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Biomedical subjects

W D Gassel

Publications and source records attributed to W D Gassel.

At least 19 recordsLinked to original sources

[Occlusion of central venous port catheters after simultaneous 24 h infusions of 5-FU and calcium-folinic acid in patients with gastrointestinal cancer].

Folinic acid-modulated 5-FU regimens are standard elements in several chemotherapy combinations like FOLFIRI, FOLFOX or AIO-regimen in the palliative treatment of patients with gastrointestinal cancer. When the simultaneous mixed infusion of 5-FU and calcium-folinic acid (Leucovorin) was authorized by the BfArM in 2002, we introduced this application regimen in the treatment of our cancer patients. 19 patients (AIO-regimen [5], FOLFIRI [12] and FOLFOX [2]) received a simultaneously mixed infusion of calcium-folinic acid and 5-FU over 24 hours with a total of 110 applications. 5-FU doses varied between 2000 and 2600 mg/m2, calcium-folinic acid was given with 500 mg/m2, infusion rate was 10 ml/hour using a 24 h pump. Central venous catheters employed included single Barth-Port in 18 cases, 1 patient had a Viggon-Port. In 3 out of the 19 patients catheter occlusion was noticed after 8-10 weekly applications of the mixed infusion. Heparine and subsequently urokinase were not successful in reversing the obstruction. All three catheters had to be explanted. Catheter tips in all cases showed a yellow cristalline precipitation. The crystallographic analysis exhibited calcium carbonate (CaCO3) in its polymorphic form (calcite). Thus, we confirmed calcite formation causing catheter occlusion as a frequent complication during a continuous 24 h-infusion of mixed high dose 5-FU and calcium-folinic acid. This reaction could not be avoided by increasing infusion volume and the application flow rate. As a result of our findings, recommending using calcium-folinic acid mixed with 5-FU has been withdrawn in the meantime.

Aged↗

Bone densitometry and histomorphometry in patients with hairy cell leukemia.

Tumor necrosis factor alpha, the cytokine that participates in the autocrine growth control of hairy cell leukemia has strong bone resorptive properties. This prompted us to look for bone involvement in HCL. Bone mineral density (BMD) was not decreased in 14 HCL patients who did not have radiographic evidence of bone destruction. Osteopenia was found in only two HCL patients with skeletal complications of the disease and bone pain preceded diagnosis in both cases. Lymphomatous infiltration of the vertebral bodies T 12/L1 was confirmed histologically in the female patient while bilateral necrosis of the femoral head preceded the diagnosis of HCL in the male patient. Histomorphometry of bone biopsy samples was performed in another 12, previously untreated male HCL patients. Trabecular bone volume was found to be reduced in 11, greatly reduced in 5 of them, while osteosclerosis was found in only one patient. The increase of trabecular bone pattern factor, a new parameter for simple quantification of trabecular interconnection indicated a poorly connected trabecular lattice in eight of these 12 patients.

Adult↗

[Chloroma in the blastic crisis of chronic myeloid leukemia--MR tomography findings].

Granulocytic sarcomas are rare manifestations of diseases of the white corpuscles. The incidence of this type of disease is not yet known because it is so rare. We observed two patients, who had had a chronic myeloid leukemia for several years, and in whom such a tumor occurred during the development of a blastomatous crisis. Both patients were examined by MRI. With this method it is possible to depict changes of the bone marrow as well as extramedullary lesions. MRI is a highly sensitive, but a less specific method.

Adult↗

CHOP-VP16 chemotherapy and involved field irradiation for high grade non-Hodgkin's lymphomas: a phase II multicentre study.

Sixty previously untreated patients with high grade non-Hodgkin's lymphomas stages II-IV received cyclophosphamide 750 mg m2 i.v., doxorubicin 50 mg m2 i.v., and vincristine 2 mg i.v. on day 1, prednisolone 100 mg p.o. on days 1-5 and etoposide 100 mg m2 i.v. on days 3-5 (CHOP-VP16). After four courses an involved field irradiation with a total dose of 25 Gy was employed and followed by two additional courses of CHOP-VP16. The overall response rate was 93%, with 49 patients (82%) achieving a complete remission (CR). Seven patients had a partial response and four patients showed no response. During a median follow-up period of 55 months, 22 of the 49 patients with CR relapsed, seven of them achieving a second complete remission with the same drug regimen. A maintained complete remission of up to 68 months was seen in 55% of all patients initially achieving CR. The median survival is 43 months. Mean side-effects of this drug regimen were alopecia (89%), nausea/vomiting (76%) and leukopenia (61%). No therapy-related deaths were seen. The results of this study demonstrate that this combined modality treatment produces high complete remission rates and that more than half of these patients achieve long-term disease-free survival.

Adolescent↗

[Multicenter study of the treatment of highly malignant non-Hodgkin's lymphomas with polychemotherapy (CHOPV) and irradiation].

