Giuseppe Sandro Mela

A Comparison of Five Maintenance Therapies for Reflux Esophagitis

BACKGROUND Patients with reflux esophagitis have a high rate of relapse within one year after therapy is discontinued. METHODS We enrolled 175 adults with endoscopy-confirmed reflux esophagitis in a prospective study comparing five maintenance therapies. All the patients were initially treated with omeprazole (40 mg orally once a day) for four to eight weeks, and healing was confirmed by endoscopy. Participants were then stratified according to their initial grade of esophagitis and randomly assigned to 12 months of treatment with one of the following: cisapride (10 mg three times a day), ranitidine (150 mg three times a day), omeprazole (20 mg per day), ranitidine plus cisapride (10 mg three times a day), or omeprazole plus cisapride. Endoscopy was repeated after 6 and 12 months of treatment; the endoscopists were blinded to the treatment assignments. Remission was defined as the absence of esophageal lesions on scheduled or unscheduled follow-up endoscopy. RESULTS In an intention-to-treat analysis, the numbers of patients in continued remission at 12 months were 19 of 35 (54 percent) in the cisapride group, 17 of 35 (49 percent) in the ranitidine group, 28 of 35 (80 percent) in the omeprazole group, 23 of 35 (66 percent) in the ranitidine-plus-cisapride group, and 31 of 35 (89 percent) in the omeprazole-plus-cisapride group. Omeprazole was significantly more effective than cisapride (P = 0.02) or ranitidine (P = 0.003), and combination therapy with omeprazole plus cisapride was significantly more effective than cisapride alone (P = 0.003), ranitidine alone (P < 0.001), or ranitidine plus cisapride (P = 0.03). Ranitidine plus cisapride was significantly better than ranitidine alone (P = 0.05). CONCLUSIONS For maintenance treatment of reflux esophagitis, omeprazole alone or in combination with cisapride is more effective than ranitidine alone or cisapride alone, and the combination of omeprazole and cisapride is more effective than ranitidine plus cisapride.

Randomised controlled trial of local allergoid immunotherapy on allergic inflammation in mite-induced rhinoconjunctivitis

BACKGROUND Non-injective routes of immunotherapy are thought to be valuable therapeutic options for respiratory allergy. We investigated the clinical efficacy and the effects of sublingual/oral immunotherapy on conjunctival allergic inflammation in patients with mite-induced respiratory allergy. METHODS We used a double-blind placebo-controlled design. 20 patients with mite-induced rhinoconjunctivitis (six of whom also had mild asthma) were randomly assigned sublingual/oral immunotherapy (n=10) or placebo (n=10) for 2 years. We assessed symptom score by diary cards and inflammatory-cell infiltrate, and expression of intercellular adhesion molecule 1 (ICAM-1) in the conjunctiva after specific allergen challenge at enrollment and after 12 and 24 months of treatment. FINDINGS We found significantly lower symptom scores in the immunotherapy group than in the placebo group in most of the winter months (p=0.05). Compared with the placebo group, inflammatory-cell infiltration after conjunctival challenge, and ICAM-1 expression on conjunctival epithelium decreased significantly in the first year of treatment in the immunotherapy group (p=0.04 and p=0.02, respectively). These effects were also seen for the minimum persistent inflammation, in symptom-free patients exposed constantly to allergens (p=0.02). Serum concentrations of eosinophil cationic protein decreased significantly (p=0.04). Immunotherapy was well tolerated and compliance was good. INTERPRETATION Our results suggest that this immunotherapy is clinically effective in rhinoconjunctivitis and that it decreases the immune-mediated inflammatory responses to the allergen.

Partial regression of Barrett's esophagus by long-term therapy with high-dose omeprazole☆☆☆★

BACKGROUND Barretts esophagus is mainly regarded as an acquired condition related to increased gastroesophageal reflux. Thus it is conceivable that abolition of acid reflux would lead to its regression. The aim of this study was to assess whether long-term treatment with high-dose omeprazole (60 mg/day) produces a consistent control of gastric acid production and normalizes the esophageal acid exposure, thus reducing the length of Barretts epithelium. METHODS Fourteen patients (8 men and 6 women, mean age 52 years) with histologic diagnosis of columnar epithelium longer than 3 cm in the distal part of the esophagus were enrolled and began receiving 60 mg of omeprazole in a single daily morning dose. Before therapy and after 6 and 12 months of therapy, all patients had endoscopy with four-quadrant biopsies at 2 cm intervals. A 24-hour esophagogastric pH recording was performed at entry and after 10 days, 6 months, and 12 months of treatment in all patients. RESULTS The initial length of Barretts epithelium (4.5 +/- 1.9 cm) was significantly reduced after 6 months (3.1 +/- 1.1; p < 0.01) and 12 months (2.1 +/- 1.6; p < 0.005) of treatment. Values were significantly lower at 12 than at 6 months (p < 0.03). The 24-hour mean gastric pH after 10 days (5.89 +/- 0.58), 6 months (5.71 +/- 0.55), and 12 months (5.54 +/- 0.76) of therapy was always higher (p < 0.001) than the basal level (1.9 +/- 0.49). No significant difference in gastric pH was seen over the treatment period. The 24-hour mean percent of time in which pH in the esophagus was below 4.0 decreased significantly (p < 0.001) from a basal rate of 29.4% to 3.5%, 3.0%, and 4.9% in the various time intervals of therapy. There was a normalization of esophageal acid exposure in all patients but two. CONCLUSIONS It can be concluded that the antisecretory effect of 60 mg/day of omeprazole is consistent and is kept constant throughout the entire 1-year treatment period. The consequent normalization of esophageal acid exposure in almost all patients in our series led to a partial, but significant, regression in the length of Barretts epithelium.

