William A. Robinson

Felty's syndrome: Effect of lithium on granulopoiesis

The effect of lithium carbonate upon granulopoiesis was studied in eight patients with Feltys syndrome. Absolute granulocyte counts increased in all patients receiving 900 mg lithium carbonate daily for six weeks. Increased urinary and serum granulocyte colony-stimulating activity was observed in all patients during lithium therapy. A casual relationship between increases in colony-stimulating activity and increased granulocytes is postulated.

Involvement of the heart and pericardium in the malignant lymphomas.

Seventeen patients with lymphomatous involvement of the heart or pericardium were studied. The series includes eight patients with Hodgkins disease and nine with non-Hodgkins lymphoma. All 17 had radiologic evidence of pulmonary, pleural, or mediastinal involvement. Cardiac or pericardial disease in seven was apparently due to direct extension of other intrathoracic tumor masses. Cardiac involvement was usually a late manifestation of lymphoma with median onset 20 months after initial diagnosis. Fourteen patients had been treated for stage IV disease prior to the onset of cardiac lymphoma. Only seven of the 17 patients with cardiac involvement were diagnosed antemortem. Four of them are alive without evidence of disease 8 to 68 months after diagnosis and treatment. Because cardiac lymphomas may respond to therapy with prolonged survival, it is imperative that clinicians suspect cardiac or pericardial involvement in lymphoma patients who have radiographic evidence of intrathoracic lesions (especially adjacent to cardiac borders), unexplained tachyar-rhythmia or conduction disturbance, evidence of outflow obstruction, or signs and symptoms suggesting pericardial effusion or tamponade.

Macrocytic anemia, thrombocytosis and nonlobulated megakaryocytes: the 5q-syndrome, a distinct entity.

The clinical, hematologic and histologic characteristics of six patients with refractory anemia with deletion of the long arm of chromosome No. 5 are described. These patients had a distinct hematologic picture with macrocytic anemia of mild to moderate severity, normal to low leukocyte count and increased platelet count. The long arm of chromosome No. 5 was deleted in the majority of bone marrow metaphases. The main cause of anemia was underproduction with decreased erythroid precursors in the bone marrow and no increase in peripheral blood reticulocytes. Two of five patients responded transiently to the administration of androgens. In vitro evaluation of the bone marrow growth pattern in semisolid agar culture system was performed in three patients and was found to be normal and distinct from that in patients with preleukemia. In a follow up of up to five years, no patient had changed hematologically and in none had leukemia developed. The 5q-syndrome is a distinct hematologic entity and probably more common than hitherto realized. This diagnosis may have therapeutic and prognostic implications.

Granulocyte Stem Cells Are Decreased in Humans with Fatal Burns

The number of granulocytic stem cells (CFU-C) was measured in the peripheral blood of surviving and nonsurviving burned humans. It has been shown that the number of CFU-C in the peripheral blood of survivors increases over time and is elevated compared to the number found in normal humans. The number found in nonsurvivors, however, falls significantly in the later stages of burn injury, suggesting perhaps a defect in stem cell production and/or differentiation in patients with severe thermal injuries. The mechanism is unclear but its delineation may have an important bearing on understanding the nature of infectious complications following thermal injury.

Deletion of the p53 gene in a patient with aggressive burn scar carcinoma

BACKGROUNDnAggressive squamous cell carcinoma (SCC) is known to occur in scars that develop after a burn injury, especially in the underdeveloped areas of the world where care is lacking. Because most SCC are associated with abnormalities in tumor suppressor genes, particularly p53, we postulated that similar mechanisms may underlie the development of burn-associated SCC.nnnMETHODSnWe analyzed tissue DNA from a patient who died from an aggressive SCC in a burn scar for evidence of p53 gene abnormalities by polymerase chain reaction and immunohistochemical staining for p53 protein.nnnRESULTSnUsing polymerase chain reaction, the p53 gene could not be detected in DNA from the patients cancer. The p53 protein was also undetectable by immunohistochemical staining.nnnCONCLUSIONnThese studies indicate that there was a homozygous deletion of the p53 gene in this burn-related carcinoma. Further studies of other patients may lead to new understanding of this cancer, explain in part the usual aggressive behavior, and lead to new methods of prevention and treatment.

The anemia of thermal injury: studies of erythropoiesis in vitro.

Anemia is invariably seen in patients who have been severely burned, and a number of factors have been implicated in its etiology. Prior studies have suggested that a depressed rate of erythropoiesis is involved. In order to study this, we evaluated the effect of serum from burned patients on red cell and white cell colony growth in vitro. We found that these sera were capable of inhibiting red cell, but not white cell, colony growth. Additional experiments indicated that this was related to the presence of some substance in the burned serum rather than the absence of a factor required for colony formation. Further studies, including review of clinical data, suggested that this effect was not due to topical medications nor to episodes of bacterial sepsis. Serial studies showed that inhibition was often not present in the immediate postburn period but developed gradually, reaching maximum intensity approximately 20 to 30 days following the burn and then returning toward normal as patients healed their injury. Our studies permit the hypothesis that inhibition of erythropoiesis plays a role in the pathogenesis of the anemia of thermal injury.

Chronic Myelogenous Leukemia: Cyclic Leukocytosis and Identical Twin Discordance

A cyclic leukocytosis with cycles of approximately 72 days and counts ranging from 4,000 to 145,000 cells/mm3 has been followed for 15 months with no treatment, in a 13-year-old white female with chronic myelogenous leukemia (Ph1 positive). An identical twin has no clinical, morphologic or cytogenetic evidence of leukemia. Differential counts of per. bl. and marrow remain unchanged during the patients cycles although marrow cellularity is increased during peaks. Studies which were normal include: Rebuck skin windows, phagocytic and bactericidal functions of neutrophils, glutathione peroxidase levels, fetal hemoglobin and immunologic responses. Epinephrine stimulation produced a total release of marginal pool ceels at the high point with only partial release of cells at a low point. Endotoxin and steroid stimulation studies indicate that mechanisms for delivery of cells from marrow are intact and of similar magnitude at both high and low points. Ph1 positive cells were seen in 81% of mitoses from per. bl. cells taken at a peak while in per. bl. specimens taken at a low point such Ph1 positive cells were absent. At both high and low points over 90% of mitoses of bone marrow cells were Ph1 positive. mixed leukocyte cultures showed a non-reciprocal response of the patients leukocytes to cells of her identical twin, suggesting partial loss of transplantation antigens in some of the patients cells. Leukokinetics with DFP32-labeled cells, alkaline phosphatase and granulopoietin levels and marrow proliferation studies with H3T were measured at high and low points. These studies would be compatible with the view that controls of leukocyte production and release as well as in immunogenetic characteristics of cells are involved in this leukemic process.