Possible relationships between headache-allodynia and nocturnal sleep breathing.

Sleep and headache are linked in a bidirectional way. Breathing quality during sleep may be a possible link between them. The objective of this study were to evaluate the prevalence of headache--and of allodynia--in a population of subjects who underwent cardiopulmonary monitoring during sleep for presumed respiratory problems; to evaluate the possible relationships between the presence of headaches--and of allodynia--and respiratory parameters. We studied 181 subjects, 112 without headache (mean age 59.4 ± 13.1 years, 97 men and 15 women); 69 with history of headache (42 men and 27 women; 41 migraineurs and 28 with tension type headache). Headache diagnosis was made according to ICHD-II criteria. A semi-structured ad hoc questionnaire was used to evaluate the presence of allodynia. Full cardiopulmonary monitoring was performed by SOMNO check(®) effort (WEINMANN) with SaO(2), T90 and AHI determination. Headache and headache-associated allodynia were particularly frequent in this population, suggesting a positive correlation between breathing problems during sleep and head pain, and allodynia. The observation that better respiratory parameters were found among headache sufferers with respect to those without headache, even in allodynic subjects, seems to reverse this point of view: headache and allodynia may possibly have an allostatic function preventing deep sleep and, in turn, avoiding prolonged apneas.

Modulation of biofilm of strains isolated from patients with chronic obstructive pulmonary disease by levofloxacin, moxifloxacin, ciprofloxacin, amoxicillin/clavulanic acid and ceftriaxone.

The ability of levofloxacin, moxifloxacin, ciprofloxacin, amoxicillin/clavulanic acid and ceftriaxone to interfere on biofilm produced by Pseudomonas aeruginosa, Haemophilus influenzae and Streptococcus pneumoniae isolated from patients with chronic obstructive pulmonary disease was evaluated. The effects of antibiotics were evaluated on formation of biofilm (at 1/2, 1/4 and 1/8 X MIC) and on preformed biofilm (at epithelial lining fluid peak concentrations) by means of a spectrophotometric method. Levofloxacin was the most active compound followed by ciprofloxacin, moxifloxacin and amoxicillin/clavulanic acid and ceftriaxone. Levofloxacin may contribute to clear the reservoir of pathogens involved in chronic obstructive pulmonary disease, thus leading to decreased occurrence of acute exacerbations.

The Charta of Milan: basic criteria for the appropriate and accurate use of antibiotics: recommendations of the Italian Society of Chemotherapy.

This article summarizes the recommendations drawn up by the Italian Society of Chemotherapy regarding the proper use of antimicrobial agents for infectious diseases.

Can CAP guideline adherence improve patient outcome in internal medicine departments?

The impact of compliance with Italian guidelines on the outcome of hospitalised community-acquired pneumonia (CAP) in internal medicine departments was evaluated. All Fine class IV or V CAP patients were included in this multicentre, interventional, before-and-after study, composed of three phases: 1) a retrospective phase (RP; 1,443 patients); 2) a guideline implementation phase; and 3) a prospective phase (PP; 1,404 patients). Antibiotic prescription according to the guidelines increased significantly in the PP. The risk of failure at the end of the firstline therapy was significantly lower in the PP versus the RP (odds ratio (OR) 0.83, 95% confidence interval (CI) 0.69-1.00), particularly in Fine class V patients (OR 0.71, 95% CI 0.51-0.98). Analysis of outcome in the overall population (2,847 patients) showed a statistically significant advantage for compliant versus noncompliant therapies in terms of failure rate (OR 0.74, 95% CI 0.60-0.90) and an advantage in terms of mortality (OR 0.77, 95% CI 0.58-1.04). Antipneumococcal cephalosporin monotherapy was associated with a low success rate (68.6%) and the highest mortality (16.2%); levofloxacin alone and the combination of cephalosporin and macrolide resulted in higher success rates (79.1 and 76.7%, respectively) and significantly lower mortalities (9.1 and 5.7%, respectively). Overall, a low compliance with guidelines in the prospective phase (44%) was obtained, indicating the need for future more aggressive and proactive approaches.

Kinetic bactericidal activity of telithromycin, azithromycin and clarithromycin against respiratory pathogens.

