Proliferative diabetic retinopathy in patients with defects of platelet function.

A 71-year-old woman had von Willebrand's disease, an inheritable abnormality of platelet activity, and developed diabetic retinal neovascularization. A 59-year-old man had a myeoloproliferative disorder with thrombocythemia but may have had retinal changes before the development of his platelet dysfunction. The occurrence of diabetic proliferative retinopathy in patients with reduced platelet activity suggests that platelet induced microcirculatory abnormalities may not be required for neovascularization.

The endocrine manifestations of hemochromatosis.

We have evaluated the endocrine changes in 10 male subjects with hemochromatosis. Two subjects initially had aplastic anemia, and the remainder had idiopathic hemochromatosis. Four of the ten patients had diabetes mellitus. Sexual dysfunction (impotence and/or decreased libido) was observed in 8 subjects. Six patients had subnormal testosterone levels; FSH levels were almost uniformly low, but LH concentrations were more variable. Only three patients had normal testosterone responses to hCG. Hypothyroidism, free T4 less than 0.9 ng/dl, was present in 4 subjects, and the etiology was heterogeneous. Basal prolactin levels were elevated in 2 patients and failed to respond adequately to TRH in 2 other patients. Growth hormone reserve was normal in all but 1 patient, and pituitary-adrenal reserve was normal in all but 1 patient. We conclude that disturbances in both pituitary and end-organ function are observed in hemochromatosis. These central and end-organ defects may exist alone or simultaneously. Hypogonadism is almost universal, and is a consequence of defective function of the hypothalamic-pituitary axis and/or primary Leydig cell disturbance. Other evidence of pituitary disturbance are observed but are rather uncommon.

Excess leukocytosis (leukemoid reactions) associated with malignant diseases.

Twenty-one patients with malignancy had a peripheral white blood cell count of 50,000/cu mm or more. The malignancies arose from several tissues, especially lung; all were carcinomas except for one osteogenic sarcoma. In no case was there evidence of leukemia as defined by disorderly marrow growth, abnormal chromosomes, or abnormal leukocyte alkaline phosphatase levels. The peripheral blood of these patients showed segmented neutrophils, bands, and occasional metamyelocytes. When young cells such as myelocytes were seen, they did not persist. A high WBC with malignancy is a late phenomenon, usually occurring shortly before death, and does not correlate with any pathologic findings such as necrosis, white cell infiltration of the tumor, or specific inflammatory changes. most of the associated tumors are of giant cell size, but serum showed no evidence of colony stimulating activity. This was true of two tumors reported in the literature, yet the tumors could be shown in vitro to produce colony stimulating activity. The tumor probably does produce some type of granulocytopoietin, but methods for detecting it are presently limited.

Hypocalcemia in leukemia.

Hypocalcemia is seen in patients with leukemia and is usually due to renal impairment or to low serum albumin concentrations. Four patients are reported who had hypocalcemia but without these usual explanations. One patient had chronic lymphatic leukemia and overwhelming infections which led to death. The other three patients had chronic myelogenous leukemia in an accelerated phase of the disease characterized by increasing blast cells in circulation, massive hepatosplenomegaly, and myelofibrosis. The cause of the hypocclcemia is unknown.

Fever in megaloblastic anemia.

Charts of 122 patients with megaloblastic anemia due to either B12 or folic acid deficiency were reviewed for the presence of fever. Fever, defined as a temperature of 100 F (37.8 C) or more, was present in approximately 40% of the patients with both. The elevation was usually minimal but was sometimes over 104 F (40 C), usually in those with more severe anemia and thrombocytopenia, and greater elevations of SGOT and bilirubin concentration. In uncomplicated cases, the temperature returned rapidly to normal after adequate vitamin therapy. Failure of the fever to disappear rapidly with treatment should suggest the probability of some cause other than megaloblastic anemia.

A test of time invariance in models of ferrokinetics.

Application of a particular mathematical property of time-invariant systems to experimental data obtained from injection and infusion of radioactive tracer iron in normal subjects is used to show that the generally applied assumption of time invariance to ferrokinetic systems is unjustified and may lead to substantial errors in analysis.

Specific health problems of Southeast Asian refugees in middle Tennessee.

Three diseases representative of specific health conditions affecting the Southeast Asian refugees living in middle Tennessee are leprosy (chronic bacterial infections), liver fluke infection (parasitic diseases), and hemoglobin E-beta-thalassemia (hematologic disorders). In this paper we discuss incidence, causative agent, mode of transmission, metabolic abnormalities, and management of these conditions.

Increased sensitivity to complement of erythroid and myeloid progenitors in paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria is an acquired hemolytic anemia characterized by a membrane defect leading to increased sensitivity of erythrocytes, granulocytes, platelets, and bone-marrow erythroid and myeloid cells to complement-mediated lysis. To determine whether the phenotype of paroxysmal nocturnal hemoglobinuria is also expressed on erythroid and myeloid progenitors, marrow cells from five patients with the disease were exposed to a sucrose hemolytic system and then assayed for colony-forming units-erythroid (CFU-E), burst-forming units-erythroid (BFU-E), and colony-forming units-granulocyte/macrophage (CFU-GM). A 50 percent or greater decrease in the numbers of erythroid and myeloid colonies was noted when marrow cells from the patients with paroxysmal nocturnal hemoglobinuria were exposed to a sucrose solution of low ionic strength in the presence of complement but not in its absence. Such a decrease was not noted in similarly treated normal marrow cells or in marrow cells from a patient with the disease in remission. These results suggest that in paroxysmal nocturnal hemoglobinuria, CFU-E, BFU-E, and CFU-GM express a membrane abnormality similar to that on erythrocytes, and that the disease is the result of a change occurring at the level of the pluripotent hematopoietic stem cell.

17 long arm isochromosome. A common anomaly in malignat blood disorders.

A cytogenetic anomaly consisting in the replacement of a 17 by its long arm isochromosome was identified as the only alteration in the marrow cells of two patients with acute granulocytic leukemia. In one case, the specific nature of the abnormal chromosome was established by newly available techniques. Since its identification in 1965, this structural anomaly, which implies 17 long arm duplication and short arm deletion, has been observed, as a sole or as an associated finding, in the malignant cells of a spectrum of blood disorders, including acute granulocytic leukemias, the blast crisis of chronic myeloid leukemia and lymphoreticular proliferative disorders. Attention is called to this particular rearrangement for its clinical as well as fundamental implications, as its presence in blood forming cells unfailingly hearalds a fast, fatal course of evolution.