G. Piatti

Lung Function in β-Thalassemia Patients: A Longitudinal Study

Patients with β-thalassemia often present with a restrictive pattern at pulmonary function tests (PFTs) due to several pathogenetic factors. However, the long-term evolution is unknown. We performed a longitudinal study of pulmonary function in asymptomatic, non-smoking patients with β-thalassemia major and intermedia. We looked for temporal changes in lung function and characteristics that would predict the development of PFT abnormalities. In 1996, 18 patients with major β-thalassemia (9 males and 9 females; age range: 18–35 years) and 11 patients with intermediate β-thalassemia (5 males and 6 females; age range: 25–51 years) underwent clinical assessment and PFT, including body plethysmography and gas transfer study (carbon monoxide diffusion capacity, DLCO). Patients were reassessed in 2003. An echocardiographic evaluation was also obtained to exclude pulmonary hypertension. In 55.5% of major and 45.4% of intermediate β-thalassemia patients, a restrictive pattern was found in 1996; in 2003 only 38.8 and 27.2% of patients, respectively, exhibited total lung capacities below the predicted values. DLCO was unchanged in both groups of patients, being reduced in 5 thalassemia major patients and within the normal range in intermediate patients. We conclude that asymptomatic patients with β-thalassemia have a high prevalence of PFT abnormalities, but without significant increases over time. An improvement may be observed when good control of the iron balance is reached with optimal chelation therapy.

Influence of subinhibitory concentrations of brodimoprim and trimethoprim on the adhesiveness, hydrophobicity, hemagglutination and motility of Escherichia coli

In the present study the ability of subinhibitory concentrations (sub-MICs) of brodimoprim (a new 2,4-dimethoxybenzylpyrimidine) to interfere with some important aspects of bacterial cell function, such as surface hydrophobicity, fimbriation, motility and adhesiveness to mucosal cells, was investigated in comparison with those of trimethoprim. The inhibitory behavior of both diaminopyrimidines concerning hydrophobicity and hemagglutination (fimbriation) were essentially the same, while for adhesiveness and motility brodimoprim was more effective than trimethoprim. Diaminopyrimidines have high affinity for the bacterial enzyme dihydrofolate reductase, and this reduces the synthesis of essential purines and as a consequence of DNA and proteins. Our findings indicate that the synthesis and/or the expression of surface adhesins, which are proteins, was also affected by both brodimoprim and trimethoprim, the former being more active.

Influence of Enoxacin Sub-MICs on the Adherence of Staphylococcus aureus and Escherichia coli to Human Buccal and Urinary Epithelial Cells

Bacterial adhesion is the first step in the sequence of events leading to infection. It has been observed that subinhibitory concentrations of antibiotics can interfere with the mechanism of bacterial adhesion. The purpose of the present study was to investigate the capacity of sub-MICs of enoxacin, a new 4-quinolone with 6-fluoro and 7-piperazino substituents, to interfere with the adhesiveness of Staphylococcus aureus and Escherichia coli to human buccal cells and of E. coli to urinary epithelial cells. A significant decrease was observed with 1/2-1/64 the MIC for the adhesion of S. aureus to buccal cells. Inhibition of adhesion was also observed for E. coli strains, but in this case a marked decrease was observed across the range from 1/2 to 1/128 the MIC for urinary cells, and from 1/2 to 1/256 the MIC for buccal cells. Enoxacin also caused elongation of E. coli.

Kinetics of filamentation of Escherichia coli induced by different sub-MICs of ceftibuten at different times.

