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Biomedical subjects

M Cazzola

Publications and source records attributed to M Cazzola.

At least 145 records · Page 8Linked to original sources

Comparative evaluation of the clinical and microbiological efficacy of co-amoxiclav vs cefixime or ciprofloxacin in bacterial exacerbation of chronic bronchitis.

In an open randomized study 218 outpatients (159 males and 59 females) ranging between 18 and 85 years of age (mean 61.9) suffering from bacterial exacerbation of chronic bronchitis have been randomly treated: 79 with co-amoxiclav (amoxicillin 875 mg+clavulanic acid 125 mg) twice daily, 69 with cefixime (400 mg) once daily, and 70 with ciprofloxacin (500 mg) twice daily for an average period of 10 days. Before treatment start, 234 bacterial strains (105 Gram-positive and 129 Gram-negative) were isolated as the cause of exacerbation; the leading pathogens were Streptococcus pneumoniae and Haemophilus spp. Eradication rates at the end of treatment were 82.2% for the co-amoxiclav group, 77.6% for the cefixime group, and 81.2% for ciprofloxacin group. Clinical success (cure+improvement) was obtained in 90.8% of the cases treated with co-amoxiclav, in 80.9% for the cefixime group and in 85.7% of patients treated with ciprofloxacin. Seven adverse events (8.9%) of which 4 cases of diarrhea and 3 of itching, were recorded in the co-amoxiclav group. Eleven adverse events (14.7%) were recorded in the cefixime group including gastrointestinal disturbances in 6 patients and mild to moderate increase of liver function in 2. Nine adverse events (12.9%) occurred in the ciprofloxacin group, including insomnia in 3 patients, gastrointestinal disturbances in 2, and serious increase of liver function tests in one patient. It can be concluded that there were no statistically significant differences among the three treatment groups. However, co-amoxiclav demonstrated a higher efficacy rate than cefixime and ciprofloxacin and was better tolerated. Therefore, it can be used as a first-choice drug in the treatment of exacerbation of chronic bronchitis.

Adolescent↗

Intravenous iron therapy for severe anaemia in systemic-onset juvenile chronic arthritis.

The role of iron supplementation in treating the anaemia of systemic-onset juvenile chronic arthritis is not clear. Eight affected children with severe persistent anaemia unresponsive to oral iron therapy were treated with intravenous iron saccharate. From a median post-oral-iron value of 8.0 g/dL (range 6.5-9.5), haemoglobin rose to 11.0 g/dL (10.1-12.1) (p = 0.01). The concentration of serum transferrin receptor, an indicator of iron deficiency, before intravenous therapy correlated with the increase in haemoglobin (r = 0.88, p < 0.01). Intravenous iron saccharate could be an effective treatment for chronic anaemia in this condition, especially with iron deficiency not responsive to oral iron.

Adolescent↗

Effect of telenzepine, an M1-selective muscarinic receptor antagonist, in patients with nocturnal asthma.

Muscarinic M1-receptor antagonists can prevent the induction of a long-lasting excitatory postsynaptic potential in autonomic ganglia. As the prolonged occupation of M1-receptors is a possible protective mechanism against vagal overstimulation, M1-antagonists might prove to be effective in preventing nocturnal wheeze. The aim of the present study was to investigate whether telenzepine, an M1-selective muscarinic receptor antagonist, administered orally at different doses (1.5 mg, 3 mg, 5 mg) for one week, reduced airway obstruction in patients with nocturnal asthma in comparison with placebo. Peak expiratory flow rate (PEFR) difference between each study medication (arithmetic means from values on days 4, 5 and 6) and baseline at 6 a.m. and at midnight on day 5 did not differ significantly. Treatment with placebo nocte (at night, 9 p.m.), or telenzepine 1.5 mg nocte, telenzepine 3 mg nocte and telenzepine 5 mg nocte did not affect significantly the 24-h time course of PEFR. The results of this study indicate that the use of telenzepine via the oral route at a dose of up to 5 mg is not effective in preventing nocturnal asthma.

