Superior sagittal sinus thrombosis: a rare complication in a child with nephrotic syndrome.

A 2-year-old boy with new-onset nephrotic syndrome developed recurrent vomiting, apathy and papilloedema. Superior sagittal sinus thrombosis was diagnosed on cranial CT and MRI. He gradually recovered after treatment with heparin, fresh frozen plasma and warfarin with complete resolution of the thrombosis after 1 month. Superior sagittal sinus thrombosis is an extremely rare complication of nephrotic syndrome in children. Early diagnosis is essential for institution of anticoagulation therapy and a successful outcome.

Thrombus in the left ventricle of a child with systemic emboli: an unusual presentation of hereditary protein C deficiency.

We present a case of left ventricular thrombus in a child with a normal functioning left ventricle. The diagnosis was made by 2-dimensional echocardiography after 2 episodes of systemic emboli. Hereditary protein C deficiency diagnosed in the patient provides the probable pathogenesis of the thrombus formation. Systemic emboli necessitates cardiac examination, and in cases of unusual thrombi, hereditary or acquired thrombophilic risk factors should be considered.

A new exon 9 glucose-6-phosphate dehydrogenase mutation (G6PD "Rehovot") in a Jewish Ethiopian family with variable phenotypes.

Hereditary nonspherocytic hemolytic anemia (HNSHA) is a rare manifestation of glucose-6-phosphate dehydrogenase (G6PD) gene mutations, caused mainly by mutations located in exon 10 of the G6PD gene and less commonly by mutations in other parts of the gene. A new, exon 9, single-base mutation representing a T --> C transition at cDNA nucleotide 964 was found in three brothers and their carrier mother of Jewish Ethiopian descent. Biochemical characterization of the resultant protein was not performed. Though clinical manifestations included HNSHA in all cases, the severity of hemolysis and the transfusion requirement differed markedly. Severe congenital neutropenia (Kostmann's syndrome)--a disorder never reported before in conjunction with G6PD deficiency--was observed in one case. Levels of white blood cell G6PD activity of the three patients were 0-5% of normal controls. Neutrophil oxidative and bactericidal activities were inherently impaired in the patient with Kostmann's syndrome, but were well preserved in his two siblings.

Effective preventive central nervous system therapy with extended triple intrathecal therapy and the modified ALL-BFM 86 chemotherapy program in an enlarged non-high risk group of children and adolescents with non-B-cell acute lymphoblastic leukemia: the Israel National Study report.

BACKGROUND: Preventive cranial radiotherapy (CRT) in childhood acute lymphoblastic leukemia (ALL), although effective, may be associated with neurologic sequelae and second malignancies. Attempts to replace CRT with intensified intrathecal therapy (IT) have shown promise in lower risk subgroups. In the Israel National Study (INS) 89 trial, the efficacy of extended triple IT (TIT) alone for cranial prophylaxis in an enlarged non-high risk group (Non-HRG) was assessed in the context of a modified ALL-Berlin-Frankfurt-Munster (BFM) systemic chemotherapy program. METHODS: Non-HRG patients included the standard-risk group (SRG) and the risk group (RG), as defined in ALL-BFM 86. In the INS 89 protocol, all Non-HRG patients were treated with extended TIT x 18 times and systemic therapy based on the BFM 86 protocol, with the addition of etoposide x 4 times. The HRG patients, classified according to BFM 86 criteria, were treated with the BFM 90 HRG protocol including CRT. RESULTS: A total of 250 patients were enrolled. At a median follow-up of 58 months (range, 2-8.5 years), the overall 5-year event free survival (EFS) was 73.5% +/- 3% (standard error ¿SE), and the cumulative central nervous system (CNS) recurrence rate was 4.3% +/- 1.4% (SE) (isolated, 2.3%; combined, 2%). Of the 220 eligible children, 189 (86%) were in the Non-HRG group, and their 5-year EFS was 77.8% +/- 3% (SE). The cumulative CNS recurrence rate for patients without CNS disease at presentation was 3.1% +/- 1% (SE) (isolated, 1.7%; combined, 1.4%). Within the risk subsets defined by the BFM 86 of the Non-HRG, the 5-year EFS rates of the RG (148 patients) and the SRG (41 patients) were 74.8% +/- 4% (SE) and 89.5% +/- 5% (SE), respectively, and the rates of CNS recurrence (isolated and combined) were 4% and 0%, respectively. For the HRG (31 patients), the 5-year EFS and CNS recurrence rates were 47.9% +/- 9% (SE) and 8. 5% +/- 6% (SE), respectively. CONCLUSIONS: Early extended TIT therapy in the context of modified BFM 86 systemic chemotherapy was found to provide adequate CNS protection and systemic leukemia control in patients with non-high risk ALL. However, no benefit for etoposide could be proven in this study.

