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Biomedical subjects

E Klotz

Publications and source records attributed to E Klotz.

At least 19 recordsLinked to original sources
PubMed2002

Reproducibility of coronary calcium quantification in repeat examinations with retrospectively ECG-gated multisection spiral CT.

High reproducibility is a key requirement for coronary calcium scoring in follow-up examinations. We investigated the inter-examination reproducibility of calcium scoring with retrospectively ECG-gated multisection spiral CT (MSCT). Fifty patients were examined twice with MSCT. Slices were reconstructed with retrospective ECG gating in the diastolic phase with 3-mm slice width and up to 125-ms temporal resolution. We calculated the Agatston score, calcium volume with and without isotropic interpolation, and calcium mass, and derived the mean and median variability. We investigated the change of variability with use of 3-mm non-overlapping and overlapping increments (2, 1.5, 1 mm). Use of overlapping increment results in considerably reduced interscan variability. We observed a minimum mean variability of 12% and a minimum median variability of 9% for the Agatston score. For volume and mass quantification we obtained a minimum mean variability of 7.5% and a minimum median variability of 5%. Multisection spiral CT enables coronary calcium quantification with high reproducibility in follow-up examinations mainly founded on image data with reduced partial-volume errors due to overlapping increment.

Adult↗
PubMed2002

[The value of multi-slice computed tomography for early diagnosis of focal cerebral ischemia].

The aim of this survey is the characterization of the present value of multi-slice computed tomography (MSCT) for the assessment of hyperacute cerebral ischemia based on our experience and a review of the literature. MSCT is compared with single-slice CT (SSCT) as to the diagnostic value of standard cranial CT, CT angiography (CTA) and perfusion CT. CTA obtained with MSCT surpasses CTA obtained with SSCT. For perfusion CT, the value added by MSCT is small. With regard to standard cranial CT, MSCT and SSCT are considered equivalent. CTA and perfusion CT should be used in patients with acute stroke if the indication for thrombolysis is entertained but diffusion and perfusion weighted MRI cannot be carried out. This applies to both SSCT and MSCT. If advanced MRI and advanced CT are available, MRI continues to be the preferred imaging modality.

Acute Disease↗
PubMed2001

Multislice CT imaging of pulmonary embolism.

In recent years CT has been established as the method of choice for the diagnosis of central pulmonary embolism (PE) to the level of the segmental arteries. The key advantage of CT over competing modalities is the reliable detection of relevant alternative or additional disease causing the patient's symptoms. Although the clinical relevance of isolated peripheral emboli remains unclear, the alleged poor sensitivity of CT for the detection of such small clots has to date prevented the acceptance of CT as the gold standard for diagnosing PE. With the advent of multislice CT we can now cover the entire chest of a patient with 1-mm slices within one breath-hold. In comparison with thicker sections, the detection rate of subsegmental emboli can be significantly increased with 1-mm slices. In addition, the interobserver correlation which can be achieved with 1-mm sections by far exceeds the reproducibility of competing modalities. Meanwhile use of multislice CT for a combined diagnosis of PE and deep venous thrombosis with the same modality appears to be clinically accepted. In the vast majority of patients who receive a combined thoracic and venous multislice CT examination the scan either confirms the suspected diagnosis or reveals relevant alternative or additional disease. The therapeutic regimen is usually chosen based on the functional effect of embolic vascular occlusion. With the advent of fast CT scanning techniques, also functional parameters of lung perfusion can be non-invasively assessed by CT imaging. These advantages let multislice CT appear as an attractive modality for a non-invasive, fast, accurate, and comprehensive diagnosis of PE, its causes, effects, and differential diagnoses.

Humans↗
PubMed2001

Multi-slice CT for visualization of pulmonary embolism using perfusion weighted color maps.

