Biomedical subjects

K Specht

Publications and source records attributed to K Specht.

At least 19 recordsLinked to original sources

PubMed2006

[Soft tissue sarcoma--epidemiology, diagnosis and treatment].

On account of the considerable variability of the clinical situation, treatment of soft tissue sarcoma requires an individually oriented multimodal approach. In the case of patients with superficial low-grade tumors measuring less than 5 cm in diameter, resection alone is usually adequate. In the event of medium-grade lesions, resection with negative margins, resection in combination with radiotherapy achieves excellent local control rates associated with an overall survival rate of almost 80%. In patients with high-grade sarcomas measuring more than 5 cm in diameter, local control can be achieved with resection and radiotherapy, although every second such patient develops metastases. For patients with local recurrence, further resection should be considered/performed. Radiotherapy is all the more effective, the smaller the postoperative tumor cell burden.

Combined Modality Therapy↗

PubMed2006

[Soft tissue carcinoma. Epidemiology, diagnostics and therapy].

The treatment of soft tissue sarcoma requires an individually tailored, multimodal therapy due to the high variability in the clinical situation. Resection is the usual treatment for patients with superficial, low grade tumors with a diameter of <5 cm. For intermediate grade, differentiated lesions, resection with negative resection edges combined with radiotherapy attains an almost 80% total survival rate. For patients with high grade sarcoma of >5 cm, local control can be attained by resection and radiotherapy, however every second patient will develop metastases. Patients with a local recurrence should consider a new resection. Radiotherapy is the more effective the lower the remaining postoperative tumor burden.

Biopsy↗

PubMed2005

Spatial attention: more than intrinsic alerting?

It has been proposed that the right hemisphere alerting network co-activates, either directly or via the brainstem, the attention system in the parietal cortex involved in spatial attention. The observation that impaired alertness and sustained attention can predict the outcome of neglect might suggest such a relationship, too. In the present fMRI study, we intended to analyse and compare the functional anatomy of two attentional conditions both involving intrinsic (endogenous) alerting and fixation but differing with respect to the degree of spatially distributed attention by using the same paradigm under two different attentional conditions. In a group of ten participants, both a focused and a distributed visuospatial attention condition evoked similar patterns of activation in dorsolateral prefrontal regions, in the anterior cingulate gyrus, in the superior and inferior parietal cortex as well as in the superior temporal gyrus and in the thalamus. These activation foci were stronger in the right hemisphere under both conditions. After subtraction of the alertness condition with focused spatial attention, distributed spatial attention with stimuli appearing at unpredictable locations within both visual fields induced additional bilateral activations only in the left and right superior parietal cortex and in the right precuneus suggesting that these regions are specific for a more widespread dispersion of spatial attention.

Adult↗

PubMed2005

Second generation of meniscus transplantation: in-vivo study with tissue engineered meniscus replacement.

INTRODUCTION: The options available after meniscus loss offer only limited chances for a long-term success. In the following experimental study, we investigated the effect of meniscus tissue engineering on properties of the collagen meniscus implant (CMI). METHODS: Autologous fibrochondrocytes, obtained per biopsy from adult Merino sheep (n=25), were released from the matrix, cultured in-vitro and seeded into CMI scaffolds (n=10, group 1). Following a 3-week in-vitro culture, the tissue engineered menisci were used for autologous transplantation. Macroscopical and histological evaluation were performed in comparison with non-seeded CMI controls (n=10, group 2) and with meniscus-resected controls (n=5, group 3) after 3 weeks (each 1 animal group 1 and 2) and 3 months. RESULTS: The lameness score did not show any difference between the groups. Meniscus tissue was found in seven knee joints (group 1), in five knee joints (group 2) and in two knee joints (group 3). The size of the transplants reduced from 25.9+/-4.5 to 20.1+/-10.8 mm (group 1) and from 25.9+/-1.5 to 14.4+/-12.5 mm (group 2). Histologically, enhanced vascularisation, accelerated scaffold re-modelling, higher content of extra-cellular matrix and lower cell number were noted in the pre-seeded menisci in comparison with non-seeded controls. Dense high-cellular fibrous scar tissue was found in two of five cases in the resection control group. CONCLUSION: Tissue engineering of meniscus with autologous fibrochondrocytes demonstrates a macroscopic and histological improvement of the transplants. However, further development of the methods, especially of the scaffold and of the cell-seeding procedure must prove the feasibility of this procedure for human applications.

