Linkage and interaction of loci on 1q23 and 16q12 may contribute to susceptibility to systemic lupus erythematosus

OBJECTIVE: Six recent genome scans of different systemic lupus erythematosus (SLE) multiplex family cohorts showed multiple putative susceptibility loci. In the present study, we examined 4 previously identified loci to replicate findings of significant linkage to 1q23 and 16q12, and to support findings of suggestive linkage to 14q21-23 and 20p12 in a cohort of 115 multiethnic nuclear families containing 145 SLE-affected sibpairs. METHODS: Model-free, multipoint linkage analyses (SIBPAL2, SAGE version 4.0) and exclusion mapping (GeneHunter) were performed. RESULTS: Linkages to 1q23 (peak at D1S2675, mean allele sharing [MAS] 0.56; P = 0.003) and to 16q12 (peaks between D16S753 and D16S757, MAS 0.57; P = 0.003) were confirmed, but linkage evidence at 20p12 was weak and inconsistent (MAS 0.52-0.56; from P = 0.005 to P not significant). Evidence for linkage to 1q23 and 16q12 was stronger in 68 non-Caucasian affected sibpairs than in 77 Caucasian affected sibpairs. Exclusion mapping ruled out linkage at 14q21-23 (lambda(s) [sib recurrence risk or genotypic risk ratio] = 1.8). Because the pericentromeric region of chromosome 16 has been identified by genome scans in several autoimmune diseases, we postulated that it might harbor an autoimmune modifier gene. To explore this possibility, we tested for an interaction between 16q12 and 1q23, and between 16q12 and 20p12. Haplotype sharing at 1q23 increased concomitantly with increased haplotype sharing at 16q12 (P = 0.008 by nonparametric Jonckheere-Terpstra exact statistical test). No evidence supporting an interaction between 16q12 and 20p12 was observed. Analysis of sibpairs sharing 2 alleles at 16q12 also showed increased allele sharing at 1q23 (MAS from 0.56 to 0.65). CONCLUSION: These data support the presence of SLE susceptibility genes at 1q23 and 16q12, particularly in non-Caucasians. The skewed distribution of haplotypes suggests that genetic interaction of these two loci may affect SLE susceptibility.     

Evaluation of model for end-stage liver disease for prediction of mortality in decompensated chronic hepatitis B

OBJECTIVES: We aimed to study the predictive ability of model for end-stage liver disease (MELD) for short-term mortality in chronic hepatitis B. METHODS: All patients admitted from 1996 to 2003 because of chronic hepatitis B and its related complications were identified by electronic search of the hospital database. MELD and Child-Turcotte-Pugh (CTP) scores on initial admissions were calculated. Cox proportional hazard model was used to determine the factors associated with mortality. The area under receiver operator characteristics curve (AUC) was used to determine the predictive abilities of the two models for 3-month and 1-yr mortalities. RESULTS: A total of 2,073 patients was admitted because of liver-related problems and 506 patients had chronic hepatitis B-related complications. Two hundred fifty-six (51%) patients died and 16 (3%) patients underwent liver transplantation. In multivariate analysis, MELD and CTP scores were independent predictors of 3-month and 1-yr mortality. Other independent predictors of mortality included older age, hepatocellular carcinoma (HCC), lamivudine treatment, and lower serum sodium. At both 3 months and 1 yr, the AUC of the MELD score (0.65 and 0.63, respectively) was significantly lower than that of the CTP score (0.75 and 0.77, respectively) (p < 0.0001). The differences remained significant when only liver cirrhosis patients without HCC at presentation were analyzed, but the AUC of the two scores became comparable when patients on lamivudine were excluded. CONCLUSIONS: The MELD score is a valid prognostic model in decompensated chronic hepatitis B. Lamivudine treatment may affect the performance of MELD score. Other variables including those in CTP score may improve its predictive ability.     

Normal atrial activation and voltage during sinus rhythm in the human heart: an endocardial and epicardial mapping study in patients with a history of atrial fibrillation

