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Biomedical subjects

W Jung

Publications and source records attributed to W Jung.

At least 19 recordsLinked to original sources

Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets. Report of the BIOMED-2 Concerted Action BHM4-CT98-3936.

Polymerase chain reaction (PCR) assessment of clonal immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements is an important diagnostic tool in mature B-cell neoplasms. However, lack of standardized PCR protocols resulting in a high level of false negativity has hampered comparability of data in previous clonality studies. In order to address these problems, 22 European laboratories investigated the Ig/TCR rearrangement patterns as well as t(14;18) and t(11;14) translocations of 369 B-cell malignancies belonging to five WHO-defined entities using the standardized BIOMED-2 multiplex PCR tubes accompanied by international pathology panel review. B-cell clonality was detected by combined use of the IGH and IGK multiplex PCR assays in all 260 definitive cases of B-cell chronic lymphocytic leukemia (n=56), mantle cell lymphoma (n=54), marginal zone lymphoma (n=41) and follicular lymphoma (n=109). Two of 109 cases of diffuse large B-cell lymphoma showed no detectable clonal marker. The use of these techniques to assign cell lineage should be treated with caution as additional clonal TCR gene rearrangements were frequently detected in all disease categories. Our study indicates that the BIOMED-2 multiplex PCR assays provide a powerful strategy for clonality assessment in B-cell malignancies resulting in high Ig clonality detection rates particularly when IGH and IGK strategies are combined.

Chromosomes, Human, Pair 11↗

Atrial arrhythmias after cardiac surgery in patients with diabetes mellitus.

BACKGROUND: Postoperative atrial fibrillation (AF) is a common complication of cardiac surgery and has been associated with increased incidence of other complications and increased hospital length of stay (LOS). Prevention of AF is a reasonable clinical goal, and, consequently, many randomized trials have evaluated the effectiveness of pharmacological and non-pharmacological interventions for prevention of AF. To better understand the role of various prophylactic therapies against postoperative AF, a systematic review of evidence from randomized trials was performed. METHODS: MEDLINE search of English-language reports published between 1966 and July 2005 and a search of references of relevant papers were conducted. Clinical studies on AF after cardiac surgery were selected for this analysis. Relevant clinical information was extracted from selected articles. RESULTS: Postoperative AF is associated with increased morbidity and mortality and longer, more expensive hospital stays. Prophylactic use of beta-adrenergic blockers reduces the incidence of postoperative AF and should be administered before and after cardiac surgery to all patients without contraindication. Prophylactic amiodarone and atrial overdrive pacing should be considered in patients at high risk for postoperative AF (for example, patients with previous AF or mitral valve surgery). For patients who develop AF after cardiac surgery, a strategy of rhythm management or rate management should be selected. For patients who are hemodynamically unstable or highly symptomatic or who have a contraindication to anticoagulation, rhythm management with electrical cardioversion, amiodarone, or both is preferred. Treatment of the remaining patients should focus on rate control because most will spontaneously revert to sinus rhythm within 6 weeks after discharge. All patients with AF persisting for more than 24 to 48 hours and without contraindication should receive anticoagulation. CONCLUSIONS: AF frequently complicates cardiac surgery. Many cases can be prevented with appropriate prophylactic therapy. A strategy of rhythm management for symptomatic patients and rate management for all other patients usually results in reversion to sinus rhythm within 6 weeks of discharge.

Adrenergic beta-Antagonists↗

Resistance against natural killer cell cytotoxicity: analysis of mechanisms.

Target cell resistance against natural killer (NK) cell-mediated cytotoxicity obstructs NK cell-based immunotherapy of leukaemia. Several mechanisms of resistance have been described. Because of lack of simple assays for analysing these mechanisms, their relative impact on a given effector-target pair is mostly unknown. We here analysed the combination of the Granzyme B (GrB) enzyme-linked immunospot assay (ELISPOT) for the assessment of NK cell reactivity and cytotoxicity assays to estimate target cell escape mechanisms. Target cell recognition failure leads to negative GrB ELISPOT results, whereas target cell resistance shows positive GrB ELISPOT results in the absence of cytotoxicity. We confronted NK cells with the sensitive target cell line K562, and with the resistant cell lines ML2, SupB15 and Raji. ML2 cells sufficiently activated GrB-release whilst being resistant against cytotoxic granules of NK cells. Partial resistance of Raji results from the interaction of HLA class I with inhibitory killer immunglobulin-like receptors (KIR) on the NK cells. Failure of target recognition by HLA class I-KIR interaction, lacking ligands to stimulatory NK cell receptors and partial resistance to cytotoxic granules all contributed to resistance of SupB15. In conclusion, revealing the mechanisms of resistance against NK cell-mediated cytotoxicity may allow improving the results of NK-based immunotherapy.

