Surgical management of intractable epilepsy in children with hemophilia.

Intracranial hemorrhage occurs in 2-8% of patients with hemophilia and can result in neurologic sequelae including seizure disorders. There is a paucity of data concerning the surgical treatment of epilepsy in children with hemophilia. We review our experience with 2 children who developed medically refractory seizure disorders. Both children underwent hemispherotomy, at 18 months (case 1) and 13 years of age (case 2), respectively. Perioperative management included continuous factor replacement. Both children tolerated surgical intervention without complications or increased neurologic deficit. Case 2 showed a 90% reduction in seizure frequency, and case 1 is seizure free. Surgical management of intractable epilepsy in children with hemophilia is safe and effective.

African-American factor VII-deficient variants in Georgia (FVII variants).

We studied African-American Factor (FVII)-deficient variants and carriers in Georgia by measuring their levels of FVII antigen (FVIIAG) and FVII procoagulant (FVIIC). Factor VIIAG was determined using enzyme-linked immunoassay (ELISA), whereas FVIIC was measured in two ways: 1) by fibrin clotting methods that employed human recombinant (HRFVIIC), human placental (HPFVIIC), rabbit brain (RBFVIIC), and bovine brain (BBFVIIC) thromboplastins; and 2) by an amidolytic method (AMFVIIC). Prothrombin time tests (PT) were also performed by standard methods. These 4 FVII-deficient patients and 3 carriers demonstrated the following results: PT: 18.2 +/- 6.5 sec; FVIIAG: 73.0 +/- 14.9%; HRFVIIC: 30.6 +/- 20.3%; HPFVIIC: 30.5 +/- 21.4%; RBFVIIC: 25.3 +/- 21.4%; BBFVIIC: 30.6 +/- 17.5%; AMFVIIC: 44.1 +/- 18.3%. We conclude that a group of clinically mild African-American FVII-deficient variants exists in Georgia. This group is characterized by the presence of FVIIAG and decreased FVIIC, using a variety of thromboplastins; and excellent correlation was noted for both human thromboplastins.

Emergency use of uncrossmatched red cells in neonatal intensive care infants.

In very rare situations, a newborn will be delivered with severe unrecognized life-threatening anemia. Two infants with severe anemia with differing etiologies were deemed to require emergency uncrossmatched O-negative blood. In one infant, the blood transfused was incompatible for the minor antigen that had caused the isoimmune hemolytic anemia. We report on the indications, potential risks and benefits in giving uncrossmatched O-negative blood to term infants with life-threatening anemia.

Divalent cation regulation of the surface orientation of platelet membrane glycoprotein IIb. Correlation with fibrinogen binding function and definition of a novel variant of Glanzmann's thrombasthenia.

An antiplatelet monoclonal antibody, PMI-1, reacts with glycoproteins (GP) GPIIb, free GPIIb, and the GPIIb-IIIa complex. This antibody binds to 40,900 sites per platelet, with a Kd = 0.95 microM, and its binding is inhibited by the presence of magnesium or calcium in the suspending medium (50% suppression at approximately 0.5 mM divalent cation). Regulation of the PMI-1 epitope is independent of disassembly of the GPIIb-IIIa heterodimer, because it occurred at 22 degrees C and in response to mM magnesium as well as calcium. PMI-1 binding inversely correlated with fibrinogen binding. In addition, we identified a variant of Glanzmann's thrombasthenia with near-normal platelet content of the GPIIb-IIIa heterodimer as judged by crossed immunoelectrophoresis and surface labeling. Binding of PMI-1 to these patients' platelets was not dependent on reduction of the divalent cation concentration. These data suggest that the surface orientation of GPIIb is important in the capacity of platelets to bind fibrinogen.

Castleman's disease in children.

