[Time course of changes in the clinical manifestations of gout in men: data of a 7-year retrospective follow-up].

AIM: To estimate the time course of changes in the clinical manifestations of gout and their risk factors during a long-term follow-up. SUBJECTS AND METHODS: A total of 160 male patients with gout were examined and followed up for a mean of 6.9 ± 2.0 years. Their clinical assessment included determination of the type of arthritis over time, the frequency of arthritis attacks during one year prior to the examination, the presence and number of subcutaneous tophi, inflamed joints, comorbid or co-occurring diseases (CD), allopurinol adherence, dietary compliance, frequency of taking non-steroidal anti-inflammatory drugs (NSAIDs), diuretics, and alcohol. The serum levels of uric acid (UA), glucose, total cholesterol, and glomerular filtration rate were estimated. RESULTS: The number of patients taking allopurinol increased from 19% to 64% (p < 0.0001), its average daily dose was 167.6 ± 94.6 mg. The serum level of UA decreased; 16% of the patients achieved its target level. The number of patients with chronic arthritis was not significantly changed. Their serum level of UA was unchanged; the detection rate of subcutaneous tophi and CD rose. During one year, arthritis attacks were absent in 13% of the patients; 90% of them took allopurinol. In these patients, serum UA levels and body mass index significantly declined and the rate of CD was unchanged. None of 18 patients who had their diet and no allopurinol achieved the target level of UA. CONCLUSION: Among the gouty patients, 36% refrain from the use of allopurinol, only 23% out of them require that its dose be adjusted to achieve the target level of UA. Dietary compliance is insufficient to reach the target level of UA. Chronic arthritis is associated with the increased incidence of CD.

[Main factors of gender dimorphism of gout (estrogens and diuretics vs alcohol and genetics)].

The article analyses factors underling gender dimorphism of gout, gender epidemiological differences. Discussion covers the role of estrogens and menopause, alcohol, diuretics, gender-associated genetic characteristics in gout genesis.

[Carbohydrate metabolic disorders in gout: incidence and clinical features].

AIM: To study the clinical features of gout concurrent with carbohydrate metabolic disturbances. SUBJECTS AND METHODS: One hundred and ninety-five patients with gout were examined. Their mean age was 54.8 +/- 10.4 years; disease duration was 10 (6-15) years. Anthropometry was estimated; the levels of uric acid (UA), creatinine, and lipid metabolic parameters were measured fasting; the concentrations of glucose were estimated fasting and 2 hours after use of 75 g of glucose; UA excretion and glomerular filtration rate were calculated. RESULTS: Carbohydrate metabolic disorders were found in 112 (57.4%) patients with gout: type 2 diabetes (T2D) in 67 (34.3%); impaired fasting glycemia in 23 (11.8%); impaired glucose tolerance in 22 (11.3%); the diagnosis of T2D was first detected in 35 patients with gout, i 12 of the 35 (34%) cases after oral glucose tolerance test (OGTT). The detection rate of carbohydrate metabolic disturbances was in direct proportion to serum UA levels. This value was 513.7 +/- 122.2 pmicromol/l in gouty patients with carbohydrate metabolic disturbances and 472.4 +/- 121.9 micromol/l in normoglycemic patients (p = 0.026). High body mass index and elevated serum were significantly determined in hyperglycemic patients; coronary heart disease (CHD) and arterial hypertension were more frequently diagnosed. CONCLUSION: OGTT causes a 34% increase in the detection rate of T2D in patients with gout. Carbohydrate metabolic disturbances are revealed in the majority of patients with gout and associated with obesity, hypertriglyceridemia, high serum UA levels, chronic disease forms, the high incidence of CHD and arterial hypertension.

[Chronic gout: causes, clinical manifestations, treatment].

Why chronic gout, that is mostly a well diagnosed and controlled disease if it is timely and systematically treated with allopurinol, becomes a topical public health problem following 50 years after the introduction of pathogenetic therapy with xantine oxidase inhibitors is under consideration. The principles of rational therapy for chronic gouty arthritis are outlined.

