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Biomedical subjects

D C Dale

Publications and source records attributed to D C Dale.

At least 127 records · Page 7Linked to original sources
PubMed1978

Canine cyclic hematopoiesis: effects of chronic endotoxin administration.

Endotoxin was given to grey collie dogs to investigate the mechanism of cyclic hematopoiesis. Over prolonged periods of daily administration, low doses of endotoxin (0.1 microgram/kg/day) failed to change the cycling of blood neutrophils or reticulocytes. However, higher doses of endotoxin maintained at a plateau level (5 microgram/kg/day) eliminated the cyclic changes in neutrophils and stabilized the reticulocyte and platelet counts in the normal range. Administration of endotoxin at this dose also eliminated the cyclic marrow differential count fluctuations characteristic of this disease. We infer from these results that endotoxin ameliorates the cyclical changes in blood cell counts by regulating hematopoietic proliferative activity at the stem cell level.

Animals↗
PubMed1977

Aetiocholanolone and prednisolone therapy in patients with severe bone-marrow failure.

Ten patients with bone-marrow failure from myelofibrosis, aplastic anaemia, paroxysmal nocturnal haemoglobinuria, and "hairy cell" leukaemia, who had failed to respond to androgens and/or glucocorticosteroids, were treated with a combination of aetiocholanolone and prednisolone. All patients except one with aplastic anaemia responded with an increase in reticulocytes, haematocrit, red blood cell mass, and blood neutrophils and platelets. These data suggest that aetiocholanolone, and similar 5beta-hydroxy steroids, may be valuable in treating certain patients with chronic marrow failure.

Adult↗
PubMed1977

Neutrophil preservation: the effect of short-term storage on in vivo kinetics.

A rabbit model was developed to study the in vivo viability of neutrophils stored in vitro for up to 72 h. Acid-citrate-dextrose anticoagulated whole blood was obtained from rabbits previously injected with tritiated thymidine ([3H]thymidine), stored under varying conditions, and then injected into recipient rabbits. Neutrophil viability and function were assessed by measuring the ability of the tagged neutrophils to circulate and to migrate into subcutaneous polyvinyl sponges. Unstored neutrophils disappeared exponentially from the circulation with a t1/2 of 3.2 h and gave a zero time recovery of 30.5%. Storage of cells at either room temperature or 4 degrees C for 24 h or longer resulted in temporary sequestration of cells from active circulation. With cells stored for up to 72 h at 4 degrees C, recovery returned to normal values after 1-2 h. Room temperature stored cells, in contrast, showed evidence of irreversible damage at 48-h storage with low recovery for the entire time span studied. With unstored blood, 8.1+/-0.9% of the injected neutrophil label was present in the subcutaneous sponges. The accumulated label progressively decreased as cell storage time increased reaching at 72 h 5.1+/-0.6 and 2.6+/-0.3% for 4 degrees C and room temperature-stored cells, respectively. The results of this study indicate that 4 degrees C storage of rabbit neutrophils is superior to storage at room temperature. The data suggest that it may be feasible to store neutrophils at least a few days without loss of in vivo functions.

Animals↗
PubMed1976

Changes in the composition of canine respiratory cells obtained by bronchial lavage following irradiation or drug immunosuppression.

Canine respiratory cells, obtained by bronchial lavage, and blood leukocytes were monitored to observe cellular changes following acute and chronic immunosuppression. Irradiation (350 R) produced bone marrow suppression and prompt peripheral blood leukopenia, but did not affect recovery of pulmonary alveolar macrophages or lymphocytes for 12 days after. Treatment for 6 weeks with daily methylprednisolone (1 mg/kg) caused a progressive decrease in the number of recoverable respiratory lymphocytes, whereas alternate day methylprednisolone (2 mg/kg) had less effect. Cyclophosphamide in combination with steroids generally augmented the progressive loss of blood and respiratiory lymphocytes. Recovery of alveolar macrophages was not changed appreciably. Thus, the population of lung macrophages, sampled by pulmonary lavage, withstood acute and chronic forms of immunosuppression very well. In contrast, canine lymphocytes seem more susceptible to injury, especially to drug regimens containing steroids.

Animals↗
PubMed1976

Glucocorticosteroid therapy: mechanisms of action and clinical considerations.

