Increased prevalence of JC polyomavirus viruria was associated with arthritis/arthralgia in patients with systemic lupus erythematosus.

OBJECTIVE: The objective of this paper is to investigate the prevalence of reactivation of the human polyomavirus John Cunningham virus (JCV) in patients with systemic lupus erythematosus (SLE) and its associated clinical manifestations. METHODS: Sixty-one patients with SLE and 22 controls were enrolled. Urine JCV viral load was quantified by real-time polymerase chain reaction (PCR). Length variants of the VP1 gene were analyzed using capillary electrophoresis. RESULTS: The prevalence of JCV viruria (63.9% vs. 18.2%, p < 0.001) and urine JCV viral load (2.92 ± 2.76 vs. 0.81 ± 1.85 copies/ml by log10 scale, p < 0.001) were significantly higher in patients with SLE compared with controls. JCV viruria (+) SLE patients had a higher occurrence of arthritis/arthralgia compared with JCV viruria (-) SLE patients (64.1% vs. 22.7%, p = 0.003). In SLE patients, the urine JCV viral load was significantly associated with the occurrence of arthritis/arthralgia. SLE patients with urine JCV viral load >10,000 copies/ml exhibited a 12.75-fold (95% confidence interval 2.88-56.40) risk in clinical arthritis/arthralgia, 18.90-fold (95% confidence interval 2.10-170.39) risk in persistent arthritis, and significantly greater number of length variants in the VP1 gene of JCV compared with JCV viruria (-) SLE patients. CONCLUSION: Reactivation of JCV in the urinary tract of SLE patients was very common. Both JCV viruria and urine JCV viral load were associated with the occurrence of arthritis/arthralgia in patients with SLE. High urine JCV viral load also was associated with the genetic variant in the VP1 gene.

A case report of spontaneous polyarthritis in cynomolgus monkeys.

Veterinary x-ray photography and examinations of synovial fluid, blood and urine were conducted on a Cynomolgus Monkey from China (5 years old) which exhibited macroscopically visible systemic joint swelling after the quarantine period. The presence of inflammatory cells in the synovial fluid obtained by arthrocentesis, high counts of neutrophils, monocytes and large unstained cells and the elevated serum CRP level suggested that the lesions in this animal were due to polyarthritis.

Prediction of response of collagen-induced arthritis rats to methotrexate: an (1)H-NMR-based urine metabolomic analysis.

Over one half the patients with rheumatoid arthritis (RA) are being treated with methotrexate (MTX). Although well proven, the efficacy of MTX varies in individual patients. This study examined the metabolic biomarkers that can be used to predict the therapeutic effect of MTX by using metabolomic analysis. Rats were immunized with collagen to rapidly cause collagen-induced arthritis (CIA) and then treated with 0.1 mg/kg MTX for 4 weeks. The clinical signs and the histopathological features of CIA were observed to evaluate the therapeutic effects. Urine samples of CIA rats were collected, and analyzed by using 600 M (1)H-nuclear magnetic resonance ((1)H-NMR) for spectral binning after the therapy. The urine spectra were divided into spectral bins, and 20 endogenous metabolites were assigned by Chenomx Suite. Multivariate analyses were performed to identify the spectral pattern of endogenous metabolites related to MTX therapy. The results showed that the clustering of the spectra of the urine samples from the responsive rats (n=20) was different from that from the non-responsive rats (n=11). Multivariate analysis showed difference in metabolic profiles between the responsive and non-responsive rats by using partial least squares-discrimination analysis (PLS-DA) (R(2)=0.812, Q(2)=0.604). In targeted profiling, 13 endogenous metabolites (uric acid, taurine, histidine, methionine, glycine, etc.) were selected as putative biomarkers for predicting therapeutic response to MTX. It was suggested that (1)H-NMR-based metabolomic analysis can be used to predict the therapeutic effect of MTX, and several metabolites were found to be related to the therapeutic effects of MTX.

Urinary heavy metals and associated medical conditions in the US adult population.

Health effects of heavy metals have been widely investigated, but further evaluation is required to comprehensively delineate their toxicity. Using data from the 2007-2008 National Health and Nutrition Examination Survey, a multivariate logistic regression analysis was performed on 1,857 adults to examine the relationship between urinary heavy metals and various medical conditions. Cardiovascular diseases were correlated to cadmium (OR: 4.94, 95% CI: 1.48-16.56) and lead (OR: 5.32, 95% CI: 1.08-26.21). Asthma was related to tungsten (OR: 1.72, 95% CI: 1.15-2.59) and uranium (OR: 1.52, 95% CI: 1.01-2.28). Hepatotoxicity was associated with molybdenum (OR: 3.09, 95% CI: 1.24-7.73) and uranium (OR: 4.79, 95% CI: 1.74-13.19). Surprising inverse relationships occurred for excessive weight with lead (OR: 0.72, 95% CI: 0.52-0.98), reduced visual acuity with cobalt (OR: 0.65, 95% CI: 0.44-0.95) and cesium (OR: 0.52, 95% CI: 0.35-0.77). This study supports some previous evidence of potential relationships and provides insights for future research.

