A randomized phase II trial of interferon-α2b versus 5-fluorouracil after trabeculectomy*

Purpose: The aim of the present study was to investigate the safety and potential efficacy of subconjunctival interferon-α2b (IFN-α), either alone or in combination with 5-fluorouracil (5-FU), in reducing the risk of failure of glaucoma surgery. Methods: A prospective, masked randomized phase II study was undertaken in which patients received three subconjunctival injections per week for 3–4 weeks postoperatively. Three treatments were compared: (i) IFN-α (1 × 10 ⁶ IU per dose); (ii) 5-FU (5 mg per dose); and (iii) alternating IFN-α and 5-FU (BOTH). The primary outcome measures were: (i) rate of successful control of intra-ocular pressure without further surgery; and (ii) the incidence of side effects. Results: Fifty-seven patients undergoing glaucoma surgery with an increased risk of failure were evaluated, including 23 patients (40%) undergoing trabeculectomy combined with extracapsular cataract extraction as well as other conventional high-risk groups. With 53 patients (93%) completing 2 years follow up, there was no significant difference in success rates among the three groups. Intra-ocular pressure was controlled without further surgery in 79% of patients (95% confidence interval (CI): 61, 97%) receiving IFN-α, in 89% of patients (76, 100%) receiving 5-FU and in 89% of patients (76, 100%) receiving BOTH. Side effects were similar among the three groups. Conclusions: These results are consistent with a beneficial effect of IFN-α2b given either alone or in combination with 5-FU after glaucoma filtering surgery. However, the lack of a clear and substantial benefit over conventional anti-fibrotic therapy does not support the further clinical evaluation of these treatments.     

Susceptibility to ankylosing spondylitis: no evidence for the involvement of transforming growth factor beta 1 (TGFB1) gene polymorphisms

BACKGROUND: Genetic factors are thought to be crucial in the pathogenesis of ankylosing spondylitis. Transforming growth factor beta 1 (TGF beta 1) is a multifunctional cytokine that plays a key role in inflammation. Two functional single nucleotide polymorphisms (SNPs) in the TGFB1 gene have been described: TGFB1 T869C and TGFB1 G915C. OBJECTIVE: To determine whether these SNPs contribute to ankylosing spondylitis susceptibility or its disease characteristics. METHODS: Genomic DNA was isolated from the peripheral blood of 134 patients with ankylosing spondylitis and 194 healthy blood donors. All subjects were unrelated and of white Dutch ethnicity. The diagnosis of ankylosing spondylitis was made according to the modified New York criteria. The TGFB1 T869C and TGFB1 G915C SNPs were genotyped by a polymerase chain reaction-single strand conformation polymorphism haplotyping method. RESULTS: No significant differences were found between patients and controls in genotype, allele, and haplotype frequencies or in the carrier rate of the rare alleles of the TGFB1 T869C and TGFB1 G915C SNPs. CONCLUSIONS: TGFB1 T869C and TGFB1 G915C SNPs are not major factors in the susceptibility to ankylosing spondylitis or its disease characteristics.     

Double blind, randomised, placebo controlled study of leflunomide in the treatment of active ankylosing spondylitis

OBJECTIVE: To assess the efficacy and safety of leflunomide in active ankylosing spondylitis (AS) compared with placebo in a 24 week pilot study. METHODS: In a single centre randomised, double blind, placebo controlled study, 45 patients with active AS were randomised to either leflunomide 20 mg daily (n=30) or placebo (n=15). Active disease was defined as a score of >or=4 on the Bath ankylosing spondylitis disease activity index (0-10), and pain of >or=4 on a visual analogue scale (0-10). The primary efficacy variable at week 24 was the 20% response rate, as recommended by the Assessments in Ankylosing Spondylitis (ASAS) working group. Secondary outcome variables included general wellbeing, metrology index, swollen joint count, erythrocyte sedimentation rate, and C reactive protein. RESULTS: In all, 13 women and 32 men were studied. Demographic and disease indices were comparable between the two treatment groups at baseline. The rate of ASAS 20% responders was not significantly different: 27% in the leflunomide treated patients and 20% in the placebo group (95% confidence interval, -32% to 19%). No significant differences were found between the treatment groups in mean changes of the secondary outcome variables. Eleven patients were withdrawn prematurely from the study because of adverse events (7), lack of efficacy (3), and non-compliance (1). Most frequently adverse events were gastrointestinal side effects and skin disorders. CONCLUSIONS: In this placebo controlled study, leflunomide treatment did not result in a significant improvement of the ASAS 20% response in active ankylosing spondylitis. No unexpected or severe adverse events occurred.     

