Gout: Nonsteroidal Anti-inflammatory Drugs and Colchicine to Prevent Painful Flares During Early Urate-Lowering Therapy

ABSTRACT

A case report on a gout patient is presented with discussion of the use of prophylactic agents for prevention of gouty flare in such a patient when beginning urate-lowering therapy. The limitations of the literature on this subject are described. Advantages and disadvantages of of prophylaxis and the burden of pain are discussed.     

Benign and malignant liver neoplasms

Several agents have recently been implicated in the development of benign and malignant liver neoplasms. Recognition of their possible role by the primary care physician may prevent serious consequences to patients exposed to these agents, which include oral contraceptives, androgens, hepatitis virus, and vinyl chloride.     

环磷酰胺、秋水仙碱联合治疗急性脑梗塞病人的随机对照试验

目的：研究环磷酰胺、秋水仙碱作为抗炎药物治疗急性脑梗塞病人是否有效。方法：６４例急性脑梗塞病人随机分为试验组和对照组（各３２例）。对照组给予一般治疗,试验组在一般治疗的基础上静滴环磷酰胺０１～０２ｇ和口服秋水仙碱１ｍｇ,每天１次,共１０天。采用改良爱丁堡—斯堪的那维亚中风量表（ｍｏｄｉｆｉｅｄＥｄｉｎｂｅｒｇｈＳｃａｎｄｉｎａｖｉａｓｔｒｏｋｅｓｃａｌｅ,ｍＥＳＳ）及ＮＩＨ中风量表（ＮＩＨｓｔｒｏｋｅｓｃａｌｅ,ＮＩＨＳＳ）分于入院时、病后７天、１４天、１月、２月、３月进行神经功能缺损评分,用ＢａｒｔｈｅｌＩｎｄｅｘ（ＢＩ）分于病后１月、２月、３月进行日常生活活动评分。结果：病后１４天、１月、２月、３月试验组神经功能缺损评分显著低于对照组（Ｐ＜００５或Ｐ＜００１）,２月、３月试验组显效率高于对照组（Ｐ＜００５）;２月、３月试验组ＢＩ评分高于对照组（Ｐ＜００５）,基本独立及轻度依赖比率高于对照组（Ｐ＜００５）。结论：环磷酰胺、秋水仙碱作为抗炎药物治疗急性脑梗塞病人,能减轻病人神经功能缺损,提高病人独立生活能力。     

健康教育对提高痛风患者治疗依从性研究

目的通过多种形式的健康教育,旨在使痛风患者能正确认识高尿酸血症和痛风的病因、临床表现及诊断治疗原则,提高监测血尿酸水平和综合治疗的依从性。方法采用自身前后对照试验设计,通过对比健康教育前后患者问卷调查表评分情况,评估健康教育对提高痛风患者治疗依从性的效果。结果本研究共纳入98例原发性痛风患者,完成研究者53例,其中男性48例,女性5例,体重超重者24例,血尿酸增高者32例,不知道应选择低嘌呤饮食者38人,不了解痛风的正确治疗者高达50人。健康教育前问卷评分为53.51±20.21分,健康教育前后问卷评分为83.02±6.45分,两阶段评分经配对t检验(P<0.0001),表明健康教育干预后的评分有明显提高,平均增高29.51±17.58分,增高率达71.12%±121.32%。结论多种形式、多种渠道的健康教育,能增强患者对痛风知识的了解,建立良好生活习惯,有助于提高患者治疗依从性,减少复发机率,改善生活质量。     

Mechanism of Action of Colchicine in Acute Urate Crystal-Induced Arthritis

Phagocytosis of urate crystals by human or rabbit neutrophils induces the synthesis and release of a glycoprotein, the crystal-induced chemotactic factor (CCF), which is chemotactically active both in vitro and in vivo. It has been proposed that CCF is a prime mediator of the acute gouty attack. Colchicine has been shown to decrease the production and release of this factor in vitro. In these studies, colchicine, at nonleukopenic doses, is shown to abrogate the acute arthritis induced by monosodium urate crystals in rabbits, but to have no effect upon the arthritis induced by the injection of the purified cell-derived chemotactic factor. Serum colchicine levels were 0.48-0.58 muM at 30 min and 0.12-0.3 muM at 90 min after intravenous injection of 0.2 mg/kg colchicine. Peripheral blood polymorphonuclear leukocytes obtained from colchicine-treated animals migrated normally towards a chemotactic stimulus but failed to produce CCF after phagocytosis of monosodium urate crystals. The dialyzed synovial fluid from rabbits injected with microcrystalline sodium urate contained chemotactic activity that was not present when animals were also given intravenous colchicine or injected intra-articularly with the chemotactic factor formyl-methionyl-leucyl-phenylalanine. Furthermore, the synovial fluid from rabbits injected with microcrystalline sodium urate significantly decreased (125)I-CCF binding to neutrophils. The binding of (125)I-CCF to its neutrophil receptor was not significantly reduced by the synovial fluid of colchicine-treated rabbits nor by the synovial fluid of control rabbits injected with the chemotactic factor formyl-methionyl-leucyl-phenylalanine. Colchicine (10 and 0.1 muM) was shown to have no effect upon the binding of (125)I-CCF to its cell receptor.     

