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D Schmidt

Publications and source records attributed to D Schmidt.

At least 73 records · Page 4Linked to original sources

[Neurocognition and PET. Strategies for data analysis in activation studies on working memory].

AIM: In cognitive neuroscience regional cerebral blood flow (rCBF) imaging with positron-emission-tomography (PET) is a powerful tool to characterize different aspects of cognitive processes by using different data analysis approaches. By use of an n-back verbal working memory task (varied from 0- to 3-back) we present cognitive subtraction analysis as basic strategy as well as parametric and covariance analyses and discuss the results. METHODS: Correlation analyses were performed using the individual performance rate as an external covariate, computing inter-regional correlations, and as network analysis applying structural equation modelling to evaluate the effective connectivity between the involved brain regions. RESULTS: Subtraction analyses revealed a fronto-parietal neuronal network also including the anterior cingulate cortex and the cerebellum. With higher memory load the parametric analysis evidenced linear rCBF increases in prefrontal, pre-motor and inferior parietal areas including the precuneus as well as in the anterior cingulate cortex. The rCBF correlation with the individual performance as external covariate depicted negative correlations in bilateral prefrontal and inferior parietal regions, in the precuneus and the anterior cingulate cortex. The network analysis demonstrated mainly occipito-frontally directed interactions which were predominantly left-hemispheric. Additionally, strong linkages were found between extrastriate and parietal regions as well as within the parietal cortex. CONCLUSION: The data analysis approaches presented here contribute to an extended and more elaborated understanding of cognitive processes and their different sub-aspects.

Brain↗

Topographic segregation and convergence of verbal, object, shape and spatial working memory in humans.

This functional magnetic resonance imaging study investigates commonalties and differences in working memory (WM) processes employing different types of stimuli. We specifically sought to characterize topographic convergence and segregation with respect to prefrontal cortex involvement using verbal, spatial, real object and shape memory items in a two-back WM task. Both the dorsolateral and ventrolateral prefrontal cortices are conjointly activated across all stimulus types. No stimulus-specific differences in the activation patterns of the prefrontal cortex could be demonstrated giving support to the view of an amodal prefrontal involvement during WM processes. However, extra-frontal regions specialized on feature processing and involved in the preprocessing of the stimuli were selectively activated by these different subtypes of WM. These selectively activated regions are assigned to parts of the ventral and dorsal stream.

Adult↗

Brain systems engaged in encoding and retrieval of word-pair associates independent of their imagery content or presentation modalities.

In this study, we aimed to characterize commonalities and differences of activation patterns during verbal episodic memory processes across different presentation modalities (visual or auditory) and different imagery content (low or high) of the presented verbal memory items. Twelve right-handed normal male volunteers took part in the study. Each subject underwent six O-15-butanol positron emission tomography scans. In six of the subjects the verbal material was presented visually, and in six subjects auditorily. The subjects had to encode and retrieve two sets of 12 word-pair associates of high (set 1) or low (set 2) imagery content (not semantically related). The presentation of nonsense words served as reference condition. Images were analyzed with statistical parametric mapping. Conjunction analysis was used to identify commonalities, and cognitive subtraction analysis was used to identify differences. The use of conjunction analyses enabled us to identify commonly activated regions involved in episodic encoding and retrieval of verbal material irrespective of the presentation modality or the imagery content. Our results add further evidence to recent findings that bilateral prefrontal activations are important for episodic retrieval and thus the role of the left prefrontal cortex has been underestimated during episodic retrieval. Furthermore, our results support the idea of functionally segregated areas in the prefrontal cortex. Finally, our results provide strong evidence that mesial parietal cortex (precuneus) involvement is not restricted to processes involving imagery.

Adult↗

[Recommendations for the oncologic pathology report and morphologic factors associated with prognosis in endometrial carcinoma].

Summary. The endometrial carcinoma (EC) is the fourth common malignant tumor in women with a reported incidence for Germany of 24.5. The prognostic evaluation shows an overall five-year survival of more than 76 %. The histopathologic report should include the tumor type in detail with special consideration of serous-papillary, clear cell and endometrioid type. Stage T2 a and T2 b should only be diagnosed with clear-cut invasion of endocervical glands or the cervical stroma. In most cases of positive endocervical curetting, endmotrial carcinoma has been dislocated during fractional curetting and represents no indication for advanced surgery (Wertheim-Meigs-procedure). Special reference should be made on isthmic carcinoma, because there is a combination of lymphatic drainage of the cervix and corpus uteri. Well established prognostic factors are surgical tumor stage (pTNM-system), pelvic lymph node metastases and tumor grading. Molecular biologic and cellkinetic parameters should be used for research purpose only.

