PubMed Health⌕ Search

Biomedical subjects

T Pabst

Publications and source records attributed to T Pabst.

At least 19 recordsLinked to original sources
PubMed2006

Mutations of the transcription factor PU.1 are not associated with acute lymphoblastic leukaemia.

The transcription factor PU.1 plays a crucial role during normal haematopoiesis in both myeloid cells and B-lymphocytes. Mice with a disruption in both alleles of the PU.1 locus were found to lack macrophages and B cells and had delayed appearance of neutrophils. In addition, critical decrease of PU.1 expression is sufficient to cause acute myeloid leukaemia (AML) and lymphomas in mice. Recently, we reported that heterozygous mutations in the PU.1 gene are present in some patients with AML. Thus, we hypothesised that PU.1 mutations might also contribute to the development of acute leukaemias of the B-cell lineage. Here, we screened 62 patients with B-cell acute lymphoblastic leukaemia (B-ALL) at diagnosis for genomic mutations by direct sequencing of all five exons of the PU.1 gene. We found no genomic alteration of the PU.1 gene suggesting that PU.1 mutations are not likely to be common in B-ALL.

Adolescent↗
PubMed2004

Implementation of the JACIE standards for a haematopoietic progenitor cell transplantation programme: a cost analysis.

The purpose of the present project was to analyse the costs incurred by the implementation of JACIE standards at a University Hospital with 1000 beds, performing some 40 autologous transplants per year. The cost analysis was performed on the basis of a prospective assessment of the time spent by all staff members involved with the implementation over a 14-month period of the quality management system (QMS) required by the JACIE standards. Two physicians worked on JACIE Section A (management=82 h), one physician and two nurses for section Ba (clinical unit adults=125.75 h), two physicians and three nurses for section Bp (clinical unit paediatrics=206 h), one physician, two nurses and one technician for section C (progenitor cell collection facility=105.75 h), and one physician and two technicians for section D (progenitor cell processing facility=426 h). The total time spent on the project amounted to 945.5 h with a total salary cost of \[euro]150 000. We concluded that implementation of the JACIE standards was accomplished within a 14-month period with a financial impact of approximately \[euro]150 000. The impact on quality parameters (eg clinical and laboratory end points, side effects) on HPC transplantation will be assessed in a second report after the first year of practical implementation.

Academic Medical Centers↗
PubMed2003

Detection of myocardial viability in acute infarction using contrast-enhanced (1)H magnetic resonance imaging.

BACKGROUND: Reperfusion strategies salvage myocardium at risk in acute myocardial infarction (MI). This clinical study was performed to determine whether areas without evidence of delayed MRI contrast enhancement in MI correspond to viability by means of percent systolic wall thickening (%SWT) and enddiastolic wall thickness (EDWT) in chronic infarction. METHODS: Twenty MRI studies were performed in ten patients within 6 days of MI and 3 months post-MI. On a segmental basis the percentage of viable myocardium as defined by contrast-enhanced MRI (no delayed MRI contrast enhancement) in acute MI was measured and was compared with %SWT and EDWT in chronic MI. RESULTS: Of the 1718 segments in acute infarction in which the percentage of viable myocardium was measured 1333 were found to be completely viable by means of contrast-enhanced MRI (no delayed MRI contrast enhancement). All of these segments revealed %SWT on day 90 post-MI, and 97% of segments were viable by means of an EDWT of more than 5.5 mm. In 85 segments the proportion of viable myocardium was 50-99% (mean 56+/-8%), with 92% segments found to be viable by means of %SWT and 92% by EDWT, and of 156 segments with viable myocardium between 1-49% (36+/-8%) 79% were found to be viable by means of %SWT and 82% by EDWT. Corresponding proportions of 144 segments with transmural delayed MRI contrast enhancement in acute MI were 45% and 17%. CONCLUSIONS: In acute reperfused MI viable myocardium as delineated by contrast-enhanced MRI is correlated with clinical parameters of viability. Delayed MRI contrast enhancement resolves nontransmural MI and may become a valuable clinical tool when planning revascularization procedures.

Adult↗
PubMed2003

[Primary diagnosis of coronary artery disease by MRI and CT].

