Normal vitamin E status in sickle hemoglobinopathies in Colorado.

Because previous studies of serum or plasma vitamin E (E) levels reported a high prevalence of E deficiency in patients with sickle cell anemia (SCA), we studied the E status in 101 patients with SCA in Colorado using both levels of serum E and ratios of serum E to total lipid (E:L). Compared with age-, sex-, and race-matched controls, 1 of 70 patients with homozygous SCA (SS), 1 of 7 with sickle beta+-thalassemia, and 0 of 24 with hemoglobin SC disease had E deficiency according to E:L and all were E-sufficient based on serum E levels. Serum cholesterol levels, lower in SS patients than in control subjects, correlated more strongly with serum E levels than did total serum lipid levels in control subjects and SS patients; hence, the ratio of serum E to cholesterol may be a useful indicator of E status in these patients. We conclude that vitamin E deficiency rarely occurs in SCA patients in Colorado.

Regression on oxymetholone-induced hepatic tumors after bone marrow transplantation in aplastic anemia.

Treatment of acquired aplastic anemia with androgens has been occasionally associated with the development of hepatic tumors. We have studied a 13-year-old boy with idiopathic aplastic anemia in whom oxymetholone treatment was associated with a partial hematological remission. Thirty-four months later, however, the patient developed multiple hepatic tumors. When oxymetholone therapy was discontinued, the aplastic anemia relapsed. He then underwent bone marrow transplantation from his HLA-A, B, and D-compatible sibling. This was followed by hematological and immunological reconstitution. The hepatic tumors underwent progressive regression after bone marrow transplantation. The patient is now 3 years post-bone marrow transplantation and is in complete remission of his aplastic anemia with no evidence of detectable liver tumors.

Probable graft-vs-graft reaction in an infant after exchange transfusion and marrow transplantation.

A newborn with graft-vs-host (GVH) disease following an exchange transfusion was treated by attempting to eradicate the incompatible graft and to reconstitute the child hematologically and immunologically with a bone marrow transplant. The patient was a female term infant (blood group B, Rh+ Coombs test positive) who received a one-unit group O, Rh- exchange transfusion from an unrelated female donor for hyperbilirubinemia due to ABO incompatibility on day 2. Signs of acute GVH disease began on day 8 and the clinical diagnosis was supported by skin biopsy. With antithymocyte globulin and high dose dexamethasone, the GVH reaction improved somewhat. Cyclophosphamide, 200 mg/kg total dose, was given over four days followed by a marrow graft from a brother who was HLA-A, B identical, and probably also D locus compatible in mixed lymphocyte culture. All signs of GVH resolved with cyclophosphamide treatment and hematologic reconstitution was evident by 14 days after transplant. Two weeks later the GVH reaction and aplastic anemia recurred and Y chromatin was detected in only 6% of marrow cells. The infant died on day 80. Autopsy showed disseminated candidiasis, disseminated cytomegalovirus infection, thymic dysplasia, hypoplastic marrow, and other histopathologic changes consistent with GVH disease. The persistence of female cells in blood and bone marrow and the destruction of the reconstituted marrow suggest that the original incompatible transfusion-derived graft was not eliminated and that it ultimately rejected the histocompatible marrow graft.

Intranasal administration of deferoxamine to iron overloaded patients.

We examined the effect of intranasal administration of deferoxamine on iron excretion in seven patients with iron overload secondary to chronic transfusion therapy. Deferoxamine was administered in doses of 0.75 to 3.0 gm given over 12 hours in a variety of dosing schedules. There was a probable, though not significant, dose response relationship between the amount of iron excreted and the dose administered. The amount of iron excreted was 10%-15% of that obtained using the same dosage of deferoxamine given by the subcutaneous route over the same time period. Hourly administration was more effective than less frequent administration. Addition of taurodeoxycholate to deferoxamine did not increase its absorption as measured by the levels of iron excretion. Side effects were few and consisted mainly of mild nasal irritation and a bad taste in the mouth. Nasal administration of deferoxamine may be a useful adjunct to iron chelation in patients receiving chronic transfusion therapy, particularly in those who are noncompliant with parenteral means of administration.

Sickling crises and altitude. Occurrence in the Colorado patient population.

