Pre-oxygenation in pregnancy: the effect of fresh gas flow rates within a circle breathing system.

We have investigated the effect of oxygen flow rate on pre-oxygenation in pregnant patients at term using a circle system. Twenty patients presenting for elective Caesarean section maintained tidal volume breathing through a standard circle system for 3 min. Subjects were pre-oxygenated using oxygen flow rates of 5 l.min(-1), 10 l.min(-1) and 15 l.min(-1) presented in random order. The mean (SD) fractional end-tidal oxygen at the end of 3 min was 0.86 (0.07) for 5 l.min(-1), 0.92 (0.05) for 10 l.min(-1)and 0.90 (0.09) for 15 l.min(-1) (p < 0.001). Entrainment of air occurred in 22% of pre-oxygenation sessions. Oxygen flow rates of 10 l.min(-1) or above provide optimal pre-oxygenation using a circle system in term parturients. In our study, entrainment of air occurred in a surprisingly high percentage of cases.

The spectrum of myositis ossiticans in haemophilia.

Myositis ossificans (MO) refers to non-neoplastic heterotopic soft tissue ossification that can have several aetiologies. Broadly it can be classified into three categories based on aetiology [1]. MO traumatica, the most common form occurs secondary to acute or chronic trauma. MO can also be associated with neurological disorders and in rare cases is congenital. The latter (progressive MO) is a genetic disorder in which congenital osseous abnormalities are associated with progressive soft tissue calcification. Despite an increased tendency to soft tissue bleeds, MO has been rarely reported in haemophilia. We treated three adolescents with haemophilia and MO of varying degrees of severity and outcome.

Lymphomas and bone tumors: clinical presentation, management, and potential late effects of current treatment strategies.

While many pediatric malignancies are seen predominantly in pre-school children, many cases of childhood non-Hodgkin's lymphoma and most cases of Hodgkin's disease and bone tumors are seen in the older child and adolescent. This review focuses on current knowledge concerning the epidemiology, histopathology, molecular biology, clinical presentation, diagnosis, staging, treatment, and prognosis for older children and adolescents diagnosed with lymphoma or either of the two commonly seen childhood bone tumors, namely osteosarcoma and Ewing's sarcoma. Survival figures for all of these childhood malignancies have increased markedly in the past two decades. We now have the relatively new experience of having an increasingly large population of childhood cancer survivors to study and, unfortunately, are beginning to see the long-term consequences of these more successful treatments. This review concludes with an overview of the potential late effects of cancer therapy, effects that may first be detected by the primary care physician caring for the adolescent who is a cancer survivor.

Phenytoin-associated thrombocytopenia in a toddler.

Hematologic side effects are rare side effects of treatment with phenytoin. We report a 2-year-old girl who developed reversible thrombocytopenia following treatment with phenytoin. Thrombocytopenia as a side effect of phenytoin treatment has usually been reported in adults and generally occurs 2 to 4 weeks after initiation of therapy. In our case, the thrombocytopenia developed on the 11th day of therapy and resolved 5 days after discontinuation of the phenytoin.

Benign transient hyperphosphatasemia in children with leukemia and lymphoma.

A temporary elevation of serum alkaline phosphatase has been described in young children who have no evidence of liver or bone disease. This phenomenon has been termed benign hyperphosphatasemia of infancy. Its occurrence is described in three children undergoing chemotherapy for acute lymphoblastic leukemia and lymphoma. All three children were in remission and in the consolidation or maintenance phase of their therapy when the hyperphosphatasemia occurred. All children were also receiving methotrexate (IM and IV), oral 6-mercaptopurine, and oral sulfamethoxazole/trimethoprim. Although these agents are associated with hepatotoxicity, other liver transaminases (ALT, AST) remained at normal concentrations, and there was an elevation only in the bone isoenzyme of alkaline phosphatase, thus making hepatic toxicity an unlikely etiology for the hyperphosphatasemia. No alteration in chemotherapy was necessary for resolution of the elevated alkaline phosphatase in these children.

