Carl H. Smith

Chronic lymphadenopathy simulating malignant lymphoma

A new symptom-complex is described characterized by onset of symptoms between 1 month and 2 years of age: significant generalized lymphadenopathy; hepatosplenomegaly; deviations in immunological status with alterations in gamma globulins and manifestations of auto-immune disease; variable lymph node histology; response to immunosuppressive drugs, and chronic course. The pathogenesis of this entity is not known but reasons are given to support the postulation of a primary immunological disorder.

Plasma thromboplastin antecedent (Factor XI) in the neonate

Plasma thromboplastin antecedent (Factor XI) levels were determined in cordblood, in the blood of women before and during the last trimester of pregnancy, and, at term, and in the blood of infants in the neonatal period and early infancy. The neonatal levels were significantly lower than the maternal levels at term and rose gradually within 60 days to near normal adult values. Vitamin K did not appear to alter the levels within the first 5 days of life and had no effect on the rate of rise. Findings in three infants suggest that decreased activity of PTA in the newborn infant may be responsible for bleeding symptoms similar to those associated with hemorrhagic disease of the newborn, and that it cannot be prevented by administration of vitamin K.

The anemias of early infancy: Pathogenesis and diagnosis

Summary The diagnosis of those anemias of early infancy which occur during the first four to six weeks of life was considered. This embraces the newborn period when adjustment to extrauterine life takes place. During this time profound alterations occur in various systems, including that of hematopoiesis. A satisfactory evaluation of the blood picture may be obscured by these changes as well as by the changes incident to growth and development. The evidence presented in this paper points to the remarkable adaptation and integration of physiologic processes by which sudden and drastic shifts in blood levels are kept in check in the early newborn period. Recent studies reveal, for instance, that the hemoglobin level is usually sustained or shows only a gradual decline during this period. Similarly, the type of nutritional anemia which depends on maternal iron deficiency is of infrequent occurrence during the first days of life. Adjustments in hematopoiesis may take place at varying rates of speed, and protective mechanisms may be upset. To facilitate the interpretation of the blood disorders of this period, normal blood formation and the forces which control hematopoietic equilibrium during fetal life and in the newborn period have been reviewed. In the light of accumulating information, it is possible to relate some of the manifestations of the anemias of this period to deficiencies of one or more hematopoietic factors. Some of the features of erythroblastosis fetalis and of hemorrhagic disease may be explained on this basis. Retarded elaboration of essential hematopoietic principles by the young infant probably contributes to the pathogenesis of a blood disorder. In addition to its other functions, transfusion may serve as an accelerating influence in the production of these elements by newborn infants. Since erythroblastic or Cooleys anemia, familial hemolytic jaundice and hypoplastic anemia may make their initial appearance during the latter part of the newborn period, it is important to look for certain hematologic features by which these conditions may be recognized.

Leucemia in childhood with onset simulating rheumatic disease

Summary 1. Three cases of lymphatic leucemia in children have been described in which, at the onset, the clinical signs and symptoms closely resembled rheumatic disease. The explanation for this confusion may rest on anatomical changes incident to the particular growth period. 2. During the course of the illness marked anemia occurred, which was associated with leucopenia or mild leucocytosis. The diagnosis was manifest from the appearance of abnormal lymphocytes in the circulation possessing the morphologic characteristics of leucemic cells. These hematologic changes were noted in the absence of the usual splenomegaly and lymphadenopathy. No abnormalities were observed in the roentgenogram of the long bones.

Effect of corticosteroids on factor VIII level

Summary An investigation was performed to determinewhether exogenous corticosteroids had any measurable effect on the plasma level of factor VIII in seven subjects with hemophilia and in 3 subjects with idiopathic thrombocytopenic purpura. The mean factor VIII levels in the hemophilic patients were 5.7 per cent, 5.9 per cent, and 5.8 per cent and in children with idiopathic thrombocytopenic purpura were 101 per cent, 103 per cent, and 101 per cent before, during, and after prednisolone therapy, respectively. It is concluded that corticosteroids in the doses administered in this investigation had no significant effect on factor VIII levels in hemophilic and nonhemophilic subjects.

