This study compared the efficacy and safety of patupilone with those of pegylated liposomal doxorubicin (PLD) in patients with platinum-refractory or -resistant epithelial ovarian, primary fallopian ...tube, or primary peritoneal cancer.
Patients with three or fewer prior regimens were eligible if they had received first-line taxane/platinum-based combination chemotherapy and were platinum refractory or resistant. Patients were randomly assigned to receive patupilone (10 mg/m(2) intravenously every 3 weeks) or PLD (50 mg/m(2) intravenously every 4 weeks).
A total of 829 patients were randomly assigned (patupilone, n = 412; PLD, n = 417). There was no statistically significant difference in overall survival (OS), the primary end point, between the patupilone and PLD arms (P = .195; hazard ratio, 0.93; 95% CI, 0.79 to 1.09), with median OS rates of 13.2 and 12.7 months, respectively. Median progression-free survival was 3.7 months for both arms. The overall response rate (all partial responses) was higher in the patupilone arm than in the PLD arm (15.5% v 7.9%; odds ratio, 2.11; 95% CI, 1.36 to 3.29), although disease control rates were similar (59.5% v 56.3%, respectively). Frequently observed adverse events (AEs) of any grade included diarrhea (85.3%) and peripheral neuropathy (39.3%) in the patupilone arm and mucositis/stomatitis (43%) and hand-foot syndrome (41.8%) in the PLD arm.
Patupilone did not demonstrate significant improvement in OS compared with the active control, PLD. No new or unexpected serious AEs were identified.
Methanol is currently the preferred feedstock to light olefins and oxygenated chemicals because it provides a thermodynamically and kinetically feasible, although indirect, route for methane ...conversion. Dimethyl ether (DME, CH3OCH3) is an attractive alternate feedstock because its conversion from synthesis gas is more economical and thermodynamically favorable than methanol and its lack of hydroxyl groups lessens its potential to form water by-products. The catalyst site requirements, kinetics, and mechanism of oxidation and carbonylation reactions of methanol and DME are examined here. Oxidative DME and methanol reactions proceed in similar pathways on supported MoOx. C-H bonds in methoxide groups, formed initially from DME or methanol dissociation, are cleaved to form formaldehyde, hydroxyl groups, and lattice oxygen vacancies. Hydroxyl groups combine and desorb as water and oxygen vacancies are re-oxidized by O2. No kinetic isotope effect was detected in separate reactions of CH3OCH3 and CD3OCD3 indicating that C-H bond cleavage is not involved in kinetically-relevant steps and transient studies involving CH 316OCH3-18O2-Mo 16Ox confirmed, instead, the kinetic relevance of C-O dissociation to form methoxide groups. First-order rate constants are about 10 times larger for methanol than for DME at 493 K because C-O dissociation steps precede C-H bond activation steps, which limit rates for methanol oxidation. Ru-, Ru-Na-, and Ru-Na-Sn/USY catalyzed the reaction of methanol (in the absence of CO) to acetic acid, detected as methyl acetate due to rapid esterification reactions, but not without the presence of methanol dehydration, decomposition, and methanation side reactions. DME, CO, H2, CO 2, and CH4 dominated the product stream leading to low (<2%) methyl acetate selectivities. Methyl acetate selectivities improved significantly in reactions of DME and CO on acidic zeolites. Acid mordenite and ferrierite catalyzed DME carbonylation with >99% methyl acetate selectivities at low temperatures. Rates are first-order in CO, zero-order in DME, and strongly inhibited by water. Methanol carbonylation reactions do not occur at similar reaction conditions (423-463 K, 100-930 kPa CO) because water, formed in dehydration reactions, competitively adsorbs onto CO binding sites or inhibits the kinetically-relevant reaction of CO with methyl groups to form acetyl intermediates.
