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Biomedical subjects

F H Gardner

Publications and source records attributed to F H Gardner.

At least 37 records · Page 2Linked to original sources
PubMed1985

Phenylalanine analyses of blood-spot control materials: preparation of samples and evaluation of interlaboratory performance.

Aliquots (0.1 mL) of whole-blood pools prepared to contain various concentrations of phenylalanine were applied to filter-paper collection cards, dried, and stored in sealed bags. We measured the phenylalanine content of the dried blood spots by bioassay, fluorometry, and "high-performance" liquid chromatography, and found that the concentrations remained constant for two years when samples were kept at -20 degrees C or lower. Intra- and interlaboratory studies showed that results for phenylalanine were greater for laboratories using bioassay procedures than for those using fluorometric procedures. Further, CVs (both among- and within-laboratory) obtained with fluorometric procedures were nearly half as great as the CVs obtained by laboratories using bioassay techniques.

Biological Assay↗
PubMed1985

Persistence of abnormal RBC and platelet phenotype during recovery from aplastic anemia.

Sixteen adults with chronic acquired aplastic anemia had abnormally large RBCs and abnormally small platelets before chemotherapy. During their therapy, transfusion initially obscured these macrocytic RBCs. In the eight who had erythropoietic recovery, endogenous RBCs again were macrocytic, and platelets remained small whether or not the platelet count increased. The percentage of cells containing hemoglobin F changed in only one of the eight subjects. In contrast, the eight who did not have erythropoietic recovery had no reappearance of macrocytes. Of 19 other previously treated patients whose hemoglobin level had recovered to normal for seven to 196 months, 16 had increased mean corpuscular volume (101 to 133 femtoliters) and abnormally small platelets. We conclude that in aplastic anemia the appearance of macrocytes reliably and easily predicts RBC recovery. Furthermore, even in treated, apparently recovered subjects, an abnormality of blood cell size remains.

Adolescent↗
PubMed1985

Use of mean platelet volume improves detection of platelet disorders.

Classification of platelet disorders has been based on the platelet count. Addition of a second variable, mean platelet volume (MPV), to the routine blood count allows classification of patients into 9 categories: high, low, or normal MPV, and high, low or normal platelet count. We studied 1,244 adult inpatients. 1,134 had both platelet values normal. 11 patients had high MPV and low platelet count: all had hyperdestructive causes. 15 patients had high MPV and normal platelet count: 12 had heterozygous thalassemia, and three had iron deficiency. Seven patients had high MPV and high platelet count: causes included myeloproliferative disorders, inflammation, iron deficiency, and splenectomy, 25 patients had high platelet counts and normal MPV: the causes were inflammation, infection, sickle cell anemia, iron deficiency, or chronic myelogenous leukemia. 52 patients had an MPV that was inappropriately low for the platelet count (high, normal, or low). All had sepsis, splenomegaly, aplastic anemia, chronic renal failure, or a disease being treated with myelosuppressive drugs. High MPV thus appears correlated with myeloproliferative disease or thalassemia; and low MPV, with cytotoxic drugs or marrow hypoplasia. Addition of MPV to the platelet count allows subtler disorders to be detected (when the platelet count is normal), and allows distinction of the cause of thrombocytopenia.

Blood Cell Count↗
PubMed1984

The effect of dexamethasone on the growth of bone marrow fibroblasts in aplastic anemia.

To study the characteristics of the microenvironment of human bone marrow, fibroblasts derived from normal and aplastic anemia bone marrow aspirates or core biopsies were grown in culture. Normal bone marrow fibroblasts had a slow logarithmic phase of growth (8 days) with doubling times of 2 to 3 days. Aplastic anemia bone marrow fibroblasts had a rapid logarithmic phase of growth (5 to 6 days) and doubling times of 1 day. Dexamethasone (1 X 10(-8) M) stimulated the growth of normal fibroblasts. Growth of fibroblasts derived from aplastic anemia marrows was, however, inhibited by dexamethasone. Specific binding sites for the hormone were present in the normal fibroblasts (Bmax: 460-770 fmole/mg protein) whereas in the aplastic anemia fibroblasts the amount was very low (Bmax 27-215 fmole/mg protein). These observations suggest that in aplastic anemia, the bone marrow fibroblast, a cell constituent of the marrow microenvironment, has the capacity to develop and grow in vitro. However, this cell is different from normal bone marrow fibroblasts in its growth characteristics and response to dexamethasone.

Anemia, Aplastic↗
PubMed1984

Abnormal marrow fibroblasts in aplastic anemia.