In a multicenter study 46 untreated patients with highly-malignant non-Hodgkin's lymphomas stage II-IV received 6 courses of the following drug combination: cyclophosphamide 750 mg/m2 i.v. day 1, adriamycin 50 mg/m2 i.v. day 1, vincristine 2 mg i.v. day 1, prednisolone 100 mg p.o. days 1-5, and etoposide 100 mg/m2 i.v. days 3-5. Between courses 4 and 5 an involved field irradiation with a total dose of 25 Gy was employed. The overall response rate was 91%, with 38 patients achieving a complete remission (82%), 4 patients achieving a partial remission (9%), and 4 patients showing no response (9%). During a median follow-up period of 34 months 16 out of 38 patients relapsed, 4 of them achieving a second complete remission with the same drug regimen. A maintained complete remission up to 52 months was seen in 51% of all patients initially achieving CR. The overall survival curve shows a plateau at 60% at 30 months, while disease-free survival shows a plateau at 51% at 36 months. Mean side effects of this drug regimen were alopecia (89%), nausea/vomiting (76%), and leukopenia (61%). No therapy-related deaths were reported. The results of this study demonstrate that this treatment produces high complete remission rates and that the majority of these patients achieves long-term disease-free survival.

Adolescent↗

Production of five human lymphokines (granulocyte-macrophage colony stimulating factor, interferon-gamma, interleukin 2, macrophage cytotoxicity factor and macrophage migration inhibitory factor) from Con A stimulated lymphocyte cultures in bioreactors.

Cultivation parameters for the production of five lymphokines, granulocyte-macrophage colony stimulating factor (GM-CSF), interferon-gamma (IFN-gamma), interleukin 2 (IL-2), macrophage cytotoxicity factor (MCF), and macrophage migration inhibitory factor (MIF) from human spleen cells or peripheral blood lymphocytes were optimized. Cultivation was done in bioreactors containing up to 200 ml of medium, usually serum-free. The reactors were equipped with surface aeration facilities, stirrers and oxygen electrodes. Whereas stirring speed alone did not influence the yields of lymphokines, good aeration was especially beneficial for high IL-2 yields. However, all lymphokines were also produced under anaerobic conditions. The concentration of the mitogen concanavalin A was mainly critical for optimal IL-2 release. Optimal cell concentrations varied from 5 X 10(6)/ml (for GM-GSF and MCF) to 10 X 10(6)/ml (for IL-2 and IFN-gamma). It was possible to increase the yields of individual lymphokines 3 to 10-fold per batch of lymphocytes by a reinduction procedure which involved a change of medium and mitogen every 24 hrs. Reinduction was possible up to 4 times, especially when serum was present in the culture media.

Cells, Cultured↗

Acute allergic reaction due to vincristine sulfate. A case report.

A patient suffering from Hodgkin's disease exhibiting acute allergic reaction to vincristine sulfate with mild to moderate dermatologic and cardiovascular signs is described. The change of therapy to vindesine sulfate led to relief of all symptoms. The therapeutic effectiveness of the altered protocol remained unchanged and no other or amplified side effects appeared.

Adult↗

Cytochemical determination of granulocyte elastase and chymotrypsin in human myeloid cells and its application in acquired deficiency states and diagnosis of myeloid leukemia.

Two cytochemical methods for detection of granulocytic elastase and chymotrypsin employing alanine and phenylalanine naphthyl esters were developed. Specificity of reaction with the ester substrates was proven by chloromethyl ketone inhibitors. The results of both staining methods were almost identical with the staining for naphthol AS-D chloroacetate (Cl Ac-O Nap AS-D) esterase, since Cl Ac-O Nap AS-D also reacts with granulocyte elastase and chymotrypsin. Mature neutrophils and myeloid precursors except myeloblasts are stained with all three substrates in peripheral blood and bone marrow. Mast cells, however, only react with Cl Ac-O Nap AS-D and the chymotrypsin substrate and not with the elastase substrate. In acute myeloid leukemia the three esterases appear in parallel at a somewhat later stage of maturation than myeloperoxidase. In blood smears from 380 hospital patients no hereditary elastase or chymotrypsin deficiency could be demonstrated. Staining for elastase and chymotrypsin was also normal in hereditary myeloperoxidase deficiency and chronic granulomatous disease. On the other hand 6% of the hospital patients and about two-thirds of patients with acute myeloid leukemia showed a partial elastase deficiency in more than 25% of the peripheral neutrophils.

Chymotrypsin↗

Culture conditions for selective and enhanced release of various murine lymphokines (CSF, IL-2, MCF, MIF and TRF).

