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T Sauer

Publications and source records attributed to T Sauer.

At least 19 recordsLinked to original sources
PubMed2006

Delay-coordinates embeddings as a data mining tool for denoising speech signals.

In this paper, we utilize techniques from the theory of nonlinear dynamical systems to define a notion of embedding estimators. More specifically, we use delay-coordinates embeddings of sets of coefficients of the measured signal (in some chosen frame) as a data mining tool to separate structures that are likely to be generated by signals belonging to some predetermined data set. We implement the embedding estimator in a windowed Fourier frame, and we apply it to speech signals heavily corrupted by white noise. Our experimental work suggests that, after training on the data sets of interest, these estimators perform well for a variety of white noise processes and noise intensity levels.

Algorithms↗
PubMed2005

BSCC, Bethesda or other? Terminology in cervical cytology European panel discussion.

The European panel agreed that reproducibility and translatability of terminology in cervical cytology were essential, arguing well for harmonization of reporting systems. The majority at this meeting use a modification of the Bethesda system (BS). Local modifications involved reporting subcategories within high grade and low grade lesions, which would not alter the overall translatability of their systems both with each other and BS. The majority agree that low grade lesions with and without koilocytosis should be managed similarly as should high grade lesions (moderate dysplasia/CIN2 or worse). Those systems linking moderate dysplasia with mild rather than severe dysplasia would need to define moderate dysplasia as such, if their results were to be translatable, which would be preferable to their using a different definition of low grade and high grade lesions. Translation between systems might anyway be facilitated by reporting moderate dysplasia as a subcategory within high grade, which was favoured by most of those present. Therefore, there is no need for exact agreement of terminology if broad principles are agreed. This useful discussion adds weight to the British Society for Clinical Cytology recommendation that the new classification should be adopted by the UK National Health Service Cervical Screening Programme. If the new classification is adopted, the UK would join the European consensus opinion on terminology.

Consensus↗
PubMed2005

Reduced expression of Claudin-7 in fine needle aspirates from breast carcinomas correlate with grading and metastatic disease.

OBJECTIVE: To study the immunocytochemical expression of the tight junction protein Claudin-7 in smears from breast carcinomas and correlate with grading, nodal status, locoregional and distant metastases and the cellular cohesion. METHODS: The material consisted of 52 air-dried smears from fine needle aspirates of breast carcinomas, both primary and metastatic and smears from seven benign lesions. A primary antibody to Claudin-7 was used for immunocytochemical staining. The degree of staining was recorded as negative, reduced or full, with full expression meaning equivalent to the staining pattern found in the fibroadenomas used as benign control. Staining intensity and the percentage of stained cells were evaluated. The control smears revealed a strong membrane and cytoplasmic positivity in all luminal epithelial cells. Cellular cohesion was graded as: (1) mainly cohesive groups, (2) groups and single cells and (3) mainly single cells. RESULTS: All primary and recurrent/metastatic breast lesions expressed Claudin-7. Full expression was demonstrated in 46% of the cases. Reduced expression was found in 54%. In cases with reduced expression, the percentage of stained cells were usually high, and no smear showed <50% stained tumour cells. The staining pattern was heterogeneous and always mixed membrane/cytoplasmic. Claudin-7 expression showed a significant correlation (P < 0.05) with grading, locoregional and distant metastases, nodal involvement and cellular cohesion in invasive carcinomas, but not with tumour size or subtype. CONCLUSION: Reduced expression of Claudin-7 correlated with higher tumour grade, metastatic disease, including loco-regional recurrences and with cellular discohesion.

Biopsy, Fine-Needle↗
PubMed2005

Demonstration of EGFR gene copy loss in colorectal carcinomas by fluorescence in situ hybridization (FISH): a surrogate marker for sensitivity to specific anti-EGFR therapy?

AIMS: To investigate EGFR gene copy number heterogeneity in colorectal carcinomas compared with copy number of chromosome 7 and immunohistochemical expression of the EGFR protein. METHODS AND RESULTS: Fluorescence in situ hybridization of the EGFR gene and CEP7 was carried out on paraffin-embedded material from 48 rectal carcinomas combined with immunohistochemical detection of EGFR with a polymer detection kit. EGFR gene copy number had a range of 1.4-7.3 with a mean of 2.5. CEP7 copy number had a range of 1.5-6.1 with a mean of 2.5. The EGFR gene/CEP7 ratio ranged from 0.4 to 1.5 with a mean of 0.96. Most cases had a balanced EGFR gene/CEP7 ratio (37 cases = 77%). Copy gain was found in seven cases (15%) with a ratio of up to 1.5, consistent with gain of one EGFR gene copy in one chromosome. Copy loss was found in four cases (8%). All cases with EGFR gene copy loss were immunohistochemically positive. CONCLUSIONS: Demonstration of EGFR gene copy loss might be a surrogate marker for EGFR mutation/deletion and could be used in a routine setting in pathology departments. Further studies are needed to determine whether this may be used to select patients that might benefit from specific anti-EGFR therapy.

