Most dialysis patients are vitamin D deficient, including deficiencies in both activated vitamin D (1, 25‐dihydroxyvitamin D) and the less active 25‐hydroxyvitamin D. These and other abnormalities associated with chronic kidney disease (CKD), if they remain untreated, lead to secondary hyperparathyroidism and bone changes, such as osteitis fibrosa cystica. Activated vitamin D has been proven to decrease parathyroid hormone (PTH) levels in dialysis patients and is currently used for this indication. There are multiple other potential “pleotrophic” effects associated with vitamin D therapy. These include associations with lower all‐cause and cardiovascular mortality, lower rates of infections and improved glycemic indexes. Meta‐analyses of multiple observational studies have shown activated vitamin D therapy to be associated with improved survival. Observational data also suggest fewer infections and better glucose control. There have been no randomized clinical trials powered to evaluate mortality or other clinical outcomes. Small trials of nutritional vitamin D (ergocalciferol and cholecalciferol) showed increases in 25‐hydroxyvitamin D levels without hypercalcemia or hyperphosphatemia, even when given in addition to activated vitamin D therapy. While activated vitamin D therapy is associated with improved outcomes, it also leads to higher fibroblast growth factor 23 (FGF‐23) levels, which may be detrimental in dialysis patients. Further research is needed to evaluate whether activated or nutritional vitamin D therapy are beneficial in dialysis patients for outcomes other than secondary hyperparathyroidism. 相似文献
The plant hormone ethylene regulates a variety of processes of growth and development. To identify components in the ethylene signal transduction pathway, we screened for ethylene-insensitive mutants in Arabidopsis thaliana and isolated a dominant etr2-1 mutant. The etr2-1 mutation confers ethylene insensitivity in several processes, including etiolated seedling elongation, leaf expansion, and leaf senescence. Double mutant analysis indicates that ETR2 acts upstream of CTR1, which codes for a Raf-related protein kinase. We cloned the ETR2 gene on the basis of its map position, and we found that it exhibits sequence homology to the ethylene receptor gene ETR1 and the ETR1-like ERS gene. ETR2 may thus encode a third ethylene receptor in Arabidopsis, transducing the hormonal signal through its “two-component” structure. Expression studies show that ETR2 is ubiquitously expressed and has a higher expression in some tissues, including inflorescence and floral meristems, petals, and ovules. 相似文献
OBJECTIVE: Tumor necrosis factor (TNF) is an important proinflammatory cytokine that mediates inflammatory synovitis and articular matrix degradation in rheumatoid arthritis (RA). We investigated the ability of adalimumab, a human anti-TNF monoclonal antibody, to inhibit the progression of structural joint damage, reduce the signs and symptoms, and improve physical function in patients with active RA receiving concomitant treatment with methotrexate (MTX). METHODS: In this multicenter, 52-week, double-blind, placebo-controlled study, 619 patients with active RA who had an inadequate response to MTX were randomized to receive adalimumab 40 mg subcutaneously every other week (n = 207), adalimumab 20 mg subcutaneously every week (n = 212), or placebo (n = 200) plus concomitant MTX. The primary efficacy end points were radiographic progression at week 52 (total Sharp score by a modified method [TSS]), clinical response at week 24 (improvements of at least 20% in the American College of Rheumatology core criteria [ACR20]), and physical function at week 52 (disability index of the Health Assessment Questionnaire [HAQ]). RESULTS: At week 52, there was statistically significantly less radiographic progression, as measured by the change in TSS, in the patients receiving adalimumab either 40 mg every other week (mean +/- SD change 0.1 +/- 4.8) or 20 mg weekly (0.8 +/- 4.9) as compared with that in the placebo group (2.7 +/- 6.8) (P < or = 0.001 for each comparison). In addition, there were statistically significant changes in the components of the TSS. At week 24, ACR20 responses were achieved by 63% and 61% of patients in the adalimumab 40 mg every other week and 20 mg weekly groups, respectively, versus 30% of patients in the placebo group (P < or = 0.001 for each comparison). At week 52, ACR20 responses were achieved by 59% and 55% of patients taking adalimumab 40 mg every other week and 20 mg weekly, respectively, versus 24% of patients taking placebo (P < or = 0.001 for each comparison). At week 52, physical function as measured by the HAQ demonstrated statistically significant improvement with adalimumab 40 mg every other week and 20 mg weekly compared with placebo (mean change in HAQ score -0.59 and -0.61, respectively, versus -0.25; P < or = 0.001 for each comparison). A total of 467 patients (75.4%) completed 52 weeks of treatment. Adalimumab was generally well tolerated. Discontinuations occurred in 22.0% of adalimumab-treated patients and in 30.0% of placebo-treated patients. The rate of adverse events (both serious and nonserious) was comparable in the adalimumab and placebo groups, although the proportion of patients reporting serious infections was higher in patients receiving adalimumab (3.8%) than in those receiving placebo (0.5%) (P < or = 0.02), and was highest in the patients receiving 40 mg every other week. CONCLUSION: In this 52-week trial, adalimumab was more effective than placebo at inhibiting the progression of structural joint damage, reducing the signs and symptoms, and improving physical function in patients with active RA who had demonstrated an incomplete response to MTX. 相似文献
Objective—To characterise the histopathology of the left ventricular hypertrophy commonly associated with Noonan syndrome by assessing the extent of myocyte disarray and therefore to define one aspect of the relation between this disease and idiopathic hypertrophic cardiomyopathy.
