Free serum histidine levels in patients with rheumatoid arthritis and control subjects following an oral load of free L-histidine.

A dose of 3.7 g of free-L-histidine was administered by mouth to 26 patients with active rheumatoid arthritis and to 29 control subjects. The patients with rheumatoid arthritis had a statistically significant (p=10(-12)) lower pretreatment concentration of free histidine in serum (1.20 mg/100 ml, SE=0.04) than the control subjects (1.90 mg/100 ml, SE=0.06). However, there were no statistically significant differences between rheumatoid and control subjects with respect to the serum histidine concentrations 1 hr, 3 hr, and 4 hr after the ingestion of L-histidine. The changes in the serum histidine concentrations at 1 hr, 3 hr, and 4 hr (compared to the pretest values) were also not significantly different in the patients with rheumatoid arthritis relative to the control subjects. This study suggests that the subnormal free serum histidine concentration of rheumatoid arthritis is not associated with abnormal serum levels of free histidine following an oral load of free histidine.     

类风湿性关节炎患者血清游离氨基酸变化及其临床意义

目的了解类风湿性关节炎（ＲＡ）患者血清游离氨基酸的变化及其临床意义。方法应用高效液相色谱分析法分析了２５例ＲＡ患者血清中２７种游离氨基酸的变化,并与正常人血清游离氨基酸做比较。结果（１）ＲＡ患者血清中存在着多种氨基酸代谢紊乱,包括支链氨基酸与芳香族氨基酸比值（ＢＣＡＡ／ＡＡＡ）的降低（Ｐ＜００１）和必需氨基酸与非必需氨基酸（ＥＡＡ／ＮＥＡＡ）比值的降低（Ｐ＜００５）;（２）单剂量氨甲喋呤（７５ｍｇ）静脉注射后血清中谷氨酸、天冬氨酸、苏氨酸、酪氨酸升高,ＢＣＡＡ／ＡＡＡ比值进一步降低（Ｐ＜００５）。结论（１）ＲＡ患者在氨甲喋呤治疗前已有肝功能的异常,治疗后此种异常加重;（２）对长期应用氨甲喋呤治疗的ＲＡ患者进行选择性补充氨基酸治疗可能对保护肝功能及缓解病情有利。     

Decreased plasma fibrinolysis in patients with rheumatoid arthritis.

We have investigated the fibrinolytic status of 56 patients with rheumatoid arthritis (RA). Plasma fibrinogen and plasminogen were significantly elevated. Levels of these two substrates, along with alpha 2 macroglobulin and antithrombin III correlated with disease activity. Plasminogen activator (PA) activity was decreased in patients with severe disease. Twelve patients were given stanozolol, a fibrinolytic enhancing agent, for two months as a test for endothelial production of plasminogen activator. This caused a significant increase in blood plasminogen and PA activity. Five patients received a two-week course of stanozolol with joint aspiration before and after. Joint plasminogen levels were increased. We suggest that inadequate fibrinolysis occurs in RA, and that this may contribute to some of the pathological features of the disease. It is possible to stimulate both blood and joint fibrinolysis by stanozolol. A more prolonged increase in plasminogen activator activity might decrease joint fibrin deposition, and stanozolol should be investigated as a therapeutic agent in RA.     

Kinetic investigations into the possible cause of low serum histidine in rheumatoid arthritis.

To investigate the cause of low serum histidine in rheumatoid arthritis (RA) single oral and intravenous doses of L-histidine were administered to patients with active RA, and to an equal number of age and sex matched control subjects. In the first study 13 patients and their controls received a 100 mg kg-1 dose of L-histidine as an aqueous slurry. Significant differences were seen in body weight, predose baseline serum histidine concentration, Cmax, t1/2, and area under curve, AUC0-infinity. In a second study six patients and six controls each received a 50 mg kg-1 dose of L-histidine both orally and intravenously on two separate occasions. The patients with RA had a lower baseline serum histidine concentration, a lower volume of distribution, and a shorter plasma half life than the controls, but these differences were not statistically significant. No difference was seen in bioavailability or clearance. Low serum histidine in RA is unlikely to be due to malabsorption from the gut, uptake by abnormal gut flora, or increased metabolism.     

