Safety considerations of intranasal corticosteroids for the treatment of allergic rhinitis.

Allergic rhinitis (AR) is a major chronic inflammatory disease of the upper airways. AR is increasing in prevalence and causes negative effects on quality of life, impairs performance and productivity, and imposes a serious economic burden. More than 20% of the American population suffers from AR. Intranasal corticosteroids (INS) are an effective and safe first-line treatment for AR, with potent anti-inflammatory properties and a high therapeutic ratio. The systemic bioavailability of the majority of INS is relatively low; however, the pharmacokinetics of absorption, first-pass metabolism, volume of distribution, half-life, and clearance of INS varies considerably, depending on lipophilicity, receptor affinity, and lipid conjugation in the nasal tissue. The short-term (e.g., effect on linear lower-leg growth rate) and long-term (e.g., effect on height) systemic side effects of INS in patients with AR are determined by these important characteristics. AR is present in up to 75% of patients with asthma, and patients with AR are three times more likely to develop asthma compared with patients without AR. Therefore, the overall increased systemic steroid burden resulting from concomitant use of inhaled corticosteroids (ICS) and INS in adult and pediatric patients with comorbid AR and asthma warrants critical monitoring of systemic side effects. This review evaluates the overall safety of INS in AR and the importance of systemic safety considerations of INS, particularly when coadministered with ICS.     

Effects of Lovastatin Alone or Combined with Irradiation on Tumor Cells in Vitro and in Vivo

PURPOSE: To evaluate the effect of lovastatin alone or combined with radiation on U87MG and FaDu cells in vitro and U87MG tumors in vivo. MATERIAL AND METHODS: Cell number, p21(WAF1) expression, apoptosis, reproductive cell death, and cell-cycle distribution were investigated after incubation of U87MG and FaDu cells in vitro. The effect of lovastatin (50 mg/kg/day) on tumor growth and on tumor growth delay after single-dose irradiation with 20 Gy was investigated using U87MG tumors in nude mice. RESULTS: Lovastatin dose dependently decreased cell number and proliferation of U87MG and FaDu cells. The proportion of cells in G0/G1 phase, apoptosis and p21 protein expression increased after lovastatin alone or combined with 4-Gy irradiation in both cell lines. Effects of lovastatin on cell cycle and cell number were more pronounced in U87MG compared to FaDu. No radiosensitization of clonogenic cells by lovastatin could be demonstrated in both cells lines, but the colony-forming ability after lovastatin alone was decreased in FaDu cells. In vivo, lovastatin decreased tumor volume over time but did not increase growth delay after irradiation of U87MG tumors with 20 Gy. CONCLUSION: The data support effects of lovastatin on proliferation, apoptosis and colony-forming ability in vitro and tumor volume in vivo. At the drug concentration achievable, lovastatin did not improve the effects of radiation on U87MG tumors in vivo.     

Defining the Role of Surgery for Primary Gastrointestinal Tract Melanoma

Objective The objective of the study was to determine the outcomes for primary gastrointestinal melanomas (PGIM). Material and methods The Surveillance, Epidemiology, and End Results database (1973–2004) was queried. Results Overall, 659 cases of PGIM were identified. The annual incidence of PGIM was approximately 0.47 cases per million in 2000. Overall median survival time was 17 months. Tumors were identified in the oral–nasopharynx (32.8%), anal canal (31.4%), rectum (22.2%), esophagus (5.9%), stomach (2.7%), small bowel (2.3%), gallbladder (1.4%), and large bowel (0.9%). Univariate analysis demonstrated age, tumor location, stage, surgery, and lymph node status were significant predictors of improved survival. MST has not been reached for tumors located in the large bowel, while tumors located in the stomach demonstrated the shortest median survival (5 months). Improvement in MST was observed for those patients undergoing surgical resection. The presence of lymph node involvement conferred a poorer prognosis. Multivariate analysis of the cohort identified that location, advanced tumor stage, failure to undertake surgical resection, positive lymph node status, and age were all independent predictors of poorer outcome. Conclusion PGIM occurs most often in the oral–nasopharynx and anal canal. Surgical extirpation is the only identifiable treatment modality that significantly improves survival.     

Hip fractures: failure of fixation and outcome of salvage arthroplasty

Between 1999 and 2005, we treated 41 patients with a total hip arthroplasty for failed fixation of a hip fracture. This study had three purposes: (1) to determine the reason/s for fixation failure (2) to record difficulties/complications encountered in converting to a salvage arthroplasty and (3) to compare the outcome of these patients (Group 1) with a matched group of patients who underwent a primary hip arthroplasty (Group 2). Failure to achieve a good reduction and optimal screw placement was evident in 80% of cases of failed fixation. A high incidence of complications was recorded in the perioperative period during conversion to a salvage arthroplasty. Functional outcome was statistically inferior in Group1; this group also had a higher incidence of complications. Radiographs at 2 years postoperatively showed evidence of femoral stem loosening in 16% of the salvage group compared with 3% in the primary hip arthroplasty group.     

The effects of paracetamol (acetaminophen) on hepatic tests in patients who chronically abuse alcohol – a randomized study

Aliment Pharmacol Ther 2010; 32: 478–486

Summary

Background Retrospective accounts suggest that therapeutic doses of paracetamol can produce severe hepatic injury in patients with putative high‐risk conditions, including alcoholism and infectious hepatitis. Metabolism of paracetamol to its hepatotoxic metabolite is enhanced in patients who abuse alcohol, who also have compromised liver defences from depressed hepatic glutathione. Aim To determine the effect of paracetamol on serum liver tests of newly abstinent subjects who abuse alcohol, including subjects with hepatitis C infection. Methods A randomized, double‐blind, placebo‐controlled study. Adult alcohol abusers with a current drinking episode longer than 7 days received either placebo or paracetamol 4 g/day for 5 days. Results Of 142 subjects enrolled, 74 received paracetamol and 68 received placebo. Mean ALT activity during treatment increased from 48 to 62 IU/L in the paracetamol group and from 47 to 49 IU/L in the placebo group. Maximum ALT was 238 and 249 IU/L in the paracetamol and control groups respectively. The INR remained unchanged and serum bilirubin decreased in both groups. Subgroup analyses for subjects with alcoholic hepatitis, hepatitis C virus antibody and other subgroups showed no statistical difference between groups. Conclusion Administration of paracetamol 4 g/day appears safe in newly abstinent patients who abuse alcohol.