Invasive coronary angiography is the gold standard for the primary diagnosis of coronary artery disease (CAD). At most, only every other examination leads to revascularization therapy. The other coronary angiographies could be replaced by non-invasive examinations. Diagnosing CAD by cardiac MRI and CT can utilize three different strategies: detection of coronary calcifications; imaging of coronary artery stenoses; and detection of restricted myocardial perfusion reserve. Applications are coronary calcification scoring by CT, coronary angiography by MRI or CT, stress cine MRI, and stress perfusion MRI. All these methods are currently used clinically because of their high negative predictive value, i.e., a normal result mostly rules out a hemodynamically significant CAD. For a reasonable implication in clinical practice, however, the pre-test probability must be considered to avoid needless examinations. High pre-test probability invariably demands invasive coronary angiography for planning or performing revascularization therapy. Intermediate pre-test probability, on the contrary, justifies to defer further imaging studies if MRI or CT is normal. Thus, adequate selection of patients for cardiac MRI and CT may reduce the number of invasive coronary angiographies in the future.

Adult↗
PubMed2002

High resolution contrast enhanced MR-angiography of the hand arteries: preliminary experiences.

BACKGROUND: In contrast to magnetic-resonance-angiography (MRA) of the peripheral vessels of the lower extremity, which gains more and more clinical application, MRA of the hand arteries is still exceptional. Our objective was to introduce an appropriate protocol for high resolution contrast-enhanced MR-angiography of the hand arteries. PATIENTS AND METHODS: 7 healthy volunteers and 13 patients with suspected hand artery obstructions underwent MRA. The examinations were performed on a 1.5 T system equipped with a flexible surface coil. A modified 3D-gradient-echo sequence was used. Criteria for image analysis were the overall image quality, vessel visibility and the timing of the contrast material bolus. RESULTS: In the volunteer group delineation of the superficial or deep palmar arch, common palmar digital arteries and of the proximal and middle segments of the digital arteries was possible. No pathologic findings were seen in the volunteer group. In 10 patients MRA revealed pathologic findings. In 9 examinations bolus-timing was correct, 7 examinations showed incomplete arterial enhancement, 4 examinations showed venous overlay. CONCLUSIONS: Contrast enhanced MR-angiography of the hand arteries in the described technique is a promising method. Compared to intraarterial digital subtraction angiography (IA-DSA) MRA still has limitations concerning spatial and temporal resolution. For clinical evaluation comparative studies with IA-DSA are necessary.

Adult↗
PubMed2002

[Time-resolved MR angiography of the renal artery: morphology and perfusion].

PURPOSE: To prove the hypothesis that renal artery stenosis and changes in renal perfusion can be detected with contrast-enhanced time-resolved MR angiography in a single examination. MATERIAL AND METHODS: In 71 patients, 137 renal arteries and 14 accessory renal arteries were studied. The examinations were performed on a 1.5 T system. A T 1 -weighted gradient echo sequence with a temporal resolution of 7 s was used. Single dose of contrast material (0.1 mmol/kg Gd-DTPA) was injected with a power injector with a flow rate of 2 ml/s. Criterion for the assessment of renal perfusion was the slope ratio of the signal intensity time curve in both kidneys. RESULTS: Forty renal artery stenoses and one occlusion of a renal artery were detected. In 48 kidneys (35 %) segmental arteries were evaluated. The accuracy of the slope ratio (limit value 0.75) concerning the detection of unilateral renal artery stenosis was 92.6 % (sensitivity 75 %, specificity 95.7 %). CONCLUSION: Time-resolved MR angiography can detect changes in renal perfusion in patients with unilateral renal artery stenosis.

Adolescent↗
PubMed2002

[Interindividual-variability of the analysis of regional myocardial wall function after myocardial infarction and revascularization].

PURPOSE: The gold standard for diagnosis myocardial viability is the functional recovery after revascularization. Aim of the study was to compare (1) qualitative analysis and (2) quantitative wall thickening by cine MRI and (3) circumferential shortening by tagged MRI the analysis of regional wall function of an infarcted area before and after revascularization. MATERIAL AND METHODS: Ten patients (age 60 +/- 11 years) with infarct-associated regional left ventricular wall motion abnormalities were examined by cine and tagged MRI on average two weeks after the myocardial infarction and re-examined three months after revascularization. Eight healthy volunteers served as a control for tagged MRI. Interobserver-variabilities of two observers were calculated using the kappa-statistics for grading of wall motion abnormalities as well as for detection of functional recovery by qualitative analysis, measurement of wall thickening of cine MRI, and measurement of circumferential shortening by tagged MRI, respectively. RESULTS: Grading of wall motion abnormalities revealed interobserver-variabilities of the study and control group of kappa = 0.8 and kappa = 0.84, kappa = 0.02 and kappa = 0.5, and kappa = 0.1 and kappa = 0.17 for qualitative analysis, wall thickening analysis and measurement of circumferential shortening, respectively. The interobserver-variability for the definition of wall motion recovery was kappa = 0.8 for all three methods. CONCLUSION: Qualitative analysis of wall motion abnormalities has the lowest interobserver-variability for the grading of wall motion abnormalities. The interobserver-variabilities of qualitative and quantitative analysis are comparable for the diagnosis of regional wall motion recovery. Thus, qualitative analysis of cine MRI can be used for grading regional wall motion in clinical studies.

