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Biomedical subjects

D Lutz

Publications and source records attributed to D Lutz.

At least 73 records · Page 4Linked to original sources
PubMed1987

Allylic compounds bind directly to DNA: investigation of the binding mechanisms in vitro.

The in vitro binding of three allyl compounds, allyl methanesulphonate, allyl bromide and allyl chloride to DNA from salmon sperm was investigated. Kinetic DNA-alkylation measurements revealed significant differences between the strongly alkylating allyl methanesulphonate and allyl bromide with half-life values of 1.5 h and 8.1 h, respectively and the weakly alkylating allyl chloride with a half-life value of 360 h. Five alkylated nucleic bases, 3-allyladenine, N6-allyladenine, N2-allylguanine, 7-allylguanine and O6-allylguanine, could be identified after DNA-alkylation with all three allyl compounds.

Alkylating Agents↗
PubMed1987

Determination of nitrates in plasma.

Because of the high efficacy of existing nitrates, alternative dosage formulations have been developed rather than new compounds. These new formulations challenge the analyst to develop analytical methods with lower sensitivity and higher precision. Isosorbide dinitrate is analysed in the presence of its major metabolites isosorbide 2-mononitrate and isosorbide 5-mononitrate. The present method is an improvement over previously published methods. It is not possible to analyse glyceryl trinitrate and its major metabolites 1,2-glyceryl dinitrate and 1,3-glyceryl dinitrate with the necessary sensitivity in one chromatogram. A 2-step procedure is therefore applied. The extraction procedures, the gas chromatographic conditions, imprecision and inaccuracy of the methods, the lower limits of quantitation, sample chromatograms and applications of all methods are described in detail. Thus, the possibilities of modern analytical methods in the determination of nitrates in the lower picogram region are demonstrated.

Biotransformation↗
PubMed1987

[Biotransformation and bioequivalence of a new nifedipine preparation].

Following a single dose of two 5 mg soft gelatine capsules with nifedipine (Pidilat as a test preparation and a commercially available reference preparation) to 12 healthy volunteers in a randomized, 2-fold cross-over trial (latin square), blood samples were drawn up to 16 h post application (p.a.). The nifedipine plasma levels were quantitatively determined by a capillary gas chromatographic assay. Some important pharmacokinetic parameters as well as the bioavailability/bioequivalence were evaluated and subsequently compared for possible statistically significant differences between the preparations. Approximately 0.5 h p.a. mean peak plasma concentrations of about 110-120 ng/ml were reached; the mean terminal half-live was 1.5 h. The plasma level-time curves were-except for the negligible different peak concentrations-virtually identical; thus both preparations are considered to be bioequivalent.

Adult↗
PubMed1987

Establishment and phenotypic characterization of three new human myeloma cell lines (U-1957, U-1958, and U-1996).

Three new human myeloma cell lines (U-1957, U-1958, and U-1996) have been established in vitro. The cell lines are Epstein-Barr virus (EBV) negative, monoclonal, and aneuploid and should thus represent malignant cell populations and not EBV-carrying non-neoplastic B lymphoblastoid cell lines. The myeloma origin of the cell lines is also suggested by their capacity for production of monoclonal complete immunoglobulin (Ig) molecules (U-1957 and U-1958) or IgG light chains (U-1996) of the same type as the myeloma protein in vivo. All the cell lines have morphological features of plasmablasts-plasma cells but appear to represent slightly different stages of B cell differentiation. Thus, the U-1958 has plasma cell morphology, expresses only PCA-1 and OKT-10 but no other B cell antigens, and secretes 1.5 micrograms/mL of IgG/10(6) cells/24 hours. The U-1957 has plasma cell morphology and expresses Fc receptors and the LB-1 antigen in addition to the PCA-1 and OKT-10 antigens. This line produces only minimal amounts of IgG, which appears not to be secreted. The U-1996, finally, is a kappa light chain producer, has a plasmablast morphology, and expresses LB-1 in addition to the PCA-1 and OKT-10 antigens. All three cell lines are chromosomally heterogeneous and contain several markers with a 14q+ abnormality as a common characteristic abnormality. These new myeloma lines have been in continuous culture for approximately 3 years and are instrumental in studies of various aspects of the biology of human myeloma.

Aged↗
PubMed1986

[Experiences with acyclovir in herpes virus infections].

