Granulocyte transfusions.
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Biomedical subjects
Publications and source records attributed to S B Shurin.
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Neonatal sepsis, accompanied by neutropenia, is associated with a high mortality. To determine whether granulocyte transfusions improve the survival of critically ill neutropenic infants, we prospectively randomized 25 infants to transfusion and nontransfusion groups, matching for birth weight (less than or equal to 1,500 g or greater than 1,500 g). Infants with necrotizing enterocolitis were randomized separately. Neutropenia was established by two successive absolute neutrophil counts less than or equal to 1,500 cells prior to randomization. The transfusion (n = 12) and nontransfusion (n = 13) groups did not differ with respect to clinical or hematologic characteristics. In 23 of 25, bone marrow aspirations were performed to determine the percentage of neutrophil storage pool. Granulocyte transfusions of buffy coats from single units of whole blood (0.1 to 0.9 X 10(9) polymorphonuclear leukocytes per kilogram) were given daily until the absolute neutrophil count increased to more than 1,500/microL. Only five infants, mostly those with necrotizing enterocolitis, required more than one transfusion. A circulating immature to total neutrophil ratio (I:T) greater than or equal to 0.80 was not predictive of an infant with a neutrophil storage pool less than or equal to 7%, and neither an I:T less than 0.80 nor a neutrophil storage pool greater than 7% were predictive of survival. Granulocyte transfusions did not improve survival when either comparing the whole group, those 17 infants with cultures positive for bacteria or viruses, the 19 infants with a circulating I:T greater than or equal to 0.80, or the nine infants with a neutrophil storage pool less than or equal to 7%.(ABSTRACT TRUNCATED AT 250 WORDS)
The capsular polysaccharide of Hemophilus influenzae type b, polyribosyl ribitol phosphate (PRP), is released from growing organisms during human infection and can be found in body fluids. It binds to untreated erythrocytes. Many patients with invasive infections with this organism develop significant hemolysis, but the mechanism has been unclear. We have found that PRP binds to human erythrocytes in vivo. PRP-coated erythrocytes have a shortened circulation time in mice, but do not lyse spontaneously or fix complement. PRP-coated erythrocytes exposed to antiserum to H. influenzae type b are undamaged in the absence of complement, but are rapidly and effectively lysed in the presence of an intact complement system both in vitro and in vivo in mice. PRP-coated red cells are taken up by liver and spleen. Antiserum to PRP increases hepatic uptake of PRP-coated red cells more than splenic, and appears to induce intravascular, complement-mediated hemolysis, as well as extravascular hemolysis. Patients with invasive infection develop hemolysis when circulating PRP and antibody to PRP are present simultaneously. PRP can sometimes be detected on patient erythrocytes when free PRP is present in serum, but this is an inconsistent finding. The hemolytic anemia that occurs during human infection with H. influenzae type b may be due to absorption of PRP to red cells and immune destruction of sensitized erythrocytes. The process requires an intact complement system; both complement-mediated cell lysis and extravascular hemolysis contribute to red cell destruction.
Twenty (5%) of 432 pediatric patients scanned during the last 36 months underwent percutaneous biopsy with CT guidance. Sixteen patients had suspected or a known malignancy. Four patients were clinically suspected of having an inflammatory process. Cytologic and histologic specimens were taken when technically possible. Total diagnostic tissue recovery rate equalled 88% in the patients with known or suspected malignancy. Diagnostic tissue was obtained in three of four patients with inflammatory disease. No immediate or delayed complications were encountered. Although the percutaneous method under CT guidance has been shown to be advantageous in various aspects of medical care, the utilization of this modality in the pediatric population, to our knowledge, has been limited. We have found this technique to be useful in the tissue diagnosis of pediatric disease, and in guiding the subsequent clinical treatment. The clinical indications, technique, and results utilizing this method are presented.
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Two female siblings died within three months after presenting with paravertebral tumors in the first year of life. The pathology of the two tumors was identical and characteristic of a malignant rhabdoid tumor. There were no identifiable tumor patterns within the kindred which have been associated with any hereditary cancer or precancer syndromes. Fibroblasts were cultured from skin biopsies obtained from the second patient and both parents. Assays of growth kinetics associated with cellular transformation revealed that fibroblasts from the affected sibling can be distinguished from those of the parents and age-matched controls by increased in vitro occurrence of tetraploidy. Such evidence suggests that increased in vitro tetraploidy occurring spontaneously in cultured fibroblasts is an expression of a cancer-prone gene. Increased in vitro tetraploidy has previously been demonstrated in some kindreds with heritable colon cancer syndromes, and may extend our understanding of the genetic etiology of some childhood cancers.
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Epidural, subdural, and intramedullary hemorrhage developed after lateral cervical (C-1, C-2) puncture in a thrombocytopenic patient with meningeal leukemia and increased intracranial pressure. Aggressive platelet support before the procedure did not prevent the hemorrhagic complication. Complete recovery from total motor paralysis with respiratory arrest followed immediate surgical decompression and continuing platelet support. The potential dangers of otherwise minor procedures in compromised patients are reiterated. Neurological recovery as seen here argues for immediate surgical intervention with the development of such potentially life-threatening events.
