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ID PMID Title PublicationDate abstract
16545987 Angiogenesis--a new target for future therapy. 2006 May Development of blood vessels from in situ differentiating endothelial cells (EC) is called vasculogenesis, whereas sprouting of new blood vessels from the pre-existing ones is termed angiogenesis or neovascularisation. Angiogenesis, the growth of new blood vessels, is essential during tissue repair, foetal development, and female reproductive cycle. In contrast, uncontrolled angiogenesis promotes tumor and retinopathies, while inadequate angiogenesis can lead to coronary artery disease. A balance between pro-angiogenic and anti-angiogenic growth factors and cytokines tightly controls angiogenesis. With the identification of several proangiogenic molecules such as the vascular endothelial cell growth factor (VEGF), the fibroblast growth factors (FGFs), and the angiopoietins, and the recent description of specific inhibitors of angiogenesis such as platelet factor-4, angiostatin, endostatin, and vasostatin, it is recognized that therapeutic interference with vasculature formation offers a tool for clinical applications in various pathologies. Inhibition of angiogenesis can prevent diseases such as cancer, diabetic nephropathy, arthritis, psoriasis, whereas stimulation of angiogenesis is beneficial in the treatment of coronary artery disease (CAD), cardiac failure, tissue injury, etc. One of the most specific and critical regulators of angiogenesis is vascular endothelial growth factor (VEGF), which regulates endothelial proliferation, permeability, and survival. Substantial evidence also implicates VEGF as an angiogenic mediator in tumors and intraocular neovascular syndromes, and numerous clinical trials are presently testing the hypothesis that inhibition of VEGF may have therapeutic value.
16821276 Anti-tumor necrosis factor-alpha-induced psoriasis. 2006 Jul We describe a patient with rheumatoid arthritis who developed psoriasis during treatment with etanercept; psoriatic lesions resolved completely after the drug was discontinued, but returned on rechallenge. No such adverse skin reaction occurred after switching therapy to infliximab. Through a Medline search we identified 11 reports involving 32 patients who developed psoriasis/psoriasiform eruptions during therapy with tumor necrosis factor-alpha (TNF-alpha) inhibitors. All TNF-alpha blocking agents have been reported to lead to or exacerbate psoriasis. In some cases skin changes were severe enough to discontinue the medication.
16008691 Epstein--Barr virus-associated B-cell lymphoma in the setting of iatrogenic immune dysregu 2005 Aug BACKGROUND: Epstein-Barr virus (EBV) has been implicated in B-cell lymphoma associated with iatrogenic immune dysregulation, primarily in the context of extracutaneous lymphoma. METHODS: We describe six patients, five transplant recipients receiving cyclosporine and one patient with rheumatoid arthritis receiving methotrexate, who developed cutaneous presentations of EBV-associated B-cell lymphoma. Human herpesvirus 8 (HHV8) and EBV thymidine kinase (vTK) expression were also explored. RESULTS: The cases comprised plasmablastic lymphoma (one case), plasmacytic marginal zone lymphoma (two cases), and diffuse large B-cell lymphoma (three cases). There was a monoclonal gammopathy in one and concurrent extracutaneous disease in two of the six patients. EBV-associated latent small nuclear RNA was detected in all cases with coexpression of HHV8 in one of the five cases and of vTK in three of the six cases. Three patients responded to a reduction in the immunosuppressive regimen and antiviral therapy. Recurrent disease developed in two, with one patient succumbing to multiorgan dissemination. CONCLUSIONS: EBV-associated cutaneous B-cell lymphoma is characterized by a long interval between the initiation of immunosuppression and the development of lymphoma. Although previous reports have reported an indolent clinical course, an aggressive clinical course may occur. HHV8 and lytic phase EBV antigens are detected in some cases, possibly suggesting a pathogenetic role.
