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M Kaufmann

Publications and source records attributed to M Kaufmann.

At least 37 records · Page 2Linked to original sources
PubMed2006

Escherichia coli O157 and non-O157 Shiga toxin-producing Escherichia coli in fecal samples of finished pigs at slaughter in Switzerland.

Fecal samples from 630 slaughtered finisher pigs were examined by PCR to assess the shedding of Escherichia coli O157 (rfbE) and Shiga toxin-producing E. coli (STEC, stx). The proportion of positive samples was 7.5% for rfbE and 22% for stx. By colony hybridization, 31 E. coli O157 and 45 STEC strains were isolated, and these strains were further characterized by phenotypic and genotypic traits. Among E. coli O157 strains, 30 were sorbitol positive, 30 had an H type other than H7, and none harbored stx genes. Intimin (eae), enterohemolysin (ehxA), EAST1 (astA), and porcine A/E-associated protein (paa) were present in 10, 3, 26, and 6% of strains. Among them, one eae-gamma1-positive O157:H7 strain testing positive for ehxA and astA and two eae-alpha1-positive O157:H45 strains were classified as enteropathogenic E. coli (EPEC). The O157:H45 EPEC harbored the EAF plasmid and the bfpA gene, factors characteristic for typical EPEC. The isolated STEC strains (43 sorbitol positive) belonged to 11 O:H serotypes, including three previously reported in human STEC causing hemolytic uremic syndrome (O9:H-, O26:H-, and O103:H2). All but one strain harbored stx2e. The eae and ehxA genes, which are strongly correlated with human disease, were present in only one O103:H2 strain positive for stx1 and paa, whereas the astA gene was found more frequently (14 strains). High prevalence of STEC was found among finisher pigs, but according to the virulence factors the majority of these strains seem to be of low virulence.

Abattoirs↗
PubMed2005

Immunohistochemical evaluation of endothelial nitric oxide synthase expression in primary breast cancer.

To evaluate the clinical potential of endothelial nitric oxide synthase (e-NOS) in human breast cancer, we performed immunohistochemical (IHC) staining of paraffin-embedded primary breast cancer tissue of 163 patients for e-NOS using a monoclonal antibody. A correlation was found between e-NOS expression and both the classic prognostic factors and survival rates. Under half the patients were premenopausal (38.5%), 61.5% being postmenopausal. The median tumour size was 2 cm; in 41.7% of the patients there was involvement of the axillary lymph nodes. Most (84.1%) of the tumours were hormone receptor positive. e-NOS staining was positive in 62%, most of the positive tumours having weak (32.5%) or medium (21.5%) staining for e-NOS. The median follow-up time was 42 months, during which 46 (28%) patients had a local recurrence or metastatic disease. A positive correlation of e-NOS with the hormone receptor status was found (P=0.031). However, no impact on survival rates was observed.

Adult↗
PubMed2005

Endocrine treatment options for advanced breast cancer--the role of fulvestrant.

For many years, tamoxifen has been the 'gold standard' amongst anti-oestrogen therapies for breast cancer. However, the selective aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, have demonstrated advantages over tamoxifen as first-line treatments for advanced disease. Anastrozole is also more effective as an adjuvant treatment in early, operable breast cancer and is being increasingly used in the adjuvant setting. Generally, the selective oestrogen receptor modulators (SERMs), such as toremifene, droloxifene, idoxifene, raloxifene, and arzoxifene, show minimal activity in tamoxifen-resistant disease and show no superiority over tamoxifen as first-line treatments. In addition to these agents, other treatment options for advanced disease include high-dose oestrogens and progestins. Response rates for high-dose oestrogens and tamoxifen are similar, but the use of oestrogens is limited by their toxicity profile. Consequently, there is a need for new endocrine treatment options for breast cancer, particularly for use in disease that is resistant to tamoxifen or AIs. Fulvestrant ('Faslodex') is a new type of steroidal oestrogen receptor (ER) antagonist that downregulates cellular levels of the ER and progesterone receptor and has no agonist activity. This paper reviews the key efficacy and tolerability data for fulvestrant in postmenopausal women in the context of other endocrine therapies and explores the potential role of fulvestrant within the sequencing of endocrine therapies for advanced breast cancer.