Animals↗

PubMed2005

Linking retinotopic fMRI mapping and anatomical probability maps of human occipital areas V1 and V2.

Using functional MRI, we characterized field sign maps of the occipital cortex and created three-dimensional maps of these areas. By averaging the individual maps into group maps, probability maps of functionally defined V1 or V2 were determined and compared to anatomical probability maps of Brodmann areas BA17 and BA18 derived from cytoarchitectonic analysis (Amunts, K., Malikovic, A., Mohlberg, H., Schormann, T., Zilles, K., 2000. Brodmann's areas 17 and 18 brought into stereotaxic space-where and how variable? NeuroImage 11, 66-84). Comparison of areas BA17/V1 and BA18/V2 revealed good agreement of the anatomical and functional probability maps. Taking into account that our functional stimulation (due to constraints of the visual angle of stimulation achievable in the MR scanner) only identified parts of V1 and V2, for statistical evaluation of the spatial correlation of V1 and BA17, or V2 and BA18, respectively, the a priori measure kappa was calculated testing the hypothesis that a region can only be part of functionally defined V1 or V2 if it is also in anatomically defined BA17 or BA18, respectively. kappa = 1 means the hypothesis is fully true, kappa = 0 means functionally and anatomically defined visual areas are independent. When applying this measure to the probability maps, kappa was equal to 0.84 for both V1/BA17 and V2/BA18. The data thus show a good correspondence of functionally and anatomically derived segregations of early visual processing areas and serve as a basis for employing anatomical probability maps of V1 and V2 in group analyses to characterize functional activations of early visual processing areas.

Adult↗

PubMed2005

Transpalpebral tonometry: reliability and comparison with Goldmann applanation tonometry and palpation in healthy volunteers.

BACKGROUND/AIM: TGDc-01 is a new, portable, transpalpebral tonometry device. The aim of this study was to evaluate the reproducibility of this method, including intraobserver and interobserver deviations, and to compare the results with those of Goldmann applanation tonometry and palpation of intraocular pressure (IOP). METHODS: A total of 40 eyes of 20 healthy volunteers were included. Two independent parallel observers (1 and 2) performed three replicate measurements per eye, respectively, both using TGDc01 tonometry, one observer (3) performed three replicate measurements using Goldmann applanation tonometry, and one observer (4) measured the IOP via palpation. Intraindividual deviations within and between both observers using TGDc-01 tonometry and between all three methods were investigated about clinically relevance by comparison of medians and quartiles, statistically significance by pairwise sign tests. Comparisons between observers and methods were based on averaged IOP values of the three individual measurements for each observer and each patient. Intraobserver deviations were analysed by means of Friedman tests. RESULTS: Observers 1 and 2 showed a statistically significant intraobserver deviation when using TGCc-01 (Friedman p = 0.007 for observer 1 and p = 0.002 for observer 2). There was no statistically significant interobserver deviation between observers 1 and 2 (sign test p = 0.200); however, in 45% of the eyes interobserver deviations were larger than plus or minus 3 mm Hg. The median intraindividual deviation between TGDc-01 and Goldmann (TGDc-01 minus Goldmann) was 0 mm Hg (interquartile range -1; 2 mm Hg; sign test p = 0.522); but deviations were larger than plus or minus 3 mm Hg for 38% of the 40 eyes. Median intraindividual deviation between TGDc-01 and palpation (TGDc-01 minus palpation) was -2 mm Hg (interquartile range -4; 1 mm Hg; sign test p = 0.018), but deviations were larger than plus or minus 3 mmHg for 43% of eyes. Median intraindividual deviation between Goldmann and palpation (palpation minus Goldmann) was 2 mm Hg (interquartile range -2; 4 mm Hg; p = 0.429), but deviations were larger than plus or minus 3 mm Hg in 48% of the eyes. CONCLUSION: Interobserver deviations using TGDc-01 tonometry and intraindividual deviations between TGDc-01 tonometry, Goldmann applanation tonometry, and palpation of IOP were found to be clinically relevant. Thus, according to our results TGDc-01 could not be established as a substitute or diagnostic alternative method for Goldmann applanation tonometry. But as deviations between TGDc01 and Goldmann turned out smaller than between palpation of IOP and Goldmann, TGDc-01 seems to provide a better choice for tonometry in patients, in whom Goldmann applanation tonometry is not possible.

