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Biomedical subjects

N Niederle

Publications and source records attributed to N Niederle.

At least 91 records · Page 5Linked to original sources
PubMed1989

A PvuII polymorphism of the bcr region in patients with hematopoietic disorders and their families.

The BCR gene on chromosome 22 has received increasing attention because of its involvement in the Philadelphia (Ph') translocation. For most restriction enzymes, this locus has been found to be nonpolymorphic. Two alleles have only been found when Taql-digested DNA is hybridized to a 5' bcr-specific probe. We describe another two-allele polymorphism detected by the same probe in PvuII-digested DNA. The polymorphism is characterized by an additional PvuII site in the bcr region: this causes the appearance of an additional band of about 2.3 kb or 2.5 kb besides a 4.8-kb fragment in hybridizations with the 5' bcr or a 3' bcr probe. The incidence of the second allele is very low. It has only been found in some patients with hematopoietic malignancies and in a group of volunteers having a leukemia patient in their families.

Deoxyribonucleases, Type II Site-Specific↗
PubMed1989

Phase I study of recombinant human tumor necrosis factor alpha in advanced malignant disease.

A phase I study with recombinant human tumor necrosis factor alpha (rhuTNF-alpha; Knoll AG, Ludwigshafen, FRG) in patients with advanced malignant disease was undertaken to evaluate drug toxicity (organ specificity, time course, predictability, reversibility, maximal tolerated dose), effectiveness, antigenicity and pharmacokinetics. TNF was administered as a test dose followed by daily i.v. infusions for 5 days, every 3 weeks (single i.v. infusion lasting 10 min, TNF dissolved in 50 ml 5% human albumin). Dosage was increased in groups of 3 or 4 patients from 0.04 mg/m2 to 0.28 mg/m2. A total of 19 patients with different cancers, including seven large-bowel carcinomas, three chronic myelogenous leukemias, three hypernephromas, two small-cell lung cancers, one malignant melanoma, one malignant lymphoma, one rhabdomyosarcoma and one fibrosarcoma were treated. Major side-effects were chills and fever (maximum 40.4 degrees C, median 38.7 degrees C, 19/19), headache (12/19), nausea and vomiting (12/19) and pronounced (greater than 20%) hypotension (4/19). Acute side-effects could be diminished by paracetamol or indomethacin pretreatment, and with one possible exception no tachyphylaxis to TNF was noted. Mild renal toxicity was seen during TNF treatment. Pharmacokinetic studies showed a serum half-life (t1/2) ranging from 11 min to 17 min for doses from 0.04 mg/m2 to 0.16 mg/m2 and prolonged clearance with t1/2 ranging from 54 min to 70 min in the 0.20-0.28 mg/m2 dose range. No objective antitumor effects were observed in this phase I study.

Adenocarcinoma↗
PubMed1988

Is there any clinical relevance of serial determinations of serum carcinoembryonic antigen in small cell lung cancer patients?

Carcinoembryonic antigen (CEA) serum concentrations were serially determined by an enzyme immunoassay before, during, and after chemotherapy and radiotherapy in 129 male patients with small cell lung cancer (SCLC). Pretherapeutic CEA concentrations were as follows: 2.5 ng/ml or less for 37% of the patients; greater than 2.5 but less than or equal to 5 for 27%; and greater than 5 for 36%. Before therapy, CEA levels in patients with extensive disease (median value, 5.8 ng/ml) were higher than those in patients with limited disease (3.0 ng/ml; P less than 0.01). Median survival in patients with pretherapeutic CEA titers of 5 ng/ml or less (median survival, 14.3 months) was significantly longer than in patients with CEA levels greater than 5 but less than or equal to 10 and CEA levels greater than 10, respectively (8.3 and 9.7 months; P less than 0.01). Patients with pretherapeutic CEA levels greater than 10 ng/ml showed a significant decrease (P less than 0.01) of CEA while reaching partial remission (PR) or complete remission (CR). In five of 16 evaluable patients, a continuous increase of CEA titers was seen starting at least 3 months before relapse could be defined by clinical, radiologic, or endoscopic means. However, the number of patients for whom CEA serum determinations reliably indicate stage of disease and outcome of therapy is small (at best, 10% of all SCLC patients), and pretherapeutic CEA level cannot be used for individual prognosis. Moreover, it is still uncertain whether earlier detection of relapse in SCLC can improve the therapeutic results. So far, the clinical relevance of serial CEA serum determinations in SCLC patients is rather low.

Adult↗
PubMed1988

Advanced male breast cancer treatment with the LH-RH analogue buserelin alone or in combination with the antiandrogen flutamide.

Ten men with advanced breast cancer were evaluated for response to treatment with the luteinizing hormone-releasing hormone (LH-RH) analogue, buserelin, alone or in combination with the antiandrogen, flutamide. One of five patients receiving buserelin as a single agent had a partial remission lasting 12 months, and with the addition of flutamide, this lasted over 24 additional months. Three patients had stable disease with a median duration of 6 months (range, two to 14). One patient had progressive disease. Of five patients receiving the combination of buserelin and flutamide from the beginning of therapy, four patients had a partial remission with a median duration of over 15 months (range, over five to 16). One patient's disease remained stable for 12 months. Major side effects were hot flushes, loss of libido, and impotence. Buserelin initiates a castration-like endocrine response and has potential in the treatment of men with disseminated breast cancer when used either alone or in combination with flutamide.

Aged↗
PubMed1988

[Pretherapeutic prognostic factors in small cell bronchial cancer].

