Pulse oximetry in sickle cell disease.

Patients with sickle cell disease usually have mild hypoxaemia and their oxyhaemoglobin dissociation curve is shifted to the right. It follows that oxygen saturation in sickle cell disease should be lower than normal. Most subjects in this clinic had normal oxygen saturation by pulse oximetry, however. To improve the understanding of this paradox, arterialised capillary oxygen tension (PO2) and oxygen saturation were compared with simultaneously measured pulse oximeter saturation in 20 children with sickle cell disease. In addition, the PO2 at 50% haemoglobin saturation (P50) was compared with saturation measured by pulse oximetry in all 20 patients. It was found that saturation measured by pulse oximetry was, on the whole, similar to that calculated from the sampled blood. Individual deviations were not random, however, and were partly explained by differences in P50 values. It is concluded that pulse oximetry gives variable results in patients with sickle cell disease and should be used with caution to predict arterial saturation in this patient group.

Accumulation of high levels of methotrexate polyglutamates in lymphoblasts from children with hyperdiploid (greater than 50 chromosomes) B-lineage acute lymphoblastic leukemia: a Pediatric Oncology Group study.

Hyperdiploidy (greater than 50 chromosomes, or a DNA index greater than 1.16) confers a favorable prognosis in B-lineage acute lymphoblastic leukemia of childhood. Children with B-lineage acute lymphoblastic leukemia whose lymphoblasts at diagnosis accumulate high levels of methotrexate (MTX) and MTX polyglutamates (MTXPGs) in vitro experience a better event-free survival than those whose lymphoblasts do not (Blood 76:44, 1990). Lymphoblasts from 13 children with hyperdiploidy (greater than 50 chromosomes) accumulated high levels of MTX-PGs (1,095 and 571 to 2,346 pmol/10(9) cells [median and 25% to 75% intraquartile range]). These levels were higher than those in B-lineage lymphoblasts from 19 children with other aneuploidy (326 and 159 to 775 pmol/10(9) cells) and 15 children with diploidy (393 and 204 to 571 pmol/10(9) cells) (P = .0015). Chromosomal trisomies in hyperdiploid cases were highly nonrandom. Chromosome 9 was not one of the chromosomes involved in trisomies, even though this chromosome contains the gene for folate polyglutamate synthetase, which is the enzyme required for MTXPG synthesis. The correlation between MTXPG level and percentage of S-phase cells was weak, suggesting that increased levels of MTXPGs could not be attributed to elevated proportions of cells in active DNA synthesis. The ability of hyperdiploid lymphoblasts to accumulate high levels of MTXPGs may increase their sensitivity to MTX cytotoxicity, accounting in part for the improved outlook for hyperdiploid patients treated with regimens that emphasize MTX as a primary component of continuation therapy.

Ventilation and gas exchange during exercise in sickle cell anemia.

Adults with sickle cell anemia (SCA) have restrictive lung impairment, increased alveolar dead space, and hypoxemia. These factors, together with increased anaerobic metabolism, are thought to cause exercise hyperventilation. To assess the role of each of these in children, 34 patients with SCA and 16 control subjects performed pulmonary function and exercise tests. Twenty-eight patients with SCA had spirometric values and lung volumes, and all but two patients with SCA had arterial saturation greater than 91% during exercise. Despite a low VO2max (30.07 +/- 6.55 ml/min/kg), the ventilatory anaerobic threshold (VAT) in the patients occurred at a similar %VO2max as in the control subjects (69 +/- 9% versus 63 +/- 12%). The slope of the delta VE/delta VCO2 relationship for sub-VAT work was steeper in the patients (29.4 +/- 6.5 versus 24.7 +/- 5.2, p = 0.01), and the ventilatory equivalent for CO2 (VE/VCO2) in steady-state exercise was greater in the patients than in the control subjects (33.2 +/- 3.5 versus 30.8 +/- 3.5, p = 0.03). End-tidal PCO2 did not differ (38.3 +/- 3.0 versus 39.2 +/- 3.1), indicating equivalent alveolar ventilation. The patients had a higher dead space:tidal volume ratio (VD/VT) than did the control subjects (0.204 +/- 0.033 versus 0.173 +/- 0.024, p = 0.0005). The PaCO2 was significantly lower in those with lower Hb, but there was no difference in pH. In conclusion, children with SCA have an increased exercise ventilatory response caused in part by increased physiologic dead space, and in part by their low Hb. The greater dead space may be the result of sickle cells impairing capillary perfusion to ventilated alveoli.

Cardiac output and oxygen delivery during exercise in sickle cell anemia.