Biomarkers, Tumor↗
PubMed2004

CIN 2/3 and cervical cancer in an organised screening programme after an unsatisfactory or a normal Pap smear: a seven-year prospective study of the Norwegian population-based screening programme.

OBJECTIVES: To estimate the risk of cervical intraepithelial neoplasia (CIN) 2/3 and invasive cervical cancer (ICC) in an organised screening programme after an unsatisfactory or a normal Pap smear. SETTING: A seven-year prospective cohort study of the Norwegian population-based co-ordinated screening programme based on the actual diagnostic and screening procedures performed. Observations of 526,661 women with a normal index Pap smear and 21,405 women with an unsatisfactory index Pap smear were made during 3.26 million women-years. METHODS: The risk of being diagnosed with CIN 2/3 or ICC was calculated by logistic regression for the first two years of follow-up. The hazard of being diagnosed with CIN 2/3 or ICC for the women who were not diagnosed during the two first years was estimated by non-parametrical survival regression. RESULTS: After two years of follow-up, 0.2% of the women were diagnosed with CIN 2/3 and 0.01% with ICC after a normal Pap smear. An unsatisfactory Pap smear indicated a 1.6-4.0 times higher risk of harbouring a CIN 2/3 or ICC compared to women with a normal Pap smear. No increased risk of ICC was found during long-term follow-up for the 70% of the women with an unsatisfactory Pap smear who were returned to ordinary screening. Prior series of low-grade Pap smears followed by a normal Pap were associated with an increased risk of CIN 2/3 and ICC. CONCLUSIONS: An unsatisfactory Pap smear indicates a risk of harbouring CIN II/III or ICC. Repeated Pap smears are adequate as a follow-up of an unsatisfactory Pap smear. Women with repeated series of equivocal/LSIL Pap smears followed by a normal Pap should be considered at high risk.

Cohort Studies↗
PubMed2003

Detection of isolated tumor cells in bone marrow is an independent prognostic factor in breast cancer.

PURPOSE: This study was performed to disclose the clinical impact of isolated tumor cell (ITC) detection in bone marrow (BM) in breast cancer. PATIENTS AND METHODS: BM aspirates were collected from 817 patients at primary surgery. Tumor cells in BM were detected by immunocytochemistry using anticytokeratin antibodies (AE1/AE3). Analyses of the primary tumor included histologic grading, vascular invasion, and immunohistochemical detection of c-erbB-2, cathepsin D, p53, and estrogen receptor (ER)/progesterone receptor (PgR) expression. These analyses were compared with clinical outcome. The median follow-up was 49 months. RESULTS: ITC were detected in 13.2% of the patients. The detection rate rose with increasing tumor size (P =.011) and lymph node involvement (P <.001). Systemic relapse and death from breast cancer occurred in 31.7% and 26.9% of the BM-positive patients versus 13.7% and 10.9% of BM-negative patients, respectively (P <.001). Analyzing node-positive and node-negative patients separately, ITC positivity was associated with poor prognosis in the node-positive group and in node-negative patients not receiving adjuvant therapy (T1N0). In multivariate analysis, ITC in BM was an independent prognostic factor together with node, tumor, and ER/PgR status, histologic grade, and vascular invasion. In separate analysis of the T1N0 patients, histologic grade was independently associated with both distant disease-free survival (DDFS) and breast cancer-specific survival (BCSS), ITC detection was associated with BCSS, and vascular invasion was associated with DDFS. CONCLUSION: ITC in BM is an independent predictor of DDFS and BCSS. An unfavorable prognosis was observed for node-positive patients and for node-negative patients not receiving systemic therapy. A combination of several independent prognostic factors can classify subgroups of patients into excellent and high-risk prognosis groups.

Biopsy, Needle↗
PubMed2002

Logistics of referral, diagnostic assessment and treatment of patients with breast symptoms and signs.

