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L Allegra

Publications and source records attributed to L Allegra.

At least 19 recordsLinked to original sources

Serological evidence of infection with Chlamydia pneumoniae is related to the severity of asthma.

There is evidence that infection with Chlamydia pneumoniae is associated with asthma of recent onset and that it can influence the severity of asthma. This has led to the suggestion that macrolide antibiotics may be useful in the treatment of asthma in subjects infected with C. pneumoniae. This study examined the association between immunoglobulin (Ig)G and IgA titres to C. pneumoniae and the severity of asthma. IgG and IgA antibodies to C. pneumoniae were measured in 619 subjects with asthma (18-60 yrs), using the microimmunofluoresence method. Subjects were asked about their use of asthma medicines, symptoms, previous hospitalization for asthma, smoking status and age of onset of asthma. In subjects with IgG titres of > or =1:64 and/or IgA titres > or =1:16 (n=212), spirometry was performed and peak expiratory flow rate (PEFR) and symptoms were recorded twice daily for 4 weeks on a diary card. The use of high dose inhaled steroids was associated with an increase of 74.1% in the titre of IgG antibodies (p=0.04) and an increase of 70.6% in the titre of IgA antibodies (p=0.0001) when compared with the use of low dose inhaled steroids. There was an inverse association between IgG antibodies and forced expiratory volume in one second (FEV1) as a percentage of predicted in those subjects with elevated IgG and/or IgA (p=0.04). In this group IgA antibodies were also associated with a higher daytime symptom score (p=0.04). Higher titres of antibodies to Chlamydia pneumoniae appears to be associated with markers of asthma severity. This raises the possibility that chronic infection with Chlamydia pneumoniae leads to an increase in the severity of asthma. Studies aimed at eradicating chronic infection with Chlamydia pneumoniae are necessary to determine whether or not this is the case.

Administration, Inhalation↗

Chlamydia pneumoniae detection in atherosclerotic plaques in Italy.

Italian investigations have shown an association between Chlamydia pneumoniae infection and atherosclerosis. With the use of several diagnostic techniques, including serology, a microimmunofluorescence test, and nucleic acid amplification methods, a temporal association was found between acute C. pneumoniae reinfection and acute myocardial infarction, suggesting that an acute infection superimposed on a chronic or latent infection may trigger the onset of acute myocardial infarction. C. pneumoniae but not Helicobacter pylori or Mycoplasma pneumoniae was found in atherosclerotic plaques of abdominal aortic aneurysms and the carotid artery. A reverse transcriptase-polymerase chain reaction process confirmed the presence of viable C. pneumoniae in carotid atheromas. Nucleic amplification of peripheral blood mononuclear cells may enable the identification of subjects carrying C. pneumoniae in the vascular wall. Macrolide treatment reduced fibrinogen and C-reactive protein plasma levels and C. pneumoniae burden in patients with atherosclerotic diseases.

Adult↗

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Journal Article↗

Inhaled porcine pancreatic elastase causes bronchoconstriction via a bradykinin-mediated mechanism.

Neutrophil elastase has been linked to inflammatory lung diseases such as chronic obstructive pulmonary disease, adult respiratory distress syndrome, emphysema, and cystic fibrosis. In guinea pigs, aerosol challenge with human neutrophil elastase causes bronchoconstriction, but the mechanism by which this occurs is not completely understood. Our laboratory previously showed that human neutrophil elastase releases tissue kallikrein (TK) from cultured tracheal gland cells. TK has been identified as the major kininogenase of the airway and cleaves both high- and low-molecular weight kininogen to yield lysyl-bradykinin. Because inhaled bradykinin causes bronchoconstriction and airway hyperresponsiveness in asthmatic patients and allergic sheep, we hypothesized that elastase-induced bronchoconstriction could be mediated by bradykinin. To test this hypothesis, we measured lung resistance (RL) in sheep before and after inhalation of porcine pancreatic elastase (PPE) alone and after pretreatment with a bradykinin B(2) antagonist (NPC-567), the specific human elastase inhibitor ICI 200,355, the histamine H(1)-antagonist diphenhydramine hydrochloride, the cysteinyl leukotriene 1 receptor antagonist montelukast, or the cyclooxygenase inhibitor indomethacin. Inhaled PPE (125-1,000 microg) caused a dose-dependent increase in RL. Aerosol challenge with a single 500 microg dose of PPE increased RL by 132 +/- 8% over baseline. This response was blocked by pretreatment with NPC-567 and ICI-200,355 (n = 6; P < 0.001), whereas treatment with diphenhydramine hydrochloride, montelukast, or indomethacin failed to block the PPE-induced bronchoconstriction. Consistent with pharmacological data, TK activity in bronchial lavage fluid increased 134 +/- 57% over baseline (n = 5; P < 0.02). We conclude that, in sheep, PPE-induced bronchoconstriction is in part mediated by the generation of bradykinin. Our findings suggest that elastase-kinin interactions may contribute to changes in bronchial tone during inflammatory diseases of the airways.

