HLA-DRB1 Genes and Susceptibility to Rheumatoid Arthritis in Three Ethnic Groups from Malaysia

Worldwide population studies have generally agreed that rheumatoid arthritis (RA) is associated with a group of HLA-DRB1 alleles which share a common amino acid sequence at residues 70-74. This represents the first study to investigate the association of HLA-DRB1 genes with susceptibility to RA amongst Malay, Chinese and Indian ethnic groups in Malaysia. One hundred and thirty three RA patients and one hundred and sixty seven healthy controls were recruited. The HLA-DRB1 alleles were studied using the Phototyping method. The subtypes of HLA-DR4 were detected by "high resolution" PCR-SSP DRB1*04 typing techniques. The prevalence of HLA-DRB1*0405 was significantly higher in Malay patients with RA than in healthy controls (28.9 vs. 8.3%, p =0.0016, OR=4.48, 95% CI=1.26-16.69 ). Similarly, DRB1*0405 was more common in Chinese RA patients than in controls (30.0 vs. 6.7%, p =0.0029, OR=6.00, 95% CI=1.67-23.48 ). In addition, DRB1*0901 was a predisposing factor (32.0 vs. 6.7%, p =0.0015, OR=6.59, 95% CI=1.85-25.64 ) and *0301/04 had a protective role (4.0 vs. 25.0%, p =0.00562, OR=0.13, 95% CI=0.02-0.62 ) in Malaysian Chinese RA. RA in Indians was associated with DRB1*1001 (51.1 vs. 8.5%, p =0.00002, OR=11.24, 95% CI=3.13-44.18 ). DRB1*0701 (13.3 vs. 42.6%, p =0.0022, OR=2.73, 95% CI=1.40-5.37 ) may have a protective effect. Therefore, in the Malaysian population, RA is primarily associated with the QRRAA motif, and we suggest that genetic factors play a crucial role in the pathogenesis of RA, compared to environmental factors.     

Higher free thyroxine levels are associated with frailty in older men: the Health In Men Study

Objective Frailty is common in the elderly and predisposes to ill‐health. Some symptoms of frailty overlap those of thyroid dysfunction, but it is unclear whether differences in thyroid status influence risk of frailty. We evaluated associations between thyroid status and frailty in older men. Design Cross‐sectional epidemiological study. Participants Community‐dwelling men aged 70–89 years. Measurements Circulating thyrotropin (TSH) and free thyroxine (FT₄) were assayed. Frailty was assessed as ≥3 of the Fatigue, Resistance, Ambulation, Illnesses and Loss (FRAIL) scale’s 5 domains: fatigue; resistance (difficulty climbing flight of stairs); ambulation (difficulty walking 100 m); illness (>5); or weight loss (>5%), blinded to hormone results. Results Of 3943 men, 27 had subclinical hyperthyroidism, 431 subclinical hypothyroidism and 608 were classified as being frail (15·4%). There was an inverse log‐linear association of TSH with FT₄. There was no association between TSH and frailty. After adjusting for covariates, men with FT₄ in the highest two quartiles had increased odds of being frail (Q3:Q1, odds ratio [OR] = 1·32, 95% confidence interval [CI] = 1·01–1·73 and Q4:Q1, OR = 1·36, 95% CI = 1·04–1·79, P = 0·010 for trend). Higher FT₄ was associated with fatigue (P = 0·038) and weight loss (P < 0·001). The association between FT₄ and frailty remained significant when the analysis was restricted to euthyroid men. Conclusions High‐normal FT₄ level is an independent predictor of frailty among ageing men. This suggests that even within the euthyroid range, circulating thyroxine may contribute to reduced physical capability. Further studies are needed to clarify the utility of thyroid function testing and the feasibility of preventing or reversing frailty in older men.     

Vitamin D levels: its relationship to bone mineral density response and disease activity in premenopausal Malaysian systemic lupus erythematosus patients on corticosteroids

Aim: To determine if baseline vitamin D levels would influence the gain in bone mineral density (BMD) in female systemic lupus erythematosus (SLE) patients on corticosteroids (CS) taking bone‐active medication. Method: Premenopausal SLE patients participating in a trial assessing the efficacy of calcium alone, calcitriol and calcium, and alendronate and calcium, on BMD in patients on CS, were studied. Patients were randomly allocated to the treatment groups at the start of the study and followed up for 2 years. Serum 25‐hydroxy vitamin D [25(OH)D] was measured at baseline. Results: Thirty‐eight patients were studied. One (2%) patient had osteoporosis, nine (24%) had osteopenia and all others had normal BMD. The mean baseline 25(OH)D levels were 21.6 ± 4.6 ng/mL (± 1 SD). Twelve (32%) patients had vitamin D deficiency [25(OH)D < 20 ng/mL]. There was a significant negative correlation between SLEDAI scores and 25(OH)D levels, that is, patients with high SLEDAI scores had significantly lower 25(OH)D levels (P = 0.033). Left femoral neck BMD was significantly lower in the deficient compared to insufficient group (P = 0.042). There was a trend toward better BMD gain at 2 years in the vitamin D insufficient compared to the deficient group, which did not reach statistical significance. Conclusion: This study showed that in female SLE patients, low vitamin D levels are associated with higher disease activity and suggests that patients who have higher vitamin D levels have a better BMD response during treatment with bone‐active agents.     

Chemotherapy in advanced ovarian cancer: four systematic meta-analyses of individual patient data from 37 randomized trials. Advanced Ovarian Cancer Trialists' Group.

The purpose of this systematic study was to provide an up to date and reliable quantitative summary of the relative benefits of various types of chemotherapy (non-platinum vs platinum, single-agent vs combination and carboplatin vs cisplatin) in the treatment of advanced ovarian cancer. Also, to investigate whether well-defined patient subgroups benefit more or less from cisplatin- or carboplatin-based therapy. Meta-analyses were based on updated individual patient data from all available randomized controlled trials (published and unpublished), including 37 trials, 5667 patients and 4664 deaths. The results suggest that platinum-based chemotherapy is better than non-platinum therapy, show a trend in favour of platinum combinations over single-agent platinum, and suggest that cisplatin and carboplatin are equally effective. There is no good evidence that cisplatin is more or less effective than carboplatin in any particular subgroup of patients.     

Kappa-晒化卡拉胶对实验动物的抗心律失常作用

Kappa-硒化卡拉胶是一含硒有机化合物。ip 9 mg·kg~(-1)·d~(-1)×5d或单次ig 35,70,140mg·kg~(-1)能显著提高乌头碱致大鼠HA的阈剂量,此作用可与Na_2SeO_3 1 mg·kg~(-1)·d~(-1)×5d ip比拟.随着Kappa-硒化卡拉胶ig剂量增加,尚可提高乌头碱所致VE,VT和VF的阈剂量。ip 9mg·kg~(-1)·d~(-1)×5 d或ig 70mg·kg~(-1)能提高BaCl_2致大鼠或哇巴因致豚鼠HA的阈剂量。对BaCl_2致大鼠VF或哇巴因致豚鼠VE的阈剂量,分别在ig70mg·kg~(-1)与140mg·kg~(-1)时有提高,而ipNa_2SeO_3 1 mg·kg~(-1)·d~(-1)×5d无此明显影响。