Signs Of Gout Research Articles

Синдром сухого глаза у пациентов с подагрой

Purpose. To determine and study the features of the development of dry eye syndrome (DES) in gout, depending on urate-lowering therapy, the duration of the gout disease and the concentration of uric acid in the tear. Material and methods. The study involved 149 male patients (261 eyes) aged 35 to 75 years (mean age 60.63 ± 11.00 years). Among them, 110 people (202 eyes) with an established diagnosis: "Cataract with concomitant gout disease" and 39 people (59 eyes) with cataracts without clinical and laboratory signs of gout. All patients underwent both standard ophthalmological examinations and special ones. The concentration of uric acid in tears was determined by high performance liquid chromatography (HPLC). The diagnosis of gout was confirmed according to the criteria recommended by ACR / EULAR (2016). Results. In patients with gout who do not take a urate-lowering drug, DES occurs more often (82.1%) than in patients without gout (23.1%). With an increase in the concentration of uric acid in the tear, there is a high tendency to a shortening of the tear film rupture time (strong correlation coefficient r=-0.51, p<0.001) and to a decrease in tear production (Schirmer I test) (strong correlation coefficient r=-0.59, p<0.001). Conclusion. The data obtained indicate clear changes in the functional parameters of total tear production (Schirmer I's test) and the stability of the pre-corneal tear film (Norn's test) in patients with gout. This can be considered as a fact of the predisposition of this category of patients to the development of DES. A strong dependence of changes in tear production and HRVP on the concentration of uric acid in the tear was established. There is an obvious need for additional examination of this category of patients and an adequate choice of therapy, as well as the timely appointment of "artificial tear" drugs. Key words: dry eye syndrome, uric acid, gout.

Особенности развития синдрома сухого глаза при подагре

Purpose. To determine and study the features of the development of dry eye syndrome in gout, depending on urate-lowering therapy, the duration of the gout disease and the concentration of uric acid in the tear. Materials and methods. The study involved 149 male patients (261 eyes) aged 35 to 75 years (mean age 60.63 ± 11.00 years). Among them, 110 people (202 eyes) with an established diagnosis: «Cataract with concomitant gout disease» and 39 people (59 eyes) with cataracts without clinical and laboratory signs of gout. All patients underwent both standard ophthalmological examinations and special ones. The concentration of uric acid in tears was determined by high performance liquid chromatography (HPLC). The diagnosis of gout was confirmed according to the criteria recommended by ACR / EULAR (2016). Results. In patients with gout who do not take a urate-lowering drug, DES occurs more often (82.1%) than in patients without gout (23.1%). With an increase in the concentration of uric acid in the tear, there is a high tendency to a shortening of the tear film rupture time (strong correlation coefficient r=-0.51, p<0.001) and to a decrease in tear production (Schirmer I test) (strong correlation coefficient r=-0.59, p<0.001). Conclusions. The data obtained indicate clear changes in the functional parameters of total tear production (Schirmer I's test) and the stability of the pre-corneal tear film (Norn's test) in patients with gout. This can be considered as a fact of the predisposition of this category of patients to the development of DES. A strong dependence of changes in tear production and HRVP on the concentration of uric acid in the tear was established. There is an obvious need for additional examination of this category of patients and an adequate choice of therapy, as well as the timely appointment of «artificial tear» drugs. Key words: dry eye syndrome, uric acid, gout.

Expression and phylogeny of multidrug resistance protein 2 and 4 in African white backed vulture (Gyps africanus).

Diclofenac toxicity in old world vultures is well described in the literature by both the severity of the toxicity induced and the speed of death. While the mechanism of toxicity remains unknown at present, the necropsy signs of gout suggests primary renal involvement at the level of the uric acid excretory pathways. From information in the chicken and man, uric acid excretion is known to be a complex process that involves a combination of glomerular filtration and active tubular excretion. For the proximal convoluted tubules excretion occurs as a two-step process with the basolateral cell membrane using the organic anion transporters and the apical membrane using the multidrug resistant protein to transport uric acid from the blood into the tubular fluid. With uric acid excretion seemingly inhibited by diclofenac, it becomes important to characterize these transporter mechanism at the species level. With no information being available on the molecular characterization/expression of MRPs of Gyps africanus, for this study we used next generation sequencing, and Sanger sequencing on the renal tissue of African white backed vulture (AWB), as the first step to establish if the MRPs gene are expressed in AWB. In silico analysis was conducted using different software to ascertain the function of the latter genes. The sequencing results revealed that the MRP2 and MRP4 are expressed in AWB vultures. Phylogeny of avian MRPs genes confirms that vultures and eagles are closely related, which could be attributed to having the same ancestral genes and foraging behavior. In silico analysis confirmed the transcribed proteins would transports anionic compounds and glucose.