Unusual presentation of Ewing sarcoma with t(21;22) in a 3-year-old boy.

PURPOSE: We describe a 3-year-old boy with widespread, metastatic Ewing sarcoma and an unusual translocation, involving chromosomes 21 and 22. MATERIALS AND METHODS: Cytogenetic studies were performed on a biopsy of the primary tumor. These included GTG banding and fluorescence in situ hybridization. RESULTS: A balanced translocation between chromosomes 21 and 22 was noted with translocation breakpoints at bands 21q22 and 22q12. CONCLUSIONS: The t(21;22) translocation represents a new cytogenetic abnormality that may be associated with Ewing sarcoma. Its prognostic significance, if any, remains to be determined.

CD3+, CD56+ aggressive variant of large granular lymphocyte leukemia.

Clonal expansions of CD3+ large granular lymphocytes (LGL) have been classified as T-LGL leukemia. The majority of patients with T-LGL leukemia have a chronic disease (years) manifested often by severe neutropenia, rheumatoid arthritis, and mild-to-moderate splenomegaly. The characteristic phenotype of the leukemic LGL is CD3+, CD8+, CD16+, CD57+, and CD56-. In this report we describe an aggressive variant of T-LGL leukemia in which leukemic LGL also expressed CD56, as identified by two-color flow-cytometry analysis. In contrast to the chronic nature typical of T-LGL leukemia, these patients presented with a severe systemic illness that was rapidly progressive and resistant to treatment. Atypical clinical features included rapidly increasing spleen size to massive proportions, extensive lymphadenopathy, and the presence of B symptoms (fever, nightsweats, weight loss). Hematologic and pathologic features were also unusual for T-LGL leukemia. These patients had very high LGL counts at diagnosis (range 11,692 to 26,312 microL), which increased rapidly despite treatment. Histopathologic examination of splenic sections showed extensive infiltration of red pulp cords and sinuses by leukemic cells with atrophy of the white pulp. These clinicopathologic features are similar to those described for patients with natural killer cell (NK)-LGL leukemia, whose cells are also CD56+. However, unlike NK-LGL leukemia, we could not show a direct pathogenic role for Epstein-Barr virus (EBV), as Southern-blot analyses using an EBV-joined termini probe were negative in these patients. Our findings suggest that CD3+, CD56+ LGL leukemia is a distinct clinicopathologic entity separate from the usual CD3+, CD56- T-LGL leukemia. The expression on leukemic LGL of CD56, an adhesion molecule, may determine the aggressive biologic nature of this newly described disease.

Aplastic anemia following therapy for absence seizures with ethosuximide.

We describe a case of aplastic anemia in an 8-year-old girl which was diagnosed 8 months after initiation of ethosuximide as treatment for absence seizures. Blood counts had been previously monitored and were normal. The patient successfully underwent allogeneic bone marrow transplantation. Only 8 cases of ethosuximide-associated aplastic anemia have been reported, and in only one of these reports, was ethosuximide used as a single antiepileptic agent. This rare, but potentially fatal complication of ethosuximide raises the question of whether routine monitoring of blood counts during ethosuximide therapy is useful and should be undertaken.

An update in pediatric oncology.

Although childhood malignancies are rare, they represent the most common cause of death from disease in children less than 15 years old. Fortunately, the outlook for children with cancer has been improving steadily as newer methods of diagnosis, staging, and treatment are developed.

Induction of tumoricidal activity and alterations of growth by interleukin-2 and manipulation of protein kinase C and cytosolic calcium in childhood acute lymphocytic leukemia cells.