Seventy-five black patients with sickle hemoglobinopathies who are followed by the Colorado Sickle Cell Treatment and Research Center, and 172 of their family members were evaluated by retrospective interview for the occurrence of sickling crises when traveling in the Rocky Mountains or by aircraft. Twenty per cent of 39 patients with sickle cell anemia (Hgb SS) (Hgbs S/C and S/T) have developed crises when traveling in the mountains above 2000m. Vaso-occlusive crises predominated in the SS group and splenic crises occurred primarily in those with Hgbs S/C and S/T. Approximately 20 per cent of those with S/C and S/T, but none with SS, had crises when flying in pressurized aircraft. Among 103 family members with sickle cell trait (Hgb AS), no significant risk of developing crises could be identified with either mountain or pressurized aircraft travel.

Splenic syndrome at mountain altitudes in sickle cell trait. Its occurrence in nonblack persons.

Six consecutive cases of splenic syndrome at mountain altitudes in persons with sickle cell trait are reported and the literature is reviewed. All six cases occurred in men who experienced the acute onset of severe left-upper-quadrant abdominal pain within 48 hours of arrival in Colorado from lower altitudes. All six patients were phenotypically nonblack. Three patients experienced their symptoms at moderate altitudes of 1,609 to 2,134 m (5,280 to 7,000 ft) above sea level. All recovered with medical management and none required splenectomy, although functional hyposplenia was a sequela in at least one patient. The possibility that nonblack persons with sickle cell trait may be at greater risk than black persons with sickle cell trait for the development of splenic syndrome at moderate altitude is discussed.

Nine cases of sphingomyelin lipidosis, a new variant in Spanish-American Children. Juvenile variant of Niemann-Pick Disease with foamy and sea-blue histiocytes.

We describe nine Spanish-American children from five families with an unusual hereditary lipid storage disease. The family origins were in two small southern Colorado towns. The clinical course varied, but all of the children were found to bruise easily and to have splenomegaly, while most had hepatomegaly. Post-natal jaundice and hepatitis occurred in four. Impairment of vertical gaze and intellectual and neurologic deterioration occurred in most of the patients, with the onset of the disease, usually in childhood. The bone marrow in all patients examined contained both foamy and sea-blue histiocytes. Sphingomyelinase levels in skin fibroblast cultures were greatly decreased in seven of the eight cases evaluated. It is believed that these patients have a sphingomyelin lipidosis and represent a variant of the Niemann-Pick disease. Clinical and enzymatic findings are compared with those of other cases in the literature.

Zinc status in children and young adults with sickle cell disease.

Previous studies have suggested an association of zinc deficiency and short stature in some children and adults with sickle cell disease (SCD). As a result, zinc supplementation has been recommended for these patients. The mechanism for zinc deficiency in certain patients with SCD is unknown, although renal loss of zinc has been suggested as a contributing factor. The zinc status of 29 subjects with SCD and 18 black controls was studied. No evidence of zinc deficiency in our population with SCD was found when plasma and cellular zinc levels were measured. Likewise, levels of two zinc-dependent enzymes, alkaline phosphatase and delta-aminolevulinic acid dehydratase, were normal in these subjects with SCD. Although adolescent subjects with SCD tended to be shorter than control subjects, there was no correlation between the height-forage z score and plasma zinc levels (r = -.31). It was concluded that zinc deficiency was not present in our population with SCD, and that there was no correlation between plasma zinc levels and the height-for-age z score in growing adolescent patients with SCD. These findings suggested that zinc supplementation may not be necessary in all patients with SCD.

Splenic sequestration syndrome at mountain altitudes in sickle/hemoglobin C disease.

The splenic sequestration syndrome was observed in five children with sickle/hemoglobin C (S/C) disease in association with a change in altitude. In four of them, it occurred during or immediately following a trip to mountain altitudes greater than 9,000 feet. In the fifth child, the crisis occurred in ten days after travel in a pressurized plane from sea level to Denver. No previous reports of this complication in S/C patients during mountain travel have been noted although the occurrence is known in association with aircraft flights.

Effect of subcutaneous deferoxamine and oral vitamin C on iron excretion in congenital hypoplastic anemia and refractory anemia associated with the 5q-syndrome.