16646029 Linkage analysis of rheumatoid arthritis in US and UK families reveals interactions betwee 2006 May OBJECTIVE: HLA is the most strongly associated locus in rheumatoid arthritis (RA), accounting for up to one-third of the genetic contribution. Conditioning on the effect of true disease loci such as HLA can lead to increased power to detect effects at other loci and, in addition, allows investigation of the underlying disease models, including interactions. The aim of this study was to detect susceptibility loci for RA by conditioning on HLA in a large sample of affected sibling pairs (ASPs) and to test for evidence of interaction between novel loci and HLA. METHODS: Genotype data from 3 whole-genome linkage scans for RA in a US population and a UK population were pooled, resulting in a combined data set of 886 ASPs. This pooling of data increased the power to detect loci showing low levels of heterogeneity. Nonparametric linkage analysis was performed to identify regions of interest. Joint 2-locus analysis was then performed for HLA and each of the loci that demonstrated evidence of linkage in the 886 ASPs. RESULTS: Evidence for linkage was most significant at HLA (P = 4 x 10(-16)), with 7 non-HLA loci showing some evidence for linkage (P = 0.05-0.003). Joint modeling of these loci with HLA provided evidence for linkage at a genome-wide significance level for loci on 6q (P = 2.7 x 10(-6)) and 16p (P = 2 x 10(-4)). CONCLUSION: These data provide the most convincing evidence to date that 6q and 16p harbor susceptibility genes. In addition, these loci may interact with HLA, facilitating the search for candidate genes within this region.
15996060 Sex hormone concentrations in patients with rheumatoid arthritis are not normalized during 2005 Jul OBJECTIVE: Androgens such as dehydroepiandrosterone sulfate (DHEAS) and testosterone are markedly lower in postmenopausal women with rheumatoid arthritis (RA) than in controls. In contrast, compared to controls, serum levels of estrogens are normal or elevated in women with RA. Since tumor necrosis factor (TNF) alters production of these hormones, we investigated changes of these hormones during anti-TNF antibody (anti-TNF) therapy with adalimumab in longstanding RA. METHODS: In this longitudinal anti-TNF therapy study in 13 patients with long-standing RA without prior prednisolone (7 infusions of anti-TNF: Week 0, 2, 4, 6, 8, 10, and 12), we measured serum concentrations of interleukin 6 (IL-6), androstenedione, DHEA, DHEAS, free testosterone, estrone, and 17ss-estradiol. Levels of these hormones in patients were compared to serum levels of 31 age and sex matched healthy controls. RESULTS: Upon treatment with anti-TNF, there was an impressive decrease of clinical markers of inflammation, erythrocyte sedimentation rate, and serum levels of IL-6. Serum levels of DHEAS and free testosterone were markedly lower at baseline in patients compared to controls, but this did not change during anti-TNF therapy. Serum levels of DHEA and 17ss-estradiol were significantly elevated in patients compared to controls, but similarly, anti-TNF therapy did not change initially increased levels. Molar ratios of hormones, which reflect hormone shifts via converting enzymes, showed typical alterations at baseline, but did not change markedly during anti-TNF therapy. CONCLUSION: Longterm therapy with anti-TNF did not change altered serum levels of typical sex hormones in patients with RA, although baseline values were largely different. In patients with RA, this indicates that alterations of sex hormones and altered activity of respective converting enzymes are imprinted for a long-lasting period over at least 12 weeks.
16947779 Insulin resistance and impaired beta cell function in rheumatoid arthritis. 2006 Sep OBJECTIVE: To identify factors that regulate glucose metabolism in rheumatoid arthritis (RA). METHODS: We evaluated the homeostatic model assessment of insulin resistance (HOMA-IR) and beta cell function (HOMA-B) in 94 RA patients. We investigated the relationship between characteristics known to affect glucose metabolism in the general population (age, abdominal obesity [waist circumference], hypertension, antihypertensive therapy) as well as characteristics of RA (disease activity, glucocorticoid therapy) and insulin resistance and beta cell function. RESULTS: Patients with high-grade inflammation (high-sensitivity C-reactive protein value >1.92 mg/liter) (n = 81) were more insulin resistant than patients with low-grade inflammation (n = 13), whereas beta cell function was similar in both groups. Insulin resistance and beta cell function were similar in both groups after adjustment for waist circumference. All recorded characteristics except for age were associated with HOMA-IR or/and HOMA-B in univariate analyses. In mixed regression models, abdominal obesity and patient's assessment of disease activity (by visual analog scale) were predictors of insulin resistance. The Disease Activity Score assessed using 28-joint counts for swelling and tenderness, tender joint count, and patient's assessment of disease activity were associated with reduced beta cell function, and the cumulative dose of glucocorticoids was associated with enhanced beta cell function. The cumulative glucocorticoid dose in all study patients was a mean of only 536 mg (95% confidence interval 239-1,173). In patients with high-grade inflammation, age was further associated with impaired beta cell function, whereas use of angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers was associated with enhanced beta cell function. CONCLUSION: The modifiable factors of abdominal obesity, antihypertensive therapy, disease activity, and use of glucocorticoids appear to affect glucose metabolism in RA.
