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BACKGROUND: Levofloxacin is used in adult patients with cystic fibrosis but its pharmacokinetics is not well characterized in this population. Patients with cystic fibrosis use calcium routinely to prevent osteoporosis. A slower intestinal transit time is common in cystic fibrosis implying that the standard 2-h spacing of minerals and levofloxacin to prevent a chelation interaction may be insufficient. The objectives of this study were to characterize the steady state pharmacokinetics of oral levofloxacin 750 mg with and without 2-h spaced calcium carbonate in patients with cystic fibrosis compared to matched healthy volunteers. METHODS: In an open-label, randomized, cross-over study of five patients with cystic fibrosis and five age, sex, race, and serum creatinine matched healthy volunteers received 750 mg of oral levofloxacin alone daily for 5 days and the same dose of levofloxacin with 2-h spaced calcium carbonate supplementation 500 mg po thrice daily with meals in random sequence. Blood was collected for plasma assay of levofloxacin pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, and 24h after the fifth levofloxacin dose. RESULTS: There was no significant interaction in healthy volunteers, however, when cystic fibrosis patients were given levofloxacin with 2-h spaced calcium, the maximum plasma concentration (Cmax) decreased by 19% and time to Cmax increased by 37% (p<0.05). This difference in peak concentrations resulted in a lack of bioequivalence (Cmax geometric mean ratio 81.6%, 90% confidence intervals: 71.8%, 91.4%) even when levofloxacin and calcium supplements were spaced by the standard 2h administration instruction in patients with cystic fibrosis. CONCLUSIONS: These results indicate that multivalent cations such as calcium should be maximally separated from oral levofloxacin administration in adult patients with cystic fibrosis to prevent this drug interaction, thereby better optimizing antibiotic efficacy and decreasing the potential for resistance development. 相似文献
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Imaging of acute mesenteric ischemia using multidetector CT and CT angiography in a porcine model 总被引:3,自引:0,他引:3
David E. Rosow M.D. Dushyant Sahani M.D. Oliver Strobel M.D. Sanjeeva Kalva M.D. Mari Mino-Kenudson M.D. Nagaraj S. Holalkere M.D. Guido Alsfasser M.D. Sanjay Saini M.D. Susanna I. Lee M.D. Peter R. Mueller M.D. Carlos Fernándezdel Castillo M.D. Andrew L. Warshaw M.D. Sarah P. Thayer M.D. Ph.D. 《Journal of gastrointestinal surgery》2005,9(9):1262-1275
Acute mesenteric ischemia, a frequently lethal disease, requires prompt diagnosis and intervention for favorable clinical
outcomes. This goal remains elusive due, in part, to lack of a noninvasive and accurate imaging study. Traditional angiography
is the diagnostic gold standard but is invasive and costly. Computed tomography (CT) is readily available and noninvasive
but has shown variable success in diagnosing this disease. The faster scanning time of multidetector row CT (M.D.CT) greatly
facilitates the use of CT angiography (CTA) in the clinical setting. We sought to determine whether M.D.CT-CTA could accurately
demonstrate vascular anatomy and capture the earliest stages of mesenteric ischemia in a porcine model. Pigs underwent embolization
of branches of the superior mesenteric artery, then imaging by M.D.CT-CTA with three-dimensional reconstruction protocols.
After scanning, diseased bowel segments were surgically resected and pathologically examined. Multidetector row CT and CT
angiography reliably defined normal and occluded mesenteric vessels in the pig. It detected early changes of ischemia including
poor arterial enhancement and venous dilatation, which were seen in all ischemic animals. The radiographic findingsd—compared
with pathologic diagnosesd—predicted ischemia, with a positive predictive value of 92%. These results indicate that M.D.CT-CTA
holds great promise for the early detection necessary for successful treatment of acute mesenteric ischemia.
Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–18,
2005 (oral presentation).
Supported by the Karin Grunebaum Research Fellowship, Harvard Medical School (D.E.R.), the German Research Fellowship, German
Research Foundation STR 690/1-1 (O.S.), and the Phillip H. Meyers Grant from the Society of Gastrointestinal Radiologists
(S.P.T.). 相似文献
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Lara Kevorkian David A. Young Clare Darrah Simon T. Donell Lee Shepstone Sarah Porter Sarah Brockbank Dylan R. Edwards rew E. Parker Ian M. Clark 《International journal of experimental pathology》2004,85(1):A23-A23
Objective To profile the expression of all known members of the matrix metalloproteinase ( MMP ), a disintegrin and metalloproteinase with thrombospondin motifs ( ADAMTS ), and tissue inhibitor of metalloproteinases ( TIMP s) gene families in normal cartilage and that from patients with osteoarthritis (OA).