Acetates↗

Demonstration of viable Chlamydia pneumoniae in atherosclerotic plaques of carotid arteries by reverse transcriptase polymerase chain reaction.

The presence of Chlamydia pneumoniae in atheromas has been demonstrated in several studies. Culture of the organism from arterial tissue has been difficult. We report the use of a reverse transcriptase polymerase chain reaction to detect viable Chlamydia pneumoniae in carotid atheromas. We analyzed 30 patients (14 females, mean age 69.6 +/- 8.8 years) who underwent surgery for the removal of atherosclerotic plaques from carotid arteries. During surgery, samples of lingual vein and superior thyroideal artery were also taken. We applied two molecular biology techniques to the carotid plaques on lingual vein or thyroideal artery samples: 1) polymerase chain reaction (PCR) and 2) reverse transcriptase-PCR (RT-PCR) for the detection of bacterial mRNA, employing PCR primers designed to detect a fragment of the 16S rRNA gene. Blood samples were obtained from the patients for determination of Chlamydia pneumoniae IgG, IgA, and IgM antibody titers by a microimmunofluorescence technique. The results of the present study confirmed the presence of viable Chlamydia pneumoniae in atheromas and support the hypothesis that the organism may be an active factor in the pathogenesis of atherosclerosis.

Aged↗

Chlamydia pneumoniae eradication from carotid plaques. Results of an open, randomised treatment study.

OBJECTIVE: to determine the effect of specific antibiotic treatment with roxithromycin in the eradication of Chlamydia pneumoniae from carotid artery plaques. DESIGN: prospective open randomised treatment study. PATIENTS AND METHODS: we analysed 32 patients (16 females, mean age 70.1+/-14.7 years) who underwent surgery for the removal of atherosclerotic plaques from carotid arteries. During surgery samples of lingual vein and superior thyroid artery were also taken. Before surgery, patients were randomised to receive either roxithromycin 150 mg twice daily or no treatment. Sixteen patients were treated with antibiotic for a mean of 26 days (range 17-35 days). The two groups of patients were comparable in terms of age, sex, risk factors, and seroprevalence for C. pneumoniae. We applied a semi-nested polymerase chain reaction (PCR) technique to the carotid plaques, lingual vein, and thyroid artery samples. Blood samples were obtained from the patients for the determination of C. pneumoniae IgG, IgA, and IgM antibody titres by a microimmunofluorescence technique. RESULTS: in twelve out of sixteen non-treated patients we found evidence of C. pneumoniae DNA in the carotid plaques. Conversely, C. pneumoniae DNA was detected in only five out of sixteen treated patients (p=0.034, Chi-squared test). In all cases PCR was negative for the lingual vein and thyroid artery samples. CONCLUSIONS: Roxithromycin seems effective in reducing the bacterial burden of C. pneumoniae within atherosclerotic plaques, although extended follow-up is needed to determine whether antibiotic treatment benefits long-term patient outcome.

Aged↗

Chlamydia pneumoniae DNA detection in peripheral blood mononuclear cells is predictive of vascular infection.

Abdominal aortic aneurysm tissue and peripheral blood mononuclear cells (PBMC) of 41 consecutive subjects undergoing abdominal aortic aneurysm surgery were analyzed by polymerase chain reaction (PCR) for the presence of Chlamydia pneumoniae, Mycoplasma pneumoniae, and Helicobacter pylori DNA. Twenty patients (49%) were positive for C. pneumoniae DNA-16 (39%) in both PBMC and aneurysm tissue, 3 (7.3%) in PBMC only, and 1 (2.4%) in the artery specimen only. Previous exposure to C. pneumoniae was confirmed in 19 (95%) of the 20 PCR positive subjects by C. pneumoniae-specific serology, using the microimmunofluorescence test. None was positive for H. pylori or M. pneumoniae DNA, either in the PBMC or in the artery specimens. In conclusion, carriage of C. pneumoniae DNA is common both in PBMC and in abdominal aortic tissue from patients undergoing abdominal aneurysm surgery. Blood PCR may be a useful tool for identifying subjects carrying C. pneumoniae in the vascular wall.