The University of Massachusetts Simmons School Health Institute delivers a series of professional development programs across Massachusetts to improve statewide delivery of comprehensive school ...health programs to children and adolescents. The programs emphasize student risk assessment, health program design and management, and school-based clinic development. Two summer programs are available. (SM)
One hundred and ninety-five patients undergoing abdominal surgical procedures completed a multicentre, randomized, open-label study comparing the safety and efficacy of cefmetazole and cefoxitin for ...the prevention of postoperative wound infection. Cefmetazole was administered iv in a single 2 g dose given within 90 min of the operation. Cefoxitin was administered in a single 2 g, similarly timed, preoperative dose and two additional doses given at 6 h intervals after surgery. For operations that exceeded 2-4 h duration an additional dose of each agent was administered. Patients undergoing colorectal operations received oral neomycin and erythromycin as bowel preparation. Colorectal operations were performed most frequently (49% of patients) followed by cholecystectomies (26%) and gastroduodenal procedures (21%). The operative site infection rate was 6.5% for cefmetazole and 7.7% for cefoxitin (P greater than 0.05). Serious drug related adverse effects were not observed. This study demonstrates that administration of single-dose cefmetazole is as effective as a standard three dose regimen of cefoxitin for prophylaxis with abdominal operations.
N-methyl-thio-tetrazole (NMTT) has been proposed as a causative factor in antibiotic-associated coagulopathy. To evaluate this hypothesis, a nationwide surveillance program was initiated to determine ...the relative frequency of antibiotic-associated coagulopathy and the importance of specific risk factors. A total of 970 patients were studied, with 491 being treated for infections and 479 receiving antimicrobial surgical prophylaxis. The NMTT-containing antibiotic cefotetan was compared with non-NMTT-containing antibiotics, for example, cefoxitin and cefazolin (prophylaxis only), and an aminoglycoside-antianaerobic (AG + AA) combination. Prothrombin time (PT) and partial thromboplastin time (PTT) were measured for each patient prior to the start of antibiotics and within 24-96 hours after the conclusion of drug administration. The patient population was relatively young mean (SD) age 51.0 (20) yrs with good nutritional status. The overall frequency of hypoprothrombinemia (4.5%) and bleeding (1.7%) was very low, and was highest with the use of AG + AA (p less than 0.05). No statistical differences were observed for the remaining antibiotic regimens in either the prophylaxis or treatment group. Logistic regression analysis identified treatment with the AG + AA combination, presence of liver disease, and renal dysfunction as factors associated with an increased risk of hypoprothrombinemia. In conclusion, this study suggests that the frequency of antibiotic-associated coagulopathy is low, regardless of antibiotic, in patients who are not critically ill and not malnourished.
The Optical Disk Solution Wing, Patricia; HECKE, JAMES F. VAN
Personnel journal,
04/1991, Letnik:
70, Številka:
4
Journal Article
The HR function at Los Alamos National Laboratory manages more than 500,000 employee documents and processes more than 72,000 pages of personnel forms and memos each month. Evaluators felt a new ...computer-managed document system would help control the paperwork. The lab is now going to use an optical disk computer system, which allows users to view screen images of documents stored away safely.
Objective
To estimate the incidence and prevalence of systemic lupus erythematosus (SLE) in a sociodemographically diverse southeastern Michigan source population of 2.4 million people.
Methods
SLE ...cases fulfilling the American College of Rheumatology classification criteria (primary case definition) or meeting rheumatologist‐judged SLE criteria (secondary definition) and residing in Wayne or Washtenaw Counties during 2002–2004 were included. Case finding was performed from 6 source types, including hospitals and private specialists. Age‐standardized rates were computed, and capture–recapture was performed to estimate underascertainment of cases.
Results
The overall age‐adjusted incidence and prevalence (ACR definition) per 100,000 persons were 5.5 (95% confidence interval 95% CI 5.0–6.1) and 72.8 (95% CI 70.8–74.8). Among females, the incidence was 9.3 per 100,000 persons and the prevalence was 128.7 per 100,000 persons. Only 7 cases were estimated to have been missed by capture–recapture, adjustment for which did not materially affect the rates. SLE prevalence was 2.3‐fold higher in black persons than in white persons, and 10‐fold higher in females than in males. Among incident cases, the mean ± SD age at diagnosis was 39.3 ± 16.6 years. Black SLE patients had a higher proportion of renal disease and end‐stage renal disease (ESRD) (40.5% and 15.3%, respectively) as compared to white SLE patients (18.8% and 4.5%, respectively). Black patients with renal disease were diagnosed as having SLE at younger age than white patients with renal disease (mean ± SD 34.4 ± 14.9 years versus 41.9 ± 21.3 years; P = 0.05).
