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M Kaufmann

Publications and source records attributed to M Kaufmann.

At least 127 records · Page 7Linked to original sources
PubMed1999

Meta-analysis of trials comparing toremifene with tamoxifen and factors predicting outcome of antiestrogen therapy in postmenopausal women with breast cancer.

Meta-analysis of all clinical data was conducted to compare toremifene 40-60 mg/day (TOR) with tamoxifen 20-40 mg/day (TAM) in postmenopausal women with estrogen receptor (ER) positive or ER unknown advanced breast cancer and assess factors predicting treatment outcome. Data from five randomized parallel group studies (all studies) were combined. Efficacy variables were the response rate in all studies and also the time to treatment failure and survival in the three major studies (pivotal studies). Of the 1421 patients, 725 received TOR and 696 TAM. Response rates were 24.0% and 25.3%, respectively (p = 0.675) with 95% confidence interval (95% CI) for the difference -5.3 to 3.4. Of the 1157 patients in the pivotal studies, 75% had progressed and 50% expired. Median treatment times were 4.9 months in TOR and 5.3 months in TAM groups (p = 0.762, hazard ratio 0.98 with 95% CI 0.87-1.11). Median survival times were 31.0 (TOR) and 33.1 (TAM) months (p = 0.758, hazard ratio 0.98 with 95% CI 0.83-1.15). All results are consistent with the criteria of statistical equivalence between TOR and TAM. More patients in TAM (20%) than in TOR (14%, p = 0.007) discontinued the treatment prematurely but overall the treatments were well tolerated. As the treatments were equally effective all data were analyzed together for predictive factors. High tumor ER concentration, long disease free time, soft tissue metastases, few metastatic sites, and good performance status all independently predicted longer survival (p<0.001). Previous adjuvant tamoxifen predicted shorter survival (p = 0.008). Objective response to treatment or disease stabilization for at least 12 months both predicted prolonged survival (p = 0.001). TOR 60 mg/day and TAM are equally effective and well tolerated in the treatment of advanced breast cancer in postmenopausal women. Probability of survival may be predicted based on patient characteristics and on the initial response to the treatment.

Aged↗
PubMed1999

Spontaneous labour at term is associated with fetal monocyte activation.

The aetiology of both term and preterm labour remains incompletely understood. Maternal infectious diseases as well as intra-uterine infections were shown to be a well established cause of uncontrollable preterm delivery, indicating that inflammatory reactions, regulated by maternal immunecompetent cells, are implicated in labour-promoting mechanisms. To investigate the possibility that the activation of the fetal immune system may be involved in labour induction, we examined cytokine production patterns of different cord blood cell populations obtained from neonates after spontaneous onset of normal term labour and vaginal delivery (n = 25), vaginal delivery but induced term labour (n = 17), and preterm delivery because of uncontrollable labour (n = 27, 20 patients received corticoid treatment for fetal lung maturation), in comparison with cells obtained from neonates after elective term caesarean delivery in the absence of labour (n = 15). Our results demonstrate that spontaneous term labour, but not induced term labour, was associated with significantly increased IL-6 production by myelomonocytic cell populations. Preterm delivery due to uncontrollable labour with resistance to tocolysis was not associated with increased IL-6 production by fetal myelomonocytic cells. Two-colour flow cytometry combined with intracellular cytokine staining was used to identify fetal monocytes as sources of labour-associated IL-6 release at term. We did not find any activation of cord blood T cells in association with spontaneous term or uncontrollable preterm labour. Therefore, fetal T cell responses may not cause monocyte activation. Our results suggest that increased release of IL-6 from fetal monocytes is involved in mechanisms promoting normal term, but not preterm labour, and that mechanisms inducing term and preterm labour are completely different.

Betamethasone↗
PubMed1999

Labour-associated expression of intercellular adhesion molecule-1 (ICAM-1) in placental endothelial cells indicates participation of immunological processes in parturition.

