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Biomedical subjects

K Höffken

Publications and source records attributed to K Höffken.

At least 109 records · Page 6Linked to original sources
PubMed1987

[Effectiveness of gamma interferon and alpha interferon in hairy cell leukemia].

Six patients with hairy-cell leukemia were treated with gamma-(IFN-gamma) and alpha-(IFN-alpha-2b) interferon; 3-35 months following splenectomy, treatment was started with 4 X 10(6) U/m2 IFN-gamma sc (iv) every second day for 9-35 weeks. Although the white blood cell counts decreased during therapy from 4.1-49 X 10(9)/l to 1.5-43 X 10(9)/l, no hematological or clinical improvement was obtained. Subsequently (interval 0-13 weeks), IFN-alpha-2b was given at an initial dose of 4 X 10(6) U/m2 sc every second day to all patients. After a treatment period corresponding to that of IFN-gamma administration, a significant hematological improvement was observed in five patients (one early death due to pulmonary embolism). At the last follow-up (9-14 months after start of treatment; maintenance therapy, 1 X 10(6) U every second day), these patients exhibited normal peripheral blood cell counts, and in bone marrow biopsy specimens a marked decrease of hairy cells was seen (1 CR, 3 PR, 1 MR). Adverse reactions including fever, headache, nausea, dryness of the mouth, myalgia, and fatigue did not significantly differ between the two interferon preparations. Whereas IFN-gamma is unlikely to have any significant impact on the course of hairy cell leukemia, IFN-alpha-2b does result in improvement of hematological values and well-being in almost all patients.

Adult↗
PubMed1987

[Progressive multifocal leukoencephalopathy. Late complication in chronic lymphatic leukemia].

In a 44 year old patient with chronic lymphatic leukemia and secondary antibody deficiency syndrome, a disorder of articulation and a left hemiparesis developed during a thrombocytopenic phase. Computer tomography of the cranium, CSF diagnostics and the electroencephalogram did not provide any indication for the cause of the rapidly progressive cerebral symptoms. In the NMR tomogram, a diffusedly increasing intensity in the T2-weighted tomograms were shown around the central region in the right brain. The patient died of a Pseudomonas septicemia. At autopsy, a typical finding of progressive multifocal leukoencephalopathy was found in the areas altered in the NMR tomography. Papova-like virions could be demonstrated in glial cells by electron microscopy.

Adult↗
PubMed1987

Invasive bronchopulmonary aspergillosis leading to rapidly progressive respiratory failure in a patient with severe aplastic anemia.

A 22-year-old man with severe aplastic anemia was treated with antilymphocyte globulin, prednisone, and oxymetholone. Fourteen days after initiation of treatment he developed a fulminant mediastinal and subcutaneous emphysema leading to respiratory failure refractory to mechanical ventilation. Fiberoptic bronchoscopy showed nodular lesions typical of aspergillus. Cultures of bronchial mucus revealed Aspergillus fumigatus as the responsible pathogen.

Adult↗
PubMed1987

Clinical pharmacology of aminoglutethimide in patients with metastatic breast cancer.

The pharmacology of aminoglutethimide (AG) was studied in two subsequent trials without hydrocortisone supplementation. A total of 79 patients with metastatic breast cancer entered the study, and their plasma and urine samples were analyzed by high-performance liquid chromatography (HPLC). Thirty evaluable patients with a median age of 57 years (range, 37-79) were treated with the standard dose of 1000 mg/day, and 37 evaluable patients with a median age of 59 years (range, 35-79) received 500 mg/day. The median follow-up in the two groups was 5 months (range, 1-16) and 4 months (range, 1-21), respectively. After the first oral dose of 500 mg, peak plasma concentrations of AG were observed 1-4 h after administration in 15 patients. The elimination half-life was 10.1 +/- 1.7 h (mean +/- SD) after initial dosage; it decreased significantly to 6.9 +/- 1.2 h after 8 weeks of treatment. The area under the curve of AG concentrations was 92.5 +/- 14.2 micrograms/ml x h. The total clearance rate was 5.5 +/- 0.9 1/h and the volume of distribution was 80 +/- 111. About 23% of the drug was excreted unchanged in the urine. The major metabolite, N-acetyl-AG (AAG), had the same half-life as AG. A comparison on day 7 of treatment revealed that doses of 1000 and 500 mg yielded AG plasma concentrations of 9.0 +/- 1.2 and 4.5 +/- 0.5 micrograms/ml, respectively. After 1 month of treatment, however, AG plasma levels of 6-7 and 4-5 micrograms/ml were observed, respectively. A 50% reduction of dose, therefore, resulted in only 30% lower AG levels during continuous treatment. Apparently, the induction of metabolism is of greater importance in standard-dose than in lower dose treatment. The plasma concentrations of AG did not bear a relationship to the clinical response.

Adult↗
PubMed1987

[Pre- and postoperative chemotherapy in bone and soft tissue tumors].

Adjuvant chemotherapy is efficacious in Ewing's sarcoma, and in osteosarcoma most data support its beneficial effect. There is evidence to suggest efficacy of adjuvant treatment in high-grade malignant soft tissue sarcomas. Neoadjuvant chemotherapy can be used as prediction for the efficacy of further adjuvant chemotherapy and may facilitate resection in osteosarcoma.

Antineoplastic Agents↗
PubMed1986

[Therapy of primary resistant or recurrent small cell bronchial carcinoma with vindesine and ifosfamide].

