Cancer risk research: what should we tell subjects?
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Biomedical subjects
Publications and source records attributed to S Shurin.
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Granulocyte transfusions are increasingly being used as therapy for newborns with sepsis and neutropenia. We injected either group B Streptococcus or phosphate-buffered saline solution intraperitoneally into adult and newborn rats. Human granulocytes, labeled with chromium 51, were transfused seven hours later. When the newborn rats were killed 13 to 19 hours after injection, they had 10(2) to 10(6) cfu/gm Streptococcus organisms in both lung and brain. Only one third of the adult rats had 10(2) to 10(4) cfu/gm Streptococcus organisms in either lung or brain. A greater proportion of the transfused granulocytes was present in lung and brain tissue of newborn rats, compared with adult rats (p less than 0.05), irrespective of infection. Granulocyte transfusion did not change the peripheral blood leukocyte count in adult rats but increased the count in newborn rats (p less than 0.05). The immature myeloid pool in the bone marrow of adult rats increased significantly with either infection or transfusion (p less than 0.01). The immature pool in newborn rats increased significantly only with infection (p greater than 0.001), although the combination of infection and transfusion also had a significant effect on the pool (p less than 0.01). Infection and both infection and transfusion, but not transfusion alone, significantly affected the mature myeloid bone marrow pool in adult and newborn rats (p less than 0.001). The depletion of the mature myeloid elements of the bone marrow in response to infection was dramatic in neonatal rats, compared with that in adult rats. Both transfused granulocytes and hematogenously spread streptococci lodge in the brains and lungs of neonatal rats more effectively than in those of adult rats.
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Fatal T-cell lymphomas developed in three patients with a chronic illness manifested by fever, pneumonia, dysgammaglobulinemia, hematologic abnormalities, and extraordinarily high titers of antibody to the Epstein-Barr virus (EBV) capsid antigen (greater than 10,000) and early antigen (greater than 640) but low titers to the EBV nuclear antigen (less than or equal to 40). To understand the pathogenesis of these tumors better, we determined the immunophenotype of the tumor cells and analyzed tumor-cell DNA for EBV genomes and for lymphoid-cell gene rearrangements. More than 80 percent of the cells in tumors had an activated helper T-cell phenotype (T4, T11, la positive). The EBV genome was found by in situ hybridization in tumor tissue from each patient. Southern blot assay of DNA digests from one patient showed the same pattern as that of the EBV-infected marmoset line, B95-8. DNA digests from two patients showed a monoclonal proliferation of T cells determined on the basis of uniform T-cell-receptor gene rearrangements and a single band for the joined termini of the EBV genome. We conclude that EBV may infect T cells and contribute to lymphomas in selected patients with severe EBV infections.
A child who developed generalized bleeding immediately after placement of a ventriculoperitoneal shunt was found to have evidence of disseminated intravascular coagulation (DIC). Infusion of fresh frozen plasma was followed promptly by improvement in laboratory values and cessation of bleeding. Complications of the acute bleeding episode included intraventricular hemorrhage, loss of 50% of the red cell volume into subcutaneous tissues, and transient peritoneal irritation. Defibrination syndrome (that is, DIC) due to release of tissue thromboplastin is a recognized complication of trauma, particularly with brain injury. Defibrination can be induced in experimental systems with administration of very small amounts of thromboplastin, which is present in high concentration in brain tissue. This has not been described previously with minor neurosurgical procedures. The diagnosis of DIC should be considered if excessive bleeding occurs after any brain insult, since early recognition and restoration of normal hemostasis by replacement of clotting factors should prevent major complications due to ongoing hemorrhage.
Fifty-nine children with congenital asplenia were reviewed for episodes of severe infection. Seven children had isolated asplenia and 52 had asplenia associated with complex congenital heart disease (asplenia syndrome). A control group of eusplenic children with comparable cardiac lesions were assembled and used for comparative statistical analysis. There were 16 instances of documented sepsis among 59 children (27%). In those less than six months of age, the invading organism was usually gram-negative (Escherichia coli or Klebsiella). In children six months of age or older, the infecting organism was usually a pneumococcus or H. influenzae. When those with asplenia syndrome were compared to the control population, the former group had a significantly greater incidence of sepsis. Children with asplenia syndrome who survived the first month of life were at greater risk of dying from sepsis than from their heart disease. It is recommended that prophylactic antibiotics be administered to children with congenital absence of the spleen, commencing at three months of age, to be continued indefinitely.
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An 11-year-old boy with multiply relapsed lymphoblastic disease became transfusion dependent with myelodysplasia and chromosomal abnormalities after 5 years of aggressive therapy. At 5 years of age, he presented with transient idiopathic hypoplastic anemia and neutropenia that spontaneously resolved within a month. Three months later, he experienced lymphoblastic lymphoma in the left parotid region and subsequently experienced disease relapse in his testicles, bone marrow, and central nervous system during a 3-year period. He has received multiagent chemotherapy, autologous peripheral blood stem-cell transplantation, and testicular and whole neuraxis irradiation therapy. After craniospinal irradiation, he did not recover normal bone marrow function. His bone marrow was hypocellular, and he required platelet and erythrocyte transfusions and granulocyte colony-stimulating factor. Marrow cytogenetic studies revealed new multiple translocations. Within a month of the initiation of intravenous amifostine at 200 mg/m2/dose three times a week, his leukocyte count, neutrophil count, and hemoglobin level normalized. His platelet count also improved sufficiently to achieve transfusion independence. He has returned to school and engages in other normal activities for his age. Amifostine may improve hematopoiesis in secondary myelodysplastic syndromes in children.