Aged↗

Changes in exhaled carbon monoxide and nitric oxide levels following allergen challenge in patients with asthma.

Carbon monoxide is a product of haem degradation by haem oxygenase (HO), activated by inflammatory cytokines and oxidants. This study examined whether allergen challenge can increase exhaled CO levels, as a reflection of HO activation. Exhaled CO and nitric oxide, an expired gas also thought to reflect cytokine-induced airway inflammation, were measured in 15 atopic steroid-naive nonsmoking patients with asthma (13 males, aged 30+/-2 yrs) before and for up to 20 h after allergen challenge. Baseline CO (4.4+/-0.3 parts per million (ppm)) and NO (20.6+/-1.2 parts per billion (ppb)) levels were elevated in asthmatic as compared with nonsmoking normal volunteers (n = 37, 2.1+/-0.2 ppm and 7.0+/-0.1 ppb, respectively, p<0.05). In 10 patients with a dual response in the forced expiratory volume in one second (FEV1) there was a maximal increase in exhaled CO at 1 h (343+/-7.1%) and at 6 h (69+/-12%, p<0.01), followed by a maximal fall in FEV1 (28+/-9%, p<0.05) at 9 h, whereas the maximal NO increase was observed at 10 h (50.2+/-11.8%). The maximal increase in exhaled CO in single response patients (n = 5) was 30+/-2% during the early asthmatic reaction and 46.3+/-9.2% between 4 and 10 h, followed by a fall in FEV1 (9+/-3%, p>0.05) at 9 h, whereas exhaled NO was not significantly changed. In five patients exhaled CO was not attenuated by inhalation of increasing concentrations of histamine causing a 20% fall in FEV1 (PC20) or its subsequent relief by beta2-agonists. In conclusion, exhaled carbon monoxide is increased during the early and late asthmatic reactions independently of the change in airway calibre, while exhaled nitric oxide is increased only during the late reaction and follows the increase in carbon monoxide and fall in the forced expiratory volume in one second in time.

Adult↗

Asthma controller therapy: role of antileukotrienes, a new therapeutic class.

Asthma is a chronic disease and should be treated with both controller and reliever drugs. Asthma controller therapy is not used sufficiently widely, probably due to low compliance with inhaled drugs, lack of response in some patients to low-medium doses of inhaled steroids and possible adverse events. This review analyses a new class of antiasthmatic drugs, leukotriene receptor antagonists (antileukotrienes). At present, two antileukotrienes are available in Italy: zafirlukast and montelukast. Antileukotrienes improve symptoms and also inhibit the effects of some of the inflammatory mediators involved in the pathogenesis of asthma; therefore, antileukotrienes may be used in monotherapy. In addition, the oral administration route is an advantage for compliance. Antileukotrienes significantly improve pulmonary function, asthma symptoms and inhaled and oral steroid and short-acting beta 2-agonist use. Moreover, antileukotrienes produce a 50% mean reduction in the incidence of asthma exacerbations compared with placebo. From the economic point of view, asthma controller therapy using antileukotrienes is associated with a > 50% (compared with placebo) reduction in healthcare costs (hospitalization due to asthma exacerbation, healthcare contact and absenteeism from work or school), which globally account for 93% of asthma-related costs. Antileukotrienes are indicated in the treatment of persistent mild-to-severe asthma, seasonal allergic asthma, exercise-induced asthma and aspirin-induced asthma. Antileukotrienes are well tolerated independently of the duration of treatment and the incidence of the observed adverse events is substantially similar to that observed using placebo. Owing to good tolerability and compliance and the economic advantages, these agents may be considered a valid therapeutic option for the control and management of asthma as a chronic disease.

Administration, Inhalation↗

Beta-thalassemia and pulmonary function.

