类风湿关节炎肾损害患者血管功能的多因素分析

目的 探讨类风湿关节炎肾损害患者血管功能的影响因素。方法 将296例类风湿关节炎患者分为肾损害组与无肾损害组。对两组临床资料进行t检验、χ2检验、Pearson相关性分析及多因素回归分析。结果 与无肾损害组相比,类风湿关节炎肾损害组脉搏波速度、颈动脉内-中膜厚度显著增加（P〈0.01）,血流介导的扩张反应显著降低（P〈0.01）。类风湿关节炎肾损害组年龄、尿酸和收缩压是脉搏波速度的独立影响因素（P〈0.05或P〈0.01）;尿酸、收缩压和肾小球滤过率是血流介导的扩张反应的独立影响因素（P〈0.05或P〈0.01）;尿酸、年龄、胆固醇和收缩压是颈动脉内-中膜厚度的独立影响因素（P〈0.05或P〈0.01）。结论 类风湿关节炎肾损害组血管功能损害较无肾损害组加重。类风湿关节炎累及肾脏后,年龄、高血压、高脂血症、尿酸升高、肾小球滤过率下降等这些因素可进一步加重血管功能损害。     

Effects of long-term aurothiomalate and D-penicillamine treatments on renal function and urinary excretion of prostanoids in patients with rheumatoid arthritis

The effects of long-term aurothiomalate and D-penicillamine treatments on renal function and the urinary excretion of prostanoids were studied in 20 patients with classic or definite rheumatoid arthritis. Twelve-hour urine was collected overnight, on the following day blood samples were taken in the morning and 12-hour urine was collected during the following day. Albumin excretion into the urine was determined by a sensitive quantitative method. Beta-2-microglobulin (B2MIGLO) and N-acetyl-beta-glucosaminidase (NAG) serum concentrations and excretions into the urine were measured to detect possible tubular or glomerular damage, respectively. The excretions of prostaglandin E2 (PGE2), thromboxane B2 and 6-keto-PGF1 alpha into urine were determined. In the aurothiomalate group, albumin excretion ranged 1-16 mg/12 h, and in the penicillamine group 0.8-31 mg/12 h. In the penicillamine group, but not in the aurothiomalate group, total protein, B2MIGLO and PGE2 excretions were higher (p less than 0.05) during the daytime than during the night. The daytime excretion of PGE2 was higher (p less than 0.01) in the penicillamine than in the aurothiomalate group. In the penicillamine group B2MIGLO excretion into urine correlated (p less than 0.01) with PGE2 excretion in the daytime. According to the results, not even long-term aurothiomalate treatment affects renal prostanoid excretion, while penicillamine increases urinary PGE2 excretion. This could be related either to the cofactor-like activity of penicillamine in the prostanoid synthesis or to damage in tubular cells. The role of prostanoids in maintaining blood flow and filtration may be more important in patients with renal damage than in normal conditions.     

Salicylates and renal function in rheumatoid arthritis.

The effect of salicylate treatment on the kidney, particularly medullary function, was investigated. In a retrospective analysis patients with rheumatoid arthritis (RA) treated with high doses of salicylates were shown to have inferior urinary concentrating power and increased excretion of N-acetyl-beta-D-glucosaminidase (NAG) when compared with patients who had not received salicylate treatment. A prospective study of renal funcition in healthy people and patients with RA starting salicylate in therapeutic doses showed that while epithelial cell excretion was only transiently raised in both groups the excretion of NAG was increased in all cases at three days and this increase was sustained at 10 days, all values being much higher in the patients than in the healthy subjects. Thus salicylate treatment does cause renal tubular damage but this damage results in only minimal impairment of function and does not constitute a reason for withholding salicylate treatment.     

Effects of clarithromycin in patients with active rheumatoid arthritis

ABSTRACT

Objective: To evaluate the clinical efficacy, safety, and tolerability of clarithromycin in patients with rheumatoid arthritis.

Research design and methods: This was a 6-month, monocenter, randomized, double-blind, placebo-controlled study. A total of 81 patients with early rheumatoid arthritis were treated with either once-daily oral clarithromycin (500?mg) or daily oral placebo for 6 months.

Main outcome measures: The primary efficacy variable was the percentage of patients who had a 20% improve­ment according to American College of Rheumatology (ACR) criteria (an ACR 20 response) at 6 months. Secondary outcome measures were 50% improvement and 70% improvement according to ACR criteria (an ACR 50 response and an ACR 70 response, respectively).

