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Biomedical subjects

L Fabbri

Publications and source records attributed to L Fabbri.

At least 19 recordsLinked to original sources

Comparative efficacy of once-daily ciclesonide and budesonide in the treatment of persistent asthma.

BACKGROUND: The aim of this study was to compare the efficacy and safety of once-daily ciclesonide, a new-generation, on-site-activated, inhaled corticosteroid, with once-daily budesonide in persistent asthma. METHODS: Eligible patients requiring budesonide or equivalent 320-640 microg (ex-mouthpiece, equivalent to 400-800 microg; Turbohalertrade mark) daily entered a 2-week baseline, and then a 2- to 4-week pretreatment period (budesonide 1280 microg/day; ex-mouthpiece, equivalent to 1600 microg/day). Patients with an increase in forced expiratory volume in 1s (FEV1) of 7% or 0.15 L were randomised to ciclesonide 320 microg (ex-actuator, equivalent to 400 microg ex-valve) via a hydrofluoroalkane-metered dose inhaler (HFA-MDI) without a spacer or budesonide 320 microg once daily in the morning for 12 weeks. Change in FEV1 was the primary endpoint. RESULTS: In all, 359 patients were randomised. The FEV1 and forced vital capacity (FVC) decreased by 0.18 and 0.12L, respectively, in the ciclesonide group, and by 0.23 and 0.21L in the budesonide group. For FEV1, ciclesonide was noninferior and numerically superior to budesonide. For FVC, ciclesonide was statistically superior to budesonide (P=0.010). Asthma symptom scores were comparable; the median percentage of symptom-free days was significantly higher for ciclesonide (43.6%) versus budesonide (25.8%) (P=0.017). Rescue medication use decreased significantly only for ciclesonide patients (P=0.009). Frequency of adverse events was low in both groups. CONCLUSION: Ciclesonide 320 microg once daily by HFA-MDI without a spacer was at least as effective as budesonide 320 microg once daily in persistent asthma.

Administration, Inhalation↗

Limits for the central production of Theta+ and Xi(--)pentaquarks in 920-GeV pA collisions.

We have searched for Theta+(1540) and Xi(--)(1862) pentaquark candidates in proton-induced reactions on C, Ti, and W targets at midrapidity and square root of s = 41.6 GeV. In 2 x 10(8) inelastic events we find no evidence for narrow (sigma approximately 5 MeV) signals in the Theta+ --> pK0(S) and Xi(--) --> Xi- pi- channels; our 95% C.L. upper limits (UL) for the inclusive production cross section times branching fraction B dsigma/dy/(y approximately 0) are (4-16) mub/N for a Theta+ mass between 1521 and 1555 MeV, and 2.5 mub/N for the Xi(--). The UL of the yield ratio of Theta+/Lambda(1520) < (3-12)% is significantly lower than model predictions. Our UL of B Xi(--)/Xi(1530)0 < 4% is at variance with the results that have provided the first evidence for the Xi(--).

Journal Article↗

Summary of recommendations for the design of clinical trials and the registration of drugs used in the treatment of asthma.

With new drugs being introduced to treat asthma it is timely to review criteria that can be used to assess efficacy in clinical trials. Anti-asthma drugs are classified into symptoms-modifying, symptom preventers and disease modifying agents. Attention is drawn to the types of experimental evidence required in preclinical studies to support further clinical development of a new therapy. Clinical trials demand careful selection of patients to maximise the strength of the efficacy signal according to the type of trial being designed. While provocation tests are useful in suggesting efficacy, negative tests do not necessarily indicate lack of anti-asthma activity. Therapeutic trial designs need to take account of duration of treatment, dose-response relationships and confirmatory trials. Outcome measures include symptoms, lung function, reduction in concomitant medication, exacerbations, quality of life and measures of inflammation. Interpretation of results need to include the clinical relevance of any changes as well as statistical significance. Special consideration needs to be given to the evaluation of drugs for acute severe asthma, asthma in children and older people, co-morbidity such as rhinitis, and inhaler devices. As with all drugs introduced into practice, careful attention needs to be paid to both short- and long-term safety.

Acute Disease↗

Reducing agents inhibit the contractile response of isolated guinea-pig main bronchi.

