Impact of interferon alpha-induced cytogenetic improvement on survival in chronic myelogenous leukaemia.

The objective of this study was to investigate the prognostic impact of the reduction of Philadelphia chromosome (Ph) positive metaphases by treatment of chronic myelogenous leukaemia (CML) with interferon (IFN) alpha. Therefore, we evaluated the outcome of patients with previously untreated chronic phase Ph-positive CML, enrolled from 1984 to 1990 into two consecutive IFN trials at our institution. Of a total of 71 patients, 62 (87%) were evaluable for cytogenetic response.

Lupus-like autoimmune disease induced by interferon therapy for myeloproliferative disorders.

Symptoms of autoimmune disease were evaluated in 125 patients with chronic myelogenous leukemia (CML) and in 12 patients with essential thrombocythemia undergoing treatment with recombinant interferon (IFN)-alpha-2b plus/minus low-dose recombinant IFN-gamma. Twenty-seven of 137 patients (20%) developed rheumatoid symptoms. Furthermore, the incidence of antinuclear antibody (ANA) formation was studied.

Relation between leukocyte counts and cortisol secretion in CML patients undergoing combined TNF alpha/IFN alpha therapy.

During long-term interferon alpha-2b (IFN) therapy of Philadelphia chromosome-positive chronic myelogenous leukemia (CML) patients, short-term effects of tumor necrosis factor alpha (TNF) on peripheral leukocyte counts, as well as cortisol and corticotropin (ACTH) release were studied. TNF (40-160 micrograms/m2) was given as a 2-h infusion on 5 consecutive days every 3 weeks, in addition to s.c.

Combination therapy with interferon alpha-2b plus low-dose interferon gamma in pretreated patients with Ph-positive chronic myelogenous leukaemia.

Between March 1988 and July 1990, 28 adults with chronic myelogenous leukaemia (CML) were treated with a combination of recombinant human interferon (IFN) alpha-2b s.c. (initial dose 4 x 10(6) U/m2) and recombinant human IFN gamma s.

Treatment of chronic myelogenous leukemia with different cytokines.

In vitro data suggest a synergistic antiproliferative effect of different cytokines. In four clinical studies chronic myelogenous leukemia (CML) patients were treated with interferon (IFN)-alpha alone or IFN-alpha combined with either low-dose IFN-gamma or tumor necrosis factor (TNF)-alpha. The best response was achieved in previously untreated patients with good prognostic factors and highest tolerable IFN dose for maintenance treatment.

A prospective randomized comparison of single-agent interferon (IFN)-alpha with the combination of IFN-alpha and low-dose IFN-gamma in chronic myelogenous leukaemia.

In patients with previously untreated chronic myelogenous leukaemia (CML) the efficacy of single-agent interferon (IFN)-alpha at an initial dose of 4 x 10(6) U/m2 (arm A) was compared with the combined administration of the identical dose IFN-alpha plus a total dose of 50 micrograms IFN-gamma (arm B). 51 patients entered this study between April 1987 and October 1989; the analysis was performed in March 1991 and was focused on response rates and toxicity. 54% of patients on arm A and 56% of arm B patients attained haematologic remission.

Tumor necrosis factor alpha modifies resistance to interferon alpha in vivo: first clinical data.

Patients with Philadelphia-positive chronic-phase chronic myelogenous leukemia (CML) resistant to interferon (IFN) alpha were treated in a phase I/II study with recombinant human tumor necrosis factor alpha to overcome IFN alpha resistance. Doses of 40, 80, 120 or 160 micrograms/m2 TNF alpha were given as 2-h infusions on 5 consecutive days every 3 weeks. IFN alpha (4 x 10(6) IU/m2 s.

Minimal residual disease in patients with chronic myelogenous leukemia undergoing long-term treatment with recombinant interferon alpha-2b alone or in combination with interferon gamma.

