Reference values of diffusing capacity of non-smoking Chinese in Hong Kong

BACKGROUND AND OBJECTIVE: This study was conducted to define normal reference values and lower limits of normal (LLN) for single-breath carbon monoxide diffusing capacity (DLco) and DLco per unit of alveolar volume (Kco) for Chinese adults in Hong Kong. METHODS: Healthy non-smoking men and women aged 18-80 years were recruited by random digit dialing. DLco and Kco were measured according to American Thoracic Society standards. Reference equations were obtained by multiple linear regression; LLN were derived by distribution-free method for estimation of age-related centiles. RESULTS: Tests from 568 subjects (259 men, 309 women) were analysed. DLco declined with age in both genders, and increased with height and the interaction term of height and age in men and women, respectively. Considering Hb values did not improve the reference equations. Kco declined with age and increased with weight in both genders, while height and its interaction term with age were additional determinants in women. The reference DLco was lower than some Caucasian values, and was only explained partially by a smaller body size and alveolar volume in Chinese. The distribution-free method yielded better overall approximation to the fifth percentile compared with the traditional method of determining LLN. CONCLUSIONS: The equations for reference values and LLN of diffusing capacity derived in this study are of clinical relevance to Chinese subjects.     

Non-tuberculous mycobacterial infection in patients with systemic lupus erythematosus

OBJECTIVES: Patients with systemic lupus erythematosus (SLE) are susceptible to opportunistic infections. To examine the clinical manifestations of non-tuberculous mycobacterial (NTM) infections with those of Mycobacterium tuberculosis (MTB) infections in SLE patients. METHODS: Medical records of a cohort of 725 SLE patients were reviewed for previous NTM infections. Demographic characteristics, predisposing factors and clinical outcomes were compared with patients who had previous MTB infections (n = 39). RESULTS: Eleven (nine female and two male) cases were identified (prevalence 1.5%). The mean +/- S.D. age at the time of infection was 42.8 +/- 13.9 yrs, 9.3 +/- 5.8 yrs after the onset of SLE. The mean +/- S.D. time taken from onset of symptoms to the diagnosis of NTM infection was 5.7 +/- 7.2 months. Sites of involvement included skin and soft tissue (n = 8), chest (n = 2) and disseminated infection (n = 1). NTM infections were more likely to involve extrapulmonary sites (P = 0.006), presented in patients with longer lupus disease duration (P < 0.001), occurred in older patients (P < 0.001) and in those who had a higher cumulative dose of prednisolone (P = 0.01) than MTB infections. Using a stepwise logistic regression, disease duration was found to be the only independent predictive factor (P = 0.005) for NTM infections. Ten (25.6%) patients with MTB infections but none of the patients with NTM infections presented concomitantly at the onset of SLE (P = 0.09). There were no differences in the recurrence rate (P = 0.64) and frequency of disseminated infections (P = 0.40) between NTM and MTB infections. CONCLUSIONS: NTM infections tended to develop in SLE patients later in their disease course than MTB infections. A high index of suspicion is required for its diagnosis.     

p21 gene polymorphisms in systemic lupus erythematosus

OBJECTIVE: Cyclin-dependent kinase inhibitor 1A (p21) is a negative regulator in the cell cycle. Development of sex-linked lupus-like syndrome in p21-/- mice and reduced p21 gene expression in patients with systemic lupus erythematosus (SLE) compared with those in healthy controls suggested that p21 is a susceptibility gene of SLE. We investigated the same by a case-control association study. METHODS: Six single nucleotide polymorphisms, p21US G/A, p21DS C/A, p21-1022 G/A, p21C31 C/A, p21In2 G/C and p21UTR T/C, were genotyped in 516 SLE patients and 693 healthy controls. Association of genotypes and alleles with disease, disease phenotypes, haplotypes construction, linkage disequilibrium analysis and p21 mRNA expression were performed. RESULTS: We found a significant association of p21US A allele (OR = 0.23, 95% CI: 0.14-0.38, P < 0.001) and p21-1022 A allele (OR = 1.95, 95% CI: 1.37-2.78, P < 0.001) with SLE. We identified significant differences in the frequencies of haplotypes ht1-ACACCC, which contains p21US A allele, and ht2-GCACCC, which contains p21-1022 A allele, between SLE patients and controls (P < 0.0001). Besides, the p21US GA was associated with SLE patients suffering from arthritis (P = 0.003). We also observed differential p21 mRNA expressions among different genotypes of p21US and p21-1022 which were statistically significant. CONCLUSION: Our results suggested that the p21US A allele and p21-1022 A allele were both associated with the development of SLE, and the p21US A allele was associated with arthritis in SLE patients.     

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.     

Inhibitory effects of blueberry extract on the production of inflammatory mediators in lipopolysaccharide-activated BV2 microglia

Sustained microglial activation in the central nervous system (CNS) has been extensively investigated in age-related neurodegenerative diseases and has been postulated to lead to neuronal cell loss in these conditions. Recent studies have shown that antiinflammatory drugs may suppress microglial activation and thus protect against microglial overactivation and subsequent cell loss. Research also suggests that fruits such as berries may contain both antioxidant and antiinflammatory polyphenols that may be important in this regard. Our previous research showed that blueberry extract was effective in preventing oxidant-induced calcium response deficits in M1 (muscarinic receptor)-transfected COS-7 cells. Extrapolating from these findings, the current study investigated the effect of blueberry extract on preventing inflammation-induced activation of microglia. Results indicated that treatments with blueberry extract inhibited the production of the inflammatory mediator nitric oxide (NO) as well as the cytokines interleukin-1beta and tumor necrosis factor-alpha, in cell conditioned media from lipopolysaccharide (LPS)-activated BV2 microglia. Also, mRNA and protein levels of inducible nitric oxide synthase and cyclooxygenase-2 in LPS-activated BV2 cells were significantly reduced by treatments with blueberry extract. The results suggest that blueberry polyphenols attenuate inflammatory responses of brain microglia and could be potentially useful in modulation of inflammatory conditions in the CNS.