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Biomedical subjects

F Walther

Publications and source records attributed to F Walther.

At least 37 records · Page 2Linked to original sources

Recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes--a phase I/II trial.

In a phase I/II study, 11 patients with myelodysplastic syndromes (MDS) and severe transfusion-dependent cytopenia were treated with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to investigate the effects of rhGM-CSF on normal hematopoiesis and leukemic cells. The treatment schedule included dose escalation from 15 micrograms/m2 to 150 micrograms/m2 administered by continuous intravenous (IV) infusion for seven to 14 days and was repeated after a two-week treatment-free interval. The blood leukocyte counts increased dose dependently by 130% to 1,800% in ten patients; a rise of monocytes and eosinophils occurred in seven and six patients, respectively. No sustained increase in reticulocytes or platelets was observed. Lymphocyte counts increased in all patients affecting both T-helper and T-suppressor cells; however, the lymphocytes were not activated as analyzed by the expression of the interleukin-2 receptor. In four of the patients, all with greater than 14% blast cells in the bone marrow, the percentage of bone marrow blast cells increased during treatment with rhGM-CSF. Cytogenetic data indicated induction of both proliferation and differentiation of the leukemic clones by rhGM-CSF. Toxic side effects were minor with slight fever, phlebitis at the infusion site, and bone pain in the minority of patients. In conclusion, rhGM-CSF effectively stimulates hematopoiesis in vivo in patients with myelodysplastic syndromes. However, as the leukemic cell population can be stimulated in patients with a higher initial blast cell count, the combination of rhGM-CSF with other differentiation-inducing or cytotoxic agents has to be considered.

Aged↗

Recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes--a phase-I/II trial.

A phase-I/II trial was initiated to study the effect of rhGM-CSF in patients with myelodysplastic syndromes who were not eligible for other kinds of therapy, rhGM-CSF was given to 9 patients in doses of 15 micrograms/m2-150 micrograms/m2 as an intravenous 8-h infusion for a cycle of 7 days followed by an interval of 14 days and a second 7-day treatment course. A dose-dependent increase in the leukocyte count was observed in 7 out of 9 patients. No change in reticulocyte numbers was seen and only 1 patient experienced an increase in platelet count. Toxicity mainly consisted of mild local phlebitis at the site of infusion and sternal pain after bolus injection.

Aged↗

In vitro and in vivo action of recombinant human GM-CSF (rhGM-CSF) in patients with myelodysplastic syndromes.

The availability of rhGM-CSF has allowed the in vivo treatment of patients with cytopenia. Therefore, a phase I-II trial was initiated to study the effect of rhGM-CSF in patients with myelodysplastic syndromes who were not eligible for other kinds of therapy. rhGM-CSF has been tested in 10 patients in doses from 15 micrograms/m2 to 150 micrograms/m2 given intravenously over 8 hours for a cycle of 7 days followed by an interval of 14 days and a second 7-day treatment course. A dose-dependent increase in leukocyte count was observed in 9 of 10 patients. No change in reticulocyte numbers was seen and only one patient experienced an increase in platelet count. Toxicity mainly consisted of mild phlebitis at the site of infusion and sternal pain after bolus injection. An increase in blast cell counts in some patients necessitated the start of low-dose Ara-C therapy.

Colony-Stimulating Factors↗

Phase I/II study with GM-CSF in patients with myelodysplastic syndromes.

The availability of rh GM-CSF has allowed the in vivo treatment of patients with cytopenia. Therefore a phase I/II trial was initiated to study the effect of rh GM-CSF in patients with myelodysplastic syndromes who were not eligible for other kinds of therapy. rh GM-CSF has been tested in 10 patients in doses from 15 micrograms/m2 to 150 micrograms/m2 given intravenously over 8 hours for a cycle of 7 days followed by an interval of 14 days and a second 7-day treatment course. A dose dependent increase in leukocyte count was observed in 9 out of 10 patients. No change in reticulocyte numbers was seen and only one patient experienced an increase in platelet count. Toxicity mainly consisted of mild local phlebitis at the site of infusion and sternal pain after bolus injection. An increase in blast cell counts in some patients necessitated the start of low dose Ara-C therapy.