Two hundred and thirty patients with histologically proven small cell lung cancer--133 patients with limited disease and 97 patients with extensive disease--were treated from 1979 to 1986 in 3 prospective clinical trials at a single institution. Univariate and multivariate statistical analyses (Cox-models) were used to determine whether pretherapeutic factors can be used to predict survival and long-term survival. Extent of disease, determined by pretherapeutic staging, turned out to be the most significant prognostic parameter. Survival beyond 2 years was almost exclusively confined to patients with limited disease. Further independent predictors of survival duration in patients with limited disease were serum levels of lactate dehydrogenase and urea. In extensive disease, however, performance status, levels of serum lactate dehydrogenase and the intensity of therapy turned out to be the best pretherapeutic prognostic factors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

[The dose of alpha interferon in induction and maintainance therapy of hairy cell leukemia].

The efficacy of different doses of interferon (IFN) alpha in the induction therapy of hairy cell leukemia was studied. Recombinant IFN alpha-2b was administered subcutaneously every second day at an initial dose of 4 x 10(6) U/m2 (7 patients), 2 x 10(6) U/m2 (14 patients) and 1 x 10(6) U/m2 (13 patients). Each dose was effective to induce a normalization of blood cell counts and a reduction of bone marrow infiltration in the majority of patients treated. A delayed increase in granulocyte counts, however, was noted in patients treated with 1 x 10(6) U/m2, and 2 of them only achieved a partial hematological remission after 1 year of treatment. After the induction of stable remission, patients were randomized into 2 different schedules of maintenance therapy. Five of 7 patients receiving IFN alpha-2b at a total dose of 1 x 10(6) U twice a week, and 6/8 patients treated with 2 x 10(6) U once weekly, respectively, received this therapy for 1 year and remained in stable remission.

Adult↗
PubMed1988

[Various aspects and results of therapy with interferon].

Aspects and Results of Interferon Therapy Interferons are effector molecules with pleiotropic biologic functions. Significant clinical activities have been seen in viral diseases and hematologic malignancies, such as hairy cell leukemia, low-grade nodular non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, and chronic myelogenous leukemia. In contrast, the efficacy in solid tumors has been less impressive. In these disorders, higher doses are necessary to induce remission. Responses to interferons are typically slow with improvement often taking several weeks to months. A wide range of both acute and chronic toxicities have been defined. Since these side effects are dose-related and are rarely tolerable for long-term treatment, optimal doses and schedules should be defined in future clinical trials. A better understanding of the mode of anticancer action is an important area of interferon research. Clinical areas might preferably include situations with minimal tumor load, especially in combination with other cytokines, different cytostatic drugs or local therapeutic modalities.

Humans↗
PubMed1987

[Detection of nephrotoxicity of human alpha 2b interferon with special reference to the analysis of urine enzymes in patients with chronic myeloid leukemia].

The nephrotoxic potential of alpha-interferon (IFN alpha-2b) was analysed in 21 patients with chronic myeloid leukemia. As particularly sensitive parameters in the detection of subclinical renal injury we measured the excretion of the following urinary enzymes: lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), leucine arylaminidase (LAP), beta-galactosidase (GAL) and N-acetyl-beta-glucosaminidase (NAG). Additionally, protein excretion and urinary sediment were analysed. In 18 of 21 patients a significant increase in the excretion of LDH, LAP, GGT and NAG was found, in 6 patients there was an additional rise in the output of GAL. Eleven patients developed proteinuria up to 2 g/l, one patient excreted up to 9 g/l. Enzymuria and protein excretion decreased in all patients after reduction of the IFN alpha-2b dosage and disappeared in two patients following cessation of therapy. The high incidence of nephrotoxic events in patients with CML during IFN alpha-2b therapy might be mostly due to immunological or substance-specific effects.

Adolescent↗
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

Treatment of chronic myelogenous leukemia with recombinant interferon alfa-2b.

Interferon alfa-2b (Intron A; Schering-Plough) was administered to 36 patients with chronic myeloid leukemia (CML) at an initial dose of 4 X 10(6) IU/m2 daily subcutaneously, adapted to changes in leukocyte counts during the course of treatment. Of 32 patients who could be fully evaluated (20 men and 12 women; median age, 34 years) 29 were in the chronic phase, one had a blast crisis and two had accelerated phase disease. Hematologic remission was achieved in 20 of the 32 patients, while a partial hematologic remission was obtained in 10. Elevated pretreatment white-cell counts returned to normal in 25 patients after 3-40 weeks. There was a parallel decrease in platelet counts after an average treatment time of six weeks and in lactate dehydrogenase, after 2-20 weeks. In conclusion, administration of interferon alfa-2b resulted in a relatively rapid cell reduction in chronic phase CML. The long-term effect of this treatment on the course of the disease and the place of interferon alfa-2b in the overall concept of CML treatment remains to be evaluated.

Adult↗
PubMed1987

Response to the combined administration of interferons alpha and gamma after failure of single interferon therapy in chronic myelogenous leukaemia.

A previously untreated patient with benign phase chronic myelogenous leukaemia (CML) was treated with recombinant Interferon alpha-2 b. Haematological remission was induced for a total of twelve months. Thereafter, the patient developed resistance to Interferon alpha manifested by an increase in leucocyte counts despite dose escalation (up to 7 x 10(6) IU/day s.c.). Subsequent treatment with recombinant Interferon gamma failed to control myeloid proliferation. However, combined administration of both Interferon alpha and Interferon gamma resulted in a renewed haematological remission which lasted six months.

Adult↗