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Biomedical subjects

M E Conrad

Publications and source records attributed to M E Conrad.

At least 55 records · Page 3Linked to original sources

Ehrlichia canis: a tick-borne rickettsial-like infection in humans living in the southeastern United States.

During the past two years, sporadic cases of a rickettsial-like illness were reported in humans living in the Southeastern United States. The illness was serologically similar to Ehrlichia canis infections in dogs. It resembled spotless Rocky Mountain Spotted Fever but was differentiated from this infection serologically with acute and convalescent sera showing increasing titers to Ehrlichia canis. E. canis infection should be suspected in patients with fever, headache, malaise, myalgia, gastrointestinal symptoms, relative bradycardia, leukopenia, thrombocytopenia, and a recent exposure to either dogs or ticks. Although recovery has been observed in humans without treatment, prompt therapy with tetracycline is advised before obtaining results of serologic studies because an immunologically similar illness in untreated dogs has been lethal.

Animals↗

Ehrlichiosis: a cause of bone marrow hypoplasia in humans.

Infection with Ehrlichia canis should be suspected in patients with fever, headache, malaise, leukopenia, thrombocytopenia, and a history of recent exposure to ticks. The cytopenia is caused by bone marrow hypoplasia which may be severe. The disease may be confused with spotless Rocky Mountain spotted fever but can be differentiated from this infection serologically with acute and convalescent sea. In humans, recovery has occurred with and without antibiotic therapy. However, prompt antibiotic therapy is advised prior to serologic studies, especially in immunocompromised individuals, splenectomized persons, and patients with AIDS-who may develop a more overwhelming rickettsial infection.

Bone Marrow↗

Aplastic crisis in sickle cell disorders: bone marrow necrosis and human parvovirus infection.

Aplastic crisis in patients with sickle cell disease who develop a parvovirus infection may be associated with extensive bone marrow necrosis as well as acute selective erythroblastopenia. This illness may be manifested by pyrexia, lymphadenopathy, bone tenderness and significant hypoxemia with minimal roentgenographic findings in the lungs. It is uncertain whether the hypoxemia is caused by the effects of the viral infection on the lungs or is secondary to sickling of red blood cells in the pulmonary vasculature or both. The hypoxia may be sufficiently severe to require treatment with both oxygen and transfusion. The physical damage to the bone marrow associated with bone marrow necrosis may be more important than selective acute erythroblastopenia in inducing aplastic crisis in patients with sickle cell disorders. Studies of bone marrow biopsy specimens collected during parvovirus-associated aplastic crisis in patients with nonsickle cell hemolytic disorders would be helpful in determining the pathophysiology of parvovirus-associated disorders.

Acute Disease↗

Systemic necrotizing vasculitis in sickle cell disease.

A patient with sickle cell disease and systemic necrotizing vasculitis is reported. Although there are a number of immune defects in patients with sickle cell disorders, this association has not been previously reported. We suspect that immunologic disorders frequently are unrecognized in these patients because the symptoms are attributed to complications of sickle cell disease.

Adult↗

Prevention of endemic icteric viral hepatitis by administration of immune serum gamma globulin.

In a further analysis of a randomized, double-blind study of 107,803 U.S. soldiers receiving either immune serum gamma globulin (ISG) or placebo, serum specimens from the first week of clinical illness from 210 soldiers consecutively hospitalized with icteric hepatitis were reexamined by using modern immunologic methods to test for evidence of hepatitis A and B. Prophylactic intramuscular injection of 5 or 10 ml of ISG containing antibody to hepatitis A virus and antibody to hepatitis B surface antigen provided significant protection against development of endemic type A, type B, and non-A, non-B icteric hepatitis for six months if it was administered before exposure. Failure to receive a second injection of either 5 or 10 ml of ISG permitted an occurrence of hepatitis that was not significantly different from that among subjects who failed to receive a second placebo injection. ISG at 2 ml appeared equally effective in preventing hepatitis A but may be less effective in preventing hepatitis B and non-A, non-B hepatitis.

Hepatitis A↗

Mycosis fungoides: carcinogens and cerebral involvement.

Three patients with mycosis fungoides, who were long-term employees of a manufacturer of solid fuel propellants, were seen. Two of these patients had tumorous involvement of the central nervous system, which was successfully treated with radiation therapy. The potential relationship of carcinogens is discussed.

Brain Neoplasms↗

Small intestinal regulation of iron absorption in the rat.

