The need for validation of large administrative databases: Veterans Health Administration ICD-9CM coding of exudative age-related macular degeneration and ranibizumab usage

We performed a validation study by chart review of data for exudative age-related macular degeneration (eAMD) and, because of the Veterans Administration (VA) therapy policy, ranibizumab usage in the largest electronic medical record system in the USA. We reviewed 5,854 distinct patients who visited an ophthalmology clinic within VA Connecticut from January 2006-December 2008. We randomly selected 98 of 138 distinct eAMD patients and 265 of 5,588 non-eAMD patients who did not receive ranibizumab. International Classification of Diseases, Ninth Revision, Clinical Modification coding of eAMD had an excellent positive predictive value of 97.8% (95% confidence interval (CI), 93.5-99.4%). The national Decision Support System (DSS) had an excellent positive predictive value of 100% (95% CI, 79.9-100%) for ranibizumab. However, the negative predictive value of the DSS dispensed ranibizumab decreased to 67.5 (95% CI, 62.1-72.4) because of a change in the way local values were stored that led to errors. Therefore, validation of clinical information over time in large databases is necessary.     

Pulmonary amniotic fluid embolism in a rhesus macaque (Macaca mulatta)

A pregnant female rhesus macaque died spontaneously during stage two labor. Gross and histopathologic findings included severe pulmonary edema, with low numbers of blood vessels containing pale basophilic mucinous material (Alcian Blue positive and PTAH negative), consistent with intravascular amniotic fluid-derived mucin resulting in pulmonary amniotic fluid embolism.     

CC chemokine receptor-3 as new target for age-related macular degeneration

CC chemokine receptor-3 (CCR3) is involved in angiogenic processes. Recently, CCR3 was accounted to participate in choroidal neovascularization (CNV) and CCR3 targeting was reported to be superior to standard antivascular endothelial growth factor-A (VEGF-A) administration when tested in an artificially induced CNV in animals. As human CCR3 studies are lacking in age-related macular degeneration (AMD) patients we sought to determine if CCR3 has any association with inflammatory processes that occur in CNV. A total of 176 subjects were included on the basis of inclusion criteria. Real time PCR was used to analyze the single nucleotide polymorphism in CCR3 of AMD (115) and normal controls (n = 61). Genotype frequency was adjusted for possible confounders like cigarette smoking, alcohol, meat consumption and other risk factors. Chi-square test was used for analysis of polymorphism. The genotype distribution of CCR3 (rs3091250) polymorphism was significantly different in AMD patients in the Indian population. GT (heterozygous) and TT (homozygous) at the rs3091250 SNP increased risk of AMD as compared to the GG genotypes (OR = 4.8, CI 95% = 2.2–10.8 and OR = 4.1, CI 95% = 1.6–10.1 respectively). Subgroup analysis of AMD patients in wet and dry revealed no significant differences. There was no significant difference for rs3091312 in AMD and control group. A significant association between AMD and CCR3 (rs3091250) polymorphism localized on chromosome 3p21.3 was detected. The results suggest the possible contribution of rs3091250, a new predisposing allele in AMD.     

Role of aquaporins in cell migration and edema formation in human brain tumors

The aquaporins (AQPs) are a family of transmembrane water channel proteins widely distributed and play a major role in transcellular and transepithelial water movement. Moreover, recent evidence indicates that AQPs may be involved in cell migration, angiogenesis, and tumor growth. This review article summarizes literature data concerning the involvement of AQP-1 and -4 in human brain tumor growth and edema formation and suggests a potential therapeutic approach by antagonizing their biological activity.     