Conclusion
SLE prevalence was higher than has been described in most other population‐based studies and reached 1 in 537 among black female persons. There were substantial racial disparities in the burden of SLE, with black patients experiencing earlier age at diagnosis, >2‐fold increases in SLE incidence and prevalence, and increased proportions of renal disease and progression to ESRD as compared to white patients.
Liver fibrosis is a wound healing response to chronic liver injury and inflammation in which macrophages and infiltrating monocytes participate in both the development and resolution phase. In ...humans, three monocyte subsets have been identified: the classical CD14++CD16−, intermediate CD14++CD16+, and nonclassical CD14+CD16++ monocytes. We studied the phenotype and function of these monocyte subsets in peripheral blood and liver tissue from patients with chronic inflammatory and fibrotic liver diseases. The frequency of intrahepatic monocytes increased in disease compared with control liver tissue, and in both nondiseased and diseased livers there was a higher frequency of CD14++CD16+ cells with blood. Our data suggest two nonexclusive mechanisms of CD14++CD16+ accumulation in the inflamed liver: (1) recruitment from blood, because more than twice as many CD14++CD16+ monocytes underwent transendothelial migration through hepatic endothelial cells compared with CD14++CD16− cells; and (2) local differentiation from CD14++CD16− classical monocytes in response to transforming growth factor β and interleukin (IL)‐10. Intrahepatic CD14++CD16+ cells expressed both macrophage and dendritic cell markers but showed high levels of phagocytic activity, antigen presentation, and T cell proliferation and secreted proinflammatory (tumor necrosis factor α, IL‐6, IL‐8, IL‐1β) and profibrogenic cytokines (IL‐13), chemokines (CCL1, CCL2, CCL3, CCL5), and growth factors (granulocyte colony‐stimulating factor and granulocyte‐macrophage colony‐stimulating factor), consistent with a role in the wound healing response. Conclusion: Intermediate CD14++CD16+ monocytes preferentially accumulate in chronically inflamed human liver as a consequence of enhanced recruitment from blood and local differentiation from classical CD14++CD16− monocytes. Their phagocytic potential and ability to secrete inflammatory and profibrogenic cytokines suggests they play an important role in hepatic fibrogenesis. (HEPATOLOGY 2013)
Objective
Examine the relationship between 1‐ and 2‐month weight loss (WL) and 8‐year WL among participants enrolled in a lifestyle intervention.
Methods
2,290 Look AHEAD participants (BMI: 35.65 ± ...5.93 kg/m2) with type 2 diabetes received an intensive behavioral WL intervention.
Results
1‐ and 2‐month WL were associated with yearly WL through Year 8 (P's < 0.0001). At Month 1, participants losing 2‐4% and >4% had 1.62 (95% CI: 1.32, 1.98) and 2.79 (95% CI: 2.21, 3.52) times higher odds of achieving ≥5% WL at Year 4 and 1.28 (95% CI: 1.05,1.58) and 1.77 (95% CI: 1.40, 2.24) times higher odds of achieving ≥5% WL at Year 8, compared to those losing <2% initially. At Month 2, 3‐6% WL resulted in greater odds of achieving ≥5% WL at Year 4 (OR = 1.85; CI: 1.48, 2.32), and >6% WL resulted in the greatest odds of achieving ≥5% WL at Year 4 (OR = 3.85; CI: 3.05, 4.88) and Year 8 (OR = 2.28; CI: 1.81, 2.89), compared to those losing <3%. Differences in adherence between WL categories were observed as early as Month 2.
Conclusions
1‐ and 2‐month WL was associated with 8‐year WL. Future studies should examine whether alternative treatment strategies can be employed to improve treatment outcomes among those with low initial WL.
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