Adult↗

PubMed2004

[Prediction of response to neoadjuvant chemotherapy in Barrett's carcinoma by quantitative gene expression analysis].

The potential of gene expression profiles to predict the response to neoadjuvant chemotherapy in patients with advanced adenocarcinoma of the esophagus was analyzed. Paraffin-embedded endoscopic esophageal tumor biopsies of 38 patients with advanced esophageal adenocarcinoma (Barrett's adenocarcinoma) were included. All patients underwent two cycles of cisplatin and fluorouracil (5-FU) therapy with or without additional paclitaxel (taxol) followed by abdominothoracal esophagectomy. RNA expression levels of 5-FU-metabolism associated genes thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), methylenetetrahydrofolate reductase (MTHFR), MAP7, ELF3, as well as of platinum and taxane associated related genes caldesmon, excision cross-complementing genes (ERCC1 and ERCC4) HER2-neu, DNA damage-inducible gene 45 (GADD45) and multidrug resistance genes (MDR1, MRP1) were determined using real-time RT-PCR. Expression levels were correlated with the histopathological response to chemotherapy assessed in surgically resected specimens. Responding patients showed significantly higher pretherapeutic expression levels of MTHFR (p = 0.012), Caldesmon (p = 0.016), MRP1 (p = 0.007) and MDR1 (p = 0.025). In addition, patients with high pretherapeutic MTHFR and MRP1 levels had a survival benefit after surgery (p = 0.013 and p = 0.015, respectively). Additionally, intratumoral heterogeneity of gene expression of selected genes (TP, DPD, MTHFR, HER2-neu, Caldesmon, ERCC4, MRP1) was additionally verified in 9 untreated Barrett's adenocarcinoma by examination of 5 distinct tumor areas and was observed in 12.7% (5.6%-23.5%, CI 95%) of all cases analyzed. Our results indicate that determination of mRNA levels of a few genes may be useful for the prediction of the success of neoadjuvant chemotherapy in individual cancer patients with advanced adenocarcinoma of the esophagus.

Adenocarcinoma↗

PubMed2003

Intrasubject reproducibility of presurgical language lateralization and mapping using fMRI.

BACKGROUND: fMRI is becoming a standard tool for the presurgical lateralization and mapping of brain areas involved in language processing. However, its within-subject reproducibility has yet to be fully explored. OBJECTIVE: To evaluate within-test and test-retest reliability of language fMRI in consecutive patients undergoing evaluation for epilepsy surgery. METHODS: Thirty-four unselected patients were investigated once (within-test reliability) and 12 patients twice (test-retest reliability). The imaging series consisted of an alternating 25-second synonym judgment condition with a 25-second letter-matching condition repeated 15 times. Reproducibility of activation maps of the first and second half of session 1 or activation maps of sessions 1 and 2 was evaluated by comparing one global and three regional lateralization indexes (Broca's area, remaining prefrontal cortex, temporoparietal area) and on a voxel-by-voxel basis (intraclass correlation coefficient, percentage overlap, correlation of t-values). RESULTS: Global and regional language lateralization was achieved with high reliability within and across sessions. Reproducibility was evenly distributed across both hemispheres but not within each hemisphere. Frontal activations were more reliable than temporoparietal ones. Depending on the statistical threshold chosen, the voxel-by-voxel analysis revealed a mean overlap of activations derived from the first and second investigation of up to 48.9%. CONCLUSION: Language fMRI proved sufficiently reliable for the determination of global and regional lateralization of language representation in individual unselected patients with epilepsy.

Adolescent↗

PubMed2001

Tissue microdissection techniques in quantitative genome and gene expression analyses.

