P. Mangiarotti

Evaluation of Systemic Host Defense Mechanisms in Chronic Bronchitis

Seventy-six chronic bronchitis patients were studied in order to determine the possible presence of disorders in their systemic defense mechanisms. No significant difference in lymphocyte subsets, in serum immunoglobulin and complement component (C3 and C4) levels was found in chronic bronchitis patients compared to normal adult controls. Skin tests for delayed hypersensitivity revealed a high frequency (39%) of hypoergic patients (with 1-2 positive reactions) in comparison to normal subjects. Altered values of many functional properties of both neutrophils and monocytes were demonstrated. The percentage of patients with intermediate (between 1 and 2 SD below the mean of controls) and defective (lower than 1.96 SD) values of chemotaxis, phagocytosis index and Candida killing was about 50%. Phagocytosis frequency and nitroblue tetrazolium reduction frequency were less frequently impaired.

Clinical Efficacy of Ofloxacin in Lower Respiratory Tract Infections A Multicentre Study

SummaryA multicentre clinical trial was carried out to determine the activity and tolerability of ofloxacin in the treatment of lower respiratory tract infections. 667 patients were randomly allocated to 1 of 3 different twice daily dosage regimens: 400mg (245 patients), 600mg (211) or 800mg (211). The mean duration of treatment was 8.77 ± 2.62 days. Satisfactory overall clinical results (i.e. cured or improved) were obtained in 612 of 667 patients (91.8%). Eradication of pathogens was achieved for 279 of 354 isolated strains (78.8%). Side effects were observed in 31 patients and consisted of gastrointestinal disturbance (22), skin rash (1), neurological disturbance (3) and others (5). No significant alteration of haematological parameters was reported.

Bombesin Enhances Monocyte and Macrophage Activities: Possible Role in the Modulation of Local Pulmonary Defenses in Chronic Bronchitis

Increased lung levels of bombesin-related peptides (BRPs) have been described in smokers and in patients with chronic obstructive pulmonary diseases (COPDs). Moreover, previous studies have shown that BRPs are endowed with immunoregulatory activities. The aim of the present study was to assess the in vitro influence of synthetic bombesin on the activity of mononuclear phagocytes obtained from healthy donors and from COPD patients. Bombesin significantly enhanced in vitro phagocytosis of monocytes and alveolar macrophages in both groups of subjects, restoring deficient phagocytosis in a group of COPD patients. Moreover, bombesin stimulated superoxide anion production and interleukin-8 release by peripheral monocytes.

Defective phagocyte Aspergillus killing associated with recurrent pulmonary aspergillus infections

SummaryAn apparently healthy boy was suffering from recurrentAspergillus infections. No classical conditions of immunodeficiency were found. Studies on the patients phagocytic system revealed neutrophils and monocytes to function normally except inAspergillus killing (microbicidal activity for bacteria andCandida was normal).Aspergillus killing mechanisms may be complex and peculiarly selective, possibly involving both oxygen-dependent and independent mechanisms.ZusammenfassungEin offensichtlich gesunder Junge machte rekurrierendeAspergillus-Infektionen durch. Klassische Formen der Immundefizienz waren nicht nachzuweisen. Bei der Untersuchung des Phagozytose-Systems wiesen die neutrophilen Granulozyten und Monozyten mit Ausnahme der Abtötung vonAspergillus normale Funktionen auf (die mikrobizide Aktivität für Bakterien undCandida war normal). Die Mechanismen für das Abtöten vonAspergillus sind wahrscheinlich komplex und auf eigentümliche Weise selektiv; dabei sind möglicherweise Sauerstoff-abhängige und -unabhängige Vorgänge beteiligt.

