Structural characterization of glycoprotein NGAL, an early predictive biomarker for acute kidney injury.

Neutrophil gelatinase-associated lipocalin (NGAL) is a promising new renal biomarker that can reduce the time to diagnose acute kidney injury (AKI). There is little information available about complex glycans on NGAL. Detailed structural characterization of NGAL is necessary to understand the structural variability of NGAL used as a standard in the NGAL immunoassay. This study demonstrated that 7-9% of mutant (C87S) recombinant NGAL was N-glycosylated and no O-glycosylation was detected. The NGAL sequence was confirmed by nanoLC/MS/MS following in gel and in solution trypsin digestion, and the N-glycosylation site was localized by MS/MS. Six different mutant recombinant NGAL samples (samples A-F) were analyzed in this study; however, these samples demonstrated two different glycan patterns. Forty-one N-glycans were detected in sample A and the more abundant N-glycans were unsialylated. Forty-three N-glycans were detected in sample F and the more abundant N-glycans were sialylated. Each of the other four samples (B-E) had a similar N-glycan pattern as sample F.

Evaluation of the ARCHITECT urine NGAL assay: assay performance, specimen handling requirements and biological variability.

OBJECTIVES: NGAL (Neutrophil Gelatinase-Associated Lipocalin) has emerged as a new biomarker for the identification of acute kidney injury. Reliable clinical evaluations require a simple, robust test method for NGAL, and knowledge of specimen handling and specimen stability characteristics. We evaluated the performance of a new urine NGAL assay on the ARCHITECT analyzer. METHODS: Assay performance characteristics were evaluated using standard protocols. Urine specimen storage requirements were determined and biological variability was assessed in a self-declared apparently healthy population. RESULTS: Assay performance data showed good precision, sensitivity and lot-to-lot reproducibility. There was good short term 2-8 degrees C sample stability, however, long term storage samples must be kept at -70 degrees C or colder. The largest variance component in a biological variance study was within-day. CONCLUSIONS: The ARCHITECT NGAL assay proved to be a precise and reproducible assay for the determination of urine NGAL.

Nonvestibular schwannomas: an evaluation of functional outcome after radiosurgical and microsurgical management.

PURPOSE: Nonvestibular cranial nerve schwannomas (NVCNS) are relatively rare tumors. We evaluated our experience with radiosurgical and microsurgical treatment alone and in combination for the management of NVCNS. METHODS: The charts of 62 patients with NVCNS who were treated between 1993 and 2005 at our institution were reviewed. Patients diagnosed with neurofibromatosis type 2 were excluded. The patients underwent microsurgery and/or radiosurgery treatment. RESULTS: Trigeminal and jugular foramen schwannomas were the most common NVCNS tumors (n = 47), and the only two groups with sufficient numbers of patients to allow comparison of the three treatment approaches. In these two groups, the mean tumor volume was significantly higher in those who received combined therapy (8.59 +/- 2.29 cc), compared with radiosurgery (4.94 +/- 3.02 cc; p = 0.05) or microsurgery alone (5.38 +/- 3.23; p = 0.027). Patients who underwent radiosurgery alone were significantly older (67.7 +/- 13.3 years; p = 0.019) than those treated with microsurgery (55.3 +/- 13.7 years) or with both modalities (48.7 +/- 12.8 years). The Karnofsky Performance Scale scores were significantly higher (p < or = 0.05) at follow-up compared with baseline for all three treatment approaches. There was no significant change in the Glasgow Outcome scores before and after treatment. CONCLUSIONS: Microsurgery and radiosurgery can both be used to manage NVCNS tumors with excellent results. When treatment with either modality alone is not reasonable, tumors can be managed effectively with combined micro- and radiosurgery treatment.

Microsurgical management of spinal schwannomas: evaluation of 128 cases.

OBJECT: The authors conducted a study to evaluate the clinical characteristics and surgical outcomes in patients with spinal schwannomas and without neurofibromatosis (NF). METHODS: The data obtained in 128 patients who underwent resection of spinal schwannomas were analyzed. All cases with neurofibromas and those with a known diagnosis of NF Type 1 or 2 were excluded. Karnofsky Performance Scale (KPS) scores were used to compare patient outcomes when examining the anatomical location and spinal level of the tumor. The neurological outcome was further assessed using the Medical Research Council (MRC) muscle testing scale. RESULTS: Altogether, 131 schwannomas were treated in 128 patients (76 males and 52 females; mean age 47.7 years). The peak prevalence is seen between the 3rd and 6th decades. Pain was the most common presenting symptom. Gross-total resection was achieved in 127 (97.0%) of the 131 lesions. The nerve root had to be sacrificed in 34 cases and resulted in minor sensory deficits in 16 patients (12.5%) and slight motor weakness (MRC Grade 3/5) in 3 (2.3%). The KPS scores and MRC grades were significantly higher at the time of last follow-up in all patient groups (p = 0.001 and p = 0.005, respectively). CONCLUSIONS: Spinal schwannomas may occur at any level of the spinal axis and are most commonly intradural. The most frequent clinical presentation is pain. Most spinal schwannomas in non-NF cases can be resected totally without or with minor postoperative deficits. Preoperative autonomic dysfunction does not improve significantly after surgical management.

Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study.

BACKGROUND AND OBJECTIVES: The authors have previously shown that urine neutrophil gelatinase-associated lipocalin (NGAL), measured by a research ELISA, is an early predictive biomarker of acute kidney injury (AKI) after cardiopulmonary bypass (CPB). In this study, whether an NGAL immunoassay developed for a standardized clinical platform (ARCHITECT analyzer, Abbott Diagnostics Division, Abbott Laboratories, Abbott Park, IL) can predict AKI after CPB was tested. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a pilot study with 136 urine samples (NGAL range, 0.3 to 815 ng/ml) and 6 calibration standards (NGAL range, 0 to 1000 ng/ml), NGAL measurements by research ELISA and by the ARCHITECT assay were highly correlated (r = 0.99). In a subsequent study, 196 children undergoing CPB were prospectively enrolled and serial urine NGAL measurements obtained by ARCHITECT assay. The primary outcome was AKI, defined as a > or = 50% increase in serum creatinine. RESULTS: AKI developed in 99 patients (51%), but the diagnosis using serum creatinine was delayed by 2 to 3 d after CPB. In contrast, mean urine NGAL levels increased 15-fold within 2 h and by 25-fold at 4 and 6 h after CPB. For the 2-h urine NGAL measurement, the area under the curve was 0.95, sensitivity was 0.82, and the specificity was 0.90 for prediction of AKI using a cutoff value of 100 ng/ml. The 2-h urine NGAL levels correlated with severity and duration of AKI, length of stay, dialysis requirement, and death. CONCLUSIONS: Accurate measurements of urine NGAL are obtained using the ARCHITECT platform. Urine NGAL is an early predictive biomarker of AKI severity after CPB.

The fate of medical knowledge and the neurosciences during the time of Genghis Khan and the Mongolian Empire.

In 25 years, the Mongolian army of Genghis Khan conquered more of the known world than the Roman Empire accomplished in 400 years of conquest. The recent revised view is that Genghis Khan and his descendants brought about "pax Mongolica" by securing trade routes across Eurasia. After the initial shock of destruction by an unknown barbaric tribe, almost every country conquered by the Mongols was transformed by a rise in cultural communication, expanded trade, and advances in civilization. Medicine, including techniques related to surgery and neurological surgery, became one of the many areas of life and culture that the Mongolian Empire influenced.