Results: A significantly greater percentage of patients treated with 500?mg clarithromycin met the ACR 20 response at 6 months compared with patients who received placebo (59 vs. 33%; p < 0.001). Greater percentages of patients treated with 500?mg clarithromycin also achieved ACR 50 responses (34 vs. 10%; p < 0.001) and ACR 70 responses (20 vs. 3%; p = 0.003) compared with patients who received placebo, respectively. Clarithromycin was well tolerated. There were no dose-limiting toxic effects.

Conclusions: In patients with early active rheumatoid arthritis, treatment with clarithromycin significantly improved the signs and symptoms of rheumatoid arthritis. Clarithromycin has been shown to be effective against rheumatoid arthritis.     

The influence of renal function on the enantioselective pharmacokinetics and pharmacodynamics of ketoprofen in patients with rheumatoid arthritis.

1. Single oral doses of 100 mg racemic ketoprofen were given to 15 patients (age range: 51-79 years) with rheumatoid arthritis and a range of creatinine clearances (CLCR) from 26 to 159 ml min-1. 2. The fractions unbound of (R)- and (S)-ketoprofen in plasma were determined for each subject after in vitro addition of rac-ketoprofen (enantiomer range: 1.00-6.00 micrograms ml-1) to pre-dose plasma. 3. An index of the antiplatelet effect of ketoprofen in vitro was measured as inhibition of platelet thromboxane B2 (TXB2) generation during the controlled clotting of whole blood (pre-dose) spiked with rac-ketoprofen. 4. In vivo studies revealed significant associations (P < 0.05) between the reciprocal of AUC for both unbound and total (bound plus unbound) (S)-ketoprofen and CLCR. Corresponding relationships were also observed for the (R)-enantiomer of ketoprofen. In addition, the half-life of each enantiomer was negatively correlated with CLCR. There was a positive relationship between the 24 h urinary recovery of combined non-conjugated and conjugated (R)-ketoprofen and CLCR while that for the (S)-stereoisomer failed to reach statistical significance (P > 0.05). 5. There was no difference between AUC for (R)- and (S)-ketoprofen for either unbound or total drug. 6. The mean +/- s.d. percentage unbound of (S)-ketoprofen in plasma (0.801 +/- 0.194%) exceeded (P < 0.05) the corresponding value for its optical antipode (0.724 +/- 0.149%). The percentage unbound of the (S)-enantiomer was higher at 6.00 micrograms ml-1 than that at enantiomer concentrations of 3.50 micrograms ml-1 and below, where it was invariant. The percentage unbound of (R)-ketoprofen was independent of plasma concentration up to 6.00 micrograms ml-1. There were no correlations between the percentage unbound of each enantiomer and either serum albumin concentration or CLCR. 7. The relationship between the serum concentration of unbound (S)-ketoprofen and the percentage inhibition of platelet TXB2 generation was described by a sigmoidal Emax equation for each patient. There was no correlation between the unbound concentration of (S)-ketoprofen in serum required to inhibit platelet TXB2 generation by 50% (EC50) and CLCR. The mean +/- s.d. EC50 was 0.216 +/- 0.143 ng ml-1. 8. These data indicate that diminished renal function is associated with an increased exposure to unbound (S)-ketoprofen, presumably due to regeneration of parent aglycone arising from the hydrolysis of accumulated acyl-glucuronide conjugates. The apparent sensitivity of platelet cyclo-oxygenase to the inhibitory effect of (S)-ketoprofen was not influenced by renal function.     

The effect of etodolac administration on renal function in patients with arthritis

The effect of etodolac 50-600 mg/d on renal function was assessed in four- to 52-week trials in 1,382 patients with arthritides. No patient was withdrawn from treatment due to an abnormal renal function test related to etodolac administration. There were no significant differences in the incidence of definite renal function abnormalities between patients receiving etodolac and those receiving placebo. Both etodolac and placebo groups had a significantly lower incidence of deviant BUN results than either aspirin- or sulindac-treated patients. Fewer than 2% of patients receiving etodolac showed either a persistent or variably persistent pattern of deviant renal function tests. The results in these studies indicate that chronic etodolac therapy did not adversely affect renal function in patients with arthritis.     

Effects of flurbiprofen on renal function in patients with moderate renal insufficiency.