Current advances in quantitative genome and gene expression analyses allow precise molecular genetic fingerprinting of tumor tissues. A crucial factor for the reliability of the data obtained with these refined techniques is the use of morphologically well-defined cell populations. Microdissection technology has been developed to procure pure cell populations from specific areas of tissue sections under microscopic control. This review covers techniques of tissue microdissection in the context of commonly used methods of quantitative genome and gene expression analysis. The first part of the review will summarize the technical aspects of various methods developed for tissue microdissection. In the latter part, current applications of quantitative genome and gene expression analysis techniques employed in microdissected tissue samples will be described.

Animals↗

PubMed2001

Quantitative gene expression analysis in microdissected archival formalin-fixed and paraffin-embedded tumor tissue.

Formalin-fixed, paraffin-embedded tissue is the most widely available material for retrospective clinical studies. In combination with the potential of genomics, these tissues represent an invaluable resource for the elucidation of disease mechanisms and validation of differentially expressed genes as novel therapeutic targets or prognostic indicators. We describe here an approach that, in combination with laser-assisted microdissection allows quantitative gene expression analysis in formalin-fixed, paraffin-embedded archival tissue. Using an optimized RNA microscale extraction procedure in conjunction with real-time quantitative reverse transcriptase-polymerase chain reaction based on fluorogenic TaqMan methodology, we analyzed the expression of a panel of cancer-relevant genes, EGF-R, HER-2/neu, FGF-R4, p21/WAF1/Cip1, MDM2, and HPRT and PGK as controls. We demonstrate that expression level determinations from formalin-fixed, paraffin-embedded tissues are accurate and reproducible. Measurements were comparable to those obtained with matching fresh-frozen tissue and neither fixation grade nor time significantly affected the results. Laser microdissection studies with 5-microm thick sections and defined numbers of tumor cells demonstrated that reproducible quantitation of specific mRNAs can be achieved with only 50 cells. We applied our approach to HER-2/neu quantitative gene expression analysis in 54 microdissected tumor and nonneoplastic archival samples from patients with Barrett's esophageal adenocarcinoma and showed that the results matched those obtained in parallel by fluorescence in situ hybridization and immunohistochemistry. Thus, the combination of laser-assisted microdissection and real-time TaqMan reverse transcriptase-polymerase chain reaction opens new avenues for the investigation and clinical validation of gene expression changes in archival tissue specimens.

Animals↗

PubMed2001

Her-2/neu gene amplification, elevated mRNA expression, and protein overexpression in the metaplasia-dysplasia-adenocarcinoma sequence of Barrett's esophagus.

SUMMARY: The importance of alterations of the Her-2/neu oncogene in the tumorigenesis of Barrett's adenocarcinoma (BCA) is discussed controversially. In the present study, we evaluated for the first time the Her-2/neu status in the metaplasia-dysplasia-adenocarcinoma sequence of BCA simultaneously at the DNA, mRNA, and protein level using resection specimens of 25 patients. The locus-specific Her-2/neu gene status was quantified by performing fluorescence in situ hybridization, and information about the ploidy status of chromosome 17 was obtained. Tissue sections from the same areas were used for quantitative RT-PCR (TaqMan RT-PCR) of laser-microdissected tumor cells and for immunohistochemistry to quantify Her-2/neu mRNA and oncoprotein expression. Her-2/neu gene amplification was observed in 35% of BCA, and all of these samples showed strong overexpression of both mRNA and oncoprotein. A polysomy 17 without Her-2/neu gene amplification was observed in 52% of BCA, showing a normal or moderately elevated mRNA expression and no or weak immunopositivity. From 13 areas of high-grade dysplasia (HGD) we found four to be amplified for the Her-2/neu locus, whereas five showed a polysomy 17. All four samples of HGD areas with Her-2/neu gene amplification displayed mRNA and strong oncoprotein overexpression; however, lower mRNA levels were seen than in the amplified BCA areas. None of the samples with low-grade dysplasia (LGD) showed a locus-specific Her-2/neu amplification, but polysomy 17 was present in four of eight cases. No changes were detected in BCA-associated intestinal metaplasia and squamous epithelium. In summary, only a locus-specific Her-2/neu gene amplification was associated with strong mRNA overexpression and strong membranous Her-2/neu immunostaining in BCA and HGD. A chromosome 17 polysomy, as found in the majority of BCA, led to no or weak mRNA overexpression and no or weak immunopositivity. In the metaplasia-dysplasia-adenocarcinoma sequence, a chromosome 17 polysomy without Her-2/neu gene amplification was already present in LGD. This may be a result of an early polyploidization, preceding the later genetic events, such as Her-2/neu gene amplification in HGD and BCA.