BACKGROUND AND AIMS: The logistics of diagnosis and treatment in a hospital with slightly above 400 new cases of breast cancer per year is analysed. MATERIALS AND METHODS: The patient flow from referral, through the diagnostic procedures and through surgical treatment is described. RESULTS AND CONCLUSIONS: The basic principle of the diagnostic assessment is the triple diagnostic procedure including mammography supplemented by ultrasonography, fine needle aspiration cytology and clinical examination. The radiologist and pathologist are working together in the breast diagnostic centre and are thus able to give a "single visit diagnosis" in most cases. The surgeon sees the patient either the same day or the next. A "consensus meeting" held each week with representatives for all specialities present has an important function in quality assurance and education. If one or more of the triple diagnostic components reach conclusion level "suspicious lesion", surgery is indicated. In hospital management is based on day surgery for all biopsies, wide excisions with or without sentinel node and some ablatio simplex mammae. For wide excision and ablation with complete axillary node clearance, the patients are transferred from the day surgery unit to a patient hotel after 3-4 hours of observation and stay till the drain can be removed. Only in rare case of high cardiopulmonary risk, beds in ordinary wards are used. This is a highly cost efficient logistic saving the hospital approximately 400,000 EUR a year compared to ordinary in hospital treatment.

Breast Neoplasms↗
PubMed2001

Immunocytochemical expression of E-cadherin on fine-needle aspirates from breast carcinomas correlate with the cell dissociation pattern seen on smears.

Altered E-cadherin expression has been suggested to be of prognostic significance in breast cancers and to correlate with tumor subtype and grade. A dysfunctional, intercellular adhesion system may be responsible for the tumor cell dissociation pattern seen on fine-needle aspirate cytology (FNAC). The aim of our study was to determine E-cadherin expression on direct FNAC smears from breast carcinomas and compare the results with the dyscohesion grade of the tumor cells and the cytological grading. The material consisted of FNAs from 56 breast carcinomas. The degree of cellular cohesion was estimated semiquantitatively. Full expression of E-cadherin was defined as a complete and strong membrane staining of virtually all tumor cells. All nonductal as well as 85% of the invasive ductal carcinomas revealed reduced expression or negativity for E-cadherin. In all, 25% of carcinomas with dyscohesion Grade 1 (mainly in groups) revealed full expression of E-cadherin, in contrast to 12.5% of tumors with dyscohesion Grade 3 (mainly dispersed cells). Nuclear positivity was seen in 21% of the tumors (12 cases) and seven of these were G3 ductal carcinomas. In conclusion, E-cadherin expression correlated with the cell dissociation pattern seen on direct smears from FNAC of breast carcinomas, but is only one of several markers that modulate this pattern. High-grade carcinomas rarely revealed full expression and had a high incidence of aberrant nuclear localization of E-cadherin.

Biopsy, Needle↗
PubMed2001

Early seizure detection.

For patients with medically intractable epilepsy, there have been few effective alternatives to resective surgery, a destructive, irreversible treatment. A strategy receiving increased attention is using interictal spike patterns and continuous EEG measurements from epileptic patients to predict and ultimately control seizure activity via chemical or electrical control systems. This work compares results of seven linear and nonlinear methods (analysis of power spectra, cross-correlation, principal components, phase, wavelets, correlation integral, and mutual prediction) in detecting the earliest dynamical changes preceding 12 intracranially-recorded seizures from 4 patients. A method of counting standard deviations was used to compare across methods, and the earliest departures from thresholds determined from non-seizure EEG were compared to a neurologist's judgement. For these data, the nonlinear methods offered no predictive advantage over the linear methods. All the methods described here were successful in detecting changes leading to a seizure between one and two minutes before the first changes noted by the neurologist, although analysis of phase correlation proved the most robust. The success of phase analysis may be due in part to its complete insensitivity to amplitude, which may provide a significant source of error.

Brain Mapping↗
PubMed2001

Detection of isolated tumor cells in bone marrow in early-stage breast carcinoma patients: comparison with preoperative clinical parameters and primary tumor characteristics.

