Future Direction of IMIA Standardization. Report from the IMIA Standardization Working Group.

OBJECTIVES: Standardization in the field of health informatics has increased its importance and global alliance for establishing interoperability and compatibility internationally. Standardization has been organized by standard development organizations (SDOs) such as ISO (International Organization for Standardization), CEN (European Committee for Standardization), IHE (Integrating the Healthcare Enterprise), and HL7 (Health Level 7), etc. This paper reports the status of these SDOs' activities. METHODS: In this workshop, we reviewed the past activities and the current situation of standardization in health care informatics with the standard development organizations such as ISO, CEN, IHE, and HL7. Then we discussed the future direction of standardization in health informatics toward "future medicine" based on standardized technologies. RESULTS: We could share the status of each SDO through exchange of opinions in the workshop. Some WHO members joined our discussion to support this constructive activity. CONCLUSION: At this meeting, the workshop speakers have been appointed as new members of the IMIA working groups of Standards in Health Care Informatics (WG16). We could reach to the conclusion that we collaborate for the international standardization in health informatics toward "future medicine".

A map of Alzheimer's disease-signaling pathways: a hope for drug target discovery.

Alzheimer's disease (AD) is a complex neurodegenerative condition, and its drug therapy is challenging. To inform AD drug discovery, we developed the "AlzPathway," a prototype of a comprehensive map of AD-related signaling pathways, from information obtained through studies in the public domain. The AlzPathway provides an integrated platform for systems analyses of AD-signaling pathways and networks.

High speed clinical data retrieval system with event time sequence feature: with 10 years of clinical data of Hamamatsu University Hospital CPOE.

OBJECTIVES: This paper illustrates a high speed clinical data retrieving system, from 10 years of data of operating hospital information system for the purposes of research, evidence creation, patient safety, etc., even incorporating time sequence of causal relations. METHODS: Total of 73,709,298 records of 10 years at Hamamatsu University Hospital (as of June 2008) are sent from HIS to retrieval system in HL7 v2.5 format. Hierarchical variable length database is used to install them. RESULTS: A search for "listing patients who were prescribed Pravastatin (Mevalotin and generic drugs, any titer)" took 1.92 seconds. "Pravastatin (any) prescribed and recorded AST >150 within two weeks" took 112.22 seconds. Searching conditions can be set to be more complex, connected by Boolean operator and/or. This system called D*D is in operation at Hamamatsu University Hospital since August 2002. It is used for 48,518 times (monthly average of 703 searches). Neither searching, nor background export of data from HIS caused delay of routine operating CPOE. CONCLUSIONS: Search database outside of routine operating CPOE, with daily export of order data in HL7 v2.5 format, is proved to provide excellent search environment without causing trouble. Hierarchical representation gives high-speed search response, especially with time sequence of events.

Postrevascularization recovery of fatty acid utilization in ischemic myocardium: a randomized clinical trial of potassium channel opener.

BACKGROUND: Abnormal fatty acid metabolism persists in hibernating myocardium, even after reperfusion. This study was designed to determine whether the K+ channel opener, nicorandil, improves fatty acid utilization after percutaneous transluminal coronary angioplasty (PTCA). METHODS: Patients undergoing elective PTCA were randomly assigned to treatment (group N, n = 26) or control groups (group C, n = 22). Group N received intracoronary and intravenous nicorandil during PTCA. Myocardial fatty acid use and perfusion were quantitatively evaluated by means of iodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid single photon emission computed tomography (I-123 BMIPP SPECT) and thallium-201 (Tl-201) imaging before PTCA, 72 hours after PTCA, and 3 months after PTCA. Left ventricular function was also evaluated by means of contrast ventriculography before and 3 to 6 months after PTCA. RESULTS: The 1-123 BMIPP defect score in group N significantly decreased, from 28%+/-13% to 20%+/-20% after PTCA and to 18%+/-17% 3 months later. In contrast, the I-123 BMIPP defect score in group C increased from 28%+/-20% to 36%+/-15% (P<.05 versus group N) after PTCA, then returned to 28%+/-17% (P<.05 versus group N) 3 months after PTCA. Recovery of left ventricular function paralleled the recovery of I-123 BMIPP uptake. CONCLUSIONS: Nicorandil improves the recovery of myocardial fatty acid utilization and cardiac function after PTCA. K(ATP) channel activation may have a protective effect during coronary artery occlusion and improve subsequent recovery.

Effect of mental stress on left ventricular ejection fraction and its relationship to the severity of coronary artery disease.

To evaluate the relationship between the mental stress-induced decrease in left ventricular ejection fraction (LVEF) and the severity of exercise-induced ischaemia, 20 patients with stable coronary artery disease (CAD) underwent radionuclide ventriculography during mental stress testing and stress myocardial perfusion single-photon emission tomography (SPET). We also examined whether changes in haemodynamic and neurohormonal parameters are related to changes in LVEF during mental stress. The LVEF decreased from 54.8% +/- 17.7% to 49.8% +/- 16.2% with mental stress (P < 0.0005). Ten of the 20 patients (50.0%) had a > or = 5% decrease in LVEF The remaining ten patients had no or a <5% decrease in LVEF There was a significant correlation between the change in LVEF during mental stress and the size of the reversible defect on stress myocardial perfusion SPET (r = -0.80, P < 0.0005), with close regional correspondence (75% identical). This correlation was less strong in the 12 patients with a total defect score at rest of <10 (r = -0.69, P = 0.014) than in the eight patients with a total defect score at rest of > or = 10 (r = -0.94, P = 0.001). The changes in blood pressure and heart rate were not significantly correlated with the change in LVEF, but the percent change in adrenaline concentration correlated with the change in LVEE It is suggested that mental stress impairs systolic function by inducing transient myocardial ischaemia. The effect of neurohormonal responses during mental stress on LV systolic function may also be important in patients with CAD.