Administration, Oral↗

Effect of salmeterol and formoterol in patients with chronic obstructive pulmonary disease.

In the present trial we investigated the time course of inhaled salmeterol and formoterol bronchodilation in comparison with that of inhaled salbutamol and placebo in 16 patients with moderate to severe chronic obstructive pulmonary disease (COPD). The study was performed using a single-blind crossover randomized study. The bronchodilator activity of 200 micrograms salbutamol, 50 micrograms salmeterol, 24 micrograms formoterol and placebo, which were all inhaled from a metered dose inhaler, was investigated. Our results showed that salmeterol and formoterol are efficacious in reducing airflow obstruction in patients suffering from COPD. We found similar times of onset to improve FEV1 by 15% for salmeterol and formoterol (salbutamol behaving faster), while the duration of action showed the expected differences between the two long-acting drugs and salbutamol. The results indicate that long-acting beta 2-agonists appear to be very effective in improving airway limitation in patients suffering from COPD. Although the onset of bronchodilation after inhaling salmeterol and formoterol is slightly delayed compared with salbutamol, this is of little clinical importance since in these patients salmeterol and formoterol must be intended for maintenance treatment and not immediate symptomatic relief.

Administration, Inhalation↗

Pulmonary penetration of dirithromycin in patients suffering from acute exacerbation of chronic bronchitis.

The aim of this study was to evaluate the concentrations of dirithromycin, a new macrolide antibiotic, in bronchial secretions (BS), bronchial mucosa (BM), epithelial lining fluid (ELF) and serum in 25 patients with acute exacerbation of chronic bronchitis after a 5-day, once-daily, dirithromycin regimen. All patients received dirithromycin, 500 mg (two 250 mg tablets) given orally once daily at 08.00 fasted, for 5 consecutive days. They were divided into five groups (n = 5 in each group) according to sampling time (24, 48, 72, 96 and 120 h, after the last dose). Mean serum concentrations remained low throughout the study (0.44 microgram/ml at 24 h, 0.31 microgram/ml at 48 h, 0.33 microgram/ml at 72 h, 0.12 microgram/ml at 96 h and 0.11 microgram/ml at 120 h, respectively), although they were higher than the MICs for Moraxella catarrhalis for up to 72 h and than that for Streptococcus pneumoniae for up to 120 h after the last dose. By contrast, in all other samples, mean concentrations were higher than the MICs for many relevant respiratory pathogens for at least 3 days, and higher than that for S. pneumonia and M. catarrhalis for up to 120 h (mean concentrations measured 2.67, 2.15, 1.74, 0.27 and 0.17 micrograms/ml, respectively, in BS; 2.59, 2.59, 1.96, 0.41 and 0.27 micrograms/g, respectively, in BM; 2.21, 2.25, 1.57, 0.22 and 0.15 micrograms/ml, respectively, in ELF). These findings demonstrate that dirithromycin is concentrated in each of these potential sites of infection for up to 3 days after a 5-day course of therapy. Therefore, short-term therapy with dirithromycin may be useful for many respiratory infections.

Anti-Bacterial Agents↗

Serum digoxin levels after concomitant ticarcillin and clavulanic acid administration.

Recently it has been recognized that steady-state serum digoxin concentrations may increase or fall to ineffective levels when the glycoside is administered together with several antibiotics. Our study was designed to assess if serum digoxin levels may be modified by the concomitant use of a ticarcillin and clavulanic acid. The study was carried out in 15 hospitalized patients suffering from exacerbation of their chronic bronchitis without liver disease and renal failure. Serum digoxin levels were not significantly modified by the concomitant use of a ticarcillin and clavulanic acid, although peak digoxin serum concentrations were slightly lower. However, the average time to achieve the maximum concentration and area under the curve over 24 h did not change.

Aged↗

Restoration of normal polyclonal haemopoiesis in patients with chronic myeloid leukaemia autografted with Ph-negative peripheral stem cells.