Endometrial Neoplasms↗

[Precancerous lesion of the endometrium and endometrial morphology in patients with tamoxifen therapy].

The endometrioid type of endometrial adenocarcinoma,(type 1-carcinoma) is estrogen-dependent and frequently associated with endometrial hyperplasia. The nomenclature of these hyperplasias is currently under discussion. The highest risk for metachronous carcinoma is associated with atypical hyperplasia of the endometrium as detected in fractional curettings. In postmenopausal patients treatment should consist of abdominal hysterectomy. The so-called type 2-carcinomas, serous-papillary and clear-cell type, do not demonstrate a similar association with precursor lesions. Pathological findings in patients treated with Tamoxifen include endometrial atrophy and fibro-cystic endometrial polyps, sometimes with cellular metaplasias. Patients with breast cancer and tamoxifen treatment have an increased risk of endometrial carcinoma. In some of these patients it could be argued whether the carcinoma has developed in a proceeding endometrial hyperplasia.

Cell Transformation, Neoplastic↗

[Cystic lymphangioma with endosalpingiosis as a rare cause of gastrointestinal bleeding].

We report on a 31-year-old woman with an iron-deficiency anemia and positive Guaiac test, existing for more than 2 years. Despite an extensive gastrointestinal examination a bleeding source could not be found. Also angiography of the abdominal arteries with injection of heparin as provocative protocol was normal. Enteroclysis showed a remarkable finding which led to laparotomy. A cystic lymphangioma with endolymphatic endosalpingiosis as the bleeding source was identified and removed. Lymphangioma is a rare benign soft tissue tumor which usually appears during the first 2 years of life. Only in some cases the lymphangioma is intraabdominal and there can be different, no specific symptoms. Endosalpingiosis is also a rare benign disease, it consists of scattered epithelium of the Fallopian tube. It is the first case to our knowledge, in which the appearance of the endosalpingiosis in a lymphangioma is described.

Adult↗

Diagnostic agreement of two calcaneal ultrasound devices: the Sahara bone sonometer and the Achilles+.

Quantitative ultrasound for the assessment of skeletal status is an evolving method in the diagnosis of osteoporosis. In this cross-sectional study we investigated the diagnostic agreement between the Sahara bone sonometer and the Achilles+ with respect to broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness/quantitative ultrasound index (QUI). 309 healthy females without diseases or medications known to influence bone metabolism (with the exception of oestrogen) were recruited at two participating centers (Erlangen and Berlin). 33% of subjects were taking oestrogens. There was no significant difference in BUA, SOS, and stiffness/QUI between oestrogen and non-oestrogen takers. In vivo precision (expressed as root mean square coefficient of variation) was calculated from two repeat measurements and analyzed in both centres. Mean values were 1.57% (BUA Achilles+), 3.64% (BUA Sahara), 0.35% (SOS Achilles+), 0.39% (SOS Sahara), 2.22% (stiffness Achilles+) and 3.04% (QUI Sahara). Between the two devices we observed a strong correlation for SOS (r=0.89, p<0.01) and stiffness/QUI (r=0.83, p<0.01), and a moderate correlation for BUA (r=0.68, p<0.01). All parameters were moderately negatively associated with age (r=-0.38 to -0.48; p<0.01 for all correlations). Kappa (kappa) scores used to report diagnostic agreement were calculated for tertiles and "equivalent T-scores". The tertiles divide the cohort on both scanners into the same number of subjects above and below a given T-score. Diagnostic agreement using tertiles was poor to moderate (kappa< or =0.51). Diagnostic agreement using equivalent T-score agreement, again, was poor to moderate for BUA but fair to good for SOS and stiffness/QUI (0.59< or =kappa< or =0.73). We conclude that diagnostic agreement between the two devices is at best comparable to the agreement of a dual X-ray absorptiometry measurement using the same densitometer at two different skeletal sites. It is therefore insufficient to compare directly two measurements of an individual patient on both ultrasound devices. Standardization of quantitative ultrasound is very much needed.

Adult↗

[Results of rectal resection procedures at the First Surgical Clinic of the First Medical Faculty of Charles University].

Conventional surgical techniques play an important role in rectal cancer. Dehiscence of the anastomosis after low anterior resection of the rectum is a serious complication. The incidence of dehiscences can be reduced when known principles of preoperative care are respected but in particular by correct surgical technique. In 92 patients operated for rectal cancer at First Surgical Clinic of Charles University we had six patients (6.5%) with dehiscences of anastomosis. The serious character of this surgical complication can be reduced by a primary derivative stomy. Authors recommend implementing a preventive ileostomy in low resection of the rectum in high-risk patients.