[Relationship between the intima-media complex thickness, the risk factors of cardiovascular diseases, and the level of C-reactive protein in gouty patients].

AIM: To estimate a relationship between the intima-media thickness (TIM), cardiovascular risk (CVR) factors, and the level of C-reactive protein (CRP) in gouty patients. SUBJECTS AND METHODS: Eighty-nine patients at an interattack interval were examined. The patients' mean age was 46.0 +/- 11.4 years; the duration of the disease was 5.2 (3.0; 8.9) years. The traditional CVR factors were analyzed. Carotid ultrasound scanning was performed to detect vascular atherosclerotic lesion. The serum CRP concentration was measured by a highly sensitive immunonefelometric assay. RESULTS: According to the TIM, the patients were divided into 2 groups: 1) 37 patients with signs of carotid atherosclerotic lesion (TIM > or = 0.9 mm); 2) 52 patients with a TIM of less than 0.9 mm. The ages at the moment of examination and at the onset of the disease, the duration of the disease, as well as systolic blood pressure, and the risk of myocardial ischemia were greater in Group 1 than those in Group 2. In patients with atherosclerosis, the concentration of CRP was statistically significantly higher than that in patients without this condition. CONCLUSION: By complementing the classical CVR factors, CRP may be a predictor of cardiovascular diseases and their complications in patients with gout at an interattack interval.

[Effect of metformin on the clinical course of gout and insulin resistance].

UNLABELLED: The aim of this prospective study was to evaluate results of metformin (MF) therapy during 1 year of uric acid (UA) metabolism and the clinical course of gout with insulin resistance (IR). The study included 30 patients (28 men and 2 women) of mean age 51 yr and duration of he disease 4-11 yr. IR was diagnosed based on the HOMA index. INCLUSION CRITERIA: the absence of anti-gout therapy, normal renal and hepatic function, abstinence. The patients were given 1500 mg MF/day. The measured parameters included anthropometric and clinical characteristics, 24 hour AP, plasma UA, glucose, insulin, urea, creatinine, ALT, AST, lipid spectrum at the first and subsequent visits. UA clearance and excreted UA fraction were calculated. UA level decreased from 569 +/- 109.5 to 442.8 +/-107.4 mcmol/l (p < 0.01) after 12 months of MF therapy. Normouricemia ( < 360 mcmol/l) was achieved in 11 patients. Fasting insulin level dropped by 35% (from 23.9 to 15.9 mcU/ml, p < 0.01), HOMA index from 6.5 to 3. 7(p < 0.01). Serum glucose, cholesterol, triglycerides, and LDL cholesterol decreased while HDL cholesterol increased. Parameters of renal UA regulation and anthropometry remained unaltered. MF therapy resulted in a decrease of serum UA, insulin, and the degree of IR. The hypouricemic effect of MF was unrelated to renal UA excretion, reduced AP and body weight. It is hypothesized that MF reduces production of UA in patients with gout due to inhibition of synthesis of free fatty acids.

[Metabolic syndrome in gout].

The presence of metabolic syndrome (MS) is characteristic for many patients with gout. MS is closely associated with a generalized disorder called insulin resistance (IR) or impaired tissue responsiveness to the normal action in insulin. MS and IR define cardiovascular disease risks and are the main factors leading to severe disease associated with chronic arthritis and struck joints in gout patients. Given serious complications associated with MS, this frequent comorbidity should be recognized and be taken into account in the long-term treatment and overall health of individuals with gout. The review is devoted to studying MS and IR in gout patients.

A modified Delphi exercise to determine the extent of consensus with OMERACT outcome domains for studies of acute and chronic gout.