Subinhibitory concentrations of some antibiotics are able to inhibit adhesion of bacteria to human host cells, to facilitate phagocytosis and to modify the shape of the bacteria cell wall, e.g., variable degrees of filamentation occur frequently in gram-negative bacteria. The kinetics of filamentation of Escherichia coli were investigated by incubation for various periods up to 18 h, with different subinhibitory concentrations of ceftibuten, from 1/2 to 1/128 of the MIC, corresponding to 0.25-0.003 micrograms/ml. Normal shapes, short and long filamentation and bacterial ghosts were observed. The morphological changes in the bacterial cells were influenced by the duration of exposure and by the antibiotic concentration. The greatest filamentation did not occur at 1/2 MIC, the concentration of ceftibuten closest to the MIC, but at 1/8 MIC, and filamentation plus ghosts were maximal between 8 and 18 h of incubation. The morphological changes observed clearly show that ceftibuten has a greater affinity for and impairs the function of penicillin-binding protein 3 (involved in synthesis of peptidoglycan for cross walls) more than other cephalosporins, such as cephaloridine or cefoxitin.

The in vitro effects of ceftibuten on the host defense mechanism

The in vitro effects of ceftibuten on human polymorphonuclear leukocyte (PMN) chemotaxis, phagocytosis and chemiluminescence were investigated. PMN from healthy adult donors were incubated for 1 h in medium alone or in medium containing increasing concentrations of ceftibuten (4, 8 and 40 times the MIC for Escherichia coli). Up to 40 MIC ceftibuten did not significantly interfere with the function of PMN.

Body plethysmographic study of specific airway resistance in a sample of healthy adults.

Background and objective:  sRaw (specific airway resistance) is a corrected index (Raw multiplied by thoracic gas volume) that describes airway behaviour regardless of lung volume. Normal values of sRaw in adult subjects have never been formally defined. To establish sRaw interpretation criteria and to define a range of reference values, we evaluated variability, reproducibility and reliability of sRaw measurements in a group of healthy adults.

Pulmonary dysfunction in thalassaemia major: is there any relationship with body iron stores?

Although pulmonary function abnormalities in thalassaemia major (TM) were described in 1980, the pathogenetic mechanism is not clear and data are contradictory, probably because of study heterogeneity and the multifactorial nature of the pathogenesis. We retrospectively analysed 73 adult TM patients to evaluate the prevalence of pulmonary dysfunction in adult TM and investigate relationships with iron load. All patients underwent body plethysmography and carbon monoxide diffusion (DLCO) was assessed in 63, in addition to blood tests, echocardiogram and T2* myocardial and liver magnetic resonance imaging. Restrictive lung disease was present in 26 (35·6%) patients. Serum ferritin levels were higher in patients with restrictive pattern (1526 μg/l vs. 975 μg/l, P = 0·05). Restrictive lung disease did not correlate with cardiac or liver iron overload. However, considering only patients with serum ferritin >2500 μg/l, those with restrictive pattern also had heart (T2* 14·28 ± 9·99 ms vs. 31·59 ± 7·43 ms) and liver iron overload (LIC 16·02 ± 8·44 mg vs. 5·02 ± 2·69 mg Fe/g dry weight) compared to those without restrictive pattern. Twenty‐five patients (39·7%) had decreased DLCO. No correlation was observed with iron parameters. In our data restrictive pattern was predominant; we observed a relationship with serum ferritin levels suggesting that iron, particularly its chronic effect, could play a role in the pathogenesis of pulmonary disease.

Thymomodulin stimulates phagocytosis in vitro by rat macrophages and human polymorphonuclear cells

Activation of non-specific host defenses can increase resistance to infection in patients and especially those with reduced immune response. Thymomodulin is a calf thymic derivative containing low molecular weight peptides, which exerts immunomodulating activity probably through an enhancement of lymphocyte functions. To explore this possibility, rat macrophages (MP) and human polymorphonuclear (HPMN) cells were incubated in vitro with 100, 200, 400 micrograms/ml of thymomodulin at 37 degrees C for 60 min and their phagocytic activity was investigated. The number of phagocytosing cells was significantly increased following increasing concentrations of thymomodulin and the percentage of phagocytosis was increased more for human PMNs in comparison with rat MP, while the values of the phagocytic index were not modified after challenge with thymomodulin both for MPs and HPMNs.