Ion mobility separation of deprotonated oligosaccharide isomers - evidence for gas-phase charge migration.

There has been increasing evidence that certain isomeric glycans can be separated efficiently by ion mobility-mass spectrometry when deprotonated ions are analyzed. To better understand the fundamentals behind these separations, we here investigate the impact of ionisation mode and adduct formation using IM-MS, density-functional theory and ab initio molecular dynamics.

Distinguishing N-acetylneuraminic acid linkage isomers on glycopeptides by ion mobility-mass spectrometry.

Differentiating the structure of isobaric glycopeptides represents a major challenge for mass spectrometry-based characterisation techniques. Here we show that the regiochemistry of the most common N-acetylneuraminic acid linkages of N-glycans can be identified in a site-specific manner from individual glycopeptides using ion mobility-mass spectrometry analysis of diagnostic fragment ions.

Identification of carbohydrate anomers using ion mobility-mass spectrometry.

Carbohydrates are ubiquitous biological polymers that are important in a broad range of biological processes. However, owing to their branched structures and the presence of stereogenic centres at each glycosidic linkage between monomers, carbohydrates are harder to characterize than are peptides and oligonucleotides. Methods such as nuclear magnetic resonance spectroscopy can be used to characterize glycosidic linkages, but this technique requires milligram amounts of material and cannot detect small amounts of coexisting isomers. Mass spectrometry, on the other hand, can provide information on carbohydrate composition and connectivity for even small amounts of sample, but it cannot be used to distinguish between stereoisomers. Here, we demonstrate that ion mobility-mass spectrometry--a method that separates molecules according to their mass, charge, size, and shape--can unambiguously identify carbohydrate linkage-isomers and stereoisomers. We analysed six synthetic carbohydrate isomers that differ in composition, connectivity, or configuration. Our data show that coexisting carbohydrate isomers can be identified, and relative concentrations of the minor isomer as low as 0.1 per cent can be detected. In addition, the analysis is rapid, and requires no derivatization and only small amounts of sample. These results indicate that ion mobility-mass spectrometry is an effective tool for the analysis of complex carbohydrates. This method could have an impact on the field of carbohydrate synthesis similar to that of the advent of high-performance liquid chromatography on the field of peptide assembly in the late 1970s.

Collision cross sections of high-mannose N-glycans in commonly observed adduct states--identification of gas-phase conformers unique to [M-H](-) ions.

We report collision cross sections (CCS) of high-mannose N-glycans as [M + Na](+), [M + K](+), [M + H](+), [M + Cl](-), [M + H2PO4](-) and [M - H](-) ions, measured by drift tube (DT) ion mobility-mass spectrometry (IM-MS) in helium and nitrogen gases. Further analysis using traveling wave (TW) IM-MS reveal the existence of distinct conformers exclusive to [M - H](-) ions.

When to use the combined sensory index.

A recently developed electrodiagnostic technique, the combined sensory index (CSI), has been recommended for its greater sensitivity in diagnosing carpal tunnel syndrome (CTS). The CSI requires a greater number of procedures and therefore involves greater time, cost, and patient discomfort than does conventional electrodiagnostic testing. The CSI is composed of three commonly used electrodiagnostic techniques. There is a close correlation between the components of the CSI, and in most cases, all three components of the CSI are in agreement. We performed a study to develop and validate an algorithm that could be used to identify subsets of patients with CTS in whom CSI testing is particularly useful. Subjects were consecutive outpatient veterans referred by a heterogeneous group of specialists and generalists for electrodiagnostic evaluation of paresthesias in a median distribution with nocturnal exacerbation of symptoms. The CSI served as our gold standard. Using our simple algorithm, we found that in approximately 95% of cases, it was unnecessary to perform the CSI. This management strategy improves patient comfort and reduces electrodiagnostic cost while identifying the minority of patients for whom the CSI is indicated.

Carpal compression test and pressure provocative test in veterans with median-distribution paresthesias.

