ALBERT

Description: Two cases of aplastic anemia following gold therapy are presented, bringing the total number of reported cases to 20. In one of the cases BAL was unsuccessfully used therapeutically.

Description: The cardiac and respiratory adjustments in chronic anemia and their clinical manifestations have been reviewed. When the oxygen carrying capacity of the blood is diminished, an adequate supply of oxygen to the tissues is maintained by an increased cardiac output, an increased velocity of blood flow, and a relatively more complete abstraction of the oxygen from the blood as it passes through the capillaries. With the increased blood flow, the average peripheral resistance is decreased but the state of the small blood vessels is not uniform everywhere; the blood flow in the hands and kidneys, for instance, may be reduced, while that of other parts of the body is increased. The total oxygen consumption of the body in anemia is not strikingly altered. The blood volume generally is slightly reduced but the plasma volume is normal. The deviations from the normal values vary from patient to patient, but generally are definite when the hemoglobin values are less than 50 per cent and are greatest at the lowest levels of hemoglobin concentration. The close interrelationship between the cardiovascular and respiratory systems is exemplified by the coincident changes in the respiratory system in anemia. The rate and depth of respiration often are increased together with a lowering in the vital capacity and its subdivisions, the reserve and complemental air volumes. The resid- ual air is somewhat increased. These deviations from the normal are similar to those observed in pulmonary congestion or edema and denote a loss of elasticity and expansibility favoring the occurrence of exertional dyspnea. The arterial blood saturation is usually normal at rest but, during exertion, a significant lowering becomes apparent. The importance of hemoglobin in the transport of carbon dioxide is reviewed; the decreased availability of hemoglobin as a buffer in carbon dioxide transport in anemia is compensated by the increased ventilation of the blood in the lungs, rendering the arterial blood somewhat alkalotic. The red cells also play an important role in regard to the respiratory enzyme, carbonic anhydrase. In the anemias due to blood loss, malnutrition, chronic infection, uremia, or leukemia, the blood carbonic anhydrase activity is parallel to the decrease in hemoglobin level leading to a deficiency not only of oxygen carrying capacity but also a decreased ability to absorb carbon dioxide from the tissues and to release it in the lungs. The following factors, many of which are closely interrelated, are operative in the production of dyspnea in anemic patients: the increased respiratory minute volume, the decreased vital capacity and its subdivisions, the abnormalities in carbon dioxide transport and dissociation, the reduced arterial oxygen capacity and the decreased blood oxygen saturation during effort, and the frequently observed elevated blood lactic acid values. The symptoms and signs exhibited by anemic patients, including palpitation and breathlessness on exertion, tachycardia, cardiac dilatation and hypertrophy, are described. In addition to an apical systolic murmur, other systolic and diastolic murmurs are occasionally heard. The arterial blood pressure is frequently lowered in anemia; the venous pressure is generally within the limits of normal. Electrocardiographic abnormalities occur in approximately one-quarter of anemic patients but are minor and not specific in character. The occurrence of angina pectoris, congestive failure, and intermittent claudication in some patients with the development of anemia, and disappearance of these conditions as the anemia is alleviated, is discussed with particular reference to the underlying physiologic mechanisms.

Description: 1. The peripheral blood changes in uncomplicated kala-azar are those of pancytopenia; namely, anemia, leukopenia and thrombocytopenia. The red blood cell morphology is normal and there is very little evidence of increased erythrogenic activity. The leukopenia is due to a reduction in all types of cells, especially neutrophils. 2. When the disease is complicated by other infections the anemia is more severe and anisocytosis, poikilocytosis, and polychromatophilia may appear and normoblasts may occasionally be seen in the peripheral blood. Leukocytosis may develop, the leukopenia may persist or the syndrome of agranulocytosis may intervene. 3. As the duration of the disease increases, the spleen tends to become larger and the anemia, leukopenia and thrombocytopenia become progressively more severe. Leukopenia generally appears first, followed by anemia and finally thrombocytopenia. The degree of leukopenia, anemia and thrombocytopenia follow closely the degree of splenic enlargement. 4. The bone marrow in kala-azar is hyperplastic and infiltrated by reticulo-endothelial cells. In spite of this there appears to be an abundance of blood forming tissue, especially erythropoietic tissue. 5. Differential cell studies on preparations of sternal marrow reveal a marked reduction in the polymorphonuclear neutrophils and eosinophils. Myeloblasts, promyelocytes, neutrophilic myelocytes and metamyelocytes are present in approximately normal proportions as are the lymphocytes and monocytes. Plasma cells are somewhat increased. Erythroid cells, especially polychromatic normoblasts are numerous and the leukocyte-erythroid ratio is altered, more than the normal proportion of normoblasts being found. Megakaryocytes are present in normal or slightly reduced numbers. Staining abnormalities are noted in these cells and there is a striking reduction in platelet production. 6. During effective anti-leishmanial therapy parasitized reticulo-endothelial cells disappear and the percentage of reticulo-endothelial cells gradually diminishes as the polymorphonuclear neutrophils increase. There is a significant increase in the eosinophilic cells. Lymphocytes become more numerous and the plasma cells diminish in number. Nucleated red cells become less numerous and the leukocyte-erythroid ratio returns to normal. At the same time the proportion of orthochromatic normoblasts to polychromatic normoblasts increases. The relative number of megakaryocytes increases and platelet formation from the megakaryocytes is accelerated even beyond the normal. Huge groups of platelets are frequently seen in the marrow smears. A rise in platelets in the peripheral blood takes place late, after there has been a significant rise in hemoglobin and leukocytes. The three cellular elements are restored to normal in the peripheral blood in the same order as their reduction from normal. 7. Evidence is presented which contradicts the view that the pancytopenia is due to a crowding out of the bone marrow by reticulo-endothelial cells. 8. Certain similarities between the hematologic changes in this disease and those accompanying the hypersplenic syndromes are noted.

