Lower airway inflammation in infants with cystic fibrosis detected by newborn screening

Controversy exists over whether the lower airway inflammation that characterizes cystic fibrosis (CF) is initiated primarily by the genetic defect. To determine if inflammation precedes infection, we examined bronchoalveolar lavage (BAL) fluid cytology, cytokines (interleukin (IL)-1beta, IL-4, IL-5, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha), and free neutrophil elastase activity from 70 CF (aged 1.5-71 months) children detected by newborn screening and 19 (aged 2.0-48 months) controls with chronic stridor. CF subjects were selected and categorized as pristine (13 aged /= 10(5) colony-forming units/ml of pathogenic bacteria in BAL), and uninfected (15 aged > 6 months, asymptomatic, not taking antibiotics at bronchoscopy, and free of pathogens in their BAL). To further resolve if inflammation develops without infection, inflammatory mediators in paired annual BAL samples from 38 CF subjects were measured, and results were grouped according to whether BAL showed persistence (n = 6), acquisition (n = 8), clearance (n = 13), or absence (n = 11) of infection. While pristine, uninfected, and control subjects had similar BAL profiles, infected patients showed elevated inflammatory indices, including increased IL-10 (P < 0.001). Pristine subjects had the fewest signs of inflammation. Analysis of BAL pairs found differences between the four infection groups for changes in neutrophil percentages, IL-8 (P < 0.001), and free neutrophil elastase (P = 0.009). Infection was associated with elevated inflammatory mediators in BAL fluid. In contrast, minimal or reduced signs of inflammation accompanied absence of eradication of infection from BAL fluid. We conclude that in CF, infection initiates and sustains airway inflammation.     

Sputum processing for evaluation of inflammatory mediators

Neutrophil-dominated inflammation is prominent in the cystic fibrosis (CF) and chronic bronchitis (CB) airways. We assessed the degree of airway inflammation by measuring the sputum concentrations of interleukin (IL)-8, myeloperoxidase (MPO), and deoxyribonucleic acid (DNA). We determined the relationship among the concentrations of these mediators and investigated methodological problems that may be responsible for reported variability in measurements. Sputa obtained from 31 patients were solubilized with phosphate-buffered saline, dithiothreitol (DTT) (0.1% or 1%), or dornase alfa (0.2 mg/mL). The sputum concentration of IL-8 and MPO was measured by enzyme-linked immunosorbent assay (ELISA), and DNA was measured using microfluorimetry. There was a significant relationship among sputum IL-8, MPO, and DNA. For MPO (means +/- SD), CF was 1,392 +/- 771 vs. CB at 75 +/- 65 mcg/mL; P < 0.0001. For IL-8: CF was 239 +/- 154 vs. CB at 121 +/- 108 ng/mL; P = 0.0002. For DNA, CF was 1.707 +/- 1.25 vs. CB at 0.184 +/- 0.272 mg/mL; P < 0.0001. The MPO concentration in CF sputum was approximately double after in vitro treatment with dornase alfa (P < 0.0001). There is a greater concentration of IL-8, MPO, and DNA in CF than in CB sputa. There is a significant relationship among these inflammatory markers in sputum. DNA polymers bind myeloperoxidase in the sputum, and we speculate that treatment with dornase alfa may remove a source of MPO inhibition.     

Early pulmonary infection, inflammation, and clinical outcomes in infants with cystic fibrosis

A thorough understanding of the early natural history of cystic fibrosis (CF) lung disease is critical for the development of effective interventions in the youngest patients. We assessed the evolution of pulmonary infection, inflammation, and clinical course among 40 infants over a 2-year period through annual bronchoalveolar lavage (BAL) for culture and measurements of pro- and anti-inflammatory cytokines, semiannual infant pulmonary function testing, and quarterly clinical evaluations. Both the prevalence of CF pathogens and their density in BAL fluid increased with age. Infants had neutrophilic lower airway inflammation and elevated IL-8 concentrations independent of whether CF pathogens were recovered. Total leukocyte and neutrophil densities and IL-8 concentrations increased with density of CF pathogens in BAL fluid, whether the isolated organism was P. aeruginosa or another pathogen. IL-10 concentrations were similar in CF subjects and non-CF historical controls. Infants generally had suboptimal growth (low weight and height percentiles) and obstructive lung disease (decreased expiratory flows and air trapping). Subjects from whom CF pathogens were isolated at > 10(5) cfu/mL had the worst air trapping and lowest Brasfield chest X-ray scores. Our findings provide a foundation for future studies of early intervention in CF lung disease, including antimicrobial and anti-inflammatory therapy.     

