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Biomedical subjects

U Hahn

Publications and source records attributed to U Hahn.

At least 73 records · Page 4Linked to original sources

Conventional high resolution versus fast T(2)-weighted MR imaging of the heart: assessment of reperfusion induced myocardial injury in an animal model.

Cardiac image quality in terms of spatial resolution and signal contrast was assessed for conventional and newly developed T(2)-weighted fast spin-echo imaging with high k-space segmentation. The capability in revealing regional myocardial edema and cellular damage was examined by a porcine model using histopathologic correlation. Twelve porcine hearts were excised from slaughtered animals and instantly perfused with 1000 mL cold cardioplegic solution. After 4 h of cold ischemia the hearts were reperfused for one hour using a "Langendorff" perfusion model followed by MR imaging at 1.5 Tesla. Three additional pig hearts served as controls and were studied by MR directly after harvesting. Histopathological analysis of regional tissue changes was performed macro- and microscopically. Short axis T(2)-weighted (3000/45 and 90) high quality fast spin-echo (FSE) images were recorded without cardiac action and signal intensity was correlated with histology. These images also served as gold standard for evaluation of newly developed faster sequences allowing measuring times shorter than 20 s. Fast T(2)-weighted imaging comprised single-slice fast spin echo (moderate echo train length of 23 echoes, FSE(m)), and multi-slice single-shot half-Fourier fast spin-echo (71 echoes, FSE(HASTE)) sequences, supplemented by versions with inversion recovery preparation (FSE(m)IR and FSE(HASTE)IR). Systolic function after reperfusion was restored in 10 porcine hearts. Tissue alterations included myocardial edema and contraction band necrosis which was found to be most severe in myocardium with maximum T(2) SI. Especially FSE(m) and FSE(m)IR sequences allowed differentiation of all categories of tissue damage on a high level of significance. In contrast, single-shot FSE(HASTE) and FSE(HASTE)IR sequences did not provide sufficient image quality to discriminate moderate and severe myocardial damage (p > 0.05). Different degrees of myocardial injury after ischemia and reperfusion can be staged by MR imaging, especially using conventional high resolution T(2)-weighted FSE sequences. The animal study indicates that fast T(2)-weighted FSE(m) and FSE(m)IR sequences lead to superior image quality and diagnostic accuracy compared to FSE(HASTE) and FSE(HASTE)IR imaging.

Analysis of Variance↗

Morpheme-based, cross-lingual indexing for medical document retrieval.

The increasing availability of machine-readable medical documents is not really matched with the sophistication of currently used retrieval facilities to deal with a variety of critical natural language phenomena. Still most popular are string-matching methods which encounter problems for the medical sublanguage, in particular, concerning the wide-spread use of complex word forms such as noun compounds. We introduce a methodology for the segmentation of complex compounds into medically motivated morphemes. Given the sublanguage patterns in our data these morphemes derive from German, Greek and Latin roots. For indexing and retrieval purposes, such a morpheme dictionary may be further structured by defining the semantic relations among morpheme sets in order to build up a multilingual morpheme thesaurus. We present a tool for thesaurus compilation and management, and outline a methodology for the proper construction and maintenance of a multilingual morpheme thesaurus.

Germany↗

[The MR signal behavior of a 4-week-old occlusive myocardial infarct in an animal experiment].

PURPOSE: To correlate signal behaviour in T1- and T2-weighted images after Gd-DTPA with regional histopathology in occlusive myocardial infarction (MI). METHODS: Ligation of a diagonal branch of the LAD was performed in seven sheep. Four weeks later 0.1 mmol Gd-DTPA/kg were injected in five sheep 15 min before cardiac arrest and the sheep were slaughtered. In vitro imaging was performed at 1.5 T included T1- and T2-weighted spin echo sequences in long and short axis views. Signal intensities (SI) were determined in 36 myocardial segments per slice and compared to macro- and microscopy. RESULTS: In all animals an antero-lateral infarct region was evident histologically. This region presented with increased T2 SI and T1 SI after Gd-DTPA. The number of segments with increased SI in T1-weighted images was higher (n = 195 segments) compared to segments with increased T2 SI (n = 122 segments). Granulation tissue could be differentiated from rarely vascularized connective tissue at a high level of significance (p < 0.001) by T1 and T2 SI analysis. Wall thickness was significantly decreased in necrotic myocardium (3.8 +/- 1.2 mm) compared to normal tissue (9.8 +/- 1.1 mm, p < 0.001). CONCLUSION: In four-week-old occlusive MI the extent of necrosis can be accurately assessed by analysis of post contrast T1-weighted images. Considering regional T2 SI, granulation tissue can be differentiated from regions with predominant fibrous organisation.