Prevalence of rheumatoid arthritis in Italy: the Chiavari study

OBJECTIVE To ascertain the prevalence of rheumatoid arthritis (RA) in an Italian general population. METHODS The study was performed in the years 1991–92 in Chiavari, a small town located on the Ligurian coast, and involved 4456 subjects aged 16 years or more from four general practices. The subjects received a postal questionnaire developed to detect patients with current or past inflammatory joint diseases. The age and sex distribution of the sample were similar to those of the Italian population from the 1992 census. Patients reporting a history of joint swelling in at least a pair of symmetrical joints were reviewed by a rheumatologist. The clinical records of non-responders and responders who failed to attend the clinic were also reviewed. RESULTS 3294 of 4456 (73.9%) subjects answered to the questionnaire. The mean (SD) age of the 3294 responders was 48.3 (19.3) years; 53.7% of them were female. Swelling in at least two symmetrical joints was reported by 230 subjects (7%). Among them, 11 patients fulfilling the 1987 ARA criteria for RA were identified. The prevalence of RA was 0.33% (95% CI 0.13, 0.53) in the general population, 0.13% (95% CI 0, 0.31) in men, and 0.51% (95% CI 0.18, 0.84) in women. CONCLUSIONS These data are consistent with the results of three earlier studies published in the fifties in the Italian literature and confirm that the prevalence of RA is low in Italy and has remained unchanged in the last 40 years.

Topical azelastine reduces eosinophil activation and intercellular adhesion molecule-1 expression on nasal epithelial cells: An antiallergic activity

BACKGROUND It is well known that allergen-specific nasal challenge (ASNC) is a fruitful tool with which to evaluate antiallergic activity exerted by a drug. Azelastine is a new antihistamine also available in topical form (i.e., nasal spray). OBJECTIVE The aim of the study was to evaluate the effects of azelastine nasal spray on inflammatory changes after ASNC in both the early-phase reaction and the late-phase reaction. METHODS The study had a double-blind, placebo-controlled, randomized, and parallel-group design. Twenty patients with pollen allergy were enrolled out of pollen season. ASNC was performed at baseline (TO) and after 1 week of washout (T7). At T7, 10 patients sprayed azelastine (1 puff) into their nostrils, and 10 patients used placebo. ASNC was performed after 30 minutes. The considered parameters (evaluated during early- and late-phase reactions) were: (1) clinical signs and symptoms, (2) cytologic assessment (neutrophils and eosinophils), (3) assay-of mediators (eosinophil cationic protein and myeloperoxidase), and (4) expression of intercellular adhesion molecule-1 (ICAM-1) on nasal epithelial cells. We focused our attention on ICAM-1 because it is the natural ligand of leukocyte functional associated antigen-1 and Mac-1, expressed on eosinophils. In addition, ICAM-1 is expressed on epithelial cells only on allergen exposure (both natural and experimental). RESULTS Placebo did not exert any modification on the considered parameters. After azelastine administration, significant decreases in total symptom score, eosinophilic and neutrophilic infiltration, and ICAM-1 expression were observed during both early- and late-phase reactions. Furthermore, serum eosinophil cationic protein levels decreased during the late-phase reaction, whereas myeloperoxidase was not affected by the treatment. These findings were confirmed by the powerful Kochs split-plot statistical analysis. CONCLUSION Azelastine exerts antiallergic activity, mainly affecting eosinophil function and downregulating ICAM-1 expression, on nasal epithelial cells.

Individual Recognition by Heart Rate Variability of Two Different Autonomic Profiles Related to Posture

BACKGROUND Power spectrum analysis of heart rate variability (HRV) can estimate the state of sympathovagal balance modulating sinus node activity. In view of the large distribution of spectral variables, a recognition of well-defined physiological conditions has never been attempted on an individual basis. METHODS AND RESULTS We considered 10 spectral variables extracted from short segments (200 to 500 cardiac cycles) of 350 ECG tracings recorded in normal subjects in both supine and upright positions (700 patterns). The tracings were first ordered consecutively and subsequently assigned alternatively to a training or to a test set (each consisting of 175 cases, providing 350 patterns considered to be independent). A forecasting linear method estimated a normalized activation index (ranging from -1 for supine to +1 for upright) that concentrated the information derived from spectral variables and that identified, in the test set, individual by individual, approximately 84% of corresponding body postures. CONCLUSIONS The combined use of spectral methodology and forecasting analysis has revealed an information content embedded, per se, in a short series of RR intervals capable of recognizing, individual by individual, two different autonomic profiles related to posture.

