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Biomedical subjects

M C Aggio

Publications and source records attributed to M C Aggio.

At least 19 recordsLinked to original sources

Serum erythropoietin and its relation with soluble transferrin receptor in patients with different types of anaemia in a locally defined reference population.

Serum erythropoietin (Epo) and soluble transferrin receptor (sTR) were measured in a locally defined reference population (n=100): healthy volunteers (n=50); iron- deficiency anaemia (n=41) and haemolytic anaemia (n=9) (beta-thalassaemia, n = 4; autoimmune, n=5). Our data demonstrated an inverse relationship between erythroid activity and Epo levels. The regression line between Ln Epo and haemoglobin (Hb) was highly significant: P < 0.0001, r2=0.8275, Ln Epo=8.5346-0.04275 Hb, confidence limit 95%. The mean observed/predicted (O/P) ratio of Ln (Epo) was 1.01 +/- 0.11. We demonstrated that the serum Epo concentration in this particular population correlated consistently with clinical measures of erythropoietic activity. sTR, a new index of erythropoiesis, varied from 16.1 to 148 nmol/l, mean 62.0 nmol/l in the anaemic patients' group. The relationship between Ln Epo and Ln sTR was highly significant: P < 0.0001. We conclude that locally defined regression analyses are crucial for correct data interpretation and can indicate whether or not Epo production is appropriate or inappropriate. Serial determinations of sTR could help in the assessment of response to therapeutic doses of Epo.

Adolescent↗

The hemopoietic system: a phylogenetic approach.

Nomadism is a true hemopoietic characteristic during vertebrate phylogeny and ontogeny. This work reviews the mechanism and developmental steps of hemopoiesis, from a phylogenetic point of view. A summary of the principal hemopoietic "foci" along the evolutionary line is also presented.

Animals↗

[Large granular lymphocytic leukemia. Case report with scarce expression in peripheral blood].

The case of a 33 year old woman with a large granular lymphocytic leukemia is presented. The main symptoms were neutropenia and recurrent respiratory bacterial infections. No enlargement of the liver, spleen or lymph nodes was noted. Circulating lymphocytes averaged 3000/microliter with 35% of large granular cells. The bone marrow biopsy showed lymphatic infiltration with both nodular and interstitial pattern. Lymphocytes bore the T suppressor phenotype (CD8+, CD45 RO+, CD20-, kappa-, lambda-). Cytogenetic studies revealed a low expression clone with 7q-: del (7)(q36). Gene rearrangements for immunoglobulins or T-cell receptors could not be demonstrated by Southern Blot. Bone marrow cultures grew normally while both normal and patient bone marrow showed marked inhibition when incubated with patients serum. Normalization of the peripheral granulocytic count was obtained with prednisone, while granulocytic-stimulating factors, chlorambucil, and cyclosporine A were partially active or inactive. We suggest that this case represents a form of the lymphoproliferative disease of granular lymphocytes. To our knowledge, the deletion of the long arm of chromosome 7 has not been described in this disease.

Adult↗

[Incidence and probable etiology of toxic agranulocytosis in a definite population in the province of Buenos Aires (1963-1976)].

The medical records of 55 patients with toxic agranulocytosis (unrelated to radiation, anticancer drugs or known industrial toxics) were reviewed in a well defined population of the Province of Buenos Aires during 1963-1976. There were 65 episodes in 30 women and 25 men, age average 49 years. Nine patients repeated the episode by reexposure to the same drug. The annual incidence rate was 8.4 cases per million/year. Nineteen (35.5%) of the patients died. Forty-three episodes (64.3%) were associated with analgesic-antipyretics, mainly dipyrone (34 cases). In most situations, drugs were prescribed for mild complaints such as pharyngitis, arthralgias or abdominal pain. Although toxic agranulocytosis is an infrequent disease, its relationship with drugs is well known and its mortality remains high.

Adolescent↗

[Enzyme replacement therapy in type 1 Gaucher's disease].

Gaucher disease is a sphingolipid storage disorder caused by a deficiency of the lysosomal enzyme glucocerebrosidase (GC) and the consequent deposition of glucocerebrosides into the cells of the macrophagic system. Among the three types of clinical disease, type 1 leads to hepatosplenomegaly, hypersplenism and skeletal abnormalities including bone pain, osteopenia and fractures. Two pediatric female patients with moderately severe type 1 Gaucher disease were treated with commercially available GC, mannose terminated to be macrophage-targeted. GC was given by intravenous infusion (30 to 60 units per kilogram of body weight every two weeks) for 8 and 18 months. The hemoglobin concentration increased and the serum acid phosphatase decreased in both patients. In the most affected child, hepatic volume decreased significantly and bony symptoms disappeared. Infusions were uneventful except for an episode of anaphylaxis that subsided rapidly, allowed resumption and did not affect efficacy. These observations are in agreement with the international experience in approximately 800 cases, with good tolerance in all type 1 patients who show objective clinical improvement; patterns of response are variable from patient to patient, independent from previous splenectomy, and dose-dependent; the dose can be tapered after a period of time. Antibodies anti-GC are seen in 13% of the patients, but their presence does not have clinical consequences. The cost of the enzyme makes it crucial to define precise indications, optimal dosing schedules, duration of treatment and cost-benefit ratio.