Nonsteroidal Anti-inflammatory Drugs and Colchicine to Prevent Gout Flare During Early Urate-Lowering Therapy: Perspectives on Alternative Therapies and Costs

ABSTRACT

Published evidence in the literature, regulatory status, and relative costs of colchicine and nonsteroidal anti-inflammatory drugs (NSAIDs) for prophylaxis of gouty flares during early urate-lowering therapy are reviewed.     

216例原发性痛风的临床表现与X线改变关系分析

本文分析了216例原发性痛风不同程度X线改变与其临床特征之关系,并探讨了其可能的影响因素及有关合并症情况。     

Colchicine Administration to Mice: A Metabolic and Ultrastructural Study

Abstract. A single injection of colchicine has been administered to normal albino mice, and the metabolic effects as well as the hepatic ultrastructural changes resulting from this treatment have been studied at various time intervals. A marked decrease in circulating triglyceride levels was evident 4 hours after colchicine injection and was maximum after 11 hours. It coincided with a marked increase in hepatic triglyceride content. Twenty hours after colchicine administration, plasma triglyceride levels and hepatic triglyceride content had returned to normal values. Similar changes in the levels of circulating proteins were observed although their magnitude was less than that observed for triglycerides. Ultrastructurally, colchicine treatment resulted in the virtual disappearance of the microtubules from the hepatocytes, and in the appearance of many clusters of vesicles containing very low density lipoprotein-like particles which eventually transformed into lipid droplets. These ultra-structural alterations were also completely reversible, the reversibility coinciding with the morphological reappearance of microtubules. Finally, colchicine treatment resulted in marked metabolic changes that are interpreted as representing an attempt, by the organism, to keep adequate energy sources during the period of lack of circulating triglycerides.     

Preservation of Renal Function during Gout Treatment with Febuxostat: A Quantitative Study

Abstract

Background: Hyperuricemia can accelerate renal decline associated with aging. Chronic kidney disease is frequently seen in patients with hyperuricemia and gout. Objectives: Assess the impact of urate–lowering therapy on renal function in subjects with gout who were treated with febuxostat for ≤ 48 months. Methods: Subjects from 2 phase 3 clinical studies were enrolled in the phase 3, long–term, open–label Febuxostat/Allopurinol Comparative Extension Long–Term (EXCEL) study. In the EXCEL study, 1086 subjects initially were treated with febuxostat 80 or 120 mg daily, or allopurinol 300 mg daily. The subjects were permitted to switch between doses of febuxostat and/or allopurinol during the first 6 months of treatment to achieve and maintain a serum uric acid (SUA) level ≥ 3 to < 6 mg/dL. For the analysis presented in this article, data from 551 subjects who received only febuxostat throughout the duration of both the phase 3 and EXCEL studies (≤ 48 months) were used to determine the impact of SUA reduction on estimated glomerular filtration rates (eGFRs). Results: At baseline of the 2 original phase 3 studies, subjects' mean SUA level was 9.8 mg/dL. Greater sustained decreases in subjects' SUA levels were associated with less renal function decline (P < 0.001)by statistical modeling. The study data predicted that for every 1 mg/dL of chronic reduction of SUA level in subjects with gout, there would be a preservation of 1.15 mL/min of eGFR. Conclusion: Sustained urate–lowering therapy with febuxostat appears to impede renal decline in patients with gout. The results discussed in this article support similar observations previously reported in 116 hyperuricemic subjects with gout who received febuxostat for ≤ 5 years.     

Colchicine administration to mice: a metabolic and ultrastructural study.

A single injection of colchicine has been administered to normal albino mice, and the metabolic effects as well as the hepatic ultrastructural changes resulting from this treatment have been studied at various time intervals. A marked decrease in circulating triglyceride levels was evident 4 hours after colchicine injection and was maximum after 11 hours. It coincided with a marked increase in hepatic triglyceride content. Twenty hours after colchicine administration, plasma triglyceride levels and hepatic triglyceride content had returned to normal values. Similar changes in the levels of circulating proteins were observed although their magnitude was less than that observed for triglycerides. Ultrastructurally, colchicine treatment resulted in the virtual disappearance of the microtubules from the hepatocytes, and in the appearance of many clusters of vesicles containing very low density lipoprotein-like particles which eventually transformed into lipid droplets. These ultrastructural alterations were also completely reversible, the reversibility coinciding with the morphological reappearance of microtubules. Finally, colchicine treatment resulted in marked metabolic changes that are interpreted as representing an attempt, by the organism, to keep adequate energy sources during the period of lack of circulating triglycerides.     

