Serum transferrin receptor concentrations in women with mild malnutrition.

We determined the influence of undernutrition on blood soluble transferrin receptor (sTfR) concentrations, an indicator of iron deficiency, in 99 Zairean women (aged 16-45 y) without inflammation. They were recruited during a survey on iron deficiency in rural Bas-Zaire. sTfR was measured by enzyme immunoassay, and indicators of nutritional status [albumin, transthyretin (or prealbumin), and retinol binding protein] were measured by radial immunodiffusion. Undernutrition was diagnosed if the concentration of any one of the indicators was below normal: albumin < 35 g/L, transthyretin < 160 mg/L, and retinol binding protein < 30 mg/L. The sTfR concentration ranged from 1.89 to 19.1 mg/L (mean: 8.7 mg/L). Mean values for indicators of nutritional status, serum ferritin, and transferrin saturation were within the normal range for health subjects. Regardless of the iron status (iron sufficiency, anemia, or iron deficiency with or without anemia) and whether women were pregnant or nonpregnant, undernutrition did not significantly reduce sTfR concentrations. A higher percentage (80%) of iron-deficient women with two or three protein values below normal had sTfR concentrations > 8 mg/L (which are suggestive of iron-deficiency erythropoiesis) compared with iron-deficient women with no (72.7%) or one (66.7%) protein value below normal, anemic women (46-60%) and iron-sufficient women (18.2-36.8%). Results suggest that sTfR can be used as an indicator of iron deficiency in field studies without in-depth assessment of nutritional status. However, the effect of severe malnutrition on this index requires further investigation.

Assessment of iron status of Zairean women of childbearing age by serum transferrin receptor.

Soluble transferrin receptor (sTfR), previously shown to be a sensitive indicator of tissue iron deficiency, was used to assess iron status of 104 Zairean women (69 lactating, 19 pregnant, and 16 nonpregnant, nonlactating women). Thirteen iron-sufficient female laboratory employees were also studied. Mean sTfR concentrations were higher in pregnant women (9.90 mg/L) than in lactating women (8.55 mg/L), nonlactating women (7.74 mg/L), and laboratory employees (5.11 mg/L) (P < 0.005). Mean serum ferritin and transferrin saturation were lower in pregnant than nonpregnant women. sTfR negatively correlated with hemoglobin (P < 0.05) and transferrin saturation (P < 0.05), and nonsignificantly with ferritin and transferrin. With 7.26 mg sTfR/L (the upper limit of laboratory employees) as the cutoff value, sTfR identified 67% of women with tissue iron deficiency compared with 11.5-57% for transferrin saturation, hemoglobin, or ferritin. Despite the moderate sensitivity (68.5%), 90% of women with sTfR > 7.26 mg/L also had another index below normal and 54% had serum ferritin < or = 50 micrograms/L.

Hemoglobin A2 levels in healthy persons, sickle cell disease, sickle cell trait, and beta-thalassemia by capillary isoelectric focusing.

Simultaneously measuring major and minor hemoglobin (Hb) variants by capillary isoelective focusing, we obtained HbA2 intervals in healthy volunteers (n = 412) (reference value) and patients with HbS or beta-thalassemia. We classified normal HbA2 reference intervals into three age groups: 5 months or younger (1.2% +/- 1.5%), 6 months to 1 year (2.2% +/- 0.9%), and 1 year or older (2.4% +/- 0.9%). These intervals were comparable to those used with other methods. Patients 1 year of age or older with HbS had significantly higher HbA2 levels (sickle cell trait, 2.9% +/- 0.9%; sickle cell anemia, 2.8% +/- 1.0%; P < .05). Although reference HbA2 intervals overlapped those in patients with HbS, no overlap in HbA2 levels was noted between these groups and patients with beta-thalassemia (observed range, 4.3% to 7.5%). The higher than normal HbA2 interval in patients with HbS must be considered before a diagnosis of sickle cell trait or sickle cell disease with beta-thalassemia is made.

Nonrandom chromosomal aberrations and clonal chromosomal evolution in acute leukemia associated with Down's syndrome.

