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Biomedical subjects

M Cazzola

Publications and source records attributed to M Cazzola.

At least 235 records · Page 13Linked to original sources
PubMed1985

Research on heterocyclic compounds. XVIII. Imidazo[2,1-b]-1,3,4-thiadiazole derivatives.

The synthesis of a series of 6-carbethoxy-, 6-carbethoxy-methyl-, and 5-carbethoxy-6-methylimidazo[2,1-b]-1,3,4-thiadiazoles was accomplished by reacting some 2-amino-1,3,4-thiadiazoles with ethyl bromopyruvate, 4-chloroacetoacetate, and 2-chloroacetoacetate, respectively; such carbethoxy derivatives afforded the corresponding carboxylic acids by hydrolysis. The antiinflammatory, analgesic, antipyretic and ulcerogenic activities were studied on three of the new acidic compounds.

Animals↗
PubMed1985

Proliferation kinetics of bone marrow cells in congenital dyserythropoietic anemia type II.

The proliferation kinetics of erythropoiesis and of myelopoiesis have been studied in a case of congenital dyserythropoietic anemia type II (HEMPAS) by means of quantitative 14-C autoradiography, Feulgen cytophotometry and 59-Fe ferrokinetics. Increased total erythropoietic activity and ineffective erythropoiesis was demonstrated by ferrokinetics. Quantitative 14-C autoradiography showed a generally delayed proliferation rate of erythroid cells, most evident in the polychromatic compartment. A deficiency of cell production of 25% was detected among the polychromatic erythroblasts. Part of this fraction is represented by cells still capable of passing to the successive stages of maturation. We conclude that only part of the deficiency of cell production in the polychromatic compartment represents real cell destruction. Most of the measured ineffectiveness is confined to later stages of maturation, such as orthochromatic erythroblasts and marrow reticulocytes.

Adult↗
PubMed1985

Classification of anaemia on the basis of ferrokinetic parameters.

Quantitative information on abnormalities of erythropoiesis and mechanisms of anaemia has been obtained in 136 anaemic patients by means of ferrokinetic studies. To derive a functional classification of anaemia based on ferrokinetic parameters, agglomerative hierarchical cluster analysis and principal coordinate analysis were utilized as techniques for unsupervised classification. Two main clusters were found and named anaemia with low potential erythropoiesis and with high potential erythropoiesis, since the most discriminant parameter between them was total erythroid iron turnover, a measure of total erythropoietic activity. A value of total erythropoiesis equal to 4 times the normal was found to discriminate these two types of anaemia in 94% of cases. Within the group with low potential erythropoiesis, three clusters showing different qualitative disturbances of erythropoiesis were singled out. Among patients with high potential erythropoiesis, two clusters were found. A value of effective erythropoiesis equal to 2.5 times the normal was shown to have a high discriminant power between these clusters. This threshold level distinguished between patients having ineffective erythropoiesis or peripheral haemolysis as the major mechanism of anaemia. The present functional classification of anaemia provides a complete picture of the different pathogenetic mechanisms and may represent the basis for a more rational diagnostic approach to erythroid disorders.

Adolescent↗
PubMed1985

Use of a monoclonal antibody against human heart ferritin for evaluating acidic ferritin concentration in human serum.

Immunoassays for acidic ferritins rich in H subunits have shown that these isoferritins are predominant in some cells such as monocytes and red blood cells but have provided conflicting results about their presence in human serum. We have used an immunoradiometric assay based on a monoclonal antibody against human heart ferritin (monoclonal 2A4) for evaluating acidic ferritin concentration in human serum. This assay proved to be highly specific for acidic isoferritins having more than 60% H subunits. Heart-type ferritin was detected in only one fifth of normal sera and sera from patients with iron overload; values were very low compared with those for basic ferritin. Acidic ferritin was found in relatively high concentrations in most patients with iron deficiency anaemia. In other disease states characterized by increased serum concentrations of basic ferritin, acidic ferritin was always less than 21% of the total ferritin. Dialysis in low-ionic-strength buffer showed that both normal and pathological sera had binding factors for human heart ferritin. We conclude that: (i) human serum contains low concentrations of acidic isoferritins which, at variance with basic ferritin, do not appear to be directly related to the amount of storage iron; (ii) the findings of the present study reinforce the opinion that basic and acidic ferritins have different functional behaviours.

Anemia, Hypochromic↗
PubMed1985

Transferrin saturation, plasma iron turnover, and transferrin uptake in normal humans.

