Transplantation of marrow to extramedullary sites.

Autologous fragments of transplanted marrow have survived in various extramedullary sites in the rat, rabbit, and dog. Survival of the fragments occurs with a complete reconstitution of the hemopoietic and adventitial structures. The process originates from a network of surviving reticular cells which proliferate and differentiate into osteoblasts and give rise to trabecular bone. Later, the reticular cells reconstruct the marrow's microcirculation. Hemopoietic repopulation of the marrow implant takes place only after its sinusoidal microcirculation has been established.

Fate of the nucleus of the marrow erythroblast.

Nucleated red cells lose their nuclei during passage through the endothelium of marrow sinuses. The passage occurs through cytoplasmic pores which are not gaps at the junction of two endothelial cells but perforations within the endothelium. Enucleation occurs because the pores are of relatively fixed size. Whereas the cytoplasm is flexible and squeezes through the pore, the nucleus is rigid and cannot conform to the pore size. It is, thus, caught, and the red cell becomes enucleated.

Bone marrow histogenesis: a comparison of fatty and red marrow.

Histogenesis of fatty marrow in extramedullary sites was compared to histogenesis of the red marrow. Both tissues undergo a similar sequence of events leading to reconstruction of hemopoietic marrow nodules. Histogenesis of yellow marrow then continues; such implants become nodules of fatty marrow, whereas implants of red marrow remain hemopoietically active. This observation supports the concept that histogenesis of the bone marrow recapitulates the ontogeny of this organ and indicates an intrinsic difference between the stroma of red and yellow marrow.

Chemical carcinogenesis. A soil fumigant, 1,3-dichloropropene, as possible cause of hematologic malignancies.

Findings from three case reports suggest a causal relationship between exposure to a soil fumigant , 1,3- dichloropropene , and hematologic malignancy. Its chemical relationship to other carcinogens is noted. The purpose of this report is to record this evidence and alert physicians that prior exposure to this chemical of patients initially observed with neoplasms should be noted in the medical history.

Blocking of iron absorption by a preliminary oral dose of iron.

Using a small-dose iron tolerance test (ITT) in mildly iron-deficient healthy adults, we have examined the phenomenon of mucosal block. First proposed and demonstrated by Hahn et al with radioiron, "mucosal block" describes diminished avidity for iron of the intestinal mucosa following an orally administered blocking dose. In the ITT, the index of absorption is an increase in plasma iron concentration, rather than retained radioactivity. The absorption of a blocked 10-mg test dose of iron was compared with that of a 10-mg control dose given to the same subject. Both 60- and 30-mg blocking doses of iron resulted in diminished absorption of the test dose. The refractory state of the intestine lasted as long as 24 hours.

Angiosarcoma with pulmonary siderosis and persistent reticulocytosis. Steroid responsiveness suggests an immune basis.

A 35-year old man with cough, hemoptysis, and dyspnea was found to have diffuse pulmonary infiltrates and iron-laden macrophages in the sputum. Pulmonary siderosis was confirmed by transbronchial biopsy. An associated hypochromic anemia required frequent transfusion. Though marrow iron stores were absent, reticulocytosis was maintained. Corticosteroid therapy resulted in cessation of hemoptysis, clearing of the pulmonary infiltration, and a substantial reduction in transfusion requirement. Splenectomy was of no benefit. The patient developed cerebral symptoms with seizures, and rapid deterioration led to cerebral symptoms with seizures, and rapid deterioration led to death. Disseminated hemangiosarcoma was found at autopsy. Steroid responsiveness of the associated pulmonary siderosis suggests that it had an immune basis.

Rapid assay for measurement of serum ferritin.

The authors present a rapid modification of the tube immunoradiometric assay for serum ferritin quantitation. The method involves gentle rotatory mixing of the tube contents at ambient temperature and can be performed in a few hours. Variables affecting different stages of the assay were systematically investigated. The performance characteristics of the shortened assay in terms of reproducibility, sensitivity and recovery were then validated. Results with this method correlate well with those obtained by the conventional assay.

Cytochemical diagnosis of acute myelomonocytic leukemia.

