This randomized trial was designed to determine whether paclitaxel plus carboplatin (PC) offered a survival advantage over vinorelbine plus cisplatin (VC) for patients with advanced non--small-cell ...lung cancer. Secondary objectives were to compare toxicity, tolerability, quality of life (QOL), and resource utilization.
Two hundred two patients received VC (vinorelbine 25 mg/m(2)/wk and cisplatin 100 mg/m(2)/d, day 1 every 28 days) and 206 patients received PC (paclitaxel 225 mg/m(2) over 3 hours with carboplatin area under the curve of 6, day 1 every 21 days). Patients completed QOL questionnaires at baseline, 13 weeks, and 25 weeks. Resource utilization forms were completed at five time points through 24 months.
Patient characteristics were similar between the groups. The objective response rate was 28% in the VC arm and 25% in the PC arm. Median survival was 8 months in both arms, with 1-year survival rates of 36% and 38%, respectively. Grade 3 and 4 leukopenia (P =.002) and neutropenia (P =.008) occurred more frequently on the VC arm. Grade 3 nausea and vomiting were higher on the VC arm (P =.001, P =.007), and grade 3 peripheral neuropathy was higher on the PC arm (P <.001). More patients on the VC arm discontinued therapy because of toxicity (P =.001). No difference in QOL was observed. Overall costs on the PC arm were higher than on the VC arm because of drug costs.
PC is equally efficacious as VC for the treatment of advanced non--small-cell lung cancer. PC is less toxic and better tolerated but more expensive than VC. New treatment strategies should be pursued.
Hyperammonemia syndrome is a fatal complication affecting immunosuppressed patients. Frequently refractory to treatment, it is characterized by progressive elevations in serum ammonia of unknown ...etiology, ultimately leading to cerebral edema and death. In mammals, ammonia produced during amino acid metabolism is primarily cleared through the hepatic production of urea, which is eliminated in the kidney. Ureaplasma species, commensals of the urogenital tract, are Mollicutes dependent on urea hydrolysis to ammonia and carbon dioxide for energy production. We hypothesized that systemic infection with Ureaplasma species might pose a unique challenge to human ammonia metabolism by liberating free ammonia resulting in the hyperammonemia syndrome. We used polymerase chain reaction, specialized culture, and molecular resistance profiling to identify systemic Ureaplasma infection in lung transplant recipients with hyperammonemia syndrome, but did not detect it in any lung transplant recipients with normal ammonia concentrations. Administration of Ureaplasma-directed antimicrobials to patients with hyperammonemia syndrome resulted in biochemical and clinical resolution of the disorder. Relapse in one patient was accompanied by recurrent Ureaplasma bacteremia with antimicrobial resistance. Our results provide evidence supporting a causal relationship between Ureaplasma infection and hyperammonemia, suggesting a need to test for this organism and provide empiric antimicrobial treatment while awaiting microbiological confirmation.
Aliment Pharmacol Ther 2011; 33: 672–678
Summary
Background Recent studies have focused on the importance of mucosal healing in ulcerative colitis (UC). However, it was still unclear whether higher ...doses of delayed‐release mesalazine (mesalamine) could provide additional benefit.
Aim To examine how two doses of delayed‐release mesalazine (4.8 g/day and 2.4 g/day) from ASCEND I and II compare in their relative ability to heal colonic mucosa over time.
Methods Primary data from two prospective 6‐week, double‐blind, randomised studies in patients with mildly to moderately active UC were pooled and analysed retrospectively. The mucosal healing analysis focuses on moderately active UC patients (n = 391), comprising a majority of patients (84%). Additional analyses examined the relationship between mucosal healing and dose, clinical response to therapy and patient quality of life (Inflammatory Bowel Disease Questionnaire, IBDQ).
