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Biomedical subjects

A Sandberg

Publications and source records attributed to A Sandberg.

33 records · Page 2Linked to original sources

Intensive remission consolidation therapy in the treatment of acute nonlymphocytic leukemia.

A pilot study was conducted to determine the possible efficacy and the toxicities associated with the administration of four courses of intensive consolidation chemotherapy to patients with acute nonlymphocytic leukemia in remission. All therapy was completed within 6 months. The median duration of remission was 22 months, with 45+% of patients in remission at 3 years and few relapses to date thereafter. Sixty percent of patients experienced significant side effects after each course of therapy. The therapy appeared to be particularly efficacious for patients less than 45 years of age, since 65% are alive at 3 years and there is no projection for a median duration of remission as yet. The cytogenetic characteristics of the leukemic cells, the percentage of S phase cells, and the height of the WBC count were the most important prognostic characteristics at diagnosis.

Acute Disease↗

Oesophageal ulcerations and plasma levels of different alprenolol salts: potential implications for the clinic.

The ulcerogenic effect of five different salts of alprenolol were tested against placebo in a porcine oesophageal test model. The salts with high water solubility, such as the hydrochloride and the fumarate, gave rise to the highest plasma concentrations of alprenolol and evoked serious oesophageal lesions, while the salts with low solubility-the benzoate, maleate and sebacate-had no irritative effect on the oesophagus. The plasma levels of alprenolol were much higher following administration of alprenolol hydrochloride in the oesophagus than after an identical intraduodenal dose of the same salt possibly because of the avoidance of the first-pass degradation during oesophageal absorption.

Absorption↗

Experimental models of bladder cancer: a critical review.

We have reviewed critically the available models of bladder cancer, and have attempted to compare their strengths and weaknesses where appropriate data are available. Further direct comparisons of the applications of each model will be needed in order to rank them, and to identify areas of research where each model will predominate. Furthermore, more information will be needed to validate each model in the context of human disease. With the increasing range and sophistication of the tools of molecular biology, a very important future direction will be the characterisation of animal and human bladder cancer, and in particular the study of the changes from normal to neoplastic urothelium: tumor markers, chromosomal patterns and oncogenes that are associated with specific biological functions, such as invasion, metastasis and ultimate prognosis. The transfection of normal tissues by oncogenes to yield transformed or immortalised lines may be of critical importance in identifying the nature of neoplastic transformation. The use of animal tumors and xenografts, each with the availability of a physiological internal milieu (although different from human metabolic conditions) may yield useful systems for the testing of new therapeutic approaches. However, of the utmost importance is the continuing need to characterise and validate each model, to avoid multiple publications and nomenclatures pertaining to common lines, and to recognise the limitations of the heavily adapted long term cell lines in vivo and in vitro. The major deficiencies of the available lines continue to be found in the method of their application to basic research, rather than being inherent in themselves. Although there are many theoretical and practical applications of these models, it should not be forgotten that the direct study of human bladder cancer, including the appropriate processing of biopsy specimens, will remain integral to understanding the biology of this disease.

Animals↗

Coexistence of myeloid metaplasia with myelofibrosis and hairy-cell leukemia.

A 42-year-old man with severe pancytopenia and myelofibrosis underwent splenectomy seven months after onset of his symptoms; the leukocyte, platelet, and hematocrit levels became normal. Myeloid metaplasia was identified in the liver and spleen. Progressive lymphocytosis started eight months after splenectomy, and after 66 months a florid hairy-cell leukemia was diagnosed; the circulating cells were B type with micro K surface markers. Anemia and thrombocytopenia reappeared and were controlled initially with daily prednisone; chlorambucil was later added. At that time, the peripheral blood had more than 150 megaloblastoid-appearing normoblasts per 100 leukocytes. The PAS stain was positive in 95% to 100% of these cells; the B-cell surface markers were no longer identified. Further treatment failed to control the lymphoproliferative and myeloproliferative syndromes; the patient died 99 months after splenectomy. On autopsy, infiltration by hairy-cell leukemia cells and erythroid precursors was observed in the bone marrow, liver, lymph nodes, and other organs.

Adult↗

Prostatic cancer--II. Inhibitors of rat prostatic 4-ene-3-ketosteroid 5 alpha-reductase derived from 6-methylene-4-androsten-3-ones.

The studied 6-methylene-4-androsten-3-ones proved to be significantly inferior to 6-methylene-4-pregnene-3,20-dione and its 17-acetoxy derivative described in Part 1 as inhibitors of 4-ene-3-ketosteroid 5 alpha-reductase [1] in vitro. Surprisingly, the 6-methylene derivative of testosterone was only weakly active until acetylated, when an effective inhibitor was obtained. Etherification of the hydroxyl-group, its replacement by a hydrocarbon chain, or introduction of a substituent at C17 or on the methylene group led to virtual loss of activity. 17 alpha-Chloro-6-methylene-4-androstene-3-one had ca 60-70% of the potency of progesterone, but was inactive as enzyme inhibitor in explants of rat prostate in tissue culture and in in vivo studies. 6-Methylenetestosterone acetate was weakly active as enzyme inhibitor in explants of human prostate in tissue culture and produced a histological picture closely resembling testosterone and differing from that of cyproterone acetate. In vivo in the rat it had 80% of the androgenic activity of testosterone propionate. The foregoing data have been used to define some structural characteristics necessary for enzyme inhibition and to draw some conclusions regarding the architecture of the androgen and progesterone receptors and of the enzyme active site.

5-alpha Reductase Inhibitors↗

Prostatic cancer. I. 6-Methylene-4-pregnen-3-ones as irreversible inhibitors of rat prostatic delta 4-3 ketosteroid 5 alpha-reductase.

Some derivatives of 6-methylene-4-pregnen-3-one were studied as inhibitors of delta 4-3-ketosteroid 5 alpha-reductase. Maximum inhibitory activity was shown by 17-acetoxy-6-methylene-4-pregnene-3,20-dione (AMPD). Irreversible inactivation was observed following preincubation of the enzyme with NADPH and AMPD. This inactivation was found to occur only in the presence of NADPH. As such enzyme inactivation was not due to the formation of a more inhibitory metabolic product, or to the formation of superoxide via a cytochrome P-450/NADPH pathway, it seemed likely that the observed inactivation was derived from an irreversible combination of the enzyme with AMPD. That this was probably the case was established by kinetic studies which revealed a pattern compatible with a kcat type of mechanism.

5-alpha Reductase Inhibitors↗

Murine myeloid leukemia: colony formation in vitro.

Normal and myeloid leukemic spleen cells from RF mice were cultured in vitro in plasma clots. In situ histochemical staining and karyotypic analysis of the colonies formed in the clot revealed that the colonies produced by leukemic and normal progenitors were indistinguishable morphologically and cytochemically. Colonies of leukemic origin were identified by in situ karyotypic analysis, a method not previously utilized in studies of hematopoietic proliferation in semi-solid matrices.

Animals↗