UNLABELLED: PURPOSE/EXPERIMENTAL DESIGN: The importance of detection of disseminated isolated tumor cells (ITCs) in bone marrow (BM) is still not settled. BM aspirates from 920 patients with primary breast cancer were analyzed for tumor cells by standardized direct immunocytochemical analysis (ICC) of 2 x 10(6) mononuclear cells (MNCs) using anticytokeratin monoclonal antibody (AE1/AE3). Samples (637) were analyzed by negative immunomagnetic enrichment (IMS) followed by ICC (10 x 10(6) MNCs). Analyses of the primary tumor specimens have been performed, including histomorphology, tumor-node-metastasis (TNM) staging, grading, and immunohistochemical analyses. RESULTS: Of the patients with infiltrating carcinoma, 63% were node negative (N0) and 33%, node positive (N+). The results show the presence of tumor cells in 13.4% of the evaluable patients after direct ICC analysis. The presence of tumor cells correlated to the nodal- and tumor stage, showing BM positivity in 9.9% of the N0 cases and 20.6% in the N+ group (P < 0.0005), 11.2% of the stage T(1) were positive, and 15.0% and 22.6% were positive in the T(2) and T(3/4) groups, respectively (P = 0.013). No correlation between detection of ITC and detection of p53 and cathepsin D expression was found. Vascular invasion and c-erbB2 expression were associated with ITCs in BM (P = 0.045 and P = 0.024, respectively). Node-negative patients with estrogen receptor (ER)+ and/or progesterone receptor (PgR)+ tumors had lower frequency of ITCs than ER-/PgR- (P = 0.004). The use of negative IMS increased the frequency of positive BM by 63% (P < 0.0005). CONCLUSIONS: The direct ICC detection of ITCs in BM correlated with primary tumor stage, nodal stage, vascular invasion, c-erbB2 expression, and ER/PgR status. Analysis of larger BM samples by negative IMS resulted in increased number of ITC-positive patients.

Antibodies, Monoclonal↗
PubMed2000

[Diagnostic and therapeutic localized breast biopsy].

Preoperative localized mammary biopsy has been used as a diagnostic tool since before 1983 in the Breast Clinic, Ullevål Hospital. The great majority of procedures have been performed in the outpatient clinic with use of local anesthesia. Since 1988 all activity has been registered prospectively in a database. We discuss the use of the procedure and the results obtained during the period 1983-95. In the later part of the observed period, the use of the procedure as a diagnostic tool has been less frequent, but it has been increasingly used as a tool to identify the pathologic process when performing breast-conserving surgery. Surveillance of the malign-benign ratio is an important parameter in the quality assurance of the procedure. The malign-benign ratio has been greater than 0.3 during the period of observation. Continuous registration of procedure-related parameters is necessary for documentation of the results.

Biopsy, Needle↗
PubMed2000

Endothelial cell autoantibodies are a marker of disease susceptibility in inflammatory bowel disease but apparently not linked to persistent measles virus infection.

Intestinal vasculitis caused by persistent measles virus infection of intestinal endothelial cells was described in Crohn's disease. Furthermore, endothelial cell autoantibodies have been demonstrated in inflammatory bowel disease (IBD). Autoantibodies against intestinal endothelial cells were visualized by indirect immunofluorescence in patients with IBD, in their healthy first-degree relatives, in patients with infectious enterocolitis, and in healthy, unrelated controls. In intestinal tissue specimens of 22 antibody-positive IBD patients a search for the measles virus genome was performed. Endothelial cell autoantibodies were significantly more frequent in patients with IBD, in both groups of first-degree relatives, and in patients with infectious enterocolitis than in the healthy controls (P = 0.0002 or less). The measles virus genome was found in none of the intestinal biopsies. Endothelial cell autoantibodies are not a genetic but rather an epigenetic (infectious) marker of disease susceptibility. The expression of these autoantibodies is unlikely to be triggered by a persistent measles virus infection.

Adolescent↗
PubMed2000

Cell cycle dependence of gene transfer by lipoplex, polyplex and recombinant adenovirus.

The aim of this study was to investigate the influence of cell cycle on transfection efficiency. Counterflow centrifugal elutriation was used which avoids possible side-effects from chemical treatment of cells. With this method, cell populations were fractionated by means of size and density, and fractions corresponding to discrete cell cycle phase-specific populations were transfected with various nonviral methods (Lipofectamine, TfpLys and TfPEI), adenovirus-enhanced transferrinfection (AVET system) and recombinant adenovirus. Transfection efficiency was found to be strongly dependent on the cell cycle stage at the time of transfection. Luciferase activity from cells transfected with polycation- or lipid-based transfection systems was 30- to more than 500-fold higher when transfection was performed during S or G2 phase compared with cells in G1 phase which have the lowest expression levels. In contrast, this effect was not observed with recombinant adenovirus which varied only four-fold. Our results indicate that mitotic activity enhances transfection not only by lipoplexes but also by polyplexes, but not a viral system which has an efficient nuclear entry machinery, suggesting that transfection close to M phase is facilitated perhaps by nuclear membrane breakdown. Furthermore, low transfection success into G1 cells indicates that DNA complexes deposited in G1 cells are probably not retained long enough to take advantage of mitosis effects or that passage of transfected cells through S phase is inhibitory. Gene Therapy (2000) 7, 401-407.

Adenoviridae↗
PubMed2000

Physicochemical analysis of purified diphtheria toxoids: is toxoided then purified the same as purified then toxoided?