Ultrastructural, biochemical, and immunologic studies of the small intestinal mucosa of rats were undertaken to investigate factors associated with the regulation of iron absorption. The quantity of iron within mucosal cells was proportionate to the degree of iron repletion. Although the quantity of iron-binding substances was similar in iron-deficient and iron-loaded animals, the unsaturated iron-binding capacity of mucosal cells varied inversely with the state of iron repletion of animals in ultrastructural, biochemical, and immunologic observations. Although only certain mucosal cells contained iron-binding substances, their number was not increased in iron-deficient animals. Greater quantities of iron and iron-binding substances were observed in duodenal mucosa than in ileal mucosa. These findings are consistent with the hypothesis that the quantity of unsaturated iron-binding substances within intestinal mucosal cells regulates iron absorption. These findings are only partially explained by changes observed in the concentration of ferritin and transferrin within intestinal mucosa and suggest that other iron-binding substances may also participate in the regulation of iron absorption.

Animals↗

Treatment of thrombotic thrombocytopenic purpura. Plasmapheresis, plasma transfusion, and vincristine.

In four patients with thrombotic thrombocytopenic purpura (TTP), the administration of plasma exchange and vincristine sulfate was associated with reversal of clinical and hematologic evidence of disease. Plasmapheresis with fresh frozen plasma replacement appears effective in acutely improving neurologic and hematologic abnormalities of patients with TTP and provides time for vincristine to become effective and induce lasting remissions. One patient with early relapse responded to a second short course of vincristine without other therapy. These data suggest that these treatment modalities should be considered as the initial treatment of TTP.

Adolescent↗

Ultrastructural localization of transferrin, transferrin receptor, and iron-binding sites on human placental and duodenal microvilli.

Ultrastructural methods were used to determine the subcellular location of the transferrin receptor, transferrin and iron-binding sites on human term placenta and human duodenum microvillus surfaces. The transferrin receptor and transferrin were localized by immunocytochemical methods employing either OKT9, a human transferrin receptor monoclonal antibody, or mouse anti-human transferrin (ATfn), both followed by a horseradish peroxidase (HRP)-conjugated goat anti-mouse IgG (GAM-HRP) and diaminobenzidine (DAB) sequence. Iron-binding sites were localized by acid ferrocyanide (AF) staining after saturation of tissue specimens with iron, accomplished with iron nitrilotriacetate (FeNTA), a known transferrin iron donor. Placental microvillus surfaces demonstrated staining for the OKT9-GAM-HRP-DAB-reactive transferrin receptor, ATfn-GAM-HRP-DAB-reactive transferrin, and FeNTA-AF-reactive iron acceptor, whereas enterocyte microvillus surfaces lacked significant staining with each of these methods. FeNTA-AF stained iron-binding substance in placental and enterocyte microvilli and cytoplasmic matrix. Thus using the same ultrastructural immunostaining and cytochemical methods transferrin receptor, transferrin, and nitrilotriacetate iron acceptor sites can be demonstrated on the microvillus surface of human placenta but not on the microvillus surface of human duodena.

Binding Sites↗

Ultrastructural cytochemical identification of the siderophilic enterocyte.

Specific iron-binding sites in the gut were visualized by the sequential incubation of glutaraldehyde-fixed specimens in iron nitrilotriacetate (FeNTA) and acid ferro-cyanide (AF). In rat duodenum, jejunum, and ileum, approximately half of the enterocytes from the crypt to the distal villus contained FeNTA-AF-reactive material. The staining intensity of individual enterocytes appeared to decrease progressively in more distal locations in the gut. Maximal FeNTA-AF staining was observed in cells in the upper half of the villus, and was localized primarily in microvilli, apical cytoplasm, and lateral membranes. In duodenal crypt cells, stain deposits were present primarily in the microvilli. FeNTA-AF stained sites in the cytoplasmic and microvillus matrix were approximately 100-fold greater in number than were sites of intrinsic iron stained with AF alone. FeNTA-AF and AF staining in human duodenal enterocytes was similar to that observed in rat duodena, demonstrating the applicability of this methodology to human samples. In rat duodena, the distribution of AF staining alone in specimens taken 10 min after the in vivo intraduodenal administration of FeCl2 was similar to that of FeNTA-AF staining in tissue from fasted animals not given iron. The distribution and frequency of iron-binding sites stainable with the FeNTA-AF method which occur in a subpopulation of enterocytes can be correlated closely with physiologic, histologic, and ultrastructural parameters of inorganic iron absorption previously reported.

Animals↗

New instrumentation in urinalysis.