The production of the lymphokines colony stimulating factor (CSF), interleukin-2 (IL-2), macrophage cytotoxicity factor (MCF), macrophage migration inhibitory factor (MIF) and T cell replacing factor (TRF) was optimized from mouse spleen cell cultures stimulated with concanavalin A (Con A). The cultivation was performed in bioreactors which allow regulation of dissolved oxygen concentration. The oxygen supply influenced the yields of individual lymphokines in different ways. High oxygen concentration was beneficial for high release of IL-2 and MCF, whereas MIF and TRF were better produced at low oxygen concentrations. CSF release did not depend on oxygen supply. Upon stimulation with Con A, lymphokine activities in the culture supernatant reached an optimum or plateau after 24 h Lymphocytes continued with lymphokine release, when they were restimulated for further 24 h. in fresh medium and mitogen. CSF could be induced for at least 4 times. MCF was released during the first 3 inductions, whereas IL-2 and TRF were only produced during the first and second induction. These findings led to specific culture conditions for selective and enhanced production of individual lymphokines.

Animals↗

Influence of the immunomodulating compound BM 12.531 (azimexone) on radioresistance and granulopoietic colony forming units in mice.

BM 12.531 (azimexone) increases the survival of mice exposed to 650 rad. Levamisole, isoprenosine or aristolochia acid have no effects in this system. After administration of 25 mg/kg azimexone to C57 Bl/6-mice a statistically significant increase in CFUc was found. Maybe this increase in CFUc can explain the radioprotective effect of azimexone.

Adjuvants, Immunologic↗

[Diagnostic value of clinical methods in the staging of abdominal Hodgkin's disease (author's transl)].

Explorative laparotomies were carried out on 68 patients with Hodgkin's disease in the University Hospital of Marburg from 1969 through 1978. These laparotomies were preceded by clinical examination, abdominal sonography in 27 cases, lymphography in 55 cases, scintigraphy of liver and spleen in 58 cases, and radiographic examinations of the intestinal tract in 18 cases. Sonography revealed a greater accuracy (90%) for splenic involvement than scintigraphy (74%); the results of sonography and scintigraphy of the liver were comparable. For the detection of para-aortal lymphomas ultrasound and lymphography can be regarded as complementary methods. Our results are compared with findings in the literature on abdominal sonography (n = 50), scintigraphy of liver and spleen (n = 185), and lymphography (n = 465) carried out before explorative laparotomy for lymphogranulomatosis. There was a better correlation for the systemic symptoms of the 68 patients with the clinical stage than with the pathologic stage. The importance of diagnosing different groups, e.g. in stage III, is stressed.

Abdominal Neoplasms↗

Chemical characterization of macrophage cytotoxicity factor, macrophage migration inhibitory factor, T-helper cell-replacing factor and colony-stimulating factor from culture supernatants of concanavalin A-stimulated murine spleen cells.

Supernatants from Concanavalin A-stimulated murine spleen cells were subjected to hydrophobic interaction chromatography on phenyl-Sepharose. Macrophage cytotoxicity factor (MCF), macrophage migration inhibitory factor (MIF), T-helper cell-replacing factor (TRF) and colony-stimulating factor (CSF) were bound at high ionic strength and were released stepwise at low ionic strength. CSF thus could be separated from MCF, MIF and TRF and the bulk of other proteins. Chromatograhy of pools containing MCF, MIF and TRF on Sephadex did not lead to a separation of the three activities which were all found in a molecular weight range of 25.000-55.000. Isoelectric focusing of these pools in pH range from 4 to 9 gave two peaks for MCF in a single sharp peak at pH 5.3. The results demonstrate that the four biological activities can be distinguished on a chemical basis and are accessible for purification and chemical characterization.

Animals↗

Humoral factors modulating growth of granulocyte macorphage progenitor cells.

The kinetic of production of colony-stimulating activity (CSA) inducing mouse and human colony-forming cells (CFU-C) was tested in different human leukocyte culture systems. Stimulated and unstimulated cultures of spleen single cell suspensions, peripheral mononuclear leukocytes and acute monocytic leukemia (AMoL) cells were investigated. With the exception of the AMoL cells, stimulated cultures always revealed higher CSA levels than unstimulated controls. The spleen cell cultures exhibited the highest overall activity showing three molecular species of 70,000, 35,000 and 10,000 daltons activating human CFU-C to form colonies in the agar culture system. Furthermore it could be demonstrated that colony formation could be inhibited by low molecular weight fibrinogen degradation products obtained by digestion of fibrinogen with granulocyte-derived elastase.

Animals↗

[The colony forming cell and its stimulation--findings in hematological diseases (author's transl)].

In modifying the agar culture technique of mouse bone marrow cells Robinson et al. in 1970 described the in vitro culture of the human colony-forming cell. Since that time a number of data accumulated which markedly improved our knowledge of the regulation of normal and pathological hematopoiesis. A summary of the up-to date results is presented focusing mainly on disturbances of the colony-forming cells in peripheral blood and bone marrow of patients with hematological disorders. Furthermore, the findings on human urinary CSF excretion which exerts an action on mouse bone marrow are discribed. The somewhat contradictory results obtained with different methods are discussed in the light of the actual hypotheses.

Adult↗