Elevation of serum IgG subclass concentration in patients with rheumatoid arthritis

A new concept of IgG subclass such as IgG4-related systemic disease including autoimmune pancreatitis, characterized by a high-serum IgG4 level, has been proposed. Our aim was to investigate serum IgG subclass levels in rheumatoid arthritis (RA). IgG subclass levels of sera from 72 patients with rheumatoid arthritis were determined by immunonephelometric assay. The patients were divided into two groups according to clinical activity of the disease: active disease and remission. The sera from 45 normal controls were also measured. All statistical analyses were carried out with SPSS software version 13.0. We found a significant increase of all the four IgG subclass concentrations in sera of patients with RA compared to those of the controls (P < 0.001). When the patients were divided according to clinical activity, the IgG subclass concentrations were similar between the two groups (P > 0.05). Our data suggest that besides IgG1, IgG2 and IgG3, IgG4 may involve in the pathogenesis of the disease.     

A specific HLA-DP beta allele is associated with pauciarticular juvenile rheumatoid arthritis but not adult rheumatoid arthritis.

Nonradioactive sequence-specific oligonucleotide probes specific for the HLA-DP beta locus have been used in a simple dot-blot format to type samples amplified by the polymerase chain reaction from 44 patients with pauciarticular juvenile rheumatoid arthritis, 32 patients with adult rheumatoid arthritis, and 50 random controls. The sequences of four new DP beta alleles derived from these patients and controls are reported, bringing the total number of alleles identified thus far to 19. The DPB2.1 allele is significantly increased in juvenile rheumatoid arthritis patients over controls; this allele is not increased in patients with adult rheumatoid arthritis. The association of juvenile rheumatoid arthritis with the DPB2.1 allele is independent of linkage with previously defined HLA-D region markers of disease. Analysis of the DPB2.1 sequence shows that it differs from the nonsusceptible DPB4.2 allele by only 1 amino acid at position 69 in the beta 1 domain.     

Defective polymorphonuclear leucocyte chemotaxis in rheumatoid arthritis associated with a serum inhibitor.

Cellular and/or serum components of polymorphonuclear leucocyte chemotaxis were assessed in 21 patients with rheumatoid arthritis. No difference in the chemotactic migration of control and patient cells in response to a number of chemotactic solutions could be detected (P = 0.38). Deficient generation of chemotactic activity in patient sera (P = 0.58) as compared to control sera (P = 0.014) after incubation of the sera with Escherichia coli lipopolysaccharide, resulted in a significant difference in the chemotactic activity of the control and rheumatoid serum preparations for polymorphonuclear leucocytes (P = 0.0012). This defect was associated with the presence of a serum inhibitor of chemotaxis, the potency of which was inversely correlated with the level of chemotactic activity generated in the rheumatoid sera (r = -0.941, P less than 0.001).     

Association of rheumatoid arthritis with an amino acid allelic variation of the T cell receptor

Objective. To investigate allelic variations of T cell receptor residues for a contribution to rheumatoid arthritis (RA) susceptibility. Methods. We conducted an RA case-control study involving 1,579 northwest Europeans: 766 patients with erosive and rheumatoid factor-positive disease and 813 control subjects. Productive changes of segments TCRAV6S1, TCRAV7S1, TCRAV8S1, TCRAV10S2, and TCRBV6S1, TCRBV6S7 were investigated by single-strand conformation polymorphisms. The TCRAV8S1 association was confirmed by restriction fragment length polymorphism. Results. In the systematic study (77 patients and 119 controls), an increase in 1 TCRAV8S1 genotype was found in the RA patients (P = 0.0004). This finding was replicated in 2 further populations, one from France (212 patients and 254 controls) and the other from Britain (477 patients and 440 controls), with a similar odds ratio (OR), which allowed pooling of the data and confirmation of the association (OR 1.3 [95% confidence interval 1.1-1.7], P = 0.008). Conclusion. These findings show evidence that TCRA is an RA susceptibility locus.     

Leptin serum levels are not correlated with disease activity in patients with rheumatoid arthritis.