The present study assessed the comparative in vitro killing kinetics of telithromycin, azithromycin and clarithromycin. Minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) were determined against Streptococcus pneumoniae, beta-haemolytic streptococci, Haemophilus influenzae and Moraxella catarrhalis strains characterized by different susceptibilities to beta-lactams and macrolides. For each bacterial species, representative strains were chosen for time-kill studies. Telithromycin showed high activity against all the tested strains with MIC ranging from < or = 0.004 to 0.5 mg/L for streptococci, from 0.008 to 8 mg/L for H. influenzae, and from 0.008 to 0.5 mg/L for M. catarrhalis. In time-kill studies, telithromycin showed an overall superior bactericidal activity in respect to macrolides, particularly against resistant strains. In conclusion, telithromycin proved to possess bactericidal activity against a wide range of respiratory pathogens, including strains resistant to common macrolides.

In vitro selection of resistance to clarithromycin in Streptococcus pneumoniae clinical isolates.

In this study the effects of exposure to serum, lung and breakpoint concentrations on Streptococcus pneumoniae susceptibility to clarithromycin, azithromycin, amoxicillin/clavulanate, levofloxacin and moxifloxacin were evaluated. Development of resistance was determined by multi-step and single-step methodologies. In the first experimental set, minimum inhibitory concentrations (MICs) were determined after 10 passages on antibiotic-gradient plates and 10 passages on antibiotic-free plates. Acquisition of resistance was defined as an increase of > or = 4-fold from the starting MIC. In single-step studies, the rate of spontaneous mutations was calculated after a passage on antibiotic-containing agar plates. Azithromycin and levofloxacin gave the highest number of strains with MIC increased of at least 4 times the starting value, followed by moxifloxacin and by clarithromycin which only at the lowest concentration tested selected for resistance in 5 strains. Amoxicillin/clavulanate never displayed > or = 4-fold MIC increase. Frequencies of mutation were lower for clarithromycin and moxifloxacin than for the comparators. At lung concentrations clarithromycin had limited potential to select for resistance.

In vitro synergy and selection of resistance by fluoroquinolones plus amikacin or beta-lactams against extended-spectrum beta-lactamase-producing Escherichia coli.

This study compared the potential synergy of levofloxacin and ciprofloxacin in combination with cefepime, ceftazidime, imipenem, piperacillin/tazobactam or amikacin, against extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli by using checkerboard and time kill studies. Moreover, selection of resistance was determined by frequency of mutations and by calculating the increase in minimum inhibitory concentrations (MICs) after five serial subcultures on antibiotic-containing plates. Synergy occurred more often with levofloxacin combined with imipenem (7/10 strains) and with levofloxacin or ciprofloxacin with amikacin (10/10) than for the other combinations. Time kill studies showed synergy for levofloxacin combined with amikacin, ceftazidime, imipenem or piperacillin/tazobactam, and for ciprofloxacin combined with amikacin, cefepime or imipenem. Antibiotic combinations selected for resistance less frequently than antibiotics alone. Mutation frequency was <10(-12) for all combinations. In conclusion, the combination of a fluoroquinolone with a beta-lactam or amikacin may provide improved antimicrobial activity and help limit the occurrence of resistance in ESBL-producing E. coli strains.

Consecutive epidemics of Q fever in a residential facility for drug abusers: impact on persons with human immunodeficiency virus infection.

Two large outbreaks of Q fever occurred in 1987 and 1988 in an agricultural community for the rehabilitation of drug users. Approximately 40% of the residents were human immunodeficiency virus (HIV)-positive. Two hundred thirty-five residents presented with clinical evidence of a flulike syndrome that was confirmed to be Q fever; moreover, a large proportion of residents developed an asymptomatic infection. Clinical signs and symptoms were rather nonspecific: fever, malaise, and muscle pain that were often associated with pulmonary symptoms. Single or multiple opacities were detected, with mild interstitial inflammation evident on chest roentgenograms. The source of infection was the sheepfold, which is part of the stock-farming activity of the community. Both outbreaks occurred just after lambing had begun. Residents who were exposed during the first epidemic were protected in the second one. The attack rate among HIV-positive residents was significantly higher than that among HIV-negative residents in the first outbreak, whereas only a slight, marginally significant difference was observed in the second outbreak. The clinical features of Q fever did not differ between HIV-positive and HIV-negative individuals. No cases of relapse or chronic disease were observed.

