Charles W. Daeschner

Zinc and growth in patients with sickle cell disease

tion for intensive treatment during this period. The indiscriminate use of high doses of Factor VIII for all elbow hemorrhages in early adolescence is one possibl e response to this situation. However , the problems of the multitransfused hemophiliac patient? make this approach less than ideal, and the selective application of high-dose replacement therapy to those hemorrhages likely to do badly is a more logical solution. We have shown that elbow hemarthroses which present with pain unaccompanied by stiffness, that are tender, and that have lost more ihan 50% of movement are likely to do badly on a dose of 11 to 16 units of Factor VIIl/kg. A delay of more than three hours from the onset of symptoms is also likely to be associated with lack of response. Bleeding into target joints was associated significantly with success when a one-tailed test was used. From our clinical experience we did not expect hemorrhages into target joints to be associated with better than average respons e to an average dose of Factor VIII, and therefore believe that in this situation the use of a one-tailed test is not permissible. We have shown that trauma does not worsen the out!ook for elbow hemorrhages and that delay in treatment UP tO three hours does not appear to increase the risk. This surprising observation does not necessarily mean that delay in treatment is acceptable. The spee d with which bleeding develops is likely to vary from case to case, and early presentation may delay the onset of high-risk features. The age of the patients did not appear to influence response , although a previous study has suggested that hemorrhages increase in severity through adolescence and peak at the age of 14 to 15 years? Forty percent of the hemorrhages associated with two or more of the four poor prognosis factors needed retransfusion, and this group of hemorrhages should provide a fruitful field for studying the effect of higher initial doses of Factor VIII,

Effects of iron, copper, zinc, calcium, and magnesium on human lymphocytes in culture

The effects of simultaneous changes of calcium, magnesium, iron, copper, and zinc concentrations were evaluated in normal human T and B lymphocytes, cultured in cation-depleted media. Optimal concentrations for thymidine incorporation (TI) in both cell populations were Fe and Zn 15 μM and Cu 5 μM; for t cells Ca 2 mM and Mg 4 mM; for B cells Ca 4 mM and Mg 6 mM. TI decreased with increasing molarity of cations and the decrease was particularly apparent with Cu. Minimal amounts of Ca and Mg (0.5 mM) were necessary for growth, even in presence of optimal concentrations of Fe, Cu, and Zn. Fe and Cu showed synergistic stimulatory effects at low concentrations and synergistic inhibitory effects at high concentrations. Antagonism between Fe and Zn, Cu and Zn, and Ca and Zn was also demonstrated. CD4/CD8 increased with PHA stimulation in presence of Zn, and decreased with ConA stimulation in presence of Zn or Fe. The results demonstrate: (1) the relationship and interdependence of Fe, Cu, and Zn concentrations in modulating the growth of normal lymphocytes; (2) the stimulatory effects of Fe on B cells and Zn on CD8 positive cells; (3) the inhibitory effect of Cu at concentrations lower than those of Fe and Zn; (4) the requirement of Ca and Mg in certain concentration and ratio for the action of the other cations; and (5) the Ca and Mg requirement for the growth of B cells higher than T cells.

Granulocytic sarcoma in childhood acute myelogenous leukemia

A 12-year-old boy with acute myelogenous leukemia developed acute weakness and paresthesias of the lower extremities after lumbar puncture. Computed tomography and magnetic resonance imaging revealed 2 large paraspinal masses (granulocytic sarcoma) causing spinal cord compression. Treatment with corticosteroids, radiation therapy, and chemotherapy caused complete resolution of symptoms; there was no evidence of tumor on subsequent magnetic resonance imaging or at autopsy. Granulocytic sarcomas (chloromas) rarely involve the nervous system in patients with acute myelogenous leukemia, although with increased survival it is apparent that the incidence may be greater than previously believed. Central nervous system prophylaxis was not administered to our patient but may be recommended for future patients if systemic disease can be controlled. General features of central nervous system complications of acute myelogenous leukemia, characteristics of granulocytic sarcoma, and review of current radiographic techniques used in the evaluation of these tumors are discussed.

Leukemia with a novel 4q11q rearrangement

Translocation (4;11)(q21;q23) is characteristic of a distinct acute leukemic syndrome. We report an 8-wk-old male patient with the clinical features ascribed to t(4;11), but with an unusual chromosome rearrangement consisting of an insertion of the 11q23 band into the q21 region of chromosome #4.