[Algorithm of channel gating and its allosteric regulation by membrane cholesterol].

A method for quantitative analysis of channel kinetics was established with the use of histograms of channel events. In this system, channel kinetics was expressed as an exponential function of temperatures. The two factors in this exponential function were independently regulated: one was the progressive index number, controlled by membrane cholesterol, and the other was the coefficient, directed by channel gramicidin. Mean frequencies of channel opening decreased depending on cholesterol concentrations in the membrane. Its sigmoidal nature suggested that cholesterol regulated the channel characteristics in allosteric manner. The theoretical formula to analyze channel kinetics from the exponental as a function of temperatures, channel and membrane cholesterol concentrations was confirmed to be valid by comparison with experimental results.

Functional evaluation of myocardial viability by 99mTc tetrofosmin gated SPECT--a quantitative comparison with 18F fluorodeoxyglucose positron emission CT (18F FDG PET).

UNLABELLED: To validate functional analysis of gated SPECT in detecting myocardial viability, seventeen patients (male 15, female 2, mean age 58) with angiographically proven chronic ischemic heart disease (RCA 6, LAD 10, LCX 1) and eight normal volunteers (all male) were studied. All patients underwent 18F FDG PET and 99mTc tetrofosmin (TF) gated SPECT within a week. After being displayed in a polar map, myocardial perfusion was regionally determined by the mean count in 9 segments at end diastole (ED) and end systole (ES) in gated SPECT. Systolic function was determined by the count increase ratio from ED to ES (WTI: ES - ED/ED). Glucose metabolism was assessed by 18F FDG PET in the segments correspondent to those defined for SPECT. TF %uptake of < 60% was defined as hypoperfusion, and FDG %uptake of < 50% was defined as reduced glucose metabolism. RESULTS: The myocardial segments were classified into 3 categories: "normal" perfusion (n = 85), "mismatch" (reduced perfusion with reserved FDG uptake, n = 25) and "matched" reduced perfusion and metabolic reduction (n = 26). Mean WTI in "mismatch" segment was 0.38 +/- 0.21, and was significantly greater than that in "matched reduced" segments, 0.15 +/- 0.20 (p < 0.001). It was also greater than that in "normal" segments, 0.27 +/- 0.16. Regression analysis showed that association between WTI and FDG %uptake was significant (r = 0.57, p < 0.0005) for the ischemic segments ("mismatch" + "matched", n = 51), but the association was weak for the entire segments although it was statistically significant (r = 0.26, p = 0.02, n = 136). CONCLUSION: For the segments determined as infarct by perfusion image, systolic functional analysis by gated SPECT is helpful in differentiation of a viable myocardial region or artifact from a scar. Nevertheless, further clinical and technical assessment is required for ECG gating to eliminate overestimation of viability and to warrant clinical use.

Temperature-induced differential kinetic properties between an initial burst and the following steady state in membrane-bound enzymes: studies on lathosterol 5-desaturase.

The NADH-dependent lathosterol 5-desaturation reaction that forms 7-dehydrocholesterol is biphasic, an initial burst followed by steady state. The steady-state phase is slower than the burst phase, because the latter diffusion of the lathosterol substrate within the microsomal membrane must occur before the next reaction can take place [Y. Takakuwa, H. Nishino, Y. Ishibe, and T. Ishibashi (1994) J. Biol. Chem. 269, 27889-27893]. In the present study, changes in the structure and function of the membrane were examined by measurement of the Arrhenius activation energy of lathosterol 5-desaturase at various temperatures between 2 and 45 degrees C. At the burst phase, there was a lack of discontinuity in the Arrhenius plots at the presumed phase transition temperature for the microsomal membrane. However, the plots of the activities of the steady state showed breaks at around 17 and 32 degrees C. It was concluded that phospholipid phase transition affects the steady-state phase but not the burst phase. Furthermore, treatment of microsomes with low concentrations of deoxycholate, known to perturb the membrane integrity, resulted in a break of the activation energy of the burst phase. These results have revealed further evidence for our previous model suggesting interaction between the substrate and enzyme within the microsomal membrane via lateral diffusion.

[Cardiopulmonary resuscitation with cardiopulmonary bypass for intraoperative cardiac arrest].

A 67-year-old man was scheduled for left upper lobectomy under epidural and general anesthesia. About 1 hour after the beginning of operation, he developed cardiac arrest due to sudden massive bleeding from the pulmonary artery. In spite of open chest cardiac massage and intravenous administration of epinephrine, we could not resuscitate him successfully. More than 30 minutes after the cardiac arrest, cardiopulmonary bypass (CPB) was started and mean arterial blood pressure was maintained at 50-60 mmHg. His pulmonary artery was repaired under CPB. One hour after CPB, the weaning from artificial circulation was attempted and the spontaneous beating was observed. However, he developed low cardiac output syndrome due to long time ischemia resulting in hemorrhagic infarction. Therefore, the intra-aortic balloon pumping was started and his hemodynamics was immediately restored. We presume that CPB is useful for intraoperative resuscitation and this gives us new application of advanced life support for the patient in whom the conventional technique is ineffective.