Adenocarcinoma↗

PubMed2000

Patched target Igf2 is indispensable for the formation of medulloblastoma and rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children (Dagher, R., and Helman, L. (1999) Oncologist 4, 34-44), whereas medulloblastoma, a highly malignant tumor of the cerebellum, accounts for 20% of childhood brain tumors (Goodrich, L. V., and Scott, M. P. (1998) Neuron 21, 1243-1257). Both tumors are associated with a deficiency in the tumor suppressor Patched (PTCH) in Gorlin syndrome (Gorlin, R. J. (1987) Medicine (Baltimore) 66, 98-113), and they are present in the corresponding murine models. RMS in Ptch mutant mice consistently contain elevated levels of the tumor growth-promoting insulin-like growth factor 2 (Igf2). We have investigated the mechanism of Igf2 overexpression and its significance in medulloblastoma and RMS tumorigenesis. Here we report that Igf2 is indispensable for the formation of medulloblastoma and RMS in Ptch mutants. Overexpression of Igf2 in RMS in these mice does not involve loss of imprinting, uniparental disomy, amplification of the Igf2 locus, or polyploidy. Since Igf2 is also overexpressed in non-tumor tissue deficient in Ptch, these observations suggest that Ptch regulates Igf2 levels through a transcriptional mechanism. They also identify Igf2 as a potential target for medulloblastoma and RMS.

Animals↗

PubMed2000

Tapping movements according to regular and irregular visual timing signals investigated with fMRI.

Whole-head functional MR images were acquired while 10 subjects were asked to tap with their right index finger in synchrony with a visual stimulus appearing regularly with a frequency of 1.5 Hz, or irregularly with a mean frequency of 1.5 Hz. Performance data show that during regular tapping most taps were close to stimulus onset. However, when the subjects paced their tapping according to the irregular stimuli, most taps appeared about 300 ms after the onset of the pacing stimuli. Comparing the brain activations resulting from regular tapping with those from irregular tapping, we found increased activation in left precuneus only. Comparing irregular versus regular tapping shows increased activity in right cerebellar nuclei and vermis, left ventrolateral thalamus, left sensorimotor cortex, left and right pre-SMA and left SMA proper. These results show that during irregular pacing the motor areas are more strongly activated than during regular pacing. In addition, further neural systems are involved in the motor control during irregular pacing: cerebellar vermis and a cerebello-thalamo-cortical system. The latter is supposedly involved in error correction in the context of visually guided movements.

Adult↗

PubMed2000

Cortical activations during paced finger-tapping applying visual and auditory pacing stimuli.

In order to study neural systems which are involved in motor timing we used whole-brain functional resonance imaging while subjects performed a paced finger-tapping task (PFT) with their right index finger. During one condition, subjects were imaged while tapping in synchrony with tones separated by a constant interval (auditory synchronisation, AS), followed by tapping without the pacing stimulus (auditory continuation, AC). In another condition, subjects were imaged while tapping in synchrony with a visual stimulus presented at the same frequency as the tones (visual synchronisation, VS) followed by a tapping sequence without visual pacing (visual continuation, VC). The following main results were obtained: (1) tapping in the context of visual pacing was generally more variable than tapping in the context of auditory stimuli; (2) during all conditions, a fronto-parietal network was active including the dorsal lateral premotor cortex (dPMC), M1, S1, inferior parietal lobule (LPi), supplementary motor cortex (SMA), the right cerebellar hemisphere, and the paravermial region; (3) stronger activation in the bilateral ventral premotor cortex (vPMC), the left LPi, the SMA, the right inferior cerebellum, and the left thalamus during both auditory conditions (AS and AC) compared to the visual conditions (VS and VC); (4) stronger activation in the right superior cerebellum, the vermis, and the right LPi during the visual conditions (VS and VC); (5) similar activations for the AS and AC conditions; but (6) marked differences between the VS and VC conditions especially in the dorsal premotor cortex (dPMC) and LPi areas; and (7) finally, there were no activations in the auditory and visual cortices when the pacing stimuli were absent. These findings were taken as evidence for a general difference between the motor control modes operative during the auditory and visual conditions. Paced finger tapping in the context of auditory pacing stimuli relies more on brain structures subserving internal motor control while paced finger-tapping in the context of visual pacing stimuli relies on brain structures relying on the subserving processing or imagination of visual pacing stimuli.