The administration of glucocorticosteroids results in a wide range of effects on inflammatory and immunologically mediated disease processes. Glucocorticosteroids cause neutrophilic leukocytosis together with eosinopenia, monocytopenia, and lymphocytopenia. A principal mechanism whereby corticosteroids suppress inflammation is their impeding the access of neutrophils and monocytes to an inflammatory site. Granulocyte function is relatively refractory, whereas monocyte-macrophage function seems to be particularly sensitive to corticosteroids. Corticosteroid administration causes a transient lymphocytopenia of all detectable lymphocyte subpopulations, particularly the recirculating thymus-derived lymphocyte. The mechanism of this lymphocytopenia is probably a redistribution of circulating cells to other body compartments. There is considerable disagreement about the direct effects of corticosteroid administration on human lymphocyte function. The corticosteroid regimen should be adjusted to attain maximal therapeutic benefit with minimal adverse side effects. Often, alternate-day dosage regimens effectively maintain disease remission with minimization or lack of Cushingoid and infectious complications.

Animals↗
PubMed1976

Colony-stimulating factor in patients with chronic neutropenia.

Urinary and serum colony-stimulating factor (CSF) levels were measured in 11 patients with chronic idiopathic neutropenia without infections and in 10 normal individuals. Urinary CSF output was determined using mouse marrow target cells, and serum CSF activity was assayed with human marrow target cells by the double agar layer technique. Using these methods, there was no significant difference between CSF levels of neutropenic and normal subjects. These data indicate that CSF levels are not inversely related to the blood neutrophil count in chronic idiopathic neutropenia and suggest that CSF is not a hormone regulating the blood neutrophil count in a manner analogous to the erythropoietin regulation of circulating erythrocyte levels.

Agranulocytosis↗
PubMed1976

Eosinophil kinetics in the hypereosinophilic syndrome.

The kinetics of 51-chromium-labeled eosinophils were studied in 6 patients with the idiopathic hypereosinophilic syndrome. The kinetics of these cells were compared with 51-chromium-labeled neutrophils of 9 normal subjects. The patient studies consistently showed that autologous labeled eosinophils transiently left the circulating cell pool in the first 3 hours after infusion, re-entered the circulating pool, and then disappeared from the circulation with a mean blood half-life of 44 +/- 2.0 hours. In contrast, the neutrophils of normal subjects left the circulation progressively with an estimated blood half-life of 12.4 +/- 2.0 hours. These data suggest that the leukocytosis of the hypereosinophilic syndrome may be due to the presence in the blood of an increased number of cells with a relatively long blood half-life.

Adult↗
PubMed1976

Experimental Pseudomonas pneumonia in leukopenic dogs: comparison of therapy with antibiotics and granulocyte transfusions.

Pseudomonas aeruginosa pneumonia was produced in dogs with radiation-induced leukopenia to study the comparative efficacy of several different therapies. In a randomized control trial, five treatment regimens were compared: no antibiotics or granulocytes (controls), gentamicin (5 mg/kg/day), carbenicillin (500 mg/kg/day), gentamicin and carbenicillin (same dosages), and daily granulocyte transfusion (minimum 5 x 10(9) cells/day) plus gentamicin (5 mg/kg/day). The most effective therapy was gentamicin plus granulocyte transfusions. Gentamicin alone was not significantly better than no specific therapy. Carbenicillin with or without gentamicin gave intermediate results. This study further supports the utility of granulocyte replacement therapy of infections in severely granulocytopenic subjects. The results also indicate that the relative value of granulocyte transfusions depends upon the specific antibiotic regimen with which these transfusions are compared.

Animals↗
PubMed1976

Defective polymorphonuclear leukocyte chemotaxis and bactericidal capacity in a boy with recurrent pyogenic infections.

A 13-year-old boy with a history of recurrent pyogenic infections had abnormalities of polymorphonuclear leukocyte (PMN) function which probably accounted for his susceptibility to infection. PMN phagocytosis and nitroblue tetrazolium dye reduction were normal but glucose 14C oxidation was abnormally increased in resting cells. The patient's PMNs possessed decreased bactericidal activity against Staphylococcus aureus and Escherichia coli. Also documented were decreased PMN chemotactic activity and leukocyte accumulation in Rebuck skin windows. PMN random motility, PMN bone marrow reserve, PMN kinetics, lymphocyte blastogenesis, and delayed cutaneous hypersensitivity were normal. This patients represents another of the growing number of distinct granulocytopathies currently being recognized which may result in increased susceptibility to infection.

Adolescent↗
PubMed1975

Eosinophilic leukemia. Remission with vincristine and hydroxyurea.

A 40 year old man with eosinophilic leukemia was treated with a variety of chemotherapeutic agents. A long-term remission, unusual for eosinophilic leukemia, was maintained with chronic hydroxyurea therapy after induction with vincristine. Hydroxyurea and vincristine may offer an effective mode of therapy for this disease.

