George E. Cartwright

Homozygosity for Hemochromatosis: Clinical Manifestations

We identified 35 homozygotes for hemochromatosis through pedigree studies. Thirteen were asymptomatic. Arthropathy was present in 20, hepatomegaly in 19, transaminasemia in 16, skin pigmentation in 15, splenomegaly in 14, cirrhosis in 14, hypogonadism in six, and diabetes in two. No homozygote was in congestive failure. Only one had the triad of hepatomegaly, hyperpigmentation, and diabetes. Serum iron was increased in 30 of 35, transferrin saturation was increased in all 35, serum ferritin in 23 of 32, urinary iron excretion after deferoxamine in 28 of 33, hepatic parenchymal cell stainable iron in 32 of 33, and hepatic iron in 27 of 27. Iron loading was 2.7 times greater in men than in women. No female had hepatic cirrhosis. Diagnosis of asymptomatic hemochromatosis is important because organ damage may be prevented by early therapy. Clinical diagnosis of early hemochromatosis is difficult. Persons with unexplained elevation of transferrin saturation should be studied for hemochromatosis.

Diurnal Variation in the Plasma Iron Level of Man.

Summary It has been shown that the plasma iron of man undergoes a regular diurnal variation. These results have been compared with those of other investigators.

Studies on copper metabolism XXIX: A critical analysis of serum copper and ceruloplasmin concentrations in normal subjects, patients with Wilson's disease and relatives of patients with Wilson's disease☆

Abstract 1.1. Total copper and ceruloplasmin concentrations have been determined in the serums of normal subjects, patients with Wilsons disease and relatives of patients with Wilsons disease. 2.2. Total serum copper was determined in 205 normal subjects. The mean value ±1 standard deviation (S.D.) was 114 ± 17.4 μg./100 ml. In two subjects the values were 68 μg./100 ml.The mean value ± 1 S.D. in thirty-six patients with Wilsons disease was 61 ± 20.8 μg./100 ml. In seven patients the values were within 2 S.D. of the normal mean. Five normal relatives of patients with Wilsons disease were found to have serum copper values below 79 μg./100 ml. 3.3. Calculation of ceruloplasmin values from the 205 normal serum copper values gave a normal range, defined as ±2 S.D., of 23 to 44 mg./100 ml. Ceruloplasmin was measured immunologically in ten normal subjects. The mean value ±1 S.D. was 34 ± 4.0 mg./100 ml. The immunologically determined values for ceruloplasmin in the two normal subjects with low serum copper values were 14 to 22 mg./100 ml. By the same method the mean value ±1 S.D. in twenty-eight patients with Wilsons disease was 9 ± 5.2 mg./100 ml. In all twenty-eight patients the value was less than 23 mg./100 ml. Ceruloplasmin values between 19 and 23 mg./100 ml. were observed in eight normal relatives of patients with Wilsons disease. 4.4. Within the group of patients studied there was poor correlation between the ceruloplasmin concentration and the duration and severity of the clinical manifestations. 5.5. It is suggested that a decreased concentration of ceruloplasmin is not the single uncomplicated determinant of the disease.

Diagnosis of treatable Wilson's disease.

IT is a tragedy for patients, their families and their physicians when the physician fails to make the diagnosis of a progressive and fatal disorder that is treatable. Wilsons disease is such a di...

Association of HLA-linked hemochromatosis with idiopathic refractory sideroblastic anemia.

Five of seven patients with idiopathic refractory sideroblastic anemia carried an HLA-A3 alloantigen (relative risk, 7.3; P = 0.02). The significance of this association was strengthened by study of two pedigrees. An abnormality in iron metabolism was found in two siblings who had an HLA-A3,B14 haplotype in common with the first proband. A second proband with idiopathic refractory sideroblastic anemia had clinically manifest hemochromatosis. His brother had clinically manifest hemochromatosis but not sideroblastic anemia. This proband and his brother shared only the HLA-A3,B12 haplotype. Our findings infer that patients with idiopathic refractory sideroblastic anemia carry a single allele for hemochromatosis, that this allele accounts for the increased iron loading in this form of anemia, and that clinically manifest hemochromatosis may develop in an occasional patient with only one allele for hemochromatosis in the presence of the sideroblastic factor.

CHEMOTHERAPY OF LEUKEMIA, HODGKIN'S DISEASE AND RELATED DISORDERS

Excerpt The object of this report is to discuss the chemotherapy of leukemia, Hodgkins disease and the related disorders in the light of our own experience since the development of interest in thi...

Ferritin metabolism in reticulated-siderocytes

Reticulated-siderocytes (reticulocytes which contain siderotic granules), obtained from the circulation of pigs after vigorous phlebotomy, were incubated in vitro. A rapid disappearance of granules from the reticulocytes was observed over 24 hr. Simultaneously with the decrease in granules, soluble ferritin accumulated in the media and siderotic granules developed in monocytes. The disappearance of the granules from the reticulated-siderocytes was oxygen-dependent and the loss of granules and the accumulation of ferritin in the media were both prevented by the addition of cyanide or dinitrophenol. It is concluded that the ferritin aggregates in the granules of reticulated-siderocytes are dispersed intracellularly into soluble ferritin, that soluble ferritin is excreted from the cell, and that one or both of these steps is dependent upon oxidative metabolism. Blood monocytes are capable of taking up soluble ferritin from the media and converting this into siderotic granules. Thus, a reticulocyte to plasma to monocyte ferritin pathway has been described.

Pyridoxine-Responsive Anemia

HYPOCHROMIC, microcytic anemia combined with normal or elevated serum iron is a syndrome characteristically found in patients harboring the thalassemia gene. This syndrome is also encountered in so...HYPOCHROMIC, microcytic anemia combined with normal or elevated serum iron is a syndrome characteristically found in patients harboring the thalassemia gene. This syndrome is also encountered in so...

Studies on the Osmotic Resistance of Incubated Leptocytes.

Excerpt Erythrocytes from patients with thalassemia minor, iron deficiency anemia, liver disease associated with the target cells and an example of elliptocytosis were studied. These red cells are ...