Pleth variability index can predict spinal anaesthesia-induced hypotension in patients undergoing caesarean delivery.

BACKGROUND: Spinal anaesthesia carries a risk of hypotension. We hypothesized that pleth variability index and perfusion index would assess maternal volume status, and thus, allow identification of patients at higher risk of developing hypotension after spinal anaesthesia for caesarean delivery. METHODS: Fifty patients undergoing elective caesarean delivery were enrolled. All patients received spinal anaesthesia with 0.5% hyperbaric bupivacaine (10 mg) and fentanyl (10 mcg). Blood pressure was measured every minute. Pleth variability index and perfusion index were automatically measured throughout the procedure using pulse oximetry on the index finger. In case of hypotension (systolic blood pressure below 90 mmHg or 80% of the baseline value), ephedrine 5 mg was administered. Receiver-operating characteristic and multivariate logistic regression analyses for spinal anaesthesia-induced hypotension were performed. RESULTS: Hypotension occurred in 32 patients (64%). The areas under the receiver-operating characteristic curve were 0.751 (95% confidence interval: 0.597-0.904) for pleth variability index before anaesthesia, 0.793 (95% confidence interval: 0.655-0.930) for pleth variability index after anaesthesia and 0.731 (95% confidence interval: 0.570-0.892) for perfusion index change (percent change in perfusion index induced by spinal anaesthesia). The optimal threshold value of pleth variability index (after anaesthesia) for predicting hypotension was 18% (sensitivity: 78.1%, specificity: 83.3%). Pleth variability index after spinal anaesthesia was an independent factor for hypotension (odds ratio: 1.21, P = 0.041). CONCLUSIONS: Pleth variability index after spinal anaesthesia was a good predictor of spinal anaesthesia-induced hypotension in patients undergoing caesarean delivery. In addition, perfusion index change after spinal anaesthesia has the potential to predict hypotension.

Usability Methods for Ensuring Health Information Technology Safety: Evidence-Based Approaches. Contribution of the IMIA Working Group Health Informatics for Patient Safety.

OBJECTIVES: Issues related to lack of system usability and potential safety hazards continue to be reported in the health information technology (HIT) literature. Usability engineering methods are increasingly used to ensure improved system usability and they are also beginning to be applied more widely for ensuring the safety of HIT applications. These methods are being used in the design and implementation of many HIT systems. In this paper we describe evidence-based approaches to applying usability engineering methods. METHODS: A multi-phased approach to ensuring system usability and safety in healthcare is described. Usability inspection methods are first described including the development of evidence-based safety heuristics for HIT. Laboratory-based usability testing is then conducted under artificial conditions to test if a system has any base level usability problems that need to be corrected. Usability problems that are detected are corrected and then a new phase is initiated where the system is tested under more realistic conditions using clinical simulations. This phase may involve testing the system with simulated patients. Finally, an additional phase may be conducted, involving a naturalistic study of system use under real-world clinical conditions. RESULTS: The methods described have been employed in the analysis of the usability and safety of a wide range of HIT applications, including electronic health record systems, decision support systems and consumer health applications. It has been found that at least usability inspection and usability testing should be applied prior to the widespread release of HIT. However, wherever possible, additional layers of testing involving clinical simulations and a naturalistic evaluation will likely detect usability and safety issues that may not otherwise be detected prior to widespread system release. CONCLUSION: The framework presented in the paper can be applied in order to develop more usable and safer HIT, based on multiple layers of evidence.

The genetic contribution of HLA-DRB5*01:01 to systemic lupus erythematosus in Thailand.

