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Biomedical subjects

M E Conrad

Publications and source records attributed to M E Conrad.

At least 91 records · Page 5Linked to original sources

Beneficial effects of hepatitis in patients with acute myelogenous leukemia.

Of 50 consecutive patients admitted with acute myelogenous leukemia, 30 developed complete remissions on antileukemic therapy. Nineteen of the 30 repeatedly had elevated serum glutamic oxalacetic transaminase (SGOT) concentrations 3 to 14 weeks after the start of therapy. Patients with SGOT elevations had a significantly greater chance of remission and a longer survival (76 +/- 11 weeks) than those with normal SGOT levels (39 +/- 5 weeks), suggesting that hepatitis may have a beneficial effect in acute myelogenous leukemia. The hepatitis was mild in all patients. Review of patients at this institution alive 2 years after the diagnosis of acute myelogenous leukemia showed that they repeatedly had elevated SGOT levels. We believe that most had non-A, non-B post-transfusion hepatitis, which may have a beneficial effect on the leukemia or serve as an indicator of patients who have greater immunocompetence and thus a better prognosis.

Adolescent↗

Pseudochloroma: extramedullary hematopoietic nodules in chronic myelogenous leukemia.

Five patients with chronic myelogenous leukemia had multiple hemorrhagic soft tissue lesions at the time of diagnosis. Histologic examination of tissue removed by biopsy and at autopsy revealed extramedullary hematopoietic nodules with associated hemorrhage and necrosis. No evidence of either blastic transformation or systemic bleeding diathesis was found. Pseudochloroma is a treatable although potentially fatal complication of uncontrolled chronic myelogenous leukemia and should not be confused with myeloblastomas occurring with blastic transformation. Early recognition of the syndrome, prompt treatment with intensive chemotherapy, and radiation therapy of intracranial lesions seem to provide effective control of this complication and reversion to a status that is responsive to conventional treatment of chronic myelogenous leukemia.

Adult↗

Ultrastructural radioautography and cytochemistry of lead absorption.

Lead is a universal environmental contaminant absorbed largely through the gastrointestinal tract by unknown mechanisms. Because lead absorption is influenced by iron content in the body and diet, we used ultrastructural radioautography and cytochemistry to study absorption of physiologic lead doses in the rat duodenal epithelial cell and compared these findings to those previously reported for iron absorption. Rat duodenal loops exposed in vivo to 210Pb for 1 minute demonstrated the majority of labels on the microvilli, terminal web, and apical cytoplasm. Specimens exposed to radiolead for 10 minutes demonstrated more abundant labeling with a relative increase in labeling of epithelial cell mitochondria, nuclei and basal cytoplasm, as well as phagocytic cells, endothelial cells, and circulating erythrocytes of the lamina propria. Timm's sulfide-silver method localized trace metals in epithelial cells. After administration of lead, a significant increase in staining was observed in microvilli, mitochondria, non-membrane-bound cytoplasm, and nuclear chromatin. The rapid appearance of absorbed lead in epithelial cell mitochondria and nuclei, as well as phagocytic cells in the lamina propria, was distinctly different from that reported for absorbed iron and suggests different mechanisms for the subcellular transport of these cations. The combination of radioautography and Timm's sulfide-silver staining provides the specificity and resolution needed for ultrastructural evaluation of lead absorption and should be useful in further studies of lead metabolism.

Animals↗

Bone marrow necrosis and degeneration.

Bone marrow necrosis, regarded as a rare finding in specimens from living patients, has been associated with a poor prognosis in patients with serious hematologic diseases and metastatic carcinoma. Two patients with extensive idiopathic bone marrow necrosis and a relatively benign course of illness were found. Therefore, we examined 500 consecutive bone marrow biopsy specimens that were obtained in a university hospital complex. Review of this material showed evidence of necrosis and degenerative changes of variable severity in one third of the biopsy specimens. It was found with approximately the same incidence in patients who underwent bone marrow biopsy for either neoplastic or nonneoplastic disorders; an increased prevalence was not observed in the group of patients who had received chemotherapy. Based on these observations, we believe necrosis and degeneration of the bone marrow is a commonplace finding that is frequently overlooked in a wide variety of acute and chronic disorders, and that requires further investigation to determine its clinical importance.

Aged↗

Splenectomy for hematologic disease.

One hundred and thirty splenectomies were performed at the University Hospital in Birmingham for hematologic disorders during a 12 year period. There were seven deaths of which four were related to sepsis in patients with malignant growths which probably impaired immune competence. Splenectomy was found to be uniformly satisfactory for hereditary hemolytic anemia, for hypersplenism complicating rheumatoid arthritis and for the rare instance of primary hypersplenism. Splenectomy was usually salutary in didopathic thrombocytopenic purpura and in antoimmune hemolytic anemia. When done for diagnosis, splenectomy was definitive in about 50 per cent of the instances. Individual patients with thrombotic thrombocyeosinophilia syndrome benefited. Splenectomy for hypoplastic or aplastic anemia in an actual circulation offered only questionable benefit and is rarely necessary for hyperplenism secondary to portal hypertension.

Adult↗

Association of presenile cataracts with heterozygosity for galactosaemic states and with riboflavin deficiency.