Pollen, mite and mould samplings by a personal collector at high altitude in Nepal.

The new personal portable sampler for detection of environmental biologic particles (Partrap FA52, Coppa, Biella, Italy) was used to evaluate both atmospheric and indoor biologic particles in bedding at high altitudes during two Italian scientific expeditions in Nepal, in 1994 and 1996 respectively. The sampling was performed outdoors and indoors at the following altitudes: Katmandu 1,330 meters (m), LuKla 2,800 m, Namche 3,500 m, Pericle 4,200 m and Piramide 5,050 m. In both expeditions each sample of outdoor and indoor air was obtained by sucking air into the sampler either against the wind during a 6-h period, from 9 am to 3 pm, or from bedding of inhabitants resident at the different altitudes for 5 min. The number of pollens, moulds and mites trapped in each sample were assessed. The statistical analysis of the results by Spearman correlation test revealed a significant inverse correlation (p < 0.02) between altitude and the number of the considered biologic particles for sampling carried out during both the 1994 and 1996 expeditions. Moreover, Wilcoxon paired test showed no significant difference between the biologic sampling obtained in the two expeditions. These results confirm the decrease of the environmental biologic charge in relation to the increase of altitude and prove the efficacy of Partrap FA52 in obtaining reproducible quantitative data.

[Treatment of Community Acquired Pneumonia (CAP) in adults with amoxicillin/clavulanic acid switch therapy: a multicenter italian study] / Trattamento della polmonite acquisita in comunita' nell'adulto, dopo fallimento dl terapia antibiotica orale domiciliare, con amoxicillina/acido clavulanico switch therapy. Esperienza italiana.

Patients with community acquired pneumonia (CAP) previously treated with other oral antibiotics (Cephalosporins 35,3%, Macrolides 26,9%, Tetracyclines 14,1%, Quinolones 12,8%, other 10,9%) for at least 72 hours at home were considered for this national multicentre study. 43 hospitalized patients (17 males and 26 females) ranging between the ages of 19 and 79 were treated with Amoxicillin/Clavulanic acid (AMC) 1,2 g e.v., T.l.D. for at least 3 days. I.V. Treatments were switched to AMC p.o. after apyrexial status. Average treatment duration was 10,8 + 3.6. Sputum/B.A.L. samples were obtained from all patients submitted for microbiological exams in order to determine microbiological aetiology of CAP in patients who have failed on previous antibiotics. At the end of treatment, 30 patients (96,8%) were considered cured, while treatment failed in 1 patient (3,2%). 12 patients were considered not evaluable because serology was positive for M.pneumoniae (5 pts); for C.pneumoniae (3 pts.); 1 patients was positive for Mycobacterium tuberculosis; 1 patient was positive for HIV and Mycobacterium spp.; 2 patients were non-evaluable for lung or bronchial tumor. Not reported adverse events.

Respiratory function at different altitudes.

For the evaluation of a respiratory test at high altitude, several factors must be taken into account: the decreased barometric pressure, the decreased density of air and the degree of acclimatization which is related to the altitude and to the length of exposure. Several studies have shown a reduction in forced vital capacity (FVC) at high altitude and using simulated conditions, mainly related to an increase in pulmonary blood volume and development of interstitial edema. To assess the daily spirometric patterns during ascending to high altitudes we studied 17 healthy subjects at both Capanna Regina Margherita on the Italian Alps (4,559 m) and the Pyramid Laboratory in Nepal (5,050 m). Respiratory function tests were performed every day. Peak expiratory flow values significantly increased. The mean percent increase was 15% at 3,200 and 3,600 m and 26% at 4,559 m. FVC and MEF25 values showed a significant decrease (p < 0.005) during the first days above 3,500 m and improved only after several days spent above this altitude. For each subject the maximal reductions in FVC and maximal expiratory flow (MEF) at 25% of FVC however were found on different days. In our opinion, these data support the hypothesis that at high altitude the respiratory function can be affected by the presence of an increased pulmonary blood volume and/or the development of interstitial edema. The observed changes in forced expiration curves at high altitude seem to reflect the degree of acclimatization that is related to the individual susceptibility, to the altitude reached and to the duration of the exposure. These changes are transient and resolve after returning to sea level.