Anastrozole↗
PubMed2005

HLXB9 activates IL6 in Hodgkin lymphoma cell lines and is regulated by PI3K signalling involving E2F3.

Multiple cytokines are secreted by Hodgkin lymphoma (HL) cells, notably interleukin-6 (IL6), which is believed to play a significant pathobiological role in this and certain other tumors. Previous work on prostate carcinoma cells has shown that IL6 expression is activated therein by the homeodomain protein GBX2, which we found to be absent in HL cells. Instead, we observed expression of a closely related gene, HLXB9, albeit restricted to HL cells coexpressing IL6. Treatment of HL cell lines with antisense-oligonucleotides directed against HLXB9, forced expression of recombinant HLXB9, and analysis of reporter gene constructs containing IL6 promoter sequences all confirmed the potential of HLXB9 to drive expression of IL6. Chromosomal rearrangements of the HLXB9 locus at 7q36 were not detected in HL cells unlike AML subsets expressing HLXB9. However, inhibition of certain signal transduction pathways revealed that the phosphatidylinositol 3 kinase (PI3K) pathway contributes to HLXB9 expression. AKT/phospho-AKT analysis revealed constitutively active PI3K signalling in HL cell lines. Downstream analysis of PI3K revealed that E2F3 may mediate activation of HLXB9. Taken together, our data show that the PI3K signalling pathway in HL cells is constitutively activated and promotes HLXB9 expression, probably via E2F3, thereby enhancing malignant expression of IL6.

Cell Line, Tumor↗
PubMed2005

[San Antonio Breast Cancer Symposium -- highlights 2004].

The adjuvant therapy of postmenopausal, hormonereceptor positive breast cancer patients with aromatase inhibitors in ATAC, ABCSG 8/ ARNO 95 and IES trial revealed just a benefit in terms of disease-free survival, but not for over-all survival. Thus MA-17 trial is so far the only study which could demonstrate a survival benefit for node positive disease by "extended adjuvant" therapy with letrozole. Node- and receptorpositive, postmenopausal women show a higher benefit by anthracycline containing chemotherapy in combination with tamoxifen, than by endocrine therapy alone. But tamoxifen should given sequentially to chemotherapy (Intergroup 0100/ SWOG-8814 trial). Adjuvant chemotherapy with three cycles FEC followed by three cycles docetaxel reveals a survival benefit compared to six cycles FEC, especially in women older than 50 years (PACS 01 trial). Furthermore there is evolving evidence that dose-dense, interval shortened chemotherapy is superior to standard chemotherapy in adjuvant setting. The impaired survival of receptornegative, nodalpositive breast cancer patients seems to be converted to a survival improvement compared with receptorpositive patients by modern adjuvant cytotoxic regimens (metaanalysis CALGB 8541, 9344, 9741). In primary systemic chemotherapy survival is strongly associated with the rate of pathohistological complete remissions (NSABP B-27). The combination of cytotoxic drugs has no further influence on survival, but the sequential administration of taxane increases the rate of pCR. A difference in survival stratified by pCR and non-pCR in breast and positive nodal status could not be detected, so that the number of involved lymph nodes seems to be the strongest prognostic factor and is independent of tumor response in the breast. The sentinel node biopsy is a safe and reliable method, but the rate of false negative findings depends on the pathohistological methods (NSABP B-32). The morbidity of this method is low compared with conventional axillary dissection in multicenter studies. Local tumor control is an important parameter which offers a significant survival benefit in all age cohorts.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

[Management of HIV-positive pregnancies -- results from a retrospective study].