Chronic refractory anemia associated with congenital hypoplastic anemia (CHA, Blackfan-Diamond syndrome) and with the 5q-syndrome may require chronic transfusion therapy to sustain life. Hemosiderosis and death from chronic iron overload may result from such a program. The effect of subcutaneous (SC) deferoxamine (DF) and supplemental oral vitamin C (vit. C) on urinary iron excretion was studied in two patients with congenital hypoplastic anemia and one patient with 5q-syndrome. In the two patients with CHA, urinary iron excretion in response to DF given SC over 24 hours was comparable to the results following intravenous (I.V.) administration. Both of these cases had low levels of plasma ascorbate on initial evaluation and excreted more iron in response to two different doses of DF after they had received supplemental vit C and their stores were repleted. Significant iron excretion occurred in all three patients for 12 hours during the SC infusion of DF and for 12 hours after the end of the infusion. In all three patients, increasing the dose of DF up to 3-4 g given SC over 12 hours resulted in a linear increase in iron excretion. Once normal body stores of ascorbate were achieved by oral supplementation, increasing doses of vit C did not appear to cause a further increment in iron excretion. DF administered by a slow SC infusion appears to be an effective approach to iron overload in patients with refractory anemia and hemosiderosis secondary to chronic transfusions. Only small amounts of supplemental vit. C necessary to sustain adequate body stores are required for optimal iron excretion.

Intermittent combination chemotherapy with or without bacillus Calmette-Guérin for treatment of acute lymphoblastic leukemia of childhood.

Seventy-four children ranging in age from 6 months to 17.5 years with acute lymphoblastic leukemia newly diagnosed between 1976 and 1979 were entered on a study incorporating intermittent chemotherapy with or without the addition of bacillus Calmette-Guérin (BCG). The chemotherapy program consisted of induction with vincristine, dexamethasone, and intrathecal methotrexate, intensification with adriamycin and asparaginase, central nervous system treatment with cranial irradiation and intrathecal methotrexate, and continuation treatment with 5-day courses of combination chemotherapy administered every three weeks. The first phase of continuation therapy incorporated vincristine, adriamycin, 6-mercaptopurine, and dexamethasone. In the second phase, oral methotrexate was substituted for the adriamycin in non-T-cell patients; in T-cell patients, cytosine arabinoside or cyclophosphamide and methotrexate in alternating cycles were substituted for the adriamycin and asparaginase was added. Total duration of therapy was approximately 2.5 years. Connaught BCG was administered by Heaf gun on days 8 and 15 of each 3-week cycle for the first 8 months of treatment in approximately one-third of the patients. Actuarial disease-free survival with a median follow-up of 59 months shows no difference in outcome between the BCG and non-BCG poor-risk patients. However, there is an improvement in disease-free survival of BCG-treated good- and average-risk girls (P = 0.04). While patients were actively receiving BCG there was also a trend toward the development of fewer significant infections than when patients were not receiving BCG (P = 0.85). Toxicities from BCG administration included satellite rashes, local tenderness, lymphadenopathy, secondary infection, and residual scars. Overall disease-free survival by actuarial analysis is 60% at 6 years; for patients with unfavorable prognostic features it is 40%. In this trial the addition of BCG prolonged the disease-free survival of girls with good- and average-risk prognostic features and also may have decreased the susceptibility to infection while it was being administered. However, the benefit does not appear sufficient to warrant its routine use, especially in view of the toxicities encountered.

Recruitment and retention program for minority and disadvantaged students.

Attracting ethnic minority and disadvantaged students to health careers and facilitating their successful completion of training program requirements have been major activities of the University of Colorado Medical Center since 1969. As a result of extensive college campus recruitment efforts, high school and college level preprofessional programs, and the participation of ethnic minority faculty members in the medical school admissions process, the number of applicants to the medical school increased from 45 in 1971 to 265 in 1977. Concurrently, medical school matriculants increased from 12 in 1971 to 24 in 1977, with a maximum of 30 in 1975. However, significantly fewer minority students have shown interest in nursing, dentistry, or allied health professions careers. Because of support programs for matriculants (including preadmission and postadmissions personal, academic, study skills, and test-taking counseling and a prefreshman year summer orientation course), 71 percent of the minority students entering medical school in 1971-73 have received the M.D. degree.