Human bone marrow fibroblasts (BMF) were grown in vitro from normal (N) subjects and patients with aplastic anemia (AA). Growth studies in vitro revealed that both the N-BMF and AA-BMF had a logarithmic growth phase of eight days. Population doubling time for six of the 12 N-BMF and seven of the 12 AA-BMF was greater than 50 h. Five of the 12 AA-BMF studied in contrast to only two of the 12 N-BMF had a population doubling time of less than 50 h. The remaining four N-BMF had a population doubling time of greater than 100 h. During a similar duration in the logarithmic phase of growth, the AA-BMF underwent an average of 2.499 population doublings in comparison to 1.586 doublings by N-BMF (P = less than 0.01). The AA-BMF grew in multiple layers compared with the N-BMF, which usually grew as a monolayer. At the end of the logarithmic phase of growth, the AA-BMF also had a significantly higher number of cells per dish than the N-BMF (P = 0.02 on analysis of variance and covariance). These data suggest that a subgroup of AA-BMF grows faster than N-BMF and that the AA-BMF lack cell-to-cell inhibition. Testosterone, 3 alpha-etiocholanolone, and dexamethasone at 1 X 10(-8)M concentration, a physiological concentration, stimulated the growth of N-BMF as evidenced by increase in cell numbers and radioactive thymidine (3H-TdR) uptake. While dexamethasone had a stimulating effect on growth of N-BMF, it suppressed the growth of AA-BMF. Specific binding of radioactive dexamethasone (3H-dexa) was determined both for the N-BMF and AA-BMF. Specific binding sites for dexamethasone (Bmax) present on the N-BMF ranged from 460 to 770 fmol/mg protein). Bmax for AA-BMF was low (27-215 fmol/mg protein). In addition, the dissociation constant (Kd) was ten times lower for AA-BMF (1.0 X 10(-7) M) than for N-BMF (1.1 X 10(-8) M). The observations on the growth studies, the paradoxical response to dexamethasone, and the difference in the number of binding sites for dexamethasone indicate that the marrow fibroblasts from patients with aplastic anemia are abnormal.

Anemia, Aplastic↗
PubMed1983

Improved classification of anemias by MCV and RDW.

New automated blood cell analyzers provide an index of red cell volume distribution width (RDW) or heterogeneity and a histogram display of red cell volume distribution. We have developed a classification of red cell disorders, based on mean corpuscular volume (MCV) or red cell size, heterogeneity, and histograms, to guide diagnosis from the peripheral blood analysis. The distinction of iron deficiency anemia from heterozygous thalassemia or the anemia of chronic disease and the detection of early iron and folate deficiency is improved. Red cell volume distribution histograms identify red cell fragmentation or agglutination, dimorphic populations, and artifactual counting of lymphocytes as red cells. We recommend the use of these new variables in the initial classification of anemia by the practicing physician.

Anemia↗
PubMed1983

Thrombocytopenia due to defective platelet production.

An increasing number of kindreds with thrombocytopenia have been described in the past decade as platelet counts have been done regularly. These patients are delineated from ITP, recognizing that some patients with hereditary thrombocytopenia may benefit from splenectomy. Until more information on platelet biochemical information is available, these disorders have been categorized by platelet size, now quantifiable as mean platelet volume (MPV). The availability of rapid and quantitative measurement of platelet count and MPV allow a better understanding of megakaryocyte proliferation and platelet production. The evolving changes of MPV during treatment and recovery from chemotherapy will now allow a forecast of marrow hypoplasia, since the platelet count and increase in MPV follow the increase in megakaryocyte ploidy to herald marrow regeneration. It is anticipated that the careful plotting of the MPV relationship to the platelet count will allow the physician to evaluate marrow function indirectly, in many cases replacing repeated bone marrow studies.

Anemia, Aplastic↗
PubMed1983

Platelet size in thrombocytopenia due to sepsis.

In normal persons, the mean platelet volume varies inversely but nonlinearly with the platelet count. Those with immune platelet destruction have a mean platelet volume that conforms to normal values. Nine patients with thrombocytopenia due to post-trauma sepsis without disseminated intravascular coagulation had a lower than normal mean platelet volume as the platelet count fell. In six patients who recovered, the mean platelet volume increased to the normal value before the platelet count began to rise. In contrast, three patients who did not recover from sepsis had no change from the low mean platelet volume and thrombocytopenia. Since mean platelet volume can now be part of the routine blood count, it is a useful variable to assay the degree of bone marrow suppression in the patient with thrombocytopenia and can be used as a predictor of recovery from thrombocytopenia.

Abdominal Injuries↗
PubMed1982

Analysis of the androgen response of 23 patients with agnogenic myeloid metaplasia: the value of chromosomal studies in predicting response and survival.