BACKGROUND: Oxidants are involved in many respiratory disorders, including asthma and chronic obstructive pulmonary diseases. Reduced glutathione (GSH), one of the most important antioxidant compounds against oxidant free radicals, is particularly abundant in the respiratory epithelial lining fluid, where its concentration is increased in inflammatory disorders. OBJECTIVE: We hypothesized that reducing agents may have a direct effect on airway smooth muscle. Therefore, we studied the effects of GSH on airway smooth muscle contractility in guinea-pig main bronchi. In parallel, we evaluated superoxide anion generation associated with in vitro bronchial smooth muscle contraction. METHODS: Guinea-pig main bronchi were mounted in organ baths filled with Krebs-Henseleit solution. Concentration-response curves to acetylcholine (Ach) (10(-9)-10(-3) M), carbachol (10(-9)-10(-4) M), or histamine (10(-9)-10(-3) M) were performed in the presence or absence of either reduced or oxidized glutathione (GSSG) (10(-5)-10(-3) M). We also evaluated the effects of GSH and GSSG on allergen-induced contraction in main bronchi obtained from ovalbumin-sensitized guinea-pig. Superoxide dismutase (SOD)-inhibited cytochrome c reduction kinetics was performed to evaluate superoxide anion (O2-) production during Ach-induced contraction. RESULTS: Reduced but not oxidized glutathione significantly decreased smooth muscle contraction induced by Ach, carbachol, and histamine. Similarly, only the reduced form of glutathione attenuated the bronchoconstriction induced by allergen exposure in bronchi from sensitized animals. Finally, SOD-inhibited cytochrome c reduction kinetics demonstrated increased O2- production following bronchial smooth muscle contraction. This production was not affected by epithelium removal. CONCLUSION: Our findings show that GSH decreases bronchial smooth muscle contraction to different stimuli and that oxidant free radicals are produced during bronchial smooth muscle contraction. We suggest that oxidants are involved in the mechanisms of bronchoconstriction and that reducing agents could be a possible therapeutic option for airway obstruction sustained by bronchospasm.

Animals↗

Barkas effect for antiproton stopping in H2.

We report the stopping power of molecular hydrogen for antiprotons of kinetic energy above the maximum (approximately 100 keV) with the purpose of comparing with the proton one. Our result is consistent with a positive difference in antiproton-proton stopping powers above approximately 250 keV and with a maximum difference between the stopping powers of 21%+/-3% at around 600 keV.

Journal Article↗

The specialist palliative care team in Forlì, Italy.

A specialist palliative care team (SPCT) for the care of terminal cancer patients was established at Forli in 1986. Over the years, its staff and the patients cared for have been increasing in numbers up to the present levels of importance. For 12 years the service was supplied by a private institution, Istituto Oncologico Romagnolo (IOR). The National Health Service (NHS) has since stepped in and is now supplying home care directly, leaving the IOR with a cultural, supporting, role and with the promotion of volunteer recruitment. The care provided by the specialist group active in the patients' homes is integrated into the primary care provided by the family doctors. A plan is being realized to establish a palliative care unit (PCU) within the city hospital. The group has also been engaged in research for many years, giving special attention both to prognostic factors in very advanced cancer patients and to the organization and evaluation of the service costs. Moreover, two training courses in palliative care are organized biennially, one for all health workers in the region and one for volunteers co-operating with the medical teams.

Home Care Services↗

Efficacy and tolerability of sumatriptan in the treatment of multiple migraine attacks.

This cross-over, double blind, randomized, multicentre study evaluated the consistency of efficacy and safety of oral sumatriptan in 233 migraneurs. The patients received 50 mg oral sumatriptan or placebo for the treatment of 12 migraine attacks. Within each group of 4 attacks, three were treated with sumatriptan and one with placebo, according to a randomization list. Over all the attacks, the efficacy rate was statistically significant for sumatriptan against placebo at 2 or 4 hours (2 hours: sumatriptan 60%, PLO 38%, p < 0.001; 4 hours sumatriptan 79%, PLO 47%, p < 0.001). Oral sumatriptan was similarly effective at relieving the associated symptoms and at reducing clinical disability in most attacks. The incidence of adverse events did not differ between treatment groups. All the events recorded were mild to moderate as intensity and resolved spontaneously.

Adolescent↗

Improving patient compliance with asthma therapy.