46 patients suffering from various malignancies (17 non Hodgkin lymphomas, 12 Hodgkin's diseases, 11 acute leukaemias, 4 myelomas, 2 carcinomas), 6 patients with haematological disorders such as ITP, SAA, myeloproliferative disease, LAS and 3 patients without preexisting disease were treated with acyclovir for herpes virus infection diagnosed by clinical means. All but 7 patients had been given intensive treatment with various cytostatic agents and/or irradiation. Most patients were treated with 1500 mg acyclovir daily for 5 to 13 days. Dosage was adjusted according to renal function and clinical response in the remaining 10 cases. 11 patients received intravenous immunoglobulins in addition. Side effects were negligible (local irritation, minimal rise in serum creatinine levels in 5 patients). All patients responded to treatment; 6 patients complained of severe neuralgia lasting for more than one month; 5 patients relapsed.

Acute Disease↗
PubMed1986

Hypo- and hypertetraploidy in a case of erythroleukemia analyzed by fluorochrome banding techniques.

Chromosome studies of a case of erythroleukemia in a 57-year-old female patient were made from bone marrow aspirates using the fluorescent primary stain/counterstain methodology. The chromosome number ranged from 42 to 110. There was a high proportion of hypotetraploid cells and a few hypertetraploid and hypooctaploid ones. Structurally normal chromosomes varied in number from cell to cell, ranging from one to seven in the polyploid cells. A number of marker chromosomes were observed, some of which occurred repeatedly in two copies per hypotetraploid cell. The chromosomes involved in aberrations were tentatively identified as #3, #5, #7, #12, #13, #15, #16, #18, #19, and #21. In the abnormal chromosome #16, which was missing a normal short arm, a new kind of heterochromatin was demonstrated by sequential staining with DA-DAPI and DAPI-AMD, suggesting de novo amplification of an A-T-rich satellite DNA sequence.

Bone Marrow↗
PubMed1986

Timentin in combination with tobramycin as empirical therapy in febrile neutropenic patients with haematological malignancies.

Timentin (5.2 g tds) and tobramycin (40 mg tds) were administered to 51 patients (22 male, 29 female, age range 17-72, mean age 40.4) with acute leukaemia, chronic myeloid leukaemia in blastic crisis, severe aplastic anaemia and acute agranulocytopenia. All patients had neutropenia (PMN less than 1000/mm3) and fever (greater than 38 degrees C). Febrile episodes consisted of 22 proved septicaemias due to Gram-positive organisms (Staphylococcus aureus, S. epidermidis, enterococcus) in 11 cases and to Gram-negative organisms (Escherichia coli, Pseudomonas aeruginosa, Alkaligenes faecalis, Serratia marcescens, Klebsiella pneumoniae) in 10 cases. One patient had a polymicrobial infection (P. aeruginosa, S. aureus, non-haemolytic streptococcus). Twenty-nine infections were diagnosed only clinically. The mean duration of treatment was 11.1 days (range 4-20 days). Eighty-seven per cent of evaluable febrile episodes improved. Among 11 infections due to Gram-positive cocci, eight (72%) resolved, and in nine (90%) of ten cases due to Gram-negative bacilli success was obtained. The polymicrobial infection also resolved. In only four patients were mild side effects seen, e.g. exanthema, pruritus, phlebitis: renal toxicity was not observed. These data suggest that the combination of Timentin and tobramycin is an effective and safe empirical antibiotic regimen in febrile neutropenic patients.

Adolescent↗
PubMed1986

Distinct histamine-induced cyclic AMP synthesis in acute leukemia.

Histamine receptors of the H2 type are found on mature hemopoetic cells such as lymphocytes and monocytes. Since little is known about histamine receptors on immature cells, we studied histamine-induced cAMP synthesis in leukemic cells of 51 patients using 73 samples of peripheral blood and/or bone marrow. Histamine-induced cAMP synthesis was found in all cALL (FAB L1, L2), but only occasionally in AML. In 1 out of 11 myelomonocytic leukemias (M4), and also in 2 out of 5 monocytic leukemias (FAB M5), histamine-inducible cAMP synthesis was found, but no induction of cAMP synthesis by histamine was found in 19 cases from the remaining subgroups (FAB M1-M3, M6). The inhibiting action of H2 antagonists on cAMP synthesis indicates that the receptor is of the H2 type. Since H2 receptors were found in all cALL blasts, we assume a compulsory expression of this receptor on immature cells of the B-lymphocytic lineage.