Only a minority of patients with chronic myeloid leukaemia (CML) benefit from allogeneic bone marrow transplantation (BMT), a potentially curative therapy, or from treatment with interferon alpha, which prolongs survival in cytogenetic responders. In Genoa a programme has been initiated in which CML patients are autografted with Ph-negative peripheral stem cells. To assess the pattern of marrow reconstitution, we studied the clonality of haemopoiesis in five females who engrafted and were Philadelphia chromosome negative. This was performed by evaluating the methylation patterns of the X-linked hypervariable DXS255 locus with the probe M27 beta. All four analysable women showed polyclonal methylation patterns in both granulocytes and T lymphocytes, suggesting that marrow reconstitution occurred from normal residual stem cells.

Adult↗

Effects of granulocyte-macrophage colony-stimulating factor and interleukin-3 on small cell lung cancer cells.

Nonhematopoietic malignant cells may express receptors for hematopoietic growth factors and respond to these peptides. The aim of the present study was to investigate whether small cell lung cancer (SCLC) cells may be stimulated to proliferate by hematopoietic growth factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3), which are currently used in clinical trials in combination with cytotoxic chemotherapy. We studied two SCLC cell lines, H69 and N417. The effects of GM-CSF and IL-3 were evaluated by studying clonal growth, 3H-thymidine incorporation, BUDR/DNA bivariate flow cytometry, c-myc and N-myc oncogene expression, and myeloid surface markers. Our experiments show that both GM-CSF and IL-3 can increase 3H-thymidine incorporation and cloning efficiency and reduce DNA synthesis time of H69 and, to a lesser extent, N417 cells, supporting the hypothesis that hematopoietic growth factors can stimulate the growth of some malignant nonhematopoietic cells in vitro. Further in vitro and in vivo studies are needed to determine whether clinical trials applying these factors for bone marrow recovery after chemotherapy of solid tumors may be hazardous by potentially stimulating growth of remaining tumor tissue.

Carcinoma, Small Cell↗

Pilot trial of combined administration of erythropoietin and granulocyte colony-stimulating factor to children undergoing allogeneic bone marrow transplantation.

We carried out a pilot study to evaluate the combined use of recombinant human erythropoietin (rhEpo) and granulocyte colony-stimulating factor (G-CSF) for accelerating marrow engraftment in children given allogeneic bone marrow transplantation (BMT). Fifteen consecutive children were enrolled in this study; 13 completed it and were evaluable. Using analysis of variance, laboratory and clinical data referring to these children were compared with those of 15 patients previously treated with rhEpo alone and with those of 16 historical controls. Erythroid repopulation, evaluated sequentially through serum transferrin receptor and reticulocyte count, was similarly accelerated in children receiving rhEpo alone and in those receiving combined treatment. These latter, however, showed a further reduction in the total number of red blood cell units required to reach transfusion independence (1.1 +/- 0.7 in the study population vs 2.7 +/- 1.2 in rhEpo group vs 4.2 +/- 2.3 in historical controls; values are mean +/- 1 SD; p < 0.001). Neutrophil engraftment, i.e. time for neutrophils to reach 0.5 x 10(9)/l, was 11 +/- 3 days in children receiving combined treatment, significantly shorter than that of the control groups (16 +/- 3 and 18 +/- 5, respectively; p < 0.001). Acceleration of neutrophil recovery translated into fewer infections: days of fever were significantly reduced in the study population (4 +/- 2 vs 11 +/- 8 vs 15 +/- 6, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Environment and development of respiratory allergy: I. Outdoors.