Patients fail to comply with asthma medication for a variety of reasons. These range from physical inability to use an inhaler, through simple forgetfulness, to a conscious decision not to use medication as prescribed due to internal or cultural health beliefs or socioeconomic factors. In some patients, poor self-care because of deep-rooted psychological factors (i.e. factors of which patients have only limited awareness) can affect compliance. Poor doctor-patient communication can be the cause in many other individuals. Thus, there is no single solution that will improve compliance in all patients. Simplifying the regimen or providing memory aids will be sufficient for some patients, while education or psychological counselling will be more appropriate for others. Doctors can also use a range of communication skills to improve the way in which they present information, motivate patients and reinforce progress. These approaches, plus respect for patients' health beliefs and involving them in treatment decisions, can help foster an atmosphere of mutual responsibility and concordance over medicine taking.

Administration, Oral↗

An epidemiological study to assess migraine prevalence in a sample of Italian population presenting to their GPs.

This multicentre, observational, cross-sectional study was conducted to determine migraine prevalence in a sample of population presenting to their GPs. The study covered all the patients who visited the GPs practice, for any reason, on 5 consecutive days of 2 different weeks. A total of 71,588 patients were interviewed by 902 GPs. The prevalence of migraine in this sample was 11.6%.

Adolescent↗

New methods for evaluating acute treatments in migraine.

The crescendo of activities in the field of migraine therapy, has led to the emergence of a class of molecules, the triptans, that are similar in terms of their activity on serotonin receptors, but which actually differ from one another, as each one has its own peculiar clinical profile. A careful examination of their clinical activity and their validation with objective methods may promote the wise use of each drug, make room for new products, and allow patients to make their own choices.

Acute Disease↗

Nociceptin receptor activation inhibits tachykinergic non adrenergic non cholinergic contraction of guinea pig isolated bronchus.

We studied the action of nociceptin (NC) on the atropine-resistant contractions of the guinea pig isolated bronchus evoked by the electrical field stimulation (EFS), an effect that is mediated by the activation of excitatory non adrenergic-non cholinergic (eNANC) nerves and the subsequent release of tachykinins. The functional site by which NC acts in this preparation was investigated using few different NC receptor agonists and the newly discovered NC receptor antagonist, [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2 ([F/G]NC(1-13)NH2). NC inhibited in a concentration dependent manner (pEC50 7.14; Em - 87 +/- 3% of control values) EFS induced contractions. NC effect was mimicked by the NC analogues, NCNH2 and NC(1-13)NH2, but not by NC(1-9)NH2. NC (1 microM) did not affect the contractile effects of exogenously applied neurokinin A (1 microM). [F/G]NC(1-13)NH2 (10 microM) completely prevented the inhibition induced by NC (1 microM), whereas naloxone (1 microM) was found inactive. Both naloxone and ([F/G]NC(1-13)NH2 were per se inactive on basal resting tone as well as on the electrically induced contractions. The present findings show that NC inhibits the atropine-resistant EFS-induced contraction in the guinea pig bronchus by inhibiting eNANC nerves, and suggest the presence of NC receptors, distinct from opioid receptors, on the nerves of the guinea pig bronchus.

Animals↗

Helicobacter pylori and chronic bronchitis.

BACKGROUND: Chronic infections such as those caused by Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus have been epidemiologically related to coronary heart disease (CHD). Other studies place H. pylori in relation to other extradigestive diseases. We carried out an epidemiologic pilot study to evaluate the prevalence of H. pylori in patients with chronic bronchitis, a respiratory disease characterized by persistent chronic inflammation, in comparison with a matched control group. METHODS: An enzyme-linked immunosorbent assay IgG test for H. pylori diagnosis was performed in 60 consecutive patients with chronic bronchitis (15 women and 45 men; age range, 50-89 years; mean age, 70.38 years) and in 69 control subjects, well matched for age and social status (19 women and 50 men: age range, 52-90 years; mean age, 71.3 years). RESULTS: Foty-nine of 60 patients with chronic bronchitis (81.6%) and 40 of 69 subjects in the control group (57.9%) were H. pylori-positive (P = 0.0079). The odds ratio, calculated by simple analysis (3.2) and confirmed by logistic regression analysis (3.399), indicated that H. pylori infection greatly increases the risk of chronic bronchitis. CONCLUSIONS: To date, CHD is the only convincing association between H. pylori infection and an extradigestive disease. The main conclusion of this pilot study is that H. pylori infection seems to increase the risk of developing of chronic bronchitis. An important step in this field will be to evaluate the possible change in the clinical conditions after successful eradication therapy in H. pylori-positive patients with chronic bronchitis.

