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Biomedical subjects

M Kummer

Publications and source records attributed to M Kummer.

At least 37 records · Page 2Linked to original sources

Regulation of insulin-like growth factor I messenger ribonucleic acid levels by serum in cultured rat fibroblasts.

Fibroblasts represent one of the in vivo sites of extrahepatic insulin-like growth factor I (IGF-I) production. In this study, cultured fibroblasts prepared from the skin of neonatal rats were used as a model to assess the role of serum in regulating IGF-I messenger RNA (mRNA) levels. IGF-I mRNA, as demonstrated by Northern blot analysis, was present in the cultured fibroblasts, and serum free media which was conditioned by fibroblasts for 20 h contained 108 pg/ml of immunoreactive IGF-I. Fetal calf serum (FCS) decreased steady state IGF-I mRNA levels, as measured by solution hybridization/RNase protection assay, in fibroblasts in a time- and dose-dependent fashion. Incubation of fibroblasts for 18 h in the presence of 0.3%, 0.6%, or 1% FCS decreased IGF-I mRNA levels to 76%, 56%, and 46% of the levels present in control cells which were maintained in serum free media with 0.25% BSA. Maximal inhibition to approximately 20% of control levels was seen with 4-10% FCS. In contrast, basic fibroblast growth factor and beta-actin mRNA levels increased 2- and 4-fold, respectively, with increasing concentrations of FCS. Treatment of the cells with 10 micrograms/ml cycloheximide resulted in partial abrogation of the inhibitory effect of FCS while protein synthesis in the cells was decreased to 6% of control levels. The addition of 2 micrograms/ml of insulin or 15-100 ng/ml of IGF-I to the fibroblasts did not reproduce the inhibitory effect of FCS. Finally, the inhibitory factor(s) present in the FCS was partially removed/inactivated by charcoal stripping or heat inactivating the serum, but delipidation of the FCS by chloroform extraction had no effect on the inhibitory effect of FCS. In summary, FCS contains a factor(s) that decreases IGF-I mRNA levels in cultured fibroblasts in a time- and dose-dependent fashion. The partial abrogation of the inhibitory effect of FCS with cycloheximide treatment suggests that this effect is at least partially dependent upon new protein synthesis. Furthermore, the studies using delipidated, heat-inactivated, and charcoal-stripped serum suggest that the inhibitory factor(s) is a peptide.

Actins↗

[Congenital hydrocephalus--an analysis of the course of pregnancy, prenatal studies and labor].

An analysis of the pool of our patients revealed few disturbances during pregnancy. In two cases the malformations were possibly due to drugs. Prenatal sonographic diagnostics were performed in one-third of the cases or documented: in 60% of the investigated cases a hydrocephalus was found, this being only 20% of the whole pool. The major part of the births were performed by Caesarean section, mainly because of a prolongation of the birth directly or indirectly due to the large circumference of the head. The hereditary trait of associated malformations and malformations of the central nervous system was frequent. Therefore, we advocate a better prenatal work-up and a birth by planned Caesarean section.

Abnormalities, Multiple↗

[Bioequivalence of piracetam following acute administration of an oral solution or two tablet formulations in volunteers].

In an open, non-randomized 3-way cross-over study, the bioavailability of 2-oxo-pyrrolidine-1-acetamide (piracetam, Encetrop) from two solid oral formulations and one liquid formulation was tested in 8 healthy male volunteers. The area under the concentration time curve, which is defined to be a measurement for bioequivalence among the three tested galenic formulations correlated very well with the area under the effect intensity-time curve, which was estimated in the same volunteers using electro-physiological methods. The different methods of estimation of bioequivalence show similarity between both solid galenic formulations, while the liquid form exhibits superiority in respect to the oral solid formulations.

Adult↗

[Cooperative studies in the treatment of acute lymphoblastic leukemia in children in Austria--report of 10 years' experience].

437 children with acute lymphoblastic leukaemia (ALL) have been treated at 9 different institutions in Austria utilizing common protocols and central registration between 1974 and 1984. 227 patients (132 boys and 95 girls, group I) were treated between 1974 and 1980 using 3 consecutive protocols (KMK, O 76, A 78), which were essentially derived from the Memphis studies VII and VIII. Patients with a high risk of relapse were treated according to the LSA 2-L2 protocol. 210 patients (112 boys and 98 girls, group II) were consecutively treated following the BFM protocols 76/79 and 81/83. In this group, treatment intensity was adjusted to the initially determined individual risk of relapse (BFM risk score or risk factor). To date, the life table analysis demonstrates that the probability of continuous complete remission for patients in group II is 60% after 5 and 3 years (BFM 76/79 and BFM 81/83, respectively), whereas group I reaches a level of 37.3%. The prognostic difference between risk and non-risk patients in both studies of group II was eliminated. Despite a higher morbidity and non-leukaemia-related mortality in group II, the therapeutic success can be attributed to the intensification of induction therapy.

Asparaginase↗

[Bioavailability of codeine and paracetamol in a combination preparation following oral and rectal administration].

The plasma concentrations of acetaminophen (paracetamol) and codeine were determined in a cross-over study in twelve healthy volunteers after oral and rectal application of a compound preparation. The relative bioavailability from the two forms of application was also computed. The two active substances showed almost parallel plasma concentration paths, and thus were systemically available at the same time. The maximum levels in plasma were already reached after one to two hours. In both active substances the suppositories displayed a classical retardation effect. In contrast to acetaminophen the rectal absorption of codeine was almost as effective as the oral absorption. Thus this application form shows almost bioequivalency vis-à-vis the capsule form. Based on these results the rectal form of administration of codeine as well as the combination of this substance with acetaminophen can be regarded, from the pharmacokinetic point of view, as a rational enhancement of the treatment of various forms of pain.