OBJECTIVES: To reach consensus with recommendations made by an OMERACT Special Interest Group (SIG). METHODS: Rheumatologists and industry representatives interested in gout rated and clarified, in three iterations, the importance of domains proposed by the OMERACT SIG for use in acute and chronic gout intervention studies. Consensus was defined as a value of less than 1 of the UCLA/RAND disagreement index. RESULTS: There were 33 respondents (61% response rate); all agreed the initial items were necessary, except "total body urate pool". Additional domains were suggested and clarification sought for defining "joint inflammation" and "musculoskeletal function". Items that demonstrated no clear decision were re-rated in the final iteration. There were six highly rated items (rating 1-2) with four slightly lower rating items (rating 3) for acute gout; and 11 highly rated items with eight slightly lower ratings for chronic gout. CONCLUSIONS: Consensus is that the following domains be considered mandatory for acute gout studies: pain, joint swelling, joint tenderness, patient global, physician global, functional disability; and for chronic gout studies: serum urate, gout flares, tophus regression, health-related quality of life, functional disability, pain, patient global, physician global, work disability and joint inflammation. Several additional domains were considered discretionary.

[Comparison of the time to analgetic and anti-inflammatory effect in the treatment of gouty arthritis with nimesulide and sodium diclofenac].

AIM: To compare the time to presentation of the analgetic and anti-inflammatory effects of granulated and tablet nimesulide and sodium diclofenac since the start of therapy for gouty arthritis (GA). MATERIAL AND METHODS: Ninety males with gout were randomized into 3 equal groups. The patients were included in the study by the following criteria: a documented diagnosis of gout (Wallace S. criteria), age over 18 years, acute arthritis for less than 3 weeks, affection of 4 and more joints. For 7 days patients of group 1 received nimesil (200 mg/day), those of group 2--aponil (200 mg/day), group 3 --sodium diclofenac (150 mg/day). Swelling, articular, pain indices were estimated daily for 7 days. RESULTS: Patients of group 1 (nimesil) experienced pain relief on min 20; patients taking nimesulide (aponil) experienced pain attenuation within the first hour. Pain (at rest and movement) and the indices declined faster in group 1 than in group 2 as well as in groups 1 and 2 compared to group 3. Arthritis was arrested in 24 (80%) patients of group 1, 11 (36%) of group 2 and 4 (13%) of group 3. CONCLUSION: Efficacy of nimesulide for arrest of an acute gout attack exceeds that of sodium diclofenac. Granulated nimesulide has advantages over tablets.

[Severity of a female gout course].

AIM: Comparison of a gout course in males and females. MATERIAL AND METHODS: The trial enrolled 34 patients (17 females and 17 males). The patients were matched by age and the disease duration. Severity of a gout course was assessed by the disease history, articular syndrome, concomitant diseases, blood biochemistry. Statistical processing was made with a computer program "Statistica 6.0". RESULTS: Events predisposing to purin metabolism disturbances and, therefore, to development of gout occur more frequently in females than in males. For the most part this concerns arterial hypertension and intake of diuretics. Women often have endocrine pathology (artificial menopause, dysmenorrhea, euthyroid goiter). In women gout runs a more severe course manifesting in early chronization, polyarticularity, lingering arthritis, rapid formation of tophuses. Both groups demonstrated marked polymorbidity with accumulation of the diseases related to atherosclerosis. Distinct group differences by content of uric acid seem to arise from early onset of chronic renal failure in women. CONCLUSION: In the absence of sex- and age-related differences, a more severe course of gout is observed in women. This may be due to hyperuricemia and a trend to the disease chronization, high prevalence of arterial hypertension and renal failure.

[Markers of vascular endothelium activation in gout].