Aged↗
PubMed2001

Optimization of ECG-triggered 3D (23)Na MRI of the human heart.

(23)Na MRI may allow distinction of normal and ischemically injured myocardium. The aim of this study was to optimize (23)Na MRI of the human heart by improvement of spatial resolution and ECG-triggering and to measure the signal/noise of blood and myocardium and the myocardium/blood signal ratios in a volunteer study. A spoiled gradient echo sequence was developed on a 1.5T scanner equipped with a (23)Na heart surface coil. 3D short axis ECG-triggered (23)Na MRI was performed in 10 healthy subjects. The signal/noise of myocardium and blood were 8.2 +/- 0.7 and 18.3 +/- 1.3, respectively, signal ratio myocardium/blood was 0.44 +/- 0.03. This value is in good agreement with the theoretical value of 0.45. ECG gated 3D (23)Na MRI of the human heart is feasible with sufficient spatial resolution and signal/noise ratio. Magn Reson Med 45:164-166, 2001.

Adult↗
PubMed2001

Time course of contrast enhancement patterns after Gd-BOPTA in correlation to myocardial infarction and viability: a feasibility study.

Our objective was to analyze contrast enhancement patterns (CEP) and their time course after myocardial infarction (MI) following injection of Gd-BOPTA in correlation with recovery of regional function. Seven patients with subacute MI (18 +/- nine days) were examined before, as well as three and six (n = six) months after, revascularization of the infarct-related artery. Regional wall motion abnormalities were assessed by cine-MRI, and repetitive images of one representative slice were acquired up to 45 minutes after 0.05 mmol/kg Gd-BOPTA using a T1-w TSE-sequence. Two patients showed mid-wall/subendocardial, one patient subendocardial enhancement of MI associated with mechanical improvement after revascularization. Three patients without improvement revealed a mid-wall hypoenhanced zone within the first five minutes after injection, which was unchanged at follow-up. One patient with partial functional improvement showed transmural enhancement and a mid-wall hypoenhanced zone in adjacent areas. With this feasibility study, we concluded that mid-wall and/or subendocardial enhancement after Gd-BOPTA was associated with viable myocardium, whereas detection of microvascular obstruction correlating with scar formation is suggested by mid-wall hypoenhancement within the first five minutes after injection.

Adult↗
PubMed2001

Advances in human cardiac 31P-MR spectroscopy: SLOOP and clinical applications.

Phosphorus magnetic resonance spectroscopy (31P-MRS) has revealed a lot about the biochemistry of physiological and pathological processes in the heart. Nevertheless, until today, cardiac 31P-MRS has not had any clinical impact, albeit some pioneering studies demonstrated that 31P-MRS can indeed provide diagnostic information. In this paper, the development of techniques for human cardiac 31P-MRS over the past decade is reviewed, and the requirements for a reliable clinical measurement protocol are discussed. Spatial localization with optimal pointspread function (SLOOP) is a new method to achieve spatial localization and absolute quantitation. Its properties are detailed, and preliminary findings in patients with dilated cardiomyopathy or myocardial infarction are presented.

Heart Diseases↗
PubMed2001

(31)P-MR Spectroscopy for the evaluation of energy metabolism in intact residual myocardium after acute myocardial infarction in humans.