Nephrogenic adenoma of bladder after ibuprofen abuse.

Nephrogenic adenoma is an infrequent benign lesion of the urinary system that occurs in patients with a history of genitourinary surgery, stone disease, trauma, chronic urinary tract infection, or renal transplantation. We report the first case of nephrogenic adenoma of the bladder in a 53-year-old man with a 5-year history of ibuprofen abuse for chronic arthritis. We stress the importance of investigating the analgesic abuser for nephrogenic adenoma if microhematuria and/or irritative lower urinary tract symptoms are present.

Evaluation of free and peptide bound collagen crosslink excretion in different skeletal diseases.

OBJECTIVE: To investigate urinary fractions of free and peptide forms of collagen crosslinks in patients with rheumatoid arthritis (n=50), osteoarthrosis (n=38), psoriatic arthritis (n=38) and in healthy volunteers (33 adults, 17 children). METHODS: Pyridinoline (PYD) and deoxypyridinoline (DPD) were measured by high performance liquid chromatography. RESULTS: In rheumatoid arthritis (RA) all fractions of PYD and DPD were significantly raised compared with osteoarthritis, psoriatic arthritis, and healthy controls. PYD and DPD correlated with disease activity in RA. In RA the collagen degradation resulted in primarily peptide bound forms. CONCLUSION: The correlation between total peptide bound or free collagen crosslinks in different chronic joint diseases varies; however, this variation does not allow for a reliable differentiation between inflammatory and degenerative joint diseases.

Antihypertensive effect of the combination of fosinopril and HCTZ is resistant to interference by nonsteroidal antiinflammatory drugs.

Nonsteroidal antiinflammatory drugs (NSAID) are frequently reported to interfere with the blood pressure lowering actions of various antihypertensive medications. We studied 17 women with arthritis and hypertension who were receiving fosinopril and HCTZ, and administered sequentially in random order ibuprofen, sulindac, and nabumetone for 1 month each, with an intervening 2-week washout period between each treatment period. During the washout period, subjects received acetaminophen. Blood pressure at the end of 2 weeks of acetaminophen was compared with blood pressure after 1 month of treatment with each of the NSAID. Mean blood pressure was unchanged before and after all NSAID: 108 +/- 7 v 107 +/- 9 for nabumetone, 108 +/-9 v 108 +/- 9 for sulindac, and 108 +/- 8 v 107 +/- 9 for ibuprofen. The 24-h urinary sodium excretion was not significantly different. We conclude that the three NSAID did not neutralize the antihypertensive effect of the combination of fosinopril and HCTZ, and hence the blood pressure lowering action of the combination may not be prostaglandin dependent.

[Detection of Borrelia DNA in urine using polymerase chain reaction in rheumatologic laboratory diagnosis of Lyme borreliosis]. / Nachweis von Borrelien-DNA im Urin mittels Polymerase-Kettenreaktion in der rheumatologischen Labordiagnostik der Lyme-Borreliose.

Borrelia burgdorferi specific DNA has been detected by polymerase chain reaction (PCR) in different specimens of patients with Lyme disease (LD). The aim of the present study is to evaluate PCR-diagnostic of urine specimens regarding rheumatologic diagnosis of Lyme disease. Urine specimens of 77 patients (LD, n = 34; undifferentiated arthritis (UA), n = 25; arthralgia/myalgia (AM), n = 18) and 15 controls were investigated. Flagellin gene (60 specimens) or OspA-plasmid (32 specimens) were used as targets. Sensitivity of the flagellin-nested-PCR was 27%, by OspA-nested-PCR only one positive PCR result was found. Despite of low sensitivity PCR enabled the correct diagnosis of LD in two patients classified as UA. Therefore, PCR can give valuable hints in single cases if LD is clinically suspected.

Tranexamic acid, an inhibitor of plasminogen activation, reduces urinary collagen cross-link excretion in both experimental and rheumatoid arthritis.

