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T Steinmetz

Publications and source records attributed to T Steinmetz.

16 recordsLinked to original sources
PubMed2007

Second-line chemotherapy with pemetrexed after gemcitabine failure in patients with advanced pancreatic cancer: a multicenter phase II trial.

BACKGROUND: A standard second-line chemotherapy regimen has yet to be defined for patients with gemcitabine (Gem)-refractory advanced pancreatic cancer (PC). PATIENTS AND METHODS: In this multicenter phase II trial, patients with unresectable or metastatic PC who had progressed on single-agent Gem or a Gem-containing regimen received pemetrexed 500 mg/m(2) as a 10-min infusion every 3 weeks until disease progression or occurrence of unacceptable toxicity. The primary end point was the 3-month survival rate. RESULTS: A total of 192 treatment cycles were given to 52 patients. The overall response rate was 3.8% (two partial responses); 10 patients (19.2%) experienced stable disease, nine of them for >12 weeks. At least one CA 19-9 reduction > or =50% occurred in 12 patients (23.1%). The 3-month survival rate was 75% (95% confidence interval 63.2% to 86.8%), the median time to tumor progression was 7 weeks (range 1-62 weeks) and the median overall survival time was 20 weeks (range 1-84 weeks). Grade 3/4 hematological toxic effects included (percent of patients): neutropenia (17.3%), thrombocytopenia (5.8%) and anemia (3.8%). The most frequent non-hematological toxic effects were diarrhea, nausea and stomatitis/pharyngitis (23.1% each). CONCLUSION: Pemetrexed is a safe treatment option with moderate activity in patients with advanced PC after failure of Gem.

Adult↗
PubMed2005

Gene organization and sequences of pediocin AcH/PA-1 production operons in Pediococcus and Lactobacillus plasmids.

AIMS: To determine the locations and sequences of pediocin AcH production genes in Pediococcus parvulus ATO77 from vegetables, Lactobacillus plantarum WHE92 from Muenster cheese, and a lactose-fermenting isolate Pediococcus pentosaceus S34 from buffalo milk. METHODS AND RESULTS: Plasmid curing, Southern blot hybridization, and DNA sequence analysis indicate that pediocin AcH production genes are encoded by highly similar operons in unique plasmids designated pATO77 from P. parvulus ATO77, pS34 from P. pentosaceus S34, and pWHE92 from Lact. plantarum WHE92. Structure, immunity and secretion system genes are linked together in the operons, and the promoter sequences are the same. The amino acid sequences of the encoded proteins are highly conserved between plasmids. CONCLUSIONS: Pediocin AcH production genes are located within a plasmid-borne operon cassette in all lactic acid bacterial strains examined to date. All four genes needed for production are present within a single plasmid in each strain. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first demonstration that the expression of a class IIa bacteriocin is directed by a common gene cassette that has been disseminated to unique plasmids in different genera of lactic acid bacteria. These plasmids should be useful for expressing pediocin AcH in Pediococcus and Lactobacillus strains used in food production.

Bacteriocins↗
PubMed2002

Elevation of soluble tumor necrosis factor receptor II in non-febrile patients with acute myeloid leukemia.

BACKGROUND: Tumor necrosis factor alpha (TNF) and its cellular and soluble (s) receptors (TNF-R) are important mediators in acute myeloid leukemia (AML) and infectious complications during cytoreductive therapy. We investigated the serum concentrations of sTNF-RII in previously untreated patients with AML at the onset of cytoreductive therapy and in non-febrile chemotherapy-associated neutropenia. PATIENTS AND METHODS: Of 54 eligible patients with AML, serum concentrations of sTNF-RII could be evaluated in 25 non-neutropenic, non-febrile and in 11 neutropenic, non-febrile patients. RESULTS: At baseline, non-neutropenic, non-febrile AML patients showed high median serum sTNF-RII concentrations of 3,804 pg/mL. In neutropenia, there was a non-significant trend (p = 0.18) to lower median sTNF-RII levels of 3,246 pg/mL. CONCLUSIONS: Serum sTNF-RII concentrations in non-febrile AML patients before chemotherapy are in the range of levels reached in uncomplicated febrile episodes in otherwise healthy individuals. This must be taken into account when evaluating the cytokine profile for sepsis in patients with therapy-associated neutropenia. Concentrations are still elevated in neutropenia, suggesting that a normal number of leukocytes is not necessarily required for the activation of the TNF ligand/TNF receptor system in AML.

Adult↗
PubMed2001

Randomized controlled monocentric comparison of once daily ceftriaxone with tobramycin and cefotaxime three times daily with tobramycin in neutropenic fever.