OBJECTIVE: The management of HIV-positive pregnancies was investigated in conjunction to pre-, peri and postpartal complications and the HIV transmission rate. PATIENTS AND METHODS: Retrospective study of 88 HIV-positive patients who were delivered at the Dept. of Obstetrics and Gynaecology during 1.1.1997-31.12.2001. RESULTS: HIV-positive patients showed significantly more prepartal complications, compared to control group. Low CD4-cell count (< or = 200/microl) or high viral load (> 10 000 HIV-copies/ml) was not associated with increased risk for transmission relevant complications. The overall HIV-transmission rate was 3.4 % (3/89 newborns; with ART 2.5 % [2/85], without ART 33.3 % [1/3]). The transmission rate increased with complications during pregnancy (7.7 % [2/26] vs. 1.6 % [1/61]). Newborns delivered < or = 35 (th) week of gestation showed a transmission rate of 5.3 % compared to 2.9 % of newborns delivered after the 35 (th) week of gestation. 98 % of the patients were delivered by cesarean section (primary: n = 71, prior: n = 15), spontaneously: n = 2). 97 % of patients (85/88) were treated with antiretroviral therapy (ART). No differences were found in the postpartal complication rate of HIV-positive to -negative patients. None of the newborns was breast fed. CONCLUSIONS: Treatment of this risk-pregnancies in HIV experienced centers significantly reduces the risk of HIV transmission.

Female↗
PubMed2005

[Reproduction after breast cancer: what advice do we have for our patients?].

Nowadays women delay their childbirth to the 30ies. Therefore, more breast cancer patients haven't completed their family planning and want to get children after the diagnosis of breast cancer. Because of anthracycline and cyclophosphamide containing polychemotherapies for the adjvuant treatment of breast cancer, about 50 % of the patients will be ammenorrhoic after finishing treatment. So far there are no valid treatment options for preserving ovarian function after chemotherapy. There is no increased risk for relapse if a breast cancer patient becomes pregnant. However, the timing of the pregnancy has not yet been fixed. It depends on the prognosis, the age, the personal situation and personal preferences.

Antineoplastic Agents↗
PubMed2005

The congruity between urine and cervical swab cultures in pregnant women with versus without amniotic fluid infection.

INTRODUCTION: We observed the congruity of bacteria found in urine and cervix of pregnant women with amniotic fluid infection (AFI) compared to healthy controls. PATIENTS AND METHODS: Over three years, we prospectively analysed urine and cervical swabs cultures in 120 pregnant women in gestational week 16-20. The patient population was divided in two groups: group I patients had clinical symptoms of AFI. The rest of the patients were designated as healthy controls (group II). Congruity between findings in both groups was observed. In patients with bacterial growth, antibiotic treatment was initiated as recommended and once ended - culture probes were repeated. RESULTS: The rates of nonsignificant and significant bacteriuria were doubled in group I. Fifty-five percent (n = 33) of patients in group I had identical bacteria cultured both from the urine sample and cervical swab, in contrast to only 13.3 % in group II. Congruity was most pronounced for Klebsiella species and E. coli, the later being single most dominant isolate in regards to both cultures. After antimicrobial treatment, microbial eradication occurred in 15 patients (45.5 %). The observed incidences of abortions and preterm deliveries were significantly lower in patients with microbial eradication versus patients with microbial persistence. CONCLUSION: Patients with clinical symptoms of AFI have high risk for bacteriuria identical to bacterial culture from cervical swab. Antimicrobial treatment was effective only partially where indicated. Screening for eradication is recommended and consensus on the most appropriate therapy is needed.

Amniotic Fluid↗
PubMed2005

In vivo chemosensitivity-adapted preoperative chemotherapy in patients with early-stage breast cancer: the GEPARTRIO pilot study.