16810668 Daily interpersonal events in pain patients: applying action theory to chronic illness. 2006 Sep Action theory proposes that individuals actively shape and then respond to their environments, highlighting the role of stable person characteristics in the development and maintenance of life's interpersonal difficulties. In this study, the authors adopt the action perspective in their examination of predictors of daily interpersonal events among chronic pain patients with rheumatoid arthritis. They probe the extent to which stable symptoms of illness explained between-person variation, and fluctuating symptoms explain day-to-day variation in both positive and negative events. Their evaluation of patients' daily diary reports indicate that between-person differences accounted for more variance in the occurrence of positive events relative to negative events (48% vs. 31%, respectively). Likewise, between-person factors accounted for more variance in appraisals of positive compared to negative events across relationship domains. Both intractable illness symptoms and disability, and daily fluctuations in pain and fatigue, were only weakly related to patients' reports of their interpersonal experiences. Consistent with action theory, these results suggest that stable person characteristics are strongly related to daily stressors and particularly daily positive events in pain patients, but still account for less than 50% of the variance in events and their appraisals. In contrast, elevations in illness-related features, both between individuals and within individuals from day-to-day, are not robust predictors of positive or negative social exchanges. These findings point to the value of capturing the experiences of individuals intensively over time, an approach that can help to elaborate the contributions of both stable factors and circumstance in shaping social contexts in chronic illness.
15934093 Tumor necrosis factor inhibits conversion of dehydroepiandrosterone sulfate (DHEAS) to DHE 2005 Jun OBJECTIVE: Use of anti-tumor necrosis factor (anti-TNF) antibody therapy in rheumatoid arthritis (RA) has expanded our understanding of possible mechanisms by which this treatment reduces inflammation. Beyond its effects on local immune responses, anti-TNF treatment may also modulate the local hormone supply. Because androgens are thought to inhibit immune responses, their presence in inflamed tissue is an additional important antiinflammatory factor. METHODS: We investigated conversion of the ubiquitous dehydroepiandrosterone sulfate (DHEAS), the biologically inactive precursor of DHEA, to the androgen DHEA in mixed synovial cells from patients with RA and patients with osteoarthritis (OA), making use of thin-layer chromatography and phosphorimaging. Using immunohistochemical analysis, we detected the key enzyme, steroid sulfatase. RESULTS: DHEAS-to-DHEA conversion in synovial cells from patients with RA was significantly lower than that in synovial cells from patients with OA (mean +/- SEM 3.3 +/- 0.5% versus 6.0 +/- 0.9% of applied (3)H-DHEAS per 10(6) synovial cells; P = 0.042). In RA, but not in OA, the level of converted (3)H-DHEA was inversely correlated with the density of synovial macrophages (for RA, R(rank) = -0.725, P = 0.005; for OA, R(rank) = 0.069, P not significant [NS]) and T cells (for RA, R(rank) = -0.621, P = 0.024; for OA, R(rank) = 0.247, P NS). Double immunohistochemistry analysis revealed that steroid sulfatase was located mainly in synovial macrophages but was also observed in fibroblasts. Neutralization of TNF largely up-regulated the conversion of DHEAS to DHEA in RA, but not in OA. A similar neutralizing effect was observed with polyclonal human immunoglobulins; this effect is most probably mediated via TNF neutralization at low TNF concentrations. CONCLUSION: These data indicate that TNF inhibits the conversion of DHEAS to DHEA in RA synovial cells. Because androgens are antiinflammatory mediators, TNF-induced inhibition of the local androgen supply is a supplementary proinflammatory factor. Consequently, anti-TNF strategies may also exert their positive effects by increasing tissue androgens.