Inflammatory cytokines induce or upregulate de novo expression of cell adhesion molecules on endothelial and epithelial cells. In order to demonstrate inflammatory reactions within placental tissues in association with normal term as well as non-infection-induced preterm labour, the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1) was examined by immunohistochemical methods in both trophoblastic villi (n=123) and umbilical cord (n=61). As a result, ICAM-1 immunoreactivity was exclusively localized in the endothelial cells of the fetal vascular system, while VCAM-1 and ELAM-1 were not detected. Whereas ICAM-1 was not expressed in early pregnancy (9-12 weeks of gestation), it could be weakly detected at the end of pregnancy in cases of elective caesarean delivery in the absence of labour, and was significantly more strongly expressed in cases of vaginal delivery after spontaneous onset of normal term labour. Significantly increased immunoreactivity of ICAM-1 within umbilical cord tissues was also found in association with uncontrollable preterm labour in the absence of intrauterine infection which was excluded after histological examination of fetal membranes, umbilical cord and chorionic plate. We conclude that ICAM-1 expression in the endothelium of the fetal vascular system is associated with the presence of labour and reflects participation of immune-inflammatory reactions in labour-promoting mechanisms.

Adult↗
PubMed1999

Identification of an alpha2,6-sialyltransferase induced early after lymphocyte activation.

We have used mRNA differential display PCR to search for genes induced in activated T cells and we identified a gene encoding an alpha2,6-sialyltransferase (ST6GalNAc IV) that is rapidly induced in lymphocytes after antigen or mitogen stimulation. The 3.6 kb full-length cDNA clone (MK45) obtained contained a single open reading frame encoding a 302 amino acid protein and a 2.5 kb 3' untranslated region. MK45 expression in in vivo-activated CD8 T cells reached the highest level 4 h after antigen triggering and then declined rapidly to nearly base levels within 45 h. Northern blot analysis further revealed that MK45 expression was also induced in LPS-activated B cells and antigen-triggered CD4 T cells in vitro. MK45 expression was low or undetectable in most other mouse tissues examined, when compared to activated lymphocytes. Importantly, the mRNA expression level of other sialyltransferases remained largely unchanged during the early stage of lymphocyte activation. Finally, increased ecto-sialyltransferase activity and an altered sialylation pattern were demonstrated on the cell surface of early activated CD8 T cells. Our report identifies a candidate sialyltransferase gene that is involved in the early alteration of the sialylation pattern of cell surface molecules in activated lymphocytes.

Amino Acid Sequence↗
PubMed1999

Phase II study of gemcitabine as first-line chemotherapy in patients with advanced or metastatic breast cancer.

In this phase II study, the efficacy and tolerability of gemcitabine were studied in 42 patients with locally advanced or metastatic breast cancer who had received up to one prior chemotherapy regimen in an adjuvant setting. Ten patients had received adjuvant chemotherapy. Twenty-eight patients (67%) had visceral disease spread at entry. Gemcitabine (1000 mg/m2) was administered weekly on days 1, 8 and 15 of a 28-day cycle. The mean number of completed cycles was 3.9 and the mean dose delivered was 942.2 mg/m2. Ninety-seven percent of injections were administered as assigned. No complete responses were observed, but there were six partial responses and 24 patients with stable disease lasting 2-9 months. The overall response rate was 14.3% (95% CI 5.4-28.5%). The median survival for all patients was 15.2 months. Maximum WHO grade 3 and 4 toxicities were observed in five patients for nausea and vomiting, one patient for diarrhea, one patient for pain, seven patients for alanine transaminase, and eight patients for segmented neutrophils. There were no grade 3 and 4 toxicities for alopecia. These data confirm modest single-agent gemcitabine activity in advanced or metastatic breast cancer. Gemcitabine's favorable toxicity profile makes it an ideal candidate for combination chemotherapy.

Adult↗
PubMed1999

Maximized reduction of primary breast tumor size using preoperative chemotherapy with doxorubicin and docetaxel.