Adolescent↗

Correlation if circulating immune complexes and disease status in patients with leukaemia.

The occurrence of soluble immune complexes (IC) was investigated in 177 serum samples from 92 patients with various leukaemias using the Raji cell immunoassay. In general, patients with myeloproliferative diseases had a higher incidence and higher quantities of IC than did patients with lymphoproliferative disorders. Elevated levels of IC were found in the sera of patients as follows: 17% with chronic lymphocytic leukaemia (mean value of 13.1 microgram/ml), 67% with acute lymphocytic leukaemia (54.1 microgram/ml), 65% with chronic myelocytic leukaemia (86.7 microgram/ml), 70% with acute myelocytic leukaemia (202.5 microgram/ml) and 56% with acute myelomonocytic leukaemia (41.9 microgram/ml). Patients in terminal blastic crisis of chronic myelocytic leukaemia had the highest levels, with a mean level of 1,364.1 microgram/ml. Serial samples were obtained, as available, from individual patients during the course of the disease in an attempt to relate severity with the incidence and quantity of IC. No significant correlation could be made between the occurrence or levels of IC and the presence of absence of systemic symptoms. Similarly, no correlations could be made between levels of IC and haematological parameters, infection, or therapy. However, the data does indicate a positive relationship between the levels of IC and the progressive state of the leukaemia, especially, the myelocytic leukaemias.

Antigen-Antibody Complex↗

Evaluation of drug-antibody conjugates in the treatment of human myelosarcomas transplanted in nude mice.

Methotrexate, daunomycin, and chlorambucil were independently conjugated to immune goat gamma-globulins specifically raised to the Ph1 + chronic myelogenous leukemia cell line K-562. The drug-antibody conjugates were then tested against myelosarcomas made up of K-562 cells growing in nude mice and their efficacy was compared with that of the drug alone, gamma-globulins, a mixture of the two, or conjugates of drugs with normal goat gamma-globulin. Conjugation methods for methotrexate and daunomycin abrogate the antibody activity as indicated by the absence of complement-mediated cytotoxicity of the conjugates in vitro and the lack of effect on myelosarcomas in vivo. Simultaneous administration of either of these drugs and antibody partially abrogated the development of myelosarcomas. Chlorambucil-antibody conjugates, however, retained their cytotoxicity in vitro and were found effective in vivo. It is the first successful attempt to covalently bind chlorambucil to gamma-globulins without the loss of drug or antibody biological activity. Although the simultaneous administration of chlorambucil and gamma-globulins and conjugated drug gamma-globulins reduced the growth of myelosarcomas considerably, the immune gamma-globulins alone either reduced their weight to a larger degree or eliminated their growth completely. Results of this study indicate that myelosarcomas made up of K-562 cells grown in nude mice are good and reproducible models for testing various therapeutic agents. The advantage of using human cells proliferating in an in vivo environment brings experimental therapy one step closer to clinical trials.

Animals↗

Hematopoiesis of hereditarily asplenic-athymic (lasat) mice.

The hematopoiesis of athymic-asplenic (lasat) mice was compared with that of normal, asplenic, and athymic littermates with the same strain background. Erythrocyte blood volume, number and survival time were normal when related to the body weight of the animals. Peripheral blood showed leukopenia with absolute and relative lymphopenia, resembling the athymic rather than the asplenic pattern. The bone marrow was hypocellular as a consequence of a decrease in both lymphocytes and erythroid precursors, while thrombocytopoiesis and granulcytopoiesis-monocytopoiesis were essentially normal. Although the percentile value of femoral stem cells was high, their absolute number was, in fact, reduced by 35% as a result of the bone marrow hypocellularity. When lasat bone marrow cells were injected into normal, lethally irradiated mice, a rapid erythropoietic recovery was observed, whereas the restoration of the granlocytic compartment was impaired. It was concluded that: 1) lasat mice depict a normal hematopoiesis in spite of the congenital absence of the thymus and the spleen; 2) bone marrow stem cells may be defective when administered to lethally irradiated hosts; and 3) the athymic status predominates over the asplenic one.

Animals↗

Postirradiation erythropoietic recovery in splenectomized mice.

The influence of splenectomy on erythropoietic recovery of lethally X-irradiated mice injected with different doses of syngeneic bone marrow was studied. Splenectomized animals showed less activation than unoperated controls in the lower dose range; however, by increasing the number of injected cells the response obtained was similar in both groups. Providing an adequate number of stem cells is administered to the splenectomized recipients, an enhanced erythropoietic activity of the graft may compensate for the absence of the spleen, which is an important organ in postirradiation recovery. Suggested explanations for this observation are lack of an haematopoietic inhibitory effect of the irradiated spleen, or changes in the environment provided by the spleenless host.

Animals↗