[Mechanisms of development of gout-related inflammation].
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Biomedical subjects
Publications and source records attributed to V G Barskova.
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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.
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.
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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.
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.
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.
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.
AIM: To study effectiveness and tolerance of monoclonal antibodies to tumor necrosis factor (the drug remicade) in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: Remicade treatment results are considered for 25 RA patients receiving methotrexate the activity of which was inadequate for these patients. Remicade was infused intravenously in a dose 200 mg 4 times for 22 weeks. RESULTS: Remicade produced positive clinical and laboratory effects as early as the first infusion. The response was observed during 22 weeks of the treatment in 17 of 25 patients. Remicade tolerance was good. One patient failed the treatment because of development of collapse. CONCLUSION: Pilot results of remicade trial point to its high therapeutic potential and perspectives in rheumatology.
AIM: To evaluate efficacy and safety of nimesil, a selective inhibitor of cyclooxigenase-2, in gouty arthritis (GA). MATERIAL AND METHODS: Nimesil was given to 20 male patients with GA (mean age 53.8 years, mean duration of the disease 8.1 years) in a dose 100 mg twice a day for 14 or 21 days depending on positive clinical changes (13 and 6 patients, respectively). The articular swelling index, supraarticular skin hyperemia, the articular index, pain in rest and movement were estimated on the treatment day 1, 5, 14 and 21. Arterial pressure was controlled in all the patients. ESR, uric acid, seromucoid, ALT, AST, gamma-GTP, glucose levels were measured before and after the treatment. RESULTS: Nimesil relieved pain and inflammation (ESR and seromucoid level lowered significantly). Effects on the other estimates were not registered. One patient developed generalized urticaria on the treatment day 5. The drug was discontinued in him. CONCLUSION: Nimesil can be used as monotherapy of an acute attack of gout. In a dose 200 mg/day nimesil provides an effective and fast treatment of gout, is well tolerated and safe.
Articular lesions in 157 patients infected with ixodes tick-borne borreliosis (ITB) in a central Russia's region set on, on the average, in 4 months after tick attack; they were associated with systemic signs of an early disseminated infection and set on less seldom in a late period. The most often encountered systemic signs were as follows: secondary erythema (32% of patients), neurological syndrome (13%), cardio-vascular lesions (22%), ocular lesions (13%) and hepatic lesions (8%). The articular syndrome manifested itself through arthralgia (53 patients) and arthritis (104 patients), which set on quite often in the tick-attack area. There was a peculiarity typical of articular lesions, which made it possible to distinguish them from other rheumatic disease. A dynamic follow-up revealed different clinical variations of Lyme's arthritis and peculiarities of the genetic profile, i.e. a higher prevalence of HLA A2, HLA-B15 and HLA-DR4 as well as of haplo-types HLA A2-B15 and HLAB15-DR4. The articular lesions were associated with an intensive specific humoral immune response. The instrumental examination methods, i.e. ultrasonography of joints as well as scintigraphy of bones and joints, did not reveal any qualitative differences between arthralgia and arthritis, which is indicative of a common nature different-intensity manifestations of arthropathy in thick-borne borreliosis.
AIM: Comparison of clinical symptoms in Lyme disease (LD) in various age groups. MATERIAL AND METHODS: 150 patients with verified LD were divided into 4 age groups: under 15 years (group 1), 16-40 years (group 2), 41-60 years (group 3), over 60 years (group 4). Antibodies to Borrelia burgdorteri were detected with indirect immunofluorescence and Western blot. RESULTS: LD clinical symptoms differed in the age groups. Patients of group 1 had more prevalent infectious syndrome with fever but they had no radiculoneuritis and polyneuritis. Patients of group 2 more frequently suffered of carditis and secondary erythema. Groups 3 and 4 were characterized by infectious syndrome, secondary erythema and aseptic meningitis, joint lesions being more frequent in group 3, nervous system lesions--in group 4. CONCLUSION: Age peculiarities of LD symptoms are very important. In particular, joint syndrome is responsible for lingering course of LD.
Lyme disease is a multisystem infection affecting all age groups. In this study an attempt was made to determine whether the patient's age influences the course of the disease. One hundred and fifty patients with diagnosed Lyme disease were included in the study. Two serological methods were used to detect antibodies to Borrelia burgdorferi and to confirm the diagnosis: an indirect immunofluorescence assay (the Russian strain Ip-21) and Western blot. The course of Lyme disease did not differ from that seen in Europe and North America. However, a few clinical differences between groups were observed. In the first age group (0-15 years) the most common manifestation was flu-like symptoms with fever. Neither radiculoneuritis nor polyneuropathy was observed in this age group. Late manifestations were rare and the outcome of the disease was benign. The course of the disease in the second group (16-40 years) was most similar to that in childhood and the also outcome was similar. Carditis and erythema multiple were significantly more common in the second group (16-40 years) than in the other age groups. No differences were found between the third (41-60 years) and fourth (> than 60 years) group in the frequency of flu-like symptoms, erythema multiple and aseptic meningitis. However, the most important clinical sign in this group was involvement of the nervous system whereas in the third group this was joint damage. This feature deserves attention because, as a rule, the presence of an articular syndrome determines the prognosis of LD.
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OBJECTIVE: To describe clinical and serologic features of Lyme borreliosis, particularly the joint abnormalities, in Russian patients. METHODS: Physicians were invited to refer patients with past or present erythema migrans to the Rheumatology Institute in Moscow; field studies were done of residents in an area endemic for Lyme borreliosis, and a serosurvey was conducted of patients with nonspecific neurologic, cardiac, or joint symptoms. Serologic testing was done by ELISA and Western blotting using a strain of Borrelia afzelii, a member of the B. burgdorferi sensu lato complex, recovered from ticks from the field study site. RESULTS: Of 86 patients with erythema migrans, neurologic abnormalities developed in 26 (30%), cardiac involvement in 5 (6%), arthritis or arthralgia in 35 (41%), and acrodermatitis in 2 (2%). Joint involvement was usually characterized by one or a few brief episodes of joint swelling or pain in one large joint at a time. However, 69 of the 86 patients (80%) received antibiotic therapy early in the infection. The majority of patients with active infection had elevated levels of IgM or IgG antibody to B. afzelii by ELISA, and those with late infection often had IgG reactivity with > or = 5 spirochetal proteins, particularly the 37, 39, 41, 60, and 93 kDa antigens. In a serosurvey of 75 patients with facial palsy, atrioventricular block, or arthritis or arthralgia of uncertain cause, 6 had IgG reactivity with > or = 5 spirochetal proteins. CONCLUSION: Lyme borreliosis in Russia is similar to that in other parts of Europe. Brief episodes of arthritis or arthralgia were a common feature of the illness.
Out of 86 Lyme's disease patients with a history of migrating erythema nervous system, cardiovascular and articular involvement was observed in 27, 6 and 43% of cases. Acrodermatitis was diagnosed in 2% of patients. Affection of locomotor system manifested with acute arthritis episodes or pains in major joints. 11 patients of 12 examined at arthritis onset showed elevated titer of anti-Borrelia IgG antibodies. Serologically, of 80 patients with arthritis or arthralgia without prior migrating erythema 6 demonstrated antibodies to 5 and more Borrelia polypeptides.