Nine Down's syndrome (DS) children, four with acute leukemia, one with acute leukemia as well as rhabdomyosarcoma, and four with other hematologic disorders, were analyzed for constitutional and acquired chromosomal aberrations. Acquired clonal chromosomal aberrations were identified only in the acute leukemia cases, and four of the five acute leukemia demonstrated numerical and/or structural aberrations involving chromosomes #8, #19, and #21. Of the 11 aneuploid stem cell lines identified in the five acute leukemia cases, trisomy 21, trisomy 8, trisomy 19, and tetrasomy or pentasomy 21 was found in 11, seven, four, and two lines, respectively. The frequent appearance of multiple stem cell lines with common and/or overlapping chromosomal aberrations in acute leukemia cases demonstrates the existence of genomic instability and heterogeneity of the neoplastic cell population, which results from clonal chromosomal evolution. Furthermore, trisomy 19 was identified only with the concurrent presence of trisomy 8, suggesting that the nondisjunction of chromosome #19 probably occurred after that of #8. Trisomy 21 was observed in every aneuploid stem cell line and, in one case, trisomy 21 was maintained in the bone marrow leukemic cells but not in the orbital rhabdomyosarcoma cells, indicating that this constitutional chromosomal aberration is probably crucial for and predisposed to the development of acute leukemia in DS patients. The association of acquired clonal chromosomal aberrations, especially those involving chromosomes #8, #19, and #21, with DS acute leukemia strongly suggests the clinical implication of cytogenetic analysis in the diagnosis of acute leukemia development in DS patients.

Neurofibromatosis, factor IX deficiency, and rhabdomyosarcoma.

A paratesticular rhabdomyosarcoma occurred in a child with factor IX deficiency and neurofibromatosis, illustrating the need to consider carefully the various etiologic possibilities of a soft-tissue mass in a child with neurofibromatosis and/or a bleeding disorder.

The evolution of chemotherapeutic agents for the treatment of pediatric musculoskeletal malignancies.

The incorporation of antineoplastic agents in the treatment of pediatric musculoskeletal malignancies and their impact in the management and outcome of patients with these types of malignancies are briefly reviewed. The role of chemotherapy in the management of these tumors with special emphasis on osteosarcoma, Ewing's sarcoma family of tumors, and rhabdomyosarcoma and undifferentiated sarcomas is discussed. Also included are complications and side effects of the antineoplastic agents.

Langerhans' cell histiocytosis.

Langerhans' Cell Histiocytosis, formerly known as Histiocytosis X, and its related syndromes (i.e., eosinophilic granuloma, Hand-Schuller-Christian disease, and Letterer-Siwe disease) are briefly reviewed. The biology, clinical manifestations, and treatment options of the localized, single form and the disseminated, multisystem form are also discussed.

Hemoglobin sickle cell disease and systemic lupus erythematosus.

An unusual association of hemoglobin sickle cell disease with systemic lupus erythematosus in an 11-year-old girl highlights the diagnostic dilemma that may arise because of the similarity of symptomatology.

Transport proteins and acute phase reactant proteins in children with sickle cell anemia.

Transport proteins, acute-phase reactant proteins (APRP), hematology, and anthropometry were studied in 34 sickle cell disease (SCD) children (20 boys, 14 girls) and 27 controls without growth deficits (13 boys, 14 girls) [corrected]. The age range was 1/2 to 16 1/2 years. Weight deficits (< 80%) by Waterlow's classification were observed in 41% of SCD boys and 25% of SCD girls, and height deficits (< 90%) were observed in 25% SCD boys and 25% girls. Mean white blood cell counts were significantly higher (P < .001) and hematocrit and hemoglobin (Hb) lower (P < .005) in SCD children than in controls. Although both groups had similar mean levels of albumin, transferrin, and APRP, SCD children had significantly lower mean levels of retinol-binding protein (RBP) (P < .001) and retinol-prealbumin (P < .001). Retinol-binding protein levels were abnormal in 18 (53%) SCD children and in only 23% controls (chi 2 = 14.06; P < 0.005); transferrin levels were abnormal in 20% of SCD children and in none of the controls. Children with SC and SF Hb phenotype had normal mean levels of RBP, whereas those with S beta thal and SS phenotype had levels below normal. Growth-retarded children by weight and height had reduced mean levels of RBP and prealbumin compared with growth-normal SCD children. The implication of primary protein-energy malnutrition on growth retardation in SCD children is under study.