BACKGROUND AND OBJECTIVE: The survival of patients with beta-thalassemia major and intermedia has improved considerably. This has focused attention on the long-term sequelae of the disease itself and its treatment. The effect of hemosiderosis in major organs (heart, liver, etc) are well-recognized, but the pathophysiology of any lung damage is less clearly understood. We studied lung function changes in 32 patients with beta-thalassemia. DESIGN AND METHODS: Respiratory function tests, CO diffusion and arterial blood gas analysis were performed on 19 patients with beta-thalassemia major (9 F, 10 M) and 13 with beta-thalassemia intermedia (6 M, 7 F). All investigations were performed 24 hours before the patients received a blood transfusion or when they were in a stable state hematologic condition. Echocardiography was performed in all patients and the ejection fraction was employed as a measure of cardiac function. RESULTS: No patient had clinical signs of pulmonary dysfunction. Pulmonary function tests, however, showed a reduction of all main parameters (TLC, FVC, FEV1 and RV) in most patients with beta-thalassemia major, indicating a restrictive type of dysfunction. The pulmonary function of patients with beta-thalassemia intermedia seemed to be preserved. Arterial blood gas values were within the normal range, while in some subjects CO diffusion approached the lower limits of normality. There was no evidence that the observed abnormalities in pulmonary function were secondary to congestive heart failure. INTERPRETATION AND CONCLUSIONS: Iron deposition due to repeated blood transfusions may play a central role in determining lung alterations although the majority of patients are well chelated, suggesting that more than one causal mechanisms could be involved.

Adolescent↗

The effects of multiple dosing with zileuton on antigen-induced responses in sheep.

In a previous study, a single dose of zileuton (10 mg/kg, po) given 2 h before antigen challenge, had a minimal effect on the antigen-induced early airway response (EAR), although it was effective in blocking the late airway response (LAR). Because our previous data indicated that 5-lipoxygenase (5-LO) products contribute to the severity of the antigen-induced EAR in these animals, we hypothesized that the lack of effect of zileuton on the EAR may have had to do with inadequate tissue levels. Therefore, in this study, we determined if multiple dosing with zileuton, which theoretically could improve tissue levels, would provide protection against the antigen-induced EAR as well as the LAR. Each sheep was used in each of the three trials (> or = 15 days apart), the order of which was randomized. For trial 1, the sheep were treated with zileuton (10 mg/kg in 0.1% methylcellulose, p.o.) once a day for 4 days; for trials 2, the sheep were treated with zileuton (10 mg/kg, p.o.) for 2 days; and, for trial 3, the animals were treated with vehicle (0.1% methylcellulose) for 4 days as in trial 1. In all trials, antigen challenge followed 1 h after the last treatment. In the placebo trial, antigen challenge resulted in characteristic EAR (407 +/- 102%, increase over baseline) and LAR (335 +/- 75%, increase over baseline). The antigen-induced effects were completely blocked by the 4-day treatment (EAR = 24 +/- 3%; LAR = 17 +/- 3%, P < 0.05 vs. placebo). In the 2-day trial, the immediate increase in R1, after antigen challenge was only partially blocked (EAR = 163 +/- 16%, P < 0.10 vs. placebo and P < 0.05 vs. 4-day trial), but the late response was completely blocked (24 +/- 3%). The protection against the EAR obtained with the 4-day treatment was significantly better (P < 0.05) than that obtained with the 2-day treatment. The results of this study show that multiple dosing with the 5-LO inhibitor, zileuton, provides protection against the antigen-induced EAR as well as LAR. The effect on the EAR is dependent on the treatment time, with dosing 4 days before antigen challenge providing a more significant effect than either dosing 2 days before challenge (this study) or on the same day as antigen challenge as was seen by us previously. This effect may be related to increased tissue levels of the drug.

Airway Resistance↗

Incidence of Chlamydia pneumoniae infection in vertically HIV-1 infected children.

The rate of seroconversion for antibody to Chlamydia pneumoniae was analysed in blood samples of 26 vertically HIV-1 infected children and 14 seroreverter children (HIV-negative children born to HIV-positive mothers) during a 3-year study period. Seroconversion for Chlamydia pneumoniae was found in 13 of 26 HIV-1 infected children and in 1 of 14 in the seroreverter group (P=0.013). A lower mean CD4+ cell count and p24 antigen positivity at enrolment were significantly associated with seroconversion for Chlamydia pneumoniae. Signs and symptoms of acute respiratory infection were recorded in the 30 to 40 days preceding collection of the blood samples showing seroconversion for Chlamydia pneumoniae in 8 of 13 HIV-1 infected children and in the single seroreverter. This study confirms the potential role of Chlamydia pneumoniae in the pathogenesis of respiratory tract infections in HIV-1 infected subjects.