Respiratory allergic diseases appear to be increasing in most countries. In particular, asthma morbidity and mortality have been reported to be increasing despite the availability of effective asthma medications. It has been also observed that subjects living in urban and industrialized areas are more likely to have respiratory allergic symptoms than those living in rural areas. This increase has been linked to air pollution, rather than to a modification of the genome of the patient. The interplay of genetic and environmental factors in the development of allergic disorders remains a subject of investigation. In the outdoor environment, the most important air pollutants are sulphur dioxide, ozone and particulate matter, in particular diesel exhaust emissions. These pollutants, besides acting as irritants, increasing airways hyper-reactivity, are thought to be causal factors which act to modulate the immune response, with an adjuvant activity on immunoglobulin E (IgE) synthesis. In other words, atopic state can be upregulated by environmental influences, and some subjects develop atopic diseases in response to these environmental factors. Since airborne allergens and air pollutants are often both increased in the same areas, potentiation, either in the degree of acquired sensitization or in the degree of the response to allergens, should be considered as an important factor which might help to explain the increasing frequency of allergic respiratory disease. In the light of our present knowledge, it is evident that further investigation in human subjects, aimed at evaluating specific agents, and their concentration in the atmosphere, which can influence pulmonary function, is needed. These studies may help to explain the increasing problem of asthma morbidity and mortality.

Air Pollutants↗

Evaluation of lung tissue and hilar lymph node concentrations of azithromycin.

Since it is believed that most infections occur in the interstitial fluid, it has been suggested to measure the concentration of antimicrobial agents in pulmonary lymph that reflects the extracellular, extra-blood-vascular milieu in the lung. The aim of this study was to investigate the lung tissue and pulmonary lymph node penetration of azithromycin after 500 mg daily oral administration for three days in patients undergoing open thoracotomy. At the end of the treatment, each subject was assigned for 5 groups of 5 patients each according to thoracotomy time after the last dose (24, 48, 96, 120 and 144 h). Azithromycin was assayed by an agar diffusion method with Sarcina lutea Z114 (DRH) used as the test organism and the Antibiotic Assay Medium 1, pH 8.5 used as the medium. All patients had a detectable concentration of azithromycin in serum 24 h after the last dose (72 h after the first dose); the concentration fell below the detection limit (0.01 mg/l-1) after 96 h (168 h after the first dose). Peak concentrations in lung tissue and lymph nodes were found after 48 h (96 h after the first dose). Tissue and lymph node concentrations of azithromycin were much greater than serum concentrations and these tissue and lymph node concentrations persisted after serum concentrations declined. The concentrations in lung tissue of azithromycin were always higher than corresponding concentrations in hilar lymph nodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Busulfan, cyclophosphamide and melphalan as conditioning regimen for bone marrow transplantation in children with myelodysplastic syndromes.

As typical disorders of the elderly, myelodysplastic syndromes (MDSs) are relatively unusual in childhood. Nevertheless, up to 17% of cases of pediatric acute myeloid leukemia may have a preleukemic phase. In young patients, the goal of treatment is eradication of the preleukemic malignant clone and reconstitution of normal hematopoiesis. Allogeneic bone marrow transplantation (BMT) has proved to be capable of this, but the optimal conditioning treatment to achieve eradication remains to be defined. Between May 1989 and June 1993, eight consecutive pediatric patients with MDS received a marrow transplant from an HLA-identical, mixed lymphocyte culture (MLC) non-reactive sibling. Diagnosis at time of presentation was refractory anemia with excess of blasts (RAEB) in two patients, RAEB in transformation (RAEB-t) in three, and juvenile chronic myelogenous leukemia (JCML, the pediatric counterpart of adult chronic myelomonocytic leukemia) in the remaining three children. Conditioning regimen consisted of busulfan, cyclophosphamide and melphalan, three alkylating agents potentially capable of killing also dormant preleukemic stem cells. The preparative regimen was very well tolerated, and all patients engrafted promptly. Six out of eight patients (75%) are alive and well with a median observation time of 20 months (range 8-34 months). Serial karyotype monitoring and molecular analyses have demonstrated a full chimerism of donor cells and the complete disappearance of trisomy 8 detected before transplant in three cases. All surviving patients have a Karnofsky score of 100%. One boy, affected by RAEB-t with monosomy 7 resistant to treatment with low-dose ara-C, relapsed 11 months after BMT, evolved in AML and died from progressive leukemia. Another patient with RAEB died on day +95 after BMT due to interstitial pneumonia of unclear etiology. This study confirms that allogeneic BMT is the treatment of choice in pediatric patients with MDS, and suggests that the employed conditioning regimen is a safe and effective means for eradicating the preleukemic malignant clone. Particularly noteworthy is that the three children with JCML obtained a complete remission and one of them is now a long-term survivor.