Tumor necrosis factor alpha in children with sickle cell disease in stable condition.

Tumor necrosis factor alpha (TNF-alpha) is known to induce wasting in humans and animals. This study was undertaken to determine TNF-alpha concentrations in children with sickle cell disease (SCD) and whether high TNF-alpha levels are more likely to be present in children with growth deficits, infection, or pain crisis. Tumor necrosis factor alpha was measured using enzyme immunoassay in 143 blood samples obtained from 101 children. Mean TNF-alpha levels were higher in patients (50 pg/mL) than in 21 control children (19 pg/mL) and in 26 laboratory employees (20 pg/mL). During the follow-up period, 35%, 38%, and 28% of children with SCD had infection, pain crisis, or a blood transfusion, respectively. Mean TNF-alpha concentrations were higher in children who had an infection than in those who did not. No significant effect of pain crisis or blood transfusion was observed. Tumor necrosis factor alpha concentrations were above normal (> 40 pg/mL) in 15% of controls, 34% of children with SCD, and 52% of children with SCD who had an infection and 33% of those who did not. A higher percentage of children who had elevated TNF-alpha levels had weight (46% versus 31%) or height (50% versus 28.6%) deficits than children who had normal TNF-alpha levels. These results indicate that most children with SCD in stable condition have normal TNF-alpha concentrations and that those with high TNF-alpha levels are more likely to have growth deficits.

Association between increased levels of TNF-alpha, decreased levels of prealbumin and retinol-binding protein, and disease outcome.

We determined whether there is an association between tumor necrosis factor-alpha (TNF-alpha), undernutrition [prealbumin (PA) <160 mg/L, retinol binding protein (RBP) <30 mg/L], disease stage, outcome (death or survival), and race in children with leukemia. TNF-alpha, PA, and RBP were measured in 52 patients (0.8 to 17 years old): 18 African Americans, 34 whites; 27 newly diagnosed (ND), and 25 in clinical remission (CR). Mean levels of TNF-alpha were higher in patients than in 46 healthy children (p < 0.05), but were not different between ND and CR groups. Mean acute phase proteins (APP) were different among groups: ND > CR > controls (p < 0.05). Mean levels of PA and RBP were lower in patients than in controls (p < 0.051, and tended to be higher in CR than in ND patients. African-American patients had lower concentrations of TNF-alpha, PA, and RBP but higher APP than white patients (p < 0.05). CR patients and African-American patients who died tended to have higher levels of TNF-alpha and APP, but lower PA and RBP than those who survived. A higher percentage of ND African Americans (45%) than of ND whites (13%) died. Results suggest that undernutrition and inflammation in CR patients and African Americans were associated with poor survival, and that ND African Americans have a poorer outcome than whites independently of TNF-alpha levels.

Alteration of Wilms' tumor staging by cytologic detection of malignant cells in chylous ascites.

Accurate staging as per National Wilms' Tumor Study (NWTS) criteria is essential for therapy of Wilms' tumor. We report a unique case of a 9-mo-old white male in whom the diagnosis based upon clinical, radiological, surgical, and initial histopathologic findings was Stage I Wilms' tumor without regard to a positive cytologic examination of a small amount (5 ml) of chylous ascitic fluid obtained intraoperatively. This problem was clarified later at the NWTS panel review when the deeper recuts of a renal hilar lymph node revealed a single cluster of Wilms' tumor cells in capsular sinus, resulting in upstaging of tumor to Stage III. The significance of these findings in relation to staging will be discussed.

Opsomyoclonus and neuroblastoma.

Three cases of neuroblastoma with opsomyoclonus are reported, reconfirming favorable prognostic significance of the association. In one case, computed tomography of the abdomen was the only confirmatory diagnostic study. Two of the cases also were unusual in that the patients had a concomitantly inherited genetic disorder not known to be associated with childhood cancer.