A prospective, randomized, controlled monocentric trial was performed to evaluate the efficacy and safety of once daily ceftriaxone 2 g plus tobramycin 5 mg/kg in comparison to cefotaxime 2 g t.i.d. plus tobramycin 5 mg/kg qd in the treatment of neutropenic fever. In cases of fever > or = 38.5 degrees C and a neutrophil count below 1000/microliter, patients with hematological malignancies were assigned to ceftriaxone or cefotaxime, each with tobramycin. The primary endpoint was defined as defervescence < 37.5 degrees C on day 4-6 followed by at least 7 afebrile days. Secondary endpoints were overall response, defined as defervescence on day 25 and toxicity. There were 160 episodes of 114 patients included. Fever of unknown origin accounted for 79 episodes (51%), microbiologically defined infection for 36 (23%), clinically defined infection for 27 (17%), and both clinically and microbiologically defined infection for 14 episodes (9%). On an intent-to-treat basis 156 episodes could be evaluated for the primary endpoint. Ceftriaxone plus tobramycin and cefotaxime plus tobramycin resulted in a primary response in 46.9% and 45.3%, respectively. Overall response was achieved on study day 25 in 87.7% and 80%, respectively. No significant difference in toxicity was observed. Once-daily ceftriaxone plus tobramycin was not inferior to cefotaxime t.i.d. plus tobramycin qd in the empirical treatment of neutropenic fever.

Adult↗
PubMed1998

3-D confocal laser scanning microscopy used in morphometric analysis of rat Purkinje cell dendritic spines after chronic ethanol consumption.

A confocal laser scanning microscope (with a 543 nm laser) was used for imaging rat Purkinje cell dendritic spines at high 3-D resolution. In a nutritionally controlled study of the rat, 5 months of ethanol consumption was demonstrated to alter the spines of Purkinje cell dendrites in rat cerebellum. Intact spines showed significant elongation after ethanol exposure, whereas this neuromorphological alteration could not be detected in controls. Spine elongation could be regarded as compensative growth of spines in search of new synaptic contacts due to alcohol induced cell loss.

Alcoholism↗
PubMed1996

Can megadoses of thiamine prevent ethanol-induced damages of rat hippocampal CA1 pyramidal neurones?

The specific aim of this study was to evaluate whether high doses of thiamine can compensate or prevent alcohol-induced damages of rat hippocampus CA1 pyramids. Twenty weeks of ethanol consumption together with a dose of thiamine in the range of 1.19 mg/100 mg food induced significant enlargement (parameters measured were length of the whole spine and diameter of the end-bulb) of dendritic spines. Hypertrophy can be interpreted as a compensation process due to alcohol-induced cell death because viable spines are in search of new synaptic contacts. In contrast, dendritic spines of the alcohol group fed at the same time with a high dose of thiamine (119 mg/ 100 g food = megavitamintherapy) showed normal data concerning these parameters. From these results it may be concluded that a megavitamin therapy supports a neuron's carbohydrate metabolism and therefore could be able to prevent or reduce alcohol-induced damages of hippocampal CA1 pyramidal cells in rat central nervous system.

Alcoholism↗
PubMed1996

Neuroprotective effects of thiamine-megadoses after long-term ethanol application in the rat brain. A structural investigation of hippocampal CA1 pyramidal and cerebellar Purkinje neurons.

Using the Golgi-impregnation technique we could document that twenty weeks of ethanol consumption induce significant elongation of dendritic spines of rat cerebellar Purkinje cells, and as demonstrated for the first time in the present study, of hippocampal pyramidal neurons. Spine hypertrophy might be the result of compensative growth of spines in search of new synaptic contacts due to neuronal cell loss caused by the prolonged ethanol intake. In contrast, this neuromorphological alteration could not be detected in the alcohol group fed at the same time with a high dose of thiamine (119 mg/100 g food) = thiaminemegadose). As thiamine participates in a number of enzymatic reactions primarily concerned with carbohydrate metabolism, it may be concluded that megadoses of thiamine are able to support neuronal energy metabolism, which was initially impaired by ethanol-induced thiamine deficiency. Therefore, a megavitamintherapy in association with chronic alcohol intake could be able to attenuate or prevent ethanol-induced damages in rat central nervous system.

Animals↗
PubMed1993

Immunophenotyping of low-grade B-cell lymphoma in blood and bone marrow: poor correlation between immunophenotype and cytological/histological classification.

Results of immunophenotypic examinations of peripheral blood and/or bone marrow (BM), involved in low-grade B-cell non-Hodgkin's lymphomas, were compared with the results of cytomorphological and histopathological examinations in 133 adult patients. 69 cases of chronic B-lymphocytic leukaemia (B-CLL), 16 centrocytic (CC) lymphomas, 14 centroblastic-centrocytic (CB/CC) lymphomas, 15 immunocytomas (IC), 10 cases of hairy cell leukaemia (HCL), four prolymphocytic leukaemias (PLL), two B-CLL in transformation, one splenic lymphoma with villous lymphocytes (SLVL), one hairy cell leukaemia variant (HCL-V), and one lymphocytic lymphoma (LC) were classified according to the Kiel and/or FAB classification. Leukaemic disease was found in 105 cases. The following markers were used for immunocytology (APAAP technique) of blood and/or BM smears: CD19, CD5, CD10, CD11c, CD14, CD21, CD22, CD23, CD25, CD38 and TdT. All cases tested showed CD19, but no TdT expression. Every case of HCL had a distinct phenotype with expression of CD11c, CD22 and CD25 and the lack of CD5 and CD23 antigens. In all other NHL cases a very heterogenous expression of CD-antigens with no significant correlations to the cytomorphological subtypes was found. The expression of CD5 is a frequent but inconstant finding in lymphoproliferative diseases other than B-CLL, so 50% of CB/CC, 75% of CC and 80% of IC were CD5 positive. Our results indicate that, with the exception of HCL, the diagnostic relevance of immunophenotyping for the classification of cytomorphologically and histopathologically defined subtypes in blood and/or BM is of very limited value.