A three and one-half-year-old girl and a 12-year-old boy presented with features of the two clinical presentations of Castleman's disease or giant lymph node hyperplasia. The girl presented with anemia, fever, night sweats, hypergammaglobulinemia, and a palpable abdominal mass. Her symptoms were consistent with those seen in the plasma-cell type of this disease. The boy presented with acute appendicitis and a left hilar mass was noted on his chest radiograph. His asymptomatic presentation was typical of the hyaline-vascular form. Both patients are well without evidence of recurrence four years following resection. Castleman's disease is a benign disorder of lymph nodes that occurs rarely in children. Since the original report in 1954 we could find only 18 cases in the 16-year and younger age group and our patient with the symptomatic form represents the youngest patient reported in the English literature. The management requires surgical resection of the enlarged nodes both for diagnosis and therapy since the enlarged nodes can mimic malignant tumors of the lymphoid system. No recurrences have been reported in pediatric patients.

Severe congenital neutropenia with unique features of dysgranulopoiesis.

Congenital dysgranulopietic neutropenia (CDN) is a recently proposed entity that describes a small subgroup of children with clinically severe neutropenia. We followed and studied a 3-year-old girl with neutropenia (less than 500/mm3) and recurrent severe infections in whom repeated marrow evaluations revealed large (30-50 microns) multinucleated promyelocytes to polymorphonuclear cells with as many as 4 to 16 nuclei or nuclear lobes, respectively. In addition to the nuclear endoreduplication, ultrastructural and cytochemical evaluation of these cells demonstrated abnormalities in granule genesis and centriole structure. Concomitantly, immunoperoxidase staining indicated that many of the granules were devoid of lactoferrin but not lysozyme. In vitro proliferation studies revealed normal to increased thymidine labeling, normal numbers of colony-forming cells, and normal colony-stimulating activity from blood and marrow mononuclear cells, findings consistent with ineffective myelopoiesis. However, serum folate, B12, and lysozyme levels were normal. The nuclear and cytoplasmic abnormalities in this patient result in an extreme example of CDN, distinct from previously described cases.

Purpura fulminans following late-onset group B beta-hemolytic streptococcal sepsis.

A 16-day-old male infant initially was in septic shock. Following intensive resuscitation, thrombohemorrhagic lesions developed over his extremities, except for the limb with an arterial line maintained by a continuous heparin sodium infusion. Blood and CSF cultures yielded group B beta-hemolytic streptococci. Results of laboratory studies and clinical appearance supported the diagnosis of purpura fulminans (PF). Systemic heparinization was therefore started, and subsequently his condition improved. Because of the distinct difference in limb sparing, we concluded heparin has a beneficial effect on the evolution of PF.

Reduced surface expression and binding of fibronectin by thrombin-stimulated thrombasthenic platelets.

Thrombin stimulation results in increased surface expression of endogeneous fibronectin and binding of plasma fibronectin to human platelets. Platelets of patients with Glanzmann's thrombasthenia, a bleeding disorder, exhibit reduced thrombin-induced platelet aggregation, little or no clot retraction, and abnormal platelet spreading on glass surfaces. Thrombin stimulation of patient platelets from four thrombasthenic kindreds resulted in little fibronectin binding. Nevertheless, thrombin did induce serotonin secretion from these cells, indicating that stimulation was occurring. Thrombasthenic platelets did not inhibit thrombin-stimulated fibronectin binding to coincubated normal cells, suggesting that their defect was not due to the presence of a soluble inhibitor of fibronectin binding. Thrombin-stimulated afibrinogenemic platelets bound similar quantities of fibronectin to normal cells, indicating that the thrombasthenic deficit is not secondary to reduced fibrinogen content or binding. The thrombasthenic cells had an endogenous fibronectin content of 2.9 +/- 0.7 micrograms/10(9) platelets, whereas cells simultaneously prepared from five normal individuals contained 1.8 +/- 0.7 micrograms/10(9) platelets, a statistically insignificant difference. Nevertheless, thrombin stimulation did not increase expression of endogeneous fibronectin antigen on the surface of the thrombasthenic platelets as judged by immunofluorescence. These defects in platelet fibronectin binding and surface expression may account for some of the manifestations of Glanzmann's thrombasthenia.

Congenital self-healing histiocytosis-X.

Histiocytosis-X (H-X) is heterogeneous clinically, varying from localized benign forms to disseminated fatal forms, but has a relatively uniform and specific pathologic appearance, both by light and electron microscopy. H-X localized to bone or lung has long been recognized. Much less frequent are patients with H-X localized to skin. We report two infants with congenital self-healing H-X, clinically confined to the skin. Prediction of the clinical course from the histology of a H-X lesion is unreliable, especially for cutaneous lesions. We feel that patients with localized forms of H-X should be followed closely for progression of disease but should not be treated aggressively until time is allowed for spontaneous resolution.