We investigated the value of the carpal compression test (CCT) and the pressure provocative test (PPT) in predicting carpal tunnel syndrome (CTS) in a predominantly male population of veterans. We performed a prospective, blinded comparison of these clinical diagnostic tests with neurophysiological testing. One cohort of 135 consecutive patients was assessed with the CCT; a separate cohort of 134 consecutive patients was assessed with the PPT. Of these 269 patients, 58.4% had electrodiagnostically confirmed CTS. The sensitivity of the CCT was 52.5%, specificity was 61.8%, positive predictive value was 66.6%, and the negative predictive value was 47. 2%. The sensitivity of the PPT was 54.5%, specificity was 68.4%, positive predictive value was 70%, and the negative predictive value was 52.7%. The CCT and PPT had minimal utility in predicting electrodiagnostically confirmed CTS. In a subset of the CCT cohort, 86 consecutive veterans were also evaluated in relation to a clinical gold standard. Of these patients, 60% had CTS based on this gold standard. CCT sensitivity was 53.8%, specificity was 61.8%, positive predictive value was 68.3%, and negative predictive value was 46.7%. The CCT thus had marginal utility in predicting CTS based on a clinical gold standard.

Lack of predictive power of the "tethered" median stress test in suspected carpal tunnel syndrome.

OBJECTIVE: To investigate the value of the "tethered" median nerve stress test (TMST) in predicting electrodiagnostically confirmed carpal tunnel syndrome (CTS) in patients with symptoms suggestive of CTS. STUDY DESIGN: Blinded comparison of a clinical diagnostic test with neurophysiologic testing. SETTING: Portland (OR) Veterans Administration Medical Center Electrodiagnostic Laboratory. PATIENTS: One hundred two consecutive patients referred for symptoms suggestive of CTS. Study inclusion criteria were referral for evaluation of symptoms of paresthesia (with or without pain) inclusive of the median nerve distribution distal to the wrist. RESULTS: Fifty-seven percent of referred patients had electrodiagnostically confirmed CTS. The sensitivity of the TMST was 50%. The specificity was 59.1%. The positive predictive value was 61.7%. The negative predictive value was 47.3%. CONCLUSION: The TMST does not have utility in predicting electrodiagnostic consult results in veteran patients with symptoms suggestive of CTS.

Use of estrogen therapy in a patient with gastrointestinal bleeding secondary to arteriovenous malformations.

OBJECTIVE: To describe a patient with gastrointestinal (GI) bleeding caused by arteriovenous malformations (AVMs) that was treated with estrogen therapy. CASE SUMMARY: A 70-year-old white man was diagnosed with multiple AVMs in the cecum, duodenum, and stomach. Pharmacologic management included the use of ferrous sulfate; however, the patient continued to have recurrent bleeding that required multiple transfusions and endoscopic cauterization. Therapy was initiated with ethinyl estradiol 0.05 mg po qd; no further transfusions have been required for 10 months. DISCUSSION: It is estimated that AVMs of the GI tract account for 1-8% of upper GI bleeding episodes and up to 6% of lower GI bleeding episodes. Hormonal agents have been reported to decrease bleeding in patients with both hereditary and acquired AVMs. CONCLUSIONS: The role of estrogen therapy in treating AVMs of the GI tract is unclear and supported by only one clinical study.

Incidence and prophylaxis of deep vein thrombosis in a high risk trauma population.

BACKGROUND: Pelvic fractures, lower extremity injuries, acute head or spinal injury, and extended bedrest place trauma patients at an increased risk for deep vein thrombosis (DVT) and pulmonary embolism (PE). We reviewed patients with traumatic brain injuries (TBI), spinal cord injuries (SCI), and lower extremity fractures (LEF) to examine our DVT and PE incidence and evaluate the success of our DVT and PE prophylaxis. METHODS: From January 1, 1994 to March 1, 1995, the records of trauma patients with TBI, SCI, and LEF who were admitted to the trauma service and transferred to an inpatient rehabilitation facility were reviewed. RESULTS: Twenty-two patients had a TBI, 16 patients with SCI, and 12 patients with LEF. Forty-nine of the 50 patients received DVT prophylaxis, with 7 inferior vena cava (IVC) filters placed. The DVT incidence was 6% and the PE incidence was 2%. CONCLUSION: The 6% incidence of DVT was lower than expected due to diligent DVT prophylaxis and appropriate screening of symptomatic patients for clinically significant DVT. The 2% incidence of PE was also lower than expected, most likely due to our lower DVT incidence and the use of IVC filters. The lower DVT and PE incidence verifies our success at DVT and PE prophylaxis.