Acoustic Stimulation↗

PubMed2000

Recognition of emotional prosody and verbal components of spoken language: an fMRI study.

This study examined the neural areas involved in the recognition of both emotional prosody and phonemic components of words expressed in spoken language using echo-planar, functional magnetic resonance imaging (fMRI). Ten right-handed males were asked to discriminate words based on either expressed emotional tone (angry, happy, sad, or neutral) or phonemic characteristics, specifically, initial consonant sound (bower, dower, power, or tower). Significant bilateral activity was observed in the detection of both emotional and verbal aspects of language when compared to baseline activity. We found that the detection of emotion compared with verbal detection resulted in significant activity in the right inferior frontal lobe. Conversely, the detection of verbal stimuli compared with the detection of emotion activated left inferior frontal lobe regions most significantly. Specific analysis of the anterior auditory cortex revealed increased right hemisphere activity during the detection of emotion compared to activity during verbal detection. These findings illustrate bilateral involvement in the detection of emotion in language while concomitantly showing significantly lateralized activity in both emotional and verbal detection, in both the temporal and frontal lobes.

Adult↗

PubMed2000

Quantitative gene expression analysis in microdissected archival tissue by real-time RT-PCR.

Laser-assisted microdissection is a powerful tool for the analysis of morphologically defined cell populations. We report here that the combination of microdissection and real-time RT-PCR technologies together with an optimized RNA microscale extraction procedure allows the reproducible determination of gene expression levels in archival formalin-fixed, paraffin-embedded tissue samples.

Dissection↗

PubMed1999

The time course of the BOLD response in the human auditory cortex to acoustic stimuli of different duration.

The relationship between activity within the human auditory cortices and the duration of heard tones was investigated by measuring the hemodynamic response with functional magnetic resonance imaging. We demonstrate that there is no significant influence of stimulus duration as used here on the intensity and spatial extent of the hemodynamic response in the auditory cortices. We found however, that the time course of the hemodynamic response to the repeated stimulus presentation exhibited a characteristic decline after the first stimulus exposure during the activation period. The possible reasons for this time course are currently unknown, however, several factors may be involved, including top-down mechanisms and/or the interplay of tissue perfusion and oxygen consumption.

Acoustic Stimulation↗

PubMed1999

The effect of finger-movement speed of the dominant and the subdominant hand on cerebellar activation: A functional magnetic resonance imaging study.

We studied the effects of different speeds of unimanual and bimanual movements on functional magnetic resonance signal changes in the cerebellum. Six healthy consistently right-handed subjects were scanned at rest and while executing a sequential finger-to-thumb-opposition task either unimanually (left or right hand) or bimanually. Movement frequency was paced by an auditory signal at rates of either 1 or 3 Hz. Significant frequency-dependent blood oxygen level-dependent signal increases were demonstrated ipsilaterally and contralaterally in the intermediate and lateral portions of the anterior cerebellum for bimanual movements and for unimanual movements with the subdominant hand. There was only a weak frequency-dependent effect for unimanual movements performed with the dominant hand. In addition, signals were stronger on the right intermediate zone of the anterior cerebellum for movements involving the right (dominant) hand while there was stronger activity on the left cerebellar hemisphere for movements involving the left (subdominant) hand. Taken together, these results suggest that rate and movement task effects on cerebellar activation are differentially sensitive to subdominant and dominant hand movements.

Adult↗