SNP-chip) analysis on 48 newly diagnosed cases. Thirty-two patients (67%) had a normal genome by SNP-chip analysis (Group A), and 16 patients (33%) had one or more genomic abnormalities including copy number changes or copy number neutral loss of heterozygosity (Group B). Two samples had copy number neutral loss of heterozygosity on chromosome 6p including the PIM1 gene; and one of these cases had E135K mutation of Pim1. Interestingly, 38% of Group B and only 13% of Group A samples had a KIT-D816 mutation, suggesting that genomic alterations are often associated with a KIT-D816 mutation. Importantly, prognostic analysis revealed that overall survival and event-free survival of individuals in Group B were significantly worse than those in Group A.
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Persistent non-verbal memory impairment in remitted major depression - caused by encoding deficits?
J Affect Disord
PUBLISHED: 05-08-2009
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While neuropsychological impairments are well described in acute phases of major depressive disorders (MDD), little is known about the neuropsychological profile in remission. There is evidence for episodic memory impairments in both acute depressed and remitted patients with MDD. Learning and memory depend on individuals ability to organize information during learning. This study investigates non-verbal memory functions in remitted MDD and whether nonverbal memory performance is mediated by organizational strategies whilst learning.
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Effect of calcium dobesilate on occurrence of diabetic macular oedema (CALDIRET study): randomised, double-blind, placebo-controlled, multicentre trial.
Lancet
PUBLISHED: 04-21-2009
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Medical treatment for diabetic retinopathy could have an important role in prevention of complications such as visual loss. We aimed to assess the effect of calcium dobesilate on occurrence of diabetic macular oedema.
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Prognostic value of histopathological findings in aneurysmal subarachnoid hemorrhage.
J. Neurosurg.
PUBLISHED: 04-08-2009
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Aneurysmal subarachnoid hemorrhage (SAH) carries a severe prognosis, which is often related to the development of cerebral vasospasm. Even though several clinical and radiological predictors of vasospasm and functional outcome have been established, the prognostic value of histopathological findings remains unclear.
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Estimation of patient accrual rates in clinical trials based on routine data from hospital information systems.
Methods Inf Med
PUBLISHED: 03-31-2009
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Delayed patient recruitment is a common problem in clinical trials. According to the literature, only about a third of medical research studies recruit their planned number of patients within the time originally specified.
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Circadian variation on oxygen consumption in preterm infants.
J Perinat Med
PUBLISHED: 03-19-2009
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We investigated the diurnal variation in oxygen consumption to determine the optimal time periods of calorimetry in preterm infants.
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Pre-treatment global quality of health predicts progression free survival in metastatic kidney cancer patients treated with sorafenib or sunitinib.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 03-11-2009
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Our goal was to prospectively evaluate self-reported quality-of-life (QoL) during second-line therapy in 51 consecutive patients with cytokine-refractory kidney cancer treated with sorafenib or sunitinib.
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Regional, age-dependent, and genotype-dependent differences in ventricular action potential duration and activation time in 410 Langendorff-perfused mouse hearts.
Basic Res. Cardiol.
PUBLISHED: 03-04-2009
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Although numerous studies have reported the effects of genetic alterations on murine electrophysiology, the range of normal values for ventricular activation, repolarization, and arrhythmias in mouse hearts is not known. We analyzed right ventricular (RV), left ventricular (LV), and septal activation times, monophasic action potential durations (APD), and right ventricular effective refractory periods during spontaneous rhythm, induced AV nodal block, right ventricular pacing (100-300 ms paced cycle length), and programmed stimulation in 410 beating, Langendorff-perfused, wild-type mouse hearts of CD1, DBAC3H, FVBN, C57/Bl6, and hybrid backgrounds (age 203 +/- 132 days). Action potential duration was longer at longer cycle lengths. LV-APD prolonged more than RV-APD, resulting in an increased heterogeneity of APD at longer pacing cycle lengths. Higher heart weight/body weight ratio and DBAC3H and FVB/N backgrounds were associated with long APD, C57Bl/6 background was associated with short APD. Activation times were longer in older hearts. There were no clear-cut sex-dependent APD differences. Sustained spontaneous arrhythmias occurred in 1% of hearts, non-sustained arrhythmias in 18%. Induction of AV block and C57Bl/6 genetic background were associated with spontaneous arrhythmias. Programmed stimulation induced arrhythmias in 51% of hearts. Inducible arrhythmias were associated with advanced age and shorter refractory periods. Ventricular APD in beating mouse hearts show rate- and site-dependent changes comparable to man and large animals. Bradycardia provokes spontaneous arrhythmias in mouse heart, while age-dependent conduction slowing and short refractory periods predispose to induced arrhythmias. Genetic background influences repolarization and arrhythmogenesis. These findings provide systematic data for the design and interpretation of arrhythmia studies in murine disease models.