16277668 Expression of ADAM15 in rheumatoid synovium: up-regulation by vascular endothelial growth 2005 ADAMs (a disintegrin and metalloproteinases) comprise a new gene family of metalloproteinases, and may play roles in cell-cell interaction, cell migration, signal transduction, shedding of membrane-anchored proteins and degradation of extracellular matrix. We screened the mRNA expression of 10 different ADAMs with a putative metalloproteinase motif in synovial tissues from patients with rheumatoid arthritis (RA) or osteoarthritis (OA). Reverse transcription PCR and real-time quantitative PCR analyses indicated that among the ADAMs, ADAM15 mRNA was more frequently expressed in the RA samples and its expression level was significantly 3.8-fold higher in RA than in OA (p < 0.01). In situ hybridization, immunohistochemistry and immunoblotting demonstrated that ADAM15 is expressed in active and precursor forms in the synovial lining cells, endothelial cells of blood vessels and macrophage-like cells in the sublining layer of RA synovium. There was a direct correlation between ADAM15 mRNA expression levels and vascular density in the synovial tissues (r = 0.907, p < 0.001; n = 20). ADAM15 was constitutively expressed in RA synovial fibroblasts and human umbilical vein endothelial cells (HUVECs), and the expression level was increased in HUVECs by treatment with vascular endothelial growth factor (VEGF)165. On the other hand, ADAM15 expression in RA synovial fibroblasts was enhanced with VEGF165 only if vascular endothelial growth factor receptor (VEGFR)-2 expression was induced by treatment with tumor necrosis factor-alpha, and the expression was blocked with SU1498, a specific inhibitor of VEGFR-2. These data demonstrate that ADAM15 is overexpressed in RA synovium and its expression is up-regulated by the action of VEGF165 through VEGFR-2, and suggest the possibility that ADAM15 is involved in angiogenesis in RA synovium.
15694363 TNF-alpha modulates angiopoietin-1 expression in rheumatoid synovial fibroblasts via the N 2005 Mar 11 Angiopoietin-1 (Ang-1) is one of a family of ligands for the Tie-2 receptor which has been demonstrated to be involved in angiogenesis. Little is known about the regulation of Ang-1 gene expression. We have previously demonstrated that TNF-alpha is able to up-regulate the expression of Ang-1 mRNA in synovial fibroblasts. This present study investigated the signal transduction pathways involved in the TNF-alpha induced expression of Ang-1. TNF-alpha signals primarily through the p38, JNK, MAP kinase, and IKK pathways resulting in the activation of the transcription factors AP-1 and NF-kappa B. Experiments with inhibitors and siRNA for these various signal transduction pathways revealed that TNF-alpha stimulation of Ang-1 expression occurs via the NF-kappa B signal transduction pathway.
16984938 Real-time quantitative PCR to detect changes in synovial gene expression in rheumatoid art 2007 Apr Synovial biomarkers are increasingly important in the development of novel therapeutic agents for the treatment of rheumatoid arthritis (RA). To identify biomarkers correlating with changes in clinical disease activity, real-time quantitative PCR (Q-PCR) was used to evaluate changes in synovial gene expression after treatment with corticosteroids. Patients with active RA received either oral prednisolone (n=10, 60 mg daily for the first week and 40 mg daily for the second week) or placebo (n=11) for 14 days. Real-time Q-PCR was used to quantify gene expression of tumour necrosis factor (TNF)alpha, IL1beta, IL8 and matrix metalloproteinase (MMP) 1 in synovial tissue samples obtained through an arthroscopic procedure before and after treatment. mRNA levels were reported as relative expression units compared with a cell-based standard. Statistical analysis was performed using an analysis of covariance model. Prednisolone markedly decreased IL8 and MMP1 expression compared with placebo, and the CIs excluded the likelihood of no effect. A trend towards reduction was seen in IL1beta and TNFalpha mRNA expression in the prednisolone group, although CIs included the value for no effect. These data suggest that Q-PCR can be used to measure synovial mRNA expression of mediators implicated in the pathogenesis of RA in small proof-of-concept trials.
16127012 Pathogenesis of rheumatoid arthritis: targeting cytokines. 2005 Jun Although considerable progress has been made by adequate treatment with traditional disease-modifying antirheumatic drugs (DMARDs), therapy of rheumatoid arthritis (RA) still remains difficult. The discovery of the importance of cytokines such as tumor necrosis factor (TNF), interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-15 (IL-15), which are also stimulated by consequences of autoimmune responses, has led to the development of anticytokine therapies ("biologicals"). Blocking TNF or also, to some extent, IL-1 has proved beneficial in DMARD-resistant RA patients in multiple clinical trials. Along with clinical improvement, TNF blockade has been shown to halt radiographic disease progression, a major risk factor for disability. Recently, clinical trials have shown a significant therapeutic benefit of biological inhibitors of IL-6, and also of IL-15, with an efficacy comparable to that of TNF blockers. All these agents are particularly efficacious when combined with methotrexate. Although clinical remission is difficult to achieve even with anticytokine treatment, these drugs offer the potential to decrease disease activity and improve quality of life in a majority of RA patients, and it is conceivable that combinations of biological therapies may pave the path to even better success, which ultimately is remission or even cure.