Human leucocyte antigen (HLA) study in patients with systemic lupus erythematosus (SLE) has been investigated in various countries, but the results are still inconclusive. This study was performed to investigate the association between HLA-DR and SLE in patients in northern Thailand. HLA-DR subtyping was performed in 70 patients with SLE and 99 normal healthy controls living in northern Thailand using the INNO-LiPA HLA-DR Decoder kit (Innogenetics) and MICRO SSP HLA DNA Typing kit (One Lambda) for reconfirmation. The allele frequency (AF) of DRB5*01:01 in SLE was significantly higher than in the controls [25.7% vs. 14.6%, P = 0.012, Pc = 0.048, OR = 2.02 (95%CI = 1.17-3.48)]. The AF of DRB1*15:01 and DRB1*16:02 showed a nonsignificant tendency to be higher in SLE (10.7% vs. 8.1%, and 17.9% vs. 11.1%). Interestingly, the DRB5*01:01 allele linked to DRB1*16:02 in 47.2% of SLE and 37.9% of controls, and the prevalence of the DRB1*16:02-DRB5*01:01 haplotype was higher in the patients with SLE [12.1% vs. 5.6%, P = 0.044, OR = 2.35 (95%CI = 1.06-5.19)]. The DRB1*16:02 linked to DRB5*02:02 and *02:03 in 18.2% and 31.8% of controls, respectively, and linked to DRB5*02:03 in 32.0% of SLE patients. The frequency of DRB1*03:01 and *15:02 alleles was not increased in Thai SLE. There was no significant association between DRB5*01:01 and any auto-antibodies or clinical manifestations of SLE. DRB5*01:01 is associated with Thai SLE, and the association is stronger than that of DRB1*15:01. The genetic contribution of DRB5*01:01 is due partially to the linkage disequilibrium between DRB1*16:02 and DRB5*01:01 in the northern Thai population.

A longitudinal study of the quantitative evaluation of patella cartilage after total knee replacement by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping at 3.0 T: preliminary results.

OBJECTIVE: To characterize the quantitative changes of patella cartilage over time after total knee arthroplasty (TKA) by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping at 3.0 T. METHOD: Twenty-six knees of 26 patients (23 women and three men, mean age, 75 years) with primary osteoarthritis and osteonecrosis of the knee underwent TKA with a zirconia ceramic implant in this prospective study. Twelve patients without patella resurfacing (NR group) and 14 patients with patella resurfacing (R group) had TKA with cemented fixation. The implant position was examined by radiograph, computed tomography (CT) and magnetic resonance imaging (MRI). The clinical scores were checked pre-operatively, 1 year post-operatively and at the final follow-up. Patella cartilage and its thickness were evaluated pre-operatively and 1 year after TKA by dGEMRIC and T2 mapping in the NR group only. Patella cartilage was divided into eight regions of interest: the deep and superficial layers of the outer lateral and medial half, and the inner lateral and medial half from the central ridge. RESULTS: The implant position was appropriate in all cases and clinical scores were not significantly different between the two groups. The post-operative dGEMRIC value of the outer medial half superficial zone in the NR group was significantly decreased compared with the pre-operation value (P<0.05), whereas T2 mapping was not significantly changed in all zones. The cartilage thickness of the outer zone was significantly thinner post-operatively (P<0.05). CONCLUSIONS: These findings indicate that osteoarthritic changes in the outer zone of patella cartilage occurred 1 year after TKA.

Peanut stunt virus 2b cistron plays a role in viral local and systemic accumulation and virulence in Nicotiana benthamiana.

To analyze the role of the 2b protein (2bP) of Peanut stunt virus (PSV) in the viral infection cycle, we constructed PSV mutants that express either no 2bP or N-terminal-truncated 2bP. The accumulation of wild-type and mutant viruses in tobacco protoplasts indicated that the 2b cistron is not essential for viral replication. Viral accumulation in Nicotiana benthamiana plants suggested that the 2b cistron is responsible for viral accumulation in inoculated and upper leaves and has a role in virulence. The involvement of eight N-terminal amino acids of 2bP in these functions is discussed.

Genetic contribution of the CD14 -159C/T dimorphism in the promoter region in Japanese RA.