Mediterranean (Cooley's) anemia in a youth ofnineteen years observed since early childhood

Summary In two generations of a family consisting of five individuals, there were two patients with typical Mediterranean anemia, while the blood of the remainder revealed distinctive red cell abnormalities. One of the patients was a youth now 19 years of age who has been under observation since 4 years of age. Transfusions were required to combat the anemia in childhood. He still presents the classical, clinical, hematologic, and roentgenographic evidence of Mediterranean anemia. In spite of chronic anemia he has without splenectomy or other recent treatment developed normally, participates in all activities, and has shown no undue susceptibility to infection. He exemplifies the type of patient with Mediterranean anemia of moderate severity who is asymptomatic until after infancy and who reaches adult life after the blood dyserasia has become arrested at a level compatible with well-being. This case adds to the increasing evidence that Mediterranean anemia may exist in other forms than that of the better-known severe and rapidly progressive type in which there is a fatal outcome before puberty. A younger brother, now 8 years of age, also has Mediterranean anemia comparable in severity with that of his older brother. The remaining members of the family include the parents and a son, 17 years of age. They appear to be clinically well and in none is the spleen palpable. Roentgenographic changes are absent in the parents, but in the son a zone of trabeculation and osteoporosis is present in the proximal portion of one ulna, a lesion which is also present in both affected brothers. Despite minimal anemia, the blood in each member of the family showed various abnormalities, and of these basophilic stippling and hypochromic macrocytes were the most common features. With the exception of the mother, the red cells of every member of this family were resistant to hemolysis in hypotonic saline solutions. The blood abnormalities in the three apparently healthy individualscharacterize them as carriers of this disease. The carrier may be detected by examination of the blood smear, by the fragility test, and by skeletal changes. Basophilic stippling, hypochromic macrocytes, and increased resistance of the red cells to hemolysis constitute important hematologic features and may be present with little or no anemia. It was pointed out in the text that the term carrier is employed in alimited genetic sense to describe the asymptomatic case. Available evidence indicates that the inheritance of this disease is direct from parent to child and the chances of transmitting it are alike in the asymptomatic as in the well-established case. The occurrence of typical Mediterranean anemia in two individualsin one family and of anemia of varying degrees in the others lends weight to the hypothesis that these blood disorders represent manifestations of a single disease.

Bivalent cations in homozygous thalassemia

The duration of survival of pediatric patients with thalassemia major has been extendedby means of transfusion therapy. Late complications are now known to include skeletal fractures and myocardopathy with disturbances in cardiac conduction. Studies of calcium and magnesium have revealed decreased urinary excretion of these minerals from an early age and decreased serum concentrations of one or both cations in patients more than 15 years of age. Increased incorporation of magnesium into erythrocytes, although documented, probably does not account for the findings in serum and urine. Comparative studies in patients with sickle cell anemia revealed normal serum values but variable reductions in urinary excretion of the same cations, suggesting that these aberrations may relate to the presence of hemolytic anemia rather than to thalassemia per se.

COAGULATION STUDIES AS A MEASURE OF LIVER FUNCTION IN COOLEY'S ANEMIA.

Sixty-six patients with severe Cooley’s anemia have been cared for by the pediatric department of the Cornell Medical Center. We have noted that many of these patients have frequent epistaxis, some severe and prolonged enough to require packing by an otolaryngologist to control the bleeding or a transfusion to replace the acute blood loss. We have also had many inquiries as to the advisability of an elective operative procedure such as tonsillectomy in the three-eight year old group of patients or splenectomy in the older age group. Since the individual with homozygous Cooley’s anemia can develop severe degrees of hemochromatosis and hemosiderosis with subsequent liver damage, i t seemed appropriate to investigate the coagulation mechanism as a possible cause for the epistaxis. In addition, we were anxious to see if abnormalities in the coagulation mechanism might serve as indicators of disturbed liver function. For this purpose coagulation studies and other liver function tests were done on a group of 21 patients with severe thalassemia. Recently some of the studies were extended to include a total of 31 patients. Death has subsequently occurred in 10 of the original group.