Description: The coagulation time is a measurement of the intrinsic power of the blood to convert fibrinogen to fibrin. It is an empirical test no matter how performed, and therefore in order to be reliable requires that the test be done on venous blood under strictly controlled conditions. A recommended procedure is outlined in detail. The coagulation time is prolonged in hemophilia, hypoprothrombinemia, afibrinogenemia and heparinemia. In hemophilia, the coagulation time theoretically is a measure of the severity of the disease but practically is of limited value since the coagulation time may be within normal limits in some patients; the prothrombin consumed in the coagulation of hemophilic blood is therefore a better guide for diagnosis. The coagulation time in hypoprothrombinemia is relatively little prolonged until a drastic reduction occurs. The test is therefore of no value for establishing a hemorrhagic condition in hypoprothrombinemia. In afibrinogenemia the blood is incoagulable. A small amount of fibrinogen restores the coagulation time to normal. The presence of heparin increases the coagulation time. The test is therefore useful in controlling the therapeutic action of this drug. The senior author, in making a survey of the literature on hemorrhagic diseases in preparation of his monograph, was impressed by the significant and diverse contributions which Dr. George R. Minot made to this field of medicine. We feel honored to contribute this study to the collection of papers offered as a fitting tribute to Dr. Minot, who has so successfully and productively combined science and clinical medicine.

Description: A method is described for the determination and charting of the fragility of the red blood cells to hypotonic sodium chloride solution. For plotting the results obtained, a new method was used, employing the principle of "hemolytic increments," i.e., plotting the additional amount of hemolysis occurring in each successive tube of solutions of decreasing saline concentration. By this method, curves are obtained somewhat similar to those of Price-Jones curves of red cell diameters. Such curves, when properly analyzed, afford an interpretation of the varying diameter thickness range of the red cell population and indirectly an insight into the types of red cells present, and of the possible hemolytic mechanisms present. Preliminary investigations indicate that they are particularly instructive in the hemolytic anemias and especially in the Mediterranean anemias. A simplified shorter method was also devised for routine clinical use. This method, although not as useful for research purposes, has proved to be more accurate and yet less time consuming than most methods currently used.

Description: 1. In individuals severely infested with Ancylostoma or Necator, it is possible to maintain the normality of blood value by the administration of a sufficient dose of an iron salt. 2. The minimum dose necessary to maintain normality of the blood in an individual weighing 45 kilograms, with 1051 helminths, was 0.2. Gm. daily of ferrous sulfate, administered in mixture with manioc flour. 3. The patient observed became clinically normal two weeks after the beginning of blood regeneration up to the end of the trial period one year later. In this period, with the various doses of iron tried, hemoglobin varied from 8.0 to 11.0 per 100 ml. of blood.

Description: 1. Data have been presented to show that most reticulocytes from patients with the sickle cell trait or sickle cell anemia sickle as readily as do more mature red blood cells. The most immature reticulocytes and normoblasts tend to sickle more slowly. 2. Orthochromatic normoblasts were the only type of normoblasts which sickled; the basophilic and polychromatophilic types could not be sickled. 3. It is suggested that the sickle cell forms seen in ordinary stained smears represent old cells which have lost their "elasticity" while stagnating in the sickle shape, and are unable to revert to a biconcave disk. This would explain the fact that these forms are so rarely found to be reticulated when stained with brilliant cresyl blue.

Description: I have tried to review and clarify steps leading to our present knowledge of pernicious anemia as a clinical and etiologic entity. The early history is most illuminating. The development of the present concept of this complicated disease is a triumph of medical research. Many great names both in clinical and research fields are associated with the advance in knowledge of pernicious anemia. Further research will almost certainly clarify problems still unsolved.