Aged↗

Efficacy and safety of sumatriptan 50 mg in patients not responding to standard care, in the treatment of mild to moderate migraine. The Sumatriptan 50 mg Italian Study Group.

The tolerability and efficacy of oral sumatriptan 50 mg for the treatment of mild to moderate migraine attacks were assessed in a double-blind, multicenter placebo-controlled study on a group of patients who had not responded sufficiently to analgesic preparations. Three-hundred-and-twenty-eight migraine sufferers treated a first migraine attack with a nontriptan standard care medication: a mixture containing phenazone, butalbital and caffeine (optalidon) or indomethacin plus prochlorperazine plus caffeine (difmetre) or paracetamol 100 mg (tachipirine), depending on their habits. Of these patients, 32.6% reported headache relief with this treatment and were not included in phase II of the study. The 219 patients not reporting relief during the first phase of the study entered the second phase and were randomized to sumatriptan 50 mg or to placebo; 167 of these patients treated a second attack according to the protocol and were evaluated for efficacy. Of the patients with migraine taking sumatriptan, 58% reported headache relief compared with 35% of placebo-treated patients (p = 0.008). The reduction of nausea and vomiting was significantly better in the sumatriptan group. No differences were detected for the recurrence rate, while rescue medication was used more by the placebo group. The safety profile of sumatriptan 50 mg was confirmed. This study demonstrates the usefulness of this dose of oral sumatriptan against the pain and the accompanying symptoms of mild and moderate migraine.

Adolescent↗

The epidemiology of migraine: a retrospective study in Italian emergency departments.

This study was conducted to measure the frequency of contact with emergency departments in Italy because of migraine, and to compare the initial diagnosi s of headache with the diagnosis after application of the International Headache Society (IHS) criteria. A retrospective observational method was used, consisting of an analysis of the records of patients admitted to nine Italian emergency departments during different 4-month periods in 1994. Comparison of the initial diagnosis with the diagnosis after application of the IHS diagnostic criteria was performed. More than 31 million emergency department contacts were reported in Italy during 1994. In the same year, 543 630 patients visited the nine emergency departments enrolled in the study, with 169 569 of these contacts occurring in the 4-month period analyzed in the study. We excluded from the analysis all cases of secondary headache fully recognized at the emergency department admission (ie, traumas, intracranial pathology, systemic diseases). The total number of patients included in our analysis was 1043 (0.6%). The 934 patients who could be fully evaluated were initially classified as having migraine; cluster headache; headache not otherwise specified; or diagnosed in the emergency department as suffering from headache, but reclassified by other departments as suffering from a different disease. After retrospective application of the IHS classification, the diagnostic distribution was modified, revealing that 18% of patients with migraine and 5% with cluster headaches had previously been classified as having headache not otherwise specified; a further 6% of cases with migraine and 0.4% of patients with cluster headache had previously been classified as having secondary headaches. The diagnosis of headache not otherwise specified was made with notable frequency, indicating the limits of emergency department logs and the difficulty in carrying out a retrospective analysis and reassessment of diagnosis. The majority (88%) of patients assessed had not taken drugs for headache in the 48 hours before the emergency department contact, suggesting that in Italy emergency departments are used instead of a visit to the general practitioner. Nonsteroidal anti-inflammatory drugs were the most frequently prescribed drugs in the emergency departments for this group of diagnoses. The research revealed, on the one hand, that headache is a numerically significant phenomenon in the emergency department setting and, on the other, the need to apply prospective designs to this kind of survey.

Cluster Headache↗

Chronic obstructive pulmonary disease international guidelines.

Although chronic obstructive pulmonary disease (COPD) has a public health importance similar to asthma, it has received less attention. The first guideline on the management of COPD was released in 1987 by the American Thoracic Society. In 1992 the Canadian Thoracic Society released its guidelines. In 1995 the European Respiratory Society and the Thoracic Society of Australia and New Zealand released their guidelines and the American Thoracic Society updated and expand its COPD guidelines. All these documents were followed in 1997 by the guidelines developed by the British Thoracic Society. These COPD guidelines show many similarities but also have some interesting differences. The aim of this paper is to review these similarities and discrepancies. Like all guidelines, COPD guidelines suffer from the limited amount of evidence-based medicine supporting them, a limitation that, however, provides a strong stimulus for further research.

Female↗