Desaturation in patients with sickle cell anemia (SCA) can lead to intravascular sickling and vascular occlusion. The increased metabolic demands of exercise tend to increase oxygen extraction, giving rise to a fall in saturation in the capillary bed that may predispose to sickling. This could be minimized with an increase in cardiac output. The aims of this study were to assess the role of increased stroke volume (SV) in augmenting cardiac output (Q) and to estimate the role of enlarged arteriovenous O2 content difference in maintaining O2 transport in children with SCA. A group of 30 children with SCA (Hb 65 to 133 g/L) and 16 healthy controls of the same racial group and of similar height and weight performed incremental and steady-state exercise at 50% Wmax. Cardiac output (Q) was measured by the indirect (CO2) Fick method during steady state. The slope of delta HR/delta VO2 during incremental exercise was higher in SCA subjects compared with controls (4.01 +/- 1.73 versus 2.80 +/- 0.61 bpm per ml/min/kg VO2, p = 0.001). Q for VO2 was abnormally high in patients, particularly older ones with lower Hb levels. HR (% predicted) was higher in patients than in controls (106 +/- 11 versus 92 +/- 8% predicted, p less than 0.0001), as was SV (113 +/- 16 versus 98 +/- 14% predicted, p = 0.002). Multiple linear regression of Q % predicted and SV % predicted on Hb and age showed a positive correlation with age and a negative correlation with Hb (r = 0.84 for Q and r = 0.76 for SV).(ABSTRACT TRUNCATED AT 250 WORDS)

Cognitive function in long survivors of childhood acute lymphoblastic leukemia.

Thirty long survivors of childhood acute lymphoblastic leukemia were compared with their healthy siblings on cognitive and neuropsychological measures. The subjects were comparable in treatment variables except for type of central nervous system prophylaxis received. Thirteen were given radiotherapy with intrathecal medication, and seventeen received only intrathecal treatment. Patients receiving only intrathecal medication did not differ from controls. Patients receiving radiotherapy scored lower on several measures including Wechsler Full Scale and Performance IQ. Irradiated girls scored lower than boys on most measures. Children whose clinical management has included radiation therapy appear to be at risk for later mild cognitive deficits. No consistent pattern of neuropsychological deficits has emerged and observed deficit patterns may reflect individual vulnerabilities.

Hodgkin's disease following Wilms' tumor: a case report.

A patient is described who developed Hodgkin's disease 16 years after treatment of Wilms' tumor with radiation and actinomycin D. The issues relating to Hodgkin's disease as a second malignancy are reviewed. The need for long-term surveillance of patients with malignant disease for late effects of the cancer and its treatment is emphasized.

Computed tomography in interstitial lung disease.

The number and scope of published articles dealing with computed tomography of interstitial lung disease are limited. We present seven cases in which computed tomography detected the presence or extent of interstitial lung disease better than conventional radiography: two patients with histiocytosis X, one with bronchopulmonary dysplasia, one with bleomycin lung toxicity, and three with radiation-induced lung injury. The computed tomography appearance of histiocytosis X and bronchopulmonary dysplasia have not been previously described. Transverse computed tomography images provide information regarding stage of activity and nature of interstitial lung processes not available with standard imaging techniques. We advocate the use of computed tomography in the initial investigation and follow-up of patients with histiocytosis X. Post-radiation pneumonitis and fibrosis can be detected earlier with computed tomography as well.

Acute lymphoblastic leukemia at relapse in a child with acute myeloblastic leukemia.

We describe a child diagnosed as having acute myelogenous leukemia (AML) at 25 months of age who relapsed with acute lymphoblastic leukemia (ALL) 1 year later. The AML was morphologically M2 by the French-American-British classification, periodic acid Schiff (PAS) stain negative and peroxidase positive. The ALL was L1 by this classification, PAS positive, and peroxidase negative. The initial AML was associated with a small segment deletion of the long arm of chromosome 11 [46, XY, de (11) (q23)] not seen in the relapse ALL, which had a normal karyotype. The child was rapidly reinduced with vincristine and prednisone, and remains in remission on maintenance lymphoma type (LSA2-L2) therapy more than 2 years later. These findings suggest the development of a new leukemic clone, rather than a phenotypic modulation of the initial leukemia.

Growth and development of long-term survivors of childhood acute lymphoblastic leukemia treated with and without prophylactic radiation of the central nervous system.