The relationship between plasma iron, transferrin saturation, and plasma iron turnover was studied in 53 normal subjects whose transferrin saturation varied between 17% and 57%, in 25 normal subjects whose transferrin saturation was increased by iron infusion to between 67% and 100%, and in five subjects with early untreated idiopathic hemochromatosis whose transferrin saturation was continually elevated to between 61% and 86%. The plasma iron turnover of all of these subjects ranged from 0.45 to 1.22 mg/dL whole blood/d. The mean values for the above-mentioned three groups were 0.71 +/- 0.17, 1.01 +/- 0.11, and 1.01 +/- 0.13 mg/dL whole blood/d, respectively. Most of this variation, estimated at 72% by regression analysis, was due to a direct relationship between transferrin saturation and plasma iron turnover. This effect was attributed to a competitive advantage of diferric over monoferric transferrin in delivering iron to tissues. This was confirmed by the demonstration of a more rapid clearance of diferric as compared to monoferric transferrin in an additional group of eight normal subjects. Calculations were made of the amount of transferrin reacting with membrane receptors per unit time. Allowance was made for the noncellular (extravascular) exchange and for the 4.2:1 preference of diferric over monoferric transferrin demonstrated in vitro. The amount of iron-bearing transferrin leaving the plasma to bind to tissue receptors for 53 subjects with a transferrin saturation between 17% and 57% was 71 +/- 13; for 25 subjects with a saturation from 67% to 100%, 72 +/- 12; and for five subjects with early idiopathic hemochromatosis, 82 +/- 11 mumol/L whole blood/d. There were no significant differences among these groups. These studies indicate that while the number of iron atoms delivered to the tissues increases with increasing plasma iron and transferrin saturation, the number of iron-bearing transferrin molecules that leave the plasma per unit time to bind to tissue receptors is relatively constant and within the limits studied, independent of transferrin saturation.

Adult↗
PubMed1984

Polycythaemia following splenectomy in myelofibrosis with myeloid metaplasia. A reorganization of erythropoiesis.

3 patients with myelofibrosis with myeloid metaplasia were splenectomized because of anaemia and disturbing splenomegaly. In the course of the 6 months following splenectomy, a polycythaemia developed. Erythrokinetic studies demonstrated that in all cases a reduction in plasma volume and an increase in red cell volume was obtained. Total erythropoiesis decreased along with normalization of ineffective erythropoiesis and peripheral haemolysis. The reappearance of an erythropoietic activity measured over the sacrum was a constant finding, while in 1 patient, a depression of activity over the liver was observed. The new distribution and organization of erythropoiesis in the splenectomized patients is hypothesized as being due to the removal of the influence of an enlarged spleen on erythropoietic organs.

Aged↗
PubMed1984

Systemic and ocular effects of alpha 2-adrenergic stimulating and beta 2-blocking agents.

The effects of alpha 2-adrenergic stimulating agents (clonidine and guanabenz) and beta-adrenolytic agents (atenolol and propranolol) on the systemic arterial pressure, heart-rate, blood glucose level and intraocular pressure, as well as on the concentrations of glucose, Na+, K+ and Ca++ in the lens and aqueous and vitreous humours, are evaluated in the rabbit. alpha 2-adrenergic stimulating agents cause a significant increase of the glucose concentration in the blood, lens, aqueous and vitreous humours; whereas the beta-adrenolytic agents cause insignificant effects. Neither of the two drugs alters the concentration of Na+, K+ and Ca++ in the lens and aqueous and vitreous humours.

Adrenergic alpha-Agonists↗
PubMed1984

Cardiovascular and respiratory effects of spermidine and spermine: an experimental study.

Spermidine (SPD) and spermine (SPM) produced in anaesthetized dogs significant cardiovascular changes at higher doses than other transmitters, i.e. l-noradrenaline, l-adrenaline, histamine, acetylcholine, which produce cardiovascular effects at doses of 0.01-0.05 micrograms/kg given intravenously. SPD was shown to be more active than SPM. The hypotensive response observed after i.v. injection is due to histamine release. The hypotensive and bradycardic effects observed after microinjection of SPD into III cerebral ventricle or into the vertebral artery and of SPM into the vertebral artery are due to an increase in parasympathetic output. Spermidine increased and spermine decreased the baroreceptor reactivity. SPD and SPM did not change the vascular beta- and alpha-adrenergic, cholinergic and histaminergic receptor reactivity.

Animals↗
PubMed1984

Spleen iron content is low in thalassemia.

We measured the iron content of the spleen in 12 patients with thalassemia major, three with thalassemia intermedia, and one with sickle-thalassemia. The iron content was unexpectedly low in all patients (0.25-2.4 g, median 1.32). These data suggest that iron deposited in the reticuloendothelial cells of the spleen is rapidly removed and redistributed throughout the body. The preferential removal of iron from the spleen did not seem to be a result of chelation therapy.