OBJECTIVE: Experimental studies have demonstrated that acute myocardial infarction (MI) alters energy metabolism even in non-infarcted adjacent tissue. In patients with subacute MI, the influence of the regional ischemic insult on energy metabolism of intact septal myocardium was analyzed using 31P-Magnetic resonance spectroscopy (MRS). PATIENTS AND METHODS: In eight patients with wall motion abnormalities in the anterior wall 31P-spectra were obtained from non-infarcted adjacent septal myocardium, as well as infarcted anterior myocardium (voxel size 25 ccm each) 29+/-8 days after MI using a 3D-CSI technique. Additionally, cardiac function was analyzed using breath-hold cine MRI. MRI was repeated 6 months after revascularization to assess viability of infarcted segments. Eight age-matched healthy volunteers served as control group. RESULTS: According to follow-up MRI 4/8 patients showed regional wall motion recovery. Here, PCr/ATP-ratios were not significantly reduced in intact septal myocardium as well as infarcted anterior myocardium compared to healthy volunteers (1.28+/-0.10 and 1.14+/-0.09 vs. 1.45+/-0.29). No recovery of regional function was detected in 4/8 patients with-therefore-non-viable anterior myocardium. PCr/ATP-ratios were significantly reduced in intact and infarcted myocardium compared with healthy volunteers as well as to patients with wall motion recovery (0.77+/-0.17 and 0.49+/-0.23; P<0.05). DISCUSSION: These preliminary results indicate that energy metabolism is reduced in patients with persisting wall motion abnormalities after myocardial infarction and revascularization in ischemically injured as well as in adjacent non-injured myocardium.

Aged↗
PubMed2001

Breath-hold 3D MR coronary angiography with a new intravascular contrast agent (feruglose)--first clinical experiences.

Demonstration of the initial results of breath-hold 3D MR coronary angiography with patients using a new intravascular contrast agent (feruglose). Contrast-enhanced 3D MR-coronary angiography was performed in 5 patients with coronary artery disease after administration of feruglose in three different doses (0.5 (n = 3), 2, 5 mg Fe/kg body weight for each patient). MR coronary angiography was performed with an ECG-triggered 3D-FLASH-sequence during breath-hold at 1.5 T (TR 6.8 ms, TE 2.5 ms, flip-angle 30 degrees ). To reduce data acquisition time, only the two anterior elements of the phased-array body coil were activated. The data acquisition window within the cardiac cycle ranged between 217-326 ms depending on the matrix. Signal-to-noise (SNR) and contrast-to-noise ratios (CNR) of the coronary arteries were analyzed, and the results for the detection of coronary artery stenoses were compared with those obtained by conventional coronary angiography. SNR and CNR revealed an improved image quality at a dose of 2 mg Fe/kg compared with the lower dose, but no further improvement was obtained by rising the dose to 5 mg Fe/kg. Except for the left circumflex artery of one patient, at minimum the proximal parts of all four main coronary arteries could be imaged for all patients. Within the visible parts of the coronary arteries, six of eight significant coronary stenoses were identified correctly. Imaging of the proximal parts of the coronary arteries including detection of stenoses is possible during breath-hold using an intravascular contrast agent.

Aged↗
PubMed2001

Dominant-negative mutations of CEBPA, encoding CCAAT/enhancer binding protein-alpha (C/EBPalpha), in acute myeloid leukemia.

The transcription factor C/EBPalpha (for CCAAT/enhancer binding protein-alpha; encoded by the gene CEBPA) is crucial for the differentiation of granulocytes. Conditional expression of C/EBPalpha triggers neutrophilic differentiation, and no mature granulocytes are observed in Cebpa-mutant mice. Here we identify heterozygous mutations in CEBPA in ten patients with acute myeloid leukemia (AML). We found that five mutations in the amino terminus truncate the full-length protein, but did not affect a 30-kD protein initiated further downstream. The mutant proteins block wild-type C/EBPalpha DNA binding and transactivation of granulocyte target genes in a dominant-negative manner, and fails to induce granulocytic differentiation. Ours is the first report of CEBPA mutations in human neoplasia, and such mutations are likely to induce the differentiation block found in AML.

Base Sequence↗
PubMed2001

AML1-ETO downregulates the granulocytic differentiation factor C/EBPalpha in t(8;21) myeloid leukemia.