PURPOSE: The purpose of our preliminary study was to evaluate the feasibility of a new technique for the perfusion weighted color display of the density of lung parenchyma derived from multi-slice CT (MSCT) data sets of clinical routine examinations for visualization of pulmonary embolism (PE). MATERIALS AND METHODS: Imaging of patients with suspected PE was performed on a commercially available MSCT (Somatom Volume Zoom; Siemens, Forchheim, Germany) after intravenous application of 120 cc of contrast-medium using a power injector. Scan parameters were 140 kV and 100 mAs, using a thin collimation of 4 x 1 mm and a table speed of 7 mm (pitch: 1.75). Derived from thin collimation axial slices (slice thicknesseff. 1.25 mm, reconstruction increment 0.8 mm), a new image processing technique was deployed. Based on these source images, an automated 3D-segmentation of the lungs was performed followed by threshold based extraction of major airways and vascular structures. The filtered volume data were color encoded and finally overlayed onto the original CT images. This color encoded display of parenchymal density distribution of the lungs was shown in axial, coronal and sagittal plane orientation. In four patients with excluded PE as well as in two patients with proven PE this new technique was performed. RESULTS: In the four patients that were considered negative regarding PE on MSCT, lung densitometry showed a homogeneous distribution of color encoded densities without circumscribed decreased or increased areas, beside the usually present gravity-dependent gradient in ventro-dorsal direction. In the two patients with proven PE, low density values on perfusion weighted color maps were found distally to the occluded pulmonary arteries. CONCLUSIONS: Our initial experience indicates that lung densitometry with an optimized display of the density distribution within the lung parenchyma may provide additional information in patients with suspected or proven PE. However, a comparison with ventilation/perfusion scintigraphy and a larger number of patients are necessary for the full clinical evaluation of this new functional imaging methodology.

Aged↗
PubMed2001

Quantitative assessment of the ischemic brain by means of perfusion-related parameters derived from perfusion CT.

BACKGROUND AND PURPOSE: Besides the delineation of hypoperfused brain tissue, the characterization of ischemia with respect to severity is of major clinical relevance, because the degree of hypoperfusion is the most critical factor in determining whether an ischemic lesion becomes an infarct or represents viable brain tissue. CT perfusion imaging yields a set of perfusion related parameters which might be useful to describe the hemodynamic status of the ischemic brain. Our objective was to determine whether measurements of the relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), and relative time to peak (rTP) can be used to differentiate areas undergoing infarction from reversible ischemic tissue. METHODS: In 34 patients with acute hemispheric ischemic stroke <6 hours after onset, perfusion CT was used to calculate rCBF, rCBV, and rTP values from areas of ischemic cortical and subcortical gray matter. Results were obtained separately from areas of infarction and noninfarction, according to the findings on follow-up imaging studies. The efficiency of each parameter to predict tissue outcome was tested. RESULTS: There was a significant difference between infarct and peri-infarct tissue for both rCBF and rCBV but not for rTP. Threshold values of 0.48 and 0.60 for rCBF and rCBV, respectively, were found to discriminate best between areas of infarction and noninfarction, with the efficiency of the rCBV being slightly superior to that of rCBF. The prediction of tissue outcome could not be increased by using a combination of various perfusion parameters. CONCLUSIONS: The assessment of cerebral ischemia by means of perfusion parameters derived from perfusion CT provides valuable information to predict tissue outcome. Quantitative analyses of the severity of ischemic lesions should be implemented into the diagnostic management of stroke patients.

Aged↗
PubMed2000

[Cerebral perfusion CT: theoretical aspects, methodical implementation and clinical experience in the diagnosis of ischemic cerebral infarction].

Cerebral perfusion CT using dynamic CT after bolus injection of contrast has recently been introduced in the clinical management of stroke patients. Based on the indicator dilution principle various theoretical models can be formulated which all aim at the quantitative determination of cerebral blood flow (CBF). Our Perfusion CT approach is based on the "maximum slope" model and allows in addition to the calculation of CBF parameter images the display of cerebral blood volume (CBV) and "time to peak" as diagnostically meaningful parameters. This approach allows the detection of acute ischemia of the supratentorial brain with a sensitivity of 91% and has proven its value as a routine diagnostic tool for acute stroke. The combination of various functional maps provides excellent information regarding the type of ischemia. Although the direct assessment of ischemia using absolute CBF values is severely restricted by patient dependent systematic errors, the severity of ischemia may reliably be assessed by using relative CBF perfusion indices.

Acute Disease↗
PubMed2000

[CT perfusion imaging in acute ischemic cerebral infarct: comparison of cerebral perfusion maps and conventional CT findings].

