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Biomedical subjects

H T Steinmetz

Publications and source records attributed to H T Steinmetz.

13 recordsLinked to original sources

[Organisation of studies].

Haemato-oncological studies in private practices for haematology and oncology have been identified as an important instrument for quality assurance in the treatment of haemato-oncological patients. As the organisational structures of private practices for haematology and oncology are usually highly complex the inclusion into studies needs a high motivation and binds resources. Workflow was observed in four private practices for haematology and oncology. With this data, suggestions for a common workflow model for study inclusion in private practices were elaborated and are discussed in this article. A common workflow-model of study inclusion for private practices is illustrated in two flow charts. If patients are to be successfully included in studies, additional structures and resources have to be implemented. Beyond this the necessary steps for study inclusion must be incorporated into the everyday routine of the practices.

Clinical Trials as Topic↗

Soluble tumor necrosis factor receptor type II in the early diagnosis of fever in neutropenia.

Sepsis in chemotherapy-associated neutropenia is a major cause of mortality in the treatment of acute myeloid leukemia (AML). Early diagnosis of sepsis is crucial for patient survival. We analyzed the value of prospectively measuring serum concentrations of soluble tumor necrosis factor receptor type II (sTNF-RII) in patients with AML for early diagnosis of sepsis in neutropenia. Therefore, 54 adult patients with AML and neutropenia were followed around the onset of fever. A total of 59 febrile episodes were documented. We could not demonstrate a significant increase in sTNF-RII levels prior to fever. sTNF-RII concentrations were not predictive of the severity of a febrile episode. Based on these data, we cannot recommend the routine screening of sTNF-RII for early detection of septic complications in patients undergoing cytoreductive therapy of AML.

Acute Disease↗

Phase-II trial of idarubicin, fludarabine, cytosine arabinoside, and filgrastim (Ida-FLAG) for treatment of refractory, relapsed, and secondary AML.

The current phase-II trial was initiated to assess the efficacy and toxicity of the Ida-FLAG regimen in patients with poor-risk acute myeloid leukemia (AML). Three subgroups of patients with AML were eligible for the study: (a) refractory, (b) first relapse, or (c) secondary AML (i.e., signs of trilineage myelodysplasia at diagnosis or the history of a myelodysplasia or myeloproliferative disorder). Fifty-seven fully evaluable patients were included in the study. Twenty patients received a second course of Ida-FLAG. Complete remission was achieved by 1/14 patients with refractory AML, 12/15 patients with relapsed AML, and 17/28 patients with secondary AML. The median duration of ANC <1000/microl was 17 days (10-36); of platelets <30,000/microl 23 days (9-65); of days with fever >38.0 degrees C 6 days (1-33). Thirteen patients (22.8%) died within 42 days of severe infection or hemorrhage. Overall survival at 20 weeks in the subgroups was 24% for patients with refractory, 78% for patients with relapsed, and 55% for patients with secondary AML. The toxicity of the first cycle of Ida-FLAG is moderate. The feasibility and subjective tolerance of the Ida-FLAG regimen are acceptable. There is no evidence for an increase of atypical infections. The efficacy for patients with secondary AML and especially those with first relapse of AML is good, with a high rate of complete remissions. Remission duration seems to be short. Therefore, an intensified post-remission therapy seems necessary.

Acute Disease↗

Cytosine arabinoside, etoposide and aclarubicin (AVA) for the treatment of acute myeloid leukemia (AML) in elderly patients.

BACKGROUND: Elderly patients (age > or = 60 years) with acute myeloid leukemia (AML) have unfavourable prognoses when polychemotherapy regimens are used, because therapy response is characterized by low remission rates, short remission duration and high toxicity. PATIENTS AND METHODS: A phase II trial in elderly AML patients was conducted to determine the efficacy of two induction courses of a moderately-dosed combination of aclarubicin (25 mg/m2, 30 min i.v., days 1-4), etoposide (100 mg/m2, 30 min i.v., days 1-3) and conventional-dose cytosine arabinoside (ara-C, 100 mg/m2, c.i.v., days 1-3 and 30 min i.v., q 12 hours, days 4-7) (AVA-7), followed by one consolidation treatment using a reduced-dose schedule over five days (AVA-5) after three months in CR. RESULTS: Thirty-two AML patients with a median age of 66.2 years (range 60-76) were included in the study: three of them had histories of preexisting myelodysplasia and one of polycythemia vera. Following 1-2 courses of AVA-7 17 patients (53%) achieved CR, two PR (6%), and nine had resistant disease (28%); the overall response rate was thus 59%. Toxicity was significant but acceptable, with an overall treatment-related death rate of five of 32 patients (16%) after 63 courses of AVA. The median disease-free survival (DFS) was 12 months, and the median survival of all patients was 16.6 months. CONCLUSIONS: These results indicate that the combination of aclarubicin, etoposide and conventional-dose ara-C is effective in elderly AML patients. The relatively brief remission duration requires new consolidation and maintenance therapy approaches.