Methods Human cartilage was obtained from femoral heads at joint replacement for either osteoarthritis or following fracture to the neck of femur. Total RNA was purified and expression of genes assayed using quantitative real-time PCR.
Results Several members of the above gene families were regulated in OA. Genes increasing in expression in OA were: at P < 0.001, MMP-13 , MMP-28 , ADAMTS-16 ; at P < 0.01, MMP-9 , MMP-16 , ADAMTS-2 , ADAMTS-14 and at P < 0.05, MMP-2 , TIMP-3 , ADAMTS-12 . Genes decreasing in expression in OA were: at P < 0.001, MMP-1 , MMP-3 , ADAMTS-1 ; at P < 0.01, MMP-10 , TIMP-1 , ADAMTS-9 and at P < 0.05, TIMP-4 , ADAMTS-5 , ADAMTS-15 . Correlation analysis revealed that groups of genes across the gene families are co-expressed in cartilage.
Conclusion This is the first comprehensive expression profile of all known MMP , ADAMTS and TIMP genes in cartilage. Patterns of expression provide a foundation on which to understand mechanisms of gene regulation in OA and potentially for refining the specificity of anti-proteolytic therapies. 相似文献
Methods Human cartilage was obtained from femoral heads at joint replacement for either osteoarthritis or following fracture to the neck of femur. Total RNA was purified and expression of genes assayed using quantitative real-time PCR.
Results Several members of the above gene families were regulated in OA. Genes increasing in expression in OA were: at P < 0.001, MMP-13 , MMP-28 , ADAMTS-16 ; at P < 0.01, MMP-9 , MMP-16 , ADAMTS-2 , ADAMTS-14 and at P < 0.05, MMP-2 , TIMP-3 , ADAMTS-12 . Genes decreasing in expression in OA were: at P < 0.001, MMP-1 , MMP-3 , ADAMTS-1 ; at P < 0.01, MMP-10 , TIMP-1 , ADAMTS-9 and at P < 0.05, TIMP-4 , ADAMTS-5 , ADAMTS-15 . Correlation analysis revealed that groups of genes across the gene families are co-expressed in cartilage.
Conclusion This is the first comprehensive expression profile of all known MMP , ADAMTS and TIMP genes in cartilage. Patterns of expression provide a foundation on which to understand mechanisms of gene regulation in OA and potentially for refining the specificity of anti-proteolytic therapies. 相似文献
109.
This paper reviews the literature on colorectal cancer from a sex and gender-based perspective. Colorectal cancer is a major cause of death in the developed world, with rates increasing in developing countries. Although described by some writers as an ‘equal opportunity’ disease, it presents more risk to men than women. Both biological, or sex-linked factors, and gender-linked factors play a part in the aetiology of the disease, while gender differences in the use of screening and treatment also help shape the mortality gap between women and men for this condition. Without an appreciation of the part played by sex and gender in the risk of colorectal cancer, and without a gender-sensitive approach to screening in particular, it is possible that the mortality gap between men and women for this condition will widen in the future. 相似文献
110.
Sarah M Cowgill Desiree V Villadolid Sam Al-Saadi Alexander S Rosemurgy 《JSLS, Journal of the Society of Laparoendoscopic Surgeons》2007,11(3):336-343
OBJECTIVES: The impact of preoperative endoscopic therapy on the difficulty of laparoscopic Heller myotomy and the impact of the difficulty of the myotomy on long-term outcome has not been determined. This study was undertaken to determine whether preoperative therapy impacts the difficulty of laparoscopic Heller myotomy and whether preoperative therapy or difficulty of myotomy impacts long-term outcomes. METHODS: Since 1992, 305 patients, 56% male, median age 49 years, underwent laparoscopic Heller myotomy and were prospectively followed. The difficulty of the laparoscopic Heller myotomy was scored by the operating surgeon for the most recent 170 consecutive patients on a scale of 1 (easiest) to 5 (most difficult). Patients scored their symptoms before and after myotomy using a Likert scale from 0 (never/not bothersome) to 10 (always/very bothersome). RESULTS: Before myotomy, 66% of patients underwent endoscopic therapy: 33% dilation, 11% Botox, and 22% both. Preoperative endoscopic therapy did not correlate with the difficulty of the myotomy (P=NS). Median follow-up was 25 months. Regardless of the difficulty of the myotomy, dysphagia improved with myotomy (P<0.0001). By regression analysis, the frequency and severity of post-myotomy dysphagia correlated with neither preoperative endoscopic therapy nor the difficulty of the myotomy. CONCLUSIONS: Laparoscopic Heller myotomy improves the frequency and severity of dysphagia. The difficulty of laparoscopic Heller myotomy is not impacted by preoperative therapy, and neither preoperative therapy nor difficulty of the myotomy impact long-term outcome. 相似文献