PURPOSE: To evaluate the findings of acute brain ischemia on different functional maps of cerebral perfusion CT in stroke patients and to compare the results with early ischemic changes on conventional CT. METHODS: The baseline CT scans of 45 acute stroke patients were retrospectively evaluated with respect to early CT findings. For each patient the extent of cerebral ischemia as shown on the maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and "time to peak" (TP) was compared and the severity of ischemia was assigned to one of three levels based on the findings of the CBF image. RESULTS: In 75% of all patients conventional CT was performed within 2 hours from symptom onset. 29 of 45 patients showed early signs of ischemia on conventional CT, whereas perfusion CT revealed cerebral ischemia in all patients. Severe ischemia was found in approximately the same rate of incidence in patients with early CT changes (55.2%) and in those with normal findings (43.8%). If the perfusion impairment was judged as mild or moderate the extent of the hypoperfused area was significantly larger on the CBF and TP images than on the CBV map. This was significantly different in patients with severe hypoperfusion where a complete correspondence of the affected area between the three functional maps was found. DISCUSSION: The use of conventional CT for the assessment of stroke in the hyperacute phase is limited. Perfusion CT yields excellent information regarding the severity and extent of ischemia. The use of various perfusion maps helps to differentiate the core of infarction from the ischemic penumbra zone.

Acute Disease↗
PubMed2000

Dynamic CT perfusion imaging of acute stroke.

BACKGROUND AND PURPOSE: Because cerebral perfusion imaging for acute stroke is unavailable in most hospitals, we investigated the feasibility of a method of perfusion scanning that can be performed rapidly during standard cranial CT. Our aim was to identify the scanning parameters best suited to indicate tissue at risk and to measure a perfusion limit to predict infarction. METHODS: Seventy patients who had suffered stroke and had undergone cranial CT 0.5 to 12 hours (median, 3.75 hr) after the onset of symptoms participated in the study. While undergoing conventional CT, each patient received a bolus of iodinated contrast medium. Maps of time to peak (TTP), cerebral blood volume (CBV), and CBF were calculated from the resulting dynamically enhanced scans. These perfusion images were compared with follow-up CT scans or MR images showing the final infarctions. RESULTS: CBF maps predicted the extent of cerebral infarction with a sensitivity of 93% and a specificity of 98%. In contrast, CBV maps were less sensitive and TTP maps were less specific and also showed areas of collateral flow. Infarction occurred in all of the patients with CBF reduction of more than 70% and in half of the patients with CBF reduction of 40% to 70%. CONCLUSION: Dynamic CT perfusion imaging safely detects tissue at risk in cases of acute stroke and is a feasible method for any clinic with a third-generation CT scanner.

Acute Disease↗
PubMed1999

Perfusion measurements of the brain: using dynamic CT for the quantitative assessment of cerebral ischemia in acute stroke.

OBJECTIVE: Perfusion CT has been successfully used as a functional imaging technique for the differential diagnosis of patients with hyperacute stroke. We investigated to what extent this technique can also be used for the quantitative assessment of cerebral ischemia. METHODS AND MATERIAL: We studied linearity, spatial resolution and noise behaviour of cerebral blood flow (CBF) determination with computer simulations and phantom measurements. Statistical ROI based analysis of CBF images of a subset of 38 patients from a controlled clinical stroke study with currently more than 75 patients was done to check the power of relative cerebral blood flow (rCBF) values to predict definite infarction and ischemic penumbra. Classification was performed using follow-up CT and MR data. RESULTS: Absolute CBF values were systematically underestimated, the degree depended on the cardiac output of the patients. Phantom measurements and simulations indicated very good linearity allowing reliable calculation of rCBF values. Infarct and penumbra areas in 19 patients receiving standard heparin therapy had mean rCBF values of 0.19 and 0.62, respectively. The corresponding values for 19 patients receiving local intraarterial fibrinolysis were 0.18 and 0.57. The difference between infarct and penumbra values was highly significant (P < 0.0001) in both groups. No penumbra area was found with an rCBF value of less than 0.20. While in the heparin group only 25% of all areas with an rCBF between 0.20 and 0.35 survived, in the fibrinolytic group 61% of these areas could be saved (P < 0.05). CONCLUSION: Perfusion CT is a fast and practical technique for routine clinical application. It provides substantial and important additional information for the selection of the optimal treatment strategy for patients with hyperacute stroke. Relative values of cerebral blood flow discriminate very well between areas of reversible and irreversible ischemia; an rCBF value of 0.20 appears to be a definite lower limit for brain tissue to survive an ischemic injury.