Cell Line, Tumor↗

Vascularization of liver tumors - preliminary results with Coded Harmonic Angio (CHA), phase inversion imaging, 3D power Doppler and contrast medium-enhanced B-flow with second generation contrast agent (Optison).

PURPOSE: To investigate the dynamic value of contrast medium-enhanced ultrasonography with Optison for appraisal of the vascularization of hepatic tumors using harmonic imaging, 3D-/power Doppler and B-flow. MATERIALS/METHODS: 60 patients with a mean age of 56 years (range 35-76 years) with 93 liver tumors, including histopathologically proven hepatocellular carcinoma (HCC) [15 cases with 20 lesions], liver metastases of colorectal tumors [17 cases with 33 lesions], metastases of breast cancer [10 cases with 21 lesions] and hemangiomas [10 cases with 19 lesions] were prospectively investigated by means of multislice CT as well as native and contrast medium-enhanced ultrasound using a multifrequency transducer (2.5-4 MHz, Logig 9, GE). B scan was performed with additional color and power Doppler, followed by a bolus injection of 0.5 ml Optison. Tumor vascularization was evaluated with coded harmonic angio (CHA), pulse inversion imaging with power Doppler, 3D power Doppler and in the late phase (>5 min) with B-flow. In 15 cases with HCC, i.a. DSA was performed in addition. The results were also correlated with MRT and histological findings. RESULTS: Compared to spiral-CT/MRT, only 72/93 (77%) of the lesions could be detected in the B scan, 75/93 (81%) with CHA and 93/93 (100%) in the pulse inversion mode. Tumor vascularization was detectable in 43/93 (46%) of lesions with native power Doppler, in 75/93 (81%) of lesions after administering contrast medium in the CHA mode, in 81/93 (87%) of lesions in the pulse inversion mode with power Doppler and in 77/93 (83%) of lesions with contrast-enhanced B-flow. Early arterial and capillary perfusion was best detected with CHA, particularly in 20/20 (100%) of the HCC lesions, allowing a 3D reconstruction. 3D power Doppler was especially useful in investigating the tumor margins. Up to 20 min after contrast medium injection, B-flow was capable of detecting increased metastatic tumor vascularization in 42/54 (78%) of cases and intratumoral perfusion in 17/20 (85%) of HCC cases. All 19 hemangiomas were correctly classified by phase inversion imaging. CONCLUSIONS: Contrast medium-enhanced ultrasound investigation of liver tumors with Optison allowed reliable detection of tumor foci and, in most cases, appraisal of tumor vascularization. The time available for evaluation of tumor margin vascularization was substantially longer in B-flow.

Adult↗

Spin-dependent scattering in multilayered magnetic rings.

Narrow mesoscopic NiFe/Cu/Co elliptical rings exhibit room-temperature giant magnetoresistance with distinct resistance levels corresponding to three different micromagnetic states. The highest and lowest resistance states of the multilayer rings correspond to the Co layer being in a bidomain state, antiparallel or parallel, respectively, to the NiFe, while the intermediate resistance corresponds to the Co layer being in a vortex state. Micromagnetic simulations suggest that the behavior of these rings is dominated by magnetostatic interactions between the domain walls in the Co and NiFe layers. Additional magnetization states in the NiFe at low applied fields can account for the minor loop behavior.

Journal Article↗

[Home Monitoring with implantable ICD--a diagnostic innovation?].

In recent years the rate of ICD implantation has grown substantially after the results of primary and secondary prevention trails have shown significant improvement in mortality and morbidity. However, the increasing number of patients with ICD indication leaves the implanting centres with large logistic problems, esp. with the number of follow-up visits. To further ensure high quality standard in therapy management new follow up routines have to be considered. Possible help may come with new methods of telecardiology, which are presently being introduced into clinical practice. Those systems differ in the way that they are capable to substitute a routine follow up and/ or deliver continuous diagnostic and device status information. Maybe the most promising solution is Home Monitoring in which the implant sends automatically daily messages with regard to therapy and ICD/CRT status without any cooperation of the patient. Interaction of the physician can be triggered by patient individual event filter. By utilizing this features in combination with event related IEGM Online Data physician are able to guide patients more effectively.

Defibrillators, Implantable↗

Two-dimensional and 3-dimensional optical coherence tomographic imaging of the airway, lung, and pleura.

