OBJECTIVES:VSL#3 is a high-potency probiotic mixture that has been used successfully in the treatment of pouchitis. The primary end point of the study was to assess the effects of supplementation with VSL#3 in patients affected by relapsing ulcerative colitis (UC) who are already under treatment with 5-aminosalicylic acid (ASA) and/or immunosuppressants at stable doses.METHODS:A total of 144 consecutive patients were randomly treated for 8 weeks with VSL#3 at a dose of 3,600 billion CFU/day (71 patients) or with placebo (73 patients).RESULTS:In all, 65 patients in the VSL#3 group and 66 patients in the placebo group completed the study. The decrease in ulcerative colitis disease activity index (UCDAI) scores of 50% or more was higher in the VSL#3 group than in the placebo group (63.1 vs. 40.8; per protocol (PP) P=0.010, confidence interval (CI)95% 0.51–0.74; intention to treat (ITT) P=0.031, CI95% 0.47–0.69). Significant results with VSL#3 were recorded in an improvement of three points or more in the UCDAI score (60.5% vs. 41.4% PP P=0.017, CI95% 0.51–0.74; ITT P=0.046, CI95% 0.47–0.69) and in rectal bleeding (PP P=0.014, CI95% 0.46–0.70; ITT P=0.036, CI95% 0.41–0.65), whereas stool frequency (PP P=0.202, CI95% 0.39–0.63; ITT P=0.229, CI95% 0.35–0.57), physician's rate of disease activity (PP P=0.088, CI95% 0.34–0.58; ITT P=0.168, CI95% 0.31–0.53), and endoscopic scores (PP P=0.086, CI95% 0.74–0.92; ITT P=0.366, CI95% 0.66–0.86) did not show statistical differences. Remission was higher in the VSL#3 group than in the placebo group (47.7% vs. 32.4% PP P=0.069, CI95% 0.36–0.60; ITT P=0.132, CI95% 0.33–0.56). Eight patients on VSL#3 (11.2%) and nine patients on placebo (12.3%) reported mild side effects.CONCLUSIONS:VSL#3 supplementation is safe and able to reduce UCDAI scores in patients affected by relapsing mild-to-moderate UC who are under treatment with 5-ASA and/or immunosuppressants. Moreover, VSL#3 improves rectal bleeding and seems to reinduce remission in relapsing UC patients after 8 weeks of treatment, although these parameters do not reach statistical significance.

Human rickettsial diseases comprise a variety of clinical entities caused by microorganisms belonging to the genera Rickettsia, Orientia, Ehrlichia, and Anaplasma. These microorganisms are characterized by a strictly intracellular location which has, for long, impaired their detailed study. In this paper, the critical steps taken by these microorganisms to play their pathogenic roles are discussed in detail on the basis of recent advances in our understanding of molecular Rickettsia-host interactions, preferential target cells, virulence mechanisms, three-dimensional structures of bacteria effector proteins, upstream signalling pathways and signal transduction systems, and modulation of gene expression. The roles of innate and adaptive immune responses are discussed, and potential new targets for therapies to block host-pathogen interactions and pathogen virulence mechanisms are considered.

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Despite the availability of all advanced diagnostic tools, fever of unknown origin (FUO) remains a diagnostic challenge for physicians. The objective was to define, through a retrospective study, the categories of the diseases of Sicilian patients admitted at the Department of Clinical Medicine and Emerging Diseases, University of Palermo, Italy, for classical FUO. Using the registration system for patients admitted from 1991 to 2002, 508 charts of patients admitted because of fever were reviewed. Of these, only 91 patients fulfilled the criteria for classical FUO. The origin of FUO was diagnosed in 62 (68.1%) patients. Infection was the most common cause of FUO with 29 cases (31.8% of total of FUO), neoplasms accounted for 13 cases (14.2%), collagen vascular disease for 11 cases (12.0%), and miscellaneous for 9 cases (9.8%). Undiagnosed FUO were 29 (31.8%) and, of them, 22 cases were followed-up for 2 years. A definite diagnosis could be established only in 8 cases, 13 subjects completely recovered and 4 of them died. In the 73.4% of cases, the FUO have been the result of misleading factors in the diagnostic approaches as made by the physician. The results of our study are similar to those already reported by other authors in other populations, with infections as first, neoplasm as second, and collagen vascular diseases as third most important causes of FUO. In our study the prognosis for undiagnosed FUO cases was good, but a definite diagnosis could be established only in few cases. Therefore, further multicentric, prospective studies of good design are required.

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