Child, Preschool↗

Age at symptom onset and distribution by sex and symptoms in patients sensitized to different allergens.

The aim of our study was to analyze the clinical features, particularly the age at symptom onset, of allergic subjects (asthma and/or rhinitis) on the basis of the etiologic elements (sensitization to various allergens). We identified a group of monosensitized patients and a group of polysensitized patients. Within these groups, we identified subgroups of subjects monosensitized to one of the five main allergenic mixes (mites, Gramineae, trees, Parietaria, and Artemisia) and five subgroups of patients sensitized nonexclusively, that is, polysensitized, to the same allergens. The comparison between the two groups and among the various subgroups enabled us to conclude that: 1) mono- and polysensitized patients present some clinical features so different as to constitute two clearly distinct clinical groups 2) analysis of the clinical features associated with the sensitization to a specific allergen brings us to significantly different conclusions when we consider subgroups of monosensitized or polysensitized patients 3) the parameter "age at symptom onset" shows great heterogeneity among both the mono- and the polysensitized subgroups--in particular, the great differences in mean age among the monosensitized subgroups (trees>Artemisia>Parietaria>Gramineae>mites) appear very interesting and are open to various interpretative hypotheses 4) unlike the polysensitized group, in the monosensitized group and subgroups, mean age is similar between men and women and, only for tree- and Parietaria-monosensitive patients, also between asthmatic and rhinitic subjects.

Adolescent↗

The role of chemotherapy in polymorphonuclear phagocytosis in pneumonia.

The efficacy of the host defense system is a determining factor for the outcome of antimicrobial events in infected patients. The neutrophil granulocyte plays a key role in the lung's defense against bacterial invasion and in the absence of a sufficient attraction of functionally intact neutrophils in the lung, following bacterial challenge, severe pulmonary infection may result. The involvement of phagocytes in pneumonia is well known: infiltration of lung parenchyma by neutrophils occurs within a short time in response to infection and is followed by an influx of monocytes. We investigated the effects of antimicrobial therapy in pneumonia on polymorphonuclear neutrophil (PMN) phagocytosis.

Adult↗

Effect of atropine on ciliary beat in human upper respiratory tract epithelial cells.

The mucociliary apparatus is a fundamental element among the defensive mechanisms of the airways. In man, average ciliary beat frequency (CBF) has been reported to be between 600 and 1,000 beats/min and does not vary significantly at different sites along the respiratory tract. Ciliary function is altered by numerous factors, including temperature, pH, cigarette smoke, drugs, and alcohol. The aim of the present study was to evaluate whether intravenous (i.v.) infusion of atropine alters CBF. We studied nine patients (six females and three males, mean age 42.9 years) with otosclerosis, a nonrespiratory disease. All patients were scheduled for surgical stapedectomy. In all patients, nasal brushing was performed before and 20 min following i.v. injection of 0.5 mg atropine sulphate. The cellular samples, maintained viable in tissue medium, were observed under a microscope and filmed. A quantitative evaluation of ciliary activity was obtained by playing the film back in slow motion. The mean CBF value prior to atropine infusion in the nine patients studied was 588.12 (+/- 53.29 SD) beats/min. After infusion of atropine, mean CBF was 442.33 (+/- 52.82 SD) beats/min. The mean percentage drop in CBF following atropine infusion was 24.79% (t = 5.82, p < 0.001). Our data show a drop in in vitro CBF following atropine infusion which, presumably, reflects a fall in the in vivo efficacy of mucociliary transport. Atropine treatment determined a loss in CBF that was inversely correlated with increasing age.

Adult↗

Bacterial adherence in smokers and non-smokers.

Bacterial adherence is thought to be a first important step in the pathogenesis of infection. It is now recognized that bacteria bind to and colonize mucosal surfaces in a highly selective manner via a lock- and key mechanism with complementary receptors on the mucosal surfaces of the host. We studied adherence to buccal cells of a panel of potential respiratory pathogens as Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae and Pseudomonas aeruginosa in 18 smokers and 18 healthy non-smokers. Our results show an increased pneumococcal adherence in smokers compared to that of non-smokers and this may explain the role of smoking as a risk factor in the susceptibility to bacterial pneumonia. The other bacterial species tested do not differ in their adhesion values and probably require previous damage of the mucosa before adhesion 1997 The Italian Pharmacological Society.

Bacterial Adhesion↗