益气活血中药肾区离子导入治疗难治慢性肾功能衰竭的临床研究

目的:探讨益气活血中药肾区离子导入治疗难治慢性肾功能衰竭的临床疗效。方法:将62例难治慢性肾功能衰竭患者随机分为治疗组和对照组,对照组予以常规治疗,治疗组在此基础上应用益气活血中药肾区离子导入治疗,比较分析两组的临床疗效。结果:治疗组总有效率为90.3%,对照组总有效率为77.4%,治疗组优于对照组(P0.05);治疗组中医症状积分、Hb、24h upq及ALB以及肾功能指标改善情况均优于对照组(P0.05)。结论:肾区离子导入益气活血中药治疗难治慢性肾功能衰竭疗效显著,不良反应较少。     

人工种植红景天不同药用部位中红景天苷的含量测定

目的：测定人工种植红景天不同药用部位花瓣、茎、根的含量。方法：取各1 g样品经过60%的乙醇溶解,超声波清洗器清洗50 min,过滤,旋蒸,加2 mL的甲醇,用微孔滤膜（0.45 μm）过滤,采用CAPCELL PAK C₁₈柱（2.0 mm× 150 mm,i.d.,3 μm）,柱温 30 ℃,波长278 nm;样品温度10 ℃,进样体积10 μL。流动相为甲醇-1%乙酸溶液 45：55,流速为1 mL·min^-1进行定量分析。结果：有效部位中的红景天苷含量从高到低依次为花瓣（35.00mg）、根（18.89mg）、茎（1.59 mg）。结论：建立了红景天中红景天苷含量的高效液相色谱方法,可适用于不同药材中红景天苷含量的测定。     

Mutation detection rate and spectrum in familial hypercholesterolaemia patients in the UK pilot cascade project

Taylor A, Wang D, Patel K, Whittall R, Wood G, Farrer M, Neely RDG, Fairgrieve S, Nair D, Barbir M, Jones JL, Egan S, Everdale R, Lolin Y, Hughes E, Cooper JA, Hadfield SG, Norbury G, Humphries SE. Mutation detection rate and spectrum in familial hypercholesterolaemia patients in the UK pilot cascade project. Cascade testing using DNA‐mutation information is now recommended in the UK for patients with familial hypercholesterolaemia (FH). We compared the detection rate and mutation spectrum in FH patients with a clinical diagnosis of definite (DFH) and possible (PFH) FH. Six hundred and thirty‐five probands from six UK centres were tested for 18 low‐density lipoprotein receptor gene (LDLR) mutations, APOB p.Arg3527Gln and PCSK9 p.Asp374Tyr using a commercial amplification refractory mutation system (ARMS) kit. Samples with no mutation detected were screened in all exons by single strand conformation polymorphism analysis (SSCP)/denaturing high performance liquid chromatography electrophoresis (dHPLC)/direct‐sequencing, followed by multiplex ligation‐dependent probe amplification (MLPA) to detect deletions and duplications in LDLR.The detection rate was significantly higher in the 190 DFH patients compared to the 394 PFH patients (56.3% and 28.4%, p > 0.00001). Fifty‐one patients had inadequate information to determine PFH/DFH status, and in this group the detection rate was similar to the PFH group (25.5%, p = 0.63 vs PFH). Overall, 232 patients had detected mutations (107 different; 6.9% not previously reported). The ARMS kit detected 100 (44%) and the MLPA kit 11 (4.7%). Twenty‐eight (12%) of the patients had the APOB p.Arg3527Gln and four (1.7%) had the PCSK9 p.Asp374Tyr mutation. Of the 296 relatives tested from 100 families, a mutation was identified in 56.1%. In 31 patients of Indian/Asian origin 10 mutations (two previously unreported) were identified. The utility of the ARMS kit was confirmed, but sequencing is still required in a comprehensive diagnostic service for FH. Even in subjects with a low clinical suspicion of FH, and in those of Indian origin, mutation testing has an acceptable detection rate.     

Group treatments for sensitive health care problems: a randomised controlled trial of group versus individual physiotherapy sessions for female urinary incontinence

Background  

The aim was to compare effectiveness of group versus individual sessions of physiotherapy in terms of symptoms, quality of life, and costs, and to investigate the effect of patient preference on uptake and outcome of treatment.     