Defining remission in patients with gout.

Criteria to define remission in gout could be valuable in clinical trials and practice. But do the available preliminary criteria truly predict the long-term absence of gout signs and symptoms?

Novel Orthobunyavirus Causing Severe Kidney Disease in Broiler Chickens, Malaysia, 2014-2017.

During 2014–2017, we isolated a novel orthobunyavirus from broiler chickens with severe kidney lesions in the state of Kedah, Malaysia; we named the virus Kedah fatal kidney syndrome virus (KFKSV). Affected chickens became listless and diarrheic before dying suddenly. Necropsies detected pale and swollen kidneys with signs of gout, enlarged and fragile livers, and pale hearts. Experimental infection of broiler chickens with KFKSV reproduced the disease and pathologic conditions observed in the field, fulfilling the Koch’s postulates. Gene sequencing indicated high nucleotide identities between KFKSV isolates (99%) and moderate nucleotide identities with the orthobunyavirus Umbre virus in the large (78%), medium (77%), and small (86%) genomic segments. KFKSV may be pathogenic for other host species, including humans.

Retraction: Novel Orthobunyavirus Causing Severe Kidney Disease in Broiler Chickens, Malaysia, 2014-2017.

During 2014-2017, we isolated a novel orthobunyavirus from broiler chickens with severe kidney lesions in the state of Kedah, Malaysia; we named the virus Kedah fatal kidney syndrome virus (KFKSV). Affected chickens became listless and diarrheic before dying suddenly. Necropsies detected pale and swollen kidneys with signs of gout, enlarged and fragile livers, and pale hearts. Experimental infection of broiler chickens with KFKSV reproduced the disease and pathologic conditions observed in the field, fulfilling the Koch's postulates. Gene sequencing indicated high nucleotide identities between KFKSV isolates (99%) and moderate nucleotide identities with the orthobunyavirus Umbre virus in the large (78%), medium (77%), and small (86%) genomic segments. KFKSV may be pathogenic for other host species, including humans.

Cardiovascular safety of febuxostat. Analysis of the CARES study

Gout is associated with the high frequency of comorbidities, among which there are cardiovascular disease and kidney diseases. In this case, cardiovascular mortality rates are in the first place among the causes of death in patients with gout and exceed the death rates in the population. This may be associated with the main signs of gout, such as a high serum uric acid (UA) level and its related chronic inflammation. Drug correction of hyperuricemia is the mainstay of gout therapy and it is supposed to be able to neutralize the negative effect of UA on the risk of its associated adverse events. Xanthine oxidase inhibitors (allopurinol and febuxostat) are first-line urate-lowering agents. Their effect on UA levels, comorbidities, long-term outcomes (including overall and cardiovascular mortality, development and progression of chronic kidney disease), and occurrence of adverse reactions is studied in large-scale studies, the results of which may affect the strategy of such therapy.The paper discusses the advantages and disadvantages of the CARES (Gout and Cardiovascular Morbidities) study that has compared the cardiovascular safety of allopurinol and febuxostat. The findings suggest that there is no substantial difference in the frequency of cardiovascular events with febuxostat and allopurinol, but at the same time these demonstrate a high risk for cardiovascular and overall mortality in the febuxostat group. Analysis of this paper cannot conclude that there is a greater cardiovascular risk with therapy with febuxostat; however, it shows that when compared with allopurinol, this risk may be higher. A more detailed study of this issue is required after obtaining the results of already started and planned investigations comparing the effects of allopurinol and febuxostat on the risk of adverse cardiovascular events in patients with asymptomatic hyperuricemia.