Blood and bone-marrow smears from adult patients with acute leukemias were stained for esterase reaction, consecutively with naphthol AS D-chloracetate (chloracetate esterase) followed by alpha naphthyl butyrate (nonspecific esterase). The two substrates were, respectively, granulocyte- and monocyte-specific. By this method three subgroups of acute nonlymphocytic leukemias could be distinguished. Leukemic cells may be positive for either chloracetate esterase or nonspecific esterases, and the authors believe these two subgroups represent "true" granulocytic and "pure" monocytic leukemias. In a third group, leukemic cells contained both esterases in the same cell, and it is believed this group may represent "true" myelomonocytic leukemias. In the majority of patients in this group, leukemia evolved from a preleukemic phase. When only Romanowsky-stained smears are used, the monocytoid feature and absolute elevated monocyte counts in acute granulocytic leukemia may lead to an erroneous diagnosis of the leukemia as acute myelomonocytic leukemia. This happened in five of the 13 cases in the study. The presence of granulocyte- and monocyte-specific esterases in a single cell supports the concept of a common origin of granulocytes and monocytes. The authors conclude that the combined esterase reaction can distinguish among acute granulocytic leukemia, acute monocytic leukemia, and acute myelomonocytic leukemia.

Practice guideline development task force of the College of American Pathologists. Hereditary hemochromatosis.

Hereditary hemochromatosis is an autosomal recessive disorder, the gene for which occurs in approximately 10% of Americans, most of whom are unaffected heterozygotes. Approximately 5/1000 white Americans are homozygous and at risk of developing severe and potentially lethal hemochromatosis. The disorder affects numerous organ systems, but the most common symptoms are fatigue, palpitations, joint pains, and impotence; the most common signs are those that relate to hypothalamic, cardiac, hepatic or pancreatic dysfunction, including poor cold tolerance, impotence in males, amenorrhea in females, cardiac arrhythmias, dyspnea, edema, hepatosplenomegaly, spider telangiectases, ascites, deformity, swelling or limitation of motion of joints, weight loss, hyperpigmentation. Characteristic abnormalities of laboratory tests include elevated serum iron concentration, high transferrin saturation, elevated serum ferritin concentration, elevated serum transaminases, hyperglycemia and low values for thyroid-stimulating hormone (TSH) and gonadotropins. Death may be the result of cardiac arrhythmia, congestive heart failure, liver failure or liver cancer. Since many of these complications cannot be reversed once they have developed, early diagnosis and treatment are essential. In view of the high prevalence in the American population (prevalence varies with ethnic background), the low cost of diagnosis and treatment, the efficacy of treatment if begun early, and, on the other hand, high costs and low success rate of late diagnosis and treatment, systematic screening for hemochromatosis is warranted for all persons over the age of 20 years. The initial screening should be by measurement of serum iron concentration and transferrin saturation. The practice guideline provides a diagnostic algorithm for cases in which the serum transferrin saturation is 60% or greater. It also provides guidelines for clinical management.

Spontaneous rupture of spleen in leukemic reticuloendotheliosis.

Leukemic reticuloendotheliosis, or "hairy cell leukemia," is a neoplasm of the reticuloendothelial system. It is characterized by the presence of many "hairy cells" in blood, marrow, lymph nodes, and spleen; by anemia, leukopenia, thrombocytopenia, and often, by massive splenomegaly. Three such patients with spontaneous rupture and one patient with multiple infarctions of the spleen all had spleens which were large, congested, and diffusely infiltrated by "hairy cells." The lacerations in all three ruptured spleens were located in areas of extensive infarction. Indications for splenectomy in this disease include hypersplenism, severe cytopenia, hemodilution, splenomegaly with severe pressure symptoms, massive splenomegaly, rupture, or infarction.

A history of phlebotomy therapy for hemochromatosis.

Hemochromatosis was recognized as an iron-storage disease for 50 years before it was proposed to treat it by removing hemoglobin. Davis and Arrowsmith are credited with the first report that demonstrated its value. Larger series have provided statistically valid evidence of improved quality of life and increased longevity. The earlier the disease is discovered, the less risk of morbidity and mortality. Screening tests (serum iron, total iron-binding capacity, serum ferritin) are recommended for all blood relatives of index cases of this hereditary disease and for all clinics where complications of hemochromatosis may be treated: liver disorder however mild, diabetes mellitus, heart disease, arthropathies, sterility, impotence, premature menopause, and abnormal pigmentation of the skin.

An historical sketch of splenic function and splenectomy.

Ideas about the spleen's functions as a blood filter, reservoir, scavenger of red cells and immunologic communication center are traced from the ancients to the present.

Clinical disorders of splenic function: the spectrum from asplenism to hypersplenism.

Pathophysiology, clinical manifestations and treatment of splenic disorders are viewed in terms of the broad spectrum of function ranging from asplenism through hypersplenism.