雷珠单抗联合复方血栓通与单独雷珠单抗治疗渗出老年性黄斑变性的前瞻性随机对照试验研究

目的:探讨复方血栓通(cFXST)对玻璃体腔注射雷珠单抗(IVR)治疗湿性老年性黄斑变性(wet-AMD)的辅助治疗作用。方法:纳入湿性老年性黄斑变性患者38例,以1:1的比例随机纳入Lucentis组(单独玻璃体腔注射雷珠单抗,19例)和cFXST组(玻璃体腔注射雷珠单抗联合复方血栓通,19例)。Lucentis组患者每月行玻璃体腔注射雷珠单抗(IVR),共计3次;cFXST组患者除IVR外,每日口服cFXST。分别在基线、玻璃体腔注射Lucentis后1个月、3个月记录最佳矫正视力(BCVA)和光学相干断层扫描(OCT)影像上视网膜新生血干至色素上皮下厚度(CNV-PED)。结果:cFXST组CNV-PED厚度在1月和3月分别降低31.7%和36.1%,高于Lucentis组的19.7%(P=0.021)、24.2%(P=0.018)。3个月后,cFXST组BCVA变化(P=0.045)及视力提高显著的患者比例(16/16 vs 8/17,P=0.001)明显高于Lucentis组。结论:每日口服cFXST治疗可提高抗VEGF治疗老年wet-AMD的短期疗效。     

Modeling the nuclear magnetic resonance behavior of lung: From electrical engineering to critical care medicine

The present article reviews the basic principles of a new approach to the characterization of pulmonary disease. This approach is based on the unique nuclear magnetic resonance (NMR) properties of the lung and combines experimental measurements (using specially developed NMR techniques) with theoretical simulations. The NMR signal from inflated lungs decays very rapidly compared with the signal from completely collapsed (airless) lungs. This phenomenon is due to the presence of internal magnetic field inhomogeneity produced by the alveolar air–tissue interface (because air and water have different magnetic susceptibilities). The air–tissue interface effects can be detected and quantified by magnetic resonance imaging (MRI) techniques using temporally symmetric and asymmetric spin‐echo sequences. Theoretical models developed to explain the internal (tissue‐induced) magnetic field inhomogeneity in aerated lungs predict the NMR lung behavior as a function of various technical and physiological factors (e.g., the level of lung inflation) and simulate the effects of various lung disorders (in particular, pulmonary edema) on this behavior. Good agreement has been observed between the predictions obtained from the mathematical models and the results of experimental NMR measurements in normal and diseased lungs. Our theoretical and experimental data have important pathophysiological and clinical implications, especially with respect to the characterization of acute lung disease (e.g., pulmonary edema) and the management of critically ill patients. Bioelectromagnetics 20:110–119, 1999. © 1999 Wiley‐Liss, Inc.     

Complement factor H deficiency combined with smoking promotes retinal degeneration in a novel mouse model

Age-related macular degeneration is the leading cause of blindness in the elderly. The Y402H polymorphism in complement factor H promotes disease-like pathogenesis, and a Cfh^+/− murine model can replicate this phenotype, but only after two years. We reasoned that by combining CFH deficiency with cigarette smoke exposure, we might be able to accelerate disease progression to facilitate preclinical research in this disease. Wild-type and Cfh^+/− mice were exposed to nose-only cigarette smoke for three months. Retinal tissue morphology and visual function were evaluated by optical coherence tomography, fundus photography and autofluorescence, and electroretinogram. Retinal pigment epithelial cell phenotype and ultrastructure were evaluated by immunofluorescence staining and transmission electron microscopy. Cfh^+/− smoking mice showed a dome-like protruding lesion at the ellipsoid zone (drusen-like deposition), many retinal hyper-autofluorescence spots, and a marked decrease in A- and B-wave amplitudes. Compared with non-smoking mice, wild-type and Cfh^+/− smoking mice showed sub-retinal pigment epithelium complement protein 3 deposition, activation of microglia, metabolic waste accumulation, and impairment of tight junctions. Microglia cells migrated into the photoreceptor outer segment layer in Cfh^+/− smoking mice showed increased activation. Our results suggest that exposing Cfh^+/− mice to smoking leads to earlier onset of age-related macular degeneration than in other animal models, which may facilitate preclinical research into the pathophysiology and treatment of this disease.