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Feasibility of azacitidine added to standard chemotherapy in older patients with acute myeloid leukemia--a randomised SAL pilot study.
PLoS ONE
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Older patients with acute myeloid leukemia (AML) experience short survival despite intensive chemotherapy. Azacitidine has promising activity in patients with low proliferating AML. The aim of this dose-finding part of this trial was to evaluate feasibility and safety of azacitidine combined with a cytarabine- and daunorubicin-based chemotherapy in older patients with AML.
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Suppression of UV-induced damage by a liposomal sunscreen: a prospective, open-label study in patients with cutaneous lupus erythematosus and healthy controls.
Exp. Dermatol.
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This study aimed to determine whether a broad-spectrum liposomal sunscreen with a very high sun protection factor (Daylong actinica) can prevent damage induced by ultraviolet (UV) irradiation in patients with cutaneous lupus erythematosus (CLE) and healthy controls (HCs) under standardised conditions. In 20 patients with CLE and 10 HCs, defined areas of sunscreen-untreated and sunscreen-treated skin on the upper back were irradiated with combined UVA/UVB light. Disease-specific skin lesions were induced by UVA/UVB light in the untreated areas of nine patients with CLE; no specific eruptions or any sun damage was observed in the sunscreen-treated areas in any of the CLE patients, nor in the HCs. Histological analysis of skin biopsy specimens confirmed the clinical results. In conclusion, the use of a high-protection, broad-spectrum sunscreen can prevent UV-induced damage in patients with CLE and HCs.
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Longitudinal analysis of serum miR-122 in a rat model of Wilsons disease.
Hepatol Int
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PURPOSE: MicroRNA-122 (miR-122) has recently been shown to represent a novel biomarker of liver disease. However, the presence of serum miR-122 after liver injury was mostly studied at singular time points. The course of serum miR-122 was determined at consecutive time points during the onset of disease. METHODS: Fulminant hepatitis was induced by a high-copper diet in Long-Evans Cinnamon (LEC) rats that were used as models for Wilsons disease (WD). Levels of serum miR-122, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and liver histology were determined. RESULTS: Toxic copper given to isolated hepatocytes induced release of miR-122 into the tissue culture medium. Levels of serum miR-122 were highly elevated (21.9 ± 5) in LEC rats after high-copper diet in fulminant hepatitis, whereas healthy rats showed low (<0.6) baseline levels of miR-122. Levels of miR-122 in the serum of LEC rats after high-copper diet continuously increased for about 4 weeks prior to the onset of fulminant hepatitis. In most of the animals (77.8%), significantly increased levels of miR-122 were detected about 2 weeks (13.7 ± 2 days) earlier as compared to hepatitis-associated serum markers ALT, AST, and bilirubin. Analysis of miR-122 in survivors after cell-based therapy of WD demonstrated a rapid decrease of miR-122 levels following hepatocyte transplantation. miR-122 expression in the serum was normalized to baseline levels in most of the (4/5) survivors. CONCLUSION: Our results suggest that longitudinal analysis of miR-122 allows detection of severe liver disease at an early stage and might be excellently suited to monitor therapy, at least when severe liver disease can be restored as observed after cell-based therapy of WD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12072-012-9348-5) contains supplementary material, which is available to authorized users.
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T-wave integral: an electrocardiographic marker discriminating patients with arrhythmogenic right ventricular cardiomyopathy from patients with right ventricular outflow tract tachycardia.
Europace
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Clinical and electrocardiographic (ECG) presentation of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and idiopathic right ventricular outflow-tract tachycardia (RVOT) may be similar. The aim of the study was to assess the validity and utility of T-wave integral measurement as an ECG discriminator of patients with ARVC and RVOT using a body surface mapping (BSM).
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DNA copy number alterations in central primitive neuroectodermal tumors and tumors of the pineal region: an international individual patient data meta-analysis.