Acetaminophen↗

Malnutrition in the hospitalized geriatric patient.

The nutritional status of 59 consecutive geriatric male patients admitted to the medical service of a Veterans Administration Hospital was evaluated and compared with that of 93 younger patients admitted during the period. Protein-calorie malnutrition was diagnosed in 61 per cent of patients aged 65 or older compared with 28 per cent of patients younger than 65. The death rate and the incidence of infection were higher in the malnourished geriatric patients, however, there was no increase in the incidences of these abnormal findings compared with well-nourished patients udder the age of 65. The presence of malnutrition on admission, regardless of age, predicted a significant increase in the risk of infection or death during the hospital course.

Age Factors↗

[The prognostic value of lymphocyte transformation by phytohemagglutinin in children with acute lymphatic leukemia].

The response to phytohemagglutinin (PHA) of lymphocytes from 62 children with acute lymphoblastic leukemia (ALL) was tested before and during cytostatic therapy. Nineteen patients were tested as well for reactivity in autologous mixed lymphocyte-blast cell cultures. The prognostic value of the results obtained has been assessed. Children remained longer in their first complete remission 1) if the response to PHA before therapy was normal or only slightly diminished, or 2) if it returned to normal as soon as complete remission was attained, and 3) if periodic intensification therapy was followed by a rebound in spontaneous lymphocyte proliferation. The stimulatory response to PHA during maintenance therapy and the reactivity in mixed lymphocyte- blast cell cultures were not helpful prognostic criteria. In conclusion, determination of the PHA responsiveness at specific times, i.e. before therapy, after remission induction and after periodic intensification therapy, could help identify poor risk patients in ALL.

Antineoplastic Agents↗

Immunological follow-up of acute lymphoblastic leukaemia.

In different treatment groups of children with acute lymphatic leukaemia and undifferentiated leukaemia, the lymphocyte count and a number of immunologic parameters were examined during the various stages of treatment. These parameters were related to the type of chemotherapy as well as the stages of treatment. This paper deals with the values of lymphocyte counts, of gamma globulin, IgG, IgM and IgA and the results of the DNCB skin tests, as a parameter for cellular immunity. IgG determined by acetate sheet electrophoresis showed no significnat change, while its significant reduction was shown during the periods of prophylactic reinduction with vincristine in the Pinkel VII scheme, The IgM level was significantly raised in the initial stage before treatment and in all periods of treatment both in the Pinkel VII group and in an earlier therapeutic group treated with methotrexate every two weeks and vincristine pulses every six weeks. IgA was raised in both groups before treatment but significantly reduced during the phases of maintenance and reinduction. About 50% of the P VII cases had negative DNCB skin tests during maintenance therapy, while all long-term survivors in the earlier methotrexate group had a positive skin test.

Antibody Formation↗

[Responsiveness of lymphocytes to stimulation by pha and autologous blasts in acute lymphatic leukemias during remission (author's transl)].

The paper deals with the question how far the lymphocytes of acute lymphatic leukemia patients in remission can be stimulated by PHA and autologous blasts in the MLC-Test. The lymphocyte stimulation by PHA showed considerable variation dependent on the phase of therapy. A significant reduction of the responsiveness to PHA stimulation was found during the prophylactic reinduction treatment with Vincristin and Prednisolon compared with the results during maintenance therapy. The examination of lymphocyte stimulation by conserved autologous blasts in the mixed lymphocyte culture-test yielded positive results in one of three children at the beginning of remission and in 2 of 3 children during the consolidated remission period.

Child↗

Prevention of meningeal leukaemia and relapses by cranial irradiation and intrathecal MTX in acute lymphatic leukaemia.

Experience with CNS prophylaxis in 35 children with acute lymphatic leukaemia is reported. Before prophylactic irradiation of the skull was given the average survival time in 36 children was 2,8 (2,7) years. Menigeal leukaemia preceeded bone marrow relapse in 9 cases and followed relapse in a further 5 cases (39%). Between 1971 and 1973 Pinkel's treatment scheme VII was given to 35 children. This included prophylactic skull irradiation and intraspinal MTX injections. 29 children are still in their first remissions which range from 10 - 35 months in length. Meningeal leukaemia has not so far been observed, in this latter group.

Child↗

[Immunologic parameters in acute lymphatic leukemias in the course of different types of chemotherapy (author's transl)].

In 2 groups of patients under treatment with acute lymphatic leukemia and undifferentiated leukemia, apart from the lymphocyte count, a number of immunologic parameters were examined during the various stages of treatment. These parameters were related to the type of chemotherapy as well as the stages of treatment. This paper deals with the values of lymphocyte counts, of gammaglobulin, IgG, IgM and IgA and the results of the DNCB skin-tests, as a parameter for cellular immunity. The determination of gammaglobulin using the acetate sheet electrophoreses, showed no significant change. However a significant reduction of the IgG was shown during the periods of prophylactic reinduction with Vincristin in the Pinkel VII scheme. IgM quantities were significantly raised in the initial stage before treatment and in all periodes of treatment both in the Pinkel VII group and in an earlier therapeutic group with methotrexate two weekly and Vincristin pulses every 6 weeks. IgA was raised in both groups before treatment but significantly reduced during maintenance and reinduction phases. About 50% of the P VII cases had negative DNCB skintests during maintenance therapy, while all long term survivors in the earlier methotrexate treatment group had positive skintests. The 2 following papers deal with the results of PHA stimulation and the B and T cell determinations.

Child↗