OBJECTIVE: To study the contribution of the CD14 gene to the pathogenesis of rheumatoid arthritis (RA) in Japanese patients. METHODS: CD14 genotyping was carried out at the -159C/T dimorphic site in 97 RA patients and 104 normal subjects by the PCR-RFLP (restriction fragment length polymorphism) METHOD: HLA-DRB1 genotyping was performed by the PCR-SSCP (sequence specific conformational polymorphism) method. RESULTS: The -159C/T dimorphism is not associated with whole RA or with female RA, and the results were compatible with a previous report from Germany. The -159C/T dimorphism was not associated with rheumatoid factor (RF)-positive RA, although the -159T allele tended to be associated with RF in the German report. The -159C/T dimorphism showed no association even in RA patients with the RA-susceptibility HLA-DRB1*0405. The -159T allele was prevalent in Japanese controls. CONCLUSION: The CD14 gene is very unlikely to be genetically involved in the pathogenesis of Japanese RA.

Improvement in respiratory function by percutaneous vertebroplasty.

BACKGROUND: Percutaneous vertebroplasty (PVP) improves back pain and corrects spinal misalignment to some extent, and thus may improve respiratory function. PURPOSE: To retrospectively investigate changes in respiratory function after PVP. MATERIAL AND METHODS: 41 patients (mean age 72.0 years, range 59-86 years; 39 women, two men) who had undergone PVP for vertebral compression fractures (37 thoracic vertebral bodies [Th6-Th12] and 50 lumbar vertebral bodies [L1-L5]) caused by osteoporosis visited our hospital for follow-up consultation between January and June 2005. At this follow-up consultation, respiratory function testing, including percent forced vital capacity (FVC%) and percent forced expiratory volume in 1 s (FEV(1)%), was performed. We retrospectively compared these values with those taken before PVP using a Wilcoxon signed-rank test. RESULTS: FVC% was 85.2+/-30.3% before PVP and 91.5+/-16.8% at follow-up (mean 10 months after PVP), which represented a significant difference (P<0.003). No significant difference in FEV(1)% was detected. Regarding the number of treatment levels, that is, single vertebroplasty versus multiple vertebroplasty, no significant difference in improvement of FVC% was confirmed (P=0.1). FVC% was abnormally low (

Using a low-cost simulation approach for assessing the impact of a medication administration system on workflow.

This paper describes the analysis of the impact of a medication administration system on clinical workflow. The methodological framework employed was based on in-depth analysis of simulated user interactions with a medication administration system. The approach involved the collection of rich data consisting of audio and video recordings of interactions between 16 subjects (5 nurses and 11 physicians) as they interacted with a medication administration system. Methodological considerations and issues in conducting such studies are discussed. The study indicated that use of the system would have a significant impact on nurse and physician workflow and that this impact could be accurately identified using simulation approaches prior to widespread release of such systems in real clinical environments.

The application of an institutional clinical data warehouse to the assessment of adverse drug reactions (ADRs). Evaluation of aminoglycoside and cephalosporin associated nephrotoxicity.

OBJECTIVES: To apply an institutional clinical data warehouse (CDW) to the assessment of adverse drug reactions (ADRs) and demonstrate its utility through a specific example. METHODS: We modeled the process for assessing ADRs through retrospective cohort design by using CDW at the Osaka University Hospital as follows: 1) We defined a drug X, an adverse drug reaction (ADR) Y, and a laboratory measurement Z to assess Y during a given study period; 2) we excluded those whose Z value exceeded the defined criteria or were not available at the inception of the cohort; 3) we divided the patients into two groups based on exposure or non-exposure to X; 4) we matched the patient characteristics between the two groups through stratification and randomization; and 5) we compared the frequency of patients who presented Y during the study period between the two groups. Aminoglycoside and Cephalosporin associated nephrotoxicity in pediatric inpatients was used as an example to demonstrate the usefulness of this approach. RESULTS: Our evaluation indicates that there is an increased risk of nephrotoxicity for pediatric inpatients who were prescribed cephalosporin either alone or in combination with aminoglycoside; further, aminoglycoside tends to increase the cephalosporin-associated nephrotoxicity. CONCLUSIONS: Our findings are consistent with those drawn from other studies, indicating that the method of applying an institutional CDW is useful for assessing ADRs.

The genetic contribution of the TNFa11 microsatellite allele and the TNFb + 252*2 allele in Japanese RA.