BACKGROUND: Methods for obtaining real-time in vivo histologic resolution by means of noninvasive endoscopic optical imaging would be a major advance for thoracic surgical diagnostics and treatment. Optical coherence tomography is a rapidly evolving technology based on near-infrared interferometry that might provide these capabilities. The purpose of this study is to investigate the feasibility of real-time 2- and 3-dimensional optical coherence tomographic imaging of airway, pleural, and subpleural lung tissues in normal, inflammatory, and malignant animal models and patients with known or suspected airway malignancy. METHODS: Freshly excised lungs and pleural tissue obtained from rabbits with inhalation lung injury and induced empyema, metastatic sarcomas, and pleural sarcomas and from patients with airway disease were imaged by using 2- and 3-dimensional optical coherence tomography with a prototype superluminescent diode optical coherence tomographic system constructed in our laboratory. Lungs and pleural tissue were subsequently processed for standard hematoxylin and eosin histology for comparison with optical coherence tomography. RESULTS: Optical coherence tomographic imaging achieved an ex vivo resolution of 10 microm and an in vivo resolution of about 30 microm with a depth penetration of 1 to 2 mm with 2- and 3- dimensional reconstruction capabilities. Tumors as small as 500 microm were detectable with optical coherence tomography. The acquired images closely matched histologic images, demonstrating details at the level of mucosal layers, glands, alveoli, and respiratory bronchioles. CONCLUSIONS: Optical coherence tomography with near-infrared interferometric methods enables near real-time in vivo near-histologic resolution optical imaging. With further advances, optical coherence tomography has the potential for real-time accurate and early pleural and subpleural diagnostics by using small-diameter flexible fiberoptic endoscopic probes for a wide range of thoracic surgical applications.

Animals↗

The isolated working heart model in infarcted rat hearts.

Congestive heart failure (CHF) is one of the most common causes of death in western countries. The aim of this study was to establish and validate the working heart model in rat hearts with CHF. In the rat model the animals show parameters and symptoms that can be extrapolated to the clinical situation of patients with end-stage heart failure. The focus of attention was the evaluation of cardiodynamics (e.g.contractility) in the isolated 'working heart' model. The geometric properties of the left ventricle were measured by planimetry (stereology). Formulae available in the past for determining certain parameters in the working heart model (e.g.external heart work) have to be fitted to the circumstances of the infarcted rat hearts with its different organ properties.CHF was induced in Wistar Kyoto (WKY/NHsd) and spontaneously hypertensive rats (SHR/NHsd) by creating a permanent (8 week) occlusion of the left coronary artery, 2 mm distal to the origin from the aorta, by a modified technique (Itter et al. 2004). This resulted in a large infarction of the free left ventricular wall. We were able to establish and adapt a new and predictive working heart model in spontaneously hypertensive rat hearts with myocardial infarction (MI) 8-12 weeks after coronary artery ligation. At this stage the WKY rat did not show any symptoms of CHF. The SHR rat represented characteristic parameters and symptoms that could be extrapolated to the clinical situation of patients with end-stage heart failure (NYHA III-IV). Upon inspection, severe clinical symptoms of CHF such as dyspnoea, subcutaneous oedema, palebluish limbs and impaired motion were prominent. On necropsy the SHR showed lung oedema, hydrothorax, large dilated left and right ventricular chambers and hypertrophy of the septum. In the working heart model the infarcted animals showed reduced heart power, diminished contractility and enhanced heart work, much more so in the SHR/NHsd than in the Wistar Kyoto rat (WKY/NHsd). The aim for the future is to find a causal therapy of heart failure treatment. At present, only palliative therapy is possible for patients with heart failure. For this reason the working heart model in CHF rat hearts should provide a valuable method for early testing of new therapeutic approaches for patients with CHF.

Animals↗

A model of chronic heart failure in spontaneous hypertensive rats (SHR).

Common models of chronic heart failure (CHF) do not always result in parameters and symptoms that can be extrapolated to the clinical situation of patients with end-stage heart failure. The aim of this study was to establish and validate a new model of CHF in the rat. CHF was induced in Wistar Kyoto (WKY/NHsd) and spontaneously hypertensive (SHR/NHsd) rats by creating a permanent (8-week) occlusion of the left coronary artery 2 mm distal to the origin from the aorta by a modified technique. This resulted in a large infarction of the free left ventricular wall. The focus of attention was the validation of the geometric properties of the left ventricle and its contractility. The validation of the geometric properties of the left ventricle was done by a non-invasive magnetic resonance imaging (MRI) technique and by planimetry (stereology). Cardiodynamics (e.g. contractility) were evaluated in the isolated 'working heart' model. We were able to establish a new and predictive model of heart failure in the spontaneously hypertensive rat 8 weeks after coronary artery ligation. At this time point, the WKY rat did not show any symptoms of CHF. The model represents characteristic parameters and symptoms that can be extrapolated to the clinical situation of patients with end-stage heart failure (NYHA III-IV). Upon inspection, severe clinical symptoms of congestive heart failure were prominent, such as dyspnoea, subcutaneous oedema, pale-bluish limbs and impaired motion. Non-invasive sequential measurements by NMR techniques showed lung oedema, hydrothorax, large dilated left and right ventricular chambers and hypertrophy of the septum. The infarcted animals showed a reduced heart power, diminished contractility and enhanced heart work, much more so in the SHR/NHsd rat than in the WKY/NHsd rat. Furthermore the infarcted animals showed enhanced levels of hydroxyproline/proline ratios, again much more so in the SHR/NHsd rat than in the WKY/NHsd rat.