Automated instrumentation and electronic data processing now assist in performing and standardizing urinalyses. These innovations include specific gravity instruments and reagent "strip readers," and one system designed to automate the physical, chemical, and microscopic urinalysis. In this article, the author reviews the features of some examples of these new instruments.

Autoanalysis↗

Febrile transfusion reaction following initial transfusion in a man with immunoblastic lymphadenopathy and granulocyte autoantibodies.

A 69-year-old man with immunoblastic lymphadenopathy and autoimmune hemolytic anemia who had no previous exposure to blood products developed a severe febrile nonhemolytic transfusion reaction following the initial infusion of packed red blood cells. The reaction recurred with transfusion of packed red blood cells, but not when freeze-thawed red blood cells were used. Immunofluorescence techniques demonstrated granulocyte antibodies in his serum and on the surface of his granulocytes. Circulating immune complex, HLA, and platelet antibodies were not present. The granulocyte antibodies fluctuated in titers with disease activities, and could be completely removed from the serum by autologous granulocyte absorption. We conclude that our patient had granulocyte autoantibodies which probably produced febrile transfusion reactions.

Aged↗

Calcium inhibition of inorganic iron absorption in rats.

Calcium significantly diminishes the absorption of ferrous and ferric iron in a dose-related manner, whether the test doses of calcium and radioiron are administered orally or introduced into isolated intestinal segments; the effect is maximal in the duodenum and jejunum. Electron microscopic observations and quantitative studies of the mucosal uptake and transfer of iron show that calcium decreases the entry of iron into the microvilli of intestinal epithelial cells. Animals fed a high-calcium, iron-replete diet developed iron depletion; animals consuming high-calcium food of marginal iron content developed mild iron deficiency anemia. Further, more radioiron was absorbed from human milk than either bovine milk or human milk supplemented with calcium. These data suggest that individuals consuming a high-calcium diet contain marginal amounts of iron could develop iron deficiency anemia and may explain why infants who are fed cow's milk have a greater incidence of iron deficiency anemia than those fed human milk.

Anemia, Hypochromic↗

Studies of nicotinamide adenine dinucleotide methemoglobin reductase activity in a Jewish population.

In the original study of the deleterious effects of oxidant drugs on persons heterozygous for nicotinamide adenine dinucleotide reductase (NADH MetHb R) deficiency, several Jewish physicians used as controls had decreased enzyme activity. We collected blood samples from 555 Jewish persons to 1) estimate the heterozygote frequency for NADH MetHb R deficiency; and 2) determine if external variables such as age, gender, and ingested medications may alter the NADH MetHb R activity and thereby alter estimates of heterozygosity. Two persons possibly heterozygous for the deficiency were identified (carrier incidence = 1/309,000 jewish births). A difference in enzyme activity was found between males and females (P less than 0.03). We have examined the influence of the mean red cell age on the activity of erythrocyte NADH MetHb R and found it not to be materially influenced by mean red cell age; thus the possible intersex differences of mean red cell age cannot explain this observation. No significant difference (P greater than 0.1) was seen between persons ingesting the following drugs and those not: Dilantin; antidepressants/sedatives; cardiac, antineoplastic, or antigout/antiinflammatory drugs; thyroid supplements, estrogen-containing preparations, and antihistamines. NADH MetHb R activity did not correlate with age or spontaneous abortion. We conclude that heterozygosity for NADH MetHb R deficiency is not prevalent among Ashkenazic Jewish persons, and that external variables should be considered to ensure accurate interpretation of NADH MetHb R activity for correct estimation of heterozygosity.

Adolescent↗

Factors affecting iron balance.

The availability of radioisotopes of iron led to the performance of physiologic studies of the absorption, excretion, and kinetics of iron. The effects of dietary constituents and intestinal secretions upon iron absorption have been thoroughly explored and have permitted the development of tools for nutritional studies in various geographic areas of the world. The basic mechanisms for regulation of iron absorption are not fully understood. However, the isolation and characterization of newer iron-binding proteins, the existence of mucosal receptors in which there is competition for iron-binding sites with other metals, and the identification of a number of animal models with genetic abnormalities of iron absorption provide promise for development in the foreseeable future. The means by which the body informs the intestine to increase or decrease iron absorption is poorly understood, and the abnormality in hemochromatosis and iron overloading disorders remains unexplained. Much has been learned in recent years regarding the structure of iron-containing proteins and the variations that exist in different species. Similar problems remain to be solved with regard to the intermediary metabolism of iron in red blood cell precursors and other cells in the body. It is postulated that the combined usage of physiologic, biochemical, and immunologic investigations will provide the basic information required.

Absorption↗