Background: The three-dimensional contributions to human atrial activation in sinus rhythm have not been specifically characterized. We evaluated the sequence of endocardial and epicardial activation and voltage of the atria during normal sinus rhythm.
Methods and Results: The study group includes 35 patients with history of symptomatic atrial fibrillation. Prior to catheter ablation of atrial fibrillation, we performed multielectrode electroanatomic mapping during sinus rhythm, endocardially of the RA, LA, and coronary sinus (CS) and, in 10 patients, epicardially of the transverse sinus and oblique sinus. Following activation of the atrial region of the sinus node, the epicardial transverse sinus was activated 11 ± 18 msec later, while the earliest endocardial LA activation occurred in the region of Bachmann's bundle at 31 ± 13 msec, significantly earlier than the earliest epicardial LA activation of the oblique sinus at 54 ± 10 msec (P < 0.002). The posterior LA revealed complex types of activation in 66% of patients analyzed, due to the convergence of wavefront propagation from the CS, oblique sinus, and endocardial LA. Bipolar voltage measurements revealed significantly higher values for the epicardium (mean 3.05 ± 1.31 mv) than for the endocardium (mean 1.65 ± 0.75 mv), P < 0.0001 between both groups.
Conclusions: In sinus rhythm, we have characterized endocardial and epicardial atrial activation and voltage, and provide an analysis and understanding of the genesis of the P wave complex in humans.     

Polymorphisms of the toll-like receptor 9 (TLR9) gene with systemic lupus erythematosus in Chinese

SIR, Systemic lupus erythematosus (SLE) patients and murinelupus models of SLE are characterized by the presence of autoantibodiesthat recognize DNA and nucleosomes. It has been shown that interactionof bacterial CpG DNA with toll-like receptor 9 (TLR9) expressedon B cells can stimulate production of antibodies [1]. In thelupus mouse model and SLE patients, DNA fragments isolated fromplasma are hypomethylated and they may mimic microbial DNA and     

基础医学多元化教学:降低"考试领导学习"的初探

目的 尝试在生理学教学方面推动考试外的其它学习项目，而非仅以研读共笔及考古题的方式评估学生成绩来评估学生的学习成效。方法 我们将生理学学习成绩分为两部分，传统考试占学期成绩70％，“非考试”之评估占30％，我们将此30％成绩分别以生理学相关论文研读及口头报告、问题导向学习（PBL）及平时成绩之方式计分。采用学生意见问卷调查，统计学生投入多少时间用于准备考试、口头报告及PBL。结果 学生在“非考试”项目中表现很高的学习意愿，且与准备考试相比学习成效并无差异。结论 本研究的结果显示，医学生实行生理学多元化教学方式不会负面影响其学习成效。     

A survey of PDA use by palliative medicine practitioners

This paper describes the results of a Web survey on the use of personal digital assistants (PDAs) by physicians across Canada involved with the delivery of palliative medicine in different settings. Seventy-two physicians responded to the survey from April to July 2005. The survey revealed 58.3% of respondents currently use PDAs on a daily basis, mostly to organize their practice and to look up medical references. Some use their PDAs to store patient information and to access a central electronic patient record (EPR). In terms of potential PDA use in palliative medicine, six thematic areas are suggested: medical references, EPR, staying connected, personal productivity, clinical research, and issues/concerns. For implications, healthcare organizations should consider mobile technology as part of their information systems strategy. The feasibility of a portable EPR for palliative medicine should be explored, and an information-based approach can help advance palliative medicine research in Canada.     

Triage rapid initial assessment by doctor (TRIAD) improves waiting time and processing time of the emergency department

Aim

To evaluate the effect of triage rapid initial assessment by doctor (TRIAD) on waiting time and processing time of an emergency department (ED) without extra staff.

Method

A senior emergency doctor was put into triage instead of a consultation cubicle for seven shifts of 9 hours each. All the patients were assessed and necessary interventions started at the time of triage. Waiting time and processing time of various categories of patients were compared with a control group that was sampled during the week before the trial period.

Results

In total, there were 1310 cases in the trial period and 1355 controls. Over a quarter (27%) of the patients received triage doctor interventions. The average waiting time was reduced by 38% and the average processing time by 23%. Patients without triage intervention also had a 24% shorter waiting time because of overall improvement in efficiency. Trauma patients and patients needing radiography particularly benefited from the new system. The waiting time and processing time of category 4 and 5 patients improved significantly as a result of more efficient processing of more urgent cases.

Conclusion

The waiting time and processing time of the ED were greatly reduced by TRIAD without extra manpower.     