OBJECTIVES: The contribution of the microsatellite polymorphisms of TNFa and TNFb, and the TNFB + 252 (TNFB) dimorphism to the pathogenesis of rheumatoid arthritis (RA) was studied among Japanese patients. METHODS: The TNFa and TNFb microsatellite polymorphisms, and the TNFB dimorphism were determined in Japanese RA patients and normal subjects using electrophoresis followed by specific PCR amplification. HLA-DRB1*04 typing was carried out by the PCR-SSCP method. RESULTS: The allele frequency of TNFa11 showed a significant increase in RA with DRB1*0405 when compared to that in RA without DRB1*0405 (28.5% Vs 12.9%, respectively, p = 0.022). An association analysis indicated that TNFa11 was not primary, but secondary to the increase in HLA-DRB1*0405, because TNFa11 showed a strong positive association with HLA-DRB1*0405 in Japanese controls. The slight increase in the TNFb4 allele observed in RA with DRB1*0405 (50.0%) may be reflective of the increase in TNFa11 and DRB1*0405. In RA with DRB1*0405, the allele frequency of TNFB*2 significantly increased compared to that of normal controls (75.0% Vs 55.3%, respectively, p = 0.007) and compared to that of RA without DRB1*0405 (45.0%, p = 0.001). No significant positive association of TNFB*2 with HLA-DRB1*0405 or TNFa11 in Japanese controls might suggest that the increase in the TNFB*2 allele might not be secondary to the increase in DRB1*0405, and that TNFB*2 might contribute additively to DRB1*0405-positive RA in Japanese. CONCLUSION: TNFB*2 may contribute additively to Japanese RA with HLA-DRB1*0405, while TNFa11 and TNFb4 are not independent genetic markers of RA among Japanese.

Genetic contribution of the tumour necrosis factor (TNF) B + 252*2/2 genotype, but not the TNFa,b microsatellite alleles, to systemic lupus erythematosus in Japanese patients.

The contribution of the tumour necrosis factor (TNF) B + 252 (TNFB) dimorphism and microsatellite polymorphisms of TNFa and TNFb to the pathogenesis of systemic lupus erythematosus (SLE) was studied in Japanese patients. The TNFB dimorphism was determined using the restriction fragment length polymorphism (RFLP) method with NcoI digestion followed by specific polymerase chain reaction (PCR) amplification. TNFa and TNFb microsatellite polymorphisms were determined using the DNA sequencer and GeneScan program (Applera Corporation, Foster City, CA) followed by specific PCR amplification. HLA-DRB1*15 typing was carried out by the PCR-sequence specific conformational polymorphism (SSCP) method. In SLE, the allele frequency of TNFB*2 significantly increased (68.9%, P < 0.05) and the genotype frequency of TNFB*2/2 also increased (52.8%, P < 0.05). TNFB*2 showed no significant linkage disequilibrium with HLA-DRB1*1501. The prevalence of TNFa13 and TNFb4 showed very slight increases, but these increases were not significant. An association analysis indicated that TNFB*2/2 conferred greater, or at least equal, susceptibility to SLE in Japanese patients in comparison with HLA-DRB1*1501. The TNFB*2/2 genotype may contribute additively with DRB1*1501 to SLE in Japanese patients. No association was observed between auto-antibodies and TNF. TNFB*2 is a genetic marker for SLE in Japanese patients, while TNFa and TNFb microsatellites are not associated with SLE.

Molecular analysis of coat protein coding region of tobacco stunt virus shows that it is a strain of Lettuce big-vein virus in the genus Varicosavirus.

To evaluate the relationship between tobacco stunt virus (TStV) and Lettuce big-vein virus (LBVV), we determined nucleotide sequences of the coat protein (CP) coding region of five TStV and three LBVV isolates and compared them with those of one Japanese and four Spanish isolates of LBVV. CP coding regions were identical in size and the nucleotide and amino acid sequence identities between TStV and LBVV were 95.6-96.5% and 97.2-98.7%, respectively. Phylogenetic analysis of nucleotide sequences indicated that TStV was very closely related to LBVV and a strain of LBVV rather than a distinct species.

Competition between wild-type virus and a reassortant from subgroups I and II of CMV and activation of antiviral responses in cowpea.