PURPOSE: To assess the toxicity and efficacy of preoperative chemotherapy with doxorubicin and docetaxel in patients with primary operable breast cancer. PATIENTS AND METHODS: Forty-two patients with histologically confirmed primary breast cancer tumors of at least 2 cm in diameter received doxorubicin (50 mg/m(2) intravenously [IV] over 15 minutes) and docetaxel (75 mg/m(2) IV over 1 hour) every 14 (24 patients) or 21 (18 patients) days for four cycles. RESULTS: The median size of the primary tumor decreased significantly, from 4 cm (range, 2 to 10 cm) to 2 cm (range, 0 to 5 cm) on physical examination and from 3.4 cm (range, 1 to 8 cm) to 1. 8 cm (range, 0 to 4 cm) on sonography (P <.001). The overall response rate as assessed by physical examination was 93%, and complete remission of the primary tumor occurred in 33% of patients. The remission rate as assessed by sonographic measurement was 67%. Two patients (5%) had histologically confirmed complete responses. Sonography was more reliable than palpation in predicting histologically determined response. No grade 4 toxicity was noted, and grade 3 toxicity was reported with alopecia (95%), lethargy (17%), loss of appetite (10%), stomatitis (7%), leukopenia (5%), skin desquamation (5%), infection (5%), motor neuropathy (2%), and nausea (2%). The 3-week schedule was associated with less toxicity than the 2-week schedule. CONCLUSION: Preoperative combination chemotherapy with doxorubicin and docetaxel is highly effective and feasible in primary operable breast cancer.

Adult↗
PubMed1999

Phenol degradation by an enterobacterium: a Klebsiella strain carries a TOL-like plasmid and a gene encoding a novel phenol hydroxylase.

Although phenol catabolism is described for many different microorganisms, there is no example for such a pathway in an enterobacterial strain. Here we characterize a Klebsiella oxytoca strain that grows on phenol as the only source of carbon and energy. As the key enzyme of phenol degradation, phenol hydroxylase was purified to apparent homogeneity. Compared with other phenol hydroxylases, the Klebsiella enzyme differs with respect to several properties: (i) SDS-PAGE and gel-filtration analysis of the purified protein revealed that the enzyme is a monomer with a molecular mass of 156 kDa; (ii) steady-state kinetic measurements resulted in a K(m) value of 0.22 mM for phenol; and (iii) the enzyme is both dependent on NADPH/FAD and sensitive to EDTA. Further degradation of catechol, the reaction product of phenol hydroxylase, may occur via the effective meta-fission pathway often located on TOL or TOL-like plasmids. Such a plasmid was prepared from the Klebsiella strain and further characterized. The given data demonstrate that the isolated strain exhibits all characteristics of an efficient phenol-degrading microorganism.

Biodegradation, Environmental↗
PubMed1999

The role of docetaxel (Taxotere) in neoadjuvant chemotherapy of breast cancer.

Neoadjuvant chemotherapy has become standard therapy in the management of breast cancer patients with locally advanced disease with inoperable tumors and inflammatory breast cancer. Patients with earlier stage breast cancer and operable tumors may also benefit from treatment with neoadjuvant chemotherapy. Docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) is thought to be one of the most potent agents in the treatment of metastatic breast cancer and is therefore being investigated for its likely benefit in preoperative, neoadjuvant regimens. Several large phase II and randomized phase III trials are evaluating docetaxel as a single agent, in combination, and/or sequentially in the preoperative setting. Preliminary findings demonstrate high complete and partial response rates and a tolerable toxicity profile. These results are consistent with the view that incorporation of docetaxel in neoadjuvant chemotherapy regimens will contribute to improved patient outcome. Ongoing studies will provide important information regarding the most appropriate regimens and schedules of docetaxel to use in the preoperative, neoadjuvant setting.

Anthracyclines↗
PubMed1999

[Value of fetal lung maturity assessment in maternal diabetes].