Double-Blind Trial RU 41740 vs. Placebo: Immunological and Clinical Effects in a Group of Patients with Chronic Bronchitis

A double-blind trail was performed to investigate the effects of RU 41740, a glycoprotein extract from Klebsiella pneumoniae, on host defenses and its efficacy in reducing the number of exacerbation in 29 evaluable patients with chronic bronchitis, out of 36 patients who entered the study. The drug enhanced the phagocytosis indexes of both polymorphonuclear and mononuclear phagocytes. Increased candidacidal activity of monocytes was also observed. These effects, already detectable after one course of therapy and during the entire period of treatment, were no longer detectable when tested 6 months after the end of treatment. A significantly (p less than 0.05) larger number of patients in the treated group than in the placebo group had no exacerbations during drug administration (0-3 months). Moreover, patients treated with RU 41740 had significantly fewer and shorter episodes of acute exacerbation. The positive decreases in these two parameters persisted throughout the follow-up.

In vitro Activity of Teichomycin against Isolates of Gram-Positive Bacteria

The in vitro activity of teichomycin has been evaluated against 189 clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis and group D streptococci. Teichomycin was as active as vancomycin, a chemically related antibiotic, on staphylococci and inhibited the in vitro growth of methicillin-resistant strains at the same concentration necessary to inhibit the sensitive ones. Against group D streptococci teichomycin was about three times more active than vancomycin (MIC50 = 0.125 mg/l, MIC90 = 0.4 mg/l). MBC:MIC ratios of both drugs against staphylococci were comparable, but teichomycin had higher bactericidal activity against group D streptococci, as shown also by killing curves. The activity of teichomycin was not significantly affected by variation of pH, even if the maximum activity was achieved at neutral pH, or by different methods of MIC evaluation. The antibiotic seemed more active when tested with a low inoculum (10(3)-10(5)/ml): a two- to threefold increase in MIC was observed at an inoculum of 10(7)/ml. A reduction of the in vitro activity could be shown when Penassay broth was used as culture medium.

Flurithromycin ethylsuccinate in the treatment of lower respiratory tract bacterial infections

SummaryEfficacy and tolerability of flurithromycin ethylsuccinate were evaluated in lower respiratory tract infections. One hundred and ten patients (38 women, 72 men; age range 18–87 years) were treates with on 375 mg tablet 12-hourly for a mean duration of 8.7 days. One hundred and five patients were evaluable for efficacy. Overall clinical cure rate was 62.9%; improvement was recorded in 19% of patients for a total satisfactory clinical response rate of 81.9%. Sputum production decreased in most patients, being absent after treatment in 47% (only one patient was negative at baseline); sputum was purulent or mucopurulent in 80% of subjects before and in 20% after treatment. Bacteriological evaluation was possible in 72 patients: pathogen eradication was achieved in 80.2% of cases. Eight patients out of 110 reported adverse reactions, mainly gastrointestinal; in one case treatment had to be discontinued. These results demonstrate that flurithromycin ethylsuccinate is safe and effective in the treatment of lower respiratory tract infections.ZusammenfassungDie Wirksamkeit und Verträglichkeit von Flurithromycin Ethylsuccinat wurde bei Patienten mit Infektionen der tiefen Atemwege geprüft. 110 Patienten (38 Frauen, 72 Männer, im Alter von 18–87 Jahren) erhielten zweimal täglich eine Tablette Flurithromycin Ethylsuccinat zu 375 mg. Insgesamt wurden 62,9% der Patienten klinisch geheilt, 19% gebessert. Die Rate an befriedigendem klinischen Ansprechen lag somit bei 81,9%. Bei den meisten Patienten ging die Sputumproduktion zurück. Bei 47% hatte die Sputumproduktion nach Behandlungsende aufgehört (nur bei einem Patienten bestand zu Therapiebeginn keine Sputumproduktion). Purulentes oder mukopurulentes Sputum bestand vor Behandlung bei 80% und nach Behandlng bei 20% der Patienten. Bei 72 Patienten war eine bakteriologische Befundung möglich. In 80,2% der Fälle wurde der Erreger eliminiert. Bei acht der 110 behandelten Patienten traten Nebenwirkungen auf, die meist den Gastrointestinaltrakt betrafen. In einem Fall mußte die Behandlung abgebrochen werden. Diese Ergebnisse zeigen, daß Flurithromycin Ethylsuccinat ein wirksames und sicheres Medikament für die Behandlung tiefer Atemwegsinfektionen ist.