To investigate the interactions between RNA3 and RNA4 from subgroups I and II in mixed infections, accumulation of CMV RNA were analyzed. In the mixed inoculation assays with CMV-LE (LE, subgroup I) and a reassortant LLm consisting of RNA1 and RNA2 from LE, and RNA3 from CMV-m2 (m2, subgroup II), LE RNA3 and RNA4 could systemically spread in the plants, whereas those of m2 could not. Furthermore, accumulation of virus short RNA and a cowpea-encoded RNA-directed RNA polymerase gene (VuRdRP1) mRNA were found in the plants, suggesting that VIGS and/or distinct antiviral responses (was) were activated by infection with CMV.

Dynamic viewer of medical events in electronic medical record.

Medical record should enable doctors to comprehend the patient's history and select suitable medical treatment. In paper based medical records, medical events (examination, treatment etc.) are recorded successively, and problem oriented recording is difficult to be applied to patients with much information and a long history. Consequently it is not easy to understand the patient's history from paper based medical records. In order to solve this problem, we developed the flow sheet system in our electronic medical record (EMR). To make a flow sheet, we analyzed the structure of the medical event data. In this paper we introduced the medical event information model for our EMR. Furthermore, we clarified the specification of the data presentation on the flow sheet. We developed the flow sheet on the basis of these analyses. Because there are 3 layers in the vertical axis of the flow sheet, many items of the medical event can be displayed on the screen. When user clicks the cell, the corresponding detail data including images are shown. This system functions to link medical event items with a problem, and shows the bundled items on the flow sheet when the user selects the problem. We implemented this system in Osaka University Hospital. The number of the types of medical events and those of detail events in inpatients are 5.0+1.7 (mean+SD) and 60+47, respectively. The medical doctors in Osaka University Hospital evaluated this system, and concludes that the flow sheet data presentation makes comprehension of the patient's history easier than paper based records. As to the function of bundling the items relevant to the problem, they feel it is especially useful for patients with chronic disease. Thus the flow sheet data presentation in EMR is useful for medical practice.

PACS linked to EPR.

We developed a new PACS linked to Electronic Patient Record system (EPR). It was a hospital-wide PACS storing all the radiological examinations. The images and reports were linked on EPR. The concept of navigation servers and segment servers was introduced for prefetchig and quick displaying. After the start of operation, increasing retrieval indicated its effectiveness on practical work in spite of remaining delivery of radiographs.

Synthesis of TiRru2 heterobimetallic and TiRuM (M = Rh, Rr, Pd, Pt) heterotrimetallic sulfido clusters from a hydrosulfido-bridged titanium-ruthenium complex.

Treatment of the hydrosulfido-bridged titanium-ruthenium heterobimetallic complex [Cp2Ti(mu2-SH)2RuCl(eta5-C5Me5)] (1; Cp = eta5-C5H5) with an excess of triethylamine followed by addition of [RuCl2(PPh3)3] and [[(cod)M]2(mu2-Cl)2] (M = Rh, Ir; cod = 1,5-cyclooctadiene) led to the formation of the TiRu2 and TiRuM mixed-metal sulfido clusters [(CpTi)[(eta5-C5Me5)Ru][Ru(PPh3)2](mu3-S)2(mu2-Cl)2] (3) and [(CpTi)[(eta5-C5Me5)Ru][M(cod)](mu3-S)2(mu2-Cl)] (M = Rh (4a), Ir (4b)), respectively. On the other hand, the reactions of 1 with [M(PPh3)4] (M = Pd, Pt) afforded the TiRuM trinuclear clusters [(CpTiCl)[(eta5-C5Me5)Ru][M(PPh3)2](mu3-S)(mu2-S)(mu2-H)] (M = Pd (5a), Pt (5b)) with an unprecedented M3(mu3-S)(mu2-S) core. The detailed structures of these triangular clusters 3-5 have been determined by X-ray crystallography. Crystal data: 3, triclinic, P1, a = 12.448(4) A, b = 12.773(4) A, c = 17.270(4) A, alpha = 100.16(2) degrees, beta = 99.93(2) degrees, gamma = 114.11(3) degrees, V = 2373(1) A(3), Z = 2; 4a, triclinic, P1, a = 7.714(2) A, b = 11.598(3) A, c = 14.802(4) A, alpha = 80.46(2) degrees, beta = 82.53(2) degrees, gamma = 71.47(2) degrees, V = 1234.0(6) A3, Z = 2; 4b, triclinic, P1, a = 7.729(1) A, b = 11.577(2) A, c = 14.766(3) A, alpha = 80.14(1) degrees, beta = 82.71(1) degrees, gamma = 71.55(1) degrees, V = 1231.1(4) A3, Z = 2; 5a, monoclinic, P2(1)/c, a = 11.259(4) A, b = 16.438(4) A, c = 26.092(5) A, beta = 102.23(3) degrees, V = 4719(2) A(3), Z = 4; 5b, monoclinic, P2(1)/n, a = 11.369(2) A, b = 16.207(3) A, c = 26.116(2) A, beta = 102.29(1) degrees, V = 4701(1) A3, Z = 4.

