Search PubMed⌕ Search

Biomedical subjects

M Cazzola

Publications and source records attributed to M Cazzola.

At least 307 records · Page 17Linked to original sources

Asthma treatment must be always tailored to the individual patient.

Several studies have shown that there are notable benefits in adding a long acting beta 2-agonist to an inhaled corticosteroid. Particularly, long acting beta 2-agonists allow to reduce the amount of steroid that is required to induce a specific response and, consequently, its possible side effects. Currently the pharmaceutical market promotes, and physicians tend in any case to privilege, the use of fixed combinations for the treatment of the asthmatic patient and this also in the first phases of the illness. Nevertheless, for the majority of patients with mild to moderate asthma, it seems more reasonable to optimize the dose of the inhaled steroid before considering the addition of a long-acting beta 2-agonist, and use this latter on an 'as needed' basis if its pharmacodynamic characteristics allow it. Use of combinations is the more reasonable therapeutic choice for patients with a more severe pathological picture, who, despite the optimized dosage of the inhaled glucocorticoid, also require a long acting beta 2-agonist. After having verified the stability of the clinical control, it is possible to continue with the combined therapy provided, however, that this allows the treatment of the patient with the lowest dose of corticosteroid able to prevent, as far as is possible, exacerbations. Asthma exacerbations are less frequent with this therapy, but when they appear it is necessary to be immediately able to increase and, sometimes, also maximize the dosage of corticosteroid without being forced to double, or even triple, the dose of the long acting beta 2-agonist unless there is a real need--and which probably, rather, would induce unwanted side effects.

Adrenergic beta-Agonists↗

Evaluation of erythroid marrow response to recombinant human erythropoietin in patients with cancer anaemia.

BACKGROUND: Anaemia is a frequent finding in patients with cancer and may be due to different causes, including blunted erythropoietin production. MATERIALS AND METHODS: In a pilot study, we administered recombinant human erythropoietin (rHuEPO) to twelve patients with solid tumours and secondary anaemia. rHuEPO was given subcutaneously 5 d per week at escalating doses (75 to 150 U/kg per day): the aim of treatment was a Hb level > or = 10 g/dl without blood transfusion. We evaluated endogenous EPO production through serum EPO levels and erythroid marrow activity by means of serum transferrin receptor (TfR). RESULTS: Six out of 12 subjects had defective endogenous EPO production. All patients but two responded to treatment with steady increases in Hb levels above 10 g/dl, and the median dose of rHuEPO required for correction of anaemia was 75 U/kg. Response was associated with an early increase in serum TfR. Six patients developed functional iron deficiency and required iron supplementation to obtain response. Treatment improved functional ability in 4/10 responders. CONCLUSIONS: Subcutaneous rHuEPO can stimulate erythroid marrow activity in cancer anaemia, even in patients with advanced disease, and marrow response can be adequately monitored by serum TfR. Functional iron deficiency as a cause of nonresponse to rHuEPO is frequent in these patients and may require parenteral iron administration. Although erythropoietin can improve the anaemia of cancer, the decision to treat should be individualised for each patient, looking more at the quality of life and cost-effectiveness than at cosmetic increases in the haemoglobin level.

Aged↗

Bronchial hyperresponsiveness and bacterial respiratory infections.

Some studies suggest a potential role for bacterial respiratory tract infections in the development of bronchospasm and the progression of chronic obstructive pulmonary disease (COPD). Patients with bronchiectasis or cystic fibrosis have exaggerated airway reactivity; croup in children can also cause exaggerated upper and lower airway responsiveness. Bronchial obstruction after inhalation of Haemophilus influenzae and other bacteria has been reported. Between January 1989 and June 1990 we and two other centers studied 193 patients suffering from acute exacerbation of asthma. Fifty-two (27%) of these patients had bacteria in their sputum. Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, Moraxella catarrhalis, and H influenzae were the most commonly isolated bacterial species. Antibiotics may be of value in the treatment of infective lung disease, not only by killing bacteria but also by preventing increases in bacterial histamine levels within the lung airways. Moreover, an antibiotic of proven efficacy can reduce airway reactivity in patients with bacterial exacerbations of COPD or bronchial asthma. In 12 patients with acute bacterial exacerbation of asthma and high airway reactivity to methacholine, a ten-day course of treatment with cefaclor and existing bronchodilators induced microbiologic cure and a slight but nonsignificant change in airway reactivity in nine patients. Antibiotic therapy has a minor but clear role in the control of acquired bronchial hyperreactivity during bacterial respiratory infections in asthmatic patients; however, because of airway inflammation, an antibiotic's efficacy is evident only when the inflammatory process subsides. Approaches designed to minimize airway reactivity may contribute to the prevention or reversal of respiratory failure during exacerbation of COPD and bronchial asthma.

Asthma↗

Bacterial isolates and cigarette smoking in patients with chronic bronchitis: results from an Italian multicenter survey.

Patients who were cigarette smokers suffering exacerbations of chronic bronchitis were examined in eight outpatient clinics in five regions of Italy, three from the South (Campania, 82 patients; Sicily, 82 patients; and Puglia, 29 patients) and two from North (Lombardy, 33 patients; and Liguria, 50 patients). Haemophilus influenzae was the most frequently isolated bacterium in the patients' sputum (in 30% of the total group), followed by Streptococcus pneumoniae (in 20%), Staphylococcus aureus (in 25%), and Branhamella catarrhalis (in 7%). H. influenzae was the most common bacterium in the South (in 37%) and S aureus in the North (in 13%). Smoking index scores (number of cigarettes smoked daily x years of smoking) were 827 in patients in whom H influenzae was isolated; 691 in patients with S aureus; 599 in patients with S pneumoniae; 542 in patients with B catarrhalis; and 446 in patients in whom no isolates were found. Pulmonary function was most severely decreased in patients positive for H influenzae and S aureus. The results indicate an association between heavy cigarette smoking and lower respiratory tract infections that is influenced by regional differences.