Aged↗

The course of the occipital artery--an anatomical investigation for biopsy in suspected vasculitis.

BACKGROUND: The occipital artery can show an inflammation in cranial arteritis. For biopsy it is essential to know the course of the occipital artery. METHODS: In 6 randomly selected specimens of the head, the occipital artery and vein were sought and examined. In addition, the topographical proximity of the greater occipital nerve was considered. RESULTS COURSE: The occipital artery followed a tortuous course, including an occasional hairpin bend in four out of 6 specimens. Lateral distance of the occipital artery from the external occipital protuberance of the occiput: The occipital artery runs at a mean distance of 3.92 cm on the right side and 4.4 cm on the left side from the midline. Variations of the course: A comparison between the right and left side showed a marked side-difference in the course of the vessel. The extent of tortuosity varied distinctly. In most of the arteries, the angle between superior nuchal line and occipital artery was 90 degrees. External diameter: The average external diameter of the occipital artery (in the area where it crosses with the superior nuchal line) was 2.3 mm on the right side and 2.7 mm on the left side. CONCLUSION: Because the greater occipital nerve enters the subcutis below the external protuberance of the occiput and shortly afterwards crosses the occipital artery, we recommend to carry out the biopsy of the occipital artery between 1 to 3 cm above (cranially) and 4 to 5 cm lateral to the external protuberance.

Aged↗

Combinatorial synthesis of cholesterol ester transfer protein-mRNA ligands and screening by nondenaturating gel-electrophoresis.

RNA, as one of the biomolecules with the most structural and functional diversity, is an attractive therapeutic target.(1) Employing combinatorial chemistry methods, small peptide ligands were found, which bind to a short RNA with important biological functions. A 23-nt RNA oligonucleotide from the cholesterol ester transfer protein mRNA was chosen as a molecular target.(2) A 27-nt RNA oligonucleotide from the human immunodeficiency virus type-1 (HIV-1) TAR RNA was used to control the binding specificity.(3) Tetrapeptide libraries, composed of the amino acids Lys, Tyr, Leu, Ile, and Arg, with and without C- and N-terminal lysines, were synthesized by a combination of combinatorial and divergent solid-phase synthesis. Gel-shift affinity screening was used to extract the peptides with the best RNA binding properties. The peptide Lys-Tyr-Lys-Leu-Tyr-Lys-Cys-NH(2) (1) showing micromolar affinity to its RNA target was characterized with circular dichroism (CD), ultra violet (UV) measurement, and (1)H NMR spectroscopy.

5' Untranslated Regions↗

Bladder cancer cells acquire competent mechanisms to escape Fas-mediated apoptosis and immune surveillance in the course of malignant transformation.

Mechanisms of resistance against Fas-mediated cell killing have been reported in different malignancies. However, the biological response of immune escape mechanisms might depend on malignant transformation of cancer cells. In this study we investigated different mechanisms of immune escape in 2 well-differentiated low-grade (RT4 and RT112) and 2 poorly differentiated high-grade (T24 and TCCSUP) bladder cancer cell lines. Fas, the receptor of Fas-ligand, is expressed and shedded by human transitional bladder carcinoma cell lines RT4, RT112, T24 and TCCSUP. Cytotoxicity and apoptosis assays demonstrate that in spite of the Fas expression, poorly differentiated T24 and TCCSUP cells are insensitive towards either recombinant Fas-ligand or agonistic apoptosis-inducing monoclonal antibody against Fas. In poorly differentiated T24 and TCCSUP cell lines we were able to detect marked Fas-ligand protein by flow cytometry and Western blot analysis. In grade 1 RT4 and RT112 cells only minor expression of Fas-ligand possibly because of proteinase action. Fas-ligand mRNA translation or post-translational processing seems to be regulated differentially in the cancer cell lines depending on malignant transformation. In co-culture experiments we show that poorly differentiated cells can induce apoptosis and cell death in Jurkat cells and activated peripheral blood mononuclear cells. This in vitro study suggests that bladder cancer cells can take advantage of different mechanisms of immune evasion and become more competent in avoiding immune surveillance during transformation to higher-grade malignant disease.

Antibodies, Monoclonal↗

Overexpression of p16(INK4A) as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri.

