Antiphospholipid antibody-induced cellular responses depend on epitope specificity : implications for treatment of antiphospholipid syndrome.

Essentials Antiphospholipid antibodies (aPL) are heterogeneous and induce different cellular responses. We analyzed signaling events induced by different monoclonal and patient aPL in monocytes. Two major signaling pathways involving either NADPH-oxidase or LRP8 were identified. Our data suggest that these two pathways mediate the majority of aPL effects on monocytes. SUMMARY: Background Antiphospholipid antibodies (aPLs) contribute to the pathogenesis of the antiphospholipid syndrome (APS) by induction of an inflammatory and procoagulant state in different cell types, and several signaling pathways have been described. Objectives To investigate whether signaling depends on the epitope specificity of aPLs. Methods Cellular effects of three human monoclonal aPLs with distinctly different epitope specificities were analyzed in vitro. Expression of tumor necrosis factor-α mRNA by mouse and human monocytes was the major readout. Analysis included cells from genetically modified mice, and the use of specific inhibitors in human monocytes. Data were validated with IgG isolated from 20 APS patients. Results Cofactor-independent anticardiolipin aPLs activated monocytes by induction of endosomal NADPH oxidase. Activation could be blocked by hydroxychloroquine (HCQ). Anti-ß2 -glycoprotein I aPL activated monocytes by interacting with LDL receptor-related protein 8 (LRP8). This could be blocked by rapamycin. Analysis of 20 APS patients' IgG showed that all IgG fractions activated the same two pathways as the monoclonal aPL, depending on their epitope patterns as determined by ELISA. Monocyte activation by APS IgG could be blocked completely by HCQ and/or rapamycin, suggesting that in most, if not all, APS patients there is no other relevant signaling pathway. Conclusions aPLs activate two major proinflammatory signal transduction pathways, depending on their epitope specificity. HCQ and rapamycin, either alone or in combination, completely suppress signaling by APS IgG. These observations may provide a rationale for specific treatment of APS patients according to their aPL profile.

Electronically signed documents in health care--analysis and assessment of data formats and transformation.

OBJECTIVES: Our objectives were to analyze and assess data formats for their suitability for conclusive and secure long-term archiving and to develop a concept for legally secure transformation of electronically signed documents that are not available in data formats appropriate for long-term archiving. METHODS: On the basis of literature review and Internet searches we developed general evaluation criteria to assess data formats with regard to their suitability for conclusive and secure long-term archiving. The assessment of data formats refers to format specifications and available literature. For the analyses of the transformation of signed documents we analyzed legal requirements on the basis of laws and ordinances as well as technical requirements by means of literature reviews, Internet searches and technical specifications. RESULTS: The following evaluation criteria are suited for this kind of assessment of data formats: transparency and standardization, stability, presentation and security. According to our assessment the following data formats are most suitable for conclusive and secure long-term archiving: PDF for formatted and unstructured text documents, XML for markup languages, TIFF for images in general, DICOM for medical images and S/MIME for the storage of e-mail. To transform electronically signed documents we propose an elementary procedure and universal basic model in form of an XML schema definition that includes the necessary legal and technical information. CONCLUSIONS: If electronic documents are to replace paper-based documents in patient records, they have to conform to the criteria for secure long-term archiving. The analyzed data formats are to be extended by mechanisms to guarantee the long-term security of electronic signatures. To transform large quantities of documents in a legally secure way, our basic model has to be extended for automated procedures.

Accuracy of heart rate assessment in atrial fibrillation.

OBJECTIVE: To determine the most accurate technique to measure the heart rate during atrial fibrillation by use of three counting intervals, 15, 30, and 60 seconds, and two methods, apical and radial pulse measurement. DESIGN: A quasi-experimental, repeated measures factorial design was used to determine absolute error (amount of error ignoring direction of error) between heart rates obtained from six randomly ordered pulse measurements taken of one man in chronic atrial fibrillation by the 94 nurses in the sample and the heart rate recorded by simultaneous electrocardiographic (ECG) and plethysmographic (pleth) recordings. SUBJECTS: Nurses in four groups comprised the sample; registered nurses (N = 29), licensed practical nurses (N = 23), nursing students (N = 21), and registered nurses with advanced degrees who are clinical specialists and in faculty positions. RESULTS: The heart rate of the man varied from 57 to 111 beats/min (mean 81 beats/min). The mean absolute error rates for the six measurements ranged from 8 beats/min to 20 beats/min, all considered to be important when a 10% error was used as the criteria for clinical significance. The apical method was significantly more accurate than the radial method regardless of whether the ECG or pleth standard was used (ECG--F1.90 = 72.91, p less than 0.0001; pleth--F1.144 = 4.68, p = 0.036). The 60-second counting interval was significantly more accurate regardless of the standard (ECG--F2.180 = 5.19, p = 0.006; pleth--F2.88 = 3.95, p = 0.02). CONCLUSIONS: Atrial fibrillation occurs in 2% to 4% of people over 60 years of age and is one of the most difficult dysrhythmias to count. Accurate counts are important when making clinical decisions, yet measurement of heart rate in this study was quite inaccurate. The 60-second count and the apical method were the most accurate statistically, although differences in counting interval error rates were not clinically significant.

Accuracy of radial pulse assessment by length of counting interval.

The purpose of this study was to determine the reliability and validity of counting resting and rapid radial pulse rates at 15-, 30-, and 60-second intervals. Difference scores were calculated between heart rates obtained by the 103 nurse subjects and rates obtained from simultaneous electrocardiographic tracings taken for the three counting intervals at resting rates and at rapid rates. Repeated-measures analysis of variance indicated no differences based on the subjects' educational level. Rapid heart rates (greater than or equal to 100 beats/min), as a whole, were significantly less accurate than resting rates (p = 0.0076). Although there was a significant main effect for length of counting interval (p = 0.0490), post hoc evaluation by Tukey's HSD test showed that only the 15-second rapid counts were significantly different from all the resting counts, but they were not different from the 30- or 60-second rapid counts. These results suggest that a 30-second counting interval may be the most accurate and efficient to use in counting the radial pulse and that the 15-second counting interval should not be used for rates faster than 100 beats/min.

Clinical evaluation of three techniques for administering low-dose heparin.

The purpose of this study was to investigate the effect of three techniques for administering subcutaneous low-dose heparin on the formation of bruises at the injection site in adult postoperative cardiothoracic surgery patients. Forty-three subjects comprised the sample. All received subcutaneous injections of heparin, 5,000 units every 12 hours postsurgery. Three subcutaneous injection techniques, identified to study the variables of needle manipulation and tracking of the medication, were administered randomly to each subject. Forty-eight hours after the third injection, the sites were observed and bruises, if present, were measured. Data were analyzed by means of the Friedman test, and a 0.569 level of significance was obtained. It was concluded that, for this sample, none of the three techniques appeared clearly superior in yielding smaller or fewer bruises.