Bronchial asthma and airway hyperresponsiveness at high altitude.

The mountain climate can modify respiratory function and bronchial responsiveness of asthmatic subjects. Hypoxia, hyperventilation of cold and dry air and physical exertion may worsen asthma or enhance bronchial hyperresponsiveness while a reduction in pollen and pollution may play an important role in reducing bronchial inflammation. At moderate altitude (1,500-2,500 m), the main effect is the absence of allergen and pollutants. We studied bronchial hyperresponsiveness to both hyposmolar aerosol and methacholine at sea level (SL) and at high altitude (HA; 5,050 m) in 11 adult subjects (23-48 years old, 8 atopic, 3 nonatopic) affected by mild asthma. Basal FEV1 at SL and HA were not different (p = 0.09), whereas the decrease in FEV1 induced by the challenge was significantly higher at SL than at HA. (1) Hyposmolar aerosol: at SL the mean FEV1 decreased by 28% from 4.32 to 3.11 liters; at 5,050 m by 7.2% from 4.41 to 4.1 liters (p < 0.001). (2) Methacholine challenge: at SL PD20-FEV1 was 700 micrograms and at HA > 1,600 micrograms (p < 0.005). In 3 asthmatic and 5 nonasthmatic subjects plasma levels of cortisol were also measured. The mean value at SL was 265 nmol and 601 nmol at HA (p < 0.005). We suppose that the reduction in bronchial response might be mainly related to the protective role carried out by the higher levels of cortisol and, as already known, catecholamines.

Role of oral antibiotics in treatment of community-acquired lower respiratory tract infections.

Amoxicillin/clavulanic acid has been one of the first choice treatments for community-acquired lower respiratory tract infection since its introduction nearly 15 years ago. Since then, it has become the "gold standard" against which most new oral antimicrobials are compared, but none of these newer agents has demonstrated a superior efficacy. To the contrary, two recent studies comparing amoxicillin/clavulanic acid with azithromycin, cefixime, or ciprofloxacin in the treatment of acute exacerbations of chronic bronchitis have demonstrated a higher efficacy rate for amoxicillin/clavulanic acid.

Evaluation of the soluble fragments of cytokeratin 19 (CK19) in non-small cell lung cancer (NSCLC).

This study compared the diagnostic efficacy of serum CK19 determination (Cyfra 21-1) with other tumour markers, such as CEA, SCC, NSE, TPA, in patients with resected non-small lung cancer. Tumour marker levels were tested in 90 patients with benign lung disease and at diagnosis in 72 patients with proven NSCLC, 39 squamous cell carcinoma and 33 adenocarcinoma. At presentation baseline levels of all tumor markers were significantly higher (p<0.05) in lung cancer patients than in control subjects, except for NSE. A significant increase (p<0.05) in serum concentrations was observed from stage I to stage IIIb only for Cyfra 21-1 (stage I/II, median=2.7 ng/ml; stage IIIb, median=6.3 ng/ml) and TPA (stage I/II, median=89.8 IU/ml; stage IIIb, median=170.7 IU/ml). Receiver operating characteristic (ROC) analysis was performed to evaluate the best threshold values and the global accuracy of each marker. The highest global sensitivity for NSCLC was reached by TPA (70.8%), whereas that of Cyfra 21-1 was 50%. According to tumour histology, significant difference (p<0.05) in serum levels were found only for CEA (adenocarcinomas, median=5.6 ng/ml; squamous cell carcinoma, median=3.2 ng/ml) and SCC (adenocarcinomas, median=1.0 ng/ml; squamous cell carcinoma, median=1.5 ng/ml). As regards squamous cell carcinoma histotype, the highest sensitivity was obtained by TPA (74.4% at a specificity of 62.2%) and for adenocarcinomas by CEA (78.8% at a specificity of 85.6%). Tumour marker levels were also determined during the follow-up of 10 patients. The best sensitivity in detecting relapses was shown by CEA (90%), followed by TPA (70%), SCC (50%), Cyfra 21-1 (40%) and NSE (10%), even though the CEA test displayed a high percentage of false positive results (98.1%) in patients with no evidence of disease (NED).