A combination of vindesine (3 mg/m2, day 1) and ifosfamide (60 mg/kg, days 1-5 + Mesna) was administered every three weeks to 11 patients with primary resistant and 23 with recurrent small-cell bronchial carcinoma. All patients had been pre-treated with chemotherapy, 16 in addition with radiotherapy. At the onset of the vindesine-ifosfamide treatment the cancer was in a localized regional stage in ten patients, while in 24 it was in a more widely spread stage. In 29 patients whose treatment results could be evaluated the remission rate was 38%, with two complete and nine partial remissions. In a further eight patients the cancer was arrested. The patients with complete remission (for 46 and 53 weeks, respectively), those with partial remission (median of 39 weeks) and those with stationary disease (median of 31 weeks) survived significantly longer than those with progressing disease (13 weeks). There was no correlation between treatment result and pre-treatment. On recurrence after complete remission or in the localized regional stage the remission rate was 70% and 60%, respectively, and the survival time was extended in 90% of cases. In addition to nausea, alopecia and myelosuppression, side-effects included vomiting, reversible CNS symptoms, polyneuropathy and urotoxicity. On the basis of acceptable toxicity, combined vindesine and ifosfamide constitute an effective treatment of otherwise treatment-refractory cases of small-cell bronchial carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Aminoglutethimide without hydrocortisone in the treatment of postmenopausal patients with advanced breast cancer.

In a phase II study, 38 evaluable patients with advanced progressive breast cancer were treated with 4 X 250 mg of aminoglutethimide per day without hydrocortisone supplementation. Partial remissions were observed in five patients (13%), with a median duration of 9 months (range, 7-15), and stable disease was observed in 17 patients (45%), with a median duration of 4 months (range, 2-11). The recorded side effects (CNS, cutaneous, gastrointestinal) were tolerable and transient and required drug discontinuation in only four patients. Serial determinations of serum hormone levels during aminoglutethimide treatment revealed a significant decrease in estradiol and an increase in gonadotropins, testosterone, and progesterone. No patients had adrenal insufficiency. In contrast, despite prolonged aminoglutethimide treatment and persisting hypoestrogenemia, both cortisol levels and adrenal responses to ACTH remained unaltered. It is concluded that aminoglutethimide alone is effective in the treatment of postmenopausal patients with breast cancer. Moreover, based on the present findings, a prospective randomized study is warranted to show that hydrocortisone supplementation appears to not be mandatory, either for increase in efficacy or for decrease in side effects of the treatment.

Adult↗
PubMed1985

[Chemotherapy of advanced lymphogranulomatosis. Results of MOPP/COPP treatment at the West German Tumor Center, Essen].

Between 1968 and 1979, a total of 271 patients with advanced Hodgkin's disease received as first systemic chemotherapy MOPP (mechlorethamine [nitrogen mustard], oncovin [vincristine], procarbazine and prednisone) or COPP (as above, but cyclophosphamide instead of nitrogen mustard). In 162 of the 271 patients (60%) full remission was achieved. Demonstration of systemic signs, bioptically confirmed bone-marrow infiltration and suboptimal cytostatic dosage correlated significantly with a lower full-remission rate. A significant trend towards a lower remission rate was demonstrated for stage IV disease, in patients with lymphocyte-poor or unclassified Hodgkin's disease and in those older than 30 years. A five-year recurrence-free period was achieved in 75.5% of patients: stage of the disease and bone-marrow infiltration had a clear influence on recurrence-free survival rate. The results show that 50% of patients with advanced Hodgkin's disease can be cured by chemotherapy.

Adult↗
PubMed1985

Changes in self-renewal potential of human leukemic cells (K562): a bidirectional stochastic process.

Daughter cells arising from a single cell division in the leukemic cell line K562 have equivalent self-renewal potential with respect to their ability to form clones in semisolid medium. However, individual cells isolated from these clones in sequence have vastly different abilities in their self-renewal potentials. Thus, cells originating from a clone with any particular self-renewal potential exhibit the full range of self-renewal potentials--from highly renewing to none renewing, cells. These results show that self-renewal potential in the K562 cell line is a random, reversible and partially noninherited characteristic. It is suggested that the stochastic variability of the intraclonal self-renewal potential of K562 progeny cells either reflects the initial expression of a differentiation program or the expression of the predeterministic portion of the normal myelopoietic differentiation pathway.

Cell Differentiation↗
PubMed1985

Commitment to differentiation of human promyelocytic leukemia cells (HL60): an all-or-none event preceded by reversible losses of self-renewal potential.

A method for clonal analysis has been developed which allows the characterization of the number and type of progeny cells produced by each single cell arising during clonal evolution. The method is based on a symmetry of self-renewal exhibited by sister cells of the human promyelocytic leukemia cell line -HL60-. This permits the use of one of the sister cells to measure the potential for self renewal of the other. Using a system of sequential daughter cell transfers in semisolid medium, we have analysed self-renewal and differentiation in individual clones exposed to all-trans retinoic acid or dimethylsulfoxide (DMSO). We find that in clones exposed to chemical inducers of differentiation commitment occurs as an all-or-none event which is preceded by coordinated but reversible losses of self-renewal potential. It is concluded that the differentiation pathway of HL60 cells has two distinct portions. These are, first, a predeterministic portion, reflected by coordinated but reversible losses of self-renewal potential, and second, a deterministic portion, reflected by irreversible phenotypic differentiation.

Cell Division↗