Resting energy expenditure in patients with thalassemia major.

The effect of non-iron-deficiency anemia was studied in seven patients with thalassemia major (beta thalassemia) ages 22-30 y. Each patient was studied before and 3 days after blood transfusion. Hemoglobin concentrations increased significantly after blood transfusion (111-153 vs 81-102 g/L, P < 0.02). Heart rate decreased from 96 +/- 12 to 81 +/- 7 beats/min (mean +/- SD; P < 0.05). No significant difference was found in venous blood pH, bicarbonate concentrations, or lactic acid concentrations before and after blood transfusion. Resting energy expenditure (REE) was greater before blood transfusion in absolute numbers and as a percentage of the predicted value, and returned to normal range thereafter (6138 +/- 112 vs 5678 +/- 738 kJ.kg-1.d-1 and 111.7 +/- 11.3% vs 103.2 +/- 7.8%, respectively). Protein contribution to REE was low before blood transfusion (9.7 +/- 4.2%) and returned to normal range thereafter (15.3 +/- 5.2%) (P < 0.09). This finding may indicate that increased protein turnover as well as increased cardiac work contribute to the observed increase in REE.

The role of anticardiolipin autoantibodies in the pathogenesis of autoimmune hemolytic anemia in systemic lupus erythematosus.

OBJECTIVE: To elucidate the role of anticardiolipin antibodies (aCL) in the pathogenesis of hemolytic anemia in patients with systemic lupus erythematosus (SLE). METHODS: Immunoglobulins (Ig) and cardiolipin reactivity were evaluated in red blood cell (RBC) eluates and in the sera of patients with SLE and controls by a solid phase enzyme linked immunosorbent assay. RESULTS: aCL were detected in sera of 2 patients with SLE with active hemolytic anemia. The RBC eluates of these patients contained Ig (mainly IgG) with significant cardiolipin reactivity. RBC eluates from healthy volunteers failed to demonstrate measurable amounts of Ig whereas Ig eluted from RBC of chronic lymphocytic leukemia patients with active hemolysis but no aCL did not react with cardiolipin. Furthermore, under treatment, one patient went into complete remission with resolution of the hemolysis, negative Coombs' tests and lower serum aCL. The other patient, however, continued to demonstrate both high sera aCL and positive Coombs' tests. CONCLUSION: aCL may play a direct role in the pathogenesis of hemolytic anemia in some patients with SLE by acting as anti-RBC autoantibodies.

Mechanism of autoimmune hemolytic anemia in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a malignant clonal expansion of CD5+B lymphocytes. The CD5+B lymphocytes have been postulated to produce autoantibodies. CLL patients may demonstrate features of autoimmunity including autoimmune hemolytic anemia. However, the origin of the autoantibodies causing the hemolysis is not clear. The present studies were performed to determine whether these autoantibodies are the products of the neoplastic B-CLL clones. Immunoglobulins (Ig) were eluted from washed red blood cells (RBC) obtained from two CLL patients at the time they had autoimmune (DAT-direct antiglobulin test-positive) hemolytic anemia. The light chain phenotypes of these eluted autoantibodies were determined and found to be monotypic with exact correlation to the light chain expressed on the surface of the B-CLL clones. Elutions from RBC of DAT negative patients or normal volunteers failed to demonstrate measurable amounts of Ig. In contrast, Ig eluted from RBC obtained from SLE patients with DAT positive hemolytic anemia found to be polyclonal autoantibodies exhibiting both light chain types. Furthermore, CD5+B lymphocytes obtained from the same two CLL patients (DAT+) produce, in vitro understimulation with phorbal myristate acetate (PMA), monoclonal antibodies which react and bind to RBC. Thus these studies provide direct evidence demonstrating that the antibodies causing the autoimmune hemolytic anemia in our two CLL patients are the products of the B-CLL neoplastic clones.