1. Renal function was assessed in eight patients with chronic renal insufficiency following the administration of flurbiprofen 50 mg as a single dose and after chronic administration of 50 mg four times daily for 8 and 27 days. Diet and fluid intake were controlled. 2. Inulin and creatinine clearances and urinary excretion of sodium were measured at baseline and every 20 min for at least 3 h after dosing. The time of the mean peak concentration of (S)-flurbiprofen was used to guide the analysis of the clearances. Creatinine clearance, urinary excretion of sodium, and serum sodium and potassium were also assessed for 24 h after the dose and on a daily basis. Body weight and blood pressure were measured on a daily basis. 3. Decrements in inulin and creatinine clearances were small and reversible within 3 h of an oral dose of flurbiprofen. Comparison of baseline clearances for the three study periods (first dose and at 8 and 27 days of chronic dosing) revealed a lack of chronic effect on glomerular filtration rate. 4. In contrast, flurbiprofen caused a substantial (73 to 86%) and progressive decrease in the urinary excretion of sodium that reached a nadir within 4-5 h after drug administration. However, comparison of baseline values did not differ, indicating that balance conditions had been re-established. 5. Results of 24 h assessments were in agreement with the clearance study results. Reduced urinary excretion of sodium appeared to be limited to the first few days of flurbiprofen administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

功能MRI在评估女性类风湿关节炎患者认知功能的应用

目的 探讨功能MRI(fMRI)在评估女性类风湿关节炎(RA)患者认知功能中的应用价值。方法 采用生活质量评价量表(SF-36)及医院焦虑和抑郁量表评估30例女性RA患者(RA组)的健康状况及焦虑、抑郁情况,采用认知障碍简明评价量表评估认知功能,用3.0 T MR扫描仪行3D动脉自旋标记成像检查评估RA组脑血流量(CBF)灌注情况。以15例女性健康志愿者作为对照组。结果 RA组认知功能障碍发生率为53.3%,认知功能障碍与焦虑、抑郁、VAS疼痛评分、躯体疼痛评分、情感职能评分、SF-36评分、28个关节疾病活动度评分(DAS28评分)和ESR相关(P<0.05)。与对照组比较,RA组额叶、颞叶和顶叶两侧的CBF分布不对称(P<0.01)。RA组认知功能障碍患者CBF减低比例高于认知功能正常患者(P<0.05)。结论 女性RA患者认知功能障碍与焦虑、抑郁、VAS疼痛评分、SF-36评分、DAS28评分和ESR相关。fMRI对于早发现RA患者认知功能障碍有一定的帮助。     

Tacrolimus: in patients with rheumatoid arthritis

Tacrolimus, a hydrophobic macrolide with immunosuppressant properties, has recently been evaluated as a new treatment for adults with active rheumatoid arthritis. Oral tacrolimus 3mg once daily was significantly more effective than placebo in patients with rheumatoid arthritis (RA) who were refractory or intolerant to disease-modifying antirheumatic drugs (DMARDs), according to results from a 6-month, phase III trial; American College of Rheumatology 20 (ACR20) response rates were 27% and 10%. Tacrolimus 3mg once daily was effective in the same patient group in a 12-month, open-label trial; the ACR20 response rate was 38%. Oral tacrolimus 3 mg once daily was effective in combination with established methotrexate therapy in patients with RA in a 6-month, open-label trial. The ACR20 response rate was 53%. Oral tacrolimus 3 mg once daily was generally well tolerated by patients with active RA refractory or intolerant to previous DMARD treatment or when administered as combination therapy in patients with RA on established methotrexate therapy.     

Pain-mood relationships in patients with rheumatoid arthritis

Pain-mood relationships were investigated in 23 patients with long-standing rheumatoid arthritis over a two-week period. Patients completed form B of the Eysenck personality inventory on entry to the study and visual analogue scales for pain, anxiety and sadness daily throughout the study period. Two pain-mood relationships were identified: a synchronous relationship in which pain and mood scores were positively correlated and an asynchronous relationship in which pain and mood scores were uncorrelated. Furthermore, in all patients reporting high pain and showing synchronous relationships, the pain and mood scores were similar in magnitude, while in all patients reporting high pain and showing asynchronous relationships, the pain and mood scores were dissimilar in magnitude. The latter patients remained calm and happy despite severe pain. All patients reporting low pain showed synchronous and close relationships between pain and mood. Extraversion, neuroticism, age, duration and severity of disease were unrelated to pain severity and the pain-mood relationships recorded. The asynchronous pain-mood relationship was attributed to a coping response to severe pain. Patient education combined with physical, psychological and pharmacological treatments might induce such a response in patients unable to cope with chronic pain.     