A 7-yr-old girl with self-limited pulmonary aspergillosis was found to have a defect in granulocyte superoxide production. Her cells produced superoxide at 3% of control rates in response to phorbol myristate acetate (PMA) and opsonized zymosan. Lag times for O-2 production were normal with PMA, opsonized zymosan, and concanavalin-A stimulation. Her granulocyte membranes depolarized in response to all of these stimuli. Superoxide produced by podosomes and a particulate fraction demonstrated an enzyme activity with a normal maximal velocity but a decreased affinity for NADPH. NADH-dependent superoxide production by particles was similar with patient and control material. The duration of superoxide production was prolonged in the patient's intact granulocytes and in the particulate fractions from her cells. Bacterial killing by the patient's granulocytes was initially low, but approached control values after 90 min of incubation. These results are explained by an enzyme activity that has a decreased affinity for its substrate and a decreased rate of inactivation. Family studies indicate an autosomal recessive mode of inheritance.
Two children with acute lymphoblastic leukemia (ALL), whose lymphoblasts lacked terminal deoxynucleotidyl transferase (TdT) by both enzyme and fluorescent antibody assay, responded poorly or not at all to vincristine and prednisone. Both patients had high presenting white counts and mixed L1-L2 morphology. Lymphoblasts from one patient, an adolescent boy with a mediastinal mass, possessed surface membrane receptors for sheep red cells (E) and for complement (EAC) and had elevated adenosine deaminase activity (ADA). Lymphoblasts from a 2.5-yr-old boy without a mediastinal mass did not form E or EAC rosettes and did not express the la-like antigen or carry surface immunoglobulin. The poor response to therapy and absence of TdT were associated with a lymphoblast phenotype suggestive of a highly differentiated T-cell-derived line in one instance and an undifferentiated cell in the other instance. It is postulated that absence of TdT may predict poor therapeutic efficacy of vincristine and prednisone in acute lymphoblastic leukemia in childhood. The absence of TdT may correlate with other developmental characteristics of lymphoblasts, such as altered function or low numbers of glucocorticoid receptors or resistance to lysis by steroid drugs. Determination of many parameters of lymphoblast phenotype at diagnosis to characterize the nature of the malignant cells more precisely may ultimately enhance our understanding of, and improve therapy for, the group of leukemic children who fail to respond to standard regimens.
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Bilateral optic atrophy developed in a 15-year-old patient receiving concomitant neuraxis radiation therapy and weekly vincristine sulfate for medulloblastoma. Other neurologic manifestations that have been associated with vincristine therapy, including inappropriate secretion of antidiuretic hormone, hypertension, confusion, and a severe peripheral neuropathy, were also observed. Neither increased intracranial pressure nor active tumor was identified. Recovery of visual function followed discontinuation of vincristine. Other neurotoxicities also reversed with drug withdrawal. Visual loss occurring in a patient receiving vincristine should alert the physician to the possibility that the process is drug related. This complication may be more likely in patients receiving concomitant or previous cranial radiation therapy. Other central neurotoxicities of vincristine may also be accentuated by neuraxis radiation. It is recommended that vincristine be discontinued in this situation if an aggressive search for a structural anatomic lesion in the optic mechanism is unrevealing, as the prognosis for recovery of visual function appears excellent.
An immunocompetent 12-year-old boy developed multiple microaerophilic streptococcal lung abscesses after application of orthodontic bands ("braces"). The dental work was done in the supine position. The data suggest that the patient aspirated the organisms and, possibly, flecks of dental cement, during orthodontic treatment. "Rubber dams" should be used to help prevent aspiration in children who receive dental work in the supine position. When a rubber dam cannot be used, as with orthodontic treatment, physicians should advise patients who are at risk for developing pulmonary infection (eg, patients with neuromuscular diseases which compromise cough and/or gag, cystic fibrosis, sickle cell anemia, primary immunodeficiency, etc) to have this dental work, including orthodontic treatment, performed in the erect position.
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We recovered capnocytophaga, a gram-negative anaerobe implicated in the pathogenesis of periodontal disease, from two patients with a history of dental infections. Neutrophils from both patients failed to acquire the asymmetric shape characteristic of normal neutrophils. Fluorescein staining of the patients' living neutrophils remained diffuse and patchy instead of showing the normal pattern in which the fluorescence is swept into the rear of the cell. The locomotion of one patient's neutrophils in vitro was less than 50 per cent of that of normal neutrophils, and migration of this patient's neutrophils into dermal abrasions was reduced, although phagocytosis and nitroblue tetrazolium reduction were normal. All abnormalities of neutrophil morphology and function disappeared after eradication of the capnocytophaga infections. Sonicates and culture medium of capnocytophaga contained a dialyzable substance that caused normal neutrophils to behave like neutrophils obtained from the infected patients.
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