Adolescent↗
PubMed1983

Red cell aplasia in myelofibrosis with myeloid metaplasia. A distinct functional and clinical entity.

Three patients with myelofibrosis with myeloid metaplasia are described. All three presented with grave anemia and red cell aplasia. Erythroid failure was the functional characteristic of erythropoiesis as resulted from erythrokinetic studies. Bone marrow was hypercellular or normocellular with hyperplasia of granuloblasts and megakaryocytes. Despite absent or mild splenomegaly at diagnosis, massive splenomegaly associated with a leukoerythroblastic blood film developed during the course of the disease. A relative young age (42-47 years), a subacute course of the disease and terminal blast crisis in two of them were the prominent clinical features of the patients. The differentiation from acute or malignant myelofibrosis is discussed. The patients appear to be a distinct subset within myelofibrosis with myeloid metaplasia.

Adult↗
PubMed1983

Juvenile idiopathic haemochromatosis: a life-threatening disorder presenting as hypogonadotropic hypogonadism.

It is generally believed that idiopathic haemochromatosis is exclusively a disease of middle age, affecting primarily men. We describe here four cases of idiopathic haemochromatosis having onset of symptoms before or around the age of 20 years. Other similar cases have previously been reported. In this juvenile form, males and females appear to be equally affected. These subjects may have a history of unexplained abdominal pain, present with hypogonadotropic hypogonadism, and, unless proper treatment is started, die early because of cardiac dysfunction. In this regard, their clinical course is very similar to that of well-transfused thalassemia major. Thus, early diagnosis is even more important in the juvenile form than in the adult form of idiopathic haemochromatosis. We suggest that evaluation of body iron stores should be performed as a screening procedure in young subjects with hypogonadotropic hypogonadism and/or cardiac dysfunction.

Adult↗
PubMed1983

Basic and acidic isoferritins in the serum of patients with Hodgkin's disease.

Ferritin concentration has been measured in the serum of patients with Hodgkin's disease (HD) by radioimmunoassays with monospecific antibodies to liver (basic) and HeLa (acidic) ferritin. Elevated levels of serum ferritin with the liver ferritin assay were found only in patients with systemic disease, and were associated with low serum iron. Basic ferritin levels returned promptly to normal when complete remission was achieved. High levels of serum ferritin with the HeLa ferritin assay were found in 94% of all untreated patients. Acidic ferritin concentration was not related to systemic symptoms or alterations of iron metabolism, and returned to within the normal range only 1-2 yr after complete remission. These findings suggest that basic and acidic isoferritins can be distinguished in terms of biological and clinical significance. Basic ferritin is synthesized by the reticuloendothelial cells and the high values found in patients with systemic symptoms are compatible with the non-specific changes known to occur in the reticuloendothelial system during inflammation. In patients with untreated HD an elevated serum concentration of basic ferritin can be considered a marker of systemic symptoms and, therefore, an unfavourable prognostic factor. Acidic ferritin may be derived from abnormal lymphocytes and/or monocytes, including malignant cells, and its serum concentration may be of value in following the course of remission.

Adolescent↗
PubMed1983

Iron loading in congenital dyserythropoietic anaemias and congenital sideroblastic anaemias.

The relationship between body iron status, degree of anaemia, erythroid expansion, age and sex has been studied in eight patients with congenital dyserythropoietic anaemia (CDA) and two patients with congenital sideroblastic anaemia, who had received no or very few blood transfusions and no medicinal iron during the course of their illness. All patients had increased iron stores. Iron load was mild in three women in the reproductive age and severe in two men, in middle age, who had evidence of parenchymal organ dysfunction. Iron loading, as judged by the plasma ferritin concentration, was independent of the degree of anaemia while it was closely related to the patient's age and the degree of increase in the total erythropoietic activity. It is concluded that patients with CDA or congenital sideroblastic anaemia are at high risk of developing haemochromatosis in middle age. Prophylactic phlebotomy or iron chelation therapy should be considered for such patients.

Adolescent↗
PubMed1983

Ferritin in the red cells of normal subjects and patients with iron deficiency and iron overload.

Red cell ferritin was measured in normal subjects and patients with iron deficiency and iron overload by means of radioimmunoassays with antibodies to liver (basic) and heart (acidic) ferritins. In most of the subjects examined, red cells were found to contain greater amounts of heart-type than liver-type ferritin. The basic ferritin content reflected the abnormal body iron status both in iron deficiency and iron overload while the acidic ferritin content was less closely related to the iron status. The two immunologically different red-cell ferritins probably represent distinct ferritin molecules and may have different metabolic functions within haem-synthesizing erythroid cells.

Anemia, Aplastic↗