Acute Disease↗
PubMed1986

CD-15 antigen detected by the VIM-D5 monoclonal antibody for prediction of ability to achieve complete remission in acute nonlymphocytic leukemia.

The prognostic value of cell differentiation antigens detected with the monoclonal antibodies of VI series was studied in 242 cases of acute nonlymphoblastic leukemia (ANLL) treated in 7 cooperating centers. A significantly higher complete remission rate was observed in patients with a higher expression of CD-15 antigen detected by VIM-D5 antibody than in those with lower values. These significant differences were proved when comparing subgroups with VIM-D5 positivity of blastic cells less than 15 and much greater than 15% (p less than 0.01) as well as in the subgroups with values less than 50% (median value) and greater than or equal to 50% (p less than 0.02). Our studies suggest the VIM-D5 positivity of ANLL cells to be favourable prognostic factor predicting the ability to achieve complete remission. Further studies are needed to establish whether the expression of the VIM-D5-defined antigen may serve as a prognostic factor related to survival.

Acute Disease↗
PubMed1986

[Clinical value of various classifications in adults with AML].

111 adults with acute myeloid leukemia were classified according to the morphological, immunological and cytogenetic features of their leukemic cells. A comparison was made between the clinical parameters on prognosis of these subgroups. Hemoglobin was the only parameter among all six FAB-subgroups to show a statistical significant difference. Other differences found applied to a few subgroups only. Again, immunologically or cytogenetically characterized subgroups did not show significant differences in clinical parameters or prognosis. Patients with pseudodiploid or hyperdiploid karyotype had a lower remission rate than the remainder. However, a cluster analysis in which all three classifications together with the clinical parameters were considered was best able to characterize groups with different prognosis.

Adolescent↗
PubMed1986

[Lineage infidelity of leukemia cells].

We phenotyped 548 blast populations from patients with acute de novo leukemia with a panel of 27 monoclonal antibodies and an antiserum against the enzyme terminal deoxynucleotidyl-transferase (TdT). In 56 cases (10,2%) we found a marker profile consisting of both myeloid and lymphoid characteristics (biphenotypic) leukemia = interlineage infidelity). In 49 out of the 56 cases the blast populations were clearly related to the myeloid (n = 41) or the lymphatic (n = 8) system. In those blast populations only one characteristic of the other differentiation could be detected. However, in 7 cases more than one myeloid as well as lymphatic characteristics were found on the same blast cells. In 4 cases (0.7%) the immunological phenotyping indicated the presence of two separate blast populations. The occurrence of a stem cell leukemia, an abnormal derepression of a genome, a defect of the membrane synthesis and the existence of a normal counterpart are taken into consideration as a cause of an "atypical" marker profile.

Acute Disease↗
PubMed1986

[Pharmacokinetics and bioavailability of diphenhydramine in man].

By the presented study the relative bioavailabilities and some important pharmacokinetic parameters should be evaluated after oral application of a single-dose of three different diphenhydramine (DPH, 2-diphenylmethoxy-N,N-dimethylethylamine)preparations in a randomized, cross-over design to 12 healthy volunteers. Additionally, some simple pharmacodynamic measurements of the volunteer's vigilance were performed and the question whether a combination with 8-chlorotheophylline influences the pharmacokinetic and/or pharmacodynamic profile of DPH was investigated. As the test preparations (Benocten as a tablet = A, as a buffered solution = B) contained 50 mg of DPH-HCl, but the reference preparation (= C) only 31 mg of DPH-HCl (+ 23 mg 8-chlorotheophylline), the biometric-statistic calculations had to be done with and without dose correction. Bioequivalence of the preparations could only then be demonstrated when the calculations were done with dose corrections: without these corrections for the reference preparation significantly lower serum levels resulted which hardly can be considered sufficient for exerting a sleep-inducing effect. The addition of 8-chlorotheophylline recommended by some other authors for an enhanced sedative effect could not be substantiated by our results. Peak serum levels of 61 and 53 ng/ml, respectively, for the test preparations and 40 ng/ml for the reference preparation were reached after 2.0 to 2.5 h p.a.; elimination half-lives were between 4 and 6 h. A statistically significant positive correlation could be found for AUC (0-24 h) and the amount excreted in urine in the same period of time, as higher mean serum levels were correlated with higher amounts excreted renally.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Pharmacokinetic evaluations with highly sophisticated analytical methods.