J. Neurooncol.
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Little is known about frequency, association with clinical characteristics, and prognostic impact of DNA copy number alterations (CNA) on survival in central primitive neuroectodermal tumors (CNS-PNET) and tumors of the pineal region. Searches of MEDLINE, Pubmed, and EMBASE--after the original description of comparative genomic hybridization in 1992 and July 2010--identified 15 case series of patients with CNS-PNET and tumors of the pineal region whose tumors were investigated for genome-wide CNA. One additional case study was identified from contact with experts. Individual patient data were extracted from publications or obtained from investigators, and CNAs were converted to a digitized format suitable for data mining and subgroup identification. Summary profiles for genomic imbalances were generated from case-specific data. Overall survival (OS) was estimated using the Kaplan-Meier method, and by univariable and multivariable Cox regression models. In their overall CNA profiles, low grade tumors of the pineal region clearly diverged from CNS-PNET and pineoblastoma. At a median follow-up of 89 months, 7-year OS rates of CNS-PNET, pineoblastoma, and low grade tumors of the pineal region were 22.9 ± 6, 0 ± 0, and 87.5 ± 12 %, respectively. Multivariable analysis revealed that histology (CNS-PNET), age (?2.5 years), and possibly recurrent CNAs were associated with unfavorable OS. DNA copy number profiling suggests a close relationship between CNS-PNET and pineoblastoma. Low grade tumors of the pineal region differed from CNS-PNET and pineoblastoma. Due to their high biological and clinical variability, a coordinated prospective validation in future studies is necessary to establish robust risk factors.
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Phagocyte-specific S100 proteins and high-sensitivity C reactive protein as biomarkers for a risk-adapted treatment to maintain remission in juvenile idiopathic arthritis: a comparative study.
Ann. Rheum. Dis.
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Juvenile idiopathic arthritis (JIA) is a chronic inflammatory joint disease affecting children. Even if remission is successfully induced, about half of the patients experience a relapse after stopping anti-inflammatory therapy. The present study investigated whether patients with JIA at risk of relapse can be identified by biomarkers even if clinical signs of disease activity are absent.
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Osteopontin is a prognostic factor for survival of acute myeloid leukemia patients.
Blood
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Osteopontin (OPN) is a glycoprotein that is secreted by osteoblasts and hematopoietic cells. OPN suppresses the proliferation of hematopoietic stem cells in vitro and may regulate the hematopoietic stem cell pool. Increased serum OPN concentrations occur in chronic myeloid leukemia, multiple myeloma, and acute myeloid leukemia (AML). In the present study, we analyzed the prognostic impact of OPN in AML by investigating the expression and relevance of OPN in newly diagnosed AML patients from 2 large study groups (the German AML Cooperative Group and the Dutch-Belgian Hematology Oncology Cooperative group). IHC (n = 84), ELISAs of blood/BM sera (n = 41), and microarray data for mRNA levels (n = 261) were performed. Expression of OPN protein was increased in AML patients both in BM blasts (IHC) and in BM serum (ELISA) compared with healthy controls. Patients expressing high levels of OPN within the BM (IHC) experienced shortened overall survival (OS; P = .025). Multivariate analysis identified karyotype, blast clearance (day 16), and the level of OPN expression as independent prognostic factors for OS. This prompted us to analyze microarray data from 261 patients from a third cohort. The analysis confirmed OPN as a prognostic marker. In summary, high OPN mRNA expression indicated decreased event-free survival (P = .0002) and OS (P = .001). The prognostic role of OPN was most prominent in intermediate-risk AML. These data provide evidence that OPN expression is an independent prognostic factor in AML.
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Validation of relapse risk biomarkers for routine use in patients with juvenile idiopathic arthritis.
Arthritis Care Res (Hoboken)
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Objectives: The myeloid-related proteins 8 and 14 (MRP8/14) and neutrophil-derived S100A12 are biomarkers of inflammation. They can be used to determine the relapse risk in patients with juvenile idiopathic arthritis (JIA) after stopping anti-inflammatory treatment. In this study we tested the performance of different enzyme-linked immunosorbent assays (ELISAs), in order to validate systems available for routine use. Methods: MRP8/14 and S100A12 serum concentrations of 188 JIA patients in remission were analysed. Commercially available test systems were compared to experimental ELISAs established in-house. The ability of the assays to identify JIA patients at risk for relapse was analysed. Results: For MRP8/14, PhiCal® Calprotectin and Bühlmann MRP8/14 Calprotectin ELISAs revealed hazard ratios of 2.3 and 2.1, respectively. For S100A12 CircuLex™ S100A12/EN-RAGE ELISA revealed a hazard ratio of 3.1. The commercial assays allowed a JIA relapse-prediction that was at least comparable to the experimental ELISAs. Conclusion: For the prediction of JIA relapse after stopping medication, the biomarkers MRP8/14 and S100A12 can be determined by using assays that are available for routine use. The tested commercial MRP8/14 and S100A12 ELISAs showed a performance comparable to well-established experimental ELISA protocols when assay-specific cut-offs for the indication of relapse prediction are thoroughly applied. © 2013 American College of Rheumatology.
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