Diphtheria toxin can be converted into a highly immunogenic and irreversibly detoxified vaccine either using the conventional process in which the crude toxin is formalinised and subsequently purified (DTxd(conv)) or by detoxification of the highly purified toxin (DTxd(new)). In this study, both DTxd(new) and DTxd(conv) were evaluated by use of physico-chemical methods. For some methods, results were also compared to those obtained for cross-reacting material (CRM197), which is a non-toxic mutant of diphtheria toxin. DTxd(new) was assayed to have a specific purity of at least 2300 LF/mg protein N, thereby exceeding Pharm. Eur. requirements by up to 35%. Superior purity of DTxd(new) could also be demonstrated by size exclusion HPLC experiments and by amino acid composition studies. Far-UV circular dichroism spectroscopy revealed that the secondary structure of DTxd(new) almost resembled that of CRM197, suggesting only minor molecular changes during detoxification. This study worked out differences between purified diphtheria toxoids. Physico-chemical means revealed the advantages of DTxd(new) being the purer and more defined product, thus making it highly efficient for its use as a vaccine carrier as well as a component of vaccine combinations.

Amino Acids↗
PubMed1999

[A prospective registration of diagnosis and treatment of breast tumors at the Ulleval hospital 1988-1995].

During the years 1988 to 1995, all diagnostic and therapeutic activities in the Breast Clinic, Ullevål Hospital, Oslo, Norway were registered prospectively. This paper presents the results from the registration. Of 4,436 new referrals, 1,169 had infiltrating mammary carcinoma and 63 ductal carcinoma in situ. 13.6% of those with breast carcinoma and 12.3% of those with benign breast disease had a first degree relative with breast cancer. The use of diagnostic biopsies for palpable and nonpalpable lesions decreased significantly through the period, from 155/112 in 1988 to 65/78 in 1995. For palpable lesions, the malign/benign ratio decreased from 0.82 in 1988 to 0.54 in 1995 while it improved from 0.43 to 0.88 for marked biopsies for nonpalpable lesions. Excluding those with mammographically and/or cytologically suspicious lesions from those who had a biopsy for a palpable lesion, we found that only seven out of 101 had cancer (ratio 0.07). Radical surgery was done in 790 cases with cytology as the only pre- and peroperative cancer verification. Three of them had a false positive cytology, as cancer was not found in the breast. One patient had metastasis later confirming that a cancer had been present; thus we had two false positive cytologies (2.5 per thousand). More than six axillary lymph nodes have to be examined in order to avoid false negative axillary status. In 1988 we had 41% with less than six nodes examined. This improved to 15% in 1995. Breast preserving therapy increased throughout the period from 4.1% in 1988 to 29.4% in 1995. Tumor size (pTI around 40%) and node positivity (35%) was fairly constant. In our opinion, a continuous prospective registration of the activity in a breast diagnostic centre is essential in order to improve and maintain service quality. The decision made by the Norwegian parliament in 1998 to introduce nation-wide mammography screening may be used to institute such continuous prospective registrations in all centres involved in the screening.

Breast Neoplasms↗
PubMed1999

Estimating loss of the wild-type p53 gene by in situ hybridization of fine-needle aspirates from breast carcinomas.

TP53 mutations have been found in 16-64% of breast carcinomas. The aim of our study was to investigate loss of the wild-type TP53 gene by in situ hybridization (ISH) of fine-needle aspirates (FNAC) from breast carcinomas. The material consisted of FNAC from 33 breast carcinomas, with histologic specimens from 19 of the cases. Routine diagnostic smears were used for cytologic grading. ISH of the wild-type TP53 gene and chromosome 17 was performed on air-dried smears. Hybridization signals were counted in at least 100 nuclei, and the percentage for each signal number was calculated. FNAC from four fibroadenomas as well as cell preparations from five lymphocyte cultures were used as normal/benign controls. Cutoff for defining loss of p53 gene signals was set at 20% of cells with zero and one gene signal only. Concomitant p53 protein expression was determined on 20 histologic sections and eight additionally available air-dried smears. Loss of wild-type p53 gene was found in 20 carcinomas (60.6%). The rate of signal loss varied from 0.4% to 75.3% of the cells. All tumors with aneusomy of chromosome 17 revealed loss of p53 gene signals, as did 42% of the disome cases. Loss of wild-type p53 gene was present in 10 of 16 grade 1 cancers (62.5%), eight of 13 grade 2 tumors (61.5%), and two of four grade 3 cases. Signal loss did not correlate with p53 protein expression. In conclusion, subpopulations with loss of the wild-type p53 gene are a common finding in breast carcinomas; they are detected in more than 60% of the tumors, including grade 1 cancers.

Biopsy, Needle↗