Cilnidipine more highly attenuates cold pressor stress-induced platelet activation in hypertension than does amlodipine.

The clinical significance of N-type calcium channel blockade has not been fully examined. We here compared the effects of the N-type calcium channel blockers cilnidipine and amlodipine on the sympathetic nervous system and platelet function in hypertension under resting and stressed conditions. Thirty-two patients with hypertension (58+/-9 years) received cilnidipine or amlodipine for 4 weeks in this crossover study. On day 28 of each treatment, plasma levels of epinephrine (EP), norepinephrine (NEP), and beta-thromboglobulin (BTG), and EC50 of ADP-induced platelet aggregation (ADPE50) were determined at rest and after a cold pressor test. On day 29, the group receiving cilnidipine was switched to amlodipine treatment, and vice versa. At rest, the blood pressure, heart rates, EP, NEP, ADPEC50, and BTG, were similar in both treatments. After the cold pressor test, increases in EP (35+/-17 to 44+/-25 pg/ml; p<0.05) and BTG (40+/-13 to 49+/-22 ng/ml; p<0.01) and a decrease in ADPEC50 (32+/-26 to 27+/-24 micromol; p<0.05) were observed in the amlodipine treatment, but not in the cilnidipine treatment. In addition, the increase in NEP was significantly greater (p<0.05) in the amlodipine (276+/-78 to 318+/-87 pg/ml; p<0.01) than in the cilnidipine treatment (273+/-88 to 291+/-100 pg/ml; p<0.05). Cilnidipine more highly attenuates the activation of platelet function in response to cold pressor stress than does amlodipine. Attenuated activation of the sympathetic nervous system via N-type calcium channel blockade may contribute to this phenomenon.

Papillon-Lefèvre syndrome: analysis of HLA antigens.

OBJECTIVES: Papillon-Lefèvre syndrome (PLS) is a rare disease associated with prepubertal periodontitis. Our previous studies demonstrated that three unrelated patients with PLS showed the similar antigen-specific immune responses to Actinobacillus actinomycetemcomitans. The initiation of antigen-specific immune responses was involved with human leukocyte antigens (HLA) on antigen-presenting cells. The aim of this study was to examine HLA haplotypes in the three patients with PLS. SUBJECTS AND METHODS: The three PLS patients, their mothers and the father of one patient participated in this study. HLA class I and class II antigens were determined serologically and DNA typing for DRB1 and DQB1 was performed using the restriction fragment length polymorphism-polymerase chain reaction method. RESULTS: The distribution of serologic HLA haplotypes, in two of three patients, was found to be quite similar. The DNA typing revealed that DRB1*0406, DRB1*08032, DQB1*0302, DQB1*06011 genotypes were shared in the two patients. The probability of sharing these four DNA types in unrelated individuals was nearly 1:40,000 in the Japanese population. CONCLUSION: Our results suggest that HLA antigen may be included as a possible host factor in the pathogenesis of PLS and that a genetically controlled immune response may account for an increased susceptibility to periodontal infection.