Adult↗
PubMed1975

Gentamicin sulfate pharmacokinetics: lower levels of gentamicin in blood during fever.

The effect of fever on serum concentrations and urinary excretion of gentamicin sulfate was studied in humans and dogs. Endotoxin-induced fever in dogs resulted in a decrease of approximately 25% in levels of gentamicin in serum 30 and 60 min after intravenous injection of the antibiotic (1.5 mg/kg) when compared with corresponding afebrile values. In six volunteers with etiocholanolone-stimulated fever, serum concentrations of gentamicin was reduced by an average of 40% in all measurements made 1.2, and 3 hr after intramuscular injection (1.5 mg/kg) as compared with afebrile control values in the same subject. Fever was thought to be the principal factor associated with lower levels of gentamicin, although the half-life of gentamicin in serum and renal clearance of the antibiotic were not significantly affected. These findings emphasize the need for frequent measurements of gentamicin in serum as a guide to adjustment of gentamicin treatment in febrile subjects, and perhaps in all patients receiving the antibiotic.

Adult↗
PubMed1975

Alternate-day prednisone therapy and human lymphocyte subpopulations.

The mechanisms and kinetics of the immunosuppressive effects of alternate-day prednisone were investigated in a group of patients with a variety of inflammatory diseases receiving a range of alternate-day prednisone doses from 5 to 120 mg. Total circulating lymphocyte and monocyte counts, as well as proportions of lymphocyte subpopulations defined both by surface markers and by in vitro functional capacities, were studied. At 8 a. m. of the day on prednisone, just before drug administration, lymphocyte and monocyte counts, proportions of lymphocyte subpopulations, as well as in vitro lymphocyte blastogenic responses to various mitogenic and antigenic stimuli were normal. 4 h after the administration of prednisone, there was a profound lymphocytopenia and monocytopenia, with a differential depletion of thymus-derived lymphocytes as well as various functionally defined lymphocyte subpopulations. Lymphocyte kinetic studies using a radioactive chromium-labeled autologous lymphocytes showed that the lymphocytopenia was due predominantly to a transient depletion of the recirculating portion of the intravascular lymphocytepool. All these parameters returned to normal by 8 a.m. of the following day (off prednisone) and remained normal throughout the day. This very transient lymphocytopenia and monocytopenia after prednisone, with normal cell numbers, proportions, and functions throughout the remainder of the 2-day cycle, was associated with suppression of disease activity, yet did not affect cutaneous delayed hypersensitivity in these patients nor increase the likelihood of infectious complications. This drug-associated cyclic and transient monocytopenia and selective lymphocytopenia is best explained by a redistribution of recirculating lymphocytes to other body compartments, particularly the bone marrow.

Adolescent↗
PubMed1975

Comparison of agents producing a neutrophilic leukocytosis in man. Hydrocortisone, prednisone, endotoxin, and etiocholanolone.

To study the potential application of glucocorticosteroid administration for the measurement of the bone marrow neutrophil reserve response, blood neutrophil count changes were measured in normal subjects after the administration of intravenous hydrocortisone (25, 50, 100, 200, and 400 mg) and oral prednisone (5, 10, 20, 40, and 80 mg). The upper three doses of both steroids increased the blood neutrophil count by approximately 4,000 cells/mm3. The neutrophilia occurring after hydrocortisone (200 mg) and/or prednisone (40 mg) was compared with that observed after endotoxin (0.8 ng/kg) and etiocholanolone (0.1 mg/kg) in 14 normal subjects, 7 patients with Wegener's granulomatosis on cyclophosphamide therapy and 10 patients with chronic idiopathic neutropenia. The normal responses (mean increase of blood neutrophils/mm3 above base line +/- 1 SEM) were: hydrocortisone 4,220 +/- 320, prednisone 4,610 +/- 360, endotoxin 6,060 +/- 880, and etiocholanolone 3,780 +/- 440. In the patient studies, etiocholanolone gave the smallest mean responses, but, in general, the results were similar for all agents. These data indicate that these glucocorticosteroids can be used as equivalent agents to endotoxin and etiocholanolone for measuring the neutrophil reserve response.

Adult↗
PubMed1975

The hypereosinophilic syndrome: analysis of fourteen cases with review of the literature.

Several closely related disease entities make up the idiopathic hypereosinophilic syndrome (HES). The syndrome is manifest by persistent and prolonged eosinophilia with organ damage. A group of 14 patients had hematologic, cardiac, and neurologic abnormalities attributable to this disease. Patient survival and response to chemotherapy was significantly better in this group than in previously reported patients. The etiology of HES remains unknown, as does the mechanism of tissue damage.

Adolescent↗