Adolescent↗

Teicoplanin with other drugs: possible pharmacological interactions.

The contemporaneous employment of two or more drugs may present the risk of modifying the required therapeutic effect or producing adverse reactions. These interactions are of a pharmacokinetic and pharmacodynamic type. Teicoplanin is an antibiotic with a glycopeptide structure, produced by Actinoplanes teichomyceticus, active against both anaerobic and aerobic Gram-positive bacteria that are resistant to various chemotherapeutic drugs (beta-lactam and macrolide antibiotics, tetracyclines, co-trimoxazole). Then the aim of this work was to verify experimentally the possible pharmacological interactions between teicoplanin and oral hypoglycemic (phenformin and glibenclamide), or oral anticoagulant (warfarin) or bronchodilator (theophylline) drugs. Teicoplanin (3-15 mg/kg/die i.p. for 4 days) administration to the rat did not significantly (p > 0.05) modify the glycemia, prothrombin and partial thromboplastin times, the hypoglycemic effect of phenformin (2.5 mg/kg/die os for 4 days) and glibenclamide (0.5 mg/kg/die os for 4 days) or the anticoagulant effect of warfarin (0.5 mg/kg/die os for 4 days); moreover it did not significantly (p > 0.05) modify the pharmacokinetics of aminophylline (5 mg/kg i.v.) on the rabbit. In conclusion our results documented that teicoplanin does not interfere with phenformin, glibenclamide, or sodium warfarin activities nor with aminophylline pharmacokinetics.

Animals↗

Clinical pharmacokinetics of theophylline during co-treatment with ticarcillin plus clavulanic acid in patients suffering from acute exacerbation of chronic bronchitis.

The effect of ticarcillin/clavulanic acid, taken for 7 days as vials containing 1000 mg of ticarcillin and 200 mg of clavulanic acid twice daily intramuscularly, on the steady-state pharmacokinetics of theophylline was studied in 12 patients suffering from acute exacerbation of chronic obstructive pulmonary disease. Initially, patients were treated for four days with theophylline as sustained-release formulation in the amount of 600 mg daily; on the last day, blood samples were taken for theophylline determination. Theophylline concentrations were measured serially for 12 hours by the method of polarized immunofluorescence (Abbott TDx system). Subsequently, while theophylline was continued at the same dosage, each patient received in addition ticarcillin/clavulanic acid vials every 12 hours. After seven days of this combined medication, the serial assays of plasma were repeated at the same time intervals as before. No influence of ticarcillin/clavulanic acid was detectable on the steady-state theophylline pharmacokinetics. It is concluded that both drugs can be administered concomitantly without any dosage adjustment of theophylline.

Bronchitis↗

Accelerated erythroid repopulation with no stem-cell competition effect in children treated with recombinant human erythropoietin after allogeneic bone marrow transplantation.

We carried out a pilot study on the use of recombinant human erythropoietin (rHuEPO) to accelerate erythropoietic engraftment in paediatric patients undergoing allogeneic BMT. rHuEPO was administered intravenously at a dose of 75 U/kg per day for 30 d after transplant. Erythroid repopulation, evaluated sequentially through the serum transferrin receptor, was faster in 15 patients receiving rHuEPO than in 16 historical controls (P = 0.0003). This faster erythroid engraftment resulted in a reduction in the total number of red blood cell units required to reach transfusion independence (2.7 +/- 1.2 v 4.2 +/- 2.3, P = 0.027). No significant difference in leucocyte or platelet regeneration was observed. These findings indicate that rHuEPO administration can accelerate erythroid recovery after allogeneic BMT and reduce red cell transfusion requirements with no stem-cell competition effect.

Adolescent↗