BACKGROUND: Response to the first two cycles of preoperative chemotherapy might differentiate subgroups of breast cancer patients with high or minimal chances for a pathologic complete response (pCR) and may be used as an in vivo chemosensitivity test. METHODS: Breast cancer patients were treated with two cycles of TAC (docetaxel 75 mg/m(2), doxorubicin 50 mg/m(2), cyclophosphamide 500 mg/m(2) every 21 days). Patients whose tumors showed a response received four more cycles. Patients whose tumors did not respond were randomized to four additional cycles TAC or NX (vinorelbine 25 mg/m(2) days 1 and 8, capecitabine 2000 mg/m(2) days 1-14, every 21 days). The primary end point was pCR at surgery. RESULTS: Two hundred and eighty-five patients showed a clinical response, in 73.0% after two cycles, in 88.4% at surgery, and a pCR was seen in 17.9%. Breast conservation was possible in 72.2%. Responding patients obtained a pCR in 22.6% whereas non-responding patients reached a pCR in 7.3% and 3.1% with TAC or NX, respectively. Grade III/IV neutropenia and febrile neutropenia were observed during TAC in 70.2% and 13.5%, respectively. Significantly less toxicity were observed with NX. CONCLUSION: Early response to TAC can reliably identify patients with a high chance of achieving a pCR. New effective treatments need to be explored for patients without an early response.

Adult↗
PubMed2005

Phase I/II study of capecitabine and vinorelbine in pretreated patients with metastatic breast cancer.

PURPOSE: To define the maximum-tolerated dose (MTD) and to evaluate the dose-limiting toxicities (DLT) of the combination of capecitabine and vinorelbine in patients with metastatic breast cancer who relapse after adjuvant and/or first-line treatment. In addition, we aimed to obtain data on efficacy and safety at the recommended dose. PATIENTS AND METHODS: Patients with measurable metastatic breast cancer after failure of prior chemotherapy (including anthracyclines and/or taxanes) were eligible. Capecitabine was administered with a fixed dose of 1000 mg/m(2) orally twice daily for 2 weeks followed by 1 week rest. One treatment cycle consisted of 6 weeks of treatment containing two treatment periods of capecitabine. Vinorelbine was given intravenously at escalated doses of 25 mg/m(2) (dose level 1) and 30 mg/m(2) (dose level 2) on days 1 and 8, and 22 and 29. RESULTS: Thirty-three patients received a total of 91 cycles of capecitabine and vinorelbine. The median number of administered cycles per patient was three (range one to six). Thirty-one patients were evaluable for toxicity. At dose level 2 four out of seven patients experienced DLTs (nausea/vomiting, febrile neutropenia, grade 4 neutropenia, infection and diarrhea); thus, the MTD was defined. In order to confirm the safety and efficacy, dose level 1 was extended to 24 patients. Two patients [8.3%; 95% confidence interval (CI) 1% to 27%] showed DLTs (hospitalization due to febrile neutropenia and prolonged neutropenia). The main toxicity was neutropenia, which was observed at National Cancer Institute Common Toxicity Criteria grade 3 and 4 in 39% of patients. The overall response rate for capecitabine and vinorelbine was 55% (95% CI 36% to 72.7%), including three patients with a complete remission. The median time to disease progression was 8 months (95% CI 4.3-11.7) with an overall survival of 19.2 months (95% CI 11.3-27.1) based on intention-to-treat analysis. CONCLUSIONS: The combination of capecitabine and vinorelbine can be administered with manageable toxicity and showed significant efficacy for patients with metastatic breast cancer even after failure of a anthracycline- and/or taxane-based therapy.

Administration, Oral↗
PubMed2005

Bendamustine prolongs progression-free survival in metastatic breast cancer (MBC): a phase III prospective, randomized, multicenter trial of bendamustine hydrochloride, methotrexate and 5-fluorouracil (BMF) versus cyclophosphamide, methotrexate and 5-fluorouracil (CMF) as first-line treatment of MBC.