Pancreatic exocrine insufficiency in LXRbeta-/- mice is associated with a reduction in aquaporin-1 expression

Liver X receptors (LXRs) α and β are nuclear oxysterol receptors with a key role in cholesterol, triglyceride, and glucose metabolism. In LXRβ^−/− mice on a normal diet, there is a reduction in size of perigonadal fat pad and, on high-fat diet there is resistance to obesity. In the present study, we investigated the reason for the resistance of LXRβ^−/− mice to weight gain. In LXRβ^−/− mice we found pancreatic exocrine insufficiency with reduced serum levels of amylase and lipase, reduced proteolytic activity in feces, chronic inflammatory infiltration, and, in the ductal epithelium, an increased apoptosis without compensatory proliferation. Electron microscopy revealed ductal dilatation with intraductal laminar structures characteristic of cystic fibrosis. To investigate the relationship between LXRβ and pancreatic secretion, we studied the expression of LXRβ and the water channel, aquaporin-1 (AQP1), in the ductal epithelium of the pancreas. In WT mice, ductal epithelial cells expressed LXRβ in the nuclei and AQP1 on the plasma membrane. In LXRβ^−/− mice neither LXRβ nor AQP1 was detectable. Moreover, in WT mice the LXR agonist (T2320) increased AQP1 gene expression. These data demonstrate that in LXRβ^−/− mice dietary resistance to weight gain is caused by pancreatic insufficiency and that LXRβ regulates pancreatic exocrine secretion through the control of AQP1 expression. Pancreatic exocrine insufficiency is the main cause of malabsorption syndrome responsible for weight loss in adults and growth failure in children. Several genes are known to be involved in the pathogenesis and susceptibility to pancreatic insufficiency. LXRβ should be included in that list.     

Double ischemic ileal stenosis secondary to mesenteric injury after blunt abdominal trauma

The authors describe a rare case in which blunt abdominal trauma resulted in mesenteric injury with delayed double ischemic ileal stenosis. Abdominal computed tomography demonstrated stenotic ileal loop with mural thickening. At surgery, a double stenotic bowel loop was found adjacent to a healed defect in the mesentery. Histological examination of the two resected segments showed fibrotic and ischemic lesions within the mesentery. Ischemic intestinal stenosis from mesenteric injury should be considered in the differential diagnosis in patients suffering from intestinal occlusion with a history of blunt abdominal trauma.     

Carnitine is associated with fatigue following chemoradiotherapy for head and neck cancer

Conclusion: Longitudinal assessments of carnitine and fatigue in patients with head and neck squamous cell carcinoma suggest that cisplatin damages the carnitine system in patients undergoing chemoradiotherapy and that carnitine deficiency increases fatigue. Objectives: The purpose of this study was to monitor carnitine levels and fatigue in patients who received cisplatin-based CRT and, for comparison, in patients treated by surgery alone. Methods: To investigate the level of carnitine, mice were administered cisplatin. Next, a prospective analysis was performed to compare plasma carnitine levels before and after cisplatin-based chemoradiotherapy and to assess the relationship between carnitine levels and fatigue. Results: The plasma levels of total carnitine (TC), free carnitine (FC), and fatty acylcarnitine (AC) were significantly lower in mice receiving cisplatin compared with control mice. Mean total carnitine and free carnitine levels were significantly lower 2 weeks after chemoradiotherapy (total carnitine: Mean = 45.6, SD = 16.5, p = 0.01; free carnitine: Mean = 37.8, SD = 12.7, p = 0.02) than before chemoradiotherapy (total carnitine: Mean = 57.7, SD = 12.2; free carnitine: Mean = 48.1, SD = 11.6). There was a significant inverse correlation between carnitine levels and fatigue after chemoradiotherapy.     