贝那普利对原发性高血压病人肾功能的影响

目的 :研究贝那普利对高血压病人尿微量清蛋白及肾功能的作用。方法 :42例高血压病人 [男性 2 9例 ,女性 13例 ;年龄 ( 49±s 4)a ;病程 ( 3.8±0 .7)a]应用贝那普利 10mg ,po ,qd× 6wk ;治疗前后检测比较病人的血压、尿微量清蛋白、肾功能等各项指标。结果 :贝那普利治疗 6wk后 ,病人血压及尿微量清蛋白降低有非常显著意义 (P <0 .0 1) ;血浆肾素活性增加有非常显著意义 (P <0 .0 1) ;其他肾功能指标无明显影响。结论 :贝那普利可在有效降低血压的同时 ,对尿微量清蛋白有减低作用 ,并提示对肾有保护作用     

艾拉莫德联合功能锻炼治疗类风湿关节炎的临床观察

目的探讨艾拉莫德联合功能锻炼治疗类风湿关节炎的临床疗效。方法选择2013年10月至2014年10月在我院确诊的60例类风湿关节炎患者,随机分为观察组和对照组,每组30例。对照组采取艾拉莫德2次/d早晚各1片(25 mg)饭后服用,观察组在对照组的基础上结合功能锻炼。观察3个月后两组的病情改善情况。结果治疗3个月后,观察组、对照组的总有效率分别为93.3%、76.6%,两组比较差异有统计学意义(P<0.05)。结论艾拉莫德联合功能锻炼治疗类风湿关节炎的临床效果良好,值得临床推广应用。     

姜黄素对类风湿关节炎患者破骨细胞生成数量和活性的影响

目的 研究姜黄素对类风湿关节炎(RA)患者破骨细胞生成数量和活性的影响。方法 采集RA患者外周血,密度梯度离心法分离外周血单个核细胞(PBMCs),经核因子κB受体活化因子配体(RANKL)和巨噬细胞集落刺激因子(M-CSF)诱导分化,分别采用不同浓度(2.5、5、10 μmol·L-1)姜黄素进行干预;根据姜黄素浓度将实验分为4组,即空白对照组、姜黄素低浓度组、姜黄素中浓度组和姜黄素高浓度组;14 d后行抗酒石酸酸性磷酸酶(TRAP)染色检测破骨细胞并计数;检测细胞TRAP活性。结果 细胞培养14 d后,姜黄素低、中、高浓度组的TRAP阳性细胞计数(个/10个视野)分别为96.89±3.51、76.44±1.88和62.56±2.70,均低于空白对照组131.00±4.03(P＜0.05);各浓度组的TRAP活性(U·L-1)分别为5.74±0.36、4.21±0.12和3.06±0.07,均低于空白对照组7.48±0.22(P＜0.05)。结论 姜黄素抑制RA患者PBMCs生成破骨细胞的数量和活性,且随着姜黄素浓度的增加,抑制作用呈增强趋势。     

Effects of nadolol and propranolol on renal function in hypertensive patients with moderately impaired renal function.

Effects of oral administration of equipotent antihypertensive doses of propranolol and nadolol on renal function were examined in 20 hypertensive patients with moderately impaired renal function. Creatinine clearance increased, and serum beta 2-microglobulin concentrations decreased, when patients were switched from propranolol to nadolol therapy (creatinine clearance = 46.7 +/- 4.9 ml min-1 on propranolol and 52.7 +/- 5.9 on nadolol; beta 2-microglobulin = 6.14 +/- 0.66 mg l-1 on propranolol and 5.62 +/- 0.62 on nadolol). When patients were put back on propranolol, their creatinine clearances (45.9 +/- 5.0 ml min-1) and serum beta 2-microglobulin concentrations (6.51 +/- 0.67 mg l-1) returned to values comparable to those obtained before the change to nadolol was made. Serum beta 2-microglobulin concentrations correlated significantly with creatinine clearance (r = -0.819, P less than 0.001).     