Peculiarities of purine metabolism at the different forms of gouty arthritis and nephropathy

Objective — to evaluate parameters of purine metabolism in case of complex variants of articular and renal syndromes in patients with gout.Materials and methods. Examinations involved 105 patients with primary gout, from them 92 % of men and 8 % of women aged between 26 to 76 years (51 years on average), and women were 8 years older. The average duration of the disease was 12 years. The first sign of gout was the joint crisis in 91 % of the patients, and renal colic in the rest of cases The ratio of the frequency of intermittent and chronic forms of arthritis was 2 : 1, the latent type of nephropathy occur-red in 66 % of cases, urolithiasis in 34 %, and the ratio of stages I, II, III and IV of chronic kidney disease was 4 : 2 : 1 : 1. The levels of purine metabolism factors were investigated: levels of uric acid in blood and urine (AUb and AUu), and serum levels of oxypurinol — OP, adenine — Ad, guanine — Gu, xanthine — Xa, hypoxanthine — HX, xanthine oxidase — XO, xanthine deaminase — XD, adenosine deaminase — AD, 5 nucleotidase — 5N, molybdenum — Mo, lead — Pb. The renal clearance tests (Cau, Cop, Cau/Cop) were performed. A spectrophotometer SF46 (Russia), an Olympus-AU 640 (Japan) bioanalyzer and an atomic absorption spectrometer with an SolAAr-Mk2-MOZe electrograph atomizer (UK) were used. Patients were examined during absence of arthritis exacerbation.Results and discussion. In cases of gout, the AUb indicators were (514.6 ± 13.65) µmol/l, AUu — (5.0 ± 0.23) µmol/l, Cau — (6.8 ± 0.32) ml/min, OP — (105.9 ± 6.62) µmol/l, Cop — (16.9 ± 0.62) ml/min, Ad — (136.8 ± 3.66) u. e., Gu — (183.7 ± 4.45) u. e., Xa — (148.2 ± 2.72) u. e., HXa — (7.1 ± 0.41) u. e., XO — (7.1 ± 0.41) nmol/ml ⋅ min, XD — (7.7 ± 0.45) nmol/ml ⋅ min, AD — (14,9 ± 2,04) nmol/ml ⋅ min, 5N — (6.0 ± 0.10) nmol/ml ⋅ min, Mo — (1.6 ± 0,08) µg/l, Pb — (63.4 ± 2.77) µg/l. The ratio of Cau to the glomerular filtration rate was (9.7 ± 0.74) %, and Cau/Cop was (53.3 ± 4.94) %. In comparison with the control group of practically healthy people, a significant increase in the parameters of AUb by 90 %, OP — in 10.7 times, XO — in 2.0 times, AD — in 9.3 times and Pb — by 59 % was observed. But the parameters of Cau were decreased by 72 % and Cop — by 15 %, which was established in 100, 93, 38, 98, 53, 100 and 59 % cases of observations respectively. The integral changes in the parameters were enhancing with the increase of the disease duration and were associated with the patients’ gender (men had higher levels of uricemia and urticaria), depended on the form of joint and kidney syndromes, the presence of peripheral and bone tophi, the stage of chronic kidney disease. They determine bone-destructive articular and structural kidney lesions and the character of the urinary syndrome. With this, the negative prognostic signs for the severity of bone-destructive changes in cases of gouty arthritis included blood levels of purine bases Ad > 175 u. e., Gu > 230 u. e., Xa > 175 u. e., HXa > 200 u. e. The blood indices of Pb > 90 µg/l are recommended for prognosing of the kidney function reduction.Conclusions. It has been established that various components of purine metabolism in patients with gout are involved in the pathogenetic development of joint and renal syndromes, the high parameters of purine bases and level of plumbemia have a high prognostic value.