Comparison of isotope ratio mass spectrometry and nondispersive isotope-selective infrared spectroscopy for 13C-urea breath test

Objectives:The 13C-urea breath test (UBT) is a sensitive and noninvasive method to diagnose Helicobacter pylori infection, but mass spectrometry (IRMS) is very expensive. The aims of this study were to compare the new low-priced infrared spectroscopy with IRMS in detecting the infection and to assess the influence of feeding on test accuracy.Methods:One hundred thirty-four patients with dyspeptic symptoms were recruited. Of these, 74 were infected and 60 uninfected on the basis of both CLO-test and histology. A subgroup of 37 patients (22 H. pylori-positive and 15 H. pylori-negative) was studied under fasting and nonfasting conditions on two different days. Duplicate breath samples were analyzed with two IRMS systems (Breath Mat and ABCA) and an infrared spectrometer (IRIS) before, 15 min, and 30 min after ingestion of 75 mg 13C-urea with citric acid. In 37 patients the test was repeated the day after the fasted one and was performed 60 min after a meal of 800 Kcal.Results:There was a close correlation between IRIS and Breath Mat (r = 0.969 at 15 min and r = 0.977 at 30 min; p < 0.0001), IRIS and ABCA (r = 0.963 at 15 min and r = 0.985 at 30 min; p < 0.0001), and Breath Mat and ABCA (r = 0.987 at 15 min and r = 0.981 at 30 min; p= 0.0001). The sensitivity ranged from 97–100% at both times with all devices, although the specificity was slightly inferior with the infrared system than with the two IRMS machines (95%vs 98–100% at 30 min), but the difference was not significant (p= NS). Food intake produced three false negative results in all three machines and a systematic shift to lower δ values in infected patients.Conclusions:Infrared spectroscopy can be considered a valid alternative to mass spectroscopy for the diagnosis of H. pylori infection. Fasting is required to guarantee an accurate test.

Impact assessment of oncology research in the European Union

In this study the distribution of papers published by authors from the European Union (EU) in oncological journals was analysed, as was the impact of oncological research in the EU compared with that produced in other countries. Papers published during 1995 in the oncological journals listed by ISI (Institute for Scientific Information, Philadelphia, U.S.A.) were downloaded. The parameters of impact factor (IF), source country population and gross domestic product (GDP) were considered. An analysis of the key words, both those reported by the authors and those attributed by ISI, was carried out using a special purpose program. 36.5% of papers published in oncological journals come from the EU (the U.K., Italy, Germany and France ranking at the top) and 40.7% from the U.S.A. The mean IF was 2.4 for EU papers, 3.3 for the US and 2.4 for other countries. Our data confirm that smaller countries performed better than larger ones. The key words analysis shows that the leading fields of research were breast cancer for diseases, cisplatin for drugs and p53 for experimental studies. A standardisation of key words on behalf of journal editors is proposed.

24-hour study of intragastric acidity in duodenal ulcer patients and normal subjects using continuous intraluminal pH-metry

The circadian pattern of intragastric acidity was assessed in 19 healthy subjects and 37 patients with active, endoscopically proven duodenal ulcer using 24-hr continuous intraluminal pH-metry. The median pH 24-hr profiles showed that ulcer patients had lower postprandial pH elevations and a smaller decline in acidity during the early morning hours when compared with controls. The after-lunch and -dinner area under the curve and maximum pH values were significantly higher in controls compared to ulcer patients. In the nighttime, the median pH values in controls were significantly higher during 9 pm to 12 pm (P=0.02), 12 pm to 4 am P=0.01), and 4 am to 8 am (P=0.0008) compared to the ulcer patients. We conclude that the 24-hr acidity is higher in ulcer patients compared to healthy subjects and that the differences are particularly evident in the postprandial and nocturnal periods.

An overview of rheumatological research in the European Union

OBJECTIVES To evaluate the distribution and scope of papers published by authors from the European Union (EU) in rheumatological journals and the impact of rheumatological research in the EU in comparison with that produced elsewhere. METHODS Papers published during the year 1995 in the 17 rheumatological journals screened by ISI were considered. The journal impact factor (IF) was noted. All key words, both those reported by the authors and those attributed by ISI, were identified and their frequency was calculated using a special purpose program. RESULTS 2331 papers were published in the rheumatological literature during 1995. Of them, 1316 (56.5%) came from the EU (29.4% from the UK, 17.4% from France, 11.5% from Germany, and 10.8 % from Italy) and 544 (23.3%) from the USA. The mean IF of EU papers was approximately 2 in comparison with 3.5 for the USA and 2.4 for other countries. In 1995, 2680 key words attributed by the authors and 5651 attributed by ISI appeared in the rheumatological literature. Less than a quarter of them was cited more than twice. The leading key words were rheumatoid arthritis for diseases and methotrexate for drugs. CONCLUSIONS Bibliometric findings are useful to follow research trends. These data show the relevance of EU rheumatological research and the high scientific production of small countries. Dispersion of key words should be avoided and journal editors should promote their standardisation.