The plasminogen activation system is one of the enzyme systems held responsible for bone and cartilage degradation in rheumatoid arthritis (RA). In this study, we evaluated the effect of tranexamic acid (TEA), an inhibitor of plasminogen activation, on urinary collagen cross-link excretion and radiological joint damage in rat adjuvant arthritis (AA) and on urinary collagen cross-link excretion in patients with RA. In the animal study, adjuvant arthritis was induced in male Lewis rats. From day 7 onward, high-dose TEA (500 mg/kg body weight, once daily) or placebo was administered orally. Study groups consisted of TEA-treated normal rats (C + TEA), placebo-treated normal rats (C + plac), AA rats treated with TEA (AA + TEA) or with placebo (AA + plac). To monitor joint destruction, urinary collagen cross-link excretion (pyridinoline, HP; deoxypyridinoline, LP) was measured by high-performance liquid chromatography at days 14 and 21. Radiological evaluation of joints was performed at day 21. In the patient study, TEA was administered to nine patients with RA as adjuvant medication (approximately 20 mg/kg body weight, three times daily) for 12 weeks. Urinary HP and LP excretion levels were measured before and during TEA treatment, and 4 weeks after the cessation of TEA treatment. In AA + TEA rats, a significant reduction of HP and a tendency towards a reduction of LP excretion were found compared with AA + plac rats (P < 0.05), at day 14, whereas the HP/LP ratio did not change. No difference was observed in HP, LP excretion, HP/LP ratio and radiological damage score between the TEA- and placebo-treated AA rats at day 21. In RA patients, a significant reduction of HP and LP excretion was found during the TEA treatment period (P < 0.05). After the cessation of TEA treatment, HP and LP excretion increased towards baseline levels. No effect on disease activity was observed. The plasmin antagonist TEA reduced the excretion of collagen pyridinoline cross-links in both experimental and rheumatoid arthritis. As such, this study not only supports the involvement of the plasminogen activation system in the destructive phase of arthritis, but also suggests a beneficial effect of therapeutic strategies directed against inhibition of matrix proteolysis.

Urinary glucaric acid excretion in rheumatoid arthritis: influence of disease activity and disease modifying drugs.

OBJECTIVE: To examine if a correlation exists between cytochrome P-450 enzyme induction and disease activity in patients with rheumatoid arthritis (RA), measuring urinary excretion of D-glucaric acid (GA) as an index of phase II drug metabolism. METHODS: Patients with RA were treated with sulphasalazine, sodium aurothiomalate, or D-penicillamine in standard dose regimens, for 24 weeks. Patients with ankylosing spondylitis (AS) or non-inflammatory arthritis (NIA) acted as controls. The urinary GA:creatinine ratio was measured at 0, 12, and 24 weeks of treatment. RESULTS: Patients with RA had a slightly greater urinary GA:creatinine ratio than patients with AS or NIA at baseline; this increased during treatment with disease modifying antirheumatic drugs (DMARDs). Sulphasalazine treatment had a greater effect on GA excretion than sodium aurothiomalate or D-penicillamine; this difference was statistically significant between weeks 0 and 12 (p = 0.01). Gamma glutamyltranspeptidase concentration showed a weak correlation with GA excretion between weeks 0 and 12 (p = 0.03), but all other measurements of changes in disease activity (plasma viscosity, C reactive protein, platelets, and articular index) were found not to correlate with GA excretion between weeks 0-12 or 0-24. CONCLUSION: The increased excretion of GA in patients with RA receiving DMARD treatment is probably the result of an indirect effect on hepatic metabolism bearing no relationship to disease activity.

Interference by nonsteroidal anti-inflammatory drugs in EMIT and TDx assays for drugs of abuse.

Fourteen nonsteroidal anti-inflammatory drugs were evaluated for interference in EMIT and TDx assays for drugs of abuse. Only tolmetin demonstrated significant interferences in the EMIT assay. Urine samples that contained high concentrations of tolmetin (1800 mg/L) had characteristic high molar absorptivity at the wavelength used in EMIT assays (340 nm). Consequently, EMIT analysis of samples resulted in instrument error alarms on a Hitachi 704 instrument and depressed milliabsorbance values (delta A) relative to calibrators. Similar results were obtained with urine samples collected from an arthritic patient after the administration of 200 and 400 mg of tolmetin. When tolmetin samples were mixed with drugs of abuse, depressed delta A values were noted in all assays. Samples containing opiates and cannabinoids tested negative, and instrument error alarms were produced with samples that contained amphetamines. A gas chromatographic-mass spectrometric (GC-MS) assay for benzoylecgonine in the presence of tolmetin was successful, and no interferences were noted. Similar interferences by tolmetin were not observed in TDx assays, probably because of the different wavelength (525 nm) used in this assay. However, a potential for false-positive results in the TDx benzodiazepine assay was noted for urine samples containing high concentrations of fenoprofen, flurbiprofen, indomethacin, ketoprofen, and tolmetin. Generally, it was concluded that the presence of tolmetin in urine samples could lead to the production of unacceptable results by the EMIT assay for drugs of abuse. However, TDx and GC-MS assays were useful alternatives for the analysis of urine samples suspected of containing tolmetin.