Two i.v. regimens, bendamustine, methotrexate and 5-fluorouracil (BMF) and cyclophosphamide, methotrexate and 5-fluorouracil (CMF) were compared as first-line therapy in a randomized, open, multicenter phase III trial including 364 patients with metastatic breast cancer (MBC). Bendamustine is an anti-neoplastic agent with alkylating, but also additional, so far unclear, mechanisms of action. We wanted to show the superiority of BMF over CMF in terms of time to progression (TTP) (primary endpoint), overall response, response duration, toxicity and quality of life (QoL). TTP was significantly longer in the BMF group (8.2 versus 6.7 months for CMF) (p=0.0071). The effect of BMF on TTP was more pronounced in the stratum 'prior adjuvant therapy, no visceral metastases' (p=0.034). Overall response rates and QoL did not significantly differ between the regimens. BMF caused more mucositis and leukopenias. Thus, bendamustine, when replacing cyclophosphamide in the CMF combination, can be expected to produce longer progression-free survival in first-line treatment of MBC.

Adolescent↗
PubMed2005

Diminished pregnancy rates in endometriosis due to impaired uterotubal transport assessed by hysterosalpingoscintigraphy.

OBJECTIVE: To investigate uterotubal transport by means of hysterosalpingoscintigraphy (HSSG) in women with and without endometriosis. DESIGN: A prospective observational study. SETTING: University Hospital, Department of Obstetrics and Gynaecology, Division of Reproductive Medicine and Gynaecologic Endocrinology with 350 in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles and 400 intrauterine insemination (IUI) cycles/year. POPULATION: Cases included 56 infertile women with laparoscopic proven endometriosis and patent fallopian tubes. Twenty-two women with partners suffering from male factor infertility served as controls. METHODS: A diagnostic cycle incorporating HSSG was performed. Subsequently, patients underwent either four cycles of timed intercourse (TI) or IUI in order to achieve pregnancy. If pregnancy did not occur, IVF or ICSI was performed. MAIN OUTCOME MEASURES: Evaluation of uterotubal transport capacity in women with endometriosis and healthy controls. RESULTS: Patients suffering from endometriosis (group I) showed a significant reduction in physiologic uterotubal transport function: While 20 patients (36%) had ipsi- or bilateral uterotubal transport, there was pathological uterotubal transport contralateral to the dominant follicle or a complete failure of transport capacity (negative HSSG) in 36 patients (64%). In the controls (group II), transport function was significantly different: 15 of 22 patients (68%) revealed ipsi- and bilateral tubal demonstration, while 5 patients (22%) showed contralateral transport and 2 patients (10%) showed negative HSSG (P= 0.01). Twenty-three pregnancies were observed (pregnancy rate: 29%). Eleven out of 14 (79%) women with ipsi- or bilateral tubal transport function fell pregnant by means of TI or IUI. In seven of nine patients (78%) with a failure in tubal transport, pregnancy was achieved by IVF/ICSI, despite acceptable semen parameters (P= 0.01). CONCLUSIONS: Endometriosis is significantly associated with a reduction in physiologic uterotubal transport capacity compared with controls. This resulted in diminished pregnancy rates even in women with normozoospermic partners. Therefore, IVF/ICSI may be required even when fallopian tubes are patent or semen quality is normal.

Adult↗
PubMed2005

Methylation of estrogen receptor beta promoter correlates with loss of ER-beta expression in mammary carcinoma and is an early indication marker in premalignant lesions.

