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Biomedical subjects

K Winkler

Publications and source records attributed to K Winkler.

At least 217 records · Page 12Linked to original sources

[Chemotherapy of brain-tumors in children (author's transl)].

The poor permeability of the blood/brain barrier for most cytostatic agents makes it difficult to achieve an adaequate drug concentration in brain-tumors. This is the main problem in developing a chemotherapy of brain tumours. On the other hand the therapeutic effect is difficult to evaluate not only because of clinically and hitherto also technically poor accessability of the brain but also because of differences in tumour classification systems, and consequently limited comparability. There is however definite knowledge on the effectiveness of several single drugs as well as strong evidence on the effectiveness of some polychemotherapeutic programs. The measure of success presently is rather prolongation of survival time for months than a change in cure rate. A general recommendation for the cytostatic treatment of brain tumors may not be given in that situation, but within a clinical study the use of cytostatic agents seems promising anyway.

Antineoplastic Agents↗

[Chemotherapy of osteosarcoma (author's transl)].

The cyclic chemotherapy scheme OS I/75 was tried in 6 patients with newly diagnosed osteosarcoma and in 3 patients with secondary metastases. The treatment consists of high dose methotrexate, followed by citrovorum-factor rescue, doxorubicine (Adriblastin) and cyclophosphamide (Endoxan). All 6 primary patients are in a continuous remission of 6+ to 21+ months (median 12+ months). The length of remission in the patients with metastases is 5.5+ and 8+ months. The haematological side effects led to an average prolongation of the cycle by 11 days in a planned cycle duration of 42 days. However, they were readily manageable. Among the other side effects two cases of Adriblastin myocardiopathy are remarkable which became apparent after methotrexate and ifosfamide. In order to improve possibilities for treatment regional centralisation of patient care and interdisciplinary and supraregional cooperation of treatment centres are necessary. A prospective treatment programme has been developed for the Federal Republic of Germany and Austria.

Adolescent↗

[Cytological classification and nomenclature of leukaemias in childhood. Present situation of the cytomorphological and cytochemical differentiation (author's transl)].

The classification and nomenclature of leukaemias in childhood under cytomorphological and cytochemical criteria is presented base on our own longstanding studies as well as on literature. Particular consideration is given to clinically relevant subtypes of acute lymphoblastic leukaemias (ALL), acute myeloid leukaemias (AML) and chronic myeloid leukaemias (CML). The more subtle differentiation leads to a more reliable diagnosis, a better estimation of the individual prognosis and is of immediate importance for the therapeutical decisions. We show the necessity of diagnosis centralisation in cooperative prospective therapy studies and in a risk dependant therapeutical approach.

Acute Disease↗

[Clinical significance of cytochemical findings of childhood acute lymphoblastic leukaemia (author's transl)].

The initial bone marrow smeasrs of 821 children with ALL have been cytochemically analysed. (PAS-, acid phosphatase-(SPH), peroxydase-(POX), alpha-N-esterase-(EST)reaction) with regard to presenting clinical data and course of disease. Granular reactions of PAS and SPH were not meaningful in this respect. The paranuclear SPH-reaction was associated with high incidence of mediastinal mass, high peripheral blas count and male preponderance. All 5 patients with histories of more than 12 weeks duration belongs to the PAS-type of ALL (cloddy reaction). The PAS-type showed a higher incidence of CNS-leukaemia and generally a less favorable prognosis as compared to the UND-type. Thereby a high proportion of PAS positive cells, independently of other risk factors, indicates a better prognosis. The highterto neglected weak EST-reaction (Grad I and II according to Löffler) seems to signalise a clincally distinct subtype of ALL with a younger age distribution maximum as compared to the UND-type, low incidence of risk factors, high rate of remissions lasting more than 2 years but unfavorable endprognosis.

Acid Phosphatase↗

[Therapy of childhood acute lymphoblastic leukemia. Treatment results 1971-75 in 78 patients (author's transl)].

From December 1971 until July 1973 44 children with ALL have been treated according to branch A of the randomised DAL study series of June 3rd 1972 (1/71), which is a slight modification of study VII of Memphis. Afterwards until July 1975 34 patients received a somewhat intensified initial therapy (11/73). The results of 1/71 with a 3-year-remission rate of 39% and an expected 5-year-remission rate of 32% are comparable to those of study VII. The results of 11/73 with an expected 3-year-remission rate of 54% seems clearly superior and unterline the importance of an intensive initial therapy, like it is introduced now in a still more aggressive manner in our running protocol III/75. Therapy mortality was found to be about 5% and seemed to be dependant on the staff's experience. Cytosin-arabinoside orally proved effective as a prophylactic measure during incubation as well as a therapeutic agent in manifest varicalla/zoster infections.

