Optimal management of constipation associated with irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a common chronic functional disorder of the gastrointestinal tract, meanly characterized by recurrent abdominal pain or discomfort and altered bowel habit. It is a complex disorder involving biological, environmental, and psychosocial factors. The diagnosis is achieved according to the Rome III criteria provided that organic causes have been excluded. Although IBS does not constitute a life-threatening condition, it has a remarkable prevalence and profoundly reduces the quality of life with burdening socioeconomic costs. One of the principal concerns about IBS is the lack of effective therapeutic options. Up to 40% of patients are not satisfied with any available medications, especially those suffering from chronic constipation. A correct management of IBS with constipation should evolve through a global approach focused on the patient, starting with careful history taking in order to assess the presence of organic diseases that might trigger the disorder. Therefore, the second step is to examine lifestyle, dietary habits, and psychological status. On these bases, a step-up management of disease is recommended: from fiber and bulking agents, to osmotic laxative drugs, to new molecules like lubiprostone and linaclotide. Although new promising tools for relief of bowel-movement-related symptoms are being discovered, a dedicated doctor\u2013patient relationship still seems to be the key for succes

Renal stone fragments following shock wave lithotripsy

Purpose: We describe a select group of asymptomatic patients with fragments and dust 3 months after extracorporeal treatment, who were followed to evaluate the long-term outcome and therapeutic implications. Materials and Methods: A total of 129 patients with dust and residual fragments (less than 4 mm.) at 3 months was re-examined at 12 months, and 95 were also evaluated at 24 months. Followup examinations consisted of radiographic studies, renal ultrasonography and urine culture. Dust and residual fragments were sought, and patients were defined as free or as having persistent lithiasis or stone regrowth. At 24 months recurrences in the patients stone-free at 12 months also were considered. Results: At the 12-month followup 60 patients (46.5%) were stone-free and 56 (43.5%) still had dust or residual fragments. The localization of the stones or fragments at 3 months and their sizes did not have a significant influence on the stone-free rate but regrowth was greater in patients with stones larger than 10 mm. (11 of 40 patients, 27.5% versus 2 of 89, 2.2%, p = 0.001). The probability of eliminating residual lithiasis at 12 months was significantly greater in patients with dust than in those with residual fragments (42 of 79 patients, 58% versus 18 of 50, 36%, p = 0.026). Regrowth of residual lithiasis was observed in 13 patients (10%). Conclusions: Based on our results, we do not believe that patients with fragments require systematic re-treatment in the short term but they may be followed long term and re-treated if symptoms persist or stones recur

Intact monoclonal antibodies separation and analysis by sheathless capillary electrophoresis-mass spectrometry

Capillary electrophoresis mass spectrometry coupling (CE-MS) is a growing technique in biopharmaceutics characterization. Assessment of monoclonal antibodies (mAbs) is well known at middle-up and bottom-up levels to obtain information about the sequence, post-translational modifications (PTMs) and degradation products. Intact protein analysis is an actual challenge to be closer to the real protein structure. At this level, actual techniques are time consuming or cumbersome processes. In this work, a 20 minutes separation method has been developed to optimize characterization of intact mAbs. Thus, separation have been done on a positively-charged coated capillary (PEI) with optimized volatile background electrolyte (BGE) and sample buffer (SB). A sheathless interface allowed to hyphenate CE to a quadrupole-time-of-flight mass spectrometer (Q-TOF) which parameters has been tuned to improve the high masses detection and identification of intact mAbs. Three world-wide health authorities approved mAbs have been used to set up a rapid and ease of use method. Intact trastuzumab, rituximab and palivizumab isoforms have been partially separated with this method in less than 20 minutes under denaturing conditions. For each mAb, 2X-glycosylated and 1X-glycosylated structures have been identified and separated. Concerning basic and acidic variants potential Iso-Asp modification and Asn deamidation have been observed. Accurate mass determination for high-mass molecular species remains a challenge, but the progress in intact mAbs separation appears very promising for biopharmaceutics characterization