痛风患者健康教育需求的调查分析及对策

目的 对痛风患者健康教育的需求进行调查与分析。方法 对2003年1月至2005年12月在我科门诊就诊及住院治疗的126例痛风患者。以问卷的形式调查有关痛风知识的了解情况。结果 男性、高收入．高职务、有饮酒史的人患痛风的概率高于其他人群;大部分患者对痛风的相关知识不了解。结论 调整饮食结构、控制饮酒是治疗痛风的基本措施,对痛风患者进行多样化的健康教育非常必要。     

河北蔚县地区人群痛风和高尿酸血症现状调查

目的：调查河北省蔚县居民高尿酸血症与痛风的流行情况,并观察高尿酸血症与体重指数、收缩压、血浆胆固醇、甘油三脂和空腹血糖的相关性。方法采用随机、分层、整群抽样的方法,调查了该县各地区7,083名20岁以上居民的高尿酸血症和痛风的患病情况。结果①血尿酸水平及高尿酸血症情况：总体血尿酸水平为（345.43±68.52）μmol/L,其中男性为（371.82±78.22）μmmol/L,女性为（315.28±73.67）μmmol/L;高尿酸血症患病率为15.40%,男性患病率为16.88%,女性为10.83%;②痛风患病率：痛风125例,痛风患病率为1.76%,其中男113例（2.11%）,女12例（0.70%）;③与血尿酸正常组比较,高尿酸血症组体重指数、收缩压、血浆甘油三酯、胆固醇和空腹血糖水平均明显升高,差异有统计学意义。结论河北省蔚县人群高尿酸血症及痛风患病率均呈现升高趋势。高尿酸血症患者易合并高血压、高脂血症、糖尿病等疾病,表明作为心血管疾病的危险因素,高尿酸血症患病率仍在继续升高,高尿酸血症已经成为危胁人类健康的重要隐患。     

急性痛风发作51例临床分析

目的:临床分析并文献复习痛风的特征,以加深对痛风的认识。方法:对临床各科室住院患者并发急性痛风性关节炎发作51例患者的临床资料进行分析,并对高尿酸血症和痛风与心血管、肾脏疾病的关系进行文献复习。结果:男性49例,发病年龄(52±11)岁;合并疾病有肥胖、高血压、糖尿病、冠心病和骨关节炎。急性痛风在使用利尿剂、高嘌呤饮食以及手术后等诱发,全身症状表现为发热、白细胞增多和血沉增快;累及第一趾跖关节36例,高尿酸血症45例;急性期持续3~16 d;长期病程出现关节骨质破坏、痛风石、痛风性肾病和肾功能衰竭。临床上痛风的误诊误治仍常见。结论:痛风是一较为复杂的代谢性疾病,临床特征明显。而临床医生需加深对其认识,减少误诊。     

The Role of Colchicine in Acute Coronary Syndromes

Purpose

Because inflammation is a key process implicated in the pathogenesis of atherosclerosis at all stages, including plaque formation, progression, instability, and rupture, and because colchicine has unique anti-inflammatory properties, this review article summarizes the pathophysiologic mechanisms underpinning inflammation in atherosclerosis and acute coronary syndrome (ACS), outlines anti-inflammatory therapeutic approaches that have been tested thus far, and evaluates the evidence supporting the potential role of colchicine in improving outcomes and reducing cardiovascular morbidity and mortality in patients after ACS.

Allergic Rhinitis

Patients with allergic rhinitis have a chronically stuffy nose. Usually their sense of smell is dulled, and their nose discharges clear mucus. To differentiate other conditions from allergic rhinitis and to establish a diagnosis, the physician must take a careful history to ferret out possible precipitating factors and meticulously examine the nose, using phenylephrine hydrochloride or similar drugs to shrink mucous membranes.     

Colchicine in Stable Coronary Artery Disease

Purpose

Disease management of stable coronary artery disease consists of controlling hemostasis and lipid regulation. No treatment strategies preventing plaque erosion or rupture are yet available. Cholesterol crystal–induced inflammation leading to plaque destabilization is believed to be an important factor contributing to plaque instability and might well be amenable to treatment with anti-inflammatory drugs. Colchicine has anti-inflammatory properties with the potential to address both the direct and indirect inflammatory mechanisms in the plaque.