The abnormal hemoglobins: Clinical and hematologic aspects

Summary To the extended list of hemoglobinsenumerated in this review, there is the almost certain likelihood of future supplementation by newer members. Thalassemia, for example, awaits the discovery of a specific hemoglobin or related compound as judged by its behavior in combination with other hemoglobins. The extraordinary phenomenon of the retardation of the synthesis of normal hemoglobin by the gene for thalassemia with the elaboration of fetal hemoglobin, and its potentiating effect on the synthesis of abnormal hemoglobins such as S, C, and F render this a plausible hypothesis. While the large number of abnormal hemoglobins are important from many viewpoints, relatively few engage the interest of the practitioner in any particular locality. In the eastern part of this country, for instance, the hemoglobins most frequently encountered are those involved in sickle-cell disease, thalassemia (for the fetal hemoglobin content in the severe disease), or in combination with each other or with hemoglobin C. Also while few instances of hemoglobin E have been found in the United States, it is present in many native Thais but absent in pure Chinese living in Thailand. 18 The population composition in each geographic area necessitates, there-fore, familiarity with specific types, not alone for their significant anthropologic connotation but for the diagnosis and management of indigenous anemias. Knowledge in many related fields has been enriched by the investigation of the hereditary hemoglobinopathies. The biochemistry and physical behavior of the hemoglobins, their distribution throughout the world, and the quantitative aspects of genetic transmission factors which modify hemoglobin structure have provided information of basic importance beyond the immediate reference to the diseases which they influence. Finally, these studies have permittedan assessment of the forces involved in establishing hematopoietic equilibrium in the hemolytic anemias. One of the most striking features in this group is the capacity of the bone marrow to respond by intensified rates of hemoglobin and red cell production in states of excessive hemolysis so that anemia is averted. This concept of compensated hemolytic disease is of fundamental importance in the interpretation of the clinical and hematologic vicissitudes of patients suffering from blood disorders in which decreased longevity of the red cells is an outstanding feature.

Treatment of the anemias of infancy and childhood.

Summary The judicious administration of an antianemia agent implies not alone the restoration of normal blood levels but an inquiry into the pathogenesis of the anemia with a view to correcting the underlying cause. In this paper the treatment of anemias was integrated with a consideration of etiology and diagnosis. In infants, for instance, the basis of an anemia requires a search of the fetal period for an appraisal of the adequacy of iron storage, for evidences of maternal isoimmunization by fetal blood elements, for anemia in the mother, and for possible extrinsic causes which may have interfered with the normal continuity of antenatal development of the blood-forming organs. In contrast to adults, in whom blood levels are static, reference must be made to normal hematic values of corresponding periods of growth in determining the need for treatment and the efficacy of an antianemia agent in infants and children. Pending recognition of the nature of the anemia, interim treatment may be given. Orientation can be facilitated by employing data from indirect sources. The relationships between the red cell count, hemoglobin, and the volume of packed red cells offer important clinical clues to treatment. The mean corpuscular volume and the mean corpuscular hemoglobin concentration are practical guides for diagnosis and therapy in various groups of anemias. Conversely, the color index may prove unreliable in infants and children because of the physiologic fluctuations in hemoglobin and red cell counts with age. Recent advances in iron, folic acid, and transfusion therapy were reviewed in relation to the anemias of infancy and childhood. In common with all age periods, these advances have been marked by a greater selectivity of wellestablished drugs rather than by the addition of new antianemia agents. The choice of treatment of erythroblastosis by replacement or repeated small transfusions was discussed. A review of the methods and major indications for exsanguination transfusion indicate that many aspects of this form of therapy are in the process of development and evaluation. The organization of an outpatient transfusion clinic for the treatment of chronic anemias was described. The benefits to the anemic child and the practical advantages to hospital administration have been amply shown in the experiences at the New York Hospital. In the therapy of the group of aplastic anemias, it was pointed out that chronic congenital aregenerative anemia should be separated as a hematologic entity distinct from hypoplastic anemia. The evidence in a case history that was cited suggested that the pathogenesis of chronic congenital aregenerative anemia, an unusual blood disorder, might be related to early isoimmunization with a blood-group factor in an incompatible pregnancy. The hypothesis that a depression in red cell production results from an antigen-antibody reaction occurring in fetal life is far-reaching and requires further investigation. Finally, the specific treatment of the common anemias in infancy and childhood was summarized in conjunction with the diagnostic features of the respective blood smears.