Sickle Cell Dwarfism

Abstract

307 Judith L. Bader and Robert W. Miller. Clinical Eoidemioloav Branch. NCI. Bethesda. Marvland To clarify' the sugg;;ted l ink between chi ldhood leukemia and neurofibromatosis (NF), we ascertained 10 previously unreported cases at 6 medical centers including our own, almost doubling the 15 adequately documented cases in the literature. Among these 25, acute lymphoblastic leukemia (ALL) developed in 9 and various forms of myelogenous leukemia (non-ALL) in 16, incl udlng 8 with acute myelomonocytic and 4 with juvenile chronic myelogenous leukemia. The ALL:non-ALL ratio of 9:16 is quite different from the predominance of ALL in U.S. whltes. 4:l; Down's syndrome, 7:3; and ataxia-telangiectasia, 7:l. By contrast, only non-ALL has been reported in Fanconl's anemia or Bloom's syndrome. Each of these 4 heritable disorders with high r~s k of leukemia has characteristic though different chromosomal abnormalities, which may be involved in leukemogenesis. In the 25 NF cases cytogenetic studies were rarely made, an opportunity that should not be missed in the future. Varlatlons in the ALL:non-ALL ratio indlcate that host factors apparently Influence the form of leukemia that develops. To refine further the relation between NF and leukemia, the existing large collaborat ive oncology groups could provlde a) ful ler ascertainment of cases with details of physical findings and family histories, b) a denominator for estimating risk, c) cytochemical and immunological clarification of leukemic subtypes, and d) elucldatlon of possible variant cases excluded from this series (N-15) The majority of granulosa cell tumors cause feminization, although in a few women virilization has occurred. MacDonald et a1 (Obstet. Gynecol. 47:649. 1976) have recently documented that a post-menopausal woman with an androstenedione (A) producing ovarian adenocarcinoma became estrogenized as a result of extraglandular conversion of A to estrogens.A 4 year old girl with a small right sided granulosa cell tumor presented with rapidly progressing breast enlargement. vaginal bleeding, but without androgen dependent signs of precocity. Pre-operative plasma steroid determinations revealed: estradiol (E2) 62 pg/ml. estrone (El) 12 pg/ml. A 0.1 ng/ml, testosterone (T) 0.02 ng/ml. Serum LH was 0.1 and roso to 1.2 MIlJ/ml (LER 907) after LHRH.while FSH remained suppressed. ACTH stimulation caused no effect, but a single injection of human chorionic gonadotropin resulted in a 20-fold rise in T and A while El and Ep increments were only 2 to 4-fold. Very high androgen concentrations were also found in right ovarian venous samples (A 94, T 11. E2 2.55 and El 0.55 ng/ml). After tumor removal, plasma steroid levels returned to prepubertal values, breast size declined and LHRH caused an exaggerated FSH but normal prepubertal LH response. It is concluded that the absence of virilization in this girl with an androgen secreting granulosa cell tumor resulted from extraglandular conversion of androgens to estrogens. An athyreotic infant presented with hypothyroidism at ...

From the Top Down: Government Promoted Citizen Participation

“…City government has tended to react to citizen groups as elements threatening the system of duly elected all-purpose government while citizens have criticized city hall as acting in a domineering fashion. The late 1960s saw a proliferation of neighborhood action groups in the U.S. and of student and workers groups in, among others, France, Italy, and West Germany (Spiegel, 1968;Castells, 1977;DiCiaccia, 1974;Meister, 1971;Fainstein, 1974). By challenging the representativeness and responsiveness of city officials, these groups appeared to be incapable of operating within the institutional system of decision-making.…”