OBJECTIVE: Results of antepartal fetal lung maturity (FLM) testing in diabetics were compared to control patients. We analysed 274 patients by phospholipid profile and 219 by phosphatidylglycerol (PG), consisting of 73, respectively 54 diabetic and 201, resp. 165 normal control subjects. MATERIAL AND METHODS: Phospholipid concentration increased exponentially with gestational age (rreg = 0.44 for diabetic and 0.57 for normal control patients). There was no significant difference between both groups. Measurement of PG showed a trend towards lung immaturity in diabetic infants for preterm and term gestations, which did not reach significance (chi-square [chi 2] test 0.07, resp. 0.06). RESULTS: Diabetic and non-diabetic pregnancies did not differ significantly in FLM and RDS frequency. Both methods show a high rate of falsely immature results. Antepartal FLM testing by measurement of phospholipids and PG does not play a role in clinical management of diabetic patients.

Amniocentesis↗
PubMed1998

Virus-activated CD8 T cells and lymphokine-activated NK cells express the mast cell function-associated antigen, an inhibitory C-type lectin.

The mast cell function-associated Ag (MAFA) is an inhibitory C-type lectin that was originally identified on the cell surface of a rat mucosal mast cell line, RBL-2H3. We have cloned the mouse homologue of the rat MAFA gene, and Northern blot analysis revealed that mouse MAFA (mMAFA) gene expression was strongly induced in effector CD8 T cells and lymphokine-activated NK cells but not in effector CD4 T cells and in mouse mast cells. Moreover, mMAFA gene expression was only found in effector CD8 T cells that had been primed in vivo with live virus because in vitro activated CD8 T cells did not express mMAFA. Primary sequence comparison revealed a high degree of conservation (89% similarity) between rat MAFA and mMAFA. Thus, the MAFA molecule in the mouse is a putative inhibitory receptor on anti-viral CD8 T cells induced in vivo and on NK cells.

Amino Acid Sequence↗
PubMed1998

Reduction in new metastases in breast cancer with adjuvant clodronate treatment.

BACKGROUND: Bisphosphonates are effective against the increased bone resorption caused by certain diseases because they inhibit the activity of osteoclasts. In patients who have breast cancer and metastatic bone disease, the bisphosphonate clodronate (clodronic acid) reduces the frequency of skeletal complications. Experiments in animals and preliminary clinical observations indicate that early clodronate therapy reduces the incidence of new bony metastases in breast cancer. We investigated the effects of clodronate on the incidence and extent of new metastases in patients with breast cancer. METHODS: Between 1990 and 1995, 302 patients with primary breast cancer and tumor cells in the bone marrow (the presence of which is a risk factor for the development of distant metastases) were randomly assigned to receive clodronate at a dose of 1600 mg per day orally for two years (157 patients) or standard follow-up (145 patients). The median length of observation was 36 months. All patients in both groups received standard surgical treatment and customary hormonal therapy or chemotherapy. RESULTS: Distant metastases were detected in 21 patients in the clodronate group and in 42 patients in the control group (P<0.001). The incidence of both osseous and visceral metastases was significantly lower in the clodronate group than in the control group (P=0.003 for both osseous and visceral metastases). Six patients in the clodronate group died, as did 22 in the control group (P=0.001). The mean number of bony metastases per patient in the clodronate group was roughly half that in the control group (3.1 vs. 6.3). CONCLUSIONS: Clodronate can reduce the incidence and number of new bony and visceral metastases in women with breast cancer who are at high risk for distant metastases.

Adult↗
PubMed1998

[Therapeutic strategy in advanced breast carcinoma].

Breast cancer metastastic to sites beyond regional axillary lymph nodes represents a historically incurable condition despite the judicious use of various hormonal manipulations and surgical and radiotherapeutic interventions, and the application of active cytotoxic chemotherapeutic agents for hormone-refractory disease. The systemic management of patients with hormone refractory breast cancer is classically characterized by the thoughtful, stepwise administration of cytotoxic chemotherapeutic agents. At various junctures in the continuum of care, a patient/physician analysis of the potential risks and benefits of chemotherapy may lead to the decision to proceed with subsequent systemic therapy, to consider an investigational strategy like new active agents or high dose therapy, or to opt for supportive care alone.

Breast Neoplasms↗
PubMed1998

Beta-galactoside-binding protein secreted by activated T cells inhibits antigen-induced proliferation of T cells.