[Assay of cross-linking molecules of collagen (pyridinolines) in the study of the degradation of bone tissue and articular cartilage]. / Le dosage des molécules de pontage du collagène (pyridinolines) dans l'étude de la dégradation du tissu osseux et du cartilage articulaire.

Recent studies aimed at studying the degradation of the fibrillar collagens of bone and articular cartilage have lead to the discovery of naturally fluorescent crosslinking compounds derived from lysine and hydroxylysine. These small molecules characterized by an aromatic 3-hydroxypyridinium ring are present in significant amounts only in bone (pyridinoline and deoxy-pyridinoline) and cartilage (pyridinoline). Diseases characterized by an increased degradation of the fibrillar collagenous network are associated with an increased urinary excretion of both compounds: Pyridinoline and deoxypyridinoline are currently the most sensitive and specific markers of bone resorption. The purpose of this paper is to review current knowledge in the area of collagen crosslinking molecules with special emphasis on the pyridinium crosslinking amino acids and their potential clinical application as a marker of bone and cartilage degradation.

Renal disease in chronic arthritis of childhood. A study of urinary N-acetyl-beta-glucosaminidase and beta 2-microglobulin excretion.

Urinalyses of randomly obtained samples from children with various types of chronic arthritis revealed proteinuria in 2.3% of patients, hemoglobinuria in 3.5%, erythrocyturia in 4.1%, and leukocyturia in 5.3%; these frequencies are within the range found by screening school children. However, raised urinary levels of N-acetyl-beta-glucosaminidase and/or beta 2-microglobulin (both sensitive measures of renal tubular damage) were found more frequently in children with chronic arthritis than in controls (P less than 0.0001). Abnormalities of either N-acetyl-beta-glucosaminidase or beta 2-microglobulin excretion were associated with active arthritis as measured by physician global estimate of disease activity, with a polyarticular onset of juvenile rheumatoid arthritis, and with the use of slow-acting antirheumatic drugs or the concurrent use of more than 1 nonsteroidal antiinflamtory drug. Abnormal renal tubular function appears to be common in chronic arthritis of childhood. The long-term consequences of this abnormality remain to be elucidated.

Compared effects of isoxicam and indomethacin on the urinary excretion of prostaglandins in degenerative articular diseases.

The effects of a 7 day-treatment with isoxicam (200 mg/24 h) on the urinary excretion of prostaglandins (PG) were compared to those of indomethacin (150 mg/24 h) in a double-blind randomized study conducted in 18 patients with degenerative arthritic disease and normal renal function. Indomethacin decreased the urinary excretion of PGF2 alpha by about 70% and 6-keto-PGF1 alpha and thromboxane (Tx)B2, the stable break-down products of prostacyclin and TxA2 respectively, by about 40%. Isoxicam effects on urinary PG did not significantly differ from those of indomethacin. During both treatments, urinary gamma-glutamyl transferase and N- acetyl-glucosaminidase remained stable and none of the changes in the urinary excretion of PGs could be related to either plasma or urinary drug concentrations. In conclusion, chronic administration of isoxicam inhibited the renal PG biosynthesis to a similar extent than indomethacin which suggests that non steroidal anti-inflammatory drugs of the oxicam group ought also be used cautiously in patients with renal impairment.

[The effect of indomethacin and dexamethasone on the excretion of epinephrine, levarterenol and dopamine in the urine of rats with adjuvant arthritis]. / Einfluss von Indometacin bzw. Dexamethason auf die Ausscheidung von Epinephrin, Levarterenol und Dopamin im Urin von Ratten mit Adjuvansarthritis.

The repeated application of indometacine or dexamethasone on rats with adjuvant arthritis results in a most cases significant inhibition of the arthritis in the primary and secondary phase as well as in a normalisation of the increased urinary excretion of epinephrine and norepinephrine of untreated arthritis rats. The dopamine excretion of adjuvant arthritis rats was also higher then the prepared rats. We suppose, that the results show the regulative endogenous excretion of epinephrine and norepinephrine in inflammatory processes. Consequently these drugs have essentially antiinflammatory activities. The inhibition of the inflammation is than connected with the normalisation of the excretion of catecholamines.