Post-exposure rate of tuberculosis infection among health care workers measured with tuberculin skin test conversion after unprotected exposure to patients with pulmonary tuberculosis: 6-year experience in an Italian teaching hospital

BackgroundThis study assesses the risk of LTBI at our Hospital among HCWs who have been exposed to TB patients with a delayed diagnosis and respiratory protection measures were not implemented.MethodsAll HCWs exposed to a patient with cultural confirmed pulmonary TB and respiratory protection measures were not implemented were included. Data on TST results performed in the past (defined as T0) were recorded. TST was performed twice: first, immediately after exposure to an index patient (T1) and three months later (T2). The period of time between T0 and T1 was used to calculate he annual rate of tuberculosis infection (ARTI), while le period of time between T1 and T2 was used to calculate the post exposure annual rate of tuberculosis infection (PEARTI).ResultsFourteen index patients were admitted; sputum smear was positive in 7 (58.3%), 4 (28.6%) were non-Italian born patients. 388 HCWs were exposed to index patients, a median of 27 (12-39) HCW per each index patient. One hundred eighty (46.4%) HCWs received BCG in the past. One hundred twenty two HCWs (31%) were TST positive at a previous routine screening and not evaluated in this subset. Among the remaining 255 HCWs with negative TST test in the past, TST at T1 was positive in 11 (4.3%). ARTI was 1.6 (95% CI 0.9-2.9) per 100 PY. TST at T2 was positive in 9 (3.7%) HCWs, that were TST negative at T1. PEARTI was 26 (95% CI 13.6-50) per 100 PY. At univariate analysis, older age was associated with post exposure latent tuberculosis infection (HR 1.12; 95% CI 1.03-1.22, p=0.01).ConclusionsPEARTI was considerably higher among HCWs exposed to index patients than ARTI. These data underscore the overwhelming importance of performing a rapid diagnosis, as well as implementing adequate respiratory protection measures when TB is suspected.

Phagocytes and their pharmacological modulation in chronic bronchitis

Altered values of many functional properties of both peripheral phagocytes (neutrophils and monocytes) and alveolar macrophages were demonstrated in patients with chronic bronchitis. Out of this population 16 patients with defective phagocytosis index were included in an open randomized trial to investigate the effect of RU41740, a glycoprotein extract of K1. pneumoniae, on this phagocytic function and its efficacy in reducing the number of exacerbations. A relationship between the restoration of the immunological parameter and the clinical improvement was demonstrated. This effect suggests that phagocytosis can play a role in protecting patients with chronic bronchitis from infectious exacerbations.

5-hydroxymethylcytosine but not MTAP methylation status can stratify malignant pleural mesothelioma based on the lineage of origin

BackgroundMalignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis, mainly associated with work or environmental exposure to asbestos. MPM’s molecular profile is largerly unexplored and effective therapies are still lacking. MPM rarely harbours those somatic genetic lesions that usually characterize solid epithelial-derived tumors. On this basis, our study aims at investigating MPM epigenetic profile.MethodsWe here assessed through immunohistochemistry, FISH and methylation specific PCR, the expression of 5-hydroxymethylcytosine (5- hmC) - an epigenetic marker and an important regulator of embryonic development and carcinogenesis - and the methylation status of the promoter of the MTAP gene - encoding for an enzyme involved in the rescue process of methionine and adenine - in two relevant series of FF-PE MPM samples derived from MPM thoracoscopic biopsies. Tissue sampling was performed at diagnosis.ResultsWithin the limitations of the study cohort, the 5-hmC immunophenotype was different among the histological MPM types analysed. In fact, 18% of the epithelial MPMs were negative, 47% weakly positive, and 35% of the cases showed an intense expression of 5-hmC. Sarcomatoid and biphasic MPMs showed intense 5-hmC expression pattern (positive and weakly positive in more than 80% of cases). Among MPM featuring epithelial lineage, none showed methylation of MTAP promoter.ConclusionsMesothelial sarcomatoid tumors featured a methylation profile characterized by a permanent gene silencing. Epithelial MPM methylation profile was in-between that of sarcomatoid MPM and the one of epithelial-derived tumors. MTAP promoter methylation level cannot be considered a suitable biomarker of epithelial MPM arousal.