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Biomedical subjects

K Kolbe

Publications and source records attributed to K Kolbe.

10 recordsLinked to original sources
PubMed1992

Clinical and prognostic significance of the Philadelphia chromosome in adult patients with acute lymphoblastic leukemia.

Between 1983 and 1991 the Philadelphia chromosome (Ph1) was found in bone marrow and/or peripheral blood cells of 25 adult patients with acute lymphoblastic leukemia (ALL). The Ph1 as sole anomaly was seen in 13 patients, while six patients had additional structural and another six structural and numerical aberrations. Most patients (23/25) received combination chemotherapy according to the BMFT protocols 1/81, 2/84, 3/87, and 4/89. For 25 evaluable patients two early deaths, two treatment failures, two partial remissions (PR), and 19 complete remissions (CR) after phase 1 or 2 of the induction regimen were recorded. Two of these 19 patients who achieved CR are presently disease free, whereas 17 have relapsed after a median duration of remission of 9 months. Actuarial median survival for all patients was 13 months. The probability of continuous complete remission (CCR) after 39 months, as well as that of survival after 40 months, is only 6%. Our results confirm that the presence of the Ph1 is associated with a poor prognosis in adult-ALL patients. Therefore, whenever first CR is obtained and an HLA-identical donor is available, allogeneic bone marrow transplantation (BMT) should be performed at once, the more so, since transplantation in second CR seems to offer no cure. Future studies will have to show whether an intensified cytotoxic therapy can improve the prognosis of Ph1(+)-ALL.

Adult↗
PubMed1990

Effect of granulocyte-macrophage colony-stimulating factor on neutropenia and related morbidity induced by myelotoxic chemotherapy.

A phase Ib/II clinical study was undertaken to assess the efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) to attenuate neutropenia and associated morbidity caused by high-dose anticancer chemotherapy administered in the presence or absence of autologous bone marrow support. We treated 22 patients with various solid tumors and lymphoid neoplasias with a single daily subcutaneous dose of GM-CSF (250 micrograms/m2) 48 h after a second cycle of highly myelotoxic chemotherapy for a period of 10 days and compared intraindividually neutropenia-related clinical and laboratory variables with data obtained from the same patients having previously received a first neutropenia-inducing cycle of identical chemotherapy in the absence of GM-CSF. We show that GM-CSF is active in neutropenic patients by significantly increasing the neutrophil nadir, reducing the time of relevant neutropenia, and reducing the duration of the patient's hospital stay and necessity for parenteral antibiotics. No significant toxicity was encountered with subcutaneous GM-CSF treatment.

Agranulocytosis↗
PubMed1990

Effect of granulocyte-macrophage colony-stimulating factor on neutropenia and related morbidity induced by myelotoxic chemotherapy.

PURPOSE: A phase Ib/II clinical study was undertaken to assess the efficacy of recombinant human (rh) granulocyte-macrophage colony-stimulating (GM-CSF) factor in attenuating neutropenia and associated morbidity caused by high-dose anticancer chemotherapy administered in the presence or absence of autologous bone marrow support. PATIENTS AND METHODS: Twenty-two patients with various solid tumors and lymphoid neoplasias were treated with a single daily subcutaneous dose of rh GM-CSF (250 micrograms/m2) 48 hours after receiving a second cycle of highly myelotoxic chemotherapy for a period of 10 days. Within-subject comparisons on neutropenia-related clinical and laboratory variables were made with data obtained from the same patients after they received the first neutropenia-inducing cycle of identical chemotherapy in the absence of GM-CSF. RESULTS: GM-CSF was active in neutropenic patients because it significantly increased the neutrophilic nadir, reduced the time of relevant neutropenia, and reduced the duration of a patient's hospital stay and the necessity for parenteral antibiotics. No significant toxicity was encountered with subcutaneous GM-CSF treatment. CONCLUSION: Although GM-CSF was shown to significantly reduce chemotherapy-associated morbidity in patients receiving myelotoxic cancer chemotherapy, additional studies are needed to assess whether the use of GM-CSF in anticancer chemotherapy will allow an increase in the dosage level, leading to improved response rates and survival among cancer patients.

Adolescent↗
PubMed1990

Hematopoietic growth factors in oncology.

Hematopoietic growth factors, or hemopoietins, are peptide hormones produced by peripheral blood cells, bone marrow stroma, as well as several other cell types, such as endothelial cells and fibroblasts. Hemopoietins play a central role in regulating peripheral blood cell number and function. By recombinant DNA technology, several of these factors, also called colony-stimulating factors (CSF) or interleukins, are now available in such quantities to allow clinical evaluation. First experiences in clinical trials show that these peptides are capable of stimulating production of various cell types of the peripheral blood by stimulation of bone marrow progenitor cells without significant toxicity for the patient under treatment. Treatment of renal anemia by erythropoietin and reduction of chemotherapy-induced myelosuppression by G- and GM-CSF are already defined indications for these hemopoietins. Further studies are under way to test the indication of these factors in other clinical situations as well as studies investigating the biology, pharmacology, and clinical efficacy of interleukin 3 (IL-3).

Hematopoietic Cell Growth Factors↗
PubMed1989

Pharmacokinetics of nicotinic acid-salicylic acid interaction.

