The aminoquinazoline group as a replacement for the salicylamide group: the design and synthesis of a novel highly selective beta 1 adrenoceptor partial agonist.

The high potency at beta 1 receptors, excellent selectivity (beta 1/beta 2) and high degree of agonism displayed by compounds such as 1 is believed to be due in part to the salicylamide side chain. Two conformations of salicylamide are known to exist in the crystal state (2 and 3), but ab initio calculations suggest that in the absence of crystal packing forces 2 should be more stable. The aminoquinazoline group was judged to be a good replacement for salicylamide in 1, and consequently the oxypropanolamine derivative 4 was prepared. 4 shows extremely high potency at the beta 1 receptor, and excellent beta 1/beta 2 selectivity. It has comparable in vitro activity to 1, although it displays a lower degree of agonism. These results suggest that in this system aminoquinazoline appears to be an excellent mimic of the salicylamide group.

Marrow biopsy and survival in multiple myeloma.

Pretreatment posterior iliac crest bone marrow biopsies were obtained from 26 multiple myeloma patients. Biopsies were processed in methacrylate. The percentage of myeloma tissue, myeloid tissue, and fat was estimated in each biopsy. In 20 patients who died there was a positive correlation between the percent of myeloid tissue in posterior iliac crest biopsies and survival time (r = 0.47, P less than 0.025), but no correlation could be demonstrated between percentage of myeloma tissue and survival time. The ratio of percentage of myeloid tissue to percentage of myeloma tissue also was related to survival. Six deceased patients with ratios greater than one had a median survival of 4.4 years, compared with 1.8 years in 12 deceased patients with ratios less than one. These medians differ significantly (P less than 0.05). Seven patients also had simultaneous biopsies of the posterior iliac crest and either or both the greater trochanter and the proximal tibia. All five greater trochanter biopsies showed extension of both myeloma tissue and myeloid tissue into the proximal appendicular skeleton.

Extension of myeloid tissue into the lower extremities in polycythemia.

Biopsies of the posterior iliac crest, greater trochanter, and proximal tibia were done for 27 polycythemic patients before myelosuppressive therapy was begun. Five had relative polycythemia, thirteen had secondary polycythemia, and nine had polycythemia vera. None of five biopsy specimens of the greater trochanter in cases of relative polycythemia contained myeloid tissue (erythroblasts, granulocytic precursors, and megakaryocytes). Four of six biopsy specimens of the greater trochanter and one of eight of the tibia in cases of secondary polycythemia contained myeloid tissue. All seven biopsy specimens of the greater trochanter and two of five biopsy specimens of the proximal tibia in cases of polycythemia vera contained myeloid tissue. A trochanter biopsy specimen devoid of myeloid tissue probably eliminates the diagnosis of polycythemia vera. Myeloid tissue extends from the axial skeleton to the greater trochanter, therafter to the tibia. Extension of myeloid tissue does not imply that marrow failure is imminent in polycythemia vera.

Intravenous iron dextran in clinical medicine.

Four hundred seventy-one adult patients and ten adult prisoner volunteers received 2,099 intravenous (IV) injections of iron dextran (Imferon), usually 250 to 500 mg at less than 100 mg/min. Intravenous iron supplies enough iron to permit RBC formation greater than 50 mL/day and repletion of tissue iron. Tissue iron did not always supply iron at an optimal rate. Hemoglobin production was higher after IV than oral or intramuscular iron if the hemoglobin level was less than 9 g/dL. Three life-threatening immediate anaphylactoid and eight severe delayed reactions were observed. There were no deaths. Delayed reactions were more frequent in women and collagen-vascular diseases and less frequent in pregnancy. Because anaphylactoid reactions are serious and unpredictable, IV iron dextran should be used only when iron deficiency anemia cannot be treated adequately with oral iron.

Hemoglobins of the opossum (Didelphis virginiana Kerr). I. Developmental changes from yolk sac to definitive erythropoiesis.

In 5- to 7-da old opossum pouch young, hemoglobins were observed. The "primitive" species I, II, and IV were shown to be electrophoretically distinct from the adult hemoglobin III. Hemoglobin I was detectable until the 7th postnatal da. Hemoglobins I, II, and IV were detected only during the period when yolk sac-derived primitive erythroblasts were seen in circulation, ei, until the 13th postnatal da, but in decreased amounts from the 6th to 13th da. The electrophoretic pattern of hemoglobin of pouch young after the 13th postnatal da was indistinguishable from that of the adult opossum.