Aged↗
PubMed1992

Bone marrow involvement in non-Hodgkin's lymphoma: increased diagnostic sensitivity by combination of immunocytology, cytomorphology and trephine histology.

Diagnostic results from cytomorphology and immunocytology of aspirated bone marrow (BM) were compared with the findings from standard trephine histology of 100 adult patients with non-leukaemic non-Hodgkin's lymphomas (NHL) in a retrospective study. Immunocytological investigations were performed by the immunoenzymatic APAAP-technique on BM smears monoclonal antibodies against CD19, Cd3, CD10 or TdT antigens and determination of positive cells in relation to total BM leucocytes. Corresponding results were obtained for trephine histology and for the combination of cytomorphology and immunocytology in 93/100 cases. Four cases with BM involvement by trephine histology were missed by the combination of immunocytology and cytomorphology. In turn, three cases negative by trephine histology, were found to be positive by the combination of immunocytology and cytomorphology. Immunocytochemistry considerably increased the number of true positive detected BM-infiltrations by cytomorphology in low grade B-cell lymphoma from 58% to 97%. For the diagnosis of BM involvement in high-grade NHL cytomorphology of the aspirate was of equal sensitivity to the biopsy and was always confirmed by immunocytology. The high diagnostic sensitivity of immunocytology was mainly due to high B-cell counts in BM involved by B-cell lymphoma (means = 38%, s = 23) in contrast to low B-cell counts in BM not involved by NHL (means = 4.5%, s = 3.8). We conclude from our data that immunocytology in addition to standard cytomorphology improves diagnostic sensitivity in the detection of BM involvement by NHL.

Adolescent↗
PubMed1990

Phase II study of recombinant human tumor necrosis factor in colorectal carcinoma.

Fifteen patients with colorectal carcinoma received a 30-min intravenous infusion of recombinant human tumor necrosis factor (rHuTNF) to investigate the value of rHuTNF in the treatment of colorectal carcinoma. Patients received 5 x 10(5) U/m2 (217 micrograms/m2) on day 1, and in the absence of serious side effects 10 x 10(5) U/m2 (435 micrograms/m2) on day 3 and 15 x 10(5) U/m2 (652 micrograms/m2) on day 5. The cycle was repeated on day 28. Full dose escalation was possible in all patients. There was a minor response in one patient (disappearance of retroperitoneal lymph nodes). All other patients showed progressive disease. At the dose and schedule used, rHuTNF had minimal therapeutic activity in colorectal carcinoma.

Adolescent↗
PubMed1988

Monoclonal glucose-oxidase-anti-glucose-oxidase (GAG) immunosandwich assay for the detection of monoclonal antibodies on routine hematological smears.

A murine monoclonal antibody specific for aspergillus niger glucose oxidase has been prepared and used in an unlabeled antibody bridge technique for the detection of monoclonal antibodies. This procedure--the monoclonal glucose oxidase anti-glucose oxidase (GAG) immunosandwich assay--provides excellent immunocytochemical labeling of routine hematological films in combination with optimal preservation of cellular details. In contrast to conventional immunofluorescence procedures, routine hematological films can be used, and these can be stored before and after the immunolabeling. Compared with other immunoenzyme techniques such as those using alkaline phosphatase or peroxidase, the GAG assay is as sensitive and has the advantage that no problems with endogenous enzyme activity are encountered. The availability of alcohol-resistant disclosing reagents allows for routine hematological counterstaining which provides a very clear visualization of both the immunoreaction and the individual morphology of the blood cells.

Antibodies, Monoclonal↗
PubMed1988

Phase I study of 24-hour continuous intravenous infusion of recombinant human tumor necrosis factor.

Sixteen patients with cancer were treated with a 24-h continuous intravenous infusion of recombinant human tumor necrosis factor (rHuTNF) to investigate the spectrum of side-effects, the maximum tolerated dose, the pharmacokinetics, and possible antitumor effects. Fever, chills, and flu-like symptoms were the most common side-effects. The maximum tolerated dose was 6 x 10(5) U/m2 (261 micrograms/m2). Severe hypotension, fluid retention, watery diarrhea, and central nervous deficits culminated in a profound prostration as the dose-limiting toxicity. No allergic reactions, positive skin tests, or antibodies against rHuTNF were observed. Plasma levels of rHuTNF were detected at doses of greater than or equal to 3 x 10(5) U/ml2. Maximal plasma levels were 19 U/ml (8.2 ng/ml). No objective tumor responses were observed.

Adult↗