Aclarubicin↗

Induction of granulocyte colony-stimulating factor by acute febrile infection but not by neutropenia in HIV-seropositive individuals.

The objective of this study was to assess endogenous granulocyte colony-stimulating factor (G-CSF) serum levels in HIV-seropositive individuals with persistent neutropenia or acute febrile infection. Serum levels of G-CSF were measured by enzyme-linked immunoabsorbent assay. HIV-seropositive subjects (n = 28) with afebrile neutropenia (< 1000 neutrophils/microliter) showed low G-CSF serum levels (i.e., median was below the detection limit) not different from those of healthy volunteers (n = 66) or nonneutropenic HIV-seropositive controls (n = 75). In contrast, patients with acute myeloid leukemia and afebrile neutropenia from chemotherapy (n = 17) demonstrated markedly elevated G-CSF levels (median, 264 pg/ml; p < 0.0001). However, HIV-seropositive patients with pneumonia (n = 17) showed increases of G-CSF serum levels (median, 152 pg/ml; p < 0.0001) similar to HIV-seronegative patients (n = 17) with pneumonia (median, 123 pg/ml; p = 0.97). The results suggest that there may be a contribution of low G-CSF serum levels to persistent neutropenia in HIV-seropositive individuals. Moreover, the different G-CSF serum levels in HIV-seropositive individuals in response to neutropenia or acute febrile inflammation suggest different mechanisms for the regulation of G-CSF.

Acute Disease↗

Increase in interleukin-6 serum level preceding fever in granulocytopenia and correlation with death from sepsis.

Serum interleukin (IL)-6 levels measured by ELISA were correlated with the clinical course of 53 adults with hematologic malignancies in 95 episodes of chemotherapy-induced leukocytopenia (< 1000/microL). The median IL-6 level was 15 pg/mL (range, < 3-123) in 27 episodes without fever. This level was 14.5 pg/mL (range, < 3-187) 72-48 h before onset of fever, 78 pg/mL (range, < 3-170) 24 h before fever in episodes with unexplained fever (FUO), and 182 pg/mL (range, 63-1076) 24 h before fever in episodes with positive blood cultures (P < .001). Within 24 h after onset of fever, median IL-6 level was 171 pg/mL (range, 53-1134) in episodes of FUO, 444 pg/mL (range, 38-7973) in episodes with gram-negative bacteremia, and 2017 pg/mL (range, 76-7253) with gram-positive bacteremia (P < .01). IL-6 levels increased before death in all 13 patients who died of sepsis. Median level was 7253 pg/mL (range, 445-95,906) within 3 days of death. Determination of IL-6 may be useful for early assessment and as a prognostic tool in leukocytopenic fever.

Adult↗

[Mechanism of resistance to tumor necrosis factor].

To find clues as to the possible mechanisms of resistance against the cytotoxic activity of tumor necrosis factor (TNF), we developed TNF-resistant and TNF-sensitive subclones of the human cervic carcinoma cell line ME 180 and the mammary carcinoma cell line BT-20. Resistant subclones were selected by gradually increasing the TNF concentration in the culture medium over 4 months or 20 passages. Resistance to TNF was conserved in the absence of TNF after nearly 3 years and less than 100 passages. There were no differences in the number and affinity of TNF receptors between the sensitive and resistant clones. Similarly, SDS-PAGE of cell lysates showed identical bands. Sensitivity to actinomycin D, mitomycin C, and interferon-gamma was the same. No TNF message could be demonstrated in either subclone. As tumors grown in nude mice derived from the sensitive and resistant clones responded equally well to an intratumoral injection of TNF, we conclude that different mechanisms are responsible for sensitivity and resistance to the cytotoxic effect of TNF in vitro and in vivo.

Animals↗

Production of monoclonal antibodies against glucose oxidase, alkaline phosphatase and peroxidase. Their application in a highly sensitive antigen spot microassay.

The production of monoclonal antibodies against peroxidase, alkaline phosphatase and glucose oxidase and the use of the respective enzyme monoclonal anti-enzyme complexes in immunoassays are described. A micromethod using nitrocellulose membranes as solid phase was developed. This microassay has the advantage of being a rapid and simple test procedure, using only 0.2 microliter of antigen solution and 25 microliter of test reagents. A high sensitivity was achieved by repeated incubation of monoclonal enzyme anti-enzyme complexes bridged by anti-mouse immunoglobulin. As little as 200 pg human IgG and 400 pg human IgM could be detected. The glucose oxidase assay together with the alkaline phosphatase assay displays the highest sensitivity and has significant advantages including easy evaluation due to high color contrast of the enzymatic reaction, availability of non-toxic substrate reactions, and no interference with endogenous enzyme activity in mammalian antigen preparations.

Alkaline Phosphatase↗