Colony-Stimulating Factors↗

Evidence for colonic absorption of protein nitrogen in infants.

The absorption of protein nitrogen by the colon was assessed in 6 infants with colostomy by giving 15N yeast protein in a dosage of 5-20 mg 15N/kg (92.4 atom-% 15N). The absorption of 15N ranged between 87.1 and 98.1% of the administered dose, and the retention in the protein pool ranged between 79.0 and 94.2%. The incorporation of 15N in the plasma proteins was demonstrated by 15N excess values between 0.02 and 0.10 atom-%. The results suggest that the colon can assimilate proteins when insufficient absorption of protein nitrogen in the small intestine occurs. The breakdown of protein is thought to result from the action of colonic flora.

Colon↗

[Resorption and metabolic utilization of D-[alpha-15N]lysine and L-[alpha-15N]lysine after oral administration, with special reference to the metabolism of intestinal bacteria].

Absorption of D-[alpha-15N]lysine and L-[alpha-15N]lysine following an oral single pulse labelling at a dosage of 5 mg 15N'/kg body weight was compared in four subjects aged 4 to 14 months. The wastages of 15N' in the faeces ranged from 0.3 to 5% of the input implying comparably high absorption rates of both the lysine enantiomers. Only about 7.6% of the 15N from the alpha-amino groups were found in the urine after loading with L-[alpha-15N]lysine. In contrast, about 80.2% of the 15N' dose from D-[alpha-15N]lysine were eliminated renally. However, 18.5% of the 15N' dose on an average were retained after D-[alpha-15N]lysine administration. This is certainly due to a partial desamination of D-lysine. The faecal bacteria isolated from the faeces contained no or only small amounts of 15N' after D-[alpha-15N]lysine loading. Following L-[alpha-15N]lysine administration a measurable 15N enrichment of the faecal bacteria of up to 0.09 at % excess was achieved in almost all cases.

Administration, Oral↗

Excretion of 15N and incorporation into plasma proteins after high-dosage pulse labelling with various tracer substances in infants.

The suitability of a biosynthetically produced [15N] yeast-protein-thermitasehydrolysate ([15N] YPTH), [15N] yeast protein and [15N] glycine for use as 15N-tracers was tested in three groups of four infants each. The [15N] YPTH was obtained by hydrolysing 15N-labelled yeast protein with thermitase, a proteinase from Thermoactinomyces vulgaris. Following oral single-pulse labelling in a dosage of 10 mg 15N/kg body weight the 15N-excretion in stools and urine as well as the 15N-abundance in plasma proteins and in the TCA-soluble plasma fraction were determined. The [15N] YPTH differs from [15N] glycine in terms of the complete distribution of 15N among all 20 amino acids. This could be demonstrated by a distinctly lower [15N]ammonia (0.5 per cent) and a higher [15N2] urea excretion (5.0 per cent) compared with [15N] glycine (1.2 and 3.4 per cent respectively). The faecal loss of 15N from the [15N] YPTH was 3.7 per cent of the tracer dose, while the corresponding value after administration of [15N] yeast protein was found to be 7.4 per cent on average. There were no differences between the tracer substances in terms of the measured 15N-abundance in the plasma proteins (mean: 0.07 atom per cent excess) and in the TCA-soluble fraction (mean: 0.21 atom per cent excess).

Blood Proteins↗

[Protein metabolism and lipid balance in dietary treatment of acute enteritis in infants with a defined standardized oligopeptide diet].

The advantage of a standardized oligopeptide formula (Peptisorb päd) for dietary management of diarrhea was proved in 10 infants aged 1 to 10 months with body weights between 4000 and 8860 g. The nitrogen balance turned to normal already at day 3 to 4 of the treatment due to the rapid increase of food supply. Whole body protein parameters estimated by 15N yeast protein thermitase hydrolyzate as a tracer substance were already normalized at that time. Protein synthesis amounted to 5.0 +/- 1.5 g/kg/day, protein breakdown to 3.7 +/- 1.5 g/kg/day and net protein gain to 1.3 +/- 0.6 g/kg/day, resp. Reutilisation rate of endogenous nitrogen was found to be 83%. This correlates with the relatively high nitrogen supply of the oligopeptide diet in comparison to mother's milk feeding. Approximately 15% of the administered amount of total nitrogen were excreted in the feces in contrast to only 5.8% of the 15N tracer dose, indicating the higher losses of endogenous nitrogen due to enteritis. The absorption of the medium chain triglycerides from the diet was 97.5% at an average and thus extremely high.