A comparison of quality of life, disease impact and risk perception in women with invasive breast cancer and ductal carcinoma in situ

We compared the health-related quality of life, impact of the disease, risk perception of recurrence and dying of breast cancer, and understanding of diagnosis of patients with ductal carcinoma in situ (DCIS) and invasive breast cancer 2-3 years after treatment. We included all women (N=211) diagnosed with DCIS or invasive breast cancer TNM stage I (T1, N0, and M0) in three community hospitals in the southern part of The Netherlands in the period 2002-2003. After verifying the medical files, 180 disease free patients proved eligible for study entry, 47 of whom had DCIS and 133 stage I invasive breast cancer. One-hundred and thirty-five patients returned a completed questionnaire (75% response). No significant differences were found between women with DCIS and invasive breast cancer on the physical and mental component scale of the RAND SF-36, nor on the WHO-5, which assesses well-being. In contrast, women with DCIS reportedly had a better physical health, better sex life and better relationships with friends/acquaintances than women with invasive breast cancer. Despite their better prognosis, the DCIS-group had comparable perceptions of the risk of recurrence and dying of breast cancer as women with invasive breast cancer. However, this did not appear to affect their well-being significantly.     

Induction of arthritis in SCID mice by T cells specific for the “shared epitope” sequence in the G3 domain of human cartilage proteoglycan

Objective

To study the immunologic function and determine the fine epitope structure of a synthetic peptide p135H (²³⁷³TTYKRRLQKRSSRHP) of the G3 domain of human cartilage proteoglycan (aggrecan), which contains a highly homologous sequence motif of the shared epitope (QKRAA), the most common sequence motif in HLA–DR4 alleles, which predispose humans to the development of rheumatoid arthritis (RA).

Methods

Synthetic p135 peptides with altered sequences were used for (hyper)immunization of arthritis‐susceptible BALB/c mice and then challenged with a single dose of cartilage proteoglycan. Human p135 (p135H) and mouse p135 (p135M) synthetic peptides of the G3 domain of aggrecan were used to prime lymphocytes, which were then used for adoptive transfer of arthritis into “presensitized” SCID mice, determining cross‐reactivity among p135 peptides and their analogous sequences, and generating T cell hybridomas. T cell hybridomas were also used for arthritis transfer into SCID mice and for characterizing the fine epitope structure of T cell receptor (TCR) and major histo‐compatibility complex (MHC) binding sites of the immunogenic/arthritogenic p135H sequence.

Results

While p135H peptide‐(hyper)immunized mice became sensitized, they developed arthritis only after injection of a single dose of cartilage proteoglycan aggrecan. An altered peptide sequence (p135H‐AA) carrying the shared epitope motif (QKRAA) was as effective as the natural peptide p135H sequence for inducing arthritis. Mouse p135M‐specific lymphocytes induced arthritis with a lower incidence, but synthetic peptides to Escherichia coli heat‐shock protein (DnaJ) or HLA–DR4 allele (both having the shared epitope sequence with different flanking regions) were also positive. Fine epitope sequence recognition of an arthritogenic T cell hybridoma derived from p135H‐primed lymphocyte population was determined. Interestingly, in the most central position, a basic amino acid triplet of p135H peptide was found to be the MHC‐binding motif, whereas the flanking amino acids bound to the TCR.

Conclusion

Peptide p135H, corresponding to the peptide sequence in the G3 domain of human cartilage proteoglycan aggrecan, is immunogenic/arthritogenic in BALB/c mice. Peptide p135H includes a highly homologous motif of the shared epitope, a sequence that is overrepresented in bacterial heat‐shock proteins, envelope protein of human JC polyomavirus, and numerous HLA–DR4 alleles. Since the G3 domain of cartilage proteoglycan aggrecan with the p135 sequence is “lost” during the normal metabolic turnover of cartilage proteoglycan or in pathologic conditions, an antigenoriented T cell migration into joints of presensitized (susceptible) individuals may contribute to the organ‐specificity of RA.