CHRONIC MYELOID LEUKEMIA IN PREGNANCY

Chronic Myeloid Leukemia (CML) is one of leukemias characterized by abnormal growth of myeloid cells in bone marrow. The Philadelphia chromosome is diagnostic parameter for CML. This chromosome is t(9;22) (q32;q21), a translocation chromosome 9 and 22 relocates a portion of proto-oncogene c-ABL from chromosome 9 to BCR on chromosome 22. Chronic myeloid leukemia consisting of three phases; Chronic, Accelerating and the Blast crisis phase. The clinicaling symptoms of CML are hypercatabolism, splenomegaly, anemia, bruising and sign of Gout. Chronic myeloid leukemia in pregnancy shows a better prognosis than acute leukemia in pregnancy. Chronic myeloid leukemia has the risk of leukocytosis which can lead to uteroplacental insufficiency giving rise to various consequences: fetal growth retardation and perinatal mortality. Moreover, the therapy of CML should be carefully administered considering the fetal effects. Both sexes have the same risk, mostly in the range of 40 to 60 years old. In this case report, a 38-year-old pregnant female (G1P0A0) with 37 weeks of gestational age was diagnosed as CML on August 2013 and was treated with 500 mg of Cytodrox/Hydroxyurea twice to three times a day until January 2014. Laboratory evaluation on November 10th, 2014, showed leucocytes 449500/µL, erythrocytes 2.58.106/µL, hemoglobin 8.0 g/dL, thrombocytes 437,000/µL and hematocrit 23%. The peripheral blood smear showed normocytic normochromic erythrocytes, anisocytosis, ovalocytes, significantly increased leucocyte count, predominance polymorphonuclear series, all maturation series of myelocytes, 7% myeloblast, normal thrombocyte count and morphology. Based on these evaluations, the patient was diagnosed as CML. The evaluation of Neutrophil Alkaline Phosphatase (NAP) scored 1.

Metabolic characteristics and renal dysfunction in 65 patients with tophi prior to gout.

Tophi typically occur many years after uncontrolled gout. Therefore, their development before gout remains unusual. Such patients might exhibit some characteristic differences compared with typical tophaceous gout patients. In this study, 65 tophaceous gout patients with tophi as the first sign of gout (tophi-first group) were enrolled. Their clinical characteristics were compared with those of 1421 patients whose tophi occurred after gout (tophi-after group). Compared with the tophi-after group, the tophi-first group had a significantly higher percentage of female patients and patients with elderly onset of disease and a lower percentage of patients with a positive family history; these patients had lower body mass indices, serum urate levels, and estimated glomerular filtration rates (eGFRs). Female sex and negative family history were identified as the principal determinants of tophi development before gout. The decreasing eGFR among the tophi-first group was not due to the group per se but was a result of older age, longer tophi duration, and hyperuricemia. The most common site of initial tophi occurrence in both groups was the toe. In the tophi-first group, the occurrence rates for initial tophi sites were significantly higher at the finger but were lower at the ankle. The tophi-first group exhibited distinct characteristics of age, gender, family history, BMI, serum urate levels, and initial tophi site. This group had fewer comorbidities but similar renal dysfunction compared with the tophi-after group. Thus, patients presenting with tophi should be treated promptly, even if they have no history of gout symptoms.

ULTRASONOGRAPHIC CHANGES IN THE HYALINE CARTILAGE: EVALUATION OF SENSITIVITY AND SPECIFICITY IN EARLY GOUTY ARTHRITIS

A sonographic sign, such as linear hyperechoic inclusions or uric acid deposits in the hyaline cartilage, has been recently introduced into the system of gout classification criteria. At the same time, the differential diagnostic value of this sign in early gouty arthritis (GA) has not been adequately explored. Objective: to evaluate specificity and sensitivity for detecting linear hyperechoic inclusions in the differential diagnosis of early GA in comparison with the increased level of uric acid, the presence of subcutaneous tophi, and the identification of intraosseous cysts at radiography. Subjects and methods. The investigators analyzed the data of examining 119 patients with arthritis with its symptom duration within 6 months at the stage of differential diagnosis. The following diagnoses were further established: GA in 32 patients, osteoarthritis (OA) in 28, rheumatoid arthritis (RA) in 28, and psoriatic arthritis (PsA) in 16. Along with clinical, laboratory, and radiological examinations, all the patients underwent ultrasonography (USG) of inflamed joints with an 18-MHz linear transducer to identify linear hyperechoic inclusions (urate deposits) in the hyaline cartilage. Results and discussion. Joint USG revealed urate deposits in 28 (87.5%) patients with GA, in 3 (10.7%) with OA, and in 1 (6.3%) with PsA. The sensitivity of the other signs of gout in early GA was 21.7% for intraosseous cysts, 25.0% for subcutaneous tophi, and 81.3% for hyperuricemia. The specificity of USG for urate deposits in GA was 94.4% and was comparable with that for the other signs of gout (86.1–98.6%). Conclusion. USG detection of urate deposits in patients with gout is characterized by high sensitivity and specificity for diagnosing GA within the first 6 months after the initial symptoms appear.

Uric acid quantification in fingernail of gout patients and healthy volunteers using HPLC-UV.