AIM: To determine clinical significance of laboratory markers of vascular endothelium activation in gout. MATERIAL AND METHODS: A total of 16 males aged 31-68 years with gout entered the study. The diagnosis satisfied Vallas' criteria, duration of the disease varied from 1.5 to 14 years. Six (37%) patients had chronic gouty arthritis, ten (63%) patients were in the attack-free period. All the patients had metabolic syndrome, 7 (43.7%) of them suffered from diabetes mellitus type 2. Arterial hypertension was diagnosed in 12 (75%) patients. Thickness of the intima-media complex (IMC) of the carotid arteries was measured in 12 patients with duplex ultrasonic scanning. Solid phase enzyme immunoassay studied serum concentrations of a soluble form VCAM-1 (sVCAM-1) and von Willebrand factor antigen (WF:Ag) as laboratory markers of endothelial activation. The above immunoassay was also used to study acute phase inflammatory changes by the levels of C-reactive protein (CRP). RESULTS: Concentration of sVCAM-1 in gout was 1385.2 +/- 341.0 ng/ml and was significantly higher than in the control group (p < 0.001). Mean values of WF:Ag and CRP in the serum were also significantly higher in the study group. The levels of both sVCAM-1 and WF:Ag were elevated in 25% patients. CRP was elevated (8 mg/l) in 6 (37.5%) patients. They had no infectious complications and age-, duration- and stage-related specific features of the disease. There was no significant differences between mean levels of sVCAM-1, WF:Ag, CRP in patients with diabetes mellitus and metabolic syndrome. There was no correlation between uric acid level and IMC thickness (r = 0.12; p > 0.05). A weak positive insignificant correlation was found between concentration of CRP, sVCAM-1 and IMC thickness of the carotid arteries (r = 0.28 and r = 0.36, respectively; p > 0.05). However, this index significantly correlated with WF:Ag(r = 0.62; p < 0.05). A moderate positive but insignificant correlation was detected between the levels of sVCAM-1 and WF:Ag (r = 0.47; p > 0.05). Concentration of sVCAM-1 weakly correlated with that of CRP (r = 0.35; p > 0.05). WF:Ag and CRP levels correlated significantly (r = 0.51; p < 0.05). CONCLUSION: Increased concentrations of sVCAM-1 and WF:Ag in gout reflect not only activation of vascular endothelium but also development of atherosclerotic process in these patients.

[Use of metformin (siofor) in patients with gout and insulin resistance (pilot 6-month results)].

AIM: To evaluate metformin efficacy and safety in patients with gout and insulin resistance (IR). MATERIAL AND METHODS: The trial included 26 patients with gout (criteria of the American collage of rheumatologists) and IR (index HOMA). The inclusion criteria were the following: absence of antigout therapy, normal hepatic and renal function, rejection of alcohol. The drug dose was 1500 mg/day. The study was made of anthropometric and clinical characteristics, 24-h blood pressure monitoring, blood tests for uric acid, glucose, insulin, urea, creatinin, alaninaminotransferase, aspartataminotransferase, lipid spectrum at the first and further visits. RESULTS: A 6-month metformin therapy significantly changed the levels of glucose, insulin, HDLP and LDLP cholesterol, uric acid, HOMA index. Normouricemia was achieved in 11 patients, a significant lowering of uric acid--in 12 patients. The number of affected joints in 23 patients reduced from 4 (1-5) to 1 (0-2), p < 0.01. Seven patients with achieved normouricemia had no arthritis attacks. In 3 of 10 patients with chronic arthritis joint inflammation persisted. Six patients had dyspepsia during the first week of therapy, 1 patient discontinued the drug because of persistent diarrhea. CONCLUSION: Metformin therapy is safe. It reduces IR. The principal result of the study was lowering of uric acid and attenuation of the articular syndrome.

[Detection of sodium monourate crystals in biopsies of gastric mucosa in patients with gout]. / Vyiavlenie kristallov monourata natriia v bioptatakh slizistoi obolochki zheludka u bol'nykh podagroi.

AIM: To examine gastric biopsies with polarization microscopy for detection of sodium monourate crystals (SMC). MATERIAL AND METHODS: The trial included 20 patients with gout diagnosis (mean age 55.7 years, mean duration of the disease 12.3 years) in whom esophagogastroduodenoscopy was made with biopsy of gastric mucosa from the antral part of the stomach and middle third of the gastric body. RESULTS: Crystals in the biopsy specimens were detected in 11 of 20 examinees. The crystals were characterized by strong double refraction, length 3-20 mcm, acicular or planiform shape, blue or yellow color depending on position in compensated polarized light. Quantitative distribution of the crystals within one biopsy specimen was uneven and varied from solitary crystals to clusters of 70-80 crystals in sight, up to formation of tophus-like structures. Clinical picture in detection of SMC was characterized by more frequent occurrence of cases with subcutaneous tophuses of various location combined with higher hyperuricemia. CONCLUSION: One of the essential lines in the research of gout concerns mechanisms of SMC formation in organs and tissues and microcrystalline gastroduodenal inflammation. Methods of correction of this inflammation are to be designed.