The function of estrogen receptor beta (ER-beta) in mammary tissue is not completely understood. While early observations were often conflicting, more recent data suggest an important role as a tumor-suppressor gene. A decrease of ER-beta expression has been observed in ductal carcinoma in situ and invasive carcinoma as compared with benign mammary epithelial cells. The loss of ER-beta resulted in abnormal growth of mammary epithelial cells. We have previously shown that the mRNA expression of the ER-beta gene is almost totally suppressed in breast carcinomas from patients with a poor prognosis. Here we analyzed whether methylation changes in the different promoters of ER-beta are responsible for the loss of expression of the gene. A methylation assay with high specificity and sensitivity was developed, and a panel of breast tissue samples (n = 175) was characterized for methylation status. In contrast to benign breast, more than two-thirds of invasive breast cancers showed a high degree of methylation. Importantly, increased methylation was also detectable in numerous premalignant lesions. By analysis of breast tumors, previously characterized by gene-expression profiling, methylation was predominantly detected in a subgroup of patients with an unfavorable prognosis, suggesting a possible prognostic value of the ER-beta methylation status. We also investigated the structural characteristics of the two ER-beta promoters, which were both found to be closely associated with a second, downstream, localized and opposite-oriented promoter. However, we could not detect endogenous antisense RNA transcribed from these promoters, which may be involved in epigenetic gene silencing. We also failed to induce ER-beta promoter methylation by expressing siRNAs in cell lines. Interestingly, by comparing the promoter sequences of ER-beta with other genes known to be epigenetically inactivated in breast cancers, we identified a sequence motif possibly involved in promoter methylation.

Base Sequence↗
PubMed2004

Predictive value of impaired uterine transport function assessed by negative hysterosalpingoscintigraphy (HSSG).

BACKGROUND: Hysterosalpingoscintigraphy (HSSG) has given insight into the dynamics of rapid sperm transport inside the female genital tract. RESULTS: While there is an increase of an ipsilateral transport on the side bearing the dominant follicle in 70% of the subjects in the periovulatory phase, 15% of the patients do not demonstrate transport to the fallopian tubes (negative HSSG). In these patients the pregnancy rate achieved spontaneously or by intrauterine insemination is significantly reduced compared to the patients who showed an intact transport mechanism confirmed by positive HSSG. On the other hand, by means of assisted reproductive techniques (ART), pregnancy rates were higher in the group of patients showing negative HSSG (P < 0.0005). CONCLUSIONS: Our data clearly indicate that HSSG is a helpful method to evaluate the integrity of the utero-tubal transport mechanism. As pregnancy rates remain low in patients with negative HSSG, this result should be considered as an indication for IVF-treatment even in patients with patent fallopian tubes and normozoospermia of the partner.

Fallopian Tube Patency Tests↗
PubMed2004

ParSeq: searching motifs with structural and biochemical properties.

SUMMARY: Searches for variable motifs such as protein-binding sites or promoter regions are more complex than the search for casual motifs. For example, in amino acid sequences comparing motifs alone mostly proves to be insufficient to detect regions that represent proteins with a special function, because the function depends on biochemical properties of individual amino acids (such as polarity or hydrophobicity). Pure string matching programs are not able to find these motifs; hence, we developed ParSeq, a program that combines the search for motifs with certain structural properties, the verification of biochemical properties, an approximate search mechanism and a stepwise creation of the motif description by allowing to search on previously obtained results. AVAILABILITY: http://www-pr.informatik.uni-tuebingen.de/parseq

Algorithms↗
PubMed2004

[Sentinel lymph node biopsy in breast cancer].

Surgical treatment of breast cancer has changed dramatically during the last few decades with the aim of reducing surgical radicality in the breast and also in the axilla. In this context sentinel node biopsy is a reliable technique to determine axillary node status of breast cancer patients and reduce morbidity associated with standard axillary lymph node dissection. Although SNB is performed with increasing frequency, an incorrect indication and lack of experience with the surgical procedure can minimize the sensitivity and specificity of this method. In consequence, this could lead to wrong tumor staging and inappropriate adjuvant therapy. Therefore, we describe the basic requirements, indications, and pitfalls of this technique. Since many issues are controversial such as the prognostic value of micrometastases and extramammary nodes as well as the use of SNB after primary chemotherapy and in ductal carcinoma in situ, further clinical studies are necessary.

Axilla↗