Acute Disease↗

[Acrocephalosyndactylia--Vogt syndrome].

A genetically remarkable case of the Vogt syndrome (combination of the Apert and Crouzon syndromes) associated with a dysraphia syndrome is described. Clinically, malformations corresponding to the Apert syndrome were prominent, and radiological examination of the skull revealed a prominent Crouzon syndrome. Investigation of the familial background revealed the presence of malformations in other members of the family, such as malformation of the extremities and acrocephalus. On the other hand, the father's age of 63 years was considerably higher than that of fathers in the average population, so that the possibility of a new mutation had to be considered. The fact that the mother suffered an attack of influenza during pregnancy, finally, brought the possibility of peristatic influences being involved in the complex malformations.

Acrocephalosyndactylia↗

[Bromocriptine in patients with idiopathic edema (author's transl)].

The diuretic therapy of patients with idiopathic edema is known to induce a secondary aldosteronism, which perpetuates edema formation and exacerbates the clinical symptoms. The observation of a decreased excretion of dopamine in these patients suggests that a treatment with the orally active dopamine agonist bromocriptine might be beneficial. Nine patients with typical symptoms of idiopathic edema, which had been present for several years, were treated with bromocriptine (Pravidel) 2 X 2.5 mg/die. The response to therapy was assessed clinically by the normalization of diurnal weight gain and general well-being. Seven patients showed a good response to bromocriptine, in one patient the response was only modest, and in one patient the medication had to be stopped because of nausea. Bromocriptine normalized diurnal weight gain without inducing weight loss. Both without therapy and during bromocriptine treatment electrolytes in serum, blood pressure, plasma renin activity and aldosterone are within the normal range. From the present pilot study it can be concluded that bromocriptine is an effective alternative to the traditional diuretic therapy in some patients with idiopathic edema. It remains unclear, whether the beneficial effect of bromocriptine reveals a dopamine deficiency, or whether bromocriptine is only a symptomatic treatment.

Adult↗

[Consequence of habitual use of laxatives (author's transl)].

Though habitual, but not excessive use of laxatives can be observed frequently, no accompanying clinical symptoms have yet been described. The frequent observation of tetany and edema is striking, there is a marked decrease of potassium clearance and an incipient impairment of creatinine clearance. A secondary hyperaldosteronism can be ruled out. The electrocardiograms of 9 patients show signs of mild hypokalemia, which in 2 patients were first misinterpreted as myocardial ischemia and in one patient taken as indication of myocarditis. Oral administration of potassium normalizes the electrocardiograms.

Adolescent↗

Human erythropoiesis in diffusion chambers.

The diffusion chamber technique has been modified in order to stimulate human erythropoiesis in addition to granulo- and monocytopoiesis. The chamber recipient mice were subjected to a combination of 750 rad irradiation and long-term non-interrupted hypoxia (0.5 atm) without chamber retransplantation. 7 d after implantation erythroid cells started to increase, reaching a maximum of up to 70% of the nucleated cells on day 12.

Animals↗

[Electrophoretic mobility of lymphocytes in chronic lymphatic leukemia (author's transl)].

Lymphocytes and other blood cells can be separated by means of free flow cell electrophoresis. Immunofluorescence of the separated lymphocytes of four healthy volunteers with antiimmunoglobulins IgD and IgM produced different distribution profiles for each immunoglobulin class, the IgD positive cells migrating faster than the IgM positive ones. Amongst five patients with chronic lymphocytic leukemia four with IgD positive lymphocytes (greater than 80%) showed an identical electrophoretic distribution. The IgM positive lymphocytes (greater than 80%) of the fifth patient migrated much more slowly. The weighted mean of each distribution profile of either the IgD or IgM positive lymphocytes in CLL is similar to that of normal subjects.

Adult↗