Animals↗

[Pulsed spray lysis with reteplase in peripheral arterial occlusions--technique and initial results].

PURPOSE: Urokinase followed by rt-PA are the most frequently used drugs approved for thrombolysis in peripheral arteries in the USA and Europe. We wanted to test the safety and efficacy of low-dose reteplase administered by pulsed spray technique. MATERIALS AND METHODS: 10 patients with acute or subacute occlusion of a peripheral artery (n = 8) or graft (n = 2) were treated (history 8 +/- 17 days; occlusion length 4-60 cm, mean 23 cm). Reteplase was administered as an intra-arterial (i.a.) bolus (0.5 U/10 cm of occlusion length) followed by pulsed spray lysis (1 U/h for the first 2 h, then 0.5 U/h). The catheter was placed into the occlusion. In addition the patients received heparin (i.a.) and aspirin (oral). The site of puncture was closed with a percutaneous suturing system prior to discontinuation of heparin treatment. RESULTS: A total dose of 3.3 +/- 1.2 U reteplase was administered. The primary success rate was 7/10. Two distal embolizations and two bleeding complications were observed (one minor bleeding at the site of puncture and one rupture of the suture which had to be treated surgically). CONCLUSION: With regard to our limited data, low-dose i.a. reteplase seems to be safe and effective. Two bleeding complications were observed which both occurred at the site of puncture. Discontinuation of heparin treatment prior to sheath removal is recommended. Fibrinolysis with reteplase may be an alternative to urokinase or rt-PA.

Aged↗

[High resolution multislice CT of the lung: comparison with sequential HRCT slices].

PURPOSE: To compare the image quality of high-resolution (HR) spiral CT scans from a multislice CT scanner with sequential HRCT scans from a singleslice CT scanner. MATERIALS AND METHODS: 20 patients with diffuse lung disease received a high-resolution spiral CT on a multislice scanner (4 slices) and 5 HRCT single slices (1 mm) on a singleslice scanner. Scan parameters of the multislice scanner were: Collimation 4 x 1 mm, pitch 6, slice thickness 1 mm. 5 HRCT slices were compared to the corresponding HR spiral CT slices using a 5-point scale by 5 radiologists with regard to the image quality and the number of artifacts. The evaluation was performed with a multivariate analysis (MANOVA test). RESULTS: Overall impression of image quality, noise, central vessels and bronchi, and all pathological changes were not significantly different between the two CT methods. Sequential HRCT scans were considered to be significantly better than HR spiral CT scans for spatial resolution (p = 0.02), depiction of peripheral vessels (p = 0.02), and of small bronchi (p = 0.05), and significantly worse for depiction of interlobar septa (p < 0.001). Diagnostically relevant differences were found in only 2.2%. Breathing and heartbeat artifacts each were 3 times higher in the sequential HRCT technique than in the multislice-spiral technique (p < 0.0001). CONCLUSION: HR spiral CT scans performed on a multislice CT scanner provide significantly less artifacts and an equal diagnostic image quality compared to sequential HRCT scans performed on a singleslice CT scanner. Multislice spiral CT in HR technique may replace the common scanning technique with conventional spiral CT and additional HRCT scans for diffuse lung diseases.

Adult↗

Ribonuclease T1 cleaves RNA after guanosines within single-stranded gaps of any length.

RNA-oligonucleotides with defined single-stranded stretches were designed to investigate the minimal requirements of a ribonuclease T1 substrate. It could be shown, that RNase T1 cleaves single-stranded RNA after a unique guanosine flanked by two double-stranded areas. However, the turnover of such a G-gap is significantly lower than that of a gap of two, three or four nucleotides.

Base Sequence↗

Fat- and water-selective MR cine imaging of the human heart: assessment of right ventricular dysplasia.