We have used mRNA differential display PCR to search for genes induced in activated T cells and have found the LGALS1 (lectin, galactoside-binding, soluble) gene to be strongly up-regulated in effector T cells. The protein coded by the LGALS1 gene is a beta-galactoside-binding protein (betaGBP), which is released by cells as a monomeric negative growth factor but which can also associate into homodimers (galectin-1) with lectin properties. Northern blot analysis revealed that ex vivo isolated CD8+ effector T cells induced by a viral infection expressed high amounts of LGALS1 mRNA, whereas LGALS1 expression was almost absent in resting CD8+ T cells. LGALS1 expression could be induced in CD4+ and CD8+ T cells upon activation with the cognate peptide antigen and high levels of LGALS1 expression were found in concanavalin A-activated T cells but not in lipopolysaccharide-activated B cells. Gel filtration and Western blot analysis revealed that only monomeric betaGBP was released by activated CD8+ T cells and in vitro experiments further showed that recombinant betaGBP was able to inhibit antigen-induced proliferation of naive and antigen-experienced CD8+ T cells. Thus, these data indicate a role of betaGBP as an autocrine negative growth factor for CD8+ T cells.

Animals↗
PubMed1998

Estimation of probability of malignancy using a logistic model combining physical examination, ultrasound, serum CA 125, and serum CA 72-4 in postmenopausal women with a pelvic mass: an international multicenter study.

BACKGROUND: To assess the differential diagnostic potential of physical examination, ultrasound, the serum CA 125 assay, and serum CA 72-4 assay, and the contribution of each parameter to a logistic model predicting the probability of malignancy in postmenopausal patients presenting with a pelvic mass. PATIENTS AND METHODS: In a multicenter, prospective study a total of 155 patients were evaluated preoperatively using a standard protocol for pelvic examination, transvaginal (occasionally additional abdominal) ultrasound, and serum CA 72-4 (cutoff level 3 U/ml) and CA 125 (cutoff level 35 U/ml). RESULTS: Fifty-nine malignant (39%) and 92 benign (61%) pelvic tumors were found in addition to 4 borderline tumors (3%). Forty-three patients appeared to have ovarian carcinoma, FIGO Stage III or IV in 28 cases. Borderline tumors were excluded from the statistical calculations. The diagnostic accuracy of each single parameter, i.e., pelvic examination, ultrasound, and serum CA 125 and CA 72-4 in discriminating between benign and malignant pelvic masses gave highly similar results (81, 76, 78, and 81% respectively). Best sensitivity was found in pelvic examination (92%); best specificity was found in CA 72-4 (93%). Using logistic regression analysis the power of pelvic examination appeared to be the most relevant (adjusted odds ratio 12.1), followed by ultrasound (odds ratio 9.7), serum CA 125 (odds ratio 5.0), and serum CA 72-4 (odds ratio 4.9). Age appeared to be nonpredictive. The logistic model gives a correct prediction in 87% of all cases. CONCLUSIONS: The addition of serum CA 72-4 to the combination of pelvic examination, ultrasound, and serum CA 125 leads to an improved discrimination between malignant and benign pelvic masses.

Aged↗
PubMed1998

Current trials of the German Adjuvant Breast Cancer Group (GABG).

Since 1981 the German Adjuvant Breast Cancer Study Group (GABG) has recruited approximately 5000 patients with primary breast cancer in randomized trials to evaluate systemic therapies. More than 70 hospitals all over Germany are participating in this group. Allocation to the different trials is based on a risk-oriented selection of patients (menopausal status, nodal involvement and hormonal receptor content). In the currently running trials chemo-endocrine or endocrine-endocrine sequences are investigated. In premenopausal patients the value of GnRH analogues are compared with conventional CMF chemotherapy. The aim of two further trials is to reduce local surgery or radiotherapy in patients with low risk for locoregional relapse. In a recently started study dose-intensified preoperative chemotherapy in combination with or without tamoxifen is evaluated in patients with operable breast tumors > or = 3 cm.

Antineoplastic Agents, Hormonal↗
PubMed1998

Control of a nosocomial outbreak of vancomycin resistant Enterococcus faecium in a paediatric oncology unit: risk factors for colonisation.