Acute Disease↗
PubMed1998

Cis-acting sequences that affect somatic hypermutation of Ig genes.

We review our studies on the mechanism of somatic hypermutation of immunoglobulin genes. Most experiments were carried out using Ig transgenes. We showed in these experiments that all required cis-acting elements are present within the 10-16 kb of a transgene. Only the Ig variable region and its proximate flanks are mutated, not the constant region. Several Ig gene enhancers are permissive for somatic mutation. Association of the enhancer with its natural Ig promoter is not necessary. However, the mutation process seems specific for Ig genes. No mutations were found in housekeeping genes from cells with high levels of somatic hypermutation of their Ig genes. The Ig enhancers may provide the Ig gene specificity. An exception may be the BCL6 gene, which was mutated in human but not in mouse B cells. Transcription of a region is required for its mutability. When the transcriptional promoter located upstream of the variable region is duplicated upstream of the constant region, this region also becomes mutable. This suggests a model in which a mutator factor associates with the RNA polymerase at the promoter, travels with the polymerase during elongation, and causes mutations during polymerase pausing. The DNA repair systems, nucleotide excision repair and DNA mismatch repair, are not required. Our recent data with an artificial substrate of somatic mutation suggest that pausing may be due to secondary structure of the DNA or nascent RNA, and the specific mutations to preferences of the mutator factor.

Animals↗
PubMed1998

Perfusion CT of the brain: diagnostic approach for early detection of ischemic stroke.

PURPOSE: To determine the value of perfusion computed tomography (CT) in a clinical study of patients with stroke and compare the results with single photon emission CT (SPECT) findings. MATERIALS AND METHODS: Perfusion CT was performed within 6 hours of symptom onset in 32 patients with possible stroke. Cerebral blood volume (CBV), cerebral blood flow (CBF), and time to peak contrast material enhancement were calculated on the basis of the CT results. Cerebral SPECT was also performed in a subgroup of 18 patients. Perfusion CT and SPECT findings were compared in a lesion-by-lesion analysis. Perfusion CT results were compared with follow-up CT and magnetic resonance imaging findings. RESULTS: Areas of reduced CBF were detected with the aid of perfusion CT in 25 of 28 patients with a proved infarct (sensitivity, 89%). The results of the CBF maps corresponded well to SPECT findings in 13 (81%) of 16 patients, but ischemia was located outside the scanning level in the other three patients and was therefore missed. Perfusion CT revealed various changes in CBF, CBV, and time to peak enhancement in ischemic territories. CONCLUSION: Perfusion CT not only allows early detection of cerebral ischemia but also yields valuable information about the extent of perfusion disturbances.

Adult↗
PubMed1998

Immunoglobulin transgenes as targets for somatic hypermutation.

This review describes studies on somatic hypermutation of immunoglobulin genes that were started in the mid-80s in collaboration with Ralph Brinster. Almost all of the experiments were carried out using Ig transgenes as targets for the somatic mutation mechanism. Ig transgenes can be very good targets of somatic mutation, despite many different transgene integration sites. Thus, the required cis-acting elements must be present within the approximately 10 kb of the transgene. Only the Ig variable region and its proximate flanks are mutated, not the constant region in unmanipulated sequences. Several Ig gene enhancers are permissive for somatic mutation and they do not have to be associated with the Ig promoter they normally interact with. However, the mutation process does seem to be specific for Ig genes. No mutations were found in several housekeeping genes isolated from cells that had very high levels of somatic hypermutation of their Ig genes. This suggests that the Ig enhancers provide the lg gene specificity. An exception is the Bcl-6 gene, encoding a transcription factor, which was found to be mutated in normal human memory B cells. When the transcriptional promoter that is located upstream of the variable region is duplicated upstream of the constant region, this region is mutated as well. This suggests a transcription coupled model in which a mutator factor associates with the RNA polymerase at the initiation of transcription, travels with the polymerase during elongation, and causes mutations during polymerase pausing. Our recent data with an artificial substrate for somatic mutation suggest that the mutations are increased by increased stability of the secondary structures in the nascent RNA, and the specific nucleotides that are mutated are due to preferences of a mutator factor.

