LDS hospital, a facility of Intermountain Health Care, Salt Lake City, Utah

On-line documentation by nurses and a comprehensive text management system are functional in several facilities of intermountain Health Care (IHC). The following articles detail factors in the design and implementation of this computerized network as experienced at LDS Hospital, part of the IHC system. Areas discussed are the system's applications for medical decision support, communication, patient classification, nurse staffing versus cost, emergency department usage, patient problem/event recording, clinical outcomes, and text publication. Users express satisfaction with the time saving, consistency of reporting, and cohesiveness of these applications.     

High-density recording and topographic analysis of the auditory oddball event-related potential in patients with schizophrenia

BACKGROUND: Prior research has shown reductions of the N1, N2, and P300 auditory event-related potential (ERP) components in schizophrenic patients. Most studies have shown a greater P300 reduction in left versus right temporal leads in schizophrenic patients. These studies were done with sparse electrode arrays, covering restricted areas of the head, thus providing an incomplete representation of the topographic field distribution. METHODS: We used a 64-channel montage to acquire auditory oddball ERPs from 24 schizophrenic patients and 24 controls subjects. The N1, P2, N2, P300, and N2 difference (N2d) amplitudes and latencies were tested for group and laterality differences. Component topographies were mapped onto a three-dimensional head model to display the group differences. RESULTS: The schizophrenic group showed reduction of the N1 component, perhaps reflecting reduced arousal or vigilance, but no N1 topographic difference. An N2d was not apparent in the schizophrenic patients, perhaps reflecting severe disruption in neural systems of stimulus categorization. In the patients, the P300 was smaller over the left temporal lobe sites than the right. CONCLUSIONS: The increased ERP spatial sampling allowed a more complete representation of the dipolar nature of the P300, which showed field contours consistent with neural sources in the posterior superior temporal plane.     

Regulation of GRP1-catalyzed ADP ribosylation factor guanine nucleotide exchange by phosphatidylinositol 3,4,5-trisphosphate

Cellular levels of phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) are rapidly elevated in response to activation of growth factor receptor tyrosine kinases. This polyphosphoinositide binds the pleckstrin homology (PH) domain of GRP1, a protein that also contains 200 residues with high sequence similarity to a segment of the yeast Sec7 protein that functions as an ADP ribosylation exchange factor (ARF) (Klarlund, J., Guilherme, A., Holik, J. J., Virbasius, J. V., Chawla, A., and Czech, M. P. (1997) Science 275, 1927-1930). Here we show that dioctanoyl PtdIns(3,4,5)P3 binds the PH domain of GRP1 with a Kd = 0.5 microM, an affinity 2 orders of magnitude greater than dioctanoyl-PtdIns(4,5)P2. Further, the Sec7 domain of GRP1 is found to catalyze guanine nucleotide exchange of ARF1 and -5 but not ARF6. Importantly, PtdIns(3,4,5)P3, but not PtdIns(4,5)P2, markedly enhances the ARF exchange activity of GRP1 in a reaction mixture containing dimyristoylphosphatidylcholine micelles, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid, and a low concentration of sodium cholate. PtdIns(3,4,5)P3-mediated ARF nucleotide exchange through GRP1 is selectively blocked by 100 microM inositol 1,3,4,5-tetrakisphosphate, which also binds the PH domain of GRP1. Taken together, these data are consistent with the hypothesis that selective recruitment of GRP1 to PtdIns(3,4,5)P3 in membranes activates ARF1 and -5, known regulators of intracellular membrane trafficking.     

Echocardiographic and biochemical evaluation of the development and progression of carcinoid heart disease

OBJECTIVES: To study the applicability of a newly developed echocardiographic scoring system in the assessment of carcinoid valvular heart disease. BACKGROUND: We investigated prospectively the development, progression and regression of carcinoid valvular heart disease in patients with carcinoid syndrome by serial echocardiography, correlating these features with urinary 5-HIAA levels and clinical data collected during therapy with somatostatin analog. METHODS: Twenty-three patients with carcinoid syndrome underwent serial echocardiographic examinations. An echocardiographic carcinoid valvular heart disease (CVHD) % score was determined from points assigned for tricuspid and pulmonary valve structure and function. RESULTS: Fifteen patients had no CVHD at study entry (group 1), while 8 patients had findings of CVHD (group 2). Five patients in group q developed new CVHD (1B), while one demonstrated progression of CVHD (2B). The remaining patients did not develop (1A) or had no progression of CVHD (2B). Despite major declines in 5-HIAA levels during therapy in most patients, CVHD did not regress. There were significantly lower levels of median baseline 5-HIAA (98.8 vs. 256 mg/24 h), posttreatment 5-HIAA (50.3 vs. 324 mg/24 h) and posttreatment 5-HIAA time integral (37.3 vs. 192 g/24 h* days) in group A vs. B (p < 0.05). However, only posttreatment 5-HIAA levels independently predicted the development or progression of CVHD by multiple step-wise regression analysis (p < 0.005), with a threshold observed in the 100 mg/24 h range. CONCLUSIONS: We designed a new echocardiographic scoring system to evaluate CVHD. Correlating echocardiographic scores with biochemical and clinical markers showed that only posttreatment 5-HIAA levels independently predicted the development or progression of CVHD. This study strengthens the association between serotonin secretion and CVHD, as well as introducing a new technique for serial follow-up of these patients.     

