Micronuclei induction, cell cycle delay and apoptosis as markers of cellular stress caused by ursodeoxycholic acid in human lymphocytes.

Ursodeoxycholic acid (UDCA) is a bile acid (BA) used for cholesterol gallstone dissolution. Since epidemiological evidence indicates that BAs can be involved in the etiology of colorectal cancer, we investigated the effects of UDCA and its physiologically produced taurine conjugate tauroursodeoxycholic acid (TUDCA) on human lymphocyte cultures in terms of genetic damage in the form of micronuclei (MN) production, cell cycle modifications and induction of apoptosis. With respect to controls, treatment with UDCA (from 10 microg/ml) caused a dose-related increase in MN, whereas TUDCA caused no significant increase (up to 1000 microg/ml). Fluorescence in situ hybridization (FISH) analysis using pancentromeric probes suggested that UDCA exerts aneugenic activity. Bromodeoxyuridine/Hoechst flow cytometry showed that both BA significantly inhibit cell cycle progression (UDCA at 100 microg/ml, and TUDCA, more markedly at 300-1000 microg/ml). Neither UDCA nor TUDCA affected induction of apoptosis, as evaluated by the Annexin-V-Fluos assay. We conclude that UDCA is potentially genotoxic. However, taking into account the characteristics of other physiological BA, our findings are in line with the concept that long-term UDCA treatment may be safely administered. The multi-assay approach reported here could be useful in the toxicological evaluation of newly developed BA analogs as candidates for pharmacological use.

[Potential antibiotic pharmaceutical cost reduction in an operative unit of infectious diseases. Projects for making savings and improvements]. / Riduzione della spesa farmaceutica per antibiotici in una Unit Operativa di Malattie Infettive. Progetti di risparmio e miglioramento.

The authors intend to evaluate the results obtained from a pharmaco-economic project included in the 1999 and 2000 budgets. The objectives of the study are: 1) to establish whether there has been a saving in expenses for antibiotic therapy (T.A.) during the first half-year of 1999 and during the first half-year of 2000 and to ascertain the reasons for any positive result; 2) to evaluate the average hospital stay in the first half-year of 2000 and to observe how many times patients were been discharged early with shift therapy. Of the 286 patients (1999) and 309 (2000) considered, we focused attention on 187 (1999) and 190 patients (2000) who were treated with antibiotic therapy. A substantial cost saving was found in antibiotic use (-31%) in the first half-year of 2000 due to the early discharge and the continuation of home therapy for a fair number of patients and due to increased attention in the choice of medicine for less serious diseases. The second objective was not achieved with the reduction of average hospital stay even if the average length of antibiotic therapies (D.M.T.) fell from 13.1 days at 1st September to 9.8 days in the first half-year of 2000 (P:NS). These results suggest that projects designed to achieve financial savings and improvements require more cooperation between clinical U.O. and services that enable hospital stay to be shortened.

[Pharmaco-economic evaluation of antibiotic therapy in a ward for infections diseases] / Alcune valutazioni di farmacoeconomia sull'antibioticoterapia in un reparto di malattie infettive.

For all hospitalized patients admitted in the first six months of 1999, we recorded the data relative to antibiotic therapy (TA) administered, establishing the period of treatment in days and the dosage, including any variations during the period in question. We calculated the prescribed daily dose (PDD) and were thus able to establish the expense incurred in antibiotic therapy, comparing the real overall cost per product used. For all patients, the discharge diagnosis was reported, and the whole case-study was aggregated into homogeneous groups. PDD was compared with DDD (defined daily doses). The Pareto curve was used to highlight the antibiotics with higher overall cost. Besides cotrimoxazole, ceftriaxone and ciprofloxacin were the antibiotics most frequently prescribed, while ceftriaxone, imipenem-cilastatine and vancomycin were the antibiotics incurring the greatest expense. With reference to the average duration of the treatment cycle, ceftriaxone (9.75 dd) and ciprofloxacin tbl (6.75 dd) were the only antibiotics (in monotherapy) used for less than 10 treatment days. Special attention was paid to analysing the TA costs in treating pneumonia, which accounted for the highest percentage of cases (50 cases). Ceftriaxone, especially pulmonary infections, was the most commonly used drug. In hospitalized subjects treated who show good therapeutic response, we recommend early discharge and continuation of the therapy at home (switch therapy). This strategy will allow the patient to return to his/her family in good time, also thereby reducing hospital management costs.

[The use of the Bullard laryngoscope]. / L'impiego del laringoscopio di Bullard.

Eighty patients were submitted to orotracheal intubation with adult bullard laryngoscope blade. Use and advantages are described, especially in difficult intubation.

[Kinetic study during amino acid infusion in catabolic patients. Comparison between two solutions]. / Studio cinetico durante infusione aminoacidica in pazienti catabolici. Confronto tra due soluzioni.

The equilibrium kinetic of two different amino acid solutions was investigated in ten catabolic patients (Parentamin, Pierrel; HBC, Baxter). Plasma amino acid pattern was determined on arterial samples before TPN and several times over 48 hours of TPN. Nitrogen balance was measured from 24 hours urine collection. Three different cinetic trends were found: a fast modification (diminution or increase), a slow adaptation, or no modification of plasmatic levels, however each amino acid reached a steady state plateau. The adequacy of the infusion of each amino acid was evaluated comparing its steady-state plasma level to the after lunch level in healthy man. This made possible to approximate metabolic needs of each of the infused amino acids and to identify the inadequacy of some metabolic pathways to synthetized non essential amino acids lacking in solutions. This made possible to identify amino acids infused in excess or in defect, and those infused in dose adapt to the metabolic needs of such patients.