Animals↗

[Cardiac resynchronization therapy by biventricular pacing. How many patients with left ventricular dysfunction are eligible?].

BACKGROUND AND OBJECTIVE: Cardiac resynchronization therapy by multisite biventricular pacing presents an additive therapeutic option in the treatment of severe congestive heart failure. The objective of the study was to evaluate how many patients with left ventricular dysfunction may potentially benefit from this therapy. METHODS: A total of 975 patients were screened for the prevalence of left ventricular dysfunction. Patients with a left ventricular ejection fraction (LVEF) <45 % were included into the investigation. Potential benefit of biventricular pacing was presumed in the presence of: LVEF < 35 %, severe heart failure (NHYA class III or IV), intrinsic left bundle branch block pattern with QRS interval > 150 ms and the absence of atrial fibrillation in the last 3 months before study inclusion. RESULTS: In 203 patients (168 male, 35 female, mean age: 64 +/- 11) an LVEF <45 % was found. A total of 12 of these patients (6 %) or 12 of 113 patients (11 %) with an LVEF <35 % were identified as appropiate candidates for biventricular resynchronization therapy. CONCLUSIONS: Cardiac biventricular pacing currently serves as a therapeutic option for a relatively small subgroup of patients with left ventricular dysfunction. Focusing on estimations that the incidence of heart failure in Germany amounts to more than 100.000 cases per year our results suggest that after all more than 6.000 patients per year may potentially benefit from electric resynchronization therapy. This number may increase substantially if prospective studies can prove that patients with heart failure and atrial fibrillation or left ventricular conduction delay due to univentricular pacing also benefit from cardiac resynchronization therapy.

Aged↗

Less intense conditioning with fludarabine, cyclophosphamide, idarubicin and etoposide (FCIE) followed by allogeneic unselected peripheral blood stem cell transplantation in elderly patients with leukemia.

The objective of this study was to assess toxicity and feasibility of achieving engraftment of allogeneic blood progenitor cells following nonmyeloablative conditioning according to the FCIE protocol (fludarabine 25 mg/m(2)/day, days -7 to -3; cyclophosphamide 200 mg/m(2)/day, days -7 to -3; idarubicin 12 mg/m(2)/day, days -7 to -5; etoposide 250 mg/m(2)/day, days -4 to -3) in elderly patients with leukemia. Eleven patients were included in the study: six patients with acute myeloid leukemia (AML) in complete remission (CR); three patients with refractory or relapsed AML; one patient with chronic myeloid leukemia; one patient with acute lymphoblastic leukemia. The median age of the patients was 62 years. All patients received blood progenitor cells from an HLA-identical sibling with 8.8 x 10(6) CD34(+) cells/kg (median; range 4.7 to 26.2 x 10(6)/kg) and 5.5 x 10(8) CD3(+)cells/kg (median; range 4.5 to 7.9 x 10(8)/kg). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and three courses of methotrexate. The median duration of white blood cell counts <1 x 10(9)/l was 17 days and of platelet counts <50 x 10(9)/l 20 days. In two patients acute GVHD grade I occurred. Nine of 10 patients analyzed developed mixed chimerism. Of seven patients transplanted in CR, three remained in CR 19 to 31 months after transplantation. Three patients with refractory leukemia did not achieve CR, while the patient with relapsed AML achieved a 3rd CR. After a median follow-up time of 22 months, chronic GVHD was mild and limited. The data from this pilot study in elderly patients with leukemia show that the combination of primarily immunosuppressive (FC) and antileukemic (IE) drugs for nonmyeloablative conditioning has moderate nonhematological toxicity and allows engraftment of allogeneic blood progenitor cells.

Adult↗

A novel class of highly potent, selective, and non-peptidic inhibitor of Ras farnesyltransferase (FTase).

Design, synthesis and structure-activity relationship of a class of aryl pyrroles as farnesyltransferase inhibitors are described. In vitro and in vivo evaluation of a panel of these inhibitors led to identification of 2 (LB42908) as a highly potent (IC(50)=0.9 nM against H-Ras and 2.4 nM against K-Ras) antitumor agent that is currently undergoing preclinical studies.

Alkyl and Aryl Transferases↗