UNLABELLED: In order to determine the extent of vancomycin resistant enterococcus (VRE) colonisation within a paediatric oncology unit, the risk factors for the acquisition of the organism, the molecular epidemiology of the isolates and the impact of infection control measures, extensive patient and environmental surveillance was undertaken with identification, antibiotic susceptibility testing and pulsed-field gel electrophoresis (PFGE) of all VRE isolates. A matched case control study was carried out. Fourteen patients (19% of screened patients) with VRE colonisation were identified (12 with Enterococcus faecium). All isolates manifested the Van A phenotype. Extensive environmental contamination with VRE was present. PFGE of E. faecium isolates from 10 patients and from five of six environmental cultures revealed patterns suggesting genetic relatedness. Following comparison of the 14 cases with 41 controls matched for age (+/- 4 years) and cohabitation on the oncology unit, risk factors for colonisation with VRE included duration of neutropenia, (OR, 3.72; 95% CI, 1.0-13.1), and antibiotic therapy, (OR, 4.07; 95% CI, 1.08-15.3), the number of antibiotic agents received, (OR, 8.4; 95% CI, 1.34-34.3) and the duration of therapy with amikacin, (OR, 10.7; 95% CI, 1.4-81.5), ceftazidime, (OR, 11.5; 95% CI, 2.2 59.9) or teicoplanin, (OR, 12.3; 95% CI, 2.25-67.4). Implementation of stringent infection control measures reduced environmental contamination from 25% of samples in week 1 to none in week 11. Two additional colonised patients were identified during the subsequent 6 months. CONCLUSION: Risk factors for VRE colonization in paediatric oncology patients included duration of neutropenia, duration of any antibiotic therapy, exposure to ceftazidime, amikacin or teicoplanin and the number of antibiotics used. The study suggests that environmental contamination played an important role in patient-to-patient transmission of VRE and interventions including implementation of infection control measures were associated with a decreased incidence of gastro-intestinal colonisation.

Adolescent↗
PubMed1998

Identification of placental cytokine-producing cells in term and preterm labor.

OBJECTIVE: To determine if the production of proinflammatory cytokines by placentally derived macrophages changes with term and preterm labor and to examine if changes in antigen expression of these cytokines can be detected by immunohistologic methods. METHODS: Enzymatically dispersed placental cell suspensions of the trophoblastic villi, obtained from 16 women with spontaneous term delivery, 16 women with elective cesarean delivery without any labor, and 22 preterm delivering women with labor unresponsive to tocolysis, were fractionated by magnetic-associated-cell-sorting, on the basis of CD11b-antigen expression. Positively and negatively sorted cell fractions were cultured and concentrations of interleukin-6, interleukin-1beta, and tumor-necrosis-factor-alpha were measured in the culture supernatants. Immunohistologic staining was used for identification of cytokine-producing cells within placental tissues. RESULTS: Positively sorted cells obtained from term (median 2027 pg/mL, P = .037) and preterm (median 3628 pg/mL, P = .001) laboring women produced significantly elevated amounts of tumor-necrosis-factor-alpha compared with nonlaboring (median 1088 pg/mL) women at term. Negatively sorted cell fractions obtained from term (median interleukin-1beta 162 pg/mL, P = .031, median interleukin-6 3134 pg/mL, P = .004) and preterm (median interleukin-1beta 934 pg/mL, P = .003, median interleukin-6 5695 pg/mL, P = .001) laboring women produced significantly elevated amounts of interleukin-1beta and interleukin-6 compared with nonlaboring (median interleukin-1beta 29 pg/mL, median interleukin-6 135 pg/mL) women at term. Immunohistologic staining revealed that tumor-necrosis-factor-alpha activity was localized in isolated stromal cells, whereas interleukin-1beta and interleukin-6 were predominantly found in endothelial cells within placental villi. CONCLUSION: The source of labor-associated release of tumor-necrosis-factor-alpha from placental tissues are macrophages, whereas interleukin-1beta and interleukin-6 are released from placental endothelial cells.

Cytokines↗