Interferon (IFN) therapy has become widely used for the treatment of chronic myelogenous leukemia. Hematologic remissions can be induced in about 60% of patients. Moreover, in a small number of patients loss of the Philadelphia (Ph) chromosome and of the BCR-ABL rearrangement is observed.

Etoposide, ifosfamide, and methotrexate with or without bleomycin in refractory or recurrent lymphomas.

The prognosis of patients with refractory or relapsed malignant lymphoma is poor. To improve the outcome of such patients, a therapeutic regimen of VIM +/- B (etoposide/ifosfamide plus mesna/methotrexate/ with or without bleomycin) was administered. Of 47 patients treated, 15 had relapsed following complete remission (CR) after first-line chemotherapy, 28 had failed to achieve CR with first-line therapy, and four failed to respond to multiple salvage regimens.

Age-dependency of alpha- and beta-adrenoceptors on thrombocytes and lymphocytes of asthmatic and nonasthmatic children.

Among the possible mechanisms which may cause wheezing or asthmatic episodes a genetically determined beta-adrenoceptor blockade and a hyperresponsiveness of alpha-adrenoceptors has been postulated. Evidence to support this hypothesis stems from an increased bronchial sensitivity to beta-blockers, a reduced formation of cyclic AMP in response to beta-adrenergic stimulation and enhanced alpha-adrenergic responses in asthmatic subjects. The recent development of techniques for measuring the specific, high-affinity binding of radiolabeled alpha- and beta-adrenergic antagonists made it possible to study alpha- and beta-adrenoceptors in vitro.

The influence of methylphenidate on the sympathoadrenal reactivity in children diagnosed as hyperactive.

In order to investigate whether catecholamines play a role in the hyperkinetic child syndrome, we determined noradrenaline and adrenaline plasma levels before and after treatment with methylphenidate. The children were separated into drug responders and non-responders according to the efficacy of methylphenidate on behavioral symptoms. 21 children, 6-13 years of age, participated in this double-blind placebo controlled cross-over study.

Influence of beta-receptor-agonists and glucocorticoids on alpha- and beta-adrenoceptors of isolated blood cells from asthmatic children.

The most attractive "adrenergic theory" has proposed that in asthmatic patients the bronchial hyperreactivity might be caused by a decreased beta-receptor and an increased alpha-receptor responsiveness. Based upon the assumption that an abnormality of adrenergic receptors might be a general phenomenon, we have performed receptor-binding studies on lymphocytes and thrombocytes from asthmatic children who had and had not undergone treatment with beta-receptor agonists and/or glucocorticoids. Iodo-cyano-pindolol and tritium-labeled yohimbine were used as beta- and alpha-receptor ligands.

A sensitive radioenzymatic assay for dihydroxymandelic acid, dihydroxypenylglycol and dihydroxyphenylacetic acid .

A sensitive radioenzymatic procedure for the simultaneous determination of dihydroxymandelic acid, dihydroxyphenylglycol, and dihydroxyphenylacetic acid has been developed. The catechols were methylated by catechol-O-methyltransferase using S-adenosyl[methyl-3H]methionine as methyl donor. The assay involved extraction into organic solvent, thin-layer chromatography and periodate oxidation.

A radioenzymatic method for determination of normetanephrine in blood plasma.

A radioenzymatic assay for determination of normetanephrine in blood plasma is described. It was based on N-methylation of normetanephrine by phenylethanolamine-N-methyltransferase using S-adenosyl[methyl-3]methionine as the methyl donor. 2981 +/- 85 cpm (mean +/- s mean, n = 32) were obtained from 1 ng normetanephrine.

Plasma catecholamines during activation of the sympathetic nervous system in a patient with Shy-Drager syndrome.

Plasma catecholamines and circulation parameters were studied in a patient with a Shy-Drager syndrome. Basal values of free noradrenaline and dopamine were within the normal range, whereas the adrenaline level was decreased. The response of plasma catecholamines to different kinds of physical activity was pathological.