Neurofibromatosis and malignancy.

Neural crest and nonneural crest tumors occur frequently in neurofibromatosis (NF). We report one case of NF and recurrent malignant fibrous histiocytoma, a tumor that is uncommon in childhood, and another case of the concomitant occurrence of NF, hemophilia B, and a paratesticular rhabdomyosarcoma.

Analysis of hemoglobin variants by capillary isoelectric focusing.

Clinical laboratory evaluation of congenital hemoglobin disorders requires both the accurate identification of major and minor hemoglobin variants, and precise quantitation of these variants over a wide range of concentrations. Capillary isoelectric focusing is an automated, microanalytical technique that produces diagnostic information comparable to that obtained from multiple conventional assays now used by most hospital laboratories. This report describes the advantages of capillary isoelectric focusing for the routine primary assessment of hemoglobinopathies and thalassemias. The use of capillary isoelectric focusing for the identification of unusual hemoglobinopathies, including an extremely rare doubly heterozygous disorder (hemoglobin C/E disease), is described. Application of the technique for rapid (< 4 minutes) neonatal hemoglobinopathy screening, and for the analysis of Hb A1c to monitor glycemic control in diabetic subjects is also discussed. In an increasingly competitive and cost-conscious clinical diagnostic market, capillary isoelectric focusing is a rapid, specific, precise, and low-cost method for comprehensive primary analysis of hemoglobin variants.

Systemic lupus erythematosus and sickle cell disease.

A case of 10-year-old girl with an unusual association of sickle cell disease (SCD) with systemic lupus erythematosus (SLE) is presented. The report discusses the clues to the diagnosis of this rare combination with review of relevant literature and highlights the diagnostic dilemma that may arise because of the similarity of symptoms.

Current treatment and prognosis of Wilms' tumor.

Thanks to the nationally and internationally organized efforts refinements in the therapy of Wilms' tumor have allowed restructuring and reduction of therapeutic strategies. A decrease in tumor relapse and long term sequelae are the immediate goals which will no doubt be the result of tailoring chemotherapy and radiation therapy exposure together with improved surgical techniques and outstanding supportive care.

Retinoblastoma: a review.

Retinoblastoma is the most common primary ocular malignancy in childhood, usually occurring below the age of five. Recent advances in molecular biology have enabled understanding of retinoblastoma tumorigenesis as well as detecting carriers of the mutant retinoblastoma allele. It is possible now to predict prenatally whether a child carries the retinoblastoma genome. This has enabled early detection of retinoblastoma and improved outcome. Also these children are at risk for mesenchymal tumors in early adult life necessitating life long vigilance. Great strides have been made in the management of retinoblastoma. Introduction of a new pathological staging system and addition of combination chemotherapy for extraocular disease has led to more than 80% long term disease free survivors in this group of patients, who earlier had a very poor outcome. For localized intraocular disease, local treatment seems to be all that is necessary. Newer radiation techniques have helped preserve useful vision and reduced radiation related side effects.

Bone marrow transplantation: a children's hospital of New Orleans experience.

Bone marrow transplantation has become an important therapeutic strategy in the treatment of pediatric malignancies and certain congenital disorders. We initiated a bone marrow transplant program at Children's Hospital in New Orleans at the start of January 1989. Both allogeneic and autologous bone marrow transplantations have been performed. To date, a total of 20 children have received transplants for a variety of diseases. Their ages ranged from 17 months to 20 years. The overall 2-year survival is 40%. For the good-risk patients, the projected 2-year disease-free survival is 85%, compared to 30% for the poor-risk patients. Regimen-related mortality has been extremely low in our settings primarily due to improvement of available supportive care. We conclude that bone marrow transplantation offers a potential cure for these otherwise fatal diseases.

Pernicious anemia and juvenile-onset diabetes mellitus in an adolescent: a case report.

We report a case of a 15-year-old black boy who developed juvenile-onset pernicious anemia in association with insulin-dependent diabetes mellitus. He had both intrinsic factor and parietal cell antibodies in addition to anti-islet cell surface antibodies. The existence of pernicious anemia and diabetes mellitus in such a young child makes this an unusual case.