Two groups of patients with at least four years of remission following treatment of acute lymphoblastic leukemia with or without prophylactic cranial irradiation (mean interval of 8 years from diagnosis) were studied. Out of 41 eligible patients, 22 patients were assessed for pubertal staging, growth velocity, cranial computed tomography scanning, and complete endocrinologic status following stimulation with arginine or insulin hypoglycemia, TRH and LHRH. Group I (N = 9, 4 male, 5 female) had received systemic chemotherapy and intratheral methotrexate, but no cranial irradiation. Group II (N = 13, 9 male: 4 female) had additionally received central nervous system irradiation (2400 rads). All patients had undergone normal spontaneous puberty, and had normal levels of thyroxine, thyrotropin, dihydroepiandrosterone sulfate, testosterone or estrogens, luteinizing hormone, follicle stimulating hormone, prolactin, and cortisol. In Group I only one patient decreased his percentile height greater than 25% but he had normal growth hormone responses. In Group II, two younger patients showed growth deceleration with inadequate provocative growth hormone responses, whereas two pubertal patients developed growth arrest post diagnosis and treatment but had normal growth hormone responses. When Groups I and II and controls were compared as to the number of growth hormone samples greater than 5 ng/ml, the peak growth hormone value, or the mean growth hormone concentration during the combined arginine-insulin test, no significant differences were noted. Brain scan abnormalities were noted in 3 out of 9 patients in Group I (33%) and in 5 out of 11 patients in Group II (45%). There was no correlation in either group between abnormal computed tomography scans and abnormal growth hormone secretory dynamics.(ABSTRACT TRUNCATED AT 250 WORDS)

Thrombotic and hemorrhagic complications in children with the lupus anticoagulant.

Endogenous circulating anticoagulants are unusual in children without a congenital factor deficiency. In particular, the lupus anticoagulant has only rarely been reported in children. Despite its functioning in vitro to prolong the partial thromboplastin time, patients more frequently have problems with thrombosis than bleeding, unless there is a coexistent prothrombin deficiency or thrombocytopenia. We report the cases of three children with the lupus anticoagulant. Two children had associated thromboses. One had a thrombosis of the iliofemoral system and the other had a partial Budd-Chiari syndrome, a thrombosis of the deep calf veins and ureteric obstruction. The third child had a concomitant prothrombin deficiency and bleeding after tooth extraction. Associated findings in these patients included a positive antinuclear antibody test in two, a positive anti-DNA antibody test in two, a false-positive VDRL test in two, and an antiphospholipid antibody test in two.

Postextraction hemorrhage in a young male patient with systemic lupus erythematosus.

A case of a 13-year-old boy with prolonged bleeding after tooth extraction is reported. This was the first manifestation of systemic lupus erythematosus found to be associated with circulating anticoagulants, including the "lupus anticoagulant," and possible hypoprothrombinemia.

Rebound thymic hyperplasia in a child with cancer.

A case of biopsy-proven thymic hyperplasia is described in a child with group I paratesticular rhabdosarcoma while on chemotherapy. Other cases of children with cancer reported with this phenomenon are reviewed. Tissue diagnosis is important to differentiate metastatic tumor and to rule out second malignancies in these patients. The initial evaluations are facilitated by CT scanning of the chest and upper extremity venography.

Malignant histiocytosis.

The clinical features, therapy, and hospital course of ten consecutive patients with malignant histiocytosis (MH) are presented. The value of bone marrow aspiration for the diagnosis is discussed. The patient's performance status as described in this report by the organ dysfunction score may predict survival and response to chemotherapy. The literature on chemotherapy in this disease is reviewed. Combination chemotherapy may be the best approach to treatment, but there is little experience with single agents. There is a great need for better characterization of the malignant cell in this disorder.

Radiologic evaluation of osteosarcoma.

Twelve patients with osteosarcoma were evaluated by plain radiographs, radionuclide bone scans and computed tomography (CT). Plain films were the primary radiologic tool for the investigation and follow-up of the skeletal lesion and were particularly helpful for the demonstration of periosteal calcification and bone permeation. The main value of the radiophosphate scan was to detect metastatic or multifocal bone disease. CT was able to show new bone formation in the soft-tissue mass not seen on plain films, to determine proximal intramedullary extension and to assess the response of the bone lesion to preamputation chemotherapy. The lungs were followed at regular intervals with plain chest radiographs and CT scans.

Significance of a (4;11) translocation in acute lymphoblastic leukemia.

This report describes a case of null cell congenital acute lymphoblastic leukemia associated with a (4;11) translocation. This chromosome abnormality is associated with acute lymphoblastic leukemia and probably more specifically with congenital acute lymphoblastic leukemia. A review of the literature is presented.

Computed tomography brain scans in long term survivors of childhood acute lymphoblastic leukemia.

There have been varying frequencies cited for the occurrence of abnormal brain CT scans in leukemic patients and conflicting evidence about the significance of these abnormalities and their relationship to sanctuary therapy. Our study of CT brain scans in 26 long survivors of acute lymphoblastic leukemia showed an overall prevalence of 35% abnormal scans. There was no statistically significant difference between the number of abnormal scans in patients given radiotherapy as part of their CNS prophylaxis and those receiving only intrathecal methotrexate. Because the children in each treatment group were evenly matched with respect to other treatment variables possibly relevant to the causation of abnormal brain scans, a strong case is made for more rigorous design of such studies, preferably in a prospective fashion, looking simultaneously at other parameters of brain structure and function.