Serum nitric oxide metabolites and disease activity in patients with systemic sclerosis

There is no surrogate marker in serum for defining disease activity in scleroderma (SSc). Nitric oxide (NO), which regulates vasodilation and possesses pro-inflammatory actions, has been implicated in the pathogenesis of SSc. We compared serum NO _x (total nitrate and nitrite) level in SSc patients to healthy controls and evaluated its correlation with detailed symptomatology and scoring systems for various organ involvement. Symptoms and physical findings that suggested disease activity in regard to various organs were documented. Lung function test, high-resolution computed tomographic (HRCT) scan of thorax and echocardiography were performed. Serum NO _x was measured by chemiluminescence. Serum NO _x levels in SSc (n = 43) were significantly higher (72.4 ± 47.8 μM) than age- and sex-matched controls (n = 41; 37.1 ± 13.5 μM; p < 0.001). Serum NO _x were not found to be associated with lung fibrosis defined by lung function parameters or inflammation and fibrosis scores on HRCT. Twenty-two patients were found to have elevated serum NO _x level defined as mean ± 2 SD of normal controls. Logistic regression analysis revealed that age (OR 1.12, p = 0.02) and elevated pulmonary arterial pressure (PAP) (n = 9; OR 145.3, p = 0.01) were predictive factors for elevated serum NO _x . Prednisolone use was associated with lower serum NO _x level (OR 0.06, p = 0.04). Elevated PAP of increasing severity was found to be associated with higher level of serum NO _x (p = 0.004 by trend). Serum NO _x in SSc patients were elevated compared to healthy controls. Serum NO _x level was determined by multiple factors including age, prednisolone use, and elevated PAP.     

Variability of the prevalence of undiagnosed airflow obstruction in smokers using different diagnostic criteria

PURPOSES: To estimate the prevalence of undiagnosed airflow obstruction (AFO) in Hong Kong smokers with no previous diagnosis of respiratory disease, and to assess its variability when applying different prediction equations and diagnostic criteria. METHODS: A multicenter, population-based, cross-sectional prevalence study was performed in smokers aged 20 to 80 years. Three different criteria (fixed 70% [Global Initiative for Chronic Obstructive Lung Disease and British Thoracic Society], fixed 75%, and European Respiratory Society [ERS]) were applied to define a lower limit of normal (LLN) of the FEV(1)/FVC ratio to compare with the Hong Kong Chinese reference equation (criterion 1), which had used a distribution-free method to obtain the lower fifth percentile of FEV(1)/FVC ratio as the LLN. RESULTS: In 525 male patients, using criterion 1 (local internal prediction equation) and defining AFO as FEV(1)/FVC less than LLN, the overall prevalence of AFO was 13.7%: 8.3% in age > or = 20 to 40 years, 14.0% in age > or = 40 to 60 years, and 17.8% in age > or = 60 to 80 years. When the local internal prediction equation was used as the comparison reference, the fixed-ratio methods tended to miss AFO in younger age groups and overdiagnose AFO in old age, while the ERS criteria, which uses an almost lower fifth percentile-equivalent method, showed less of such a trend but still only showed moderate agreement with criterion 1. CONCLUSIONS: Undiagnosed AFO was prevalent in Hong Kong smokers. Estimated prevalence rates were highly affected by the criteria used to define AFO. The predicted lower fifth percentile values calculated from a local reference equation as the LLN of FEV(1)/FVC ratio should be used for the diagnosis of AFO.     

Perceptions Related to Bird-to-Human Avian Influenza,Influenza Vaccination,and Use of Face Mask

Background  H5N1 avian influenza may become pandemic in humans in the near future. According to the severe acute respiratory syndrome (SARS) experience, anticipation of the pandemic may have impact on behaviors related to influenza vaccination (IV) and relevant public health behaviors such as wearing a face mask when having influenza-like-illnesses (ILI), which would play an important role in the control of human avian influenza outbreaks. This paper investigated the prevalence and factors related to IV uptake and use of face mask in public venues when having ILI symptoms. Methods  An anonymous cross-sectional population-based random telephone survey of 302 Hong Kong Chinese adults aged 18–60, using a structured questionnaire, was conducted in November 2005. Results  In the last 3 months, 17.9% of the respondents received IV; 36.6% of those presenting ILI symptoms often used face mask in public venues. Anticipation of a bird-to-human H5N1 outbreak, perceptions that such an outbreak would be worse than SARS, that IV was efficacious in preventing bird-to-human avian influenza transmission were associated with the studied IV behavior (OR=2.64–3.97, p < 0.05). Exposure to live birds, perceived similar symptoms between influenza and bird-to-human H5N1 avian influenza, that bird-to-human avian influenza was more lethal than SARS were predictive use of face mask when having ILI symptoms (OR = 4.25–8.34, p < 0.05). Conclusion  The prevalence of IV and use of face mask in the study population may be increasing, which may be related to concerns of avian influenza. Perceptions related to human avian influenza were associated with IV and mask use behaviors. This can potentially be turned into opportunities of promoting desirable public health behaviors. The study was supported by the Li Ka Shing Institute of Health Science.