Leptin, the ob gene product, has been proposed as a mediator of inflammatory cytokine-dependent decreased food intake and cachexia in rodents. In humans, leptin serum levels increase after administration of tumor necrosis factor-alpha (TNF-alpha) or interleukin-2 or during septicemia. However, the effect of human chronic inflammatory disease on serum leptin is unknown. We therefore determined the serum leptin level (radioimmunoassay), body mass index (BMI), percent body fat ([%BF] bioelectrical impedance analysis), and disease activity (Disease Activity Score [DAS]) in 58 patients with rheumatoid arthritis (RA) and 16 controls. The BMI, %BF, serum leptin, and ratio of leptin to %BF (leptin/%BF) did not differ significantly in 25 patients with moderate RA activity (DAS, 3.6 +/- 0.5), 33 patients with low RA activity (DAS, 1.8 +/- 0.5), and controls. A positive correlation for serum leptin and %BF was detected in all groups. Our data indicate that in RA, a human chronic cytokine-mediated inflammatory disease, the serum leptin level is directly related to %BF but not to disease activity.     

Association of serum uric acid with cardiovascular disease in rheumatoid arthritis

OBJECTIVES: Elevated serum uric acid (SUA) levels have been associated with cardiovascular disease (CVD) in the general population. Rheumatoid arthritis (RA) is not thought to associate with high SUA but is characterized by increased CVD morbidity and mortality. We aimed to explore a potential association of SUA with CVD in RA patients and to evaluate whether such an association is present when the traditional CVD risk factors are taken into account. METHODS:. 400 consecutive RA patients were recruited in this cross-sectional study and had all traditional CVD risk factors and SUA assessed. The association of SUA levels with other variables was assessed using bivariate correlations. Subsequent binary logistic models with appropriate adjustments were used to test the independence of the association between SUA and CVD. RESULTS: SUA levels were significantly higher in RA patients with CVD (RA + CVD) compared with RA patients without CVD (RA - CVD) (5.68 +/- 1.81 mg dl(-1) vs 5.06 +/- 1.41 mg dl(-1), P = 0.001). After adjusting for CVD risk factors, physical function (health assessment questionnaire, HAQ) and use of diuretics and/or statins the association between SUA and CVD in RA patients remained significant [Odds ratio (OR) = 1.36, 95% confidence interval (CI) 1.04-1.79, P = 0.025]. Compared with subjects with SUA levels in the lowest quintile (<3.86 mg dl(-1)), those within the highest quintile (>/=6.38 mg dl(-1)) had a 6-fold increase in the odds of having CVD (adjusted OR 6.46, 95% CI 1.66-25.05, P = 0.007). CONCLUSIONS: This cross-sectional study suggests that SUA may be independently associated with CVD in RA patients. This needs to be confirmed in prospective studies.     

A tumour necrosis factor alpha polymorphism is not associated with rheumatoid arthritis.

OBJECTIVE--To determine whether a polymorphism within the tumour necrosis factor alpha (TNF alpha) gene is associated with susceptibility to, or severity of, rheumatoid arthritis (RA). METHODS--Consecutive patients with recent onset RA were enrolled in a prospective trial. DNA was collected, disease activity was measured at presentation, and radiographic progression at three years was assessed. Typing of TNF alpha was by polymerase chain reaction and single stranded conformation polymorphism analysis. RESULTS--No association of TNF alpha alleles and susceptibility to, or severity of, RA was demonstrated. CONCLUSIONS--These results indicate that this TNF alpha polymorphism does not play a part in the genetic background of RA.     

Correlations between transaminase concentrations and serum salicylate concentration in juvenile rheumatoid arthritis.

Simultaneous measurements of serum salicylate, SGPT, and SGOT concentrations were made on 92 children receiving salicylates for arthritis during a 13-month period. Statistical correlations were found between salicylate and transaminase concentrations in patients with juvenile rheumatoid arthritis when in active stages. However elevated transaminase levels occurred with low salicylate levels and during inactive stages, and were inconstant in individual patients. Marked transaminase abnormalities were transient and appeared unpredictably in individual patients. Some factor in addition to salicylate concentration must be involved in raising serum transaminase levels. No evidence of chronic hepatotoxicity was noted.     