Central Nervous System↗

[Acute lymphoblastic leukemia and lymphoblastic lymphoma. Two names for one disease (author's transl)].

Of 14 non-T-cell malignant non-Hodgkin lymphomas (mNHL) 5/14 presented with leukemic transformation of the bone marrow; in three more cases bone marrow involvement developed during an observation period of 60--200weeks. In 2/14 cases mNHL terminated the first continuous and complete remission of acute lymphoblastic leukemia (ALL). CNS involvement has been observed without preceding bone marrow involvement. Only 4/14 mNHL remained local diseases. These clinical courses as well as hematological findings and further clinical observations suggests a very close relationship between mNHL and ALL if not basic identity. With the same systemic treatment additional to local treatment, prognosis of mNHL is by no means worse but rather better than the prognosis of ALL.

Bone Marrow Cells↗

[Malignant mediastinal lymphoblastic lymphoma with t-cell ALL (author's transl)].

29 cases of T-cell derived lymphoblastic lymphoma and T-ALL have been analyzed. There is a striking prevalence of the male sex. In the peripheral blood we often find initially an excessive number of white blood cells combined with normal values for the other constituents in about half of the patients; This may be an expression for the rapid occurrence of leukaemia in T-cell lymphosarcoma. In addition to systemic ALL-therapy we performed X-ray irradiation of the mediastinum in 8 of our patients. This yielded to significantly longer first complete remissions. All patients with T-cell LSA/ALL with or without mediastinal mass should be treated in this manner. Cytochemically a strong focal acid phosphatase reaction was found to be acharacteristic of these cells. It has proved to be a screening method for this disease. The cells are T-cell derived and their pattern of surface markers is similar to that found in fetal thymocytes.

Acid Phosphatase↗

Cytologie and cytochemistry of colony cells in soft agar gel culture from normal and leukemic bone marrow.

In order to judge differentiation of cells in soft agar colonies, cytological and cytochemical classification of single cells within these colonies is necessary. In this study, 1,026 colonies from 15 normal and 95 leukemic bone marrows have been evaluated using cytological, cytochemical, and immunocytochemical techniques. In 180 colonies from 15 normal controls no segmented neutrophils have been observed. The colonies mostly consisted of monocytes and macrophages, rarely pure eosinophil colonies were observed. The number of monocyte/macrophage colonies in untreated AML and the percentage of pure eosinophil colonies in AML and ALL in remission are reduced, as compared to normal controls. In 174 colonies from a total of 926 colonies derived from bone marrows of leukemic patients, plasma cells and in 20 colonies, blast cells have been observed. In contrast to normal colonies, growth of colonies containing blast cells does not depend upon the conditioned medium of the leukocyte feederlayer. This investigation has demonstrated the necessity of cytological and cytochemical classification in addition to quantiative evaluation of soft agar colonies when studying the effect of factors on proliferation and differentiation of normal and leukemic stem cells.

Bone Marrow Cells↗

Michaelis-Menten kinetics of galactose elimination by the isolated perfused pig liver.

The relation between galactose elimination rates and blood concentrations in the isolated perfused pig liver was analyzed by a mathematical kinetic model. It assumes that the substrate, under steady-state conditions, is removed from the blood that flows through the sinusoids by an irreversible process which follows Michaelis-Menten (i.e., saturation) kinetics. The experiments consisted of successive periods with constant infusions of galactose. The model fitted the data to within the experimental uncertainty. The estimated maximal rate (Vmax) ranged from 0.34 to 0.57 mmol-min(-1)-kg(-1) liver, and the Michaelis constant, Km, ranged from 0.12 to 0.30 mmol-liter(-1) plasma water in nine experiments. The ratio between the galactose concentration in hepatocyte water and plasma water was not significantly different from 1.0, indicating that membrane transport is not rate limiting for the elimination of galactose. In experiments with increasing concentrations of galactose in hepatocyte water and approximately saturated elimination rates, the concentrations of galactose 1-phosphate, UDPgalactose, and UDPglucose remained essentially constant. This indicates that the phosphorylation of galactose to galactose 1-phosphate is the rate-determining process.

Animals↗

The effect of vasopressin and triglycyl lysine vasopressin (glypressin) on the splanchnic circulation in cirrhotic patients with portal hypertension.

In four cirrhotic patients with portal hypertension we have measured some hemodynamic parameters over 60-120 min; portal venous pressure, hepatic venous pressure, mean arterial blood pressure, hepatic blood flow, transsinusoidal vascular resistance and splanchnic oxygen uptake under treatment with Vasopressin (1 IU/min for 10 min) and glypressin (50 mug/kg body weight). The effect on the parameters was less pronounced with glypressin but of longer duration.

Abdomen↗