Red cells and the lens of the eye are non-nucleated cells; moreover, they have metabolic similarities. Cataracts develop in childhood in homozygotes for galactosaemic abnormalities, which can be detected by biochemical measurements in red blood-cells. It has not been determined whether heterozygotes for these defects are at greater risk for cataract development later in life. Similarly, riboflavin deficiecy for which the erythrocyte is a sensitive indicator, has been associated with cataracts in animals. Red-cell studies were carried out in 22 patients, aged under 50, with cataracts. Heterozygosity for galactokinase deficiency was detected in 5 patients, for galactose-uridyl transferase in 2, and evidence of an erythrocytic deficiency of riboflavin in 8. Even when Black subjects were excluded from analysis because of their high incidence of polymorphism for galactokinase, these findings are significantly different from those expected from population surveys and suggest that many patients with presenile cataracts have a biochemical abnormality which can be detected by examination of red blood-cells and which may be corrected by dietary restrictions or supplements.

Adolescent↗

Effects of calcium on the absorption and retention of lead.

An inverse relationship between lead retention and dietary calcium content has been known to exist for many years, but the reasons for this association remained unknown. In rats, the manipulation of dietary calcium had no significant effect upon the absorption of lead, but calcium-deprived animals had decreased excretion and thus increased body retention of lead. Intraluminal calcium decreased the absorption of test doses of lead from the small intestine in a dose-related manner. We postulated that this occurred because the two metals competed for similar binding sites on intestinal mucosal proteins which were important in the absorptive process. In vivo, lead bound to two heat-stable intestinal mucosal fractions which have been shown to bind calcium. Although more lead bound to the higher molecular weight fraction and more calcium bound to the lower molecular weight vitamin D-induced CaBP, substantial amounts of lead and calcium were found in both fractions. Further, the addition of calcium to test doses of lead markedly diminished the amount of lead bound by both fractions. Shared binding sites on absorptive proteins would explain why dietary calcium decreases lead absorption.

Animals↗

Factors affecting the absorption and excretion of lead in the rat.

A reliable method for studying lead absorption and excretion in rats is described. Lead absorption occurs primarily in theduodenum where lead enters the epithelial mucosal cells. There is a relative mucosal block for lead with increasing intraluminal doses. Certain substances which bind lead and increase its solubility enhance its absorption. Iron, zinc, and calcium decrease the absorption of lead without affecting its solubility, probably by competing for shared absorptive receptors in the intestinal mucosa. The total body burden of lead does not affect lead absorption. Thus, lead does not have a feedback mechanism which limits absorption. Lead absorption is increased during rapid periods of growth and in iron-deficient animals. It is diminished with starvation and in iron-overloaded animals. The excretion and kinetics of tracer doses of radiolead were quantified. Erythrocytes seem to serve an important role in transport. Excretion occurs in urine and stool. Bile is an important route of excretion in the gut. Although most of a tracer dose is rapidly excreted, the excretory process is limited permitting lead accumulation primarily in bone.

Anemia, Hypochromic↗

Effects of iron on the absorption and retention of lead.

An inverse relationship between lead retention and dietary iron content has been suspected for many years, but the reasons for this association remained unknown. In rats, the state of body iron repletion had significant effects on the absorption of lead but no effect on lead excretion. Intraluminal iron decreased the absorption of test doses of lead from the small intestine in a dose-related manner. We postulated that this occurred because the two metals competed for similar binding sites on intestinal mucosal proteins which were important in the absorptive process. In vivo, both lead and iron bound to two heat-stable intestinal mucosal fractions, particularly the higher-molecular-weight fraction. Addition of iron to test doses of lead markedly diminished the amount of lead bound by the high-molecular-weight fraction. Further investigation revealed that this fraction, with a molecular weight of approximately 370,000, bound both lead and iron. Shared binding sites on this protein may explain why dietary iron decreased lead absorption and iron deficiency increased it.

Animals↗

Ultrastructural cytochemistry of iron absorption.

Conventional ultrastructural autoradiographic and morphologic studies of the duodenal mucosal cell have generally corroborated physiologic observations of iron absorption, but such methods have limited resolution and fail to distinguish ferric and ferrous iron. This study describes the application of the Prussian blue reaction as an electron microscopic cytochemical stain to the investigation of inorganic iron absorption in iron-deficient, normal, and iron-loaded rats. Ferrous iron is converted to ferric iron at the microvillus membrane. Subsequently intraepithelial ferric iron appears bound to a non-heme acceptor substance in microvilli and later appears as small non-membrane-bound stain deposits which are concentrated in the apical cytoplasm. The appearance of larger stain deposits in the lateral intercellular spaces, in the basal extracellular spaces, and along the intraluminal and extraluminal outer plasmalemma of adjacent endothelial cells of the lamina propria suggests passage of iron from epithelial cells through the lamina propria to blood vessels. The extreme sensitivity of the method compared with simultaneous ultrastructural autoradiographic techniques is demonstrated and suggests usefulness of the method in further studies of iron metabolism.

Animals↗

von Willebrand's disease and hemorrhagic telangiectasia: association of two complex disorders of hemostasis resulting in life-threatening hemorrhage.

The clinical and laboratory findings in a patient with uncontrolled gastrointestinal bleeding secondary to combined hemostatic defects (von Willebrand's disease and hemorrhagic telangiectasia) are described. Evidence for von Willebrand's disease was found in five family members, but no other affected relative was found to have hemorrhagic telangiectasia. Complete assestivity, factor VIII antigen and von Willebrand factor levels. The patient described also was evaluated for her response to transfusion utilizing these same measurements. Previous reports of the coexistence of hemostatic defects with hereditary hemorrhagic telangiectasia are reviewed. The importance of complete hemostatic evaluation of patients with mucocutaneous bleeding is stressed in light or current knowledge of the diagnostic specificity of available laboratory tests.

Blood Coagulation Tests↗