Evidence for a symmetrical requirement for Rab5-GTP in in vitro endosome-endosome fusion

Early endosome fusion, which has been extensively characterized using an in vitro reconstitution assay, is Rab5-dependent. To examine the requirement for Rab5 on both fusion partners, we prepared cytosol and endosomes depleted of Rab5. Unlike control cytosol, Rab5-depleted cytosol was only marginally active in the in vitro endosome fusion. However, fusion could be restored by the addition of wild-type Rab5 or Rab5 D136N, a mutant whose nucleotide specificity favors xanthine over guanine. The addition of Rab5 D136N restored fusion only in the presence of XTP. In the absence of XTP or in the presence of XDP, Rab5 D136N failed to restore fusion. When fusion was carried out with endosomal vesicles depleted of Rab GTPases (by preincubation of vesicles with GDP dissociation inhibitor), together with cytosol immunodepleted of Rab5, fusion was virtually absent. We then used immunodepleted cytosol and GDP dissociation inhibitor-treated vesicles to determine whether Rab5 is required by both fusion partners. Using separate sets of endosomal vesicles, we found that priming both sets of Rab5-depleted vesicles with Rab5 Q79L, a GTPase-defective mutant, substantially stimulated endosome fusion. Priming one set of vesicles with Rab5 Q79L and a second set of vesicles with Rab5 S34N failed to activate fusion. When both sets of Rab5-depleted vesicles were primed with Rab5 D136N supplemented with XTP, endosome fusion was stimulated, similar to that observed with Rab5 Q79L. However, when one set of vesicles was preincubated with Rab5 D136N plus XTP and the second set with Rab5 D136N and XDP, no stimulation of fusion was observed. We conclude that Rab5-GTP is required on both fusion partners for docking and fusion of early endosomes. To confirm the fusion of Rab5-GTP-positive vesicles in vivo, we expressed GFP-Rab5 Q79L in fibroblasts and observed fusion of Rab5-positive vesicles. We failed to record fusion of Rab5-positive vesicles with Rab5-negative vesicles. We conclude that Rab5-GTP is required on both sets of endosomes for fusion in vitro and in living cells.     

Failure micromechanisms in continuous carbon-fibre/epoxy-resin composites

This study is concerned with the influence of the strength of the fibre/matrix interface on the strength and failure process in uniaxial arrays of carbon fibres in an epoxy resin. A batch of high-strength carbon fibres has been supplied with several levels of an oxidative surface treatment to produce composites with various interface strengths. Tensile tests have been conducted on single fibres, on loose bundles and on tows impregnated with an epoxy resin. Further tests have been conducted to estimate the interface strength. A hybrid-tow test configuration has then been used to follow the sequence of failure within a single tow of the carbon fibre in a uniaxial composite. The results indicate that the fibre strength is affected only slightly by the surface treatment, the strength of impregnated tows is reduced, and their mode of failure and that of the hybrid tows is affected significantly.     

Implementation of quantitative perfusion imaging techniques for functional brain mapping using pulsed arterial spin labeling

We describe here experimental considerations in the implementation of quantitative perfusion imaging techniques for functional MRI using pulsed arterial spin labeling. Three tagging techniques: EPISTAR, PICORE, and FAIR are found to give very similar perfusion results despite large differences in static tissue contrast. Two major sources of systematic error in the perfusion measurement are identified: the transit delay from the tagging region to the imaging slice; and the inclusion of intravascular tagged signal. A modified technique called QUIPSS II is described that decreases sensitivity to these effects by explicitly controlling the time width of the tag bolus and imaging after the bolus is entirely deposited into the slice. With appropriate saturation pulses the pulse sequence can be arranged so as to allow for simultaneous collection of perfusion and BOLD data that can be cleanly separated. Such perfusion and BOLD signals reveal differences in spatial location and dynamics that may be useful both for functional brain mapping and for study of the BOLD contrast mechanism. The implementation of multislice perfusion imaging introduces additional complications, primarily in the elimination of signal from static tissue. In pulsed ASL, this appears to be related to the slice profile of the inversion tag pulse in the presence of relaxation, rather than magnetization transfer effects as in continuous arterial spin labeling, and can be alleviated with careful adjustment of inversion pulse parameters.