16945726 An unusual presentation of methotrexate-induced B-cell lymphoma of the metacarpophalangeal 2006 Sep We report a unusual presentation of B-cell lymphoma in the chronically inflamed synovium of a 64-year-old man with an 18-year history of rheumatoid arthritis that was treated with methotrexate.
15848223 Apolipoprotein A-I-dependent cholesterol esterification in patients with rheumatoid arthri 2005 May 20 Growing evidence suggests that atherogenesis is associated with inflammation or defective removal of cholesterol excess from peripheral cells. Apolipoprotein A-I [ApoA-I] activates the enzyme Lecithin-Cholesterol Acyl-Transferase to esterify cell cholesterol for transport to liver. Haptoglobin [Hpt] was previously found able to bind ApoA-I, and suggested to reduce the enzyme activation. The aim of this study was to demonstrate that enhanced levels of Hpt, as present during inflammation, are associated with low enzyme activity and increased thickness of the arterial wall. Enzyme activity and Hpt concentration were analysed in patients with rheumatoid arthritis having the same plasma levels of antioxidants (ascorbate, urate, alpha-tocopherol, retinol) or oxidation markers (nitrotyrosine, lipoperoxide) of healthy subjects. Cholesterol esterification, determined as ratio of cholesteryl esters with cholesterol in high-density lipoproteins, was lower in patients than in controls, and negatively correlated with the intima-media wall thickness of the common carotid. The ratio of Hpt with ApoA-I was negatively correlated with the enzyme activity, while positively correlated with intima-media wall thickness. The results suggest that high Hpt levels might severely impair the enzyme activity, thus contributing to cholesterol accumulation in vascular cells, and lesion formation in the endothelium.
16572446 The HLA-DRB1 shared epitope alleles are primarily a risk factor for anti-cyclic citrullina 2006 Apr OBJECTIVE: The shared epitope (SE)-containing HLA-DRB1 alleles represent the most significant genetic risk factor for rheumatoid arthritis (RA). Recent studies indicate that the SE alleles are associated with only RA that is characterized by the presence of anti-cyclic citrullinated peptide (anti-CCP) antibodies, and not with anti-CCP-negative disease. In this study we investigated whether the SE alleles contribute to the development of anti-CCP-positive RA, or whether they are associated solely with the presence of anti-CCP antibodies. We therefore determined the influence of the SE alleles and anti-CCP antibodies on the progression from recent-onset undifferentiated arthritis (UA) to RA. METHODS: Patients with recent-onset UA at the 2-week visit (n=570) were selected from the Leiden Early Arthritis Cohort. SE alleles, rheumatoid factor (RF) status, and anti-CCP antibody levels were determined. Progression to RA or other diagnoses was monitored. RESULTS: One hundred seventy-seven patients with UA developed RA during the 1-year followup, whereas the disease in 393 patients remained unclassified or was given other diagnoses. The SE alleles correlated with the presence of anti-CCP antibodies, but not with the presence of RF. Both in SE-positive and in SE-negative patients with UA, the presence of anti-CCP antibodies was significantly associated with the development of RA. More intriguingly, however, no apparent contribution of the SE alleles to the progression to RA was found when analyses were stratified according to the presence of anti-CCP antibodies. In patients with anti-CCP-positive disease, the presence of SE alleles was associated with significantly higher levels of anti-CCP antibodies, suggesting that the SE alleles act as classic immune response genes. CONCLUSION: The SE alleles do not independently contribute to the progression to RA from UA, but rather contribute to the development of anti-CCP antibodies.