Animals↗
PubMed1996

The mechanism of somatic hypermutation studied with transgenic and transfected target genes.

Somatic hypermutation of Ig genes is beginning to be understood in molecular terms. Ig transgenes have served as model test genes and been shown to mutate, just as endogenous genes, with a peak of mutation over the VJ region and a sparing of the C region. The levels of somatic mutation appear to be related to the expression of the transgenes. DNA hypermethylation of modified Ig transgenes interferes with both expression and somatic hypermutation. Test substrates consisting of bacterial lacZ alpha or supFtRNA inserted within x transgenes were shown to be rescuable as expressible bacterial plasmids, but did not seem to be targeted. A synthetic sequence consisting of alternating restriction enzyme sites, that cannot be subject to methylation, was found to be a reliable transgenic substrate for easy assay of somatic mutation. The generation of a transgenic mouse with a x transgene in which the transcriptional promoter has been duplicated upstream of the C region has given new clues to the mutation mechanism. In this transgene, transcripts initiate from both the C region and the V region promoters, and both regions, but not the sequences between them, are hypermutated. These results suggest that somatic hypermutation is linked to the initiation of transcription. A model is proposed in which somatic mutation is dependent on transcription coupled DNA repair.

Animals↗
PubMed1992

N region diversity of a transgenic substrate in fetal and adult lymphoid cells.

The rearrangement of immunoglobulin (Ig) and T cell receptor (TCR) genes requires the activity of an as yet undefined V(D)J recombinase. One component of the recombinase appears to be a terminal transferase which may be involved in the addition of untemplated nucleotides (N regions) to the V(D)J joints. It has been observed that rearranged Ig and TCR genes isolated from fetal liver have few if any N regions, whereas in the adult mouse, these genes have a large number of untemplated nucleotides. The presence of N regions greatly alters the composition of the third hypervariable, complementarity determining region of the respective proteins, thus playing a major role in the conformation of the binding site. It was possible that, for functional reasons, N region-containing Ig and TCR genes were not permissible at the fetal stage of development. We have produced transgenic mice with a rearrangement test gene which, after V-J recombination, does not result in the production of functional Ig or TCR proteins. We report here that the rearrangement products have no N regions in fetal liver, but that the majority of joints in adult lymphoid tissues have N additions. The study is also an interesting demonstration of the randomness of rearrangements and the enormous variability that can be created from a single pair of V and J sequences.

Animals↗
PubMed1992

Rearrangement and expression of immunoglobulin genes in transgenic mice.

Transgenic mice are discussed which carry a rearrangement test transgene. The methylation status of the transgene varies, depending on the background mouse strain. When the transgene is bred into the C57BL/6 strain, it is completely methylated and not rearranged in lymphoid organs. After several generations of crossing into DBA/2 or SJL the transgene becomes unmethylated and rearranges at high frequency. A strain specific modifier of DNA methylation (Ssm-1) was mapped close to the Friend virus susceptibility locus (Fv-1) on mouse chromosome 4. Rearranged transgenes from spleen, bone marrow and thymus of adult mice or fetal liver were cloned and sequenced. A great variety of joints was found, with about 1/3 being in the correct reading frame. Small deletions into the V- and J-coding ends as well as N region additions contributed to the variability. The fetal joints showed no N regions. Since no functional immunoglobulin (Ig) gene can be created from this artificial test gene, the data indicate that the rearrangement mechanism of the fetus differs from that of the adult.

Animals↗
PubMed1992

[Radiation exposure during defecography].

The introduction of a new radiological method requires the assessment of the advantage-risk ratio. On measuring the radiation doses during defecography, skin entrance and gonadal exposure values were found to be lower than during well-known and well-established examinations of the small pelvis, such as colon enema and CT of the lower abdomen. Defecography, as a radiological tool for diagnosing the anorectal function is, therefore, also suitable for young persons.

Defecation↗