The responses of 23 patients with agnogenic myeloid metaplasia (AMM) to androgen therapy were studied. Various clinical and laboratory parameters were analyzed for their value in determining response to therapy and length of survival. Fifty-seven percent of patients responded, as determined by a sustained increase in hematocrit within three months of therapy which thus eliminated the need for transfusions. Chromosome study of the abnormal hemic population was the best predictor of response: 92% of patients with normal chromosomes responded, while 78% of patients with chromosomal abnormalities did not. Responders had a mean survival time of five and a half years from the time of diagnosis as compared with two years for the nonresponders. The degree of thrombocytopenia, suppression of the ferrokinetic, and lack of activity in axial skeleton on bone marrow scans indicated severely compromised hemopoiesis in the nonresponders. The results suggest that in some patients with AMM, more extensive cytogenetic alterations in the abnormal hematopoietic cells result in an inability to respond to androgen therapy and that the chromosome study is the test most accurate for predicting the outcome of therapy.

Adolescent↗
PubMed1982

The uptake of etiocholanolone by human bone marrow immature granulocytes.

A cell fraction enriched in immature granulocytes was obtained after fractionation of human bone marrow by a three-step procedure. This fraction sediments at an average density of 1.073 and has a high content of myelocytes and metamyelocytes. It showed the highest specific uptake of etiocholanolone when compared to other bone marrow cell fractions. Autoradiographic studies demonstrated a higher number of silver grains over myelocytes and metamyelocytes than in other cell types. These results suggest the presence in human bone marrow of a target cell for etiocholanolone, located in the late mitotic or postmitotic pool or granulocytes.

Autoradiography↗
PubMed1982

Indications for platelet transfusion in children with acute leukemia.

In an attempt ot determine the indications for platelet transfusion in thrombocytopenic patients, we randomized 56 children with acute leukemia to one of two regimens of platelet transfusion. The prophylactic group received platelets when the platelet count fell below 20,000 per mm3 irrespective of clinical events. The therapeutic group was transfused only when significant bleeding occurred and not for thrombocytopenia alone. The time to first bleeding episode was significantly longer and the number of bleeding episodes were significantly reduced in the prophylactic group. The survival curves of the two groups could not be distinguished from each other. Prior to the last month of life, the total number of days on which bleeding was present was significantly reduced by prophylactic therapy. However, in the terminal phase (last month of life), the duration of bleeding episodes was significantly longer in the prophylactic group. This may have been due to a higher incidence of immunologic refractoriness to platelet transfusion. Because of this terminal bleeding, comparison of the two groups for total number of days on which bleeding was present did not show a significant difference over the entire study period.

Actuarial Analysis↗
PubMed1982

Growth of human malignant micromegakaryocytes in vitro.

Mononuclear cells from the peripheral blood of a patient with megakaryoblastic transformation of Philadelphia chromosome-positive chronic myelogenous leukemia were cultured. Morphological and cytochemical studies and cell ploidy determinations were done daily for 4 days. PAS staining of the cells increased progressively during culture. Ultrastructural study of circulating and cultured cells revealed demarcation membranes and alpha granules indicating the cells were micromegakaryocytes. Deoxyribonucleic acid synthesis, determined by 3H-thymidine uptake, peaked at 72 hours. The DNA content of cultured cells was diploid at all times. All 15 metaphases analyzed at 72 hours were Ph1-positive. Malignant (Ph1-positive) megakaryoblasts and micromegakaryocytes grown successfully were capable of partial cytoplasmic maturation as demonstrated by glycogen deposition and increase in subcellular organelles, while endoreduplication was impaired. Malignant megakaryoblasts and micromegakaryocytes can be grown successfully in short term liquid culture and have more complete maturation in vitro than observed in vivo.

Cell Division↗
PubMed1982

Bone-marrow imaging with indium-111 chloride in aplastic anemia and myelofibrosis: concise communication.

Twenty-nine patients with aplastic anemia and 11 patients with myelofibrosis were evaluated with indium-111 chloride bone-marrow imaging, ferrokinetics, and bone-marrow core biopsies. There was good correlation between the erythrocyte cellularity of the marrow and the In-111 bone-marrow scan grades in most patients. In some, the overall scan grade tended to underestimate the erythroid elements because the core biopsy had been taken from the area of the greatest radionuclide concentration on the scan. In patients with aplastic anemia, there was good correlation between the plasma iron clearance t1/2 and the scan grade. Less agreement was found in the comparison between the Fe-59 sacral and organ counts and the red-cell iron utilization. In patients with myelofibrosis, there was poor correlation between the surface counts over the sacrum and the red-cell iron utilization. Plasma iron clearances were abnormally short and were unrelated to the transferrin saturation levels. Eighteen patients were studied several times to evaluate their responses to steroid therapy. In all, there was good correlation between the bone-marrow imaging, the erythrocyte cellularity, ferrokinetics, and the patient's response to therapy. Indium-111 bone-marrow imaging is useful both in evaluating marrow erythroid activity and in following the response to therapy in patients with these diseases.

Adolescent↗