Cytological screening for cervical cancer or its precursors using Papanicolaou's smear test (Pap test) has been highly efficient to reduce the morbidity and mortality of cervical cancer. However, evaluation of the Pap test relies on subjective diagnostic parameters and is affected by a high rate of false-positive and false-negative results. More objective diagnostic parameters to identify truly dysplastic or neoplastic cells in cervical smears as well as in cervical biopsy samples would therefore avoid insecurity for many patients and the high screening costs associated with repeated testing. Cervical dysplasia is induced by persistent infections through high-risk types of human papillomaviruses (HPVs). Outgrowth of dysplastic lesions is triggered by increasing expression of two viral oncogenes, E6 and E7, which both interact with various cell cycle-regulating proteins. Among these is the retinoblastoma gene product pRB, which is inactivated by E7. pRB inhibits transcription of the cyclin-dependent kinase inhibitor gene p16(INK4a). Increasing expression of the viral oncogenes in dysplastic cervical cells might thus be reflected by increased expression of p16(INK4a). In line with this hypothesis, we observed marked overexpression of p16(INK4a) in all cervical intraepithelial neoplasm (CIN) I lesions (n = 47) except those associated with low-risk HPV types (n = 7), all CIN II lesions (n = 32), all CIN III lesions (n = 60) and 58 of 60 invasive cervical cancers. In contrast, no detectable expression of p16(INK4a) was observed in normal cervical epithelium (n = 42), inflammatory lesions (n = 48) and low-grade cervical lesions (CIN I) associated with low-risk HPV types (n = 7). Dysplastic cells could also be identified in cervical smears using a specific p16(INK4a) monoclonal antibody. These data demonstrate that p16(INK4a) is a specific biomarker to identify dysplastic cervical epithelia in sections of cervical biopsy samples or cervical smears.

Biomarkers, Tumor↗

Cotton-wool spots associated with pancreatic carcinoma.

BACKGROUND: Malignant tumors of different organs may cause changes in the eye. PATIENTS: A 62-year-old woman and a 47-year-old man who both had a metastasizing carcinoma of the pancreas suffered from visual disturbances. RESULTS: The 62-year-old woman experienced cloudy vision in her left eye. The 47-year-old man noticed a left visual deterioration. Both patients exhibited cotton-wool spots in both eyes. In addition, the man revealed a metastasis of the choroid in the right eye. The woman was treated with Gemcitabine (1999), and the man with 5 Fluo-Uracil/Leukovorin (1997). The cotton-wool spots were reduced in size in the woman after treatment with Gemcitabine. The patients had no diabetes mellitus and no arterial hypertension. After termination of treatment, their general condition deteriorated and they died within a few weeks. CONCLUSION: Cotton-wool spots are unusual findings in the retina of a metastasizing carcinoma, suggesting the presence of a retinal ischemia. Therefore, early screening of patients with metastasizing pancreas carcinoma for retinal abnormalities may be important.

Adrenal Gland Neoplasms↗

3-[123I]Iodo-alpha-methyl-L-tyrosine uptake in cerebral gliomas: relationship to histological grading and prognosis.

3-[123I]Iodo-alpha-methyl-L-tyrosine (IMT) is employed clinically as a tracer of amino acid transport in brain tumours using single-photon emission tomography (SPET). This study investigates the role of IMT SPET in the non-invasive histological grading and prognostic evaluation of cerebral gliomas. The files of patients investigated by IMT SPET in our clinic between 1988 and 1996 were evaluated retrospectively. Complete follow-up was available for 58 patients with cerebral gliomas investigated by IMT SPET shortly after tumour diagnosis. Seventeen patients had low-grade gliomas (WHO grade II), 14 had anaplastic gliomas (WHO grade III) and 27 had glioblastomas (WHO grade IV). Thirty-six cases were primary tumours and 22 cases, recurrences. Maximal and mean tumour-to-brain (T/B) ratios of IMT uptake at the first IMT SPET investigation were related to histological grading and survival time. Patients with low-grade gliomas showed significantly longer survival than patients with high-grade (grade III or IV) tumours. Gliomas without contrast enhancement on computed tomography or magnetic resonance imaging scans were associated with longer patient survival than tumours with contrast enhancement. The T/B ratios of IMT SPET showed no differences in relation to histological grading [WHO grade II: 1.73+/-0.59; WHO grade III: 1.74+/-0.38; WHO grade IV: 1.59+/-0.35, (mean+/-SD, T/B ratios of mean tumour uptake)]. The median survival time of patients with a high T/B ratio on IMT SPET was not significantly different from that of patients with a low T/B ratio (T/B ratio <1.6, 14.8 months; T/B ratio > or =1.6, 13.0 months). Thus, no evidence could be found for a relationship between IMT uptake in cerebral gliomas and either histological grading or survival time. Nevertheless, IMT SPET constitutes a useful method for the detection of primary and recurrent gliomas, determination of tumour extent and individual follow-up.

Adult↗