Bronchitis↗

Transferrin receptor expression in the human placenta.

Iron transport from the mother to the fetus is mediated by transferrin receptors located at the maternofetal interface of the placenta. Transferrin receptors bind iron-loaded transferrin molecules from the maternal plasma, thus allowing iron uptake by trophoblastic cells which then deliver the metal to the fetal plasma. We have measured the transferrin receptor content in the placentas from 16 normal-term pregnancies and investigated the relationships between transferrin receptor expression and non-haem iron content, as well as maternal and fetal iron status. Transferrin receptor content was evaluated indirectly by determining the transferrin binding capacity of a placenta extract. Transferrin receptor content of the placenta ranged from 20 to 154 micrograms/g of tissue, with a mean value of 96 +/- 37 micrograms/g. The mean non-haem iron content was 78 +/- 11 micrograms/g of tissue, corresponding to 47 +/- 10 mg for the whole placentas. The amount of transferrin receptors in the placenta was found to be inversely related to the amount of non-haem iron (r = 0.64; p less than 0.025). No significant relationship was observed between each of these two parameters and the iron status of either the mother or the fetus. We conclude that placental non-haem iron, which represents a storage form of this element, is likely to play a regulatory role in the expression of transferrin receptors, and consequently in the process of iron uptake by the placenta.

Female↗

Myelodysplastic syndromes: a multiparametric study of prognostic factors and a proposed scoring system.

In 72 consecutive patients with previously untreated myelodysplastic syndromes (MDS) having a median follow-up of 44.9 (range: 6-198) months, a multiple regression analysis was conducted of the prognosis significance of 26 clinical and laboratory parameters, including bone marrow (BM) biopsy characteristics. Parameters which had independent prognostic meaning served to construct a scoring system for survival prediction. Only 7 parameters were significant: hemoglobin, BM cellularity, BM blast percentage, abnormal location of immature precursors (ALIP), fibrosis, dysmegakaryopoiesis and the erythro/myeloid ratio. They enabled us to predict 42% of all MDS patient survival (p less than 0.03) and 84% (p less than 0.02) of survival of patients who lived over 20 months. Based on the value of these parameters in individual cases, the patient population had a score ranging from 0 to 13, with a median value of 5. Median survival of patients with a score less than or equal to 5 was 117, while that of patients with a score greater than 6 was 33 mos. This scoring system, which has been draw from a wide panel of clinical and laboratory parameters, will be verified on prospective studies.

Humans↗

In vitro growth of bone marrow-derived multipotent and lineage-restricted hematopoietic progenitor cells in myelodysplastic syndromes.

The aim of the present study was to evaluate the incidence of bone marrow-derived multipotent (CFU-GEMM), megakaryocytic (CFU-Mk), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitor cells in 22 patients with myelodysplastic syndromes (MDS), and to investigate the role of hematopoietic accessory cells (T-lymphocytes and monocytes) as a possible cause of growth derangement. As compared to normal controls (n = 15), growth values in the 22 patients (mean +/- SEM) were significantly reduced for CFU-GEMM (0.4 +/- 0.1 versus 7 +/- 1, P less than 0.0005), CFU-Mk (1.4 +/- 0.5 versus 18 +/- 4, P less than 0.0005), BFU-E (2.2 +/- versus 40 +/- 6, P less than 0.0005), and CFU-GM (19 +/- 5 versus 65 +/- 10, P less than 0.0005). The growth of CFU-GEMM was abnormal at an early stage in the clinical development of MDS, sometimes even when CFU-GM formation was still normal. Colony-formation was unaffected by removal of hematopoietic accessory cells. Although no correlation was found between the incidence of lineage-restricted progenitors and the degree of peripheral cytopenia, derangement of colony growth was more pronounced in patients with worse prognosis. We conclude that: (i) the grossly defective CFU-GEMM growth supports the concept of MDS as clonal disorders of hematopoietic multipotent stem cells; (ii) a progressive impairment of in vitro hematopoiesis occurs in association with the clinical progression of the myelodysplastic syndromes.

Anemia, Refractory↗

In vitro and in vivo effects of recombinant interferon gamma on the growth of hematopoietic progenitor cells from patients with myelodysplastic syndrome.

Recombinant interferon gamma (rIFN-gamma) has been shown to have antiproliferative effects on normal and leukemic hematopoietic cells, to induce cell differentiation and to modulate hematopoietic growth factor production. We have studied the effects of rIFN-gamma on the growth of hematopoietic progenitors from 3 patients with myelodysplastic syndrome who were treated with rIFN-gamma (0.01 mg/m2 given subcutaneously three times a week) as part of an Italian pilot study. When bone marrow cells were cultured in semisolid medium in the continuous presence of rIFN-gamma (10-10(4) U/ml), inhibition of colony formation was the most common response. However, an enhancement of hematopoietic progenitor growth was observed in one patient at the lowest concentration tested (10 U/ml). Preincubation of bone marrow mononuclear cells with low concentrations of rIFN-gamma in suspension culture for 5 days induced or enhanced in vitro colony formation in two cases; again, higher concentrations resulted in inhibition of hematopoietic progenitor growth. Two patients showed a slight improvement of in vitro progenitor growth after one month of treatment with rIFN-gamma. Although preliminary, these data indicate that rIFN-gamma may have both stimulatory and inhibitory effects on myelodysplastic hematopoiesis, depending on both the effective concentrations and the interactions with accessory cells.

Adult↗