Biomedical subjects
Publications and source records attributed to B Mödder.
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Several side-effects of asparaginase therapy have been said to be a consequence of the glutaminase activity of Escherichia coli asparaginase, especially the deleterious influence on the liver function. We report here the drug-induced impairments of asparagine and glutamine metabolism in correlation to concentrations changes of plasma proteins, synthesized in the liver, in patients with acute lymphatic leukaemia. One hour after asparaginase application, plasma glutamine decreased to 5% (0-39%: median, range) of the initial values, with a subsequent rise to concentrations slightly lower than those prior to therapy. During the 14 days of drug application the fasting plasma concentrations of glutamine fell to a median of 63% of the pre-therapeutic levels, indicating a depletion of the glutamine pools. Two days after the end of asparaginase application, in one patient the glutamine concentrations increased to the pre-therapeutic range. Plasma concentrations of fibrinogen and antithrombin III decreased to 46% and 56%, respectively, of the initial values, with a slight increase 2 days after the end of therapy. The changes of plasma protein concentrations followed the course of plasma glutamine and asparagine. From that we deduce that the hepatic synthesis of the plasma proteins might be influenced by asparagine and glutamine depletion as a consequence of the therapy with E. coli asparaginase.
In 10 patients with heavily pretreated Hodgkin's disease (stage IVA or IVB) a third-line salvage therapy consisting of CCNU, etoposide and chlorambucil (CECh) was tested. All patients were resistant to both COPP and ABVD. Acceptance and tolerance of CECh were very satisfactory. The observed response rate (3 complete remissions and 4 partial remissions) is encouraging. The survival time after CECh therapy is in excess of 32 months (complete remission) and 15 months (partial remission). The main possible adverse effect is a prolonged myelosuppression. The CECh therapy is an effective alternative chemotherapy in patients resistant to both COPP and ABVD, moderately toxic, easy to administer and well tolerated in heavily pretreated patients.
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Cell membrane fluidity (CMF), Ig receptor expression and ecto-ATPase activity were investigated in lymphocytes from patients with chronic lymphocytic leukemia (CLL) and from healthy controls. Significant differences were observed in the parameters of individual CLL cases as compared to normal controls. These findings suggest that malignant transformation of lymphocytes to CLL cells is accompanied by disturbances in cell membrane structure and function, which can be modulated to some extent by exogenous influences on the lipid composition of the cell membrane. The results also suggest, however, that CLL is apparently an inhomogeneous disease with major variations in the investigated parameters among individual cases.
In 80 patients with different platelet counts serum and plasma potassium concentration was measured, 30 minutes after blood sampling and three and six hours of storage. Serum and plasma concentrations differed, depending on the platelet count. In reactive thrombocytosis the mean difference was 0.7 mmol/l, independently of the time since sampling. In myeloproliferative diseases and with platelet counts of more than 1000 X 10(9)/l is was time-dependent. The mean difference was between 0.8 and 1.8 mmol/l, in individual cases as much as 2.6 mmol/l. Plasma potassium levels were independent of time and platelet count. The possibility of pseudohyperkalaemia in serum must be kept in mind whenever the platelet count is increased, regardless of its cause. In case of doubt potassium must be measured in platelet-free plasma.
Busulfan is known to damage hematological stem cells. On the other hand, numerous steroid hormones have a stimulating effect on hematopoiesis. We wished to find out whether steroids have a protective effect on hematopoiesis in the case of busulfan treatment. This possibility was tested in vitro in rabbit bone marrow cultures, with and without in vivo pretreatment, with regard to erythropoiesis. The stimulating effect of testosterone or 5 beta-dihydrotestosterone on the CFU-E number in rabbit bone marrow cultures was blocked in the presence of busulfan. When rabbits were pretreated with either steroid before the administration of busulfan, however, the reduction of the CFU-E number seen after busulfan therapy alone was compensated. These results indicate that testosterone and the nonandrogenic 5 beta-dihydrotestosterone provide some protective effect on erythroid precursor cells when administered with reference to the cell-cycle-dependent action of busulfan.
In a retrospective study of 111 patients with aplastic anaemia iliac crest biopsies were evaluated for the presence of morphological features statistically related to the evolution of the disease. Prognostic variables for a transition to acute non-lymphatic leukaemia were: cellular atypias of the three haemopoietic lineages, as observed in the myelodysplastic syndrome, and especially "micromegakaryocytes"; high numbers or irregular distribution of megakaryocytes, or both; and (slight) marrow fibrosis. Clinical variables did not influence these prognostic correlations. Prognosis in relation to death from bone marrow failure without leukaemia might well have been influenced by a strong plasma cell reaction, but this correlation was weakened by clinical factors. On the basis of this study aplastic anaemia can thus be subdivided morphologically into two disease entities--namely, hypocellular myelodysplastic syndrome with a 23-82% risk of acute non-lymphatic leukaemia developing within three years, depending on how many variables associated with acute non-lymphatic leukaemia are present, and non-dysplastic myelohypoplasia.
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Seven patients are presented with a chronic lymphoproliferative disorder characterized clinically by splenomegaly, no or discrete lymphnode enlargement, and a varying degree of cytopenia. In blood and bone-marrow smears lymphoid cells of "hairy" appearance are demonstrable which may contain tartrate-resistant acid phosphatase. The finding of a nodular bone-marrow infiltration without fibrosis as well as that of a nodular infiltration of the spleen originating in the white pulp are incompatible with the diagnosis hairy-cell leukemia and place the disease near to chronic lymphocytic leukemia (CLL) or leukemic immunocytoma respectively. A detailed cytologic and cytochemical examination of the infiltrating cells shows deviations from the typical enzymatic pattern of hairy cells and from known enzymatic constellations in CLL and related lymphoproliferative disorders. Thus, we are dealing with an intermediate form, difficult to classify, the separation of which nevertheless seems to be important for therapeutical reasons.
Burkitt tumors are malignant lymphoblastic lymphomas occurring predominantly in Africa in children and young adults and involving in many cases the intestinal tract; these tumors occur rather seldom outside Africa. A case report is given of a white 21 old female suffering from this disease; that first manifestation was an isolated ulcerating tumor of the rectum without involvement of other organs of lymph nodes. Diagnosis was confirmed by rectum biopsy. X-ray therapy, cytostatic therapy and amputation of the rectum did not prevent a fast progression of the disease and final death, which is the usual course of the disease when it occurs outside Africa.