Both nicotinic acid and salicylic acid undergo glycine conjugation in human beings. Competitive inhibition may therefore be possible when these substances are used concomitantly in patients with hyperlipidemic disorders. The aim of this study was to determine, in six healthy subjects, whether nicotinic acid steady-state levels and total clearance are affected by concomitant aspirin administration. Steady-state nicotinic acid concentrations were obtained in all six volunteers by infusion of nicotinic acid solutions at constant rates (0.075 to 0.100 mg/kg/min) for 6 hours; aspirin (1 gm) was administered orally 120 minutes after the beginning of the infusion of nicotinic acid. Plasma samples were analyzed for nicotinic acid, nicotinuric acid, and salicylic acid. After aspirin administration an immediate marked decrease of nicotinuric acid levels could be observed in all six volunteers, whereas nicotinic acid concentrations increased. We hypothesize that salicylic acid causes a concentration-dependent decrease of total nicotinic acid clearance that results in the saturation (and effective elimination) of the nicotinuric acid conjugation pathway.

Administration, Oral↗
PubMed1983

[CEA determination to differentiate between pheochromocytoma with ectopic calcitonin formation and type-II multiple endocrine neoplasms].

Plasma levels of calcitonin and carcinoembryonic antigen (CEA) were determined pre-operatively and two months postoperatively in ten patients with C-cell carcinoma as part of multiple endocrine neoplasia type II. In addition, CEA was measured in extracts from 20 different phaeochromocytomas (five from patients with multiple endocrine neoplasia type II, 15 from patients with sporadic phaeochromocytoma). In comparison, CEA concentration was determined in extracts from five C-cell carcinomas of patients with multiple endocrine neoplasia type II. When correlating pre- and postoperative calcitonin and CEA levels, there was a significant linear relationship (P less than 0.001). CEA concentration in extracts from phaeochromocytomas was at the lower level of sensitivity (4.7 +/- 12.2 pg/mg tumour wet-weight). In extracts from C-cell carcinomas they were much higher (6402 +/- 4570 pg/mg tumour wet-weight). The results suggest that it is possible, in patients with phaeochromocytoma and high calcitonin levels, to differentiate by additional CEA determination between C-cell carcinoma in the course of multiple endocrine neoplasia type II and sporadic phaeochromocytoma with ectopic calcitonin liberation.

Adrenal Gland Neoplasms↗
PubMed1982

Difference in plasma membrane structure between two sublines of Ehrlich-Lettrè ascites tumor cells.

The plasma membranes of the glycogen-free and the glycogen-containing subline of Ehrlich-Lettrè ascites cells were purified and compared with respect to their enzyme activity, chemical, lipid and protein composition, and membrane fluidity. Both membrane fractions differed in a number of parameters which are discussed as differences in the expression of malignant transformation of the two sublines. 1. The 5'-nucleotidase activity was 3-5 times higher and the sialic acid content 3-times lower in the glycogen-containing than in the glycogen-free subline. 2. Differences were also observed with respect to the phospholipid composition, that is in the relative proportions of mainly phosphatidylcholine, -inositol and -serine. 3. The fatty acid spectrum of the two sublines differed in the C-18 series and in the percentage of polyunsaturated acids, which was about 6% lower in the glycogen-containing line. 4. Measurements of fluorescence polarization (P) using 1,6-diphenyl-1,3,5-hextriene as probe generally gave higher P values, indicating a decreased membrane fluidity for the plasma membranes of the glycogen-containing subline both below and above the transition temperature at 33 degrees C. 5. Polyacrylamide gel electrophoresis revealed different protein patterns mainly in the molecular weight range of around 90 000 and in the range between 31 000 and 14 000.

Animals↗
PubMed1980

Plasma membrane heterogeneity in ascites tumor cells. Isolation of a light and a heavy membrane fraction of the glycogen-free Ehrlich-Lettré substrain.

In this work we report on the isolation of two plasma membrane fractions of a glycogen-free substrain of Ehrlich-Lettré ascites cells, a light fraction sedimenting in a sucrose gradient at 1.10 g/ml, and a heavy fraction sedimenting at nuclei by a combination of short-term swelling and mild Dounce homogenization. A 12 000 X g postnuclear pellet (PII) containing major portions of the plasma membrane marker enymes, 5'-nucleotidase, ouabain-sensitive (Na+ + K+)-ATPase and the alkaline phosphatase, was prepared by differential centrifugation. The two plasma membrane fractions were obtained by centrifugation on a discontinuous sucrose gradient, from which they were further purified on a linear sucrose gradient applying sedimentation velocity conditions only. Enrichment factors for the three marker enzymes were between 5- and 14-fold for the light fraction and between 3- and 7-fold for the heavy fraction with an overall yield of 1--4% and 0.5--1.7%, respectively, of cellular protein. Contamination of both fractions with nuclear material was minor. Mitochondrial contamination was about 8% for the light material and somewhat higher for the heavy material. In the light fraction, co-sedimentation of lysosomal and Golgi marker enzymes was detected. The presence of membrane structures of these organelles could not be confirmed definitely by electron microscopy. Differences in sialic acid content and phospholipid composition within the two fractions, especially in the relative proportion of lecithin to sphingomyelin, suggests differences in membrane fluidity. The light material showed mostly unit membrane vesicles in thin-section and freeze-etch electron microscopy, whereas the heavy fraction mainly consisted of sheet-like membrane fragments.

5'-Nucleotidase↗