The presence of elevated uric acid (UA) levels is a sign of gout, that is, hyperuricemia. In this study the monitoring of the UA levels in less-invasive biological samples, such as the human fingernail, is suggested for the diagnosis and therapy of gout. Twenty-six healthy volunteers (HV) and 22 gout patients (GP) were studied. The UA was extracted from human fingernail samples, then separated on an Inertsil ODS-3 column (250 × 4.6 mm i.d., 4.0 μm, GL Sciences) by isocratic elution using methanol-74 mm phosphate buffer (pH 2.2) 2:98 (v/v). A UV detector was used to monitor the samples at 284 nm. Using the developed method, different UA concentrations were found in the GP and HV. When comparing the concentrations from GP with those from HV, a statistically significant correlation was observed between the UA (p < 0.01). In this study, the UA was confirmed as a potential biomarker for the diagnosis and therapy of gout. We have developed a novel sensitive, and simple method for the determination of UA in the fingernails of GP and HV. The human fingernail may serve as a noninvasive biosample for the diagnosis of gout. Copyright © 2016 John Wiley & Sons, Ltd.

SAT0533 Utility of Joint Ultrasonography in the Diagnosis of Suspected Acute Crystal Arthritis – Results of A Prospective Controlled Study of 90 Patients

BackgroundUltrasound (US) features of gouty and CPP arthritis have been described (1,2), and the technique has been proposed as a diagnostic tool in acute arthritis. There have been limited studies...

The Broad Spectrum of Urate Crystal Deposition: Unusual Presentations of Gouty Tophi

Gout is typically described as an inflammatory arthropathy that affects the peripheral joints. Our aim was to describe atypical and rare clinical presentations of gouty tophi to help increase physician awareness and aid in patient care. The relevant English literature of unusual gout manifestations was searched using the keywords gout, toph*, monosodium urate, uric acid, unusual, and rare. Well-described case reports, case series, and review articles were evaluated and included, if relevant, in the literature review. Review of the literature revealed many unusual manifestations of gouty tophi involving the head and neck, skin, viscera, bones, tendons, ligaments, nerves, and axial skeleton. Transplant recipients, women, and elderly people are particularly susceptible to developing tophi. Furthermore, gout can cause diagnostic dilemmas, as it can be a great mimicker of and can coexist with infection, malignancy, and other connective tissue diseases. Imaging modalities can help detect tophi in atypical locations. Tophi can present in unexpected locations, even as the first sign of gout, and vigilance is required when unusual symptoms or signs occur in a patient with gout.

Tolerance of pyrazinamide in short course chemotherapy for pulmonary tuberculosis in children.

This prospective study was performed to evaluate the tolerance of pyrazinamide in short course chemotherapy in children. A total of 114 children ages 6 months to 15 years (4.5 +/- 3.4 years) with diagnosed pulmonary tuberculosis from 1985 to 1995 entered the trial. A 2-month regimen of isoniazid, rifampin and pyrazinamide, followed by rifampin and isoniazid for the remaining 4 months, was administered orally to all children. Clinical adverse effects specifically investigated were gastrointestinal disturbances, rash, signs of hepatotoxicity and arthralgias. Laboratory toxicity data (number of leukocytes, erythrocyte sedimentation rate, aspartate aminotransferase, alanine aminotransferase and serum uric acid) were collected before treatment and 1, 3 and 5 months after the beginning of chemotherapy. Clinical adverse effects were mild in all cases. Three children (2.6%) had fever and 5 (4.4%) had gastrointestinal disturbances. Aspartate aminotransferase and alanine aminotransferase mean values showed no differences along time and no patients had clinical signs of hepatotoxicity. Only 11 children (19.6%) showed a slight increase in alanine aminotransferase (< 194 units/l). Serum uric acid increased in 92.2% of the children compared with pretreatment values. This increase remained within the normal range in all but 9.8% of patients. There was a significant increase in uric acid mean concentrations after 1 month of therapy (from 3.7 +/- 0.7 mg/dl to 5.7 +/- 1.6 mg/dl, P < 0.05), which fell again (4.0 +/- 1.1) 1 month after pyrazinamide was stopped. There were no signs of gout or arthralgias. In no case was the treatment interrupted. The addition of pyrazinamide in chemotherapy for pulmonary tuberculosis in children was found to be safe. The slight increase in uric acid concentration during its administration had no recognized adverse consequences.