[Scurvy from self-imposed diet].

Scurvy, a rare disease, is still found today in malnourished patients. We recently diagnosed a case of scurvy in a 64-year-old woman resulting from a self-imposed diet. She had severe anemia and the characteristic gingival and skin lesions, which responded dramatically to ascorbic acid therapy. We report this case to make physicians aware of the possibility of scurvy and of its clinical symptoms.

Transient anticardiolipin antibodies, functional protein S deficiency, and deep vein thrombosis.

A 30-year-old man presented with an episode of deep vein thrombosis. He was found to have primary antiphospholipid syndrome with anticardiolipin antibodies and protein S deficiency. All other investigations were negative. Three months later, anticardiolipin antibodies were negative and protein S levels were normal. The transient presence of anticardiolipin antibodies and functional protein S deficiency in this patient suggests a new mechanism for the association between anticardiolipin antibodies and venous thrombosis.

Micromethod for demonstrating increased platelet surface immunoglobulin G: findings in acute, chronic, and human immunodeficiency virus-1-related immunologic thrombocytopenias.

A method has been developed for the demonstration of increased platelet surface IgG that uses 1 ml of blood regardless of the platelet count. Platelets are gel filtered to remove plasma and contaminating lymphocytes. They are then reacted with fluorescein-conjugated antihuman IgG and analysed by flow cytometry. Percent positive staining cells vary from 10% to 80% of total cells examined. A platelet antibody index is derived from the product of percent positive staining cells X mean fluorescence intensity of positive staining cells. All patients studied with chronic idiopathic thrombocytopenia purpura (ITP) or human immunodeficiency virus-1 (HIV-1)-related thrombocytopenia had increased platelet surface IgG. Twelve acute children and 11 chronic children had indices averaging 3.5- and 8.9-fold greater than 12 normal children, respectively. Five of 12 children with acute ITP had normal platelet IgG. There was no linear correlation between the platelet antibody index and platelet count. Platelets of patients with acute, chronic, or HIV-1-related ITP displayed autofluorescence. In chronic ITP, the percentage of platelets displaying autofluorescence had a significant negative correlation with the platelet count. This technique will be a valuable diagnostic tool in the pediatric population.

Protein S in the first year of life.

Total protein S, free protein S and C4b binding protein were measured in healthy term infants in order to establish the normal levels of these proteins during the first year of life. Total protein S rose from 36.5% of the adult mean level on day 1 of life to 90% between 6 and 12 months of age. Free protein S was 54.2% of the adult mean on day 1 of life, all values were in the adult range by 2 months and the mean value was no different from the adult at 4 months. This relatively high level of free and presumably active protein S reflects low levels of C4bBP at birth (28.8% of the adult mean) and a slow postnatal rise.

Blood pressure determinations in Israeli schoolchildren aged 5 to 14 years.

Blood pressure (BP) determinations were made by three physicians in 1,554 healthy Israeli schoolchildren aged 5 to 14 years, of whom 783 wer boys and 771 were girls. Subjects were divided into four groups according to ethnic origin: Yemenite--560, North African--357, Iraqi-Iranian--246, and European-American--391. There were no statistically significant differences in either systolic (S) or diastolic (D) BP between ethnic groups or between sexes. Comparing our data with those compiled by the United States Task Force on Blood Pressure Control in Children, we found that the SBP tended to be lower than in American children by about 10 mm Hg, while the DBP was lower by about 7 mm Hg. An additional 4,460 children were examined by public health nurses, and 25 (0.6%) children were found to have a DBP above the 97th percentile for their age, and 46 (1.0%) children were found to have an SBP above the 97th percentile for their age. None of the children had an SBP or DBP exceeding the mean for their age by 2.5 SD, nor had any child any sign or symptom of high BP. Based on these results, we doubt the usefulness and cost-effectiveness of BP screening of children.