[Insulin resistance syndrome in patients with gout and its influence on formation of clinical characteristics of the disease]. / Sindrom insulinorezistentnosti u bol'nykh podagroi i ego vliianie na formirovanie klinicheskikh osobennostei bolezni.

AIM: To evaluate the occurrence of immunoresistance (IR) syndrome in gout and its correlation with a gout course. MATERIAL AND METHODS: Anthropometric parameters, blood lipid spectrum, levels of glucose, uric acid (UA), immunoreactive insulin, HOMA index were studied in 55 male patients with gout (mean age 50.1 +/- 7.9 years, mean duration of the disease 7.5 +/- 7.2 years). Statistic processing was made with computer program Statistica 6.0. RESULTS: IR was revealed in 49% patients. Immunoresistant patients had visceral obesity, arterial hypertension, abnormal lipid profile, high UA concentrations, longer disease, chronic articular syndrome, high occurrence of diabetes mellitus and vascular events significantly more frequently. CONCLUSION: IR in gout patients is the risk factor of cardiovascular diseases; combination of IR and hyperinsulinemia is characterized by marked hyperuricemia and a trend to chronic course of the articular syndrome. Longer duration of gout, especially treated inadequately, raises the risk of IR. IR deteriorates prognosis in relation to cardiovascular diseases, diabetes mellitus type 2, course of gout itself.

[The effectiveness and safety of nimesulide (nimesile) in patients with gouty arthritis]. / Effektivnost' i bezopasnost' primeneniia nimesulida (nimesila) u bol'nykh podagricheskim artritom.

Patients with gout are at a high risk for drug-induced complications associated with the use of nonsteroidal anti-inflammatory drugs due to the baseline renal and hepatic abnormalities, metabolic disturbances, and concomitant diseases, such as arterial hypertension or type 2 diabetes mellitus. In this connection, it is expedient to use safer selective cycloxygenase-2 (COG-2) inhibitors. However, there are only single reports dealing with studies of the effectiveness and safety of selective COG-2 inhibitors in gout. The study was undertaken to evaluate the effectiveness and safety of the selective COG-2 inhibitor nimesulide (nimesile) in acute gouty arthritis (GA). Twenty male patients (whose mean age was 51.1 +/- 8.4 years) with PA were examined. Seven patients were found to have monoarthritis of 1 metatarsophalangeal joint, oligoarthritis was present in 9 patients and 4 patients had polyarthritis. The history of arthritis was as long as 6 days in 16 patients and 21-30 days in 4. Nimesulide was given in a dose of 200 mg/day for at least 14 days. The time course of changes in the objective and subjective symptoms of arthritis was studied. The tolerability of the drug was evaluated by its effect on renal (the levels of creatinine and urea, creatinine clearance) and hepatic (alanine transferase (ALT), aspartate transferase (AST), gamma-glutamyltranspeptidase (gamma-GTP)) functions, and blood pressure (BP) [24-hour BP monitoring (24-h BPM) before and after treatment. There were clear positive changes in the major parameters of arthritis: the swelling index was 4.5 +/- 2.7 and 0.5 +/- 0.5 scores before and after treatment, respectively; hyperemia, 3.5 +/- 2.5 and 0.1 +/- 0. 1 scores; articular index, 3.6 +/- 2.0 and 0.7 +/- 0.6 scores; pain (visual analogue scale) when resting, 53.8 +/- 17.6 and 4.7 +/- 4.6 scores, and that when moving, 68.3 +/- 16.0 and 9.0 +/- 8.8 mm, respectively. Negative changes in the levels of creatinine and uric acid and a reduction in creatinine clearance were not observed. There were no increases in the levels of ACT, ALT, gamma-GTP. 24-h BPM did not reveal any significant changes in the mean 24-hour, mean diurnal and nocturnal variables of BP. The 24-hour BP profile became better in some patients. Thus, nimesulide is an effective and safe drug for the treatment of PA.