The transcription factor CCAAT/enhancer binding protein alpha, or C/EBPalpha, encoded by the CEBPA gene, is crucial for the differentiation of granulocytes. Conditional expression of C/EBPalpha triggers neutrophilic differentiation, and Cebpa knockout mice exhibit an early block in maturation. Dominant-negative mutations of CEBPA have been found in some patients with acute myeloid leukemia (AML), but not in AML with the t(8;21) translocation which gives rise to the fusion gene RUNX1-CBF2T1 (also known as AML1-ETO) encoding the AML1-ETO fusion protein. RUNX1-CBF2T1 positive-AML blasts had eight-fold lower CEBPA RNA levels and undetectable C/EBPalpha protein levels compared with other subgroups of AML patients. Conditional expression of RUNX1-CBF2T1 in U937 cells downregulated CEBPA mRNA, protein and DNA binding activity. AML1-ETO appears to suppress C/EBPalpha expression indirectly by inhibiting positive autoregulation of the CEBPA promoter. Conditional expression of C/EBPalpha in AML1-ETO-positive Kasumi-1 cells results in neutrophilic differentiation. We suggest that restoring C/EBPalpha expression will have therapeutic implications in RUNX1-CBF2T1-positive leukemias.

Animals↗
PubMed2001

Cardiac metabolism and function in patients with multiple sclerosis: a combined 31P-MR-spectroscopy and MRI study.

OBJECTIVE: Involvement of the autonomic system in multiple sclerosis (MS) may concur with dysfunction of the cardiovascular system. The introduction of potentially cardiotoxic immunosuppressive drugs like Mitoxantrone into the treatment of MS warrants proper assessment of preexisting heart disease. However, systematic analyses of functional and metabolic derangements in MS are missing. Using quantitative 31P-MR-spectroscopy (MRS) and MR-imaging (MRI) metabolic and functional parameters were analyzed in patients with MS in comparison to healthy volunteers. SUBJECTS/METHODS: 14/15 patients with MS could be included in the study, as the MRS examination of one patient had to be excluded from analysis due to movement during the examination. Using chemical shift imaging (CSI) and AMARES, phosphocreatine (PCr) to adenosine triphosphate (ATP) ratios, characterizing myocardial high-energy phosphate metabolism, were determined. Additionally, absolute concentrations of PCr and ATP were calculated by SLOOP (Spatial Localization with Optimal Pointspread Function). Analysis of functional changes was performed by Cine-MRI. 14 healthy volunteers matched for age and gender served as control. RESULTS: A significant decrease of absolute PCr concentration was observed in patients with MS compared to matched volunteers (p < 0.05), whereas ATP concentrations showed no significant changes (p = 0.27). Metabolite ratios calculated by SLOOP or AMARES showed a tendency to be reduced in patients, however, did not reach significance (p = 0.08, SLOOP; p = 0.47, AMARES). Using volunteers' mean values +/- 2 x SD as cut off value revealed PCr changes in 5 of 14 patients, whereas only 2 also had pathologic PCr/ATP ratios. Functional analysis by MRI depicted depressed left ventricular ejection fraction in 4 patients. CONCLUSIONS: The reduction in cardiac high-energy phosphates in some patients with MS points to a subclinical involvement of the heart. This may be important for treatment with potentially cardiotoxic drugs. Longitudinal studies are need to understand the clinical relevance of our findings.

Adenosine Triphosphate↗
PubMed2001

[31P-MR spectroscopy of all regions of the human heart at 1.5 T with acquisition-weighted chemical shift imaging].

AIM: Aim of this study was to show whether or not acquisition-weighted chemical shift imaging (AW-CSI) allows the determination of PCr and ATP in the lateral and posterior wall of the human heart at 1.5 T. METHODS: 12 healthy volunteers were examined using a conventional chemical shift imaging (CSI) and an AW-CSI. The sequences differed only in the number of repetitions for each point in k space. A hanning function was used as filter function leading to 7 repetitions in the center of the k space and 0 in the corners. Thus, AW-CSI had the same resolution as the CSI sequence. The results for both sequences were analyzed using identically positioned voxels in the septal, anterior, lateral and posterior wall. RESULTS: The determined averaged AW-CSI signal to noise ratios were higher for PCr by a factor of 1.3 and for ATP by 1.4 than those of CSI. The PCr/ATP ratios were higher by a factor of 1.2 - 1.3 and showed a smaller standard deviation in all locations for AW-CSI. The mean PCr/ATP ratios determined by AW-CSI of septal, lateral and posterior wall were almost identical (1.72 - 1.76), while it was higher in the anterior wall (1.9). CONCLUSIONS: The reduced contamination in AW-CSI improves the signal to noise ratio and the determination of the PCr/ATP ratio in cardiac (31)P spectroscopy compared to CSI with the same resolution. The results in volunteers indicate that AW-CSI renders (31)P spectroscopy of the lateral and posterior wall of the human heart feasible for patient studies at 1.5 T.

Adenosine Triphosphate↗