RATIONALE AND OBJECTIVES: The purpose of this study was to develop and implement MR sequences for chemical shift-selective breath-hold cine imaging of the heart. Fibroadipose conversion of myocardium in cases suspected of right ventricular dysplasia should be revealed in fat- and water-selective MR images of high quality. METHODS: Frequency-selective saturation of one chemical shift component was applied in modified k-space-segmented, electrocardiography-gated sequences, allowing high-quality cine imaging of the human heart in a single breath-hold. Phantom studies and human examinations in eight normal subjects (aged 24-62 years) and in seven patients (aged 31-47 years) with suspected right ventricular dysplasia were performed. The patients showed suspicious findings, such as a dyskinetic and dilated right ventricle combined with ventricular arrhythmia, and underwent MR imaging after exclusion of other possible reasons (eg, coronary artery disease or pulmonary hypertension). RESULTS: High selectivity to the desired chemical shift component was confirmed by test measurements in a phantom containing water and lipids. In the human subjects, minor problems with magnetic field inhomogeneities appeared in the thoracic walls only. Four patients with suspected right ventricular dysplasia showed clearly abnormal signal behavior of the right myocardial wall in both fat- and water-selective cine images. Bright transmural structures were exhibited in fat-selective images, but the origin of the fat (epicardium or infiltrated myocardium) was often difficult to assess. CONCLUSIONS: Right ventricular areas with fibrosis and fatty degeneration often show normal signal intensity in standard T1-weighted images but can be differentiated from normal tissue by the new chemical shift-selective breath-hold cine techniques.

Adipose Tissue↗

So concepts aren't definitions, but do they have necessary or sufficient features?

Rips (1989) is one of the most widely cited demonstrations of the relevance of critical features in conceptual structure. A critical feature will impose constraints on how an object is classified, regardless of other factors, such as overall similarity. We review and clarify critical features proposals in terms of whether an assumption is being made about necessary features, sufficient features, or both (i.e. a definition). On the basis of this, we scrutinize Rips' investigation and present our own empirical re-evaluation of this work. The results reported here do not support any strong view of necessary or sufficient features.

Concept Formation↗

Analysis of the RNase T1 mediated cleavage of an immobilized gapped heteroduplex via fluorescence correlation spectroscopy.

We report a new method for studying the activity of hydrolytic enzymes. Fluorescence correlation spectroscopy was used to observe online the hydrolyzation of a rhodamine B-labeled substrate by ribonuclease T1. A gapped heteroduplex substrate - a hybrid of a ribooligonucleotide and two smaller complementary deoxyribooligonucleotides - was immobilized via biotin to a streptavidin-coated surface of a coverslip. The reported method opens the possibility to study the cleavage of small substrates differing only slightly in molecular weight from the enzyme reaction product. The use of fluorescence correlation spectroscopy allows the detection of very low enzyme concentrations (down to 10(-21) mol 0.05 fM of RNase T1, corresponding to about 600 RNase T1 molecules in 0.02 ml).

Binding Sites↗

Automated coding of diagnoses--three methods compared.

In Germany, new legal requirements have raised the importance of the accurate encoding of admission and discharge diseases for in- and outpatients. In response to emerging needs for computer-supported tools we examined three methods for automated coding of German-language free-text diagnosis phrases. We compared a language-independent lexicon-free n-gram approach with one which uses a dictionary of medical morphemes and refines the query by a mapping to SNOMED codes. Both techniques produced a ranked output of possible diagnoses within a vector space framework for retrieval. The results did not reveal any significant difference: The correct diagnosis was found in approximately 40% for three-digit codes, and 30% for four-digit codes. The lexicon-based method was then modified by substituting the vector space ranking by a heuristic approach that capitalizes on the semantic structure of SNOMED, thus raising the number of correct diagnoses significantly (approximately 50% for three-digit codes, and 40% for four-digit codes). As a result, we claim that lexicon-based retrieval methods do not perform better than the lexicon-free ones, unless conceptual knowledge is added.

Abstracting and Indexing↗

MedSynDiKATe--design considerations for an ontology-based medical text understanding system.