16372823 Clinical pharmacology of lumiracoxib: a selective cyclo-oxygenase-2 inhibitor. 2005 Lumiracoxib (Prexige) is a selective cyclo-oxygenase (COX)-2 inhibitor developed for the treatment of osteoarthritis, rheumatoid arthritis and acute pain. Lumiracoxib possesses a carboxylic acid group that makes it weakly acidic (acid dissociation constant [pKa] 4.7), distinguishing it from other selective COX-2 inhibitors. Lumiracoxib has good oral bioavailability (74%). It is rapidly absorbed, reaching maximum plasma concentrations 2 hours after dosing, and is highly plasma protein bound. Lumiracoxib has a short elimination half-life from plasma (mean 4 hours) and demonstrates dose-proportional plasma pharmacokinetics with no accumulation during multiple dosing. In patients with rheumatoid arthritis, peak lumiracoxib synovial fluid concentrations occur 3-4 hours later than in plasma and exceed plasma concentrations from 5 hours after dosing to the end of the 24-hour dosing interval. These data suggest that lumiracoxib may be associated with reduced systemic exposure, while still reaching sites where COX-2 inhibition is required for pain relief. Lumiracoxib is metabolised extensively prior to excretion, with only a small amount excreted unchanged in urine or faeces. Lumiracoxib and its metabolites are excreted via renal and faecal routes in approximately equal amounts. The major metabolic pathways identified involve oxidation of the 5-methyl group of lumiracoxib and/or hydroxylation of its dihaloaromatic ring. Major metabolites of lumiracoxib in plasma are the 5-carboxy, 4'-hydroxy and 4'-hydroxy-5-carboxy derivatives, of which only the 4'-hydroxy derivative is active and COX-2 selective. In vitro, the major oxidative pathways are catalysed primarily by cytochrome P450 (CYP) 2C9 with very minor contribution from CYP1A2 and CYP2C19. However, in patients genotyped as poor CYP2C9 metabolisers, exposure to lumiracoxib (area under the plasma concentration-time curve) is not significantly increased compared with control subjects, indicating no requirement for adjustment of lumiracoxib dose in these subjects. Lumiracoxib is selective for COX-2 compared with COX-1 in the human whole blood assay with a ratio of 515 : 1 in healthy subjects and in patients with osteoarthritis or rheumatoid arthritis. COX-2 selectivity was confirmed by a lack of inhibition of arachidonic acid and collagen-induced platelet aggregation. COX-2 selectivity of lumiracoxib is associated with a reduced incidence of gastroduodenal erosions compared with naproxen and a lack of effect on both small and large bowel permeability. Lumiracoxib does not exhibit any clinically meaningful interactions with a range of commonly used medications including aspirin (acetylsalicylic acid), fluconazole, an ethinylestradiol- and levonorgestrel-containing oral contraceptive, omeprazole, the antacid Maalox, methotrexate and warfarin (although, as in common practice, routine monitoring of coagulation is recommended when lumiracoxib is co-administered with warfarin). As such, dose adjustments are not required when co-administering these agents with lumiracoxib. In addition, moderate hepatic impairment and mild to moderate renal impairment do not appear to influence lumiracoxib exposure.
16816753 Comparison of the anatomical risk for vertebral artery injury associated with the C2-pedic 2006 Jul 1 STUDY DESIGN: We evaluated the trajectories of atlantoaxial transarticular and C2-pedicle screws in 3 dimensions using computerized tomography. OBJECTIVE: To compare the anatomic risk for vertebral artery injury associated with C2-pedicle and atlantoaxial transarticular screws. SUMMARY OF BACKGROUND DATA: The atlantoaxial fixation technique using C1-lateral mass screws combined with C2-pedicle screws is considered a safer technique for preventing vertebral artery injury than atlantoaxial transarticular fixation. However, few reports have compared the anatomic risk of vertebral artery injury associated with C2-pedicle screws with that of transarticular screws. METHODS: A total of 62 consecutive patients with cervical lesions were evaluated using 3-dimensional images reconstructed by a computer-assisted navigation system. We compared the maximum possible diameters of the atlantoaxial transarticular screw and C2-pedicle screw trajectories, and examined whether the maximum possible diameters were limited by the height or width of the bony structure in screw trajectories < or = 4 mm in diameter. RESULTS: Mean maximum possible diameters did not differ significantly between the trajectories of 124 atlantoaxial transarticular and 124 C2-pedicle screws. In screw trajectories < or = 4 mm in diameter, 57.1% of transarticular screw trajectories were limited by the height of the bony structure, and all pedicle screw trajectories were limited by the width. CONCLUSIONS: C2-pedicle screw placement has nearly the same anatomic risk of vertebral artery injury as transarticular screw placement. Preoperative 3-dimensional evaluation may be useful for choosing the best surgical technique.