正清风痛宁联合甲氨喋呤治疗类风湿关节炎

目的评价正清风痛宁缓释片联合甲氨喋呤(MTX)治疗类风湿关节炎(RA)的疗效。方法RA患者69例,随机分成2组,正清风痛宁缓释片联合MTX治疗组35例,采用正清风痛宁缓释片2粒,每日2次口服,同时服用MTX10mg,每周1次;对照组34例,MTX10mg口服,每周1次,于治疗8周后,观察两组疗效。结果正清风痛宁组35例,其中显效21例,占60%,有效14例,占40%,无效0例,总有效率为100%;对照组34例,其中显效7例,占20.6%,有效24例,占70.6%,无效3例,占8.8%,总有效率为91.2%。两组疗效相比,经秩和检验,有显著性差异(P<0.05)。治疗组和对照组关节疼痛、肿胀、压痛、晨僵、血沉、C-反应蛋白、类风湿因子治疗后均明显低于治疗前(P<0.01或P<0.05)。治疗后正清风痛宁组与对照组晨僵、关节疼痛、肿胀、压痛、握力、ESR、CRP、PLT相比有显著差异(P<0.05)。结论正清风痛宁口服联合MTX治疗类风湿关节炎的疗效优于单用MTX组。     

The effects of suprofen in rats with Mycobacterium butyricum-induced arthritis.

The activity of alpha-methyl-4-(2-thienylcarbonyl)benzeneacetic acid (suprofen) was studied in rats with established Mycobacterium butyricum-induced arthritis. The arthritic response was evaluated by measuring the diameter changes of the hind paws and tibiotarsal joints, using a new apparatus. Treatment once daily by gavage during 14 days revealed activity at the dose of 1.25 mg/kg and above. The lowest ED50 was 6.2 mg/kg. In comparison with simultaneously studied reference compounds, this corresponded approximately to the activity of phenylbutazone. In the higher dose range, 10 to 40 mg/kg, the reduction of external arthritic symptoms was associated with marked reversal of multiple bone deformations. A treatment schedule with 4 administrations of 2.5 mg/kg/day was significantly more effective than a single daily administration of 10 mg/kg and comparable to that of 10 mg/kg once daily. Mixing of suprofen with the diet, to give the low daily dose of 1.28 mg/kg confirmed the high activity expected from the maintenance of a practically constant compound level in the treated rats. In a comparative study involving suprofen, acetyl-salicylic acid, indometacin, phenylbutazone and tolmetin, all administered over 14 days with the diet in a dose range up to toxic dose levels, dose-related anti-inflammatory and toxic effects were obtained. The potency order and ED50's of the compounds were: indometacin (0.31 mg/kg) greater than suprofen (1.48) greater than tolmetin (18.0) = phenylbutazone (18.2) greater than acetyl-salicylic acid (440). Suprofen had by far the largest safety margin (48), followed by phenylbutazone (20), tolmetin (16), indometacin (8) and acetyl-salicylic acid (2). In conclusion, three major symptoms of adjuvant arthritis: joint inflammation, impaired growth and bone erosion, were markedly reduced by different doses of suprofen, which revealed to be a safe compound when compared to several reference compounds.     

卡维地洛对原发性高血压患者的肾脏保护作用

目的 探讨卡维地洛对原发性高血压(EH)患者肾功能的影响.方法 56例EH患者经2周冲洗期后,接受卡维地洛一日2次,每次10 mg口服,疗程16周.治疗4周后若舒张压仍然≥90mmHg则剂量加倍,观察治疗前后血压和肾功能各项指标的变化.结果 治疗后患者收缩压由(156.2±11.8)mmHg降至(134.5±10.9)mmHg,舒张压由(101.5±3.7)mmHg降至(85.3±5.6)mmHg,治疗前后相比,差异有统计学意义的显著性(P<0.01);24h尿白蛋白由(107.2～50.1)mg降至(69.5±31.2)mg(P<0.01):24 h尿总蛋白由(0.28±0.071)g/L降至(0.19-1-0.049)g/L(P<0.01):血β2微球蛋白(β2-MG)由(2.43±0.45)mg/L降至(1.82±0.41)mg/L(P<0.01):尿β2-MG由(0.124±0.038)mg/L降至(0.109±0.016)mg/L(P<0.01).治疗前后肾小球滤过率,血尿素氮、肌酐和内生肌酐清除率,血糖,血脂,血电解质等的差异均无统计学意义(P>0.05).结论 卡维地洛能显著降低EH患者的收缩压和舒张压,且能减少其24 h尿白蛋白的排泄,降低血、尿β2-MG,对患者的肾功能具有保护作用.