Sodium urate arthritis: effects on the sensory properties of articular afferents in the chicken

The physiological properties of joint capsule mechanoreceptors in the ankle joint of the chicken were studied in the 3-h period immediately after intra-articular injection of microcrystal sodium urate. The electrical activity was recorded from single C- and A-delta sensory fibres dissected from the parafibular nerve. C-fibres showed high levels of spontaneous activity and receptive fields that varied from single spots 1 mm in diameter up to 4×4 mm. Thresholds to mechanical stimulation ranged from 0.1 to 8 g and 80% of the units responded to movement of the joint. A-delta fibres showed little spontaneous activity and receptive fields that varied from 1 mm to 9×1 mm. Thresholds to mechanical stimulation ranged from 0.1 to 16 g and 17% responded to joint movement. A comparison of the physiological properties of the C- and A-delta fibres in sodium urate arthritis with similar fibres in normal and monoarthritic animals indicated an increased sensitivity in the C-fibres but not in the A-delta fibres. Sensitisation was observed in the significantly increased receptive field size, decreased response thresholds, increased response to joint movement and the high level of spontaneous activity. These changes in the sensitivity of the joint capsule C-fibre receptors provides peripheral neural evidence for the pain experienced in acute gouty arthritis.     

环磷酰胺和秋水仙碱联合应用对急性缺血性中风病人粘附分子的影响

目的 :探讨环磷酰胺、秋水仙碱联合应用对急性缺血性中风病人CD11a、CD11b、CD18和CD5 4的影响。方法 :84例发病 72小时内的脑梗死病人 ,随机分为处理组 (4 3例 )和对照组 (4 1)例。对照组接受急性脑梗死的基本治疗 ,处理组除接受对照组的治疗外 ,再加上环磷酰胺 0 1～ 0 2g/d静滴和秋水仙碱 1mg/d口服共 10天治疗。两组病人分别于治疗前后测CD11a、CD11b、CD18和CD5 4。结果 :处理组CD18在单核细胞、中性粒细胞上表达减少的百分率 ,以及CD5 4在单核细胞、中性粒细胞及淋巴细胞上表达减少的百分率与对照组相比 ,差异有显著性 (P <0 0 5 ) ;CD11a在单核细胞、中性粒细胞及淋巴细胞上表达减少的百分率 ,CD11b在单核细胞、中性粒细胞上表达减少的百分率两组无显著性差异 (P >0 0 5 )。结论 :环磷酰胺、秋水仙碱联合应用能减少急性缺血性中风病人白细胞上CD18、CD5 4的表达 ,对白细胞上CD11a、CD11b的表达无明显影响     

Colchicine analogues: Effect on amyloidogenesis in a murine model and, in vitro, on polymorphonuclear leukocytes

Colchicine has been used in diverse clinical settings such as gout, familial Mediterranean fever, liver cirrhosis, Behcet's disease and pericarditis. It also has an antimitotic potential hitherto unexplored due to its narrow therapeutic toxic ratio. The aim of the present study was to compare the effectiveness and the toxicity of colchicine and three analogues: thiocolchicine, 2,3 dimethyl-colchicine and 3-dimethylthiocolchicine in the blockage of amyloid synthesis in a murine model. 3-demethylthiocolchicine was equipotent to colchicine in the blockage of casein induced amyloidogenesis. However, it was markedly less toxic (LD50 11.3 mg kg-1 vs. 1.6 mg kg-1). Thiocolchicine was toxic (LD50 1.0 mg kg-1) and 2,3 didemethyl-colchicine was far less effective. The effect of 3-dimethylthiocolchicine on polymorphonuclear leukocytes was then compared to colchicine. The effect of this analogue on inhibition of chemotaxis was equivalent to that of colchicine whereas the latter was superior to the analogue in the suppression of phagocytosis (by a ratio of 2:1) and in the inhibition of bactericidal activity (by a ratio of 10:1). Since in therapeutic concentrations the only detectable effect of colchicine on PMNs is inhibition of chemotaxis, our data may point to 3-demethylthiocolchicine as an optional, perhaps superior alternative to colchicine for some of its therapeutic indications.     

Why Colchicine Should Be Considered for Secondary Prevention of Atherosclerosis: An Overview

Purpose

Colchicine is a widely available, inexpensive drug with a range of antiinflammatory properties that may make it suitable for the secondary prevention of atherosclerosis. This review examines how past and contemporary approaches to antiinflammatory therapy for atherosclerosis have led to a better understanding of the nature of the disease and sets out the reasons why colchicine has the potential to become a cornerstone therapy in its management.