26 patients, aged between 53 and 72 years, with chronic myocardial insufficiency of different degrees, proved radiologically by an enlargement of the heart and a mean reduction of left ventricular ejection fraction by more than 50%, were subjected to 4 weeks of treatment with 3 x 60 drops/day Miroton, (Chemische) Werke Minden GmbH), a cardioactive glycoside mixture, following a washout phase of 4 weeks. The effect on end-diastolic volume (EDV) and left ventricular ejection fraction (LVEF) was recorded and calculated by ECG-triggered radionuclide angiography both before, and after 2 and 4 weeks of medication with Miroton. On therapy with Miroton the EDV decreased by 4% after 14 days and by 18% after 4 weeks (compared to the baseline value of 126.8 ml). In contrast to this, the LVEF increased to 47.2% after 14 days and to 56% after 4 weeks (baseline value 43.7%). The inverse relation between EDV and LVEF shows a positive inotropic influence on the myocardium which was more pronounced in the last 2 weeks of treatment than in the first 2 weeks.

Kinetics↗
PubMed1986

Pharmacokinetics and bioavailability of three different galenic nifedipine preparations.

In a randomized three-way crossover study with twelve volunteers the bioavailability and main pharmacokinetic parameters of three different galenic formulations of nifedipine (hard gelatine capsule with pellets = preparation A, soft gelatine capsule with liquid nifedipine = preparation B, retard-tablet = preparation C) were determined. Plasma concentrations of nifedipine were measured by capillary gas-liquid chromatography up to 24 h after single dosing as well as up to 48 h after multiple doses of the drugs (steady state). Statistically significant differences between the preparations were found for AUC, Cmax, and Tmax. In all respects preparation A was intermediate to the other preparations. Plasma levels of 40 ng/ml or more were reached for most subjects within the first half hour after application of a single dose of preparation A and under steady state conditions plasma concentrations of 25 ng/ml or more could be upheld with this preparation for a longer time than with the reference retard tablet (preparation C). No accumulation of nifedipine in plasma occurred following multiple dosing.

Adult↗
PubMed1985

[Acute myelomonocytic and monoblastic leukemia with polyradicular symptoms].

Meningeal leukaemia, developed in 4 female patients with M4 or M5 leukaemia during a period of haematological remission. Polyradicular symptoms and signs dominated neurologically, but 3 patients also exhibited cranial nerve palsies. The neurological findings showed no reversal following intrathecal chemotherapy with normalization of liquor cytology. Patchy demyelinization in the region of the anterior spinal roots and of the proximal segments of the affected cranial nerves were responsible for the neurological features. Peripherally located streaky demyelinization of the olfactory bulb and of the optic chiasm were not found to cause any neurological manifestations.

Abducens Nerve↗
PubMed1985

[Various induction therapies in older patients with acute myeloid leukemias].

Due to unmanageable complications the results of high-dose chemotherapy for remission induction were significantly worse in a group of elderly patients with AML than for younger ones (greater than vs. less than 50 years: CRR 44% vs. 78%, p = less than 0.005). Hence, different induction schedules were studied for older patients with AML. A high response rate to low-dose cytosine-arabinoside (LD-CAR) was observed in myeloblastic and promyelocytic leukaemias, but the complete remission rate was low. Induction treatment with VP 16-213, aclacinomycin, cytosine-arabinoside and thioguanine resulted in a high complete remission rate (69%). Toxic side effects cannot be excluded in individual cases. These results justify prospective studies to evaluate the significance of the efficacy of these induction schedules.

Aclarubicin↗
PubMed1985

[Specific chromosome aberrations in 3 patients with Burkitt-like leukemia (Fab: L3)].

Karyotype analysis using the Tri-staining-technique (Chromomycin A3/Distamycin A/DAPI) and subsequent DAPI/AMD staining (Schweizer, 1981) was performed on the bone marrow and peripheral blood of three patients with "Burkitt-like" acute lymphatic leukaemia (FAB: L3). In two patients we found the specific translocation t(8;22). One patient displayed in addition a structural abnormality of chromosome 9, visualized with C-banding using the DA/DAPI stain, and in two patients we found specific abnormalities of chromosome 1. Several patterns of the abnormal chromosome 1 revealed an intercalated DA/DAPI positive C-band in the elongated long arm.

Adolescent↗