High altitude exposure reduces bronchial responsiveness to hypo-osmolar aerosol in lowland asthmatics.

It is well-known that many patients with asthma undergo clinical improvement during a stay at high altitude. At high altitude, the atmospheric and climatic conditions (such as hypoxia, cold and dry air inhalation) could modify the bronchial responsiveness in asthmatics. Our study was designed to assess the difference in bronchial responsiveness to hypotonic aerosol between sea level and high altitudes in nonresident asthmatic subjects. The results were obtained during two mountaineering expeditions above 4,000 m i.e. at 4,559 m on Mt Rosa, Italy; and at 5,050 m near the Mt Everest base camp in Nepal. Eleven mild asthmatics performed standard bronchial challenges with ultrasonically nebulized distilled water (5 min inhalation, delivery 2 mL-min-1) at sea level and after staying at least 72 h at the above mentioned altitudes. The decrease in forced expiratory volume in one second (FEV1) from baseline was used as index of bronchial response. There was no significant difference in pre-challenge FEV1 between sea level and high altitude in either study. However, the bronchoconstriction response to ultrasonically nebulized distilled water was significantly reduced at high altitude in both studies. At sea level the mean FEV1 decrease was 22.2% (range 15-35%), whereas as the maximal altitude it was 6.7% (range 2-11%). Our results indicate that there is a reduction in bronchial responsiveness to hypoosmolar aerosol at high altitude. This suggests that atmospheric and climatic conditions, or physiological adaptations, via mediators such as atrial natriuretic peptide, are beneficial to patients with asthma at high altitude.

Outbreak of Chlamydia pneumoniae infection in former injection-drug users.

In a retrospective analysis of lower respiratory tract infections in an ex-injection-drug users community, we found an outbreak (April to July 1991) of Chlamydia pneumoniae infection. The epidemic occurred in a group of 26 community members (23 men and 3 women, mean age, 28.9--3 years) living and working together, who underwent acute and convalescent serologic tests for Mycoplasma pneumoniae, Legionella pneumophila, cytomegalovirus, adenovirus, Coxiella burnetii, and Chlamydia pneumoniae. All subjects were submitted to chest radiograph, while sputum and blood cultures were performed in symptomatic patients. Antibodies to C pneumoniae were determined by a microimmunofluorescence test. Among all subjects studied (13 HIV-1 positive and 13 HIV-1 negative), 11 (8 HIV-positive and 3 HIV-negative) developed pneumonia, 2 (1 HIV-positive and 1 HIV-negative) developed pharyngitis, and 2 (1 HIV- positive and 1 HIV-negative) developed flu-like syndromes sustained by C pneumoniae; in 4 subjects (2 HIV-positive and 2 HIV-negative) suffering from flu-like syndrome, no causal agents were found. Seven subjects (one HIV-positive and six HIV- negative) remained asymptomatic without any evidence of infection. The prevalence of antibodies to C pneumoniae in HIV-1-positive subjects observed in a sample of community members was significantly higher than in HIV-1-negative subjects. C pneumoniae seems to be involved in respiratory tract infections in HIV-1-infected subjects. Our data suggest that C pneumoniae should be included in the diagnostic approach of respiratory infections in HIV-infected subjects.

Incidence of community-acquired pneumonia caused by Chlamydia pneumoniae in Italian patients.

The incidence of Chlamydia pneumoniae as a cause of community-acquired pneumonia was evaluated in a one-year prospective study in 108 patients with community-acquired pneumonia. The bacteriological diagnosis was based on culture of sputum or bronchial aspirate and examination of acute and convalescent phase sera for Mycoplasma pneumoniae, Legionella pneumophila and Chlamydia pneumoniae. A definitive microbiological diagnosis was obtained in 58 (54%) patients. Chlamydia pneumoniae was the causative agent in 14 patients (13%) on the basis of positive serological tests; in 10 of the 14 patients Chlamydia pneumoniae was also detected by means of an indirect immunofluorescence test using pharyngeal swab specimens. In conclusion, Chlamydia pneumoniae seems to be a common etiological agent of community-acquired pneumonia, as increasingly reported in the last six to seven years.