Subsidence of total ankle component associated with deterioration of an ankle scale in non-inflammatory arthritis but not in rheumatoid arthritis

Objectives: Modern three-component total ankle arthroplasty (TAA) has favorable clinical results and survival rates. However, radiographic deterioration and worsening of clinical symptoms may occur in patients with rheumatoid arthritis (RA) or non-inflammatory arthritis (NA). The associations between outcomes and clinical and radiological factors are not clear. We compared midterm clinical and radiographic outcomes after TAA between patients with RA and those with NA.

Methods: Twenty-six TAAs were performed using a three-component prosthesis, the FINE Total Ankle System during the study period. Fourteen TAAs with 11 RA patients undergoing primary TAA were compared with twelve TAAs with 12?NA patients. Clinical and radiographic outcomes were evaluated before and after operation, and at the final follow-up.

Results: The Japanese Society for Surgery of the Foot (JSSF) scale improved significantly following TAA in both groups (p?=?0.0039 and 0.0156, respectively). Tibial subsidence, talar subsidence and age were significantly associated with postoperative JSSF score only in the NA group (p?=?0.0027, 0.0017 and p?F?=?10.3).

Conclusions: The final clinical outcome was negatively influenced by talar subsidence in patients with NA, but not in those with RA.     

Decreased iron absorption in patients with active rheumatoid arthritis, with and without iron deficiency.

Mucosal uptake, mucosal transfer, and retention of a physiological dose of ferrous iron were studied in women with active rheumatoid arthritis (RA): 19 with normal and 17 with depleted bone marrow iron stores. Control subjects were 26 normal women and 20 women with uncomplicated iron deficiency. Iron absorption was measured with 59Fe as a tracer and by whole body counting. Compared with controls, final iron retention was considerably decreased in both groups of patients with RA. Analysis of the two sequential steps of iron absorption showed that mucosal uptake was normal in iron replete patients with RA but was significantly lower in patients with RA with depleted iron stores compared with iron deficient controls. Mucosal transfer of iron was considerably decreased in patients with RA with normal iron stores. The impaired absorption of iron in patients with active RA may delay the correction of the haemoglobin concentration when anaemia of chronic disease is complicated by iron deficiency.     

Serum osteoprotegerin concentration is associated with carotid atherosclerotic plaque in patients with rheumatoid arthritis

Objective

Osteoprotegerin (OPG), a regulator of bone resorption, is involved in the pathogenesis of rheumatoid arthritis (RA) and atherosclerosis. OPG is elevated in patients with coronary artery disease, and high OPG levels are associated with cardiac disease severity and mortality in the general population. The purpose of this study was to investigate the relationship of serum OPG levels, traditional coronary risk factors, and RA-related factors to carotid atherosclerosis in RA patients.

Methods

Ninety-one RA patients were studied (85 % women, age 60 ± 10 years). Serum OPG levels were measured by an enzyme-linked immunosorbent assay. The prevalence of carotid plaque was assessed by ultrasonographic imaging in all patients. The relationship between various clinical characteristics, OPG, and carotid plaque was examined.

Results

Serum OPG levels were significantly higher in patients with carotid plaque than in those without plaque (median level 1,397 vs. 887 pg/mL, respectively; P = 0.006). There were no significant differences between RA patients with and without carotid plaque with respect to sex, duration of RA, blood pressure, body mass index, smoking, low-density lipoprotein cholesterol, Disease Activity Score-28, van der Heijde-modified Sharp score, and prednisolone dose. After adjusting for age, sex, and C-reactive protein, elevated levels of OPG were still associated with a higher prevalence of carotid plaque in patients with RA (P = 0.038).

Conclusion

RA patients suffer from accelerated atherosclerosis and also have increased levels of OPG. The serum OPG level is independently associated with carotid plaque.     

Initial methotrexate dosage is not associated with an increased risk of liver toxicity in patients with rheumatoid arthritis

Clinical Rheumatology - The objective of this study is to determine whether an initial methotrexate (MTX) dosage is associated with an increased risk of liver toxicity in patients with rheumatoid...