Observations on the use of a cation exchange resin for the preparation of metal-depleted media for lymphocyte culture.

A chelating resin specific for divalent cations (Chelex) was used to prepare metal-depleted media for lymphocyte culture. A batch procedure (resin in pH 7.4 phosphate buffer/specimen, 1:1) removed 70-80% of iron, 77-87% of copper and 88-98% of zinc, calcium and magnesium. At variance with other reports, when a resin/specimen ratio of 1:4 was used, iron chelation decreased to 40%, whereas other cation chelation remained unchanged. Best chelation for iron and calcium was obtained at pH 5-6.4; for copper, zinc and magnesium, at pH 7.4-8.0. During the procedure protein content decreased by 8-10%; arginine and lysine by 80%; asparagine, cystine, tyrosine and phenylalanine by 60%, other amino acids by 35%. These new data suggest that cation-depleted media prepared with Chelex may be used to study the effects of cations on lymphocytes in culture, provided that the most appropriate pH and resin/specimen ratio are selected and adequate amino acid replacement is performed. Results on normal human lymphocytes are reported.

Glucose-6-phosphate dehydrogenase Beaumont: a new variant with severe enzyme deficiency and chronic nonspherocytic hemolytic anemia.

Studies were carried out on erythrocytes and fibroblasts from a 3-year-old white male with severe glucose-6-phosphate dehydrogenase (G6PD) deficiency and chronic non-spherocytic hemolytic anemia. Red blood cell G6PD activity was less than 0.02% of normal values. Since the childs fibroblasts had 2-4% of normal enzymic activity, they were utilized as a source of enzyme for kinetic studies. The G6PD demonstrated marked heat lability, a normal Km value for glucose-6-phosphate (56 mumol/l), a nearly normal pH-activity curve, and increased utilization of 2-deoxyglucose-6-phosphate (76% of the rate with glucose-6-phosphate). These studies clearly indicate that this is a new molecular variant (G6PD Beaumont).

Lactoferrin (LF), prostaglandin E (PGE) and neutrophils in children with sickle cell disease (SCD)

Sir, We studied serum and neutrophil LF and,serum and monocyte PGE in the venous blood of a randomly selected group of 13 black children with SCD during asymptomatic periods and vasoocclusive crises and 16 healthy black children of similar ages (mean 7 years, range 3-12 years). Reasons for the study were the common finding of neutrophil increase in children with SCD [1] and the description of LF and PGE among the proposed regulators (inhibitors) of neutrophil production [2, 3]. Neutrophils (95°7o pure) isolated on Ficoll-Hypaque were ruptured in buffered saline with Tween-20 and centrifuged at 70,000 × g. LF was quantitated in the supernatant and serum by ELISA technique [4] (Dr. R. Goldblum), using antihuman LF antibodies (Dako Corporation, Santa Barbara, CA, USA) and human LF (99% pure), (Cal-biochem, San Diego, CA). PGE was evaluated by radioimmunoassay [5] in the serum and supernatant of ruptured monocytes (97o7o pure), isolated by adherence to polystyrene culture dishes [6] and identified by morphology and alpha-naphtylacetate esterase staining. The results (mean and SD) showed a good correlation between the significantly increased values of LF and PGE (Students t test: p < 0.001) and the absolute number of neutrophils. They were as follows:

The Use of Steroids as Pharmacologic Agents in Diseases of Children, Part 3: Renal Diseases

Steroid therapy usually is of value in the idiopathic nephrotic syndrome of short duration. It is sometimes of value in the idiopathic nephrotic syndrome of long duration and in the nephrotic syndrome associated with disseminated lupus erythematosus or periarteritis nodosa.The complications of high-dosage steroid therapy for pharmacologic or anti-inflammatory purposes are discussed, with emphasis on the importance of using the lowest dosage that will control symptoms when maintenance therapy is required.

The Use of Steroids as Pharmacologic Agents in Diseases of Children, Part I

Some uses of corticosteroids as pharmacologic and anti-inflammatory agents in diseases of children are summarized, pointing out the limitations and complications. The hematologic disorders responding most effectively to steroids are the auto-immune hemolytic anemias, acute leukemia (particularly the lymphocytic type), and idiopathic thrombopenic purpura. Cortisone, hydrocortisone and prednisone are remarkably similar in hematologic effect.In part 2 of the paper, the authors will discuss the use of steroids in hypersensitivity states.