Utility of monoclonal antibodies in the immunologic phenotyping of acute lymphoblastic leukemia.

Peripheral blood and/or bone marrow lymphoblasts from 34 children and 11 adults with acute lymphoblastic leukemia (ALL) were evaluated with a monoclonal anti-Ia antibody and a monoclonal anti-pan T-cell antibody (T101) specific for a 65,000-dalton T-cell antigen (T65). Seventy-six per cent of cases were Ia+T65-, 20% were Ia-T65+ and the remaining 4% were Ia-T65-. Anti-Ia and T101 reactivity were mutually exclusive and no Ia+T65+ cases were identified. In childhood ALL, the Ia+T65- phenotype was associated with good prognostic factors and longer median disease-free survival than Ia-T65+ patients whose clinical parameters resembled those characteristic of high-risk T-cell ALL. Included in the Ia-T65+ group were three E-rosette negative cases with clinical features of T-cell disease. Our findings compare favorably with the results of other investigators utilizing polyclonal antisera and suggest that these monoclonal antibodies, which offer the advantages of monospecific standardized reagents, will prove useful in the immunologic characterization of ALL.

Thrombocytopenia in children.

Thrombocytopenia in children can be classified on the basis of understanding of the production, life span, and fate of platelets. Thrombocytopenia may be familial, associated with drug-ingestion as a result of immune mediated mechanisms, direct toxicity to circulating platelets, or injury to megakaryocytes, or associated with other disease states.

Immune suppression of erythropoiesis in transient erythroblastopenia of childhood.

Serum and IgG from four children with transient erythroblastopenia of childhood (TEC) was tested to see what effect it would have on development of erythroid colonies from bone marrow mononuclear cells. Serum and IgG specimens obtained at the time of diagnosis uniformly suppressed erythroid colony development from CFU-E. Washed bone marrow mononuclear cells from a child with TEC failed to grow in the presence of his own serum, but grew normally in the presence of isologous serum. Serum specimens obtained from patients after recovery from TEC had no effect on erythroid colony development. The anemia of TEC appears to be due to transient immune suppression of erythroid colony development.

Platelet-associated immunoglobulin G in childhood idiopathic thrombocytopenic purpura.

Childhood ITP is an acquired hemorrhagic disorder with a heterogeneous clinical course. We measured PAIgG levels in 20 children with ITP (7 acute, 13 chronic). Both groups had significantly greater PAIgG values than age-matched normal subjects and thrombocytopenic controls (P less than 0.001). In addition, PAIgG values in chronic ITP were significantly lower than those in acute ITP (P less than 0.003). Serial PAIgG values were obtained in some patients; most returned to normal in association with clinical recovery. The measurement of PAIgG is useful in the diagnosis and follow-up of childhood ITP. PAIgG values may assist in differentiating acute and chronic disease in children.

The role of the spleen in "autoimmune" blood disorders.

Several immune-mediated blood disorders in both children and adults have findings compatible with an autoimmune etiology, although the autoantigen in most instances is not clearly established. In the present report, we review briefly the clinical features of immune hemolytic anemia, immune thrombocytopenic purpura, and immune neutropenia in children and discuss the possible pathogenetic mechanisms based on present experimental and clinical observations. The role of the spleen in the pathophysiology of these disorders is emphasized.

Antibody-dependent lymphocytotoxicity induced by immunoglobulin G from Hodgkin's disease splenic lymphocytes.

Immunoglobulin G, produced in cultures of splenic lymphocytes obtained from patients with Hodgkin's disease, bound to a population of homologous peripheral blood lymphocytes and initiated antibody-dependent cell cytotoxicity in cultures from five out of eight patients. Two patients whose cultures produced negative results had minimal disease; the other was in remission. The target cells appear to be T lymphocytes; the effector cells bear Fc receptors that are inhibited by antigen-antibody complexes. Antibody-dependent cell cytotoxicity events may produce the anergy and lymphopenia often seen in Hodgkin's disease.