散发性大肠癌肿瘤相关基因位点杂合性丢失分析

目的　分析大肠癌组织中抑癌基因及肿瘤相关基因位点的变化与预后的关系。方法　７９例大肠癌组织经组织微解剖分离癌组织和正常组织,分别进行１１ 个染色体上１４ 个位点的杂合性丢失（ｌｏｓｓｏｆｈｅｔｅｒｏｚｙｇｏｓｉｔｙ,ＬＯＨ）分析。结果　肿瘤组织中ＬＯＨ呈现一复杂的征象,５ｑ１２ 及ＲＢ基因位点的ＬＯＨ 与较好的预后有关。结论　不同的抑癌基因及肿瘤相关基因与大肠癌发生有关。５ｑ１２ 位点的ＬＯＨ 与较好预后相关的意义有待今后进一步研究。     

Magnetic resonance colonography with automated carbon dioxide insufflation: Diagnostic accuracy and distension

Objectives

To evaluate the diagnostic performance of MR colonography using automated carbon dioxide (CO₂) insufflation for colonic distension, with colonoscopy serving as the reference standard.

Methods

Ninety-eight symptomatic patients underwent MR colonography with faecal tagging and automated CO₂ insufflation. Three readers (one expert (reader 1), and two less experienced (readers 2 and 3)) evaluated the images for the presence of colorectal lesions. Bowel distension was evaluated on a 4-point scale. Results were verified with colonoscopy and histopathological analysis.

Results

Per-patient sensitivity for lesions ≥10 mm was 91.7% (11 of 12) (reader 1), 75.0% (9 of 12) (reader 2), and 75% (9 of 12) (reader 3). Specificity was 96.5% (82 of 85) (reader 1), 97.7% (83 of 85) (reader 2), 95.3% (81 of 85) (reader 3). Per-patient sensitivity for lesions ≥6 mm was 85.7% (18 of 21) (reader 1), 57.1% (12 of 21) (reader 2), and 57.1% (12 of 21) (reader 3). Specificity was 86.8% (66 of 76), 98.7% (75 of 76), 90.8% (69 of 76), respectively. Per-patient sensitivity for advanced neoplasia of ≥10 mm and ≥6 mm was 88.9% (8 of 9) for all readers. Specificity for ≥10 mm and ≥6 mm was 98.9% (87 of 88) (reader 1), 97.7% (86 of 88) (reader 2), 96.6% (85 of 88) (reader 3). 94.4% of the colon segments were adequate to optimal distended with dual positioning.

Conclusion

MR colonography can accurately detect lesions ≥10 mm, and advanced neoplasia ≥6 mm. Sufficient distension was achieved using automated CO₂ insufflation for colonic distension in MR colonography.     

Prevalence of Chlamydia trachomatis in urine of male patients with ankylosing spondylitis is not increased

OBJECTIVE: To compare the prevalence of Chlamydia trachomatis infections in ankylosing spondylitis (AS) patients with controls, using DNA amplification assays in urine specimens. METHODS: The prevalence of C trachomatis infections was assessed in 32 male AS patients and 120 age and sex matched controls. Urine specimens were tested by ligase chain reaction and polymerase chain reaction. In addition, blood samples of AS patients were tested on serum antibodies to C trachomatis (IgA and IgG) by a specific peptide based solid phase enzyme immunoassay. A questionnaire was used to assess the differences in sexual behaviour and ethnic origin between the two groups. AS patients were also asked about disease characteristics. RESULTS: No significant differences were found between cases and controls in the prevalence of C trachomatis infections. No associations were found between C trachomatis antibodies and disease characteristics, except for acute anterior uveitis (AAU). Four of eight (50%) AS men positive for IgG had a history of AAU in comparison with three of 24 (12.5%) IgG negative men (OR = 7.0; 95% confidence intervals: 1.1, 44.1). CONCLUSION: The prevalence of Chlamydia trachomatis infections, as detected by commercially available DNA amplification assays in urine specimens, in AS patients is not higher compared with male controls of the same age. However, there seems to be an association between specific antibodies to C trachomatis and AAU.