Francesco Cardì

For biliary diseases, routinely we performed an extensive preoperative diagnostic workup with the help of MRCP, which avoided in our case unnecessary cholecystectomy. In the future, we suggest that there will be no more unnecessary cholecystectomies for symptomatic gallbladder agenesis.

Nowadays, laparoscopic cholecystectomy (LC) is undoubtedly considered the "gold standard" in the surgical treatment of symptomatic gallstones, gallbladder adenomas and acute cholecystitis. Among the alternative energy sources proposed (monopolar, bipolar electric scalpel, radiofrequency sealers) with the aim to dissect and/or seal, the ultrasonic energy has been frequently adopted, however without a widespread acceptance among surgeons for routine or emergency laparoscopic cholecystectomy. This study investigates the possible beneficial aspects of ultrasonic dissection and its efficacy in the closure of the cystic artery and duct. Patients were retrospectively divided into 2 groups according to the instruments used for division of the cystic artery and duct as well as for dissection of the liver bed: 121 patients in whom dissection and coagulation were performed using monopolar coagulation and 43 patients who were all treated with the ultrasonically activated scalpel harmo...

The skeletal muscle relaxant tizanidine is approved by the US FDA and the European Medicines Agency for treating spasticity and is supplied as tablets for oral administration. However, tizanidine has a poor bioavailability, due to extensive first-pass metabolism. Therefore, the nasal route of administration, which bypasses portal circulation, may increase the bioavailability of tizanidine and, possibly, reduce the time to peak plasma concentration, thereby shorting the latency of therapeutic effect. The objective of this study was to evaluate the pharmacokinetic profile of tizanidine nasal spray and compare it to the profile of tizanidine oral tablets. This open-label, phase I study comprised two protocols: protocol 1, tizanidine HCl solution (32.73 mg/mL) intranasally at single doses of 2 and 4 mg versus 4 mg tizanidine oral tablets (randomized, three periods crossover, 12 healthy subjects); and protocol 2, tizanidine HCl solution (16.36 mg/mL) intranasally at a single dose of 1 mg vs. 4 mg tizanidine oral tablets (randomized, two periods crossover, 12 healthy subjects, one dropout). Tizanidine plasma concentrations were determined by liquid chromatography/mass spectrometry. There was a linear relationship between different dosages of intranasal formulation and the area under the concentration-time curve and maximum plasma concentration (C(max)). The relative bioavailability of the different dosages of intranasal formulation were 1.29, 1.93, and 4.23 for 1, 2, and 4 mg intranasal administration, respectively. Comparison of C(max) values gave the following ratios: 0.91, 1.39, and 2.73, for 1, 2, and 4 mg intranasal administration, respectively. The mean time to C(max) (t(max)) was 0.99, 0.43, and 0.63 h for 1, 2, and 4 mg intranasal administration, respectively, whereas it was 1.13 and 1.30 h for the two series of 4 mg tizanidine oral tablets. The bioavailability of the tizanidine intranasal formulation was higher than that of tizanidine oral tablets. The t(max) was also shorter with the intranasal formulation. No serious adverse events occurred throughout the study, such that the two formulations resulted equally well-tolerated. The intranasal formulation of tizanidine results are therefore worthy of subsequent clinical testing in phase II.