Evaluating Direct Medical Expenditures Estimation Methods of Adults Using the Medical Expenditure Panel Survey: An Example Focusing on Head and Neck Cancer

ObjectiveTo inform policymakers of the importance of evaluating various methods for estimating the direct medical expenditures for a low-incidence condition, head and neck cancer (HNC).MethodsFour methods of estimation have been identified: 1) summing all health care expenditures, 2) estimating disease-specific expenditures consistent with an attribution approach, 3) estimating disease-specific expenditures by matching, and 4) estimating disease-specific expenditures by using a regression-based approach. A literature review of studies (2005–2012) that used the Medical Expenditure Panel Survey (MEPS) was undertaken to establish the most popular expenditure estimation methods. These methods were then applied to a sample of 120 respondents with HNC, derived from pooled data (2003-2008).ResultsThe literature review shows that varying expenditure estimation methods have been used with MEPS but no study compared and contrasted all four methods. Our estimates are reflective of the national treated prevalence of HNC. The upper-bound estimate of annual direct medical expenditures of adult respondents with HNC between 2003 and 2008 was $3.18 billion (in 2008 dollars). Comparable estimates arising from methods focusing on disease-specific and incremental expenditures were all lower in magnitude. Attribution yielded annual expenditures of $1.41 billion, matching method of $1.56 billion, and regression method of $1.09 billion.ConclusionsThis research demonstrates that variation exists across and within expenditure estimation methods applied to MEPS data. Despite concerns regarding aspects of reliability and consistency, reporting a combination of the four methods offers a degree of transparency and validity to estimating the likely range of annual direct medical expenditures of a condition.     

全髋关节和双极人工股骨头置换术用于老年股骨颈骨折治疗的对比观察

目的：研究并分析全髋关节和双极人工股骨头置换术治疗老年股骨颈骨折的效果。方法：选择本院收治的60例老年股骨颈骨折患者为研究对象,按随机数字表法分为观察组与对照组,观察组采用全髋关节术进行治疗,对照组采用双极人工股骨头置换术进行治疗,对两组治疗疗效进行详细记录与分析。结果：两组在手术时间、术中出血量、引流量与住院时间以及手术1年优良率方面比较差异均无统计学意义（P＞0.05）;两组手术第2年与第3年手术优良率组间比较差异有统计学意义（P＜0.05）。结论：全髋关节置换术与双极人工股骨头置换术近期疗效相当,但全髋关节置换术的远期疗效优于双极人工股骨头置换术,该种手术方式值得在临床中推广和使用。     

胎儿先天性肺囊腺瘤超声诊断价值

目的：探讨胎儿先天性肺囊腺瘤的超声诊断价值,并对预后进行分析。方法：2007年1月-2014年3月,对本院产前超声诊断为胎儿先天性肺囊腺瘤的11例孕妇进行观察,重点扫查胎儿双侧肺,观察病灶二维超声声像图特征,应用彩色多普勒显示病灶血供情况,并注意观察有无胎儿水肿和其他胎儿异常畸形存在,随访临床、影像或病理检查结果。结果：检出的11例胎儿先天性肺囊腺瘤中,10例病灶位于单侧肺,1例病灶双侧肺均有;单侧肺病例中,6例位于左侧,4例位于右侧;Ⅰ型3例,Ⅱ型5例,Ⅲ型3例;4例伴有羊水过多;2例Ⅲ型伴有胎儿水肿;1例Ⅱ型伴有同侧胸腔少量积液及合并胎儿唇裂畸形;2例Ⅱ型定期复查显示病灶逐渐缩小;1例Ⅰ型出生后经手术治疗,术后患儿如常;7例选择终止妊娠,引产后病理证实与超声诊断相符。结论：产前超声检查能准确诊断胎儿先天性肺囊腺瘤畸形,可对病灶进行分型并评估预后。