N-acetylcysteine (NAC), an analogue and precursor of reduced glutathione, has been in clinical use for more than 30 yrs as a mucolytic drug. It has also been proposed for and/or used in the therapy and/or prevention of several respiratory diseases and of diseases involving an oxidative stress, in general. The objective of the present study was to evaluate the effect of long-term treatment with NAC on influenza and influenza-like episodes.A total of 262 subjects of both sexes (78% ≥65 yrs, and 62% suffering from nonrespiratory chronic degenerative diseases) were enrolled in a randomized, doubleblind trial involving 20 Italian Centres. They were randomized to receive either placebo or NAC tablets (600 mg) twice daily for 6 months. Patients suffering from chronic respiratory diseases were not eligible, to avoid possible confounding by an effect of NAC on respiratory symptoms.NAC treatment was well tolerated and resulted in a significant decrease in the frequency of influenza-like episodes, severity, and length of time confined to bed. Both local and systemic symptoms were sharply and significantly reduced in the NAC group. Frequency of seroconversion towards A/H 1 N 1 Singapore 6/86 influenza virus was similar in the two groups, but only 25% of virus-infected subjects under NAC treatment developed a symptomatic form, versus 79% in the placebo group. Evaluation of cell-mediated immunity showed a progressive, significant shift from anergy to normoergy following NAC treatment.Administration of N-acetylcysteine during the winter, thus, appears to provide a significant attenuation of influenza and influenza-like episodes, especially in elderly high-risk individuals. N-acetylcysteine did not prevent A/H 1 N 1 virus influenza infection but significantly reduced the incidence of clinically apparent disease. Eur Respir J 1997; 10: 1535-1541

Colonic adenomas represent the natural precursor lesions of most colorectal cancers. The treatment of choice is endoscopic polypectomy. However, after endoscopic removal, polyps recur in a large fraction of cases. Thus, we evaluated the effect of antioxidant vitamins or lactulose on the recurrence rate of adenomatous polyps. After polypectomy, 255 individuals were randomized into three groups. Group 1 was given vitamin A (30,000 IU/day), vitamin C (1 g/day), and vitamin E (70 mg/day); Group 2 was given lactulose (20 g/day); Group 3 received no treatment. Forty-six subjects had to be excluded because the histologic diagnosis was not consistent with adenoma. The remaining 209 individuals were included in the analysis according to the "intention to treat" criterion, though 34 did not adhere to the scheduled treatment or were lost during the follow-up. Subjects were followed at regular intervals for an average of 18 months. Polyps recurring before one year from index colonoscopy were considered missed by the endoscopist. In the 209 evaluable subjects, the percentages of recurrence of adenomas were 5.7 percent, 14.7 percent, and 35.9 percent in the vitamins, lactulose, and untreated groups, respectively. The fraction of subjects remaining free of adenomas, estimated by Kaplan-Meier survival curves, was significantly different among the three groups (log-rank chi-squared = 17.138; P < 0.001). Using Cox's regression analysis, treatment was the only variable that significantly contributed to the model (regression coefficient = 0.905; P < 0.001). In conclusion, either antioxidant vitamins or, to a lesser extent, lactulose lower the recurrence rate of adenomas of the large bowel and can be proposed as chemopreventive agents, at least in high-risk individuals.

The aim of the present open prospective study is to evaluate the efficacy and safety profile of fosfomycin trometamol in the chemoprophylaxis of urinary tract infections following transurethral diagnostic and/or therapeutic manoeuvres. 712 patients were enrolled in 72 urological surgical centres. All the enrolled patients received an initial dose of fosfomycin trometamol (Monuril sachet containing 3 g of active drug in powder) 3 h before and a second dose 24 h after the transurethral manoeuvres. Clinical and microbiological examinations were carried out before the intervention, and then on the second and seventh days after the manoeuvres. 94 patients with positive baseline tests were excluded from the microbiological follow-up for non-compliance with the main inclusion criteria. Out of 618 patients with sterile urine or with bacteriuria less than 10(5) ml on baseline screening, 20 (3.2%) developed UTI on the second day and 22 (3.6%) on the seventh day after treatment. Clinical follow-up is in agreement with these microbiological data. Overall, a total of 24 side effects were observed (3.3%), 16 of which were associated with Monuril treatment. The results of this open study agree with the preliminary observations in the controlled studies.

The effects of ursodeoxycholic acid (UDCA, 450 mg daily) in patients with histologically proven chronic active hepatitis (CAH) have been evaluated in a randomized, double-blind, placebo-controlled study. Twenty-six patients with serum alanine aminotransferase (ALT) values at least twice the normal upper limit in two of three pre-treatment tests received UDCA or a placebo for twelve weeks. In all UDCA-treated patients, serum aspartate amino-transferase (AST), ALT, gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase (AP) fell significantly after 4 weeks of treatment. There was a further decrease at the end of therapy, as well as a small but significant fall in total serum bilirubin. Conversely, 4 weeks after suspension of therapy, serum enzyme levels had increased, reaching values not much lower than those recorded before treatment. Total serum protein, albumin and gamma-globulin did not change after UDCA treatment. In the placebo group no significant variation in the test results were found. The results indicate that UDCA therapy in CAH, as has been observed in primary biliary cirrhosis and primary sclerosing cholangitis, is able to improve several indices of liver damage, without producing any toxic adverse effects.

In a double-blind, crossover study, 10 cirrhotic patients (Child B rating) with steatorrhoea (daily output of faecal fat greater than 8 g) and dyspepsia were placed on a controlled diet for 14 days. Patients then received 150 mg ursodeoxycholic acid (UDCA) or placebo twice daily for 14 days. Faecal fat excretion was reduced from 14.7 to 10.6 g/day by UDCA and dyspepsia symptom scores were also reduced. Serum aspartate aminotransferase concentrations declined significantly (P less than 0.02) following UDCA treatment, whereas serum bile acid levels increased from 35 to 40.5 microM and the percentage of UDCA increased to 22%. It is concluded that UDCA may be useful for many of the symptoms present in patients with liver cirrhosis.