Results At week 3, mucosal healing (endoscopy subscore of 0 or 1) was achieved in 65% of moderately active UC patients on 4.8 g/day and 58% of patients on 2.4 g/day (P = 0.219). At week 6, this increased to 80% for 4.8 g/day and 68% for 2.4 g/day (P = 0.012). Healing rates with the higher dose were also greater across all extents of disease and in patients with prior steroid use. At 6 weeks, clinical response to therapy and mucosal healing were found to be well correlated (kappa = 0.694). Likewise, the change in IBDQ at week 6 showed a significant relationship with mucosal healing (P < 0.0001).
Conclusion Mucosal healing rates in UC achieved at 6 weeks were statistically significantly higher with delayed‐release mesalazine at 4.8 g/day vs. 2.4 g/day (Clinicaltrials.gov: NCT00577473, NCT00073021).
We report an extended measurement of the neutron cross section on argon in the energy range of 95-720 MeV. The measurement was obtained with a 4.3-hour exposure of the Mini-CAPTAIN detector to the ...WNR/LANSCE beam at LANL. Compared to an earlier analysis of the same data, this extended analysis includes a reassessment of systematic uncertainties, in particular related to unused wires in the upstream part of the detector. Using this information we doubled the fiducial volume in the experiment and increased the statistics by a factor of 2.4. Here we also shifted the analysis from energy bins to time-of-flight bins. This change reduced the overall considered energy range, but improved the understanding of the energy spectrum of incoming neutrons in each bin. Overall, the new measurements are extracted from a fit to the attenuation of the neutron flux in five time-of-flight regions: 140ns-180ns, 120ns-140ns, 112ns-120ns, 104ns-112ns, 96ns-104ns. The final cross sections are given for the flux-averaged energy in each time-of-flight bin with statistical and systematic (syst) uncertainties: σ(146 MeV) = 0.60 $^{+0.14}_{-0.14}$ ±0.08(syst) b, σ(236 MeV) = 0.72 $^{+0.10}_{-0.10}$ ± 0.04(syst) b, σ(319 MeV) = 0.80 $^{+0.13}_{-0.12}$ ±0.040(syst) b, σ(404 MeV) = 0.74 $^{+0.14}_{-0.09}$ ±0.04(syst) b, σ(543 MeV) = 0.74 $^{±0.09}_{-0.09}$ ± 0.04(syst) b.
We report the first measurement of the neutron cross section on argon in the energy range of 100-800 MeV. The measurement was obtained with a 4.3-h exposure of the Mini-CAPTAIN detector to the ...WNR/LANSCE beam at LANL. The total cross section is measured from the attenuation coefficient of the neutron flux as it traverses the liquid argon volume. A set of 2631 candidate interactions is divided in bins of the neutron kinetic energy calculated from time-of-flight measurements. These interactions are reconstructed with custom-made algorithms specifically designed for the data in a time projection chamber the size of the Mini-CAPTAIN detector. The energy averaged cross section is 0.91±0.10(stat)±0.09(syst) b. A comparison of the measured cross section is made to the GEANT4 and FLUKA event generator packages, where the energy averaged cross sections in this range are 0.60 and 0.68 b, respectively.
Summary
Background
While allergic sensitization and atopic dermatitis (AD) are known to increase the risk for allergic diseases, the impact of different temporal and clinical patterns of ...sensitization and AD is less well defined.
Objective
We investigated patterns of sensitization and AD from early infancy to age 3, and the differential risk of developing allergic diseases within each pattern in a general cohort.
Methods
Children (n = 2629) from the Canadian Healthy Infant Longitudinal Development (CHILD) Study underwent skin prick tests and were assessed clinically for AD at ages 1 and 3 years. We applied an unsupervised latent class analysis (LCA) to the following 5 factors at these ages: AD, food sensitization, inhalant sensitization, poly‐sensitization to foods and poly‐sensitization to inhalants. The risks for developing asthma, allergic rhinitis and food allergy at 3 years were evaluated for each identified group.