16098542 Lack of a difference in increased capillary blood cell velocity in the skin over proximal 2005 Jul Early detection of synovitis in rheumatoid arthritis (RA) and distinction from osteoarthritis (OA) are important to establish the most appropriate treatment. Increased perfusion over affected joints observed by laser Doppler perfusion imaging was supposed to arise from the underlying joint, because it was detected only by a near-infrared laser and not by a less penetrating red laser source. Using laser Doppler anemometry, this study addressed two questions: (1) whether capillary blood cell velocity (CBV) is increased in the skin over finger joints affected by RA or OA; (2) whether there is a difference between RA and OA in CBV above affected proximal interphalangeal (PIP) joints. Levels of soluble adhesion molecules were measured, because they indicate rheumatoid vasculitis raising flow resistance. Thirty-one patients with RA and 20 with OA were investigated. Compared to 18 controls, CBV (mean+/-SEM) was elevated above PIP joints clinically affected by RA (0.35+/-0.06 mm/s vs. 0.21+/-0.02 mm/s; P<0.05) and over PIP (0.27+/-0.02 mm/s vs. 0.21+/-0.02 mm/s; P<0.05) and distal interphalangeal joints (0.27+/-0.02 mm/s vs. 0.17+/-0.01 mm/s; P<0.001) affected by OA. Levels of soluble adhesion molecules were not correlated with CBV over PIP joints in RA. These observations demonstrated that elevated blood cell velocity is detectable by laser Doppler anemometry in skin capillaries over interphalangeal joints affected by RA or OA and contradict the previous assumption that there is hyperemia only in the affected joint. The lack of a significant difference in CBV over PIP joints between RA and OA patients might be due to some inflammation also occurring in OA rather than to vasculitic processes in RA associated with elevated levels of soluble adhesion molecules.
16969149 Removal of methotrexate by peritoneal dialysis and hemodialysis in a single patient with e 2006 Sep BACKGROUND: Although methotrexate is highly bound to albumin, it is thought to be removed by hemodialysis and not by peritoneal dialysis. We are not aware of any direct comparison in the same patient. CASE REPORT/METHODS: A 60-year-old patient on continuous ambulatory peritoneal dialysis was admitted to the East Alabama Medical Center for stomatitis and pancytopenia after being given 10 mg of methotrexate for his rheumatoid arthritis. Measurements of total methotrexate levels were made before, during, and after sequential peritoneal and hemodialysis treatments. RESULTS: We found that the clearance of methotrexate measured in the dialysate was equal in the first hour of dialysis for both types of dialysis, although serum levels were markedly lower in hemodialysis compared to peritoneal dialysis. CONCLUSION: Methotrexate was cleared by peritoneal dialysis in the first hour of an exchange and was not associated with a rebound in serum levels. Hemodialysis was associated with lower serum levels; however, there was also a significant rebound 2 hours after the procedure ended. Since neither procedure was able to preclude the death of the patient, other more effective means of methotrexate elimination should be employed.
17124600 Differing distributions of CXCR3- and CCR4-positive cells among types of interstitial pneu 2007 Jan Interstitial pneumonia (IP) is an important complication in collagen vascular diseases (CVDs). We examined the distribution of helper T cell subsets in lung biopsies of cases of IP associated with CVD (CVD-IP). The tissues from 27 CVD-IP patients with rheumatoid arthritis (RA), 8 with polymyositis or dermatomyositis (PM/DM), and 8 with systemic sclerosis (SSc) were compared with those from 10 patients with idiopathic pulmonary fibrosis (IPF) in our previous study. The expressions of CXCR3 and CCR4 (chemokine receptors associated in vitro with Th1 and Th2 cells, respectively) in the mononuclear infiltrate were analyzed immunohistochemically. The positive cells were semiquantified in fibrosing areas of the CVD-IP and IPF cases. The number of CXCR3-positive cells was significantly greater in RA-IP than in PM/DM-IP, SSc-IP, or IPF, whereas there were fewer CCR4-positive cells in RA-IP, PM/DM-IP, and SSc-IP than in IPF. The CXCR3-/CCR4-positive cells ratio was significantly higher in RA-IP and PM/DM-IP (but not in SSc-IP) than in IPF. These results support previous reports of the dominance of Th2 cells in some SSc-IP and IPF cases. However, Th1-type immune responses may predominate in RA-IP and PM/DM-IP. Our findings suggest that the pathogenesis of CVD-IPs differs with the helper T cell subset.