MedSynDiKATe is a natural language processor for automatically acquiring knowledge from medical finding reports. The content of these documents is transferred to formal representation structures which constitute a corresponding text knowledge base. The general system architecture we present integrates requirements from the analysis of single sentences, as well as those of referentially linked sentences forming cohesive texts. The strong demands MedSynDiKATe poses to the availability of expressive knowledge sources are accounted for by two alternative approaches to (semi)automatic ontology engineering.

Evaluation Studies as Topic↗

Modeling anatomical spatial relations with description logics.

Although spatial relations are essential for the anatomy domain, spatial reasoning is only weakly supported by medical knowledge representation systems. To remedy this shortcoming we express spatial relations that can intuitively be applied to anatomical objects (such as 'disconnected', 'externally connected', 'partial overlap' and 'proper part') within the formal framework of description logics. A special encoding of concept descriptions (in terms of SEP triplets) allows us to emulate spatial reasoning by classification-based reasoning.

Anatomy↗

Semantic analysis of medical free texts.

The semantic interpretation of natural language utterances is usually based on a large number of transformation rules which map syntactic structures (parse trees) onto some kind of meaning representation. However, those interpretation rules exhibit an insufficient degree of abstraction so that the scalability and portability of such natural language processing systems is hard to maintain. In this paper, we introduce an approach that is able to cope with a wide variety of semantic interpretation patterns in medical free texts by applying a small inventory of abstract semantic interpretation schemata. These schemata address generalized graph configurations within syntactic dependency parse trees, which abstract away from specific syntactic constructions.

Computer Graphics↗

Knowledge engineering the UMLS.

In order to transform a major portion of the Unified Medical Language System (UMLS) into a formally sound description logics system we have developed a four-step knowledge engineering approach. We report on experiments with a Loom knowledge base which consists of 164,000 concepts and 76,000 relations covering human anatomy and pathology. We discuss the fully automatized as well as interactive semiautomatic steps. The latter ones focus on the manual work necessary to render the formal target representation structures complete and adequate.

Artificial Intelligence↗

Structural analysis of an RNase T1 variant with an altered guanine binding segment.

The ribonuclease T1 variant 9/5 with a guanine recognition segment, altered from the wild-type amino acid sequence 41-KYNNYE-46 to 41-EFRNWQ-46, has been cocrystallised with the specific inhibitor 2'-GMP. The crystal structure has been refined to a crystallographic R factor of 0.198 at 2.3 A resolution. Despite a size reduction of the binding pocket, pushing the inhibitor outside by 1 A, 2'-GMP is fixed to the primary recognition site due to increased aromatic stacking interactions. The phosphate group of 2'-GMP is located about 4.2 A apart from its position in wild-type ribonuclease T1-2'-GMP complexes, allowing a Ca(2+), coordinating this phosphate group, to enter the binding pocket. The crystallographic data can be aligned with the kinetic characterisation of the variant, showing a reduction of both, guanine affinity and turnover rate. The presence of Ca(2+) was shown to inhibit variant 9/5 and wild-type enzyme to nearly the same extent.

Amino Acid Sequence↗

Modification of ribonuclease T1 specificity by random mutagenesis of the substrate binding segment.

Attempts to modify the guanine specificity of ribonuclease T1 (RNase T1) by rationally designed amino acid substitutions failed so far. Therefore, we applied a semirational approach by randomizing the guanine binding site. A combinatorial library of approximately 1.6 million RNase T1 variants containing permutations of 6 amino acid positions within the recognition loop was screened on RNase indicator plates. The specificity profiles of 180 individual clones showing RNase activity revealed that variant K41S/N43W/N44H/Y45A/E46D (RNaseT1-8/3) exhibits an altered preference toward purine nucleotides. The ApC/GpC preference in the cleavage reaction of this variant was increased 4000-fold compared to wild-type. Synthesis experiments of dinucleoside monophosphates from cytidine and the corresponding 2'3'-cyclic diesters using the reverse reaction of the transesterification step showed a 7-fold higher ApC synthesis rate of RNase 8/3 than wild-type, whereas the GpC synthesis rates for both enzymes were comparable. This study shows that site-directed random mutagenesis is a powerful additional tool in protein design in order to achieve new enzymatic specificities.

Amino Acid Sequence↗