Results
Five distinct classes were revealed by LCA: healthy (81.8%), atopic dermatitis (7.6%), inhalant sensitization (3.5%), transient sensitization (4.1%) and persistent sensitization (3.2%). Using healthy children as the baseline, children in the “atopic dermatitis” group had the next lowest risk for all allergic outcomes at 3 years; those in the “inhalant sensitization” group had the highest risk for allergic rhinitis; children in the “transient sensitization” group were at an increased risk for food allergy; while children in the “persistent sensitization” group had the highest risk for all allergic diseases.
Conclusion and Clinical Relevance
There is substantial heterogeneity among allergen‐sensitized children. Researchers and clinicians need to be aware of the non‐specificity associated with labelling children simply as “atopic” and “non‐atopic” without considering the timing of their atopic history, type of sensitization and AD status. Children with AD who were poly‐sensitized to foods at an early age appear to be at greatest risk of developing other allergic diseases.
Elevated plasma homocysteine is a risk factor for arteriosclerosis, but a cause-and-effect relationship remains to be fully established. Endothelial dysfunction, an early event in the atherogenic ...process, has been shown to be associated with hyperhomocysteinemia in experimental and human studies. To further establish a direct relationship between changes in plasma homocysteine and endothelial dysfunction, we investigated whether moderate hyperhomocysteinemia induced by an oral methionine load would acutely impair flow-mediated endothelium-dependent vasodilatation in healthy adults.
Twenty-four healthy volunteers completed a randomized crossover study in which an oral methionine load (0.1 g/kg) was administered on 1 of 2 study days, 7 days apart. At each visit, plasma homocysteine and brachial artery endothelium-dependent and -independent dilatation were measured at baseline and at 4 hours. To further elucidate the temporal relationship between methionine, homocysteine, and endothelial function, an oral methionine load was administered in 10 subjects on a separate visit, and the time courses of plasma methionine, homocysteine, and flow-mediated brachial artery dilatation were measured at baseline and after 1, 2, 3, 4, and 8 hours. After oral methionine, plasma homocysteine increased from 7. 9+/-2.0 micromol/L at baseline to 23.1+/-5.4 micromol/L at 4 hours (P<0.0001, n=24) and was associated with a decrease in flow-mediated brachial artery dilatation from 0.12+/-0.09 to 0.06+/-0.09 mm (P<0. 05). The time course of the impairment of flow-mediated vasodilatation mirrored the time course of the increase in homocysteine concentration.
Oral methionine loading raises plasma homocysteine and impairs flow-mediated endothelium-dependent vasodilatation. This supports the view that homocysteine may promote vascular disease by inducing endothelial dysfunction.
Background
The effect of infant feeding practices on the development of food allergy remains controversial. We examined the relationship between timing and patterns of food introduction and ...sensitization to foods at age 1 year in the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study.
Methods
Nutrition questionnaire data prospectively collected at age 3, 6, 12, 18, and 24 months were used to determine timing of introduction of cow's milk products, egg, and peanut. At age 1 year, infants underwent skin prick testing to cow's milk, egg white, and peanut. Logistic regression models were fitted to assess the impact of timing of food exposures on sensitization outcomes, and latent class analysis was used to study patterns of food introduction within the cohort.
Results
Among 2124 children with sufficient data, delaying introduction of cow's milk products, egg, and peanut beyond the first year of life significantly increased the odds of sensitization to that food (cow's milk adjOR 3.69, 95% CI 1.37‐9.08; egg adjOR 1.89, 95% CI 1.25‐2.80; peanut adjOR 1.76, 95% CI 1.07‐3.01). Latent class analysis produced a three‐class model: early, usual, and delayed introduction. A pattern of delayed introduction, characterized by avoidance of egg and peanut during the first year of life, increased the odds of sensitization to any of the three tested foods (adjOR 1.78, 95% CI 1.26‐2.49).
Conclusions
Avoidance of potentially allergenic foods during the first year of life significantly increased the odds of sensitization to the corresponding foods.
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