Design—Blinded histological analysis.
Setting—Hospital medical school.
Patients—Six hearts of children with the Noonan phenotype and isolated ventricular hypertrophy were compared with age and sex matched controls.
Methods—Histological analysis was performed with an image analyser under light microscopy. Representative sections from the entire left ventricular free wall were examined. Results were expressed as the percentage of fields showing disarray related to the number of fields evaluated: 100 fields were examined for each patient.
Results—In the patients with Noonan syndrome myocardial disarray was present in the ventricular septum in 24 (5·7)% (mean (SD)) of fields and in the free wall in 22·2 (6·8)%. In the controls disarray was present in the septum in 3·8 (2·3)% of fields and in the free wall in 2·4 (2·8)%. In both regions the extent of disarray was significantly greater in patients with Noonan syndrome (p < 0·0005; 95% confidence interval 14 to 26·3 for the septum: p < 0·005, 95% confidence interval 11·4 to 28·2 for the free wall).
Conclusions—The ventricular hypertrophy associated with Noonan syndrome is histologically similar to hypertrophic cardiomyopathy but whether the two diseases are the expression of the same genetic defect remains to be determined.
Ischemic hepatitis is a devastating cause of acute liver injury. Data are limited regarding its incidence and outcomes.
Methods
Systematic review and meta-analysis of studies from PubMed, EMBASE, and Web of Science with specific search terms. Inclusion criteria included case series with >10 patients and clear case definition (especially liver enzyme levels >10 times the upper limit of normal).
Results
Twenty-four papers met inclusion criteria. A total of 1782 cases were identified in these papers (mean 78 per paper, range 12-322). The pooled average age of the included patients was 64.2 years, and their mean peak aspartate aminotransferase level, alanine aminotransferase level, and total bilirubin were 2423 IU/L, 1893 IU/L, and 2.55 mg/dL, respectively. Ischemic hepatitis was present in 2 of every 1000 admissions; including 2.5 of every 100 intensive care unit admissions and 4 of 10 admissions associated with an aminotransferase level >10 times the upper limit of normal. The pooled proportions of patients with ischemic hepatitis who had a predisposing acute cardiac event or sepsis were 78.2% and 23.4%, respectively. The proportion of patients with a documented hypotensive event of any duration was 52.9%. Overall, the pooled rate of survival to discharge was 51% (range 23.1%-85.7%).
Conclusions
Ischemic hepatitis is a common cause of severe acute liver injury and is associated with a significant risk of in-hospital death. A major opportunity in the management of ischemic hepatitis is recognition of the condition without documented hypotension. 相似文献
Objectives To profile the clinical presentation and treatment results of esthesioneuroblastomas at the University of California, Los Angeles (UCLA), from 2002 to 2013.
Design Retrospective review.
Setting Tertiary academic institution.
Participants Forty-one patients with esthesioneuroblastomas treated at UCLA.
Main Outcome Measures Overall survival (OS) and recurrence-free survival (RFS).
Results Thirty-six patients were included with a mean age of 50.1 years and a median duration of follow-up of 33 months. The 5-year RFS and OS were 54% and 82%, respectively. Modified Kadish stage was the only factor identified to affect OS. Multivariate analysis demonstrated that tumor grade was the only factor that had an independent impact on RFS. There was no statistical difference in survival among the surgical approaches chosen.
Conclusions The updated data on the UCLA experience reveals that all three surgical approaches chosen provide comparable survival, although longer follow-up will be needed to ascertain if these findings hold true. The endoscopic approach had a statistically significant decrease in length of hospital stay and a trend toward reduced blood loss, intensive care unit admission, and complications. The modified Kadish staging was the only factor identified to predict OS. Multivariate analysis revealed that tumor grade was an independent predictor of recurrence; therefore, its importance should be emphasized in future staging systems. 相似文献
Priapism is defined as an erection lasting for more than 4 hours and can be grouped into 3 distinct subtypes: ischemic (low-flow), stuttering and non-ischemic (high-flow). Herein, we present an interesting case of conversion from a low-flow to high-flow priapism after a distal shunting procedure. This is a rare phenomenon that has a paucity of documented cases. Diagnosis requires prompt clinical suspicion and confirmatory testing including penile cavernosal blood gases and Doppler ultrasound.Key Words: Priapism, Ischemic priapism, Non-Ischemic priapism相似文献