Signals from many receptor-ligand interactions are mediated by enhancement of phospholipid hydrolysis which generates metabolic intermediates stimulating protein kinase C (PKC) and elevating cellular calcium. Pharmacologic agents such as phorbol 12, 13-dibutyrate (PDBu) and ionomycin selectively stimulate PKC and elevate intracellular calcium to directly stimulate downstream mechanisms critical to cell growth and function. This study examines the effects of PDBu, ionomycin, and rIL-2 on childhood ALL blasts of early B lineage with respect to various aspects of cell activation, including DNA synthesis, induction of non-MHC restricted tumoricidal activity, and changes in morphology and phenotype. Five childhood ALL samples were tested. A marked heterogeneity was seen among the ALL samples with respect to in vitro growth following manipulation with PDBu, ionomycin, and/or rIL-2, whereas normal peripheral blood lymphocytes (PBL) were consistently stimulated to grow with the combination of PDBu and ionomycin. Growth responsiveness did not appear to correlate with morphologic or phenotypic classification of the leukemia samples. Four of the five leukemia samples developed substantial non-MHC restricted cytotoxicity to K562 (natural killer cell (NK) sensitive) and Daudi (NK resistant) targets in response to rIL-2. This functional cytotoxic response correlated with morphologic changes in the cells and the appearance of granules. Phenotypic analyses of the ALL samples at the time of their peak cytotoxic function were consistent with the fresh ALL phenotype and showed no major change in cell populations. Three of the five ALL samples also retained rIL-2 induced cytotoxic capabilities when exposed simultaneously to the combination of PDBu and ionomycin, whereas rIL-2 induced tumoricidal activity in normal PBL and bone marrow cultures was inhibited by these reagents. These data show that morphologically and phenotypically similar ALL blasts have heterogeneous proliferative responses to the PKC and calcium modulators PDBu and ionomycin, as well as to rIL-2. Cytotoxic responses are also different from those of normal PBL and bone marrow cells with respect to kinetics and responsiveness to inducing agents. Thus current morphologic and phenotypic classifications of ALL may not adequately reflect the heterogeneity of this disorder as described here.

Monte Carlo computer simulations of ground-based and space-based coherent DIAL water vapor profiling.

Ground-based and space-based coherent DIAL water vapor measurement performance at the 2.1-microm Ho:YAG wavelength is presented using a Monte Carlo computer simulation. The stochastic simulation allowed improved modeling of lidar system, platform, atmospheric, and data processing parameter effects on performance and better understanding of their interrelationships. Results indicate that accurate water vapor measurements in the lower troposphere are potentially achievable from both ground- and space-based platforms.

Immunologic and clinicopathologic features of common acute lymphoblastic leukemia antigen-positive childhood T-cell leukemia. A Pediatric Oncology Group Study.

The immunologic and clinicopathologic features of common acute lymphoblastic leukemia antigen (CALLA)-positive and CALLA-negative T-acute lymphoblastic leukemia (ALL) and of CALLA-positive non-T, non-B ALL (common ALL) of childhood were compared. Twenty-seven percent of children with T-ALL had blasts that expressed CALLA. This expression was not associated with a significantly different incidence of expression of sheep erythrocyte-rosette receptors, glucocorticoid receptors, peanut agglutinin receptors, or T-cell antigens. CALLA-positive T-cell blasts were more likely to express a p24 leukemia-associated antigen (CD9, 50% versus 8%) and Ia antigens (39% versus 8%) than were CALLA-negative blasts. Patients with CALLA-positive and CALLA-negative T-ALL had similar clinicopathologic features at diagnosis. In contrast, compared to patients with common ALL, patients with CALLA-positive T-ALL were older, had higher leukocyte counts, and an increased incidence of splenomegaly, lymphadenopathy and mediastinal mass, similar to patients with CALLA-negative T-ALL. Patients with CALLA-positive T-ALL were more likely to achieve a complete remission (95% versus 83%, P = 0.055) and tended to have an increased duration of event-free survival (P = 0.07) than did patients with CALLA-negative T-ALL. The expression of T-cell antigens is more important than the expression of CALLA in defining biologically similar subgroups of childhood ALL. Preliminary evidence suggests that within T-ALL the expression of CALLA may be prognostically important.

An analysis of the presence of Fc receptors on bone marrow lymphoblasts in acute lymphoblastic leukemia. A Pediatric Oncology Group study.

The presence or absence of the Fc receptor (FcR) on bone marrow lymphoblasts was evaluated in 279 cases of acute lymphoblastic leukemia (ALL) by member institutions of the Pediatric Oncology Group (POG). The case material was classified as follows: 19 cases of positive (greater than or equal to 20% +), 24 additional cases as intermediate (greater than or equal to 10% but less than 20%), and the remaining 236 cases as negative (less than 10%). Intermediate and positive cases were relatively equally distributed between null cell leukemia and pre-B-cell leukemia, and there were one intermediate and two positive T-cell cases. One of two cases of B-cell leukemia was also positive. There were no distinguishing clinical or laboratory characteristics which distinguished the FcR+ cases, nor was the FcR of prognostic significance within ALL as a group or within immunologically defined phenotypes.

Childhood leukemia with simultaneously expressed myeloid and lymphoid markers suggesting stem cell origin.

A case study is presented of a leukemic patient whose cells express markers of both myeloid and lymphoid cells. Cells were identified from bone marrow which expressed either myeloid antigens, lymphoid antigens, or both myeloid and lymphoid antigens, indicating a possible common stem cell capable of differentiating along either a lymphoid or myeloid cell lineage. Using specific monoclonal antibodies, 40-70% of the cells were reactive with anti-T-cell antibodies, 50% of the cells were reactive with antibodies to the common ALL antigen (CALLA), and 80-90% of the cells were reactive with antibodies directed against myeloid antigens. Using double staining techniques, some cells were found to demonstrate only myeloid markers; others, only lymphoid markers; and others, both myeloid and lymphoid markers. These results suggest that a common stem cell is capable of differentiating along both lymphoid and myeloid lineages.

Ultrastructural analysis of acute lymphoblastic cells: peanut lectin binding correlates with degree of differentiation of the leukemic cells.

Peanut agglutinin (PNA) has been shown to bind selectively to immature cells. Bone marrow cells from some children having acute lymphocytic leukemia (ALL) bind PNA while cells from other ALL patients do not bind, the significance being that the patients whose cells bind PNA have a poorer prognosis than those not binding PNA. In the present study, PNA was conjugated to horseradish peroxidase and the two cell types were compared. Cells binding PNA are immature compared with the non-PNA-binding cells.

Alternatives to splenectomy in the management of chronic idiopathic thrombocytopenic purpura in childhood.

Chronic idiopathic thrombocytopenic purpura (ITP) in childhood exerts influence on the medical, social, and psychologic life of the child. Chronic platelet destruction takes place in the spleen and splenectomy results in complete and permanent recovery of normal platelet counts in most patients. Splenectomy is not without risks, however, and alternative methods of management have been sought. Chronic corticosteroid administration, immunosuppressive agents, infusions of fresh-frozen plasma, plasmapheresis, and high-dose intravenous gammaglobulin administration have all met with variable degrees of success. At the present time, there appears to be no completely satisfactory alternative to splenectomy in the management of the child with chronic ITP.

Characterization of non-human primate antisera to acute lymphoblastic leukemia (ALL): evidence for unique antigen(s) on childhood ALL of "T" phenotype.

A non-human primate antiserum was prepared to acute lymphoblastic leukemia of T-cell phenotype (T-ALL) and, after absorptions with normal blood elements, reacted by immunofluorescence and microcytotoxicity to all the T-ALL tested. In addition, the antiserum reacted with cells from about 70% of the common ALL studied and immunoprecipitated the common ALL antigen of 100,000 daltons. However, when the anti-T-ALL serum was absorbed with with lymphoblasts from common ALL, it failed to react with common ALL lymphoblasts, yet reacted significantly with cells from patients with T-ALL phenotype and defined a 100,000-dalton membrane component not found on common ALL lymphoblasts. In addition, sequential immunoprecipitation of 125I-labeled T-ALL membranes by anti-common-ALL serum followed by anti-T-ALL serum detected the T-ALL membrane